EDITORS

De nnis W. Boulwa re , MD
Professor of Medicine
University of Ala ba ma a t Birmingha m
Chief of Rheuma tology
Ha wa ii Perma nente Medica l Group
Honolulu, HI

Gusta vo R. He ude be rt, MD

Division of Genera l Interna l Medicine
The University of Ala ba ma a t Birmingha m
Birmingha m, AL
A cquisitions Editor: Son ya Se iga fu s e
Product Manager: Ke rry Ba rre t t
Production Manager: Alicia Ja cks on
Senior Manufacturing Manager: Be n ja m in Rive ra
Marketing Manager: Kim Sch on be rge r
Design Coordinator: Dou g Sm ock
Production Serv ice: Ap t a ra , In c.

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ISBN-13: 978-1-60913-808-0
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Library of Con gre s s Catalogin g-in -Pu blication Data

Lip p in cot t ’s p rim a ry ca re rh e u m a t ology / [e d it e d by] De n n is W. Bou lw a re

a n d Gu s t avo R. He u d e be rt .
p . ; cm . – (Prim a ry ca re s e rie s )
Prim a ry ca re rh e u m a t ology
In clu d e s bibliogra p h ica l re fe re n ce s a n d in d e x.
ISBN 978-1-60913-808-0 (h a rd ba ck)
1. Rh e u m a t ology. 2. Prim a ry ca re (Me d icin e ) I. Bou lw a re, De n n is W.
II. He u d e be rt , Gu s t avo R. III. Tit le : Prim a ry ca re rh e u m a t ology.
IV. Se rie s : Prim a ry ca re s e rie s (Ph ila d e lp h ia , Pa .)
[DNLM: 1. Rh e u m a t ic Dis e a s e s –d ia gn os is . 2. Prim a ry He a lt h
Ca re –m e t h od s . 3. Rh e u m a t ic Dis e a s e s –t h e ra py. W E 544]
RC927.L47 2012
616.7'23–d c23
2011020565

Ca r e h a s b e e n t a k e n t o c o n fir m t h e a c c u r a cy o f t h e in fo r m a t io n p r e s e n t e d a n d t o
d e s cr ib e ge n e ra lly a cce p t e d p ra ct ice s . How eve r, t h e a u t h o rs , e d it o rs , a n d p u blis h e r a re
n ot re s p on s ible for e rrors or om is s ion s or for a n y con s e q u e n ce s from a p p lica t ion of t h e
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t h e cu rre n cy, co m p le t e n e s s , o r a ccu ra cy o f t h e co n t e n t s o f t h e p u blica t io n . Ap p lica t ion
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t h e p ra ct it ion e r.
Th e a u t h o r s , e d it o r s , a n d p u blis h e r h a ve e x e r t e d eve ry e ffo r t t o e n s u re t h a t d r u g
s e le ct ion a n d d os a ge s e t fort h in t h is t e xt a re in a ccord a n ce w it h cu rre n t re com m e n d a -
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He u d e b e r t , a n d o u r fa m ilie s ? Fo r t h e ir e n d le s s love , s u p p o r t , p a t ie n ce ,
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book a n d ou r ca re e rs , t h is book is d e d ica t e d t o a ll of t h e m .

iii
Contributors

Gracie la S. Alarcón , MD Carlos A. Es trada , MD, MS

Jane Knight Low e Ch a ir of Me d icin e in
Rh e u m a t ology, Em e rit u s
Divis ion of Clin ica l Im m u n ology a n d
Rh e u m a t ology
Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Birm in gh a m , AL
Profe s s or of Me d icin e
Dire ct or, Divis ion of Ge n e ra l In t e rn a l Me d icin e
Un ive rs it y of Ala ba m a a t Birm in gh a m
Fe llow s h ip Dire ct or, Birm in gh a m VA Na t ion a l
Qu a lit y Sch ola rs Progra m
Birm in gh a m , AL

Se th M. Be rn ey, MD Barri Fe s s le r, MD, MSPH

Dep a rt m e n t of Rh e u m a t ology As s ocia t e Profe s s or of Me d icin e
Lou is ia n a St a t e Un ive rs it y Divis ion of Clin ica l Im m u n ology a n d
Sh reve p ort , LA Rh e u m a t ology
Un ive rs it y of Ala ba m a a t Birm in gh a m
De n n is W. Bou lw are , MD Birm in gh a m , AL
Profe s s or of Me d icin e
Un ive rs it y of Ala ba m a a t Birm in gh a m An ge lo Gaffo , MD, MSPH
Ch ie f of Rh e u m a t ology Divis ion of Clin ica l Im m u n ology a n d
Ha w a ii Pe rm a n e n t e Me d ica l Grou p Rh e u m a t ology
Hon olu lu , HI Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Birm in gh a m , AL
S. Lou is Bridge s Jr, MD, Ph D
Marguerite Jones Harbert-Gene V. Ball, MD, Gu s tavo R. He u de be rt , MD
Profe s s or of Me d icin e Divis ion of Ge n e ra l In t e rn a l Me d icin e
Un ive rs it y of Ala ba m a a t Birm in gh a m Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Birm in gh a m , AL Birm in gh a m , AL

Am y C. Can n e lla , MD Kath e rin e Holm an , MD

Se ct ion of Rh e u m a t ology Fe llow
Un ive rs it y of Ne bra s ka Me d ica l Ce n t e r Divis ion of In fe ct iou s Dis e a s e s
Om a h a , NE De p a rt m e n t of Me d icin e
Un ive rs it y of Ala ba m a a t Birm in gh a m
W. Win n Ch ath am , MD Birm in gh a m , AL
Divis ion of Clin ica l Im m u n ology a n d
Rh e u m a t ology Lau ra B. Hu gh e s , MD, MSPH
Th e Un ive rs it y of Ala ba m a a t Birm in gh a m Divis ion of Clin ica l Im m u n ology a n d
Birm in gh a m , AL Rh e u m a t ology
Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Gre gory A. Clin e s , MD, Ph D Birm in gh a m , AL
As s is t a n t Profe s s or of Me d icin e a n d Ce ll Biology
Th e Un ive rs it y of Ala ba m a a t Birm in gh a m Bao Qu yn h N. Hu yn h , MD
En d ocrin ology Se ct ion , Birm in gh a m VA Me d ica l Se con d Ye a r Fe llow in t h e Divis ion of
Ce n t e r Rh e u m a t ology a n d Clin ica l Im m u n ology
Birm in gh a m , AL Un ive rs it y of Ala ba m a a t Birm in gh a m
Birm in gh a m , AL
Carol Croft , MD
Profe s s or of Me d icin e Kris tin M. In grah am , DO, MBA
Divis ion of Ge n e ra l In t e rn a l Me d icin e Le h igh Va lley He a lt h Ne t w ork
Un ive rs it y of Te xa s -Sou t h w e s t e rn Alle n t ow n , PA
Da lla s , TX
v
vi Con t ribu t ors

William F. Iobs t , MD Iris Navarro-Millán , MD

Vice Pre s id e n t , Aca d e m ic Affa irs Rh e u m a t ology Fe llow
Am e rica n Boa rd of In t e rn a l Me d icin e Divis ion of Clin ica l Im m u n ology a n d
Ph ila d e lp h ia , PA Rh e u m a t ology
Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Arth u r Kavan au gh , MD Birm in gh a m , AL
Profe s s or of Me d icin e
Dire ct or, Ce n t e r for In n ova t ive Th e ra py Jam e s R. O’De ll , MD
Divis ion of Rh e u m a t ology, Alle rgy, a n d Divis ion of Rh e u m a t ology & Im m u n ology
Im m u n ology De p a rt m e n t of In t e rn a l Me d icin e
Dep a rt m e n t of Me d icin e Un ive rs it y of Ne bra s ka Me d ica l Ce n t e r
Th e Un ive rs it y of Ca liforn ia a t Sa n Diego Om a h a , NE
Sa n Diego, CA
Maika On is h i , MD
Mich ae l Locks h in , MD Me d ica l St u d e n t
Profe s s or of Me d icin e a n d Obs t e t rics /Gyn e cology, Un iversity of Ca liforn ia , Sa n Diego Sch ool of Med icin e
We ill Corn e ll Me d ica l College Sa n Diego, CA
Dire ct or, Ba rba ra Volcke r Ce n t e r for Wom e n a n d
Rh e u m a t ic Dis e a s e a n d Co-Dire ct or, Ma ry Mich e lle A. Pe tri , MD
Kirkla n d Ce n t e r for Lu p u s Re s e a rch Divis ion of Rh e u m a t ology
Hos p it a l for Sp e cia l Su rge ry-Corn e ll Joh n s Hop kin s Hos p it a l
New York, NY Ba lt im ore, MD

Carlos J. Lozada , MD Zach ary M. Pru h s , MD

Profe s s or of Clin ica l Me d icin e Divis ion of Rh e u m a t ology & Im m u n ology
Dire ct or, Rh e u m a t ology Fe llow s h ip Progra m Dep a rt m e n t of In t e rn a l Me d icin e
Un ive rs it y of Mia m i Mille r Sch ool of Me d icin e Un ive rs it y of Ne bra s ka Me d ica l Ce n t e r
Mia m i, FL Om a h a , NE

Le an n Mas ka , MD Martin Rodrigu e z , MD

Rh e u m a t ology Fe llow As s is t a n t Profe s s or of Me d icin e
Divis ion of Rh e u m a t ology a n d Im m u n ology Divis ion of In fe ct iou s Dis e a s e s
Un ive rs it y of Ne bra s ka Me d ica l Ce n t e r Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Om a h a , NE Birm in gh a m , AL

Te d R. Miku ls , MD Ke n n e th G. Saag , MD, MSc

Divis ion of Rh e u m a t ology Jane Knight Low e Profe s s or of Me d icin e
Un ive rs it y of Ne bra s ka Me d ica l Ce n t e r Dire ct or, Ce n t e r for Ou t com e s Effe ct ive n e s s
Om a h a , NE Re s e a rch a n d Ed u ca t ion (COERE) a n d Ce n t e r for
Ed u ca t ion a n d Re s e a rch on Th e ra p e u t ics (CERTs )
Fre de rick W. Mille r, MD, Ph D of Mu s cu los ke le t a l Dis ord e rs
Ch ie f, En viron m e n t a l Au t oim m u n it y Grou p Divis ion of Clin ica l Im m u n ology a n d
Office of Clin ica l Re s e a rch Rh e u m a t ology
NIEHS/NIH Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Be t h e s d a , MD Birm in gh a m , AL

Sarah L. Morgan , MD, RD, FADA, FACP, CCD
Profe s s or of Nu t rit ion Scie n ce s a n d Me d icin e
Me d ica l Dire ct or, UAB Os t e op oros is Preve n t ion a n d
Tre a t m e n t Clin ic
Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Birm in gh a m , AL
Te rry Sh an eyfe lt, MD, MPH
Ch ie f, Ge n e ra l Me d icin e
Birm in gh a m VA Me d ica l Ce n t e r
As s ocia t e Profe s s or of Me d icin e
UAB Dep a rt m e n t of Me d icin e
Birm in gh a m , AL
 Con t ribu t ors vii

Je rom e Van Ru is w yk , MD, MS Ire n e Z. Wh itt , MD

Divis ion of Ge n e ra l In t e rn a l Me d icin e St a ff Clin icia n
Profe s s or of Me d icin e NIH | NIEHS | EAG
Me d ica l College of W is con s in Be t h e s d a , MD
Za blocki VA Me d ica l Ce n t e r
Milw a u ke e, W I Lis a L. Wille tt , MD
Divis ion of Ge n e ra l In t e rn a l Me d icin e
Mary S. Walton , MD As s ocia t e Profe s s or of Me d icin e
Fe llow, Divis ion of Rh e u m a t ology a n d Im m u n ology Th e Un ive rs it y of Ala ba m a a t Birm in gh a m
Ce n t e r of Exce lle n ce for Art h rit is a n d Birm in gh a m , AL
Rh e u m a t ology
Lou is ia n a St a t e Un ive rs it y He a lt h Scie n ce s Ce n t e r
Sch ool of Me d icin e
Sh revep ort , LA
Introduction to Lippincott’s
Prima ry Ca re Series

We lcom e t o Lip p in cot t ’s Prim a ry Ca re Se rie s . Th e in t e n d e d goa l of t h is

s e rie s is t o h e lp a s s is t you in a ll of t h e u s e -ca s e s ce n a rios t h a t you m igh t
e n cou n t e r e a ch d a y.

In t h is p rod u ct , Prim a ry Ca re Rh e u m a t ology, you w ill fin d :

1. Book: Th e book con t a in s bot h bu lle t e d p oin t s for q u ick look-u p a cce s s
w h e n you n e e d a n a n sw e r righ t aw a y, a s w e ll a s lon ge r t e xt for t h e
occa s ion s w h e n you n e e d a lit t le m ore in form a t ion .
Ad d it io n a lly w e h a ve in clu d e d p e d a go gy t o h igh ligh t ce r t a in
a s p e ct s of t h e t e xt . Th e s e e le m e n t s in clu d e :

Patient As s es s m ent—Quick reference for the phys ical ex am ination

Not to Be Mis s e d—Th ings to w atch ou t for or pos s ible diagnos e s

to ke e p in m ind durin g th e e x am in ation

Wh e n to Re fe r—Wh e n to s u gge s t fu rth e r option s to you r patie n t

Patie n t Edu cation In form ation Available On lin e

2. We bs ite t h a t in clu d e s :
• Fu lly s e a rch a ble t e xt of t h e book
• Im a ge ba n k t h a t ca n be d ow n loa d a ble in t o Pow e rPoin t for
p re s e n t a t ion s
• PDF d ow n loa d a ble Pa t ie n t In form a t ion Sh e e t s

3. An atom ical Ch art for You r Office

We ce rt a in ly h op e t h is p rod u ct is u s e fu l a n d m e e t s you r n e e d s .

Ple a s e look for ot h e r t it le s in t h e Lip p in cot t ’s Prim a ry Ca re Se rie s .

ix
Prefa ce

Cu r re n t clin ic life fo r a p rim a ry ca re clin icia n is fa s t p a ce d a n d m u lt id im e n s io n a l

re q u irin g t h e clin icia n t o m a n a ge a h os t of clin ica l p roble m s q u ickly, e ffe ct ive ly, a n d
e fficie n t ly. Th e p reva le n ce a n d s co p e o f a r t h r it is a n d m u s cu lo s k e le t a l p ro ble m s
a re la rge a n d e xp e ct e d t o in cre a s e in t h e fu t u re a s t h e w orld ’s p op u la t ion a ge s a n d
life e xp e ct a n cy le n gt h e n s . Tod a y’s p rim a ry ca re clin icia n s a re e xp e ct e d t o m a n a ge
m ore clin ica l p roble m s for m ore p e op le a n d w it h im p rove d ou t com e s in t h e fu t u re
m a kin g re lia ble, fa ct u a l, p ra ct ica l, a n d e a s ily a cce s s ible re s ou rce s a key t ool for t h e ir
clin ics .
To m e e t t h e a n t icip a t e d n e e d s of t h e b u s y p rim a ry ca re clin icia n , t h is book is
form a t t e d t o a llow t h e clin icia n q u ick a n d e a s y a cce s s t o re lia ble a n d p ra ct ica l in for-
m a t ion . Th e op e n in g ch a p t e r fo cu s e s on t h e u s e fu ln e s s a n d p it fa lls o f t h e clin ica l
p r e s e n t a t io n a n d p h ys ica l e x a m in a t io n ; it d e s cr ib e s a s ys t e m a t ic ye t e fficie n t
a p p roa ch le a d in g t o t h e corre ct d ia gn os e s of m u s cu los ke le t a l d is ord e rs . Th e follow -
in g ch a p t e rs a re orga n ize d by com m on clin ica l com p la in t s of u n d ia gn os e d clin ica l
p roble m s like t h e p a in fu l kn e e, p a in fu l fe e t , a n d n e ck or low ba ck p a in a s w e ll a s
com m on m u s cu los ke le t a l d ia gn os e s like os t e oa rt h rit is , gou t , or rh e u m a t oid a rt h rit is .
Th e fin a l ch a p t e rs a d d re s s s p e cia l d ia gn os t ic a n d t h e ra p e u t ic con s id e ra t ion s s u ch a s
u s e of t h e la bora t ory, m on it orin g p a t ie n t s on d is e a s e m od ifyin g a n t irh e u m a t ic d ru gs ,
a n d a rt h roce n t e s is a n d in je ct ion .
Ea ch ch a p t e r is form a t t e d on a com m on t e m p la t e s u ch t h a t t h e re a d e r ca n con -
s is t e n t ly fin d in form a t ion on clin ica l p re s e n t a t ion , t h e p h ys ica l e xa m in a t ion , d ia g-
n os t ic s t u d ie s , t re a t m e n t op t ion s , a n d t h e clin ica l cou rs e or ou t com e in a com m on
loca t ion w it h in e a ch ch a p t e r. Ta ble s a n d illu s t ra t ion s a re u s e d libe ra lly t o m a ke in for-
m a t ion re t rieva l q u icke r a n d e a s ie r. All ch a p t e rs w e re w rit t e n a n d e d it e d by a t e a m
com p ris in g e xp e rie n ce d clin ica l rh e u m a t ologis t s a n d p rim a ry ca re p h ys icia n s .
We a p p re cia t e im m e n s e ly t h e t im e a n d e ffort s of ou r m a n y a u t h ors w h o con t rib-
u t e d t ow a rd t h is n ew t e xt bo ok a n d p rovid e d t h e e xp e rt is e , k n ow le d ge , s kills , a n d
clin ica l ju d gm e n t for t h e be n e fit of a ll p a t ie n t s .

De n n is W. Bou lw a re , MD
Gu s t a vo R. He u d e be rt , MD

xi
Acknowledgments

Th is book is t h e ou t com e of a colla bora t ive e ffort from m a n y p e op le. Ou r d e e p e s t

a p p re cia t ion is e xt e n d e d t o Lis a Con s oli, Deve lop m e n t a l Ed it or, for h e r gu id a n ce a n d
a bilit y t o ke e p u s w orkin g a t a p rod u ct ive p a ce t h rou gh t h e ge s t a t ion a l p e riod of t h is
book. Th e “h e a t a n d p re s s u re ” w a s m a in t a in e d a t a n op t im a l ba la n ce t o p reve n t bu rn
ou t or w ors e ye t , fa ilu re t o p rod u ce. We a ls o w a n t t o re cogn ize a n d e xt e n d ou r a p p re -
cia t io n t o So n ya Se iga fu s e, Se n ior Acq u is it io n s Ed it or, a n d t o Ke rry Ba rre t t , Se n io r
Prod u ct Ma n a ge r, for e xt e n d in g t h is op p ort u n it y t o u s a n d a s s is t in g u s in cre a t in g
t h is t e xt bo o k. Fin a lly, w e a re in d e bt e d t o ou r m a n y co n t r ibu t in g a u t h o r s for t h e ir
con t ribu t ion of t h e ir e xp e rt is e, t im e, a n d e ffort s in w rit in g t h is book.

x iii
Contents

Con t ribu t ors v

Pre fa ce xi
Ackn ow le d gm e n t s xiii

Se ctio n 1 Intro ductio n to the Rhe uma tic Dise a se s 1

CHAPTER 1: Eva lu a tio n o f Pa tie n ts w ith Rh e u m a tic
Dis e a s e s 3
Carlos A . Estrada and Gustav o R. Heudebert

Se ctio n 2 Spo rt- Re la te d, Occupa tio na l, a nd Othe r

Re g io na l Pa in Syndro me s 9
CHAPTER 2: Ne ck Pa in 11
Jerom e Van Ruisw yk

CHAPTER 3: Low Ba ck Pa in a n d Lu m b a r Ste n o s is 23

Lisa L. W illett

CHAPTER 4 : Sh o u ld e r Pa in 30
Dennis W. Boulw are

CHAPTER 5: Pa in fu l Fe e t 37
Dennis W. Boulw are and Gustav o R. Heudebert

CHAPTER 6: Me ch a n ica l Dis o rd e rs o f th e Kn e e 48

Dennis W. Boulw are

CHAPTER 7: Hip Pa in 55
Carol Croft

CHAPTER 8: Sp orts -Re la te d Con d ition s a n d In ju r ie s 66

Lisa L. W illett

Se ctio n 3 Spe cific Rhe uma tic Dise a se s: Dia g no sis

a nd Tre a tme nt 75
CHAPTER 9: Rh e u m a to id Arth r itis , In clu d in g Sjö gre n ’s
Sy n d ro m e 77
Zachary M. Pruhs, Jam es R. O’Dell, and Ted R. Mikuls

xv
x vi Con t e n t s

CHAPTER 10 : Th e Se ro n e ga tive
Sp o n d y lo a rth ro p a th ie s 95
Dennis W. Boulw are

CHAPTER 11: Sy s te m ic Lu p u s Ery th e m a to s u s 103

Michelle A . Petri

CHAPTER 12: Ra y n a u d ’s Ph e n o m e n o n a n d Sy s te m ic
Scle ro s is 111
Laura B. Hughes and Barri Fessler

CHAPTER 13: In fla m m atory Myop a th ie s : Polym yos itis ,

De rm a to m yo s itis , a n d Re la te d
Co n d itio n s 118
Irene Z. W hitt and Frederick W. Miller

CHAPTER 14 : Va s cu litis 132

Bao Quynh N. Huynh and S. Louis Bridges, Jr

CHAPTER 15: Gia n t Ce ll Arte r itis a n d Po ly m ya lgia

Rh e u m a tica 140
A ngelo Gaffo

CHAPTER 16: Ove rla p Sy n d ro m e s a n d Un cla s s ifie d

o r Un d iffe re n tia te d Co n n e ctive Tis s u e
Dis e a s e 150
Iris Navarro-Millán and Graciela S. A larcón

CHAPTER 17: Fib ro m ya lgia 158

Graciela S. A larcón

CHAPTER 18: Pre gn a n cy a n d Rh e u m a tic Dis e a s e s 167

Michael Lockshin

Se ctio n 4 Oste o a rthritis a nd Me ta bo lic Bo ne

a nd Jo int Dise a se 171
CHAPTER 19: Os te o a rth r itis 173
Mary S. W alton, Carlos J. Loz ada, and Seth M. Berney

CHAPTER 20 : Go u t a n d Cry s ta l-In d u ce d

Arth ro p a th ie s 183
A ngelo Gaffo

CHAPTER 21: Os te o p e n ic Bo n e Dis e a s e s a n d

Os te o n e cro s is 199
Kenneth G. Saag, Gregory A . Clines, and Sarah L. Morgan
 Con t e n t s x vii

CHAPTER 22: Arth ro p a th ie s As s o cia te d w ith Sy s te m ic

Dis e a s e s 223
Leann Maska and A m y C. Cannella

Se ctio n 5 Infe ctio us Arthritis 237

CHAPTER 23: Ba cte r ia l Arth r itis 239
A rthur Kavanaugh and Maika Onishi

CHAPTER 24 : Ly m e Dis e a s e 247

W illiam F. Iobst and Kristin M. Ingraham

CHAPTER 25: Vira l Arth r itis 257

Katherine Holm an and Martin Rodriguez

Se ctio n 6 Spe cia l Dia g no stic a nd The ra pe utic

Co nditio ns 2 6 7
CHAPTER 26: Us e o f th e La b o ra to r y in Dia gn o s in g
Rh e u m a tic Dis o rd e rs 269
Terry Shaneyfelt and Gustav o R. Heudebert

CHAPTER 27: Te ch n iq u e s o f Arth ro ce n te s is 274

Dennis W. Boulw are

CHAPTER 28: Mo n ito r in g o f Pa tie n ts o n An tirh e u m a tic

Th e ra p y 280
W. W inn Chatham

INDEX 297
SECTION
1

Introduction to the
Rheuma tic Disea ses

Chapter 1 Evalu ation of Patie n ts w ith

Rh e u m atic Dis e as e s
Carlos A . Estrada and
Gustav o R. Heudebert

1
CHAPTER
1 Evaluation of Patients
with Rheumatic Diseases
Carlos A . Estrada and Gustav o R. Heudebert

Appro a ch to the
A 24-ye ar-o ld f e m ale co m e s

s
Pa tie nt w ith Articula r

e
s
t o t h e Em e rg e n cy De p art m e n t

a
Co mpla ints

e
s
w it h a 3-d ay h ist o ry o f p ain in

i
D
CLINICAL PRESENTATION

c
t h e rig h t k n e e t h at re so lve d

i
t
a
Th e clin ica l p re s e n t a t ion of rh e u m a t ic

m
in 48 h o u rs, f o llo w e d b y p ain

u
d isea ses is fra m ed on t h e u n iq u e p a tien t’s

e
in h e r le f t w rist (m ig rat o ry

h
R
ba ckgrou n d in clu d in g a ge, ge n d e r, e t h -
art h rit is). Sh e h as also n o t ice d

e
n icity, a s s ocia t ed con d it ion s , fa m ily h is -

h
t
dif culty holding to atw are on her right hand (tenosynovitis). tory, a n d h abits. Su ch ch a ra cteris tics ca n

o
t
p rovid e u sefu l clu es for p a tien ts p resen t-

n
She not ice d onse t of sym pt om s short ly af te r he r m e nse s (se e n

o
i
in g w it h s ign s or s ym p t om s con s is t e n t

t
c
in d isse m in at e d g o n o co ccal in f e ct io n ). Ph ysical e xam in at io n

u
w it h a rh e u m a t ic d is e a s e. We w ill con -

d
o
re ve als p ain w it h m o t io n o f t h e le f t w rist w it h a t h ick e n e d s id e r t h e s e ch a ra ct e ris t ics s e p a ra t e ly,

r
t
n
I
syn o viu m ; e xio n o f d ig it s is t e n d e r at t h e rig h t h an d con sid er m ostly a d u lt p a tien ts, orga n ize

1
N
(t e n o syn o vit is), h o w e ve r, w rist e xio n is n o t p ain f u l. Th e re on th e ba sis of etiologic ca u ses, a n d p ro-

O
vid e exa m p les. We recogn ize th a t typ ica l

I
T
are a f e w p u st u le s n o t e d in t h e le f t f o re arm an d rig h t f o o t

C
p a t t e r n s o c c u r in a fe w in s t a n ce s ;

E
(art h rit is–d e rm at it is syn d ro m e ).

PATIENT ASSESSMENT
• De t e rm in e t h e p a t t e rn o f
jo in t in vo lve m e n t :
• Nu m b e r o f jo in t s
in vo lve d : m o n o a rt icu la r,
o lig o a rt icu la r, p o lya rt ic-
u la r ( 3 jo in t s)
• Evolution of involvement:
a d d it ive , m ig ra t o ry
• An a t o m ic lo ca t io n : a xia l,
p e rip h e ra l
• Sym m e t ry: sym m e t ric,
a sym m e t ric
• De t e rm in e p re se n ce o f
in a m m a t io n :
• Jo in t s, t e n d o n in se rt io n ,
syn o viu m
(Con t in ue d )
S
h ow eve r, w e p re s e n t a fra m ew o r k t o
e f cie n t ly re cogn ize d is e a s e p a t t e rn s .
Ta ble 1.1 su m m a rizes th e p a tien t’s ba ck-
grou n d a n d com m on clin ica l en tit ies.
Patie nt’s Backg ro und
Ag e
Crys t a l-in d u ce d a rt h rop a t h ie s (gou t a n d p s e u d ogou t ) ca n p re s e n t a t a n y a ge ;
a lt h ou gh , p s e u d ogou t u s u a lly p re s e n t s in t h e ft h or s ixt h d e ca d e of life. Gou t
d ia gn os e d in t h e t w e n t ie s s h ou ld ra is e t h e s u s p icion of le a d e xp os u re (s a t u r-
n in e gou t ), in cre a s e d e n d oge n ou s p rod u ct ion of u ric a cid (e.g., lym p h op rolif-
e ra t ive d is ord e r), or a n in h e re n t d e fe ct of p rod u ct ion or e xcre t ion of u ric a cid .
Os t e oa rt h rit is (OA) u s u a lly p re s e n t s in in d ivid u a ls old e r t h a n 50 ye a rs of
a ge. OA ca n be d ia gn os e d in you n ge r p a t ie n t s w it h p a s t t ra u m a (e.g., gym n a s t s )
or in t h e fa m ilia l form of t h e d is e a s e.
Th e in fe ct iou s e t iology of a rt h rit is va rie s ba s e d on a ge. H. in uenz a a rt h rit is
p re s e n t s a lm os t e xclu s ive ly in ch ild re n , w h e re a s gon ococca l a rt h rit is is d ia g-
n os e d a lm os t e xclu s ive ly in s e xu a lly a ct ive in d ivid u a ls 40 ye a rs of a ge. Old e r
p a t ie n t s a re m ore like ly t o h ave com orbid it ie s or u n d e rlyin g a rt icu la r d is e a s e s
s u ch a s OA o r jo in t re p la ce m e n t . Th e a ffe ct e d jo in t s a re m o re vu ln e ra ble t o
s yn ovia l in va s ion , e s p e cia lly in t h e p re s e n ce of ba ct e re m ia .
An kylos in g s p on d ylit is , p s oria t ic a rt h rit is , Re it e r’s s yn d rom e, a n d re a ct ive
a r t h r it is (s e ro n e ga t ive s p o n d ylo a r t h ro p a t h ie s ) a re m o re co m m o n ly s e e n in
3
 4 Se ctio n 1 In t rod u ct ion t o t h e Rh e u m a t ic Dis e a s e s

PATIENT ASSESSMENT (Co n t in u e d) Table 1.1 Pat ient ’s Background and Diagnosis of Pat ient s
Present ing wit h Art icular Complaint s
• De t e rm in e p a t t e rn o f
m u scle in vo lve m e n t :
AFRICAN–
• Pro xim a l ve rsu s d ist a l FEMALE MALE AMERICAN WHITES
• Pa in fu l ve rsu s p a in le ss Ag e 40 y Ta ka ya su ’s Reiter’s syndrome, Sa rco id o sis Reiter’s syndrome,
a rt e rit is, SLE, SS AS AS
• Ca re fu l n e u ro lo g ica l
e xa m in a t io n fo r p a t ie n t s Ag e 50 y RA, OA, GCA Gout, pseudogout OA, GCA
w it h m u scu la r co m p la in t s
AS, a n kylo sin g sp o n d ylit is; GCA, g ia n t ce ll a rt e rit is; OA, o st e o a rt h rit is; RA, rh e u m a t o id a rt h rit is; SLE,
• Ca re fu l a sse ssm e n t o f t h e syst e m ic lu p u s e ryt h e m a t o su s; SS, syst e m ic scle ro sis.
skin , e ye s, a n d m u co u s
m e m b ra n e s

you n g a d u lt s . Sys t e m ic s cle ros is p re s e n t s in t h e t h ird a n d fou rt h d e ca d e s of

life. Sys t e m ic lu p u s e ryt h e m a t os u s (SLE) m os t ly a ffe ct s w om e n d u rin g t h e ir
S
re p rod u ct ive ye a rs . Rh e u m a t oid a rt h rit is (RA) p re s e n t s in t h e fou rt h a n d ft h
E
C
d e ca d e s of life.
T
I
O
Sys t e m ic va s cu lit is e xh ibit s a w id e ra n ge of a ge d is t ribu t ion . For e xa m p le,
N
He n och -Sch ön le in p u rp u ra is s e e n m os t ly in ch ild re n (s om e p re s e n t in t h e ir
1
t w e n t ie s ), Ta ka ya s u ’s a rt e r it is p re s e n t s in you n g fe m a le s , gia n t ce ll a r t e rit is
I
n
t
r
m o s t ly occu rs in t h e e ld e rly, a n d p olym ya lgia rh e u m a t ica is s e ld om s e e n in
o
d
in d ivid u a ls 50 ye a rs of a ge.
u
c
t
i
o
Ge n d e r
n
t
Th e be s t kn ow n rh e u m a t ic d is e a s e s w it h fe m a le p re d ile ct ion a re SLE a n d s ys -
o
t
t e m ic s cle ros is . Ot h e r con d it ion s w it h fe m a le p re d om in a n ce in clu d e Ta kaya s u ’s
h
e
a r t e r it is , gia n t ce ll a r t e r it is , Sjö gre n s yn d ro m e , a n d r h e u m a t o id a r t h r it is .
R
h
How eve r, t h e ge n d e r d iffe re n ce in RA is le s s p rom in e n t a m on g old e r p a t ie n t s .
e
u
m
Rh e u m a t ic con d it ion s w it h m a le p re d om in a n ce in clu d e gou t , Re it e r’s s yn d rom e,
a
a n d a n kylos in g s p on d ylit is . Mos t of t h e s ys t e m ic va s cu lit id e s e xh ibit a s m a ll
t
i
c
m a le p rep on d e ra n ce.
D
i
s
e
Et h n icit y
a
s
A cle a r e t h n ic p re d ile ct ion is s e e n in few rh e u m a t ic d is ord e rs . More com m on
e
s
in w h it e s a re t h e HLA-B27-p os it ive s e ron ega t ive s p on d yloa rt h rop a t h ie s (Re it e r’s
s yn d rom e a n d a n kylos in g s p on d ylit is ), gia n t ce ll a rt e rit is , a n d OA. Sa rcoid os is
is m ore com m on in you n g bla cks , a t le a s t in t h e Un it e d St a t e s . For e xa m p le,
s a rco id o s is s h o u ld b e co n s id e re d in a yo u n g bla ck p a t ie n t p re s e n t in g w it h
a n kle a rt h ra lgia s . Ta kaya s u ’s a rt e rit is t e n d s t o be p re s e n t in w om e n of As ia n
d e s ce n t . Be h çe t ’s d is e a s e is m ore com m on in t h e Me d it e rra n e a n ba s in , e s p e -
cia lly a m on g Tu rkis h p e op le. Fa m ilia l Me d it e rra n e a n feve r is s e e n m ore com -
m on ly in in d ivid u a ls from t h e Mid d le Ea s t .
Pa t ie n t s w it h rh e u m a t ic co n d it ion s ca n p re s e n t w it h a m yr ia d o f com -
p la in t s . Sym p t om s ca n be loca lize d a n d s p e ci c for a ce rt a in d ia gn os is ; h ow -
eve r, s ym p t om s ca n be ill-d e n e d a n d p h ys ica l n d in gs s u bt le on m a n y occa -
s ion s . Rh e u m a t ic d is e a s e s le n d t h e m s e lve s w e ll t o a s ys t e m a t ic a p p roa ch of
a s s e s s m e n t a n d d ia gn os is . Th e p a t ie n t ’s ba ckgrou n d , a s p reviou s ly m e n t ion e d ,
ca n p rovid e u s e fu l clu e s . Th e p a t t e rn o f jo in t in vo lve m e n t , t h e p re s e n ce o f
in a m m a t ion (s e e p h ys ica l n d in gs be low ), a n d s ign s a n d s ym p t om s in ot h e r
orga n s ca n a ls o gu id e t h e d iffe re n t ia l d ia gn os is .

Sympto mato lo g y
Pa t t e rn o f Jo in t In vo lve m e n t
A s u m m a ry of t yp ica l p a t t e rn s of join t in volve m e n t a n d ce rt a in d ia gn os is is
in clu d e d in Ta ble 1.2 . Th e n u m be r of join t s in volve d , evolu t ion of join t in volve -
m e n t , a n a t om ic loca t ion of join t s , a n d s ym m e t ry a re im p ort a n t fe a t u re s in t h e
h is t ory a n d p h ys ica l e xa m in a t ion of p a t ie n t s w it h join t com p la in t s .
 Ch a p te r 1 Eva lu a tion of Pa tien ts w ith Rh eu m a tic Disea ses 5

Table 1.2 Pat t ern of Joint Involvement and Diagnosis

AXIAL PERIPHERAL ADDITIVE MIGRATORY SYMMETRIC ASYMMETRIC

Mo n o - OA Go u t , OA
Olig o - Re it e r’s Go n o co cci, Go n o co cci, Re it e r’s syn d ro m e ,
Syn d ro m e . AS rh e u m a t ic fe ve r vira l AS
Po ly- SLE, RA, SS, RA, rh e u m a t ic Go n o co cci, SLE, RA, SS, Re it e r’s syn d ro m e ,
p so ria t ic fe ve r vira l p so ria t ic AS

AS, a n kylo sin g sp o n d ylit is; OA, o st e o a rt h rit is; RA, rh e u m a t o id a rt h rit is; SLE, syst e m ic lu p u s e ryt h e m a t o su s; SS, syst e m ic scle ro sis.

Join t in volvem en t ca n be m on oa rticu la r (on e join t), oligoa rt icu la r or p a u ci-

a rticu la r (tw o to th ree join ts), or p olya rticu la r ( 3 join ts). In gen era l, m on oa rticu la r

s
e
in volvem en t is ch a ra cteristic of ba cteria l in fection s, crysta l-in d u ced d isea se, a n d

s
a
tra u m a . Oligoa rticu la r in volvem en t is seen in p a tien ts w ith seron ega tive sp on dy-

e
s
i
D
loa rth rop a th ies a n d ju ven ile RA. Fin a lly, p olya rth ritis is typ ica l in p a tien ts w ith

c
a d u lt on set RA a n d freq u en tly seen in p a tien ts w ith SLE a n d system ic sclerosis.

i
t
a
Th e evolu t ion of join t in volve m e n t ca n be a d d it ive or m igra t ory. Ad d it ive

m
u
refers w h en a secon d join t becom es a ffected w h ile th e rst on e is still in volved —

e
h
R
ch a ra ct e ris t ic of RA a n d Re it e r’s s yn d rom e. Migra t ory re fe rs w h e n a n ot h e r join t

e
be com e s a ffe ct e d a ft e r re s olu t ion of t h e la s t on e —ch a ra ct e ris t ic of gon ococca l

h
t
a n d vira l a rt h rit is .

o
t
Th e a n a t om ic loca t ion of join t s ca n be broa d ly d ivid e d a s a xia l or p e rip h -

n
o
i
e ra l. Th e jo in t s o f t h e a x ia l s ke le t o n in clu d e t h e s p in e , s a cro ilia c, s t e rn o cla -

t
c
u
vicu la r, a crom ioclavicu la r, s h ou ld e r, a n d h ip join t s . Se ron ega t ive s p on d yloa r-

d
o
t h rop a t h ie s a n d os t e on e cros is t yp ica lly in volve t h e a xia l s ke le t on . Th e join t s of

r
t
n
I
t h e p e rip h e ra l s ke le t o n in clu d e t h e join t s d is t a l t o t h e e lb ow s a n d k n e e s —

1
N
ch a ra ct e ris t ic of RA a n d m a n y of t h e con n e ct ive -t is s u e d is e a s e s . Fu rt h e rm o re,

O
d is t in ct jo in t s ca n h e lp in t h e d iffe re n t ia l d ia gn o s is . Fo r e x a m p le , b ila t e ra l

I
T
C
h a n d in vo lve m e n t o f t h e m e t a ca r p o p h a la n ge a l (MCP) a n d p ro x im a l in t e r-

E
S
p h a la n ge a l (PIP) join t s is ch a ra ct e ris t ic of RA, w h e re a s in volve m e n t of t h e d is -
t a l in t e rp h a la n ge a l (DIP) join t s is m ore com m on in OA a n d p s oria t ic a rt h rit is .
Th e co m bin a t ion o f a n e n t h e s it is (e .g., Ach ille s t e n d on it is , p la n t a r fa s ciit is )
w it h s a croiliit is s h ou ld ra is e t h e s u s p icion of Re it e r’s s yn d rom e.
Jo in t s a ffe ct e d ca n be s ym m e t ric o r a s ym m e t ric. Mo n oa rt icu la r a n d o li-
goa rt icu la r d is e a s e s a re by d e n it ion a s ym m e t ric. Bila t e ra l in volve m e n t , s ym -
m e t ric, of t h e DIP join t s is s e e n in p s oria t ic a rt h rit is a n d in occa s ion a l p a t ie n t s
w it h p olya rt icu la r gou t . Of t h e p olya rt icu la r e n t it ie s , RA a n d t h e con n e ct ive -
t is s u e d is e a s e s a re m ore like ly t o p re s e n t in a s ym m e t ric fa s h ion .
Pre se n ce o f In a m m a t io n
De t e rm in in g t h e p re s e n ce of in a m m a t ory ch a n ge s is on e of t h e m os t im p or-
t a n t a s p e ct s in t h e eva lu a t ion of p a t ie n t s w it h join t com p la in t s . Th e h is t ory is
h e lp fu l, a s p a t ie n t s ca n a ccu ra t e ly d e s cribe if a join t h a s be e n or is cu rre n t ly
w a rm , re d , sw olle n , or s im p ly p a in fu l.
Crys t a l d ep os it ion d is e a s e u s u a lly p re s e n t s w it h in a m m a t ion . Gou t t e n d s
t o b e a n a cu t e m o n o a r t h r it is t yp ica lly a ffe ct in g t h e r s t m e t a t a r s a l jo in t
(p od a gra ), follow e d by t h e kn e e (gon a gra ), or t h e w ris t (ch in a gra ). Occa s ion a lly,
gou t ca n m im ic RA w it h p olya rt icu la r in volve m e n t . Us u a lly, p a t ie n t s w it h gou t
h ave t op h i e ls ew h e re. Ps e u d ogou t ca n m im ic gou t in t e rm s of a cu t e n e s s a n d
d egre e of in a m m a t ion ; t h e join t s m os t com m on ly a ffe ct e d in p s e u d ogou t a re
t h e kn e e, s h ou ld e r, a n d w ris t .
De t e rm in in g t h e d u ra t ion of m orn in g s t iffn e s s is a ls o ve ry h e lp fu l. Ch a ra c-
t e ris t ica lly, p a t ie n t s w it h RA a n d ot h e r in a m m a t ory a rt h rop a t h ie s e xp e rie n ce
 6 Se ctio n 1 In t rod u ct ion t o t h e Rh e u m a t ic Dis e a s e s

s t iffn e s s for m ore t h a n a n h ou r a ft e r aw a ke n in g, for w e e ks or m on t h s . Con -

CLINICAL POINTS: HISTORY ve rs e ly, p a t ie n t s w it h OA u s u a lly fe e l loos e n in g of t h e ir join t s be fore t h e h ou r
OF PRESENT ILLNESS h a s e la p s e d .
• Ma n y rh e u m a t o lo g ic Pa t ie n t s w it h s ys t e m ic va s cu lit is com m on ly com p la in of d iffu s e, s ym m e t -
co n d it io n s a re clo se ly ric a rt h ra lgia s w it h lit t le in a m m a t ion . For e xa m p le, s ign i ca n t a rt h ra lgia s is
a sso cia t e d w it h t h e a g e co m m o n ly s e e n in p a t ie n t s w it h He n o ch -Sch ö n le in p u rp u ra a n d cryoglo b -
a n d g e n d e r o f t h e p a t ie n t
u lin e m ia .
• Pattern of jo int in volveme nt In s u m m a ry, n o s in gle p a rt icu la r s ign or s ym p t om is like ly t o h ave e n ou gh
is u se fu l in t h e d iffe re n t ia l d is crim in a t ory q u a lit y t o d ia gn os e a rh e u m a t ologic con d it ion . A d e t a ile d h is -
d ia g n o se s
t ory, a com p le t e or re leva n t review of s ys t e m s , a n d a s ys t e m a t ic a p p roa ch p ro-
• In a m m a t o ry a rt h ro p a t h ie s vid e t h e n e ce s s a ry fra m ew ork for a n in it ia l d iffe re n t ia l d ia gn os is .
a re m o re like ly t o b e
a sso cia t e d w it h m o rn in g Sig n s a n d Sym p t o m s in Ot h e r Org a n s
st iffn e ss a n d t h e “ g e llin g ” Th e p re s e n ce of s ign s or s ym p t om s in ot h e r orga n s ca n gu id e t h e d iffe re n t ia l
phenomena
d ia gn os is . For e xa m p le, t h e p re s e n ce of s u bcu t a n e ou s n od u le s in e xt e n s or s u r-
fa ce s ra is e s t h e p os s ibilit y of t op h a ce ou s gou t or RA n od u le s . Alt h ou gh eye
n d in gs s u ch a s con ju n ct ivit is , irit is , a n d ep is cle rit is a re n on s p e ci c, t h ey ca n
S
E
occu r in m a n y rh e u m a t ic con d it ion s . Th e re ce n t h is t ory of d ia rrh e a or s e xu a lly
C
T
t ra n s m it t e d d is e a s e s h ou ld a le rt t h e p os s ibilit y of re a ct ive a rt h rit is . Th e p re s -
I
O
N
e n ce of h ila r a d e n op a t h y in t h e s e t t in g of s ym m e t ric a d d it ive p olya rt h rit is of
1
t h e a n kle s a n d kn e e s a n d e ryt h e m a n od os u m ch a ra ct e rize s Lofgre n s yn d rom e
I
n
(s a rco id o s is ). Pu rp u ra , a rt h ra lgia s , a n d p ro t e in u r ia a re ch a ra ct e r is t ic o f cry-
t
r
o
d
oglobu lin e m ia in p a t ie n t s w it h ch ron ic h ep a t it is C in fe ct ion .
u
c
t
i
o
n
Co mo rbiditie s and Asso ciate d Co nditio ns
t
o
Co m o r b id it ie s a n d a s s o cia t e d co n d it io n s a re a ls o im p o r t a n t in fra m in g t h e
t
h
clin ica l p ro ble m . Fo r e x a m p le , co n d it io n s a s s o cia t e d w it h d ia b e t e s m e llit u s
e
R
in clu d e d iffu s e id io p a t h ic s k e le t a l h yp e ro s t o s is (DISH), a d h e s ive ca p s u lit is ,
h
e
t r igge r n ge r, s t iff-h a n d s yn d ro m e , s cle re d e m a , Du p u yt re n ’s co n t ra ct u re ,
u
m
ca r p a l t u n n e l s yn d ro m e , a n d re e x s ym p a t h e t ic s yn d ro m e a m o n g o t h e r s .
a
t
Occa s ion a lly, p a t ie n t s p re s e n t w it h u n u s u a l p a t t e rn s of a rt icu la r in volve m e n t
i
c
D
t h a t m igh t be h igh ly ch a ra ct e ris t ic of ce r t a in clin ica l e n t it ie s . Fo r e xa m p le ,
i
s
e
p a t ie n t s w it h h e m och rom a t os is p re s e n t w it h a rt h ra lgia s of t h e MCP join t s a n d
a
s
s p a rin g of t h e DIP a n d PIP join t s .
e
s
PHYSICAL FINDINGS
An im p ort a n t rs t s t e p in p a t ie n t s p re s e n t in g w it h com p la in t s re la t e d t o t h e
join t s is t o d e t e rm in e if t h e p roble m is a rt icu la r, p e ria rt icu la r, or n on a rt icu la r.
Ca re fu l e xa m in a t ion of p e ria rt icu la r liga m e n t ou s s t ru ct u re s , p a in a t t h e s it e of
t e n d on in s e rt ion (i.e., e n t h e s it is ), or p a in a rou n d t h e join t it s e lf (p e ria rt h rit is )
is im p ort a n t t o d e t e rm in e t h e like ly e t iology of t h e p a t ie n t ’s “a rt icu la r” com -
p la in t . Als o, d u rin g t h e p h ys ica l e xa m in a t ion , t h e clin icia n m a y con r m or
re fu t e t h e p re s e n ce of in a m m a t ion a n d p a t t e rn join t in volve m e n t obt a in e d in
t h e h is t ory. Th e re a d e r is re fe rre d t o s t a n d a rd books on p h ys ica l e xa m in a t ion
for a d e t a ile d review.
Th e p h ys ica l e xa m in a t ion is ve ry h e lp fu l in d e t e rm in in g t h e p re s e n ce of
NOT TO BE MISSED in a m m a t ion . For e xa m p le, t h e e lbow a n d kn e e a re n orm a lly cold e r t h a n t h e
re s t of t h e bod y—eve n a s ligh t ly w a rm t e m p e ra t u re in t h e s e loca t ion s s u gge s t s
• Fe a t u re s o f t h e h ist o ry in a m m a t ion . Art h ra lgia s a lon e d o n ot s u p p ort in a m m a t ion .
t h a t a re co n sist e n t w it h Ba ct e ria l ca u s e s o f in fe ct iou s a rt h rit is a re like ly t o p re s e n t w it h o bvio u s
a n in a m m a t o ry
a rt h ro p a t h y in a m m a t ory ch a n ge s ; t h e m os t com m on clin ica l p a t t e rn is t h a t of a n a cu t e
m on oa rt h rit is . In a m m a t ory ch a n ge s m igh t n ot be p re s e n t in p a t ie n t s on s t e r-
• Pa t t e rn o f in vo lve m e n t oid s or t h os e w it h s eve re n e u t rop e n ia . An ot h e r s p e cia l ca s e of in fe ct iou s a rt h ri-
m ig h t h e lp d iffe re n t ia t e
in fe ct io u s ve rsu s t is w it h o u t o r w it h m in im a l in a m m a t io n is t h a t o f b a ct e r ia l in fe ct io n s
n o n in fe ct io u s e t io lo g ie s in p ros t h e t ic d evice s . Fu n ga l a n d m ycoba ct e ria l in fe ct ion s ca n p re s e n t w it h
lit t le or n o in a m m a t ory ch a n ge s . Vira l in fe ct ion s p re s e n t clin ica lly m ore like

CLINICAL POINTS: PHYSICAL
EXAMINATION
• No t a ll jo in t p a in is t ru ly
a rt icu la r; p o in t a t t e n d o n
in se rt io n a n d a lo n g
t e n d o n s a re h e lp fu l
in d iffe re n t ia t in g
rh e u m a t o lo g ic co n d it io n s
• Jo in t p a in m ig h t n o t
b e a sso cia t e d w it h
in a m m a t o ry ch a n g e s
• Pattern of joint involve ment
is h e lp fu l in t h e d iffe re n t ia l
d ia g n o se s
NOT TO BE MISSED
• Se p t ic a rt h rit is
• In a m m a t o ry
a rt h ro p a t h ie s
Ch a p te r 1 Eva lu a tion of Pa tien ts w ith Rh eu m a tic Disea ses 7
a rt h ra lgia s t h a n a rt h rit is ; p a rvoviru s B19 in fe ct ion s u s u a lly p re s e n t a s a ve ry
a cu t e a n d d is a blin g p olya rt h ra lgia .
Rh e u m a t o id a r t h r it is a lm o s t u n ive r s a lly p re s e n t s w it h in a m m a t o ry
ch a n ge s in t h e a ffe ct e d jo in t s . Pa t ie n t s w it h “b u r n o u t ” r h e u m a t o id jo in t s
p re s e n t w it h s eve re d e form it ie s a s s ocia t e d w it h lit t le or n o a p p re cia ble in a m -
m a t o ry ch a n ge s . Ove r t im e p a t ie n t s w it h a d va n ce OA e x h ib it d e fo r m in g
ch a n ge s of t h e a ffe ct e d join t s w it h lit t le or n o in a m m a t ory ch a n ge s . Th e m a in
d iffe re n ce be t w e e n a d va n ce d RA a n d OA w it h d e form it ie s re s id e s in t h e join t s
be in g a ffe ct e d (i.e., la rge join t s in OA like t h e kn e e vs . s m a ll join t s in RA like
MCP or PIP). Th e p re s e n ce of a n ew in a m e d -a p p e a rin g join t in a p a t ie n t w it h
OA s h o u ld a le rt t h e clin icia n t o t h e p o s s ib ilit y o f a n in fe ct io u s o r crys t a l-
in d u ce d e t iology.
Pa t ie n t s w it h con n e ct ive -t is s u e d is e a s e s ca n p re s e n t w it h e it h e r a rt h ra l-
gia s or a rt h rit is . Ch a ra ct e ris t ica lly, t h e join t in volve m e n t in SLE t e n d s t o be
m o re o f a p o lya rt h ra lgia t h a n p o lya r t h rit is . Pa t ie n t s w it h s ys t e m ic s cle ro s is
p re s e n t w it h d iffu s e a rt h ra lgia s ; t h e ch a n ge s obs e rve d in t h e d igit s (s a u s a ge -
s
like ch a n ge s ) a re d u e t o in lt ra t ion of t h e s kin a n d n ot d u e t o t h a t of t h e s yn o-
e
s
via l s p a ce.
a
e
Pa t ie n t s w it h s e ro n e ga t ive s p o n d ylo a r t h ro p a t h ie s ca n m a n ife s t jo in t
s
i
D
in volve m en t in va riou s w ays : t h os e w it h p s oria t ic a rt h rit is ca n h ave a s ym m e t ric
c
i
t
p olya rt h rit is in d is t in gu is h a ble from t h a t in p a t ie n t s w it h RA; t h e m os t s eve re
a
m
form of p s oria t ic a rt h rit is p rod u ce s a cla s s ic d e s t ru ct ion of t h e d is t a l p h a la n x
u
e
k n ow n a s a r t h r it is m u t ila n s . Pa t ie n t s w it h a n kylo s in g s p o n d ylit is u s u a lly
h
R
p re s e n t w it h lit t le or n o evid e n ce of a p e rip h e ra l a rt h rit is ; t h e s e in d ivid u a ls
e
h
h a ve p re d om in a n t in volve m e n t of t h e a xia l s ke le t on . In d ivid u a ls w it h in a m -
t
o
m a t ory bow e l d is e a s e ca n p re s e n t w it h e it h e r oligoa rt h rit is or, m ore com m on ly,
t
n
oligoa rt h ra lgia s .
o
i
t
c
u
d
Appro a ch to Pa tie nts w ith Muscle Diso rde rs
o
r
t
n
I
1
CLINICAL PRESENTATION
N
O
Ce r t a in d e m ogra p h ic ch a ra ct e ris t ics ca n b e lin k e d t o s p e ci c in a m m a t o ry
I
T
C
m u s cle d is o rd e r s . Fo r e x a m p le , in clu s io n b od y m yos it is is ch a ra ct e r is t ica lly
E
s e e n in e ld e rly m e n ; p olym yos it is /d e rm a t om yos it is (PM/DM) occu r m ore com -
S
m o n ly in fe m a le s . Age is a n im p o rt a n t cr it e rio n fo r d iffe re n t ia t io n b e t w e e n
in a m m a t ory a n d n on in a m m a t ory m yop a t h ie s . Ad u lt p a t ie n t s w it h p olym y-
os it is a n d d e rm a t om yos it is a re u s u a lly d ia gn os e d in t h e ft h d e ca d e of life ;
p a t ie n t s w it h p a ra n e op la s t ic PM p re s e n t a t a rou n d 60 ye a rs of a ge. Th e n on in -
a m m a t ory m yop a t h ie s of glycoge n or lip id s t ora ge d is e a s e s p re s e n t in ch ild -
h ood or in e a rly a d u lt h ood ; t h e m yop a t h ie s a s s ocia t e d w it h con n e ct ive -t is s u e
d is e a s e u s u a lly p re s e n t in t h e s e con d or t h ird d e ca d e of life.
Th e p a t ie n t w it h m yop a t h y m a y p re s e n t w it h : (a ) p a in le s s w e a kn e s s t h a t is
d iffu s e (s u ch a s in p olym yos it is ) or loca lize d (d is t a l, s u ch a s in clu s ion bod y
m yo s it is ); (b ) p a in fu l w e a k n e s s (s u ch a s in p o lym ya lgia r h e u m a t ica ); a n d
(c) p a in w ith ou t w ea kn ess th a t ca n be gen era lized (in u en za , system ic in fect ion s)
or loca lize d ( brom ya lgia ).
PHYSICAL FINDINGS
Dis t in gu is h in g m u s cle w e a kn e s s of a n e u rop a t h ic ve rs u s m yop a t h ic e t iology
ca n be d if cu lt . We a kn e s s d u e t o u p p e r m ot or n e u ron d is e a s e t yp ica lly p re s e n t
w it h a s ym m e t r ic w e a k n e s s (s u ch a s h e m ip a re s is ), h yp e r re e x ia , p o s it ive
Ba bin s ki’s s ign , a n d u lt im a t e ly, s p a s t icit y. Pa t ie n t s w it h low e r m ot or n e u ron
d is e a s e m igh t be m ore ch a lle n gin g t o d iffe re n t ia t e from p a t ie n t s w it h a p ri-
m a ry m yo p a t h ic p ro ce s s ; t h ey p re s e n t w it h d is t a l w e a k n e s s , fa s cicu la t io n s ,
h yp ore e xia , a n d u lt im a t e ly, d e cre a s e d m u s cle t on e. Pa t ie n t s w it h d is ord e rs
a ffe ct in g t h e n e u ro m u s cu la r ju n ct io n a re ch a lle n gin g t o d iffe re n t ia t e fro m
 8 Se ctio n 1 In t rod u ct ion t o t h e Rh e u m a t ic Dis e a s e s

CLINICAL POINTS: PHYSICAL Table 1.3 Demographic and Clinical Charact erist ics of Pat ient s
FINDINGS Present ing wit h Muscular Complaint s
• Like lih o o d o f ce rt a in
d ia g n o se s is a sso cia t e d MALE FEMALE PROXIMAL DISTAL
w it h a g e a n d g e n d e r.
Ag e 50 y CTD En d o crin e , CTD LMN (?)
• Pa t t e rn o f in vo lve m e n t
Ag e 50 y In clu sio n b o d y PM/DM PM/DM e n d o crin e In clu sio n b o d y
(p ro xim a l vs. d ist a l) is
m yo sit is m yo sit is
im p o rt a n t fo r t h e
d iffe re n t ia l d ia g n o se s.
CTD, connective-tissue disorder; DM, dermatomyositis; LMN, lower motor neuron disease; PM, polymyositis.
• Co n sid e r m e t a b o lic a n d
n e u ro lo g ica l co n d it io n s
ca re fu lly w h e n a sse ssin g
p a t ie n t s w it h m u scle
co m p la in t s. p a t ie n t s w it h m yop a t h ic p roce s s e s , a s t h ey s h a re s im ila r ch a ra ct e ris t ics (p roxi-
m a l d is t ribu t ion , n orm a l re e xe s , n o Ba bin s ki’s s ign , a n d n orm a l m u s cle t on e ).
Not u n com m on ly, clin icia n s re s ort t o e le ct rom yogra p h ic s t u d ie s (EMG/NCV) a n d
S
E
m u s cle biop s ie s t o d is t in gu is h be t w e e n t h e s e la t t e r t w o grou p s of p a t ie n t s . Ta ble
C
T
1.3 s u m m a rize s t h e p a t ie n t ’s d e m ogra p h ics a n d com m on m u s cu la r d is ord e rs .
I
O
Th e p a t t e rn of m u s cle in volve m e n t ca n be h e lp fu l in t h e d iffe re n t ia l d ia g-
N
1
n os is of p a t ie n t s w it h w e a kn e s s . Proxim a l m u s cle w e a kn e s s of in s id iou s on s e t
I
n
is m ore ch a ra ct e ris t ic of p olym yos it is . In d ivid u a ls w it h in clu s ion bod y m yos it is
t
r
o
t e n d t o h ave bot h p roxim a l a n d d is t a l m u s cle w e a kn e s s . Proxim a l w e a kn e s s is
d
u
ch a ra ct e ris t ic of t h e m e t a bolic m yop a t h ie s (h yp oka le m ia , h yp e rca lce m ia ) a n d
c
t
i
o
t h e m yop a t h ie s a s s ocia t e d w it h e n d ocrin e d is ord e rs (t h yroid d is ord e rs , h yp e r-
n
t
ca lce m ia ). Pa t ie n t s w it h p e riod ic h yp oka le m ic p a ra lys is ca n p re s e n t w it h p ro-
o
t
fou n d ge n e ra lize d w e a kn e s s of ra t h e r a cu t e on s e t ; a s e a rch for h yp e rt h yroid is m
h
e
is w a rra n t e d in s u ch p a t ie n t s , e s p e cia lly if t h ey a re of As ia n d e s ce n t .
R
h
In d ivid u a ls p re s e n t in g w it h re gio n a l p a in a n d / o r w e a k n e s s n e e d t o b e
e
u
m
a p p roa ch e d in a d iffe re n t m a n n e r. Pa t ie n t s w it h cle a r regio n a l m u s cle p a in
a
s h ou ld be ca re fu lly q u e s t ion e d for a h is t ory of t ra u m a . Occa s ion a lly, in fe ct ion s
t
i
c
m igh t be re s p on s ible for t h e region a l n a t u re of t h e p a in . Pyom yos it is , a re la -
D
i
s
t ive ly u n u s u a l d is ord e r ou t s id e of t h e t rop ics , s h ou ld be s u s p e ct e d in p a t ie n t s
e
a
w it h kn ow n h u m a n im m u n od e cie n cy viru s w h o p re s e n t w it h feve r a n d loca l-
s
e
s
ize d m u s cle p a in . On occa s ion t h e s e p a t ie n t s m igh t a ls o h a ve a s s ocia t e d w e a k-
n e s s . Th e p re s e n ce of glu t e a l m u s cle w e a kn e s s a n d a t rop h y a m on g d ia be t ics
s h ou ld a le rt t h e clin icia n t o t h e p os s ibilit y of d ia be t ic a m yot rop h y. Dia be t ics
w it h lon g-s t a n d in g, p oorly con t rolle d d ia be t e s ca n p re s e n t w it h loca lize d p a in
a n d w e a kn e s s d u e t o d ia be t e s m yon e cros is . More com m on , h ow eve r, is t h e
p a t ie n t w it h brom ya lgia w h o p re s e n t s t o t h e clin icia n w it h com p la in t s of p ro-
fou n d ge n e ra liz e d fa t igu e a n d d iffu s e m u s cle p a in s . Diffe re n t ia t in g fa t igu e
from w e a kn e s s ca n be ch a lle n gin g. In t h e s e p a t ie n t s d ocu m e n t a t ion of n orm a l
m u s cle s t re n gt h a n d t on e is of gre a t im p ort a n ce. Elicit a t ion of p a in fu l t rigge r
p oin t s m igh t h e lp t h e clin icia n t o m a ke t h is d ia gn os is .

Additio na l Re a ding
1. Bow e n JL. Ed u ca t io n a l s t ra t e gie s t o p ro m o t e clin ica l d ia gn o s t ic re a s o n in g . N Engl J Med 2006 ;355 :
2217 –2225 .
2. Ch ew FS. Ra d iologic m a n ife s t a t ion s in t h e m u s cu los ke le t a l s ys t e m of m is ce lla n e ou s e n d ocrin e d is ord e rs .
Radiol Clin North A m 1991 ;29 :135 –147 .
3. De Gow in RL. DeGow in & DeGow in’s Diagnostic Exam ination . New York : McGraw -Hill, In c , 1994 .
4. McClu s key P, Rich a rd J, Pow e ll RJ. Th e eye in s ys t e m ic in a m m a t ory d is e a s e s . Lancet 2004 ;364 :2125 –2133 .
5. Na s ch it z JE, Ros n e r I, Roze n ba u m M , e t a l. Rh e u m a t ic s yn d rom e s : clu e s t o occu lt n e op la s ia . Sem in A rthritis
Rheum 1999 ;29 :43 –55 .
6. Sa p ira JD. The art and science of bedside diagnosis . Ba lt im o re –Mu n ich : Urba n & Sch w a rze n be rg , 1990 .
SECTION
2

Sport-Rela ted,
Occupa tiona l, a nd Other
Regiona l Pa in Syndromes

Chapter 2 Ne ck Pain
Jerom e Van Ruisw yk

Chapter 3 Low Back Pain an d

Lu m bar Ste n os is
Lisa L. W illett

Chapter 4 Sh ou lde r Pain

Dennis W. Boulw are

Chapter 5 Pain fu l Fe e t
Dennis W. Boulw are and
Gustav o R. Heudebert

9
10 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

Chapter 6 Me ch an ical Dis orde rs

of th e Kn e e
Dennis W. Boulw are

Chapter 7 Hip Pain

Carol Croft

Chapter 8 Sports -Re late d Con dition s

an d In ju rie s
Lisa L. W illett
CHAPTER
2 Neck Pa in
Jerom e Van Ruisw yk

A 62-year-old m an presents w ith chronic

Clinica l
neck and left arm pain that have been
Pre se nta tio n
getting progressively w orse over the last 2 Ne ck p a in is a co m m o n p re -
s e n t in g com p la in t in p rim a ry
years. The pain radiates dow n to the left

s
ca re s e t t in gs . St u d ie s s u gge s t

e
m
forearm and up into the head; he does ad- t h a t u p t o t w o t h ird s of in d i-

o
r
m it som e associated num bness in the left vid u a ls e x p e r ie n ce n e ck p a in

d
n
a t le a s t on ce d u rin g t h e ir life -

y
hand and occasionally in the right hand.

S
t im e . Th e p reva le n ce of n e ck

n
He denies bow el or bladder incontinence

i
p a in in cre a s e s w it h a ge a n d is

a
P
but feels that his sense of balance has m ore com m on in w om e n t h a n

l
a
n
been off for years. He has a history of prior in m e n . Alt h ou gh u p t o 10% of

o
i
t h e a d u lt p op u la t ion h a s n e ck

g
lum bar decom pression for lum bar spinal stenosis and radiculopathy.

e
R
p a in a t a n y o n e t im e , m o s t
On e xam in at io n , h e h as d im in ish e d lig h t t o u ch se n sat io n o n t h e

2
n e ck p a in is s e lf-lim it e d . Con -

N
d o rsu m o f t h e le f t f o re arm an d h an d . St re n g t h in t h e arm s is 5 /5 in t h e s e q u e n t ly, p a t ie n t s s e e k in g

O
I
T
d e lt o id s, b ice p s, t rice p s, an d h an d g rip . De e p t e n d o n re e xe s in t h e ca r e fo r n e ck p a in t e n d t o

C
E
arm s an d le g s are n o rm al e xce p t t h e le f t b ice p s is 3 . Ho ff m an ’s re e x h a ve m ore s eve re p a in , ot h e r

S
a s s o c ia t e d s y m p t o m s , o r
is n e g at ive . Th e re is n o an k le clo n u s.
ch ro n ic s ym p t o m s t h a t h a ve
A m agnetic resonance im aging of the cervical spine show s severe m ul- n ot re s p on d e d t o re s t or ove r-
tilevel degenerative disc disease w ith broad-based disc protrusion at C3-C4 t h e - c o u n t e r a n a lg e s ic s ; o r
resulting in spinal cord deform ity (see im age), severe foram inal narrow ing t h ey re p ort n e ck p a in a s a s e c-
o n d a ry s ym p t o m o f a m o re
at bilateral C5, left C7, and bilateral C8 nerve roots. Electrom yogram
ge n e ra liz e d co n d it io n . Th o s e
show s a chronic neurogenic lesion affecting the left C7 nerve root. p a t ie n t s s e e k in g ca r e w it h
He is in it ially m an ag e d co n se rvat ive ly. Ho w e ve r, 3 m o n t h s lat e r h e n e ck p a in a s a p rim a ry com -
p re se n t s w it h a w o rse n in g o f sym p t o m s w it h n u m b n e ss an d t in g lin g in p la in t t e n d t o h ave s ym p t om s
b o t h e rs o m e e n o u gh t o ca u s e
b o t h arm s an d h an d s t h at is e xace rb at e d b y m o ve m e n t o f h is n e ck . He
fu n ct io n a l lim it a t io n s . Fu n c-
co n t in u e s t o d e n y b o w e l o r b lad d e r in co n t in e n ce . His n e u ro lo g ic e xam - t io n a l cla s s i ca t io n s ys t e m s
in at io n is u n ch an g e d e xce p t t h at h e n o w h as a p o sit ive Ho ff m an ’s s u ch a s t h e Wo r ld He a lt h
re e x in t h e rig h t arm . Orga n iz a t io n ’s In t e r n a t io n a l
Cla s s i ca t io n of Fu n ct io n in g,
Because of progression of sym ptom s and subtle signs of m yelopathy,
Dis a bilit y, a n d He a lt h (ICF) ca n
he undergoes posterior cervical decom pression and fusion. Postoperatively, be u s e d t o m ore fu lly d e s cribe
his neurologic sym ptom s abate, but his pain continues, and his neurologic p a t ie n t im p a irm e n t s .
exam ination continues to show dim inished light touch sensation on the Mu lt ip le -r is k fa ct o r s fo r
n e ck p a in h a ve b e e n id e n t i-
dorsum of the left hand and 5/5 m otor strength in both arm s except for
e d (1 ) in clu d in g in cre a s in g
4 /5 m otor strength in the left w rist extensors and triceps. a ge, obe s it y, s m okin g, u n u s u a l
p os t u re s , a n d h e a vy lift in g or
11
12 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
CLINICAL POINTS
• Pa t ie n t s p re se n t in g w it h
n e ck p a in ca n re p re se n t a
d ia g n o st ic ch a lle n g e
b e ca u se o f a n e xt e n sive
d iffe re n t ia l d ia g n o sis
t h a t in clu d e s e m e rg e n t
a n d se rio u s u n d e rlyin g
co n d it io n s.
• Pa t ie n t s w it h a h ist o ry o f
t ra u m a a n d t h o se w it h
p o ssib le m ye lo p a t h y,
in fe ct io n , o r m a lig n a n cy
sh o u ld h a ve fu rt h e r p ro m p t
e va lu a t io n w it h im a g in g .
• Be ca u se o f t h e p o o r
co rre la t io n o f im a g in g
n d in g s w it h sym p t o m s, it
ca n b e d if cu lt t o lo ca lize
n e ck p a in t o a sp e ci c
a n a t o m ic so u rce .
• Dia g n o st ic sp e ci cit y in
t h e e va lu a t io n o f n e ck
p a in re lie s o n re co g n it io n
o f p a t t e rn s o f sym p t o m s,
sig n s, a n d t e st re su lt s sin ce
a h ig h p ro p o rt io n o f
a sym p t o m a t ic p a t ie n t s w ill
h a ve d e g e n e ra t ive ch a n g e s
o n im a g in g .
• Pa t ie n t s w it h o u t u n d e rlyin g
sp in a l in st a b ilit y, in fe ct io n ,
ca n ce r, o r m ye lo p a t h y
ca n in it ia lly b e m a n a g e d
co n se rva t ive ly.
o t h e r h e a vy w o rk. How eve r, a n eve n gre a t e r n u m be r of p s ych o s ocia l fa ct o rs
h a ve be e n a s s ocia t e d w it h n e ck p a in in clu d in g d ep re s s ion , d ru g a bu s e, low job
s a t is fa ct ion , m on ot on ou s or d is s a t is fyin g w ork, la ck of cow orke r s u p p ort , a n d
la ck of con t rol ove r t h e w ork s it u a t ion . Ps ych os ocia l a n d cu lt u ra l fa ct ors ca n
a ls o im p a ct t h e p reva le n ce a n d n a t u ra l h is t ory of n e ck p a in . For e xa m p le, in
Au s t ra lia , a ft e r legis la t ion re m ove d n a n cia l com p e n s a t ion for p a in a n d s u ffe r-
in g from w h ip la s h in ju rie s , s u bs e q u e n t w h ip la s h p a t ie n t s re p ort e d low e r p a in
s core s a n d be t t e r fu n ct ion a l ou t com e s com p a re d w it h h is t orica l con t rols (2 ).
In t e re s t in gly, in Lit h u a n ia w h e re t h e re is n o lega l t ort s ys t e m , la t e w h ip la s h
s yn d rom e d oe s n ot e xis t (3 ).
W h e n eva lu a t in g n e ck p a in , t h e h is t ory s h ou ld in clu d e t h e e le m e n t s of a ll
ba s ic p a in h is t orie s in clu d in g loca t ion , s eve rit y, q u a lit y, on s e t , d u ra t ion , a ggra -
va t in g a n d a llevia t in g fa ct ors , ra d ia t ion , h is t ory of in ju ry or ove ru s e, a n y a s s o-
cia t e d s ym p t o m s e s p e cia lly n e u ro logic o r co n s t it u t io n a l s ym p t o m s , ch ro n ic
a n d p rior con d it ion s e s p e cia lly in fe ct ion s or m a lign a n cy, com m on w ork or le i-
s u re a ct ivit ie s a n d a n y re ce n t u n u s u a l a ct ivit ie s , a n d re s p on s e t o p rior in t e r-
ve n t ion s or t re a t m e n t s .
In clin ica l p ra ct ice, p a t ie n t s p re s e n t m u ch m ore com m on ly w it h p os t e rior
n e ck p a in t h a n w it h a n t e rior n e ck p a in . Th e m os t com m on ICD-10 cod e s s p e -
ci ca lly a s s ocia t e d w it h n e ck p a in in clu d e ce rvica lgia (M54.2), s p ra in a n d s t ra in
of ce rvica l s p in e (S13.4), s p on d ylos is w it h ra d icu lop a t h y (M47.2), ce rvica l d is c
d is ord e r w it h ra d icu lop a t h y (M50.1), a n d ce rvicocra n ia l s yn d rom e (M53.0).
Th e n e ck is t h e m os t e xible p a rt of t h e s p in a l colu m n . Th e le s s rigid bon y
s t ru ct u re t h a t a llow s t h is e xibilit y, p a rt icu la rly t h e u n iq u e s t ru ct u re of C1 a n d
C2, m e a n s t h a t t h e n e ck m u s t re ly m ore h e avily on s oft t is s u e s t ru ct u re s for
s u p p ort w h ich con t ribu t e s t o t h e p a t h op h ys iology of s om e im p ort a n t ce rvica l
s p in e con d it ion s . Th e a t la s (C1) is a rin g w it h ou t a n y ve rt e bra l bod y (Fig. 2.1A).
Th e s u p e rior la t e ra l bod ie s of t h e a t la s a rt icu la t e w it h t h e occip it a l con d yle s t o
form t h e a t la n t o-occip it a l join t , w h ich is re s p on s ible for a bou t 50% of t h e exion
a n d e xt e n s ion in t h e n e ck. Th e a xis (C2) m ore clos e ly re s e m ble s t h e re m a in d e r
o f t h e ve rt e bra e w it h a ve rt e bra l bod y, rin g, a n d p rom in e n t s p in ou s p roce s s
(e s p e cia lly n ot ice a ble on la t e ra l ce rvica l s p in e x-ra ys ), bu t it a ls o h a s a n od on -
t oid p roce s s or d e n s p roje ct in g s u p e riorly off it s ve rt e bra l bod y (Fig. 2.1B). A
t ra n s ve rs e liga m e n t h old s t h e d e n s t o t h e a n t e rior a rch of t h e a t la s ; t h is fu n c-
t ion a l p eg-in -h ole join t p rovid e s a bou t 50% of t h e rot a t ion of t h e n e ck. In a m -
m a t ion of t h e s yn ovia l join t t h a t a rt icu la t e s t h e a xis t o t h e a t la s , from con d it ion s
s u ch a s rh e u m a t oid a rt h rit is , ca n d a m a ge t h is liga m e n t le a d in g t o s u blu xa t ion
of t h e C1-C2 join t . Ra d iologic evid e n ce of C1-C2 s u blu xa t ion ca n be s e e n on
e xion –e xt e n s ion view s of 20% p a t ie n t s w it h rh e u m a t oid a rt h rit is . Th e re fore,
s cre e n in g la t e ra l e xion –e xt e n s ion x-rays s h ou ld be obt a in e d d u rin g p re op e ra -
t ive eva lu a t ion of p a t ie n t s w it h rh e u m a t oid a rt h rit is w h o w ill be u n d e rgoin g
e n d ot ra ch e a l in t u ba t ion .
Th e re m a in d e r of t h e ce rvica l ve rt e bra e h a ve s t a n d a rd ve rt e bra l a n a t om y
w it h a bod y, a p os t e rior a rch t h a t p rovid e s bon y p rot e ct ion for t h e s p in a l cord
a n d w it h in t e rve rt e bra l d is cs be t w e e n t h e ve rt e bra l bod ie s of a ll t h e re m a in in g
ce rvica l ve rt e bra e (Fig. 2.1C). Th e in t e rve rt e bra l d is c h a s a n ou t e r a n n u lu s bro-
s is a n d a n in n e r n u cle u s p u lp os u s w it h s u p e rior a n d in fe rior e n d p la t e s . Th e
ge la t in ou s n u cle u s p u lp os u s a ct s a s a s h ock a bs orbe r for com p re s s ive force s ,
w h e re a s t h e a n n u lu s bros is a ct s a s a brou s s h e a t h re s t ra in in g t h e n u cle u s
p u lp os u s . W h e n re n t s occu r in t h e a n n u lu s bros is , t h e in n e r n u cle u s p u lp os u s
m a y p rot ru d e o r be p a rt ia lly e xt ru d e d ; w h e n t h e re s u lt in g bu lge occu rs in a
p os t e rola t e ra l loca t ion it m ay com p re s s a n e rve root , a n d w h e n it occu rs in a
p os t e rior m id lin e loca t ion it m a y com p re s s t h e a n t e rior s p in a l cord . An t e rior
a n d p os t e rior lon git u d in a l liga m e n t s ru n a lon g t h e ve rt e bra l bod y fron t a n d
ba ck, re s p e ct ive ly. Th e p os t e rior lon git u d in a l liga m e n t ca n be com e ca lci e d in
co n d it io n s s u ch a s d iffu s e id io p a t h ic s k e le t a l h yp e ro s t o s is . In p a t ie n t s w it h
eith er a cq u ired or con gen ita l sten osis of th e sp in a l colu m n , th is ca lci ed liga m en t
 Ch a p te r 2 Ne ck Pa in 13

Dorsal View
Dens Superior
articulate facet

Transverse
POSTERIOR foramen
Superior View Transverse
Posterior tubercle process
Posterior arch Vertebral
foramen
Location of Inferior articular Lamina
transverse process
ligament Spinous process Dens
Transverse Lateral View
Articular surface foramen
for dens of axis Articular facet for anterior arch of atlas
Superior articular facet
Lamina

Transverse
process Superior
Lateral

s
articular

e
mass facet POSTERIOR ANTERIOR

m
Location

o
Groove for vertebral of dens

r
Spinous

d
artery and first cervical
Anterior tubercle

n
spinal nerve process

y
S
Anterior arch Inferior articular Transverse Transverse

n
process process foramen

i
a
A ANTERIOR B

P
l
a
n
Posterior

o
Anterior

i
g
e
Pedicle

R
Superior articular facet

2
Lamina

N
Vertebral body

O
Spinous process

I
Spinous process

T
Intervertebral disk

C
E
Superior Inferior articular

S
Lamina facets facet Nerve root
Posterior

Transverse process
Spinal nerve
Pedicle
Anterior
Vertebral body

Figure 2.1 (A) Ana tomy of a tla s; (B) a na tomy of a xis; a nd (C) a na tomy of typica l vertebra . All illustra tions from Oa tis CA. Kinesiology. The Mecha nics a nd
Pa thomecha nics of Huma n Movement. Ba ltimore: Lippincott Willia ms & Wilkins; 2003.

m a y co m p re s s t h e a n t e r io r s p in a l co rd , e s p e cia lly w it h n e ck e x io n w h ich

ca u s e s a 3-m m re d u ct ion in s p in a l ca n a l d ia m e t e r.
Th e p os t e rior a rch of e a ch ve rt ebra is form e d by p e d icle s , la t e ra l bod ie s , a n d
la m in a e. Th e la t e ra l bod y is form e d on e a ch s id e w h e re t h e p e d icle m e e t s t h e
la m in a . Th e re a re ve a rt icu la t ion s be t w e e n e a ch of t h e t yp ica l ve rt e bra : t h e
in t e rve rt e bra l d is k, a lon g w it h u n cove rt ebra l join t s (join t s of Lu ch s ka ), a n d fa ce t
(zyga p op h ys e a l) join t s a lon g e a ch s id e of t h e ve rt ebra . Th e u n cin a t e p roce s s is
a ve rt ica l p roje ct ion from t h e p os t e rola t e ra l ve rt e bra l bod y t h a t con t a ct s t h e
a d join in g ve rt ebra l bod y t o form t h e u n cove rt e bra l join t . Th e u n cove rt ebra l join t
is n ot a t ru e s yn ovia l join t bu t it is a fre q u e n t s it e of os t e op h yt e s . Tw o a rt icu la r
p roje ct ion s a ris e from e a ch la t e ra l bod y—a s u p e rior a rt icu la r p roje ct ion t h a t
 14 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

fa ce s p os t e riorly a n d a n in fe rior a rt icu la r p roje ct ion t h a t fa ce s a n t e riorly. Ea ch

p roje ct ion form s a t ru e s yn ovia l join t w it h it s n e igh borin g ve rt e bra , a n d n ot ch e s
a n t e rior t o t h e s e p roje ct ion s coa p t w it h com p le m e n t a ry n ot ch e s on a d ja ce n t
ve rt e bra e t o form t h e in t e rve rt e bra l fora m in a . Th e fa ce t join t s form e d by t h e
a rt icu la t ion of t h e s e p roje ct ion s w it h n e igh borin g ve rt ebra a re s u bje ct t o d ege n -
e ra t ion or ca n be a ffe ct e d by in a m m a t ory a rt h rit is . Pa in a ris in g from a rt h rit is
in t h e s e join t s t yp ica lly is e xa ce rba t e d by e xt e n s ion of t h e n e ck. For p a t ie n t s
w it h foca l p os t e rior n e ck p a in , in je ct ion of loca l a n e s t h e t ic in t o t h e fa ce t join t is
s om e t im e s u s e d t o con rm t h e join t a s t h e ge n e ra t or of p a in s ym p t om s . Os t e o-
p h yt e s a ris in g from u n cove rt e bra l join t s ca n ca u s e a n t e rior n a rrow in g of t h e
in t e rve rt e bra l fora m in a a n d os t e op h yt e s a ris in g from t h e fa ce t join t s ca n ca u s e
p os t e rior n a rrow in g of t h e in t e rve rt e bra l fora m in a , w h ich in e it h e r ca s e ca n
con t ribu t e t o ce rvica l s p in a l n e rve com p re s s ion ca u s in g ra d icu la r s ym p t om s .
Th e liga m e n t u m avu m join s a d ja ce n t la m in a e ; t h icke n in g of t h is liga m e n t by
d ege n e ra t ive p roce s s e s ca n con t ribu t e t o s p in a l s t e n os is a n d t o s p in a l cord in ju -
rie s in p a t ie n t s w it h s p on dylos is w h o s u ffe r a h yp e re xt e n s ion in ju ry of t h e n e ck.
A t ra n s ve rs e p roce s s off t h e s id e of t h e a rch in t h e a re a of e a ch la t e ra l bod y
a n d a m id lin e p os t e rior s p in ou s p roce s s s e rve a s a n ch or leve rs for m u s cu la t u re
S
a n d liga m e n t s . An in t ra s p in ou s liga m e n t join s a d ja ce n t s p in ou s p roce s s e s a n d
E
C
h e lp s p reve n t h yp e r e xion of t h e n e ck. Th e t ra n s ve rs e p roce s s from C1 t o C6
T
I
O
a ls o h a s a t ra n s ve rs e fora m e n w h e re t h e ve rt e bra l a rt e ry cou rs e s u n t il it e n t e rs
N
t h e s ku ll; in s om e p a t ie n t s e xt re m e e xt e n s ion of t h e n e ck h a s be e n s h ow n t o
2
le a d t o occlu s ion of t h e ve rt e bra l a rt e ry.
R
e
Th e re a re e igh t ce rvica l s p in a l n e rve s w it h e a ch ce rvica l n e rve root e xit in g
g
i
o
t h rou gh t h e in t e rve rt e bra l fora m in a a bove it s corre s p on d in g ve rt e bra e xce p t
n
a
C8 w h ich e xit s be t w e e n C7 a n d T1. Ea ch ce rvica l s p in a l n e rve is form e d from
l
P
a n a n t e rior root a ris in g from m ot or n e u ron s in t h e ve n t ra l h orn of t h e s p in a l
a
i
cord a n d a p os t e rior root t h a t ca rrie s a ffe re n t s e n s ory be rs from t h e d ors a l
n
S
ro o t ga n glio n . Aft e r e x it in g t h ro u gh t h e in t e r ve rt e b ra l fo ra m in a , t h e s p in a l
y
n
n e rve s s p lit in t o a n t e rior a n d p os t e rior ra m i. Th e a n t e rior ra m i form t h e bra -
d
r
o
ch ia l p le xu s a n d p rovid e m ot or in n e rva t ion t o t h e p reve rt e bra l a n d p a rave rt e -
m
bra l m u s cle s , w h e re a s t h e p os t e rior ra m i p rovid e m ot or a n d s e n s ory fu n ct ion
e
s
o f t h e p o s t e r io r n e ck m u s cle s , b on e s , a n d s k in . Te m p o ra ry a n d p e r m a n e n t
blocks of t h e m e d ia l bra n ch of t h e p os t e rior ra m i ca n be u s e d t o d ia gn os e a n d
t re a t p a in a ris in g from p os t e rior n e ck s t ru ct u re s .
Sin ce t h e m a jor s t ru ct u re s of t h e p os t e rior n e ck a re t h e s p in a l colu m n a n d
it s con t e n t s a n d t h e s u p p ort in g m u s cu la t u re, it ca n be h e lp fu l t o e licit m ore
d e t a ile d h is t ory a bou t p rior s p in a l colu m n con d it ion s s u ch a s lu m ba r d ege n -
e ra t ive d is k d is e a s e, d ege n e ra t ive join t d is e a s e, ra d icu lop a t h y, or n on s p e ci c
low ba ck p a in . It ca n a ls o be h e lp fu l t o in q u ire a bou t e rgon om ic p os it ion s of t h e
n e ck d u rin g w ork or s le ep a n d t h e e ffe ct of p os it ion a l or p os t u ra l ch a n ge s on
s ym p t om s . For p a t ie n t s w it h on s e t of n e ck p a in a ft e r t ra u m a , it is im p ort a n t t o
obt a in a d e t a ile d h is t ory of t h e eve n t t o h e lp e s t im a t e t h e a m ou n t , d ire ct ion ,
a n d loca t ion of m a jor force s a ct in g on t h e n e ck a n d a n y p rot e ct ive or re s t ra in t
s ys t e m s s u ch a s s e a t be lt s or h e a d re s t s in m ot or ve h icle s t h a t m ay h ave m it i-
ga t e d t h e im p a ct of t h e force s ; t h is d e t a ile d d a t a ca n h e lp d e t e rm in e t h e like li-
h ood of s e riou s m u s cu los ke le t a l or n e u rologic in ju rie s . In p a t ie n t s w it h p ot e n -
t ia l m a jor t ra u m a t o t h e h e a d or t h e n e ck, t h e n e ck s h ou ld be im m obilize d u n t il
t h e p os s ibilit y of u n d e rlyin g ce rvica l fra ct u re or s p in a l in s t a bilit y is ru le d ou t .
De s p it e a d e t a ile d h is t ory, it ca n be d if cu lt t o loca lize n e ck p a in t o a s p e -
ci c a n a t om ic s ou rce. Ne ck p a in m ay be re fe rre d from m u lt ip le orga n s or a re a s
in clu d in g t h e h e a rt , bra ch ia l p le xu s , ja w or e s op h a gu s , u p p e r t h ora x, or t h e
s h ou ld e r gird le or u p p e r a rm . Eve n for p a in origin a t in g from s om a t ic n e rve s ,
p a t ie n t s u s u a lly p re s e n t w it h n on foca l p a in m a kin g it d if cu lt t o p in p oin t t h e
in cit in g a n a t om ic p a t h ology, a n d d ege n e ra t ive ch a n ge s on im a gin g s t u d ie s h ave
ve ry p oor corre la t ion w it h t h e p re s e n ce or s eve rit y of p a t ie n t s ym p t om s . Th e re -
fore, d ia gn os t ic s p e ci cit y in t h e eva lu a t ion of n e ck p a in re lie s on re cogn it ion

PATIENT ASSESSMENT
• Th e h ist o ry sh o u ld in clu d e
t h e e le m e n t s o f a ll b a sic
p a in h ist o rie s, p lu s d e t a ils
a b o u t a n y p re ce d in g t ra u -
m a , a h ist o ry o r risk fa ct o rs
fo r in fe ct io n o r ca n ce r,
a n d a n y co n st it u t io n a l o r
n e u ro lo g ic sym p t o m s.
• Th e p h ysica l e xa m in a t io n
sh o u ld scre e n fo r n e u ro -
lo g ic a b n o rm a lit ie s o f t h e
u p p e r a n d lo w e r e xt re m i-
t ie s; sp e cia lize d m a n e u ve rs
m a y a d d a d d it io n a l se n si-
t ivit y a n d sp e ci cit y t o t h e
e xa m in a t io n .
• Th e n e e d fo r a n d t h e t yp e
o f d ia g n o st ic t e st in g a re
d e t e rm in e d b y t h e w o rk-
in g d iffe re n t ia l d ia g n o sis
a ft e r a ca re fu l h ist o ry a n d
p h ysica l e xa m in a t io n .
• Pa t ie n t s w it h a xia l n e ck
p a in w it h o u t n e u ro lo g ic
sym p t o m s o r sig n s a n d
w h o a re n o t su sp e ct e d
o f h a vin g a n e m e rg e n t
o r se rio u s u n d e rlyin g
co n d it io n d o n o t re q u ire
in it ia l im a g in g .
• An u n d e rst a n d in g o f
ce rvica l sp in a l a n a t o m y
is re q u ire d t o a llo w in t e r-
p re t a t io n o f im a g in g
n d in g s a n d re p o rt s.
Ch a p te r 2 Ne ck Pa in 15
of p a t t e rn s of s ym p t om s , s ign s , a n d t e s t re s u lt s , w h ile e xclu d in g e m e rge n t or
o t h e r s e rio u s u n d e rlyin g con d it ion s . In p a rt icu la r, p a t ie n t s s h ou ld be a s ke d
a b o u t co n s t it u t io n a l s ym p t o m s a n d ris k fa ct o r s fo r in fe ct io n s , h is t o ry o f o r
s ym p t om s of m a lign a n cy, p rior t ra u m a , a n d s ym p t om s s u gge s t ive of m ye lop a -
t h y s u ch a s clu m s in e s s of t h e h a n d s , w e a kn e s s of t h e a rm s , bow e l or bla d d e r
d ys fu n ct ion , low e r e xt re m it y w e a kn e s s or n u m bn e s s , or ga it p roble m s . Pa in
from t u m or or in fe ct ion s is t yp ica lly con s t a n t a n d p rogre s s ive a n d u n re lieve d
by re s t or ch a n ge in p os it ion . W h e n m orn in g s t iffn e s s is a p rom in e n t s ym p t om ,
a rh e u m a t ologic con d it ion s u ch a s rh e u m a t oid a rt h rit is , a n kylos in g s p on d ylit is ,
or p olym ya lgia rh e u m a t ic s h ou ld be con s id e re d .
Physica l Exa mina tio n
Th e p h ys ica l e xa m in a t ion of a p a t ie n t w it h n e ck p a in s h ou ld s t a rt w it h ge n e ra l
e le m e n t s s u ch a s review o f vit a l s ign s a n d o b s e rva t io n o f p a t ie n t p o s t u re ,
m ove m e n t , a n d ga it . Pre s e n ce o f feve r s h o u ld ra is e s u s p icio n o f in fe ct io n —
p a rt icu la rly in IV d ru g a bu s e rs , p a t ie n t s w it h va s cu la r a cce s s d evice s , or im m u -
n ocom p rom is e d h os t s . Abn orm a l ca rryin g p os it ion s of t h e n e ck m ay be d u e t o
s
e it h e r a p rim a ry u n d e rlyin g m u s cu los ke le t a l a bn orm a lit y or a re e x s p a s m of
e
m
t h e p os t e rior n e ck m u s cle s . In e it h e r ca s e, s p on t a n e ou s m ove m e n t of t h e h e a d
o
r
is t yp ica lly re d u ce d . It is im p ort a n t t o obs e rve for a s p a s t ic ga it t h a t m a y origi-
d
n
n a t e from ce rvica l s p in a l cord d ys fu n ct ion .
y
S
Exa m in a t ion s h ou ld t h e n focu s on in s p e ct ion a n d p a lp a t ion o f t h e n e ck
n
i
a
w it h s p e cia l a t t e n t ion t o t h e a re a of m a xim a l s ym p t om s . It is oft e n h e lp fu l t o
P
h a ve t h e p a t ie n t s p oin t t o t h e s p e ci c a re a w h e re t h ey a re e xp e rie n cin g s ym p -
l
a
n
t om s a n d h a ve t h e m p oin t ou t a n y a bn orm a lit ie s t h a t t h ey h a ve p e rce ive d .
o
i
Ra s h e s or bru is e s m ay s u gge s t zos t e r or p rior t ra u m a , re s p e ct ive ly. For p a t ie n t s
g
e
R
re p or t in g a n t e rio r n e ck p a in , rs t in s p e ct t h e a n t e rior ce rvica l t ria n gle bor-
2
d e re d by t h e s t e rn ocle id om a s t oid m u s cle, m a n d ible, a n d s t e rn a l n ot ch on e a ch
N
s id e lookin g for d e form it ie s a n d a s ym m e t ry; a n d t h e n bot h p os t e rior ce rvica l
O
I
T
t ria n gle s bord e re d by t h e s t e r n ocle id o m a s t oid , cla vicle , a n d t ra p e ziu s . Bo t h
C
E
a re a s s h ou ld t h e n be p a lp a t e d for loca lize d t e n d e rn e s s . Th e m u s cle bod ie s a n d
S
t h e ir u n d e rlyin g s t ru ct u re s s h ou ld be p a lp a t e d a n d t h e p re s e n ce of lym p h a d -
e n op a t h y or m a s s e s d e t e rm in e d . For p a t ie n t s w it h re s p ira t ory s ym p t om s or
d ys p h a gia , t ra ch e a l loca t ion , a n d t h yroid s ize, s h a p e, loca t ion , a n d m ove m e n t
w it h sw a llow s h ou ld be n ot e d . Th e ve s s e ls of t h e n e ck s h ou ld be obs e rve d a n d
t h e ca rot id p u ls e p a lp a t e d . A s cre e n in g ca rd iop u lm on a ry e xa m in a t ion s h ou ld
a ls o be d on e s in ce n e ck p a in m a y be re fe rre d from in t ra t h ora cic s t ru ct u re s .
For p a t ie n t s w it h p os t e rior n e ck p a in , begin t h e e xa m in a t ion w it h in s p e c-
t ion of t h e ce rvica l s p in ou s p roce s s e s by lookin g a t t h e ir a lign m e n t a n d n ot in g
a n y d e form it ie s . Als o look for d e form it y or a s ym m e t ry of t h e p a ra ce rvica l m u s -
cle s , s ca p u la , a n d s u rrou n d in g m u s cle s . Th e n p a lp a t e t h e s p in ou s p roce s s e s a n d
p os t e rior n e ck s oft t is s u e s a n d m u s cu la t u re from t h e occip it a l in s e rt ion s t o t h e
in fe rior a n gle of t h e s ca p u la a n d la t e ra lly ou t t o t h e s h ou ld e rs lookin g for p oin t
t e n d e rn e s s a n d s p a s m . Th e a s s ocia t e d leve l of a n y s p in ou s t e n d e rn e s s , d e form -
it y, or s t ep -off s h ou ld be n ot e d ; t h e p rom in e n t C7 s p in ou s p roce s s ca n be u s e d
a s a p oin t of re fe re n ce ; p oin t t e n d e rn e s s a t a p a rt icu la r leve l w a rra n t s fu rt h e r
in ve s t iga t ion w it h im a gin g. For p a t ie n t s w it h m ore t h a n on e p oin t of m u s cu la r
t e n d e rn e s s , a s e a rch for a n y t rigge r p oin t s in ot h e r body a re a s is w a rra n t e d .
Th e a ct ive a n d p a s s ive ra n ge s of m ot ion of t h e n e ck s h ou ld t h e n be obs e rve d .
Fu ll ce rvica l s p in e ra n ge of m ot ion in you n g a d u lt s is 60 d egre e s of e xion ,
75 d egre e s of e xt e n s ion , 45 d egre e s of la t e ra l be n d t o e a ch s id e, a n d 90 d egre e s
of rot a t ion t o e a ch s id e. In p a t ie n t s old e r t h a n 50 ye a rs , ext e n s ion is re d u ce d t o
60 d egre e s a n d la t e ra l be n d is re d u ce d t o 30 d egre e s (4 ). Pos it ion s t h a t a ggrava t e
or a llevia t e t h e n e ck p a in or it s ra d ia t ion s h ou ld be n ot e d . Ne ck m u s cle s t re n gt h
t e s t in g s h ou ld t h e n be d on e. Th e s t e rn ocle id om a s t oid s a re t h e m a in exors a n d
rot a t ors of t h e n e ck, w h ile t h e m a in e xt e n s ors a re t h e p a rave rt e bra l m u s cle s
 16 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

C1
C2

C3

C4

C5
T1
T2
C6

C7 C8

C6
C7
C8
S
T1
E
C
T2
T
I
O
N
2
Figure 2.2 Derma tomes of the cervica l spine.
R
e
g
i
o
n
a n d t h e t ra p e zii. Th e exors a re t e s t e d by p u t t in g a h a n d be low t h e ch in ; t h e
a
l
e xt e n s ors a re t e s t e d by p la cin g a h a n d on t h e occip u t w h ile t h e ot h e r h a n d
P
a
h old s t h e s h ou ld e r, a n d t h e rot a t ors a re t e s t e d by p u t t in g a h a n d on t h e s id e of
i
n
t h e ch in ; t h e t ra p e zii ca n be t e s t e d by a s kin g t h e p a t ie n t t o s h ru g h e r s h ou ld e rs
S
y
a ga in s t re s is t a n ce. Rep rod u ct ion or a ggrava t ion of s ym p t om s d u rin g s t re n gt h
n
d
t e s t in g s u gge s t s a p os s ible m u s cu los ke le t a l e t iology of t h e p a in .
r
o
m
A d e t a ile d n e u rologic e xa m in a t ion of t h e u p p e r e xt re m it ie s s h ou ld t h e n be
e
d on e t o h e lp d e t e ct a n a s s ocia t e d ra d icu lop a t h y or m ye lop a t h y. For p a t ie n t s
s
w it h a re a s of s e n s ory d e cit s , d e rm a t om e ch a rt s ca n be u s e d t o d e t e rm in e t h e
m a t ch of t h e n d in gs t o a n a s s ocia t e d corre s p on d in g ce rvica l n e rve root leve l
(Fig. 2.2 ). W h e n t e s t in g for m ye lop a t h y, in clu d e ligh t t ou ch a n d p rop riocep t ion
t e s t in g t o a s s e s s p os t e rior s p in a l cord fu n ct ion a n d t e m p e ra t u re a n d p in p rick
t e s t in g t o a s s e s s a n t e rola t e ra l s p in a l cord fu n ct ion . Alt h ou gh t h e m a t ch of ce r-
vica l n e rve root s t o in d ivid u a l m u s cle s is ve ry n on s p e ci c, s e le ct e d m ot or t e s t -
in g ca n h e lp loca lize a n in volve d ce rvica l n e rve leve l, e s p e cia lly if t h e p a t t e rn
co r ro b o ra t e s a d e r m a t o m a l p a t t e r n o f s e n s o ry lo s s (s e e Ta ble 2.1 ). Mu s cle
s t re n gt h s h ou ld be gra d e d on t h e s t a n d a rd 0 t o 5 s ca le :
0. No con t ra ct ion
1. Vis ible t w it ch bu t n o join t m ove m e n t
2. Able t o m ove join t w it h gravit y e lim in a t e d
3. Join t m ove m e n t a ga in s t gravit y bu t n ot a ga in s t re s is t a n ce
4. Join t m ove m e n t a ga in s t s om e re s is t a n ce
5. Join t m ove m e n t a ga in s t fu ll re s is t a n ce
Bra ch iora d ia lis , bicep s , a n d t ricep s d e ep t e n d on re e xe s s h ou ld be ch e cke d
a n d gra d e d u s in g t h e s t a n d a rd s ca le :
0. Abs e n t
1. Tra ce
2. Norm a l
3. Bris k
4. 3 be a t s clon u s
5. Su s t a in e d clon u s
 Ch a p te r 2 Ne ck Pa in 17

Table 2.1 Localizing Neurologic Sympt oms and Signs Associat ed wit h Cervical
Nerve Root s

ROOT PAIN NUMBNESS WEAKNESS AFFECTED REFLEX

C4 Up p e r n e ck Up p e r p o st e rio r a n d No n e No n e
a n t e rio r n e ck
C5 Ne ck, sca p u la , sh o u ld e r, An t e ro la t e ra l a sp e ct Sh o u ld e r a b d u ct io n Bice p s, b ra ch io ra d ia lis
a n t e rio r a rm o f a rm
C6 Ne ck, sca p u la r, sh o u ld e r, La t e ra l a sp e ct o f a rm Fo re a rm e xio n Bice p s, b ra ch io ra d ia lis
la t e ra l a rm , a n d fo re a rm a n d fo re a rm in t o t h u m b
in t o 1st , 2n d d ig it s
C7 Ne ck, sh o u ld e r, la t e ra l a rm , Po st e ro la t e ra l a sp e ct Trice p s, ra d ia l w rist Trice p s
m e d ia l sca p u la , e xt e n so r o f a rm a n d fo re a rm e xt e n so rs, a n d
su rfa ce fo re a rm in t o 3rd a n d d o rsu m h a n d in t o e xo r ca rp i ra d ia lisa
d ig it 3rd d ig it
C8 Ne ck, m e d ia l sca p u la , m e d ia l Dist a l m e d ia l fo re a rm , Fle xo r d ig it o ru m Fin g e r e xo rs
a sp e ct a rm , a n d fo re a rm in t o la t e ra l h a n d in t o 4t h , su b lim is t o rin g
n g e rb

s
4t h , 5t h d ig it s 5t h d ig it s

e
m
o
a
Wrist e xt e n so r t e st in g : Fle x n g e rs t o e lim in a t e w rist e xt e n sio n b y n g e r e xt e n so rs a n d t h e n e xt e n d w rist in ra d ia l d ire ct io n . Fle xo r ca rp i ra d ia lis

r
d
t e st in g : Ext e n d n g e rs t o e lim in a t e w rist e xio n b y n g e r e xo rs a n d t h e n e x w rist in ra d ia l d ire ct io n .

n
y
b
Fle xo r d ig it o ru m su b lim is t o rin g n g e r t e st in g : St a b ilize lo n g , in d e x, a n d lit t le n g e rs in e xt e n sio n a n d e x n g e rs.

S
n
i
a
P
l
a
n
o
W h e n s e n s ory a n d m ot or a bn orm a lit ie s a re fou n d bu t t h e ir p a t t e rn s d o n ot

i
g
NOT TO BE MISSED t w e ll w it h a s p e ci c ra d icu la r p a t t e rn , com m on u p p e r e xt re m it y p e rip h e ra l

e
R
n e u rop a t h ie s s h ou ld be e xp lore d a s a p ot e n t ia l e t iology for t h e n d in gs . Te s t s

2
• Sp in a l in st a b ilit y d u e t o

N
for u p p e r m ot or n e u ron s ign s s u ch a s Hoffm a n ’s a n d Ba bin s ki’s re e xe s a n d a n
fra ct u re s o r so ft t issu e

O
e xa m in a t ion of low e r e xt re m it y m ot or s t re n gt h a n d t on e s h ou ld a ls o be d on e

I
T
in ju ry d u e t o t ra u m a o r

C
in a m m a t o ry co n d it io n s t o s cre e n for ce rvica l m ye lop a t h y.

su ch a s rh e u m a t o id
a rt h rit is.
• Sp in a l co rd co m p re ssio n
o r im p e n d in g co m p re ssio n
d u e t o in fe ct io n , ca n ce r,
a n d d e g e n e ra t ive o r
co n g e n it a l co n d it io n s.
• Pa in t h a t is a risin g fro m
visce ra l o rg a n s su ch a s
t h e h e a rt , va scu la t u re ,
lu n g s, o r g a st ro in t e st in a l
t ra ct t h a t is re fe rre d t o
t h e n e ck.
• Syst e m ic in fe ct io u s
(e .g ., m e n in g it is) o r
in a m m a t o ry (e .g .,
t e m p o ra l a rt e rit is)
co n d it io n s t h a t m a y
p re se n t w it h n e ck p a in
a s a n e a rly sym p t o m .
• Pro g re ssive n e u ro lo g ic
co n d it io n s t h a t m a y
p ro d u ce sym p t o m s t h a t
a re sim ila r t o t h o se
se e n w it h sp in a l co rd
co m p re ssio n o r sp in a l
n e rve co m p re ssio n .
E
S
Seve ra l s p e cia lize d m a n e u ve rs a re oft e n re com m e n d e d t o fu rt h e r eva lu a t e
for p os s ible ra d icu lop a t h y or m ye lop a t h y. Sp u rlin g’s t e s t in volve s p la cin g t h e
n e ck in p o s it io n s t h a t re d u ce t h e d ia m e t e r o f t h e ce r vica l in t e r ve r t e b ra l
fora m in a w h ich m a y ca u s e com p re s s ion of t h e s p in a l n e rve ; t h e t e s t is con s id -
e re d p o s it ive if ra d icu la r s ym p t o m s a re e licit e d w h e n t h e p a t ie n t ’s n e ck is
e xt e n d e d a n d rot a t e d t ow a rd t h e s ym p t om a t ic s id e. Th e com p le m e n t a ry t e s t
t h a t a t t e m p t s t o m a xim iz e t h e fo ra m in a l op e n in g is ca lle d t h e “d is t ra ct io n
t e s t .” Th e p a t ie n t is p la ce d s u p in e a n d t h e e xa m in e r t h e n ge n t ly p u lls on t h e
h e a d ; re lie f o f s ym p t o m s s u gge s t s u n d e r lyin g ce r vica l ra d icu lo p a t h y. Th is
m a n e u ve r s h ou ld n ot be d on e in p a t ie n t s w h o m igh t h ave u n d e rlyin g s p in a l
in s t a bilit y. Bot h t e s t s h a ve low s e n s it ivit y, bu t fa ir s p e ci cit y, yie ld in g a p os it ive
like lih ood ra t io of 3 a n d a n ega t ive like lih ood ra t io of 0.6 (5 ). A la n cin a t in g p a r-
e s t h e s ia w it h n e ck e xion , t e rm e d “Lh e rm it t e ’s s ign ,” m a y be s e e n w it h com -
p re s s ion of t h e s p in a l cord in p a t ie n t s w it h s p in a l s t e n os is .
Studie s
Fu rt h e r d ia gn os t ic t e s t in g is n e e d e d w h e n t h e h is t ory or p h ys ica l e xa m in a t ion
u n cove rs p os s ible e m e rge n t o r s e riou s u n d e rlyin g con d it ion s ; w h e n t h e p a t -
t e rn or s eve rit y of p a in or a s s ocia t e d s ym p t om s s u gge s t t h e n e e d for t re a t -
m e n t s ot h e r t h a n a n a lge s ics , re s t , or p h ys ica l t h e ra py; or w h e n t h e re m ay be
e xt e n u a t in g n on m e d ica l is s u e s s u ch a s w or k, a ccid e n t , or d is a bilit y-re la t e d
cla im s . Im a gin g s h ou ld be obt a in e d in p a t ie n t s w it h a h is t ory of t ra u m a , con -
s t it u t ion a l s ym p t om s , u n d e rlyin g s ys t e m ic illn e s s e s in clu d in g ca n ce r or in fe c-
t ion , or n e u rologic s ym p t om s , a n d s h ou ld be con s id e re d in p a t ie n t s old e r t h a n
 18 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

50 ye a rs w it h n ew on s e t of p a in a n d in p a t ie n t s w it h ch ron ic p a in p e rs is t in g
m ore t h a n 6 w e e ks d e s p it e con s e rva t ive t h e ra p ie s .
Th e t yp e of t e s t in g d ep e n d s on t h e w orkin g d iffe re n t ia l d ia gn os is a ft e r t h e
h is t ory a n d p h ys ica l e xa m in a t ion , e s p e cia lly for p a t ie n t s p re s e n t in g w it h a n t e -
rior n e ck p a in , s in ce a n t e rior s ym p t om s a re n ot t yp ica lly ca u s e d by s p in a l-
re la t e d con d it ion s . In a d d it ion t o t e s t in g re la t e d t o s p e ci c d ia gn os e s s u gge s t e d
by t h e h is t ory a n d p h ys ica l e xa m in a t ion , if a n u n d e rlyin g s ys t e m ic illn e s s is
s u s p e ct e d , a s cre e n in g CBC w it h d iffe re n t ia l, ESR a n d /or C re a ct ive p rot e in , a n d
a lka lin e p h os p h a t a s e s h ou ld be obt a in e d .
Ne ck p a in p a t ie n t s w h o re p or t a h is t ory of t ra u m a s h o u ld h a ve fu rt h e r
eva lu a t io n w it h im a gin g. For p a t ie n t s w it h m ild or m od e ra t e t ra u m a , h igh -
q u a lit y ce rvica l s p in e p la in ra d iogra p h s h ave a d e q u a t e s e n s it ivit y t o e xclu d e
s e riou s u n d e rlyin g fra ct u re, bu t it is im p ort a n t t o re m e m be r t h a t s e n s it ivit y for
fra ct u re d e t e ct ion ca n be re d u ce d in p a t ie n t s w it h os t e op e n ia or p rior ce rvica l
s p in e s u rge rie s . Th e fu ll ce rvica l s p in e s e rie s in t h e n e u t ra l p os it ion in clu d e s
la t e ra l a n d PA view s a n d a n od on t oid view w h ich is obt a in e d w it h t h e m ou t h
op e n t o e lim in a t e t e e t h ove rlyin g t h e a re a of C1-C2 a n d a llow a d e q u a t e vis u -
a liza t ion of t h e od on t oid p roce s s . If fra ct u re is ru le d ou t , le ft a n d righ t obliq u e
S
view s a re obt a in e d t o com p le t e t h e s e rie s . In s om e p a t ie n t s , it m ay be d if cu lt
E
C
t o ge t a d e q u a t e view s of e it h e r C1 or C7; in fa ct , in a d e q u a t e vis u a liza t ion of C7
T
I
O
is t h e m o s t co m m o n e r ro r m a d e in t h e x -ra y a s s e s s m e n t o f ce rvica l s p in e
N
in ju ry. PA a n d la t e ra l view s s h ow t h e h om oge n e it y, h e igh t , a n d a lign m e n t of
2
t h e ve rt e b ra l bo d ie s a n d t h e in t e r ve r t e bra l d is cs , a n d t h e la t e ra l view a ls o
R
e
s h ow s t h e s p in ou s p roce s s e s a n d fa ce t join t s a n d a llow s e s t im a t ion of t h e p re -
g
i
o
ve rt e bra l s oft t is s u e w id t h w h ich m ay be in cre a s e d in p a t ie n t s w it h a re la t e d
n
a
ve rt e bra l fra ct u re or p reve rt e bra l s oft t is s u e in ju ry; obliq u e view s a re be t t e r for
l
P
vis u a liz in g t h e in t e r ve r t e b ra l fo ra m in a . If t h e re a re co n ce r n s a b o u t s p in a l
a
i
in s t a bilit y d u e t o s oft t is s u e in ju ry or a n u n d e rlyin g in a m m a t ory con d it ion
n
S
s u ch a s rh e u m a t oid a rt h rit is , t h e n la t e ra l e xion a n d e xt e n s ion view s ca n be
y
n
obt a in e d if t h e n e u t ra l p os it ion view s e xclu d e fra ct u re. In ge n e ra l, it is d if cu lt
d
r
o
t o fu lly eva lu a t e a ll e le m e n t s of t h e p os t e rior ve rt e bra l a rch w it h p la in lm s
m
be ca u s e of s u m m a t ion e ffe ct s of ove rlyin g s h a d ow s . For p a t ie n t s w it h a h is t ory
e
s
of p os s ibly s eve re t ra u m a or t ra u m a p a t ie n t s w it h a n y n e u rologic s ign s s u gge s -
t ive of ra d icu lop a t h y or m ye lop a t h y, t h e h igh e r s e n s it ivit y of ce rvica l com p u t e d
t om ogra p h y (CT) or m a gn e t ic re s on a n ce im a gin g (MRI) is n e e d e d t o ru le ou t
occu lt fra ct u re s a n d ce rvica l s p in a l cord or s oft t is s u e in ju rie s .
For p a t ie n t s w it h p os t e rior n e ck p a in , t h e p a t t e rn of s ym p t om s a n d n d in gs
ca n d ire ct t h e t yp e of s u bs e q u e n t t e s t in g. Im a gin g of ch ron ic p a in t h a t h a s n ot
re s p on d e d t o con s e rva t ive m e a s u re s a n d is loca lize d t o t h e a xia l a n d p a ra s p i-
n a l a re a w it h ou t a n y ra d ia t ion or a s s ocia t e d s ym p t om s s u gge s t ive of ra d icu -
lop a t h y or m ye lop a t h y s h ou ld s t a rt w it h a ce rvica l s p in e s e rie s . X-rays w ill fre -
q u e n t ly s h ow s ign s of d ege n e ra t ive d is e a s e of t h e in t e rve rt e bra l d is cs or fa ce t
join t s a n d /or n a rrow in g of t h e in t e rve rt e bra l fora m in a . In fa ct , in a s ym p t om a t ic
p a t ie n t s old e r t h a n 40 ye a rs , ce rvica l d ege n e ra t ive ch a n ge s (s p on d ylos is ) a re
com m on , a n d a ft e r t h e a ge of 50 ye a rs , ce rvica l s p on d ylos is is p re s e n t in m ore
t h a n 90% of in d ivid u a ls (6 ). Th e re fore, t h e s e d ege n e ra t ive ch a n ge s a re re leva n t
on ly if t h ey s p e ci ca lly t w it h t h e re s t of t h e p a t ie n t ’s s ym p t om s a n d s ign s .
For p a tien ts w ith ra d icu la r sym p tom s a n d con sisten t p h ysica l exa m in a tion
n d in gs, fu rth er testin g cou ld be d eferred d u rin g a p eriod of in itia l con serva tive
m a n a gem e n t sin ce sym p tom s te n d to a ba t e over tim e; h ow ever, fu rt h er in itia l
eva lu a tion is w a rra n ted if th ere is sign i ca n t w ea kn ess. W h en w ea kn ess is p resen t,
w orku p w ith electrom yogra m ca n con rm th a t th e etiology of th e w ea kn ess is d u e
to cervica l ra d icu lop a th y a n d ca n h elp con rm th e su sp ected n erve root; h ow ever,
electrom yogra p h ic testin g w ill be n orm a l in p a tien ts w ith ou t in volvem en t of th e
m otor p a rt of th e sp in a l n erve. For p a tien ts w ith in con sisten t or u n clea r n eu ro-
logic exa m in a tion n d in gs in th e u p p er extrem ities, electrod iagn ostic testin g ca n
h elp u n cover a n u n d erlyin g p erip h era l or en tra p m en t n eu rop a th y.

WHEN TO REFER
• Pa t ie nt s w it h sp in a l co rd
co m p re ssio n o r in st a b ilit y
should be urge ntly re fe rre d
to a spina l surge on.
• Pa t ie n t s w it h ce rvica l
ra d icu lo p a t h y w it h w e a k-
n e ss o r p e rsist e n t sym p -
t o m s a ft e r a co u rse o f co n -
se rva t ive t h e ra p y ca n b e
re fe rre d fo r e p id u ra l in je c-
t io n s o r sp in a l su rg e ry.
• Pa t ie n t s w it h ce rvica l st ra in
ca n b e re fe rre d t o p h ysica l
t h e ra p y fo r in st ru ct io n in
h o m e e xe rcise s, p o st u re ,
e rg o n o m ics, a n d p o ssib le
a ct ivit y m o d i ca t io n s.
• Pa t ie n t s w h o a re fe lt t o
h a ve p a in a risin g fro m a
d e g e n e ra t ive fa ce t jo in t
w h o h a ve p e rsist e n t p a in
d e sp it e co n se rva t ive
m e a su re s ca n b e re fe rre d
fo r d ia g n o st ic fa ce t jo in t
in je ct io n , m e d ia l b ra n ch
b lo ck, a n d /o r p e rcu t a n e o u s
n e u ro t o m y.
• Pa t ie n t s fo u n d t o h a ve
syst e m ic co n d it io n s p re -
se n t in g w it h n e ck p a in
m a y n e e d t o b e re fe rre d t o
a p pro p ria t e sp e cia list s fo r
d ia g n o st ic co n rm a t io n
and management.
Ch a p te r 2 Ne ck Pa in 19
Pa t ie n t s w it h p os s ible m ye lop a t h y, in fe ct ion , or m a lign a n cy re q u ire eva lu -
a t ion w it h e it h e r CT or MRI. Com p u t e d t om ogra p h ic s ca n p rovid e s e xce lle n t
im a gin g of os s e ou s s t ru ct u re s a n d re q u ire s le s s t im e t o p e rform bu t in volve s
s ign i ca n t ra d ia t io n e x p o s u re . MRI s ca n n in g p rovid e s e x ce lle n t s oft t is s u e
d e t a il a n d ca n p rovid e be t t e r d e t a il of s p in a l cord ch a n ge s , bu t it ca n n ot be
p e rform e d in p a t ie n t s w it h ce rt a in im p la n t s or e m be d d e d fe rrom a gn e t ic m a t e -
ria ls . Non con t ra s t MRI is a d e q u a t e for m os t s it u a t ion s , bu t con t ra s t MRI h a s
be t t e r s e n s it ivit y for t u m ors , in fe ct ion , a n d p os t s u rgica l ep id u ra l bros is ; h ow -
eve r, ga d olin iu m con t ra s t s h ou ld n ot be u s e d in p a t ie n t s w it h s ign i ca n t re n a l
d ys fu n ct io n be ca u s e o f t h e p os s ible co m p lica t io n o f n e p h roge n ic s ys t e m ic
s cle ros is . Com p u t e d t om ogra p h ic m ye logra m m ay be n e ce s s a ry if fu rt h e r eva l-
u a t ion is n e e d e d t o ru le ou t s p in a l cord com p re s s ion be ca u s e com p u t e d t om o-
gra p h ic or MRI n d in gs a re e q u ivoca l, w h e n cord com p re s s ion is s u s p e ct e d a t
m u lt ip le leve ls , a n d w h e n s u rgica l d e com p re s s ion is be in g con s id e re d . Un for-
t u n a t e ly, a s is t h e ca s e for C s p in e x-rays , t h e re ca n be p oor corre la t ion of MRI
a bn orm a lit ie s w it h n e ck p a in s ym p t om s . Fin d in gs of d is c h e rn ia t ion m a y be
s e e n in u p t o 50% of a s ym p t om a t ic old e r in d ivid u a ls a n d s p in a l cord com p re s -
s io n in u p t o 25% (7 ). Th e re fore, im a gin g s ym p t om s m u s t be ca re fu lly corre -
s
la t e d w it h t h e h is t o ry, p h ys ica l e x a m in a t io n , a n d o t h e r d ia gn o s t ic t e s t in g
e
m
be fore m a kin g a clin ica l d ia gn os is of ce rvica l m ye lop a t h y.
o
r
Bon e s ca n is ra re ly d on e in t h e eva lu a t ion of p a t ie n t s w it h n e ck p a in , s in ce
d
n
bot h CT a n d MRI h ave e xce lle n t s e n s it ivit y for in fe ct ion a n d t u m or. Th e p h ys i-
y
S
ologic in form a t ion of bon e s ca n ca n s om e t im e s be h e lp fu l t o con rm a s p e ci c
n
i
fa ce t join t a s a n u n d e rlyin g p a in ge n e ra t or; a d ia gn os t ic in je ct ion of loca l a n e s -
a
P
t h e t ic in t o t h e s u s p e ct join t ca n t h e n be d on e t o s e e w h e t h e r t h e p a t ie n t ’s p a in
l
a
n
is e lim in a t e d . Com bin e d bon e a n d ga lliu m s ca n s a re s om e t im e s n e ce s s a ry t o
o
i
eva lu a t e for p os s ible in fe ct ion in p a t ie n t s w it h s p in a l h a rd w a re, w h ich d is t ort s
g
e
R
com p u t e d t om ogra p h ic a n d MR im a ge s .
2
N
Tre a tme nt
O
I
T
C
E
In it ia l t re a t m e n t of n e ck p a in d e p e n d s on t h e re m a in in g d iffe re n t ia l d ia gn os is
S
a ft e r h is t o ry, p h ys ica l e xa m in a t ion , a n d in d ica t e d d ia gn os t ic s t u d ie s . Tre a t -
m e n t is d ire ct e d a t t h e u n d e rlyin g con d it ion for p a t ie n t s w it h a s p e ci c con -
rm e d d ia gn os is . For e xa m p le, p a t ie n t s fou n d t o h ave in t e rve rt e bra l d is cit is or
ce rvica l s p in a l os t e om ye lit is a re t re a t e d w it h a p p rop ria t e a n t ibiot ics a ft e r cu l-
t u re s a re o b t a in e d . Pa t ie n t s w it h s p in a l co rd co m p re s s io n d u e t o e p id u ra l
a bs ce s s or ca n ce r s h ou ld be e m e rge n t ly re fe rre d t o n e u ros u rge on s , a n d in t h e
ca s e of m a lign a n t t u m ors a p p rop ria t e ca n ce r s p e cia lis t s , t o h e lp p reve n t w ors -
e n in g of m ye lop a t h y. Pa t ie n t s w it h ce rvica l s p in a l fra ct u re s or in s t a bilit y d u e t o
t ra u m a s h ou ld a ls o be e m e rge n t ly re fe rre d t o n e u ros u rge on s for p os s ible s p i-
n a l s t a biliza t ion . Pa t ie n t s w it h s p in a l cord com p re s s ion d u e t o ce rvica l s p on d -
ylos is or s p in a l s t e n os is s h ou ld a ls o be re fe rre d t o s p in e s u rge on s w h o ca n
p re s e n t t h e p a t ie n t w it h t h e be n e t s a n d ris ks of s u rgica l d e com p re s s ion .
In it ia l t re a t m e n t for p a t ie n t s w it h ou t a n u n d e rlyin g e m e rge n t or s e riou s
co n d it io n is o ft e n a im e d a t s ym p t o m co n t ro l. Pa t ie n t s w it h ce rvica l ra d icu -
lop a t h y a re t yp ica lly t re a t e d con s e rva t ive ly for 6 t o 8 w e e ks . Th e n on p h a rm a -
cologic con s e rva t ive m od a lit ie s m os t fre q u e n t ly u s e d a re avoid a n ce of a ggra -
va t in g a ct ivit ie s a n d t h e n p ro gre s s ive m o b iliz a t io n a n d p h ys ica l t h e ra p y
e xe rcis e s on ce p a in is t ole ra ble. Ce rvica l colla rs m ay be u s e d in t h e s h ort t e rm
if t h ey p rovid e s om e s ym p t om a t ic re lie f, bu t lon g-t e rm u s e s h ou ld be avoid e d ,
s in ce it ca n con t ribu t e t o d is u s e a t rop h y of t h e ce rvica l m u s cu la t u re.
Ph a rm a cologic t re a t m e n t of ce rvica l ra d icu lop a t h y t yp ica lly in clu d es a n a l-
ge s ics s u ch a s n on s t e roid a l a n t i-in a m m a t orie s d ru gs a n d m ay a ls o in clu d e
m u s cle re la xa n t s in p a t ie n t s w it h p a ra s p in a l m u s cle s p a s m d e t e ct e d on exa m i-
n a t ion ; n e u rop a t h ic p a in m e d ica t ion s s h ou ld be con s id ere d in p a t ie n t s w h os e
ra d icu la r s ym p t om s a re n ot con t rolle d w it h s im p le a n a lges ics . Th e s e le ct ion of
 20 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

w h ich a ge n t s t o u s e in e a ch cla s s w ill d ep e n d on p a t ien t com orbid it ies a n d t h eir

ot h e r ch ron ic m e d ica t ion s . Pa t ien t s s h ou ld in it ia lly be s t a rt e d on low d os e s of
t h e s e m e d ica t ion s t o h e lp avoid d os e -re la t ed s id e e ffect s . Sin ce m u s cle re la xa n t s
a n d n eu rop a t h ic p a in m e d icin e s ca n be s e d a t in g, s om e p a t ie n t s n d t h a t a bed -
t im e d os e ca n h e lp t h e m s le ep, bu t t h ey s h ou ld be w a rn e d t o avoid a ct ivit ie s
s u ch a s d rivin g d u e t o p os s ible res id u a l s ed a t ion .
Pa t ie n t s w it h ce rvica l ra d icu lop a t h y w h o h ave p e rs is t e n t s ym p t om s or p ro-
gre s s ive w e a kn e s s s h ou ld be re fe rre d t o a s p in e s u rge on bu t m a y rs t be offe re d
t h e op t ion of a t ria l of e p id u ra l in je ct ion s . A re ce n t ly p u blis h e d ra n d om ize d
con t rolle d t ria l s u gge s t s t h a t a m a jorit y of p a t ie n t s obt a in re lie f a ft e r ep id u ra l
in je ct ion s of a n e s t h e t ic e it h e r w it h or w it h ou t s t e roid , bu t w it h ou t a p la ce bo
con t rol grou p it is d if cu lt t o ru le ou t t h a t t h e obs e rve d im p rove m e n t s w e re
n ot d u e t o t h e n a t u ra l cou rs e of ce rvica l ra d icu lop a t h y (8 ).
Pa t ie n t s w it h p os t e rior n e ck p a in w it h ou t ra d icu la r or m ye lop a t h ic s ym p -
t om s a re m a n a ge d con s e rva t ive ly w it h n on p h a rm a cologic a n d p h a rm a cologic
m e a s u re s . In t h is com m on clin ica l s ce n a rio, loca liza t ion of p a in t o a s p e ci c
u n d e rlyin g e t iology or s p e ci c a n a t om ic p a in ge n e ra t or is oft e n n ot p os s ible.
Th e re fore, t re a t m e n t is a im e d a t s ym p t om con t rol a n d m a in t e n a n ce or re s t o-
S
ra t ion of fu n ct ion . Ph ys ica l t h e ra p y w it h p a t ie n t e d u ca t ion , e xe rcis e s , a n d p os -
E
C
s ibly e rgo n o m ic eva lu a t io n a n d re m e d ia t io n ca n b e p a r t icu la rly h e lp fu l in
T
I
O
im p rovin g n e ck p a in a n d p reve n t in g re cu rre n ce s . Ph a rm a cologic t re a t m e n t of
N
p a t ie n t s w it h n on ra d icu la r p os t e rior a xia l n e ck p a in in clu d e s a n a lge s ics a n d
2
m a y in clu d e m u s cle re la xa n t s in p a t ie n t s w it h p a ra s p in a l m u s cle s p a s m o n
R
e
e xa m in a t ion . In a d d it ion , p a t ie n t s w it h ch ron ic n e ck p a in , w h o oft e n h ave con -
g
i
o
com it a n t d ep re s s ive or brom ya lgia s ym p t om s , m ay ge t a d d it ion a l re lie f w it h
n
a
t h e t ricyclic a n t id e p re s s a n t s a m it rip t ylin e or n ort rip t ylin e, o r t h e s e rot o n in
l
P
n e u roe p in ep h rin e re u p t a ke in h ibit or a n t id ep re s s a n t s ve n la fa xin e, d u loxe t in e,
a
i
or m iln a cip ra n . Th e re is s om e lim it e d evid e n ce t h a t t rigge r p oin t in je ct ion s
n
S
w it h lid oca in e m ay a ls o p rovid e p a rt ia l re lie f of n on ra d icu la r a xia l ch ron ic p os -
y
n
t e rior n e ck p a in (9 ).
d
r
o
Ma n y p a t ie n t s w it h ch ron ic n e ck p a in s e e k t re a t m e n t w it h com p le m e n t a ry
m
a lt e rn a t ive t h e ra p ie s . Som e of t h e m ore com m on ly u s e d t h e ra p ie s in clu d e ch i-
e
s
rop ra ct ic or os t e op a t h ic m a n ip u la t ion , m a s s a ge, a cu p u n ct u re, t ra n s cu t a n e ou s
e le ct ric n e rve s t im u la t ion , or t ra ct ion . In ge n e ra l, t h e re is lit t le evid e n ce t o s u p -
p ort or re fu t e t h e e ffe ct ive n e s s of a n y of t h e s e t h e ra p ie s . Som e review s h ave
s u gge s t e d t h a t t h e s e t h e ra p ie s m ay p rovid e s om e be n e t w h e n u s e d in com bi-
n a t ion w it h n e ck e xe rcis e s bu t n ot w h e n u s e d a lon e. How eve r, ra re bu t s e riou s
com p lica t ion s s u ch a s s t roke s a n d p a t h ologic fra ct u re s h a ve be e n d e s cribe d in
t h e lit e ra t u re re la t e d t o m a n ip u la t ion s . Th e re fore, t h e s e t h e ra p ie s s h ou ld be
d e live re d on ly by q u a li e d p ra ct it ion e rs a n d s h ou ld n ot be a p p lie d in p a t ie n t s
a t h igh ris k for t h e s e com p lica t ion s (1 ).

Clinica l Co urse
Pa t ie n t s p re s e n t in g w it h n e ck p a in ca n re p re s e n t a d ia gn o s t ic ch a lle n ge
be ca u s e of a n e xt e n s ive d iffe re n t ia l d ia gn os is t h a t in clu d e s e m e rge n t a n d s e ri-
ou s u n d e rlyin g con d it ion s a n d t h e p oor corre la t ion of d ia gn os t ic t e s t n d in gs
t o clin ica l s ym p t om s in p a t ie n t s w it h ch ron ic, n on u rge n t con d it ion s . Pa t ie n t s
w it h a h is t ory of m a jor n e ck t ra u m a , or m a jor blu n t t ra u m a w it h a lt e re d m e n -
t a l s t a t u s , or “d is t ra ct in g” in ju rie s (w h os e p a in m a y s u p e rs e d e p a in from a con -
cu rre n t n e ck in ju ry) n e e d ce rvica l s p in e im m obiliza t ion a n d e m e rge n t im a gin g
t o ru le ou t s p in a l fra ct u re or ot h e r s p in a l cord t h re a t e n in g s oft t is s u e in ju ry.
In fe ct ion m u s t be ru le d ou t w it h im a gin g a n d blood t e s t s in p a t ie n t s w it h IV
d ru g a bu s e, va s cu la r a cce s s d evice, or im m u n ocom p rom is e d s t a t e, or w h o h ave
con s t it u t ion a l s ym p t om s or feve r on e xa m in a t ion ; a n d m e t a s t a t ic ca n ce r m u s t
be ru le d ou t in p a t ie n t s w it h a h is t ory of m a lign a n cy. Pa t ie n t s w it h n e u rologic
s ym p t om s or p h ys ica l e xa m in a t ion s ign s of m ye lop a t h y n e e d u rge n t im a gin g
 Ch a p te r 2 Ne ck Pa in 21

t o ru le ou t s p in a l cord com p re s s ion w h ich m a y re q u ire in t e rve n t ion t o p reve n t

fu rt h e r los s of n e u rologic fu n ct ion . Prom p t in t e rve n t ion is e s s e n t ia l in p a t ie n t s
w it h a n y of t h e s e s e riou s u n d e rlyin g con d it ion s t o p re s e rve re m a in in g n e u ro-
logic fu n ct ion . In m a n y of t h e s e ca s e s , t h e n a l fu n ct ion a l ou t com e w ill a ls o
d e p e n d o n t h e s eve rit y of t h e u n d e rlyin g s ys t e m ic co n d it ion , ot h e r p a t ie n t
com orbid it ie s , a n d t h e p a t ie n t ’s p re m orbid leve l of fu n ct ion in g.
Ne ck p a in p a t ie n t s w it h ou t t h e s e u rge n t or s e riou s u n d e rlyin g con d it ion s
t yp ica lly h a ve good clin ica l ou t com e s w it h con t rol of s ym p t om s a n d m a in t e -
n a n ce of n e u rologic fu n ct ion . Pa t ie n t s w it h a cu t e ce rvica l s t ra in from t ra u m a
or in cre a s e d m u s cle u s e w ill t yp ica lly h ave re s olu t ion of s ym p t om s ove r a few
d a ys t o w e e ks w it h re s t a n d p rogre s s ive p h ys ica l t h e ra p y. Re s u m p t ion of n or-
m a l a ct ivit ie s a n d re t u rn t o w ork s h ou ld be e n cou ra ge d a s s oon a s p o s s ible.
Ne ck p a in t h a t d eve lop s s h ort ly a ft e r s u d d e n e xion –e xt e n s ion m ove m e n t in
t h e fa ce of n orm a l im a gin g s t u d ie s is la be le d a s “w h ip la s h .” Th e m a jorit y of
p a t ie n t s w it h w h ip la s h in ju rie s w ill gra d u a lly im p rove w it h con s e rva t ive m e a s -
u re s ove r t h e cou rs e of a few w e e ks . How eve r, a s u bs e t of p a t ie n t s , oft e n in clu d -
in g t h os e w it h p s ych os ocia l ris k fa ct ors for n e ck p a in or e xt e n u a t in g n on m e d -
ica l is s u e s s u ch a s w o r k , a ccid e n t , o r d is a b ilit y-re la t e d cla im , m a y h a ve

s
p e rs is t e n t p a in a n d p oore r fu n ct ion a l ou t com e s .

e
m
Alt h ou gh d e ge n e ra t ive d is c d is e a s e a n d d ege n e ra t ive fa ce t join t d is e a s e

o
r
a re fre q u e n t ly fou n d on im a gin g in a s ym p t om a t ic p a t ie n t s , t h e s e s t ru ct u re s

d
n
a re fe lt t o be t h e p a in ge n e ra t ors in m a n y p a t ie n t s w it h n e ck p a in . In p a rt icu la r,

y
S
a xia l n e ck p a in w it h ou t n e u rologic s ym p t om s t h a t h a s a n a cu t e on s e t is t yp i-

n
i
ca lly a t t rib u t e d t o a n o b s e rve d co rre s p o n d in g d is c h e rn ia t io n —e s p e cia lly in

a
P
you n ge r p a t ie n t s , a n d ch ron ic n e ck p a in is oft e n a t t ribu t e d t o obs e rve d corre -

l
a
n
s p o n d in g fa ce t d ege n e ra t ive jo in t d is e a s e —e s p e cia lly in o ld e r p a t ie n t s . Th e

o
i
m a jorit y of p a t ie n t s d ia gn os e d w it h a cu t e d is c h e rn ia t ion im p rove ove r a few

g
e
R
w e e ks . Pa t ie n t s d ia gn os e d w it h d ege n e ra t ive fa ce t a rt h rit is t e n d t o h ave ch ron ic

2
s ym p t o m s t h a t ca n b e co n t ro lle d w it h co n s e r va t ive t h e ra p ie s . Fo r t h o s e

N
p a t ie n t s w it h s eve re s ym p t om s d e s p it e con s e rva t ive t re a t m e n t s , a d ia gn os t ic

O
I
T
fa ce t join t in je ct ion w it h loca l a n e s t h e s ia ca n be u s e d t o con rm t h a t it is t h e

C
E
p a in ge n e ra t or. If t h e p a t ie n t obt a in s re lie f w it h t h e t a rge t e d d ia gn os t ic in je c-

S
t ion , fu rt h e r m e a s u re s s u ch a s p e rcu t a n e ou s ra d iofre q u e n cy n e u rot om y of t h e
m e d ia l b ra n ch o f t h e co r re s p o n d in g s p in a l n e r ve m a y p rovid e lo n ge r t e r m
re d u ct ion of s ym p t om s (10 ).
Sim ila rly, a lt h ou gh fa ce t join t os t e op h yt e s , in t e rve rt e bra l d is c h e rn ia t ion s ,
a n d t h icke n in g of t h e p os t e rior lon git u d in a l liga m e n t a n d liga m e n t u m avu m
a re o ft e n s e e n o n co m p u t e d t o m ogra p h ic o r MR im a ge s in a s ym p t o m a t ic
p a t ie n t s , t h ey a re fre q u e n t ly fou n d t o ca u s e s p in a l cord or n e rve com p re s s ion
in p a t ie n t s w it h ce rvica l m ye lop a t h y or ra d icu lop a t h y, re s p e ct ive ly. Dege n e ra -
t ive ch a n ge s of t h e ve rt e bra l bod y a n d a s s ocia t e d s oft t is s u e s t r u ct u re s a re
re fe rre d t o by t h e n on s p e ci c t e rm “s p on d ylos is .” Th e s e d ege n e ra t ive ch a n ge s
a re s e e n m ore fre q u e n t ly in t h e low e r ce rvica l ve rt e bra e. Con s e q u e n t ly, ce rvica l
m ye lo p a t h y a n d ra d icu lo p a t h y m o re fre q u e n t ly o ccu r a t t h e s e leve ls . Ma n y
p a t ie n t s w it h ce rvica l s p on d ylit ic m ye lop a t h y h a ve cord com p re s s ion a t m ore
t h a n on e leve l. Th e m a jorit y of p a t ie n t s w ill im p rove a ft e r s u rgica l d e com p re s -
s ion , bu t p oore r ou t com e s a re s e e n in old e r p a t ie n t s w h o h ave lon ge r d u ra t ion
of a n d m ore s eve re s ym p t om s be fore s u rge ry. Sim ila rly, t h e m a jorit y of p a t ie n t s
w ill im p rove a ft e r s u rgica l d e com p re s s ion o f ce rvica l ra d icu lop a t h y. Ce rvica l
ra d icu lop a t h y p a t ie n t s h avin g s u rgica l d e com p re s s ion h ave q u icke r im p rove -
m e n t of p a in a n d m ore im p rove m e n t in s t re n gt h t h a n p a t ie n t s m a n a ge d con -
s e rva t ive ly, bu t by 1 ye a r p a in s ym p t om s of con s e rva t ive ly m a n a ge d p a t ie n t s
a re s im ila r t o t h os e p a t ie n t s w h o h a d s u rgica l d e com p re s s ion .
In n e ck p a in p a t ie n t s w it h n e u rologic s ym p t om s , it is im p ort a n t t o con s id e r
ot h e r e t iologie s for t h e obs e rve d n e u rologic s ym p t om s or n d in gs . Dia gn os e s
t o con s id e r in t h e d iffe re n t ia l for p a t ie n t s w it h ra d icu la r s ym p t om s in clu d e
p e r ip h e ra l o r u p p e r e x t re m it y e n t ra p m e n t n e u ro p a t h ie s ; b ra ch ia l p le x u s
in ju rie s , d ege n e ra t ion , or in a m m a t ion ; h e rp e s zos t e r; a n d ot h e r in fe ct iou s ,
 22 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

in a m m a t ory, or d ege n e ra t ive n e u rop a t h ie s . Ad d it ion a l d ia gn os e s t o con s id e r

in p a t ie n t s w it h s ym p t om s of m ye lop a t h y in clu d e m u lt ip le s cle ros is , t ra n s -
ve rs e m ye lit is , vira l m ye lit is , a m yot ro p h ic la t e ra l s cle ros is , ep id u ra l a rt e riov-
e n ou s m a lform a t ion s , a n d s p in a l cord in fa rct ion .

Co nclusio ns
In p a t ie n t s w it h a n t e rior n e ck p a in , t h e d iffe re n t ia l d ia gn os is ca n be ve ry broa d ,
s in ce t h is is a com m on s it e for re fe rre d vis ce ra l p a in . Tre a t m e n t a n d clin ica l
ou t com e s w ill d ep e n d on t h e s p e ci c d ia gn os is u n cove re d .
Sim ila rly, in p a t ie n t s w it h n e ck p a in d u e t o ot h e r s ys t e m ic con d it ion s s u ch
a s rh e u m a t oid a rt h rit is , a n kylos in g s p on d ylit is , or p olym ya lgia rh e u m a t ica , t h e
s p e ci c t re a t m e n t a n d eve n t u a l clin ica l ou t com e is d ep e n d e n t on t h e u n d e rly-
in g con d it ion .

Re fe r to Patie nt Education

ICD9
S
E
C
723.1 Ce rvicalg ia
T
I
De g e ne ratio n, de g e ne rative
O
N
722.4 ce rvical, ce rvico t h o racic
2
722.71 w it h m ye lo p at h y
R
e
Displace me nt, displace d
g
i
722.0 ce rvical, ce rvico d o rsal, ce rvico t h o racic
o
n
729.2 Radiculitis (p re ssu re ) (ve rt e b ro g e n ic)
a
l
723.4 ce rvical NEC
P
a
756.11 Spo ndylo lysis (co n g e n it al)
i
n
S
738.4 acq u ire d
y
n
756.19 ce rvical
d
r
721.90 Spo ndylo sis
o
m
721.0 w it h ce rvical, ce rvico d o rsal
e
s
721.1 w it h m ye lo p at h y
Ste no sis (cicat ricial)
723.0 ce rvical

Re fe re nce s
1. Rin d e is ch JA. Ne ck p a in . In : Integrativ e Medicine, 2n d e d . Ph illa d e lp h ia , PA: W B Sa u n d e rs Com p a n y ;
2007 ,697 –708 .
2. Ca m e ro n ID, Re b be ck T, Sin d h u s a ke D, e t a l. Legis la t ive ch a n ge is a s s ocia t e d w it h im p rove d h e a lt h
s t a t u s in p e op le w it h w h ip la s h . Spine 2008 ;33 :250 .
3. Obe lie ie n e D, Sch ra d e r H , Bovim G, e t a l. Pa in a ft e r w h ip la s h : a p ros p e ct ive con t rolle d in cep t ion coh or t
s t u d y. J Neurol Neurosurg Psychiatr 1999 ;66 :279 –282 .
4. Devin C, Sillay K, Ch e n g J. Ne ck p a in . In : Kelley’s Textbook of Rheum atology , 8t h e d . Vol. 1. Ph ila d e lp h ia , PA:
W B Sa u n d e rs Com p a n y ; 2008 ;571 –584 .
5. Ch ild s JD, Cle la n d JA, Elliot t JM , e t a l. Ne ck p a in : clin ica l p ra ct ice gu id e lin e s lin ke d t o t h e In t e r n a t ion a l
Cla s s i ca t ion of Fu n ct ion in g, Dis a bilit y, a n d He a lt h from t h e Ort h op e d ic Se ct ion of t h e Am e rica n Ph ys i-
ca l Th e ra p y As s ocia t ion . J Orthop Sports Phys Ther 2008;38 (9):A1 –A34 .
6. Elia s F. Roe n t ge n n d in gs in t h e a s ym p t om a t ic ce rvica l s p in e . N Y State J Med 1958 ;58 :3300 .
7. Te re s i LM , Lu fkin RB, Re ich e r MA, e t a l. As ym p t om a t ic d ege n e ra t ive d is k d is e a s e a n d s p on d ylos is of t h e
ce rvica l s p in e : MR im a gin g . Radiology 1987 ;164 :83 .
8. Ma n ch ika n t i L, Ca s h KA, Pa m p a t i V, e t a l. Th e e ffe ct ive n e s s of u oros cop ic ce rvica l in t e rla m in a r e p i-
d u ra l in jection s in m a n agin g ch ron ic cervica l d isc h ern ia tion a n d ra d icu litis: p relim in a ry resu lts of a ra n -
d om ized , d ou ble -blin d , con t rolle d t ria l . Pain Physician 2010 ;13 :223 –236 .
9. Pe lo s o P, Gros s A, Ha in e s T, e t a l. Me d icin a l a n d in je ct ion t h e ra p ie s for m e ch a n ica l n e ck d is ord e r s .
Cochrane Database Syst Rev 2007 ;2:CD000319 .
10. Nie m ist o L, Ka lso E, Ma lm iva a ra A, et a l. Ra d iofreq u e n cy d en e rva t ion for n eck a n d ba ck p a in . A s ys t em a t ic
review of ra n d o m ize d con t rolle d t ria ls . Cochrane Database Syst Rev 2003 ;3:CD004058 .
CHAPTER
3 Low Ba ck Pa in a nd
h ist o ry o f f e ve r, ch ills, an d w e ig h t lo ss. Th e re is n o h ist o ry
o f t rau m a o r an u n u su al act ivit y t h at p re ce d e d t h e o n se t
o f t h e se sym p t o m s. Th e re is n o h ist o ry o f m alig n an cy o r
in t rave n o u s d ru g u se .
CLINICAL POINTS
• Pa t ie n t s w it h lo w b a ck
p a in sh o u ld b e cla ssi e d
in t o a risk ca t e g o ry b a se d
o n n o n sp e ci c lo w b a ck
p a in , p a in a sso cia t e d w it h
ra d icu lo p a t h y (in clu d in g
h e rn ia t e d d isc o r sp in a l
stenosis), and pain associated
w it h syst e m ic d ise a se .
• Mo t o r w e a kn e ss, fe ca l
in co n t in e n ce , a n d u rin a ry
re t e n t io n a re sym p t o m s o f
ca u d a e q u in a syn d ro m e
a n d re q u ire im m e d ia t e
su rg ica l e va lu a t io n .
• Pa t ie n t s w it h p sych o so cia l
st re sso rs a re m o re like ly t o
d e ve lo p ch ro n ic p a in .
Lumba r Stenosis
Lisa L. W illett
A 62-ye ar-o ld f e m ale p re se n t s
Clinica l Pre se nta tio n
Low ba ck p a in is on e of t h e m os t com -
s
w it h co m p lain t s o f lo w e r b ack
e
m on re a s on s t h a t p a t ie n t s s e e k m e d ica l
m
p ain and n um bne ss in he r fe e t ,
o
a t t e n t ion . It is e s t im a t e d t h a t t w o t h ird s
r
d
int e rm itt e n tly f or 8 m o nt hs. o f a d u lt s h a ve e x p e r ie n ce d low b a ck
n
y
S
Pain is w o rse at t h e e n d o f p a in a t le a s t o n ce, a n d a p p roxim a t e ly
n
7% h a ve h a d a t le a s t on e s eve re ep is od e
i
d ay an d g e t s b e t t e r w it h
a
P
w it h in a 1 ye a r p e riod . Th e t yp ica l a ge of
l
re cu m b e n cy; p ain is also m o re
a
o n s e t o f low b a ck p a in is b e t w e e n 30
n
o
n o t ice ab le w it h am b u lat io n a n d 50 yea rs, w ith m en a n d w om en bein g
i
g
e
an d g e t s b e t t e r w h e n n o eq u a lly a ffected (1,2). Low ba ck p a in orig-
R
in a tes from m a n y sp in a l s tru ctu res, a n d
2
lo n g e r w alk in g . Th e re is n o
N
in clu d es liga m en t stra in , d egen era tion of
O
fa ce t join t s , h e rn ia t e d d is cs , a n d s p in a l
I
T
C
s t e n o s is (Figs . 3.1A, 3.1B). Sym p t o m s
E
S
ra n ge from m ild , s e lf-lim it in g p a in , t o
severe, in ca p a cita tin g p a in w ith ra d icu la r
sym p t om s , n e u rologic com p rom is e, a n d
ch ron ic m orbid ity.
Be ca u s e of t h e com p le xit y of t h e s p in e a n a t om y, a p re cis e a n a t om ica l d ia g-
n os is for p a t ie n t s w it h low ba ck p a in is d if cu lt . It is e s t im a t e d t h a t on ly 15%
of p a t ie n t s w it h low ba ck p a in a re a ble t o be d ia gn os e d w it h a p re cis e s p in a l
a bn orm a lit y or s p e ci c e t iology (1). In a n e ffort t o a ch ieve a ccu ra t e d ia gn os is
a n d e ffe ct ive t h e ra py, cos t ly im a gin g a n d s u rgica l re fe rra l is p u rs u e d . De s p it e
w id e va ria t ion s in t h e clin ica l eva lu a t ion a n d m a n a ge m e n t of low ba ck p a in ,
ove ra ll ou t com e s a re s im ila r for p a t ie n t s . Pu blis h e d gu id e lin e s e xis t t o gu id e
t h e clin icia n on t h e be s t a p p roa ch t o eva lu a t e a n d m a n a ge a cu t e a n d ch ron ic
low ba ck p a in in t h e p rim a ry ca re s e t t in g.
W h e n t a kin g t h e m e d ica l h is t o ry, clin icia n s s h o u ld a t t e m p t t o p la ce t h e
p a t ie n t in t o a ca t egory of ris k (2). Th e t h re e a re a s of ris k a re : (a ) n on s p e ci c low
b a ck p a in , (b ) p a in a s s o cia t e d w it h ra d icu lo p a t h y o r s p in a l s t e n o s is , a n d
(c) p a in from a s ys t e m ic ca u s e. In a d d it ion t o t h e p a in loca t ion , s eve rit y, a n d
d u ra t ion , a p rior h is t ory of ba ck p a in a n d t h e clin ica l cou rs e is a ls o im p ort a n t .
Th e r s t p r io r it y is t o r u le o u t n e u ro lo gic co m p ro m is e . Qu e s t io n s s h o u ld
in clu d e t h e p re s e n ce of low e r e xt re m it y m ot or w e a kn e s s , fe ca l in con t in e n ce,
a n d u rin a ry re t e n t ion w it h ove r ow in con t in e n ce. Of t h e s e, u rin a ry re t e n t ion
is t h e m os t fre q u e n t s ym p t om of ca u d a e q u in a s yn d rom e.
Th e n e xt leve l of q u e s t ion s s h ou ld eva lu a t e for s ys t e m a t ic d is e a s e s , e s p e -
cia lly ca n ce r w it h s p in a l m e t a s t a s is , fra ct u re s from os t e op oros is or s t e roid u s e,
a n d s p in a l in fe ct io n s . Ris k fa ct o rs fo r ca n ce r, in clu d in g m u lt ip le m ye lo m a ,
23
 24 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

SAGITTAL VIEW OF LOWER SPIN E

Spinal cord Tumor

(cauda equina) of the
spinal
cord

Bone spur
impinging
on spinal
nerves
S
E
C
Compression
T
fractures
I
O
N
2
R
e
g
i
o
Herniated disc
n
N ote: discs can be herniated and not be painful
impinging on
a
l
spinal nerve,
P
causing pain
a
i
n
S
y
n
d
r
o
m
e
s
A B

Figure 3.1 A: Sa gitta l view of the norma l spine. Ima ge provided by Ana tomica l Cha rt Co. B: Ca uses of low ba ck pa in. From Nettina SM. Lippincott Ma nua l
of Nursing Pra ctice , 9th ed. Phila delphia : Wolters Kluwer Hea lth; 2010.

in clu d e t h e follow in g: a ge 50 ye a rs , a h is t ory of ca n ce r, u n e xp la in e d w e igh t

lo s s , n igh t t im e p a in o r p a in w ors e n e d w it h re cu m be n t p os it io n s , a n d p a in
6 w e e k s in d u ra t io n . Ris k fa ct o r s fo r in fe ct io n in clu d e feve r, u n e x p la in e d
w e igh t los s , h is t ory of in t rave n ou s d ru g u s e, in d w e llin g ca t h e t e rs , re ce n t in fe c-
t ion s , a n d h is t ory of ba ct e re m ia .
Of p a t ie n t s w h o p r e s e n t t o p r im a r y ca re w it h low b a ck p a in , s p in a l s t e -
n os is a n d s ym p t om a t ic h e rn ia t e d d is cs a ccou n t for 3% a n d 4%, re s p e ct ive ly (2).
Pa t ie n t s p re s e n t w it h n e u r o ge n ic cla u d ica t io n , o r s cia t ica , t h e la t t e r b e in g
d e n e d a s b a ck p a in ra d ia t in g in t o t h e b u t t o ck a n d low e r le g in a lu m b a r
n e r ve ro o t d is t r ib u t io n . Pa t ie n t s w it h s p in a l s t e n o s is a r e t yp ica lly ove r t h e

PATIENT ASSESSMENT
• Ph ysica l e xa m in a t io n
sh o u ld e va lu a t e fo r fe ve r,
ve rt e b ra l t e n d e rn e ss, a n d
n e u ro lo g ic d e cit s
• Ra d icu la r sym p t o m s a re
se e n w it h h e rn ia t e d d iscs
o r sp in a l st e n o sis
• He rn ia t e d d iscs ca u se
a cu t e se ve re b a ck p a in ,
involve L4/L5 and L5/S1,
a n d h a ve a p o sit ive
st ra ig h t le g -ra isin g t e st
• Sp in a l st e n o sis o ccu rs in
e ld e rly p a t ie n t s w it h a
h ist ory of chronic low b ack
p ain, w orse with walking
o r stan ding, improve d w ith
b end ing forward, ind uce d
w hen be nding backward,
and has bilateral pla nta r
n umb ness
Figure 3.2 The stra ight leg-ra ising test. MediClip ima ge copyright ©
2003 Lippincott Willia ms & Wilkins. All rights reserved.
Ch a p te r 3 Low Ba ck Pa in a n d Lu m ba r St e n os is 25
a ge o f 60 ye a r s a n d h a ve a h is t o ry o f ch ro n ic low b a ck p a in fo r m o n t h s t o
ye a r s . Th e p a in is w o r s e w it h w a lk in g o r s t a n d in g, im p rove d w it h b e n d in g
fo r w a rd , a n d , a t t im e s , in d u ce d w h e n b e n d in g b a ck w a rd (3,4). In a s t u d y o f
p a t ie n t s p re s e n t in g t o a n o r t h o p e d ic s u rge o n w it h p a in o r n u m b n e s s in t h e
le gs , t h e m o s t s p e ci c s ym p t o m s fo r lu m b a r s p in a l s t e n o s is w e r e a h is t o ry
o f u r in a r y s y m p t o m s , im p r o ve m e n t w it h b e n d in g fo r w a rd , a n d b ila t e r a l
p la n t a r n u m b n e s s (5). He r n ia t e d lu m b a r d is cs ca n a ls o p re s e n t w it h s cia t ica ,
b u t ca n b e d is t in gu is h e d fro m s p in a l s t e n o s is by a n a cu t e o n s e t o f p a in a n d
e x a m in a t io n fe a t u r e s , s u ch a s a p o s it ive s t ra igh t le g-ra is in g, w h ich is s u g-
ge s t ive o f a h e r n ia t e d d is c.
Fin a lly, a s s e s s m e n t o f p s ych os o cia l d is t re s s is im p o rt a n t . Pa t ie n t s w it h
d e p re s s ion , s om a t iza t ion d is ord e r, s u bs t a n ce a bu s e, job d is s a t is fa ct ion or d is -
a bilit y com p e n s a t ion , a n d t h os e in volve d in lit iga t ion a re m ore like ly t o h a ve
p rolon ge d ba ck p a in a n d p e rs is t e n t u n e xp la in e d s ym p t om s (5).
Exa mina tio n
As w it h t h e h is t ory, t h e p h ys ica l e xa m in a t ion for p a t ie n t s w it h low ba ck p a in
s
e
s h ou ld focu s on t h e n e u rologic e xa m in a t ion a n d s h ou ld e n s u re t h a t t h e re a re
m
o
n o d e cit s . Aft e r a s s e s s in g for feve r a n d t h e p re s e n ce of ve rt e bra l t e n d e rn e s s
r
d
w it h p a lp a t ion , a focu s e d n e u rologic e xa m in a t ion s h ou ld be p e rform e d . More
n
y
t h a n 90% of h e rn ia t e d d is cs occu r a t t h e L4/L5 a n d L5/S1 leve ls a n d t h e n e u ro-
S
n
lo gic e x a m in a t io n fo cu s e s o n t h e s e n e r ve ro o t s , a n d in clu d e s t h e s t ra igh t
i
a
P
leg-ra is in g t e s t (Fig. 3.2 ), a n d t h e m ot or a n d s e n s ory fu n ct ion t e s t s (2).
l
A s t ra igh t leg-ra is in g t e s t in volve s h a vin g t h e p a t ie n t s u p in e on t h e e xa m -
a
n
o
in a t ion t a ble. Th e e xa m in e r h old s t h e leg s t ra igh t w it h on e h a n d a n d cu p s t h e
i
g
h e e l w it h t h e ot h e r. Th e s t ra igh t leg is lift e d off t h e e xa m in a t ion t a ble from t h e
e
R
h e e l in a n e ffo rt t o re p rod u ce t h e p a t ie n t ’s s cia t ica . A p os it ive t e s t p ro d u ce s
2
p a in t h a t ra d ia t e s be low t h e kn e e be t w e e n 30 a n d 70 d egre e s of e leva t ion . A
N
O
p os it ive t e s t on t h e ip s ila t e ra l s id e h a s a s e n s it ivit y of a p p roxim a t e ly 90% for a
I
T
C
h e rn ia t e d d is c, w h e re a s a p os it ive t e s t w h e n t h e op p os it e leg is ra is e d (a cros s e d
E
t e s t ) h a s a s p e ci cit y of a p p roa ch in g 90% (2). Fu rt h e r n e u rologic eva lu a t io n
S
in clu d e s s e n s o ry a n d m o t o r n d in gs o f t h e L4 t h ro u gh S1 n e r ve ro o t , a n d
in clu d e s a s s e s s in g kn e e s t re n gt h a n d re e xe s (L4), gre a t t oe a n d foot d ors i e x-
ion (L5), foot p la n t a r e xion a n d a n kle re e xe s (S1).
Studie s
Fin d in gs on ra d iologic im a gin g corre la t e p oorly w it h
t h e s eve rit y of s ym p t om s in p a t ie n t s w it h low ba ck
p a in . Th ere fore, rou t in e im a gin g is n ot clin ica lly u s e fu l
for p a t ie n t s w it h n on s p e ci c low ba ck p a in . Im a gin g is
re com m e n d e d for p a t ie n t s w it h con ce rn s for ca n ce r,
fra ct u re, or in fe ct ion , a n d for p a t ie n t s w it h n e u rologic
n d in gs. Gu id e lin es re com m en d p la in ra d iogra p h y for
p a t ie n t s w it h a p os s ible s ys t e m ic illn e s s , in clu d in g
p a tien ts w ith fever, u n exp la in ed w eigh t loss, a h istory of
ca n cer, a lcoh ol or d ru g in jection , tra u m a , foca l vertebra l
ten d ern ess on p a lp a tion , a n d age old er th a n 50 yea rs.
Pla in ra d iogra p h y is n ot s e n s it ive for ea rly ca n ce r or
in fe ct ion . Th u s , if t h e clin ica l s u s p icion is h igh , fu rt h e r
t es t in g s u ch a s a n e ryt h rocyt e s ed im e n t a t ion ra t e (ESR)
or C-re a ct ive p rot e in (CRP), a com p le t e blood cou n t
(CBC), a n d a com p u t e d t om ogra p h y (CT) or m a gn e t ic
re s on a n ce im a gin g (MRI) s h ou ld be p e rform e d . Pa t ie n t s
w it h s eve re or p rogre s s ive n e u rologic d e cit s s h ou ld
 26 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

h ave p rom p t im a gin g w it h a CT or MRI, a n d e m erge n t eva lu a t ion for s p in a l cord

com p rom is e. Delaye d d ia gn os is a n d t re a t m e n t for s p in a l cord com p rom is e from
in fe ct ion , ca n cer, or ca u d a e q u in a s yn d rom e h a s p oore r ou t com e s . MRI is a m ore
s en s it ive t e s t t h a n CT, a n d h a s rep la ce d CT m yelogra p h y for d ia gn os t ic t e s t in g.
Eld e rly p a t ie n t s , s p e ci ca lly t h os e ove r t h e a ge of 65 ye a rs , a re a t in cre a s e d
ris k for s p in a l s t e n o s is , ca n ce r, com p re s s ion fra ct u re s , a n d a ort ic a bd om in a l
a n e u rys m s (AAA) (1). In t h e s e p a t ie n t s , on e s h ou ld h ave a low e r t h re s h old for
im a gin g a n d s h ou ld con s id e r a lt e rn a t e s t u d ie s . For p a t ie n t s w it h n d in gs s u g-
ge s t ive of s p in a l s t e n os is , a n MRI ca n con rm t h e d ia gn os is ; if n u m bn e s s a n d
w e a kn e s s a re p re s e n t , a n e le ct rom yogra p h y a n d n e rve con d u ct ion s t u d y ca n
d e n e t h e e xt e n t of n e u rologic in volve m e n t a n d ru le ou t a p e rip h e ra l n e u rop a -
t h y. An a bd om in a l u lt ra s ou n d ca n d e m on s t ra t e a n AAA. Th e s e p a t ie n t s s h ou ld
h a ve clos e follow u p t o e n s u re t h a t t h e a p p rop ria t e d ia gn os is w a s m a d e.

Tre a tme nt
Tre a t m e n t fo r low b a ck p a in rs t in vo lve s e d u ca t in g t h e p a t ie n t a b o u t t h e
e xp e ct e d clin ica l ou t com e. Ove ra ll, t h e p rogn os is is good , a n d m os t p a t ie n t s
S
w ill im p rove w it h in 4 w e e ks . For p a t ie n t s w it h n on s p e ci c low ba ck p a in , evi-
E
C
d e n ce is lim it e d bu t s u gge s t s t h a t con s e rva t ive m a n a ge m e n t is e ffe ct ive for
T
I
O
s ym p t om re lie f. Pa t ie n t s s h o u ld re s u m e n orm a l a ct ivit ie s w h e n a ble t o, a n d
N
s h ou ld a void be d re s t . He a t in g p a d s a n d bla n ke t s m a y p rovid e re lie f, bu t t h e re
2
is in s u f cie n t evid e n ce t o re com m e n d lu m ba r s u p p ort s or ice p a cks . He a vy lift -
R
e
in g a n d t w is t in g s h ou ld be avoid e d .
g
i
o
Me d ica l t h e ra p y h a s be e n s h ow n t o p rovid e s h ort t e rm re lie f t o p a t ie n t s
n
a
w it h a cu t e low ba ck p a in (1,2). Pa t ie n t s s h ou ld be p re s cribe d n on s t e roid a l a n t i-
l
P
in a m m a t ory d ru gs (NSAIDS) a n d m u s cle re la xe rs a s rs t lin e t h e ra p y, u n le s s
a
i
n
t h e re is a con t ra in d ica t ion s u ch a s re n a l in s u f cie n cy or a ris k of ga s t roin t e s -
S
t in a l ble e d in g. Ace t a m in op h e n is le s s e ffe ct ive t h a n NSAIDS bu t a s a fe a n d
y
n
re a s on a ble rs t -lin e op t ion for p a t ie n t s w h o ca n n ot t a ke NSAIDS. Th e re is n o
d
r
o
d a t a t o gu id e clin icia n s on t h e d os e a n d d u ra t ion of t h e ra p y.
m
For p a tien ts w it h severe p a in , u n relieved w ith NSAIDS a n d m u scle rela xa n t s,
e
s
op ioid a n a lgesics a n d tra m a d ol ca n be con s id ered , w eigh in g th e risk of ch ron ic
u sa ge a n d a bu se p oten tia l. Tricyclic a n tid ep ressa n ts a re effective for ch ron ic low
ba ck p a in ; s elective seroton in reu p ta ke in h ibitors (SSRIs) a n d t ra zod on e a re n ot.
NOT TO BE MISSED Ga ba p en tin h a s lim ited d a ta sh ow in g s m a ll s h ort-term ben e t in p a tien ts w it h
ra d icu lop a th y; system ic corticosteroid s h ave n ot been sh ow n to be effective a n d
• Ne u ro lo g ic co m p ro m ise
a re n ot recom m en d ed for p a tien ts , w ith or w ith ou t scia t ica .
a n d ca u d a e q u in a
Mu lt ip le in t e rve n t ion s s u ch a s s p in a l m a n ip u la t ion , p h ys ica l t h e ra p y, m a s -
• Meta sta t ic ca n ce r, fra ctu re, s a ge t h e ra p y, a n d a cu p u n ct u re h a ve b e e n u s e d t o t re a t a cu t e low b a ck p a in
o r spin a l infe ct ion
(1,2). Alt h o u gh evid e n ce is la ck in g, ce r t a in p a t ie n t s m a y d e rive re lie f w h e n
• Fo ca l ve rt e b ra l t e n d e rn e ss u s e d a s s e con d lin e t h e ra p y. Tra ct ion , fa ce t -join t in je ct ion s , a n d t ra n s cu t a n e -
t o p a lp a t io n o u s e le ct r ica l n e r ve s t im u la t io n a ls o la ck s u p p o r t in g evid e n ce o f e f ca cy.
• Fe ve r Be ca u s e t h e m a jorit y of low ba ck p a in im p rove s w it h in 4 w e e ks , re fe rra l for
s u ch a lt e rn a t e in t e rve n t ion s s h ou ld be d e la ye d u n t il t h e n .
• Un e xp la in e d w e ig h t lo ss
Th era py op tion s for p a tien ts w ith h ern ia ted d isks a re th e sa m e a s for n on sp e-
• Hist o ry o f ca n ce r, a lco h o l, ci c low ba ck p a in . Un less th ere is ca u d a eq u in a syn d rom e or p rogressive n eu ro-
o r d ru g in je ct io n
logic d e cits , t h e m a jorit y of p a t ien ts im p rove. Th e p a in m ay be m ore s evere,
• Tra u m a req u irin g n a rcotic a n a lgesia , a n d ep id u ra l corticosteroid s m ay p rovid e a d d ition a l
• Ag e o ve r 50 ye a rs relief; system ic corticosteroid s h ave n ot been sh ow n to p rovid e ben e t. Pa tien ts
w ith severe p a in , d esp ite th era py, a n d th ose w it h p ersisten t n eu rologic d e cit s
• Pa in d u ra t io n 6 w e e ks
sh ou ld be eva lu a ted w ith a n MRI or CT a n d referred for su rgica l eva lu a tion .
• Life -t h re a t e n in g Evid e n ce t o gu id e n on s u rgica l t h e ra py for p a t ie n t s w it h lu m ba r s p in a l s t e -
co n d it io n s o u t sid e t h e n os is is la ckin g, a n d t h e re is w id e va ria t ion in t h e m e t h od s u s e d . Alt h ou gh d a t a
sp in e , su ch a s a o rt ic
s u p p ort t h e be n e t of s u rgica l d e com p re s s ion , t h e be n e t of s u rge ry com p a re d
a n e u rysm , p a n cre a t it is,
a n d e n d o ca rd it is t o n on s u rgica l a p p roa ch e s is u n kn ow n . Me d ica l t h e ra p y is re com m e n d e d for
p a t ie n t s w it h h igh s u rgica l ris k a n d m ild -t o-m od e ra t e s ym p t om s (3,4).

WHEN TO REFER
• Ne u ro lo g ic d e cit s o n
p h ysica l e xa m in a t io n ,
e sp e cia lly ca u d a e q u in a
• Se ve re p a in u n re sp o n sive
t o m e d ica l m a n a g e m e n t
• Sp in a l st e n o sis w it h
se ve re p a in o r fu n ct io n a l
lim it a t io n s
Ch a p te r 3 Low Ba ck Pa in a n d Lu m ba r St e n os is 27
Th e rs t lin e of n on s u rgica l t h e ra p y for s p in a l s t e n os is is t o m od ify t h e
p a t ie n t ’s a ct ivit y. Pa t ie n t s ca n o b t a in s ign i ca n t p a in re lie f by lim it in g t h e
a ct ivit ie s t h a t in d u ce t h e p a in , s u ch a s p rolon ge d w a lkin g a n d s t a n d in g. Pos -
t u ra l a d ju s t m e n t w it h a ca n e or w a lke r p rovid e s re lie f by p rom ot in g forw a rd
e xion of t h e lu m ba r s p in e, re lievin g t h e s t e n os is .
Ph ys ica l t h e ra py t o in cre a s e s t re n gt h a n d a bd om in a l core m u s cle s p rovid e
re lie f t o s om e p a t ie n t s , a n d u p t o 30% of p a t ie n t s m ay ge t s ign i ca n t re lie f (4).
Exe rcis e bikin g a n d ot h e r m od a lit ie s t o in cre a s e leg s t re n gt h , a n d avoid in g s e d -
a t ive s a n d a lcoh ol a re im p ort a n t for fa ll p reve n t ion .
Ora l a n a lge s ics a re give n t o p a t ie n t s for s ym p t om a t ic re lie f, a lt h ou gh s t u d -
ie s s p e ci c t o lu m ba r s p in a l s t e n os is a re la ckin g. Ga ba p e n t in w a s s h ow n in on e
u n blin d e d s t u d y t o im p rove p a in a n d w a lkin g d is t a n ce a s com p a re d t o p la ce bo.
Lu m ba r e p id u ra l s t e ro id in je ct io n s a re co m m o n ly u s e d , b u t w it h n o d a t a t o
s u p p ort e f ca cy, it is a s e con d lin e t h e ra py op t ion .
Su rgica l in t e rve n t io n w it h d e com p re s s ive la m in e ct om y is t h e t ra d it ion a l
rs t lin e re com m e n d e d t h e ra py. St u d ie s s u p p ort im p rove d ou t com e s in p a t ie n t s
w it h p e rs is t e n t s cia t ica , ra d iologic s ign s of s t e n os is , n e rve root com p re s s ion ,
a n d n o p rior ba ck s u rge ry. Su rgica l t e ch n iq u e s h ave evolve d a n d n ow in clu d e
s
h e m ila m in e ct o m y a n d t e ch n iq u e s t o p re s e r ve t h e in t e r s p in o u s liga m e n t s .
e
m
Alt h ou gh s t u d ie s s h ow lon g t e rm ou t com e s t o be s u cce s s fu l in p a t ie n t s w it h
o
r
a d va n ce d a ge, eve n in t h e ir 80s , op e ra t ive ris k m u s t be w e igh e d ca re fu lly a s
d
n
s u rgica l com orbid it ie s a re oft e n p re s e n t in t h e e ld e rly (4).
y
S
n
i
a
P
Clinica l Co urse
l
a
n
o
In p a t ie n t s w it h a cu t e low ba ck p a in , it h a s be e n rep ort e d t h a t 90% im p rove
i
g
w it h in 2 w e e ks (1). Th e m a jorit y of p a t ie n t s w it h n on s p e ci c low ba ck p a in , a n d
e
R
eve n t h os e w it h a h e rn ia t e d d is c, im p rove w it h in 4 w e e ks w it h con s e rva t ive
2
t re a t m e n t . Th e re fore, p a t ie n t s w it h p a in t h a t p e rs is t s lon ge r t h a n 4 t o 6 w e e ks ,
N
O
d e s p it e con s e rva t ive t h e ra p y, s h ou ld be re eva lu a t e d a n d h ave im a gin g t o ru le
I
T
C
ou t a s ys t e m ic p roce s s . Som e cros s -s e ct ion a l s t u d ie s of p a t ie n t s follow e d in
E
p rim a ry ca re s h ow t h a t m ore t h a n 60% of p a t ie n t s im p rove d w it h in 7 w e e ks ,
S
bu t re cu rre n ce w a s com m on , a ffe ct in g 40% of p a t ie n t s w it h in 6 m on t h s (1).
Mos t p a t ie n t s w it h s p in a l s t e n os is w h o a re m a n a ge d m e d ica lly d o n ot h ave
s ign i ca n t clin ica l p rogre s s ion ove r t h e cou rs e of a ye a r. Sym p t om s a n d n e u ro-
logic e xa m in a t ion s h ou ld n ot a cu t e ly w ors e n ; likew is e, d ra m a t ic s ym p t om a t ic
im p rove m e n t is u n com m on . Th e re fore, p a t ie n t s ca n be follow e d clin ica lly ove r
t im e, a n d if t h e p a t ie n t ’s p a in p rogre s s e s d e s p it e n on s u rgica l t h e ra p y, re fe rra l
for la m in e ct om y s h ou ld be con s id e re d . Su rge ry re s u lt s in be t t e r p a in re lie f for
s eve ra l ye a r s . How eve r, in co h o r t s t u d ie s , 30% o f p a t ie n t s h a d s eve re p a in
4 ye a rs a ft e r s u rge ry a n d 10% re q u ire d re op e ra t ion (1).
Ch ron ic low ba ck p a in is ch a lle n gin g for bot h t h e p a t ie n t a n d clin icia n . In
s t u d ie s , p re d ict o r s o f p e r s is t e n t b a ck p a in a n d w o r s e o u t co m e s a t 1 ye a r
in clu d e d t h e p re s e n ce of n on orga n ic s ign s , m a la d a p t ive p a in cop in g be h aviors ,
h igh ba s e lin e fu n ct ion a l im p a irm e n t , p s ych ia t ric com orbid it ie s , a n d low ge n -
e ra l h e a lt h s t a t u s . Dep re s s ion , job d is s a t is fa ct ion or d is a bilit y com p e n s a t ion ,
a n d t h os e in volve d in lit iga t ion a re a ls o m ore like ly t o h a ve p rolon ge d ba ck
p a in a n d p e rs is t e n t u n e xp la in e d s ym p t om s . Ba s e lin e p a in a n d t h e p re s e n ce of
ra d icu la r s ym p t om s w e re n ot p re d ict ive of p e rs is t e n t p a in (6).
Co nclusio ns
Low ba ck p a in is com m on a n d w ill a ffe ct t h e m a jorit y of a d u lt p a t ie n t s in t h e ir
life t im e. De s p it e w id e va ria t ion s in t h e clin ica l eva lu a t ion a n d m a n a ge m e n t of
low ba ck p a in , ove ra ll ou t com e s for m os t p a t ie n t s a re good , a n d eve n w it h a
h e rn ia t e d d is c, clin ica l im p rove m e n t is a ch ieve d w it h in 6 w e e ks . Mo s t b a ck
 28 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

p a in is n on s p e ci c, a lt h ou gh on e s h ou ld eva lu a t e for p a in w it h ra d icu lop a t h y

from a h e rn ia t e d d is c or s p in a l s t e n os is , a n d p a in from a s ys t e m ic illn e s s s u ch
a s ca n ce r or in fe ct ion . Sp in a l s t e n os is is m ore com m on in e ld e rly p a t ie n t s w it h
a h is t ory of ch ron ic low ba ck p a in for m on t h s t o ye a rs , w ors e w it h w a lkin g or
s t a n d in g, a n d im p rove d w it h be n d in g forw a rd . Ot h e r ca u s e s of ba ck p a in , s u ch
a s re fe rre d p a in from p a n cre a t it is , AAA, n e p h rolit h ia s is , or s p on d yloa rt h rop a -
t h y, s h ou ld be con s id e re d in t h e d iffe re n t ia l d ia gn os is in p a t ie n t s w it h h is t ory
or p h ys ica l e xa m in a t ion s u gge s t ive of t h e s e con d it ion s .
Th e h is t ory a n d p h ys ica l e xa m in a t ion s h ou ld focu s on e n s u rin g t h a t t h e re
is n o n e u rologic com p rom is e or ca u d a e q u in a s yn d rom e a n d in clu d e s a s s e s s -
in g for low e r e xt re m it y m ot or w e a kn e s s , fe ca l in con t in e n ce, a n d u rin a ry re t e n -
t ion . Evid e n ce of s ys t e m ic illn e s s , s u ch a s w e igh t los s a n d feve r, ra is e s con ce rn
for m a lign a n cy or in fe ct ion a n d s h ou ld be fu rt h e r eva lu a t e d . For p a t ie n t s w it h
s cia t ica , a s t ra igh t leg-ra is in g t e s t ca n be s e n s it ive for h e rn ia t e d d is c.
Rou t in e im a gin g is n ot in d ica t e d for t h e m a jorit y of p a t ie n t s w it h n on s p e -
ci c low ba ck p a in . Im a gin g is re co m m e n d e d fo r p a t ie n t s w it h con ce rn s fo r
ca n ce r, fra ct u re, or in fe ct ion , a n d for p a t ie n t s w it h n e u rologic n d in gs . Pa t ie n t s
w it h feve r, u n e xp la in e d w e igh t los s , a h is t ory of ca n ce r, a lcoh ol or d ru g in je c-
S
t ion , t ra u m a , foca l ve rt e bra l t e n d e rn e s s on p a lp a t ion , a n d a ge ove r 50 ye a rs
E
C
s h ou ld h a ve p la in ra d iogra p h s . If t h e clin ica l s u s p icion is h igh for ca n ce r or
T
I
O
in fe ct io n , la b o ra t o ry s t u d ie s a n d im a gin g w it h a CT o r MRI s h o u ld b e p e r-
N
form e d . Pa t ie n t s w it h s eve re or p rogre s s ive n e u rologic d e cit s s h ou ld h ave a n
2
e m e rge n t eva lu a t ion for s p in a l cord com p rom is e w it h a n MRI.
R
e
Firs t lin e t re a t m e n t for p a t ie n t s w it h n on s p e ci c low ba ck p a in is con s e rv-
g
i
o
a t ive t h e ra py a n d in clu d e s NSAIDS a n d m u s cle re la xe rs , a n d p a t ie n t e d u ca t ion
n
a
a bou t t h e ove ra ll good p rogn os is w it h in 4 t o 6 w e e ks . Pa t ie n t s s h ou ld re s u m e
l
P
n orm a l a ct ivit ie s a n d avoid be d re s t . Pa t ie n t s w it h a h e rn ia t e d d is c ca n h ave
a
i
s eve re p a in , s u ch t h a t op ia t e t h e ra p y m ay be re q u ire d . For p a t ie n t s w it h p ro-
n
S
gre s s ive s eve re p a in a n d fu n ct ion a l lim it a t ion s from s p in a l s t e n os is , la m in e c-
y
n
t om y s h ou ld be con s id e re d . Ps ych os ocia l s t re s s ors , in clu d in g p s ych ia t ric con -
d
r
o
d it ion s or lit iga t ion , a re p re d ict ive of a d is a blin g ch ron ic p a in .
m
e
s
ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
721.3 lu m b ar
724.5 Backache (p o st u ral)
924.9 Co ntusio n (sk in su rf ace in t act )
922.31 W it h b ack
De g e ne ratio n, de g e ne rative
722.6 in t e rve rt e b ral d isc
722.70 w it h m ye lo p at h y
722.52 lu m b ar, lu m b o sacral
722.73 w it h m ye lo p at h y
722.51 t h o racic, t h o raco lu m b ar
722.72 w it h m ye lo p at h y
Displace me nt, displace d
722.2 in t e rve rt e b ral d isc (w it h n e u rit is, rad icu lit is, sciat ica,
o r o t h e r p ain )
722.10 lu m b ar, lu m b o sacral
722.73 w it h m ye lo p at h y
722.11 t h o racic, t h o raco lu m b ar
729.2 Radiculitis (p re ssu re ) (ve rt e b ro g e n ic)
724.4 lu m b ar NEC
724.2 lu m b o sacral
 Ch a p te r 3 Low Ba ck Pa in a n d Lu m ba r St e n os is 29

ICD9 (Co n t in u e d )
729.0 Rhe umatism, rhe umatic (acu t e NEC)
724.9 b ack
756.12 Spo ndylo listhe sis (co n g e n it al) (lu m b o sacral)
738.4 acq u ire d
738.4 d e g e n e rat ive
738.4 t rau m at ic
756.11 Spo ndylo lysis (co n g e n it al)
738.4 acq u ire d
756.11 lu m b o sacral re g io n
721.90 Spo ndylo sis
721.3 lu m b ar, lu m b o sacral
721.42 w it h m ye lo p at h y
Sprain, strain (jo in t ) (lig am e n t ) (m u scle )
846.9 lo w b ack
846.0 lu m b o sacral
724.6 ch ro n ic o r o ld

s
e
Ste no sis (cicat ricial)

m
724.00 sp in al

o
r
d
724.02 lu m b ar, lu m b o sacral

n
y
724.09 sp e ci e d re g io n NEC

S
724.01 t h o racic, t h o raco lu m b ar

n
i
a
P
l
a
n
o
i
Re fe re nce s

g
e
R
1. Deyo RA, We in s t e in JN . Low ba ck p a in . N Engl J Med 2001 ;344 (5 ):363 –370 .

2
2. Ch ou R, Qa s e e m A, Sn ow V, e t a l. Dia gn os is a n d t re a t m e n t of low ba ck p a in : a jo in t clin ica l p ra ct ice

N
gu id e lin e from t h e Am e r ica n Colle ge o f Ph ys icia n s a n d t h e Am e r ica n Pa in So cie t y. A nn Intern Med

O
I
2007 ;147 :478 –491 .

T
C
3. Ka t z JN , Ha rris MB. Lu m ba r s p in a l s t e n os is . N Engl J Med 2008 ;358 (8 ):818 –825 .

E
4. Ma rkm a n JD, Ga u d KG. Lu m ba r s p in a l s t e n os is in old e r a d u lt s : cu rre n t u n d e rs t a n d in g a n d fu t u re d ire c-

S
t ion s . Clin Geriatr Med 2008 ;24 :369 –388 .
5. Ebe ll MH . Dia gn os in g lu m ba r s p in a l s t e n os is . A m Fam Physician 2009 ;80 (10 ):1145 –1147 .
6. Ch o u R, Sh e k e lle P. W ill t h is p a t ie n t d eve lop p e rs is t e n t d is a blin g low b a ck p a in ? JA MA 2010 ;303 (13 ):
1295 –1302 .
 CHAPTER
4 Shoulder Pa in
Dennis W . Boulw are

A 26-ye ar-o ld m an p re se n t s
Clinica l Pre se nta tio n
Sh ou ld e r p a in is on e of t h e m os t com -
S
w it h a 10-d ay h ist o ry o f rig h t
E
m on com p la in t s s e e n in a p rim a ry ca re
C
sh o u ld e r an d u p p e r arm p ain ,
T
s e t t in g e s p e cia lly w it h e ld e rly p a t ie n t s .
I
O
w o rse w it h lif t in g h is arm o ve r Most ca u ses of sh ou ld er p a in a re d u e to
N
soft tiss u e p eria rticu la r p roblem s s u ch a s
2
h is h e ad an d in t e rf e rin g w it h
R
rota tor cu ff im p in gem en t or in ju ry, bu rs i-
e
sle e p as h e can n o t n d a
g
tis , a n d /or a n a d h esive ca p su litis (frozen
i
o
p o sit io n o f co m f o rt . He h as s h ou ld e r) a s op p os e d t o gle n oh u m e ra l
n
a
t rie d re st an d ace t am in o p h e n a r t h r it is . Th e clin ica l co n t e x t of t h e
l
P
a
w it h o u t re lie f . No t rau m a o r sh ou ld er p a in often p rovid es in sigh t in to
i
n
t h e s o u rce o f t h e p r o b le m s u ch a s a
S
p re cip it at in g e ve n t is re co lle ct -
y
h is t ory of a s ys t e m ic in a m m a t ory or
n
e d , b u t h e h ad re ce n t ly co m p le t e d re -p ain t in g h is b e d ro o m
d
d egen era tive con d ition , rep etitive u se, or
r
o
o ve r t h e w e e k e n d , 2 w e e k s ag o .
m
recen t in ju ry. Th is ch a p ter a d d resses th e
e
clin ica l s e t t in g of n on t ra u m a t ic is ola t e d
s
s h ou ld e r p a in , a n d for a d is cu s s ion of
sh ou ld er p a in d u e to system ic or gen era lized d isea ses su ch a s rh eu m a t oid a rth ri-
t is , p olym ya lgia rh e u m a t ica , or os t e oa rt h rit is , t h e re a d e r s h ou ld re fe r t o t h os e
sp eci c ch a p ters.
Mo s t ca u s e s of s h ou ld e r p a in ca n b e a t t ribu t e d t o s oft -t is s u e s t ru ct u re s
s u r ro u n d in g t h e gle n o h u m e ra l jo in t , a s o p p o s e d t o t h o s e o rigin a t in g fro m
gle n oh u m e ra l a rt h rit is . An u n d e rs t a n d in g of t h e a n a t om y a n d biom e ch a n ics of
t h e s h ou ld e r, cou p le d w it h a focu s e d p h ys ica l e xa m in a t ion t o loca lize t h e a n a -
t om ic s ou rce of p a in , t yp ica lly p rovid e s t h e clin icia n w it h a n a ccu ra t e d ia gn o-
s is (Fig. 4.1 ). Prop e r a n d e ffe ct ive m a n a ge m e n t ca n be im p le m e n t e d on ly a ft e r
t h e s ou rce of t h e p a in is id e n t i e d a ccu ra t e ly.
Th e s h ou ld e r is t h e m os t e xible a n d m obile join t in t h e bod y. Th is m obilit y
is a ch ieve d by h avin g a bon y ba ll-a n d -s ocke t join t w it h a la rge ba ll a n d a re la -
t ive ly s m a ll s ocke t . Th is re la t ive ly u n s t a ble a rra n ge m e n t is m a d e s e cu re by t h e
s u rrou n d in g e xt ra -a rt icu la r s t ru ct u re s in clu d in g t h e va riou s liga m e n t s , la bru m ,
ro t a t o r cu ff, b icip it a l t e n d o n , d e lt o id m u s cle s , a n d s o o n . Typ ica lly, s h o u ld e r
p a in is d u e t o d ys fu n ct ion or d is ru p t ion of t h e s u p p ort in g s oft -t is s u e s t ru c-
t u re s , a s o p p o s e d t o gle n o h u m e ra l a r t h r it is . Th e m o s t co m m o n ly in vo lve d
s t ru ct u re s ca u s in g s h ou ld e r p a in a re t h e rot a t or cu ff, t h e s u ba crom ia l bu rs a ,
t h e bicip it a l t e n d on , a n d t h e s yn ovia l ca p s u le.
Th e rs t s t e p in eva lu a t in g t h e p a t ie n t is t o co n rm t h a t t h ey a re d e s cr ib -
in g a s h o u ld e r jo in t p a in o r a jo in t -re la t e d p ro ble m a s t h ey o ft e n re fe r t o p a in
in t h e t ra p e z iu s m u s cle a s “s h o u ld e r p a in .” Pa in fro m t h e s h o u ld e r jo in t o r it s
re la t e d p e r ia r t icu la r s t r u ct u re s is fe lt in t h e a re a ove r t h e d e lt o id m u s cle o r
30
 Ch a p te r 4 Sh ou ld e r Pa in 31

Coracoclavicular Coracoclavicular
ligament (conoid) ligament (trapezoid)
Clavicle
Coracoacromial
ligament Acromioclavicular
ligament
Acromion

Subdeltoid bursa
Subscapular Coracohumeral
bursa ligament

Glenohumeral
ligament

Synovial sheath
around biceps
tendon

Biceps brachii Subscapularis

tendon

s
e
m
o
r
d
n
y
Figure 4 .1 The shoulder joint illustra ting the rela tionship of the glenohumera l joint, the supra spina tus tendon

S
of the rota tor cuff, a nd the long hea d of the biceps tendon. The a rea between the humera l hea d a nd a cromion

n
i
process is occupied by the suba cromia l bursa . From Hendrickson T. Ma ssa ge for Orthopedic Conditions .

a
P
Ba ltimore: Lippincott Willia ms & Wilkins; 2002.

l
a
n
o
i
g
t h e u p p e r bra ch iu m . Pa in d e s cr ib e d in t h e t ra p e z iu s m u s cle is like ly d u e t o

e
R
t ra p e z iu s m u s cle s t ra in o r re fe r re d from t h e ce rvica l s p in e . If t h e p a t ie n t con -

2
N
r m s t h a t t h e p a in is lo ca liz e d t o t h e d e lt o id a re a a n d / or t h e u p p e r b ra ch iu m ,

O
t h e n p ro ce e d w it h a n eva lu a t io n o f t h e s h o u ld e r jo in t a n d it s p e r ia r t icu la r

I
T
C
s t r u ct u re s .

CLINICAL POINTS
• Sh o u ld e r p a in is o ft e n d u e
t o a so ft t issu e ca u se su ch
a s t e n d o n it is o r b u rsit is,
ra t h e r t h a n a rt h rit is.
• Th e p h ysica l e xa m in a t io n
o f t h e sh o u ld e r is e sse n t ia l
in id e n t ifyin g t h e ca u se .
• The pain frequently radiates
in t o t h e b ra ch iu m .
• Exp lo rin g re ce n t o ve ru se o r
t ra u m a m a y h e lp id e n t ify
t h e ca u se .
• Wh e n e xa m in a t io n o f t h e
sh o u ld e r is fru it le ss in
id ent ifying a cause, con sid er
re ferred pa in fro m a ce rvical
ra d icu lo p a t h y.
E
S
His t orica l q u a lit ie s rega rd in g s eve rit y or q u a lit y of p a in a re lim it e d in id e n -
t ifyin g t h e ca u s e of p a in , w h e re a s p re cip it a t in g a n d a llevia t in g fa ct ors , re ce n t
re p e t it ive n on rou t in e a ct ivit ie s (h ou s e p a in t in g, w a llp a p e r h a n gin g, e t c.), a n d /
or in ju rie s ca n p rovid e s om e in s igh t . Sh ou ld e r p a in p re cip it a t e d by u s e is t h e
m os t com m on p re s e n t in g com p la in t a n d ce rt a in u s e s of t h e a ffe ct e d a rm ca n
be h e lp fu l. Th e rot a t or cu ff is t yp ica lly a ffe ct e d in t h e e xt e rn a l rot a t ors , e s p e -
cia lly t h e s u p ra s p in a t u s . Pa in fe lt w it h fo rw a rd e x io n , a b d u ct io n , o r a ct ive
e xt e rn a l rot a t ion of t h e s h ou ld e r t yp ica lly s u gge s t s in volve m e n t of t h e rot a t or
cu ff. Pa in on a bd u ct ion , bu t n ot on e xt e rn a l rot a t ion or forw a rd e xion of t h e
s h ou ld e r s u gge s t s t h e s u ba crom ia l bu rs a a s t h e ca u s e of p a in . Noct u rn a l p a in
d u rin g s le ep a n d t h e in a bilit y t o n d a re s t fu l re cu m be n t p os it ion in be d a re
a ls o com m on com p la in t s of a rot a t or cu ff p roble m or t h e s u ba crom ia l bu rs a .
Exa mina tio n
Th e p h ys ica l e x a m in a t io n o f t h e s h o u ld e r is cr it ica l in id e n t ifyin g t h e ca u s e
a n d m a n a gin g s h o u ld e r p a in . A s ys t e m a t ic r o u t in e e x a m in a t io n o f t h e
s h o u ld e r w ill h e lp t h e c lin ic ia n id e n t ify t h e c a u s e o f t h e s h o u ld e r p a in
q u ick ly a n d e ffe ct ive ly. Th e e x a m in a t io n w ill fo cu s o n t h e ra n ge o f p a s s ive
m o t io n in ro t a t io n , a b d u ct io n , a n d fo r w a rd e x io n a s w e ll a s p r ovo ca t ive
m a n e u ve r s t o a t t e m p t t o re p ro d u ce t h e p a in by a ct ive m o t io n , p a lp a t io n , o r
re s is t a n ce . Te n d e r n e s s p re s e n t o n a ct ive m o t io n t h a t is a b s e n t o n t h e s a m e
m o t io n p a s s ive ly u s u a lly s u gge s t s a t e n d in it is a s t h e p a in is e licit e d w h e n
t e n s io n is p la ce d o n t h e t e n d o n . Typ ica lly, t h e p a t ie n t w ill b e gu a rd in g t h e
p a in fu l s h o u ld e r vo lu n t a r ily o r in vo lu n t a r ily a n d t h e e x a m in a t io n w ill b e
 32 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
S
E
C
T
I
O
Figure 4 .2 Mea suring pa ssive rota tion. From Berg D, Worza la K. Atla s of Figure 4 .3 Mea suring pa ssive glenohumera l
N
Adult Physica l Dia gnosis . Phila delphia : Lippincott Willia ms & Wilkins; 2006. a bduction a nd forwa rd exion. From Berg D,
2
Worza la K. Atla s of Adult Physical Diagnosis .
R
Philadelphia: Lippincott Williams & Wilkins; 2006.
e
g
i
o
n
a
in s igh t fu l o n ly if t h e p a t ie n t is re la x e d a n d co o p e ra t ive . Th e p r u d e n t clin i-
l
P
cia n w ill e x a m in e t h e n o n -t e n d e r s h o u ld e r r s t t o p re p a r e t h e p a t ie n t fo r
a
i
n
e x a m in a t io n o f t h e p a in fu l s h o u ld e r.
S
St a r t t h e e x a m in a t io n w it h t h e p a t ie n t s it t in g on t h e e xa m in a t ion t a ble
y
n
in fro n t o f yo u . Pa s s ive ly e x t h e e lb ow t o 90 d e gre e s w it h t h e p a t ie n t ’s e lb ow
d
r
o
t o t h e ir s id e a n d ge n t ly u s e t h e fo re a r m t o ro t a t e t h e s h o u ld e r join t in t e r n a lly,
m
a s it t yp ica lly w ill n o t p re cip it a t e t e n d e r n e s s a n d w ill a id in ga in in g t h e
e
s
p a t ie n t ’s co n d e n ce , a n d t h e n t e s t fo r e x t e r n a l ro t a t io n (Fig. 4.2 ). Pa s s ive
in t e r n a l ro t a t io n t o 90 d e gre e s a n d p a s s ive e x t e r n a l ro t a t io n t o 90 d e gre e s a re
n o r m a l, a n d is t yp ica lly p a in le s s b u t d im in is h e s s ligh t ly w it h a ge . In t e r n a l
ro t a t io n is ra re ly t e n d e r o r lim it e d , b u t d e cre a s e d p a s s ive e x t e r n a l ro t a t io n
w ill s u gge s t s t r u ct u ra l b a r rie rs t o fu ll p a s s ive m ot ion in clu d in g b on y a n d s oft
t is s u e s t r u ct u re s . Os t e o p h yt e s from d e ge n e ra t ive join t d is e a s e o r a co n t ra ct e d
jo in t ca p s u le fr o m a d h e s ive ca p s u lit is , o r a fro z e n s h o u ld e r, a r e co m m o n
ca u s e s a n d w ill re q u ire im a gin g s t u d ie s t o d iffe re n t ia t e . No n -t e n d e r d e cre a s e d
p a s s ive ro t a t io n m a y in d ica t e t h e la t e r s t a ge s o f a d h e s ive ca p s u lit is o r s t a ble
d e ge n e ra t ive jo in t d is e a s e . Te n d e rn e s s on p a s s ive e xt e rn a l ro t a t io n o n ly m a y
in d ica t e a n a ct ive a d h e s ive ca p s u lit is o r a ct ive o s t e o a r t h r it is , w h e re a s t e n -
d e rn e s s o n p a s s ive in t e r n a l a n d e x t e r n a l rot a t ion s ca n s u gge s t a ct ive s yn ovi-
t is from in fe ct io u s o r in a m m a t o ry ca u s e s .
Ne xt , p os it ion you rs e lf a t t h e p a t ie n t ’s s id e a n d s t a bilize t h e s ca p u la w it h
you r h a n d clos e r t o t h e p a t ie n t ’s ba ck by p la cin g you r n ge rs on t h e h orizon t a l
s ca p u la r s p in e a n d you r t h u m b a lon g t h e s ca p u la ’s la t e ra l bord e r in h ibit in g it s
a bilit y t o s lid e la t e ra lly ove r t h e ribs . Us e you r forw a rd h a n d t o gra s p t h e e lbow
a n d w it h t h e p a t ie n t re la xe d , p a s s ive ly a bd u ct t h e s h ou ld e r t o m e a s u re gle n o-
h u m e ra l a bd u ct ion (Fig. 4.3 ). Norm a l gle n oh u m e ra l a bd u ct ion is 90 d egre e s , bu t
a ga in d im in is h e s w it h a gin g. Un le s s t h e p a t ie n t is co m p le t e ly re la xe d , t h e
t e ch n iq u e m a y n e e d t o b e d o n e s eve ra l t im e s t o a s s e s s a ccu ra t e ly t h e t r u e
ra n ge of m ot ion . Aft e r m e a s u rin g gle n oh u m e ra l a bd u ct ion , re le a s e t h e s ca p u la
a n d m e a s u re fu ll a bd u ct ion w h ich s h ou ld a p p roa ch 180 d egre e s . Th e n m e a s u re
forw a rd e xion by p a s s ive ly e xin g t h e s h ou ld e r a n t e riorly t o m e a s u re e xion ,
w h ich s h ou ld be 180 d egre e s . Th e s u p ra s p in a t u s t e n d on re s id e s in t h e s p a ce

PATIENT ASSESSMENT
• Alle via t in g a n d
e xa ce rb a t in g fa ct o rs ca n
b e h e lp fu l, e sp e cia lly
re ce n t o ve rh e a d u se
o f a rm .
• Te n d e rn e ss o n a ct ive
iso m e t ric lo a d in g b u t n o t
p a ssive ra n g e o f m o t io n
su g g e st s t e n d in it is.
• Te n d e rn e ss o n p a ssive
ra n g e o f m o t io n b u t n o t
a ct ive iso m e t ric lo a d in g
su g g e st s a ct ive a d h e sive
ca p su lit is o r a ct ive
o st e o a rt h rit is.
• Reserve imaging studies for
recurrent or recalcitrant
sh o u ld e r p a in .
Ch a p te r 4 Sh ou ld e r Pa in 33
be t w e e n t h e h u m e ra l h e a d a n d a crom ion p roce s s ; a s p a ce t h a t d e cre a s e s in
s ize w h e n t h e h u m e ru s is a bd u ct e d or e xe d forw a rd . Te n d e rn e s s on p a s s ive
gle n oh u m e ra l a bd u ct ion a n d forw a rd e xion is ve ry in d ica t ive of a n in a m e d
s u p ra s p in a t u s t e n d on . Te n d e rn e s s on p a s s ive a bd u ct ion bu t n ot e xio n s u g-
ge s t s s u ba crom ia l bu rs it is , w h ich ca n be con rm e d by d ire ct p a lp a t ion of t h e
s u ba crom ia l bu rs a t h a t lie s la t e ra l a n d in fe rior of t h e a crom ion p roce s s . Th e s e
t e ch n iq u e s w ill id e n t ify p roble m s w it h p rim a rily t h e s u p ra s p in a t u s in volve -
m e n t of t h e ro t a t or cu ff. Act ive is o m e t ric lo a d in g t o t e s t a ct ive ro t a t io n w ill
h e lp id e n t ify in volve m e n t of in fra s p in a t u s a n d t e re s m a jor m u s cle s a s a ca u s e
of s h ou ld e r p a in . To loa d t h e s h ou ld e r in is om e t ric rot a t ion , h ave t h e p a t ie n t
h old t h e ir a rm a t t h e ir s id e w it h t h e e lbow e xe d a t 90 d egre e s . As k t h e p a t ie n t
t o m a in t a in t h a t p os it ion a n d re s is t t h e e xa m in e r’s a t t e m p t t o m ove t h e fore -
a rm . Te n d e rn e s s w h e n t h e e xa m in e r a t t e m p t s t o m ove t h e s h ou ld e r in in t e r-
n a l rot a t io n in d ica t e s a p roble m w it h t h e ro t a t o r cu ff’s e x t e r n a l ro t a t o r s ; t h e
s u p ra s p in a t u s , in fra s p in a t u s , a n d / o r t e re s m a jo r. Te n d e rn e s s w h e n t h e e x a m -
in e r a t t e m p t s t o m ove t h e s h o u ld e r in e x t e r n a l r o t a t io n r e q u ir in g a ct ive
in t e r n a l ro t a t io n fro m t h e p a t ie n t im p lica t e s t h e in t e r n a l ro t a t o r s ; t h e s u b -
s ca p u la r is . Th e s e m a n e u ve r s w ill u s u a lly e licit t e n d e r n e s s w h e n t h e ro t a t o r
s
cu ff is in vo lve d . Th e s e m a n e u ve r s w ill n o t in d ica t e if t h e re is a t e a r o f t h e
e
m
ro t a t o r cu ff, ro t a t o r cu ff t e n d in it is , o r ca lci c t e n d in it is o f t h e s u p ra s p in a t u s
o
r
t e n d o n , w h ich a re a ll co m m o n ca u s e s o f s h ou ld e r p a in .
d
n
Bicip it a l t e n d in it is is a le s s com m on ca u s e of s h ou ld er p a in t h a n p roble m s
y
S
w it h t h e rot a t or cu ff or s u ba crom ia l bu rs it is , a n d s h ou ld be s u s p e ct ed if t h e p re-
n
i
ce d in g exa m in a t ion fa ils t o e licit a n y t e n d ern e s s . Bicip it a l t e n d in it is m os t com -
a
P
m on ly occu rs a s t h e t e n d on t rave rs e s t h e h u m e ra l h e a d t h rou gh t h e bicip it a l
l
a
n
groove on t h e a n t e rior s u rfa ce of t h e h u m e ra l h e a d . Bicip it a l t en d in it is a t t h is
o
i
level ca n be d et e ct e d by t h e p re s e n ce of t e n d ern e s s on d ire ct p a lp a t ion of t h e
g
e
R
t e n d on w it h in t h e bicip it a l groove of t h e h u m e ra l h e a d a n d /or t h rou gh Ye r-
2
ga s on ’s m a n e u ve r, a p rovoca t ive t es t . Pla ce you r t h u m b w it h m od e ra t e p res s u re
N
on th e a n t e rior s u rfa ce of t h e s h ou ld e r a n d p a s s ively rot a t e t h e s h ou ld e r u s in g
O
I
T
t h e fore a rm a s a leve r w it h t h e p a t ie n t h old in g t h e e lbow a t 90 d egre e s . You r
C
E
t h u m b w ill s e n s e t h e bicip it a l groove a s it d ip s in t o it a n d t h e p a t ie n t w ill fe e l
S
t e n d e rn e s s a s you r t h u m b rid es ove r t h e t e n d on w it h in t h e bicip it a l groove. Con -
rm a t ion ca n be a ch ieve d t h rou gh Yerga s on ’s m a n e u ve r, w h ich t e s t s t h e t e n d on
by a ct ive is om e t ric loa d in g. Have t h e p a t ien t p la ce h is or h er fu lly exe d e lbow
a t t h e s id e w it h t h e w ris t fu lly s u p in a t e d . Gra s p t h e p a t ien t ’s h a n d a n d a s k t h e
p a t ien t t o res is t you r a t t e m p t t o s im u lt a n e ou s ly ext e n d t h e e lbow a n d p ron a t e
t h e w ris t . Th is m a n eu ve r a ct ive ly loa d s t h e bicep s t e n d on a n d s h ou ld e licit t e n -
d e rn e s s a t t h e s h ou ld e r w h e n a n a ct ive bicip it a l t e n d in it is is p res en t .
Occa s ion a lly, s h ou ld e r p a in is n ot d u e t o d ys fu n ct ion or d is ru p t ion of t h e
s h ou ld e r join t or it s s u rrou n d in g s u p p ort ive s oft -t is s u e s t ru ct u re s . If t h e p re -
ce d in g e xa m in a t ion fa ils t o rep rod u ce t h e p a t ie n t ’s com p la in t a n d id e n t ify t h e
s ou rce of t h e p a in w it h in t h e s h ou ld e r a re a , t h e n a con s id e ra t ion of re fe rre d
s h ou ld e r p a in is m e rit e d . Pa in from a ce rvica l ra d icu lop a t h y oft e n ra d ia t e s t o
t h e s h ou ld e r a re a . Ke e p in g t h e s h ou ld e r in a n e u t ra l n on -t e n d e r p os it ion w h ile
t e s t in g t h e ce rvica l s p in e for p a s s ive h yp e re xt e n s ion com bin e d w it h p a s s ive
la t e ra l b e n d in g a n d / o r ro t a t io n m a y p re cip it a t e a n d re p ro d u ce t h e p a t ie n t ’s
ch ie f com p la in t of s h ou ld e r p a in . Le s s com m on ly, vis ce ra l p a t h ology from t h e
p a n cre a s or ga llbla d d e r w ill re fe r p a in t o t h e s h ou ld e r.
Studie s
Th e la bora t ory is of n o h e lp in eva lu a t in g t h e p a t ie n t w it h s h ou ld e r p a in ; t h e
p h ys ica l e xa m in a t ion is m ore e n ligh t e n in g.
In a cu t e s h ou ld e r p a in , im a gin g is ra re ly h e lp fu l a n d s h ou ld be a void e d
u n le s s a fra ct u re is a con s id e ra t ion .
 34 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

NOT TO BE MISSED Tre a tme nt

For t h e n on t ra u m a t ic ca u s e s of s h ou ld e r p a in d is cu s s e d e a rlie r, a p rogre s s ive
• Pa in t h a t is n o t
co n s e rva t ive t re a t m e n t p rogra m is u s u a lly s u cce s s fu l. Th is p rogra m s h o u ld
re p ro d u ce d o n t h e
e xa m in a t io n m a y b e s t a rt w it h n on p h a rm a cologic m a n a ge m e n t , in clu d in g re s t a n d ju d iciou s p h ys -
re fe rre d fro m t h e n e ck. ica l t h e ra p y. Re s t in g t h e a cu t e ly p a in fu l s h ou ld e r m a y re q u ire t h e u s e of a s lin g
w h e n u p righ t t o s u p p ort t h e a rm . Ove rh e a d u s e of t h e a rm w it h t h e s h ou ld e r
in p rolon ge d a bd u ct ion is t o be a void e d a s it w ill ce rt a in ly a ggrava t e t h e p a in .
Ph ys ica l t h e ra py in t h e a cu t e ly p a in fu l s e t t in g s h ou ld be lim it e d t o p a s s ive
ra n ge -o f-m o t io n e x e rcis e s , s u ch a s Cod m a n p e n d u lu m sw in gin g e x e rcis e s .
Ra n ge of m ot ion e xe rcis e s h e lp avoid t h e d eve lop m e n t a n d com p lica t ion s of
a d h e s ive ca p s u lit is , or a froze n s h ou ld e r. Pa s s ive m ove m e n t s a ft e r loca l h e a t or
cold a p p lica t ion , or a ft e r a n a lge s ic a d m in is t ra t ion , a re a d vis a ble. Th e s e m ove -
m e n t s s h o u ld s t a rt s low ly, w it h p rogre s s ive ly in cre a s e d ra n ge o f m o t io n a s
s ym p t o m s s u b s id e . A go o d s t a rt in g p o in t is t h e s im p le p e n d u lu m e x e rcis e
(Fig. 4.4 ). In s t ru ct t h e p a t ie n t t o u s e t h e u n a ffe ct e d a rm for s u p p ort by p la cin g
it on a s t a ble t a ble or ch a ir. Th e p a t ie n t ca n e x t h e t ru n k a t t h e h ip s or w a is t
a n d s u s p e n d t h e a ffe ct e d a r m u n t il a p p rox im a t e ly 90 d e gre e s o f e x io n is
S
a ch ieve d . Th e p a t ie n t ca n sw in g t h e s u s p e n d e d a ffe ct e d a rm p a s s ive ly like a
E
C
p en d u lu m . Th e exercise sh ou ld be d on e in th e sagitta l p la n e for exion –exten sion ,
T
I
O
a n d in t h e coron a l p la n e for a bd u ct ion –a d d u ct ion . W it h t im e t h e d egre e s of
N
sw in gin g ca n be in cre a s e d a n d t h e p a s s ive sw in gin g ca n be re p la ce d by a n
2
a ct ive ra n ge of m ot ion e xe rcis e s , eve n t u a lly w it h re s is t a n ce.
R
e
An a lge s ia ca n be p rovid e d t h rou gh n on p h a rm a cologic m e a s u re s s u ch a s
g
i
o
h e a t a n d cold p a cks , or u lt ra s on ic t h e ra p y. If in e ffe ct ive, t h e n s im p le a n a lge s ics
n
a
a n d n on s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs ) a re u s u a lly a d e q u a t e. Na r-
l
P
co t ic a n a lge s ics m a y b e n e ce s s a ry fo r s eve re p a in b u t s h o u ld b e u s e d o n a
a
i
lim it e d ba s is .
n
S
If t h e p a in is s eve re or t h e p re ce d in g ba s ic m e a s u re s h ave a lre a d y fa ile d ,
y
n
t h e n loca l cort icos t e roid s a re u s u a lly in d ica t e d a n d ca n be a d m in is t e re d in t o
d
r
o
t h e s u ba crom ia l bu rs a or in t o t h e gle n oh u m e ra l join t .
m
e
s
Figure 4 .4 The sta rting position for Codma n pendulum exercises for pa ssive motion of the shoulder. From
Koopma n WJ, Morela nd LW, eds. Arthritis a nd Allied Conditions A Textbook of Rheuma tology, 15th ed.
Phila delphia : Lippincott Willia ms & Wilkins; 2005.
 Ch a p te r 4 Sh ou ld e r Pa in 35

In m os t ca s e s , t h e re w ill be s ign i ca n t a n d s a t is fa ct ory im p rove m e n t in 1

WHEN TO REFER
• St ru ct u ra l a b n o rm a lit ie s
like in fe rio r a cro m io cla vic-
u la r o st e o p h yt e s, ro t a t o r
cu ff co m p le t e t e a rs, o r
se ve re d e g e n e ra t ive
g le n o h u m e ra l ch a n g e s
m a y re q u ire re fe rra l t o a n
o rt h o p e d ic su rg e o n .
t o 4 w e e ks . Pa in t h a t p e rs is t s beyon d t h is t im e or re cu rs w it h a re s u m p t ion of
u s u a l a ct ivit y s u gge s t s ch ron ic im p in ge m e n t , in s t a bilit y, or a lt e rn a t ive ca u s e.
At t h is t im e, a re fe rra l t o a rh e u m a t ologis t m ay be a d vis a ble.
Clinica l Co urse
In m os t ca s e s , a cu t e s h ou ld e r p a in w ill re s olve s p on t a n e ou s ly w it h m ild a n a l-
ge s ia , p a s s ive ra n ge of m ot ion e xe rcis e s , a n d t im e. Eve n w it h p rop e r t re a t m e n t ,
s h ou ld e r p a in ca n be re cu rre n t a n d re fra ct ory if a n u n d e rlyin g ca u s e of in s t a -
bilit y or im p in ge m e n t is u n corre ct e d . Th e p a t ie n t w h o re t u rn s w it h re cu rre n t
o r re fra ct o ry p a in s h o u ld u n d e rgo t h e s a m e clin ica l e x a m in a t io n in it ia lly
d e s cribe d t o con rm t h e s a m e d ia gn os is . At t h is t im e, im a gin g ca n be h e lp fu l
a n d p la in ra d iogra p h s of t h e s h ou ld e r m ay reve a l t h e u n d e rlyin g ca u s e.
In ca s e s of ch ron ic or re cu rrin g p a in , im a gin g s t u d ie s ca n id e n t ify t h e ca u s e
in ca s e s of ch ron ic rot a t or cu ff p a t h ology or ca lci c t e n d in it is . Th e follow in g
a re ra d iogra p h ic n d in gs of com m on ca u s e s of re cu rre n t or p e rs is t e n t s h ou ld e r
p a in :

s
e
m
1. In fe rior os t e op h yt e of a d ege n e ra t ive a crom iocla vicu la r join t . Th e os t e op h yt e

o
r
w ill e n croa ch in t o t h e a crom ioh u m e ra l s p a ce a n d re s u lt in a bon y im p in ge -

d
n
m e n t of t h e rot a t or cu ff. Th is n d in g m ay in d ica t e t h e n e e d for a s u rgica l

y
S
con s u lt a t ion .

n
i
2. Ca lci c t e n d in it is . Ca lci ca t ion of t h e rot a t or cu ff is a con s e q u e n ce of t h e

a
P
ch ron icit y of t h e in a m m a t ion a n d n ot a ca u s e of t h e t e n d in it is . It in d ica t e s

l
a
a m ore ch ron ic con d it ion a n d t h e n e e d for con t in u e d t h e ra py. Eve n t u a lly t h e

n
o
i
ca lci ca t ion m a y re s olve a s w ill t h e con d it ion .

g
e
3. Scleros is a n d cys t ic d ege n e ra t ion of t h e h u m era l gre a t e r t u be ros it y. Th is im -

R
2
p lie s a ch ron ic a n d s eve re im p in ge m e n t of t h e h u m e ra l h ea d a ga in s t t h e a c-

N
rom ion w it h con cu rre n t im p in gem e n t of t h e rot a t or cu ff w it h con s eq u e n t ia l

O
I
join t in s t a bilit y. Th is n d in g im p lie s t h e n e e d for a s u rgica l con s u lt a t ion .

T
C
4. Na rrow in g or oblit e ra t ion of t h e a crom ioh u m e ra l s p a ce. Th is n d in g ca n

E
S
on ly occu r w it h a t t rit ion or a com p le t e t e a r of t h e rot a t or cu ff, in d ica t in g
in s t a bilit y of t h e join t . If s e e n on p la in ra d iogra p h y, a s u rgica l con s u lt a t ion
m a y be re q u ire d .

ICD9
727.3 Bursitis NEC
726.10 sh o u ld e r
726.90 Capsulitis (jo in t )
726.0 ad h e sive (sh o u ld e r)
De g e ne ratio n, de g e ne rative
718.01 sh o u ld e r
De rang e me nt
718.30 re cu rre n t
718.31 sh o u ld e r re g io n
718.91 sh o u ld e r re g io n
Diso rde r
727.9 b u rsa
726.10 sh o u ld e r re g io n
733.90 cart ilag e NEC
718.01 sh o u ld e r re g io n
716.60 Mo no arthritis
716.61 sh o u ld e r (re g io n )
(Co n t in u e d )
 36 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

ICD9 (Co n t in u e d )
715.91 Oste o arthro sis/ Oste o arthritis sho ulde r (d e g e n e rat ive )
(h yp e rt ro p h ic)
780.96 Pain(s)
719.40 jo in t
719.41 sh o u ld e r (re g io n )
726.90 Pe riarthritis (jo in t )
726.2 sh o u ld e r
726.90 –Te ndinitis, te ndo nitis
727.82 calci c
726.11 sh o u ld e r

Additio na l Re a ding
1. Hu s n i EM , Don oh u e JP. Pa in fu l s h ou ld e r a n d re e x s ym p a t h e t ic d ys t ro p h y s yn d rom e . In Koo p m a n W J,
S
More la n d LW, e d s ; A rthritis and A llied Conditions , 15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s & W ilkin s ;
E
C
2005 :2133 –2151 .
T
2. Bou lw a re DW. Th e p a in fu l s h ou ld e r . In Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of
I
O
Rheum atology . Ph ila d e lp h ia : Lip p in cot t Willia m s & Wilkin s ;2003 :43 –47 .
N
3. Wood w a rd TW , Be s t TM . Th e p a in fu l s h ou ld e r: p a rt 1. Clin ica l eva lu a t ion . A m Fam Physician 2000 ;61 :3079 –
2
3088 .
R
4. Woo d w a rd TW, Be s t TM . Th e p a in fu l s h ou ld e r : p a rt 2. Acu t e a n d ch ron ic d is ord e rs . A m Fam Physician
e
g
2000 ;61 :3291 –3300 .
i
o
n
a
l
P
a
i
n
S
y
n
d
r
o
m
e
s
CHAPTER
5 Pa inful Feet
in vo lve s w e arin g d re ss sh o e s ap p ro p riat e f o r h e r p o sit io n an d
o f t e n lo n g p e rio d s o f st an d in g w h ile m ak in g p re se n t at io n s.
He r b u sin e ss f o o t w e ar is t yp ically e le vat e d h e e ls an d h e r
e xam in at io n re ve als a p e s cavu s t yp e o f f o o t w it h n u m e ro u s
h ard co rn s o n h e r t o e s.
CLINICAL POINTS
• Fo o t p a in is a sym p t o m a n d
n o t a d ia g n o sis.
• Ca re fu l e xa m in a t io n o f t h e
fo o t w ill p ro vid e g re a t
in sig h t in t o t h e d ia g n o sis.
• Ort h o se s a n d p ro p e r fo o t -
w e a r ca n p ro vid e re lie f in
m a n y ca se s.
Dennis W. Boulw are and Gustav o R. Heudebert
A 42-ye ar-o ld f e m ale
Intro ductio n
s
Foot p a in a n d los s of fu n ct ion m a y be
m ark e t in g e xe cu t ive
e
m
ca u s e d by a n u m be r of p roblem s a n d ca n
co m p lain s o f p ain f u l
o
be t h e m a n ife s t a t ion of a la rge n u m be r
r
d
f e e t t h at are in t e rf e r-
n
of d e n e d clin ica l e n t it ie s . Foot p a in is a
y
S
in g w it h h e r ab ilit y s ym p t om , n ot a d ia gn os is , a n d a p re cis e
n
i
d ia gn o s is s h o u ld b e m a d e t o e n s u re
a
t o w o rk . He r w o rk
P
p rop e r t re a t m e n t , w h ich is s p e ci c for
l
a
t h a t p a rt icu la r p roble m . If t h e p h ys icia n
n
o
p e rce ive s t h e p roble m s im p ly a s “foot
i
g
e
p a in ,” a s u cce s s fu l ou t com e is u n like ly
R
a n d eve n t h o u gh fo o t p ro ble m s a re
2
N
ext re m e ly com m on , t h e foot is la rge ly a n
O
I
ign ored a re a .
T
C
Fo r p ra ct ica l p u r p o s e s , t h e fo o t is
E
S
d ivid e d a n a t o m ica lly a s t h e fo re fo o t ,
t h e m id foot , a n d t h e h in d foot . Th e fore foot com p ris e s t h e t oe s , t h e ir re s p e ct ive
m e t a t a rs a l bon e s , a n d s u rrou n d in g s oft t is s u e s . Th e h in d foot is d e n e d a s t h e
e ra co m p ris in g t h e ca lca n e o u s a n d t h e t a lu s w it h t h e ir co r re s p o n d in g s u r-
rou n d in g s oft t is s u e s . Fin a lly, t h e m id foot is t h e a re a occu p ie d by t h e cu boid ,
n avicu la r, a n d t h re e cu n e iform bon e s (la t e r, in t e rm e d ia t e, a n d m e d ia l) a n d t h e
corre s p on d in g s u rrou n d in g s oft t is s u e. Mos t of t h e n on t ra u m a t ic d is ord e rs of
t h e foot w ill occu r in t h e fore foot a n d h in d foot a re a ; fu rt h e rm ore, a n d for t h e
p u rp os e s of cla rit y, w e w ill cla s s ify t h e s e d is ord e rs n os ologica lly a s re la t e d t o
m e ch a n ica l or n e u rologica l e t iologie s .
Clinica l Pre se nta tio n
MECHANICAL PROBLEMS
Fo re fo o t Varus and Valg us De fo rmitie s
Fore foot va ru s or va lgu s is a n a bn orm a lit y of t h e foot in w h ich t h e fore foot is
in ve rt e d (va ru s ) or eve rt e d (va lgu s ) in re la t ion t o t h e h in d foot w h e n t h e s u bt a -
la r join t is in t h e n e u t ra l p os it ion . Th e h e a d of t h e rs t a n d ft h m e t a t a rs a ls a re
n o lon ge r in t h e s a m e h orizon t a l p la n e of e a ch ot h e r w it h t h e rs t m e t a t a rs a l
h e a d d or s a l (va ru s ) or ve n t ra l (va lgu s ) re la t ive t o t h e ft h m e t a t a r s a l h e a d .
Fore foo t va r u s is a m a jo r ca u s e o f co m p e n s a t o ry s u bt a la r p ro n a t ion o f a n
a bn orm a l d egre e d u rin g t h e s t a n ce p h a s e of ga it .
37
 38 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

Figure 5.1 Pes pla nus deformity with loss of the Figure 5.2 Severe pes ca vus seen in spa stic neurologi-
longitudina l arch of the foot. From Berg D, ca l disorders.
Worza la K. Atla s of Adult Physical Dia gnosis .
Phila delphia , PA: Lippincott Willia ms & Wilkins;
2006.

Pe s Planus
S
E
Pe s p la n u s , or a t fe e t , is oft e n a s ym p t om a t ic bu t ca n ca u s e fa t igu e of t h e foot
C
T
m u s cle s a n d a ch in g w it h in t ole ra n ce t o p rolon ge d w a lkin g or s t a n d in g (Fig. 5.1 ).
I
O
Th e m os t com m on t yp e is t h e exible a t foot a lt h ou gh ot h e r ca u s e s of a t fe e t
N
2
a re t a rs a l coa lit ion , con ge n it a l ve rt ica l t a lu s , a n d ru p t u re of t h e t ibia lis p os t e rior
R
t e n d on , w h ich ca u s e s t h e t yp ica l u n ila t e ra l, a cq u ire d a t foot . In p e s p la n u s ,
e
g
t h e re is los s of t h e lon git u d in a l a rch on t h e m e d ia l a s p e ct of t h e foot , t h e ca l-
i
o
n
ca n e u s is eve rt e d (va lgu s ), a n d on a m bu la t ion ou t -t oe in g ca n be s e e n ; t h e s e
a
l
ch a n ge s a re m ore a p p a re n t on w e igh t be a rin g. Th is con d it ion is la rge ly in h e r-
P
a
it e d a n d is s e e n w it h ge n e ra lize d h yp e rm obilit y.
i
n
S
y
Pe s Cavus
n
d
An u n u s u a lly h igh m e d ia l lon git u d in a l a rch ch a ra ct e rize s p e s cavu s , or cla w
r
o
foot , a n d in s eve re ca s e s ca u s e s a h igh lon git u d in a l a rch re s u lt in g in s h ort e n -
m
e
in g of t h e foot (Fig. 5.2 ). W it h t h e a bn orm a lly h igh lon git u d in a l a rch , t h e re is
s
re la t ive s h ort e n in g of t h e e xt e n s or liga m e n t s ca u s in g d ors i e xion of t h e m e t a -
t a rs op h a la n ge a l (MTP) join t s a n d p la n t a r e xion of t h e p roxim a l in t e rp h a la n -
ge a l a n d d is t a l in t e rp h a la n ge a l join t s givin g t h e cla w in g a p p e a ra n ce of t h e
t oe s . Th e p la n t a r fa s cia m a y be con t ra ct e d a n d t h e ca lca n e u s is u s u a lly in a
va ru s (in ve rt e d ) p os it ion . In ge n e ra l, t h e t e n d e n cy t o p e s cavu s is in h e rit e d bu t
ca n be a clu e t o a n u n d e rlyin g n e u rologic d is ord e r, s u ch a s m ye lom e n in goce le,
Ch a rco t –Ma r ie –Too t h d is e a s e , o r Frie d re ich a t a xia . Alt h ou gh p e s ca vu s ca n
ca u s e foot fa t igu e, p a in , a n d t e n d e rn e s s ove r t h e m e t a t a rs a l h e a d s w it h ca llu s
form a t ion , it ca n be a s ym p t om a t ic. Ca llu s e s ca n be p re s e n t ove r t h e d ors u m of
t h e t oe s from in cre a s e d frict ion t o foot w e a r.

Hallux Valg us
In h a llu x va lgu s , d evia t ion of t h e la rge t oe la t e ra l t o t h e m id lin e a n d d evia t ion
of t h e rs t m e t a t a rs a l m e d ia lly occu r. A bu n ion (a d ve n t it iou s bu rs a ) of t h e h e a d
of t h e rs t MTP join t m ay be p re s e n t , oft e n ca u s in g p a in , t e n d e rn e s s , a n d sw e ll-
in g. Ha llu x va lgu s is m ore com m on in w om e n a n d m ay re s u lt from a ge n e t ic
t e n d e n cy, p oorly t t e d foot w e a r, or s e con d a ry t o ch ron ic a rt h rit id e s s u ch a s
rh e u m a t oid a rt h rit is , ch ron ic gou t , or os t e oa rt h rit is .

Hallux Rig idus

In h a llu x rigid u s , im m obilit y of t h e rs t MTP join t e s p e cia lly on e xt e n s ion is
p re s e n t . Pa in is oft e n p re s e n t a t t h e ba s e of t h e big t oe a n d is a ggrava t e d by
w a lkin g, e s p e cia lly in foot w e a r w it h e leva t e d h e e ls . A p rim a ry t yp e of h a llu x
rigid u s is s e e n in you n ge r p e rs on s , a n d t h e a cq u ire d form m a y be s e con d a ry t o
t ra u m a , os t e oa rt h rit is , rh e u m a t oid a rt h rit is , or gou t . Os t e op h yt e s a n d s cle ros is
 Ch a p te r 5 Pa in fu l Fe e t 39

of t h e rs t MTP join t ca n be s e e n on ra d iogra p h s . Th e t e rm hallux lim itus is

s om e t im e s u s e d t o d e n ot e a m ild e r d egre e of im m obilit y of t h e rs t MTP join t .

Bunio ne tte
A bu n ion e t t e, or t a ilor's bu n ion , is a p rom in e n ce of t h e ft h m e t a t a rs a l h e a d
re s u lt in g from t h e ove rlyin g bu rs a a n d a loca lize d ca llu s . Pre s s u re from s h oe s
ca n ca u s e p a in , a n d t e n d e rn e s s m a y be p re s e n t ove r t h e sw olle n bu rs a .

Hamme r To e
In h a m m e r t oe s , t h e p roxim a l in t e rp h a la n ge a l join t is e xe d a n d t h e t ip of t h e
t oe p oin t s d ow n w a rd . Th e s e con d t oe is m os t com m on ly in volve d a n d ca llu s e s
m a y fo rm a t t h e t ip o f t h e t o e a n d ove r t h e d o r s u m o f t h e in t e rp h a la n ge a l
join t s , re s u lt in g from frict ion a ga in s t t h e s h oe. Ha m m e r t oe m a y be con ge n it a l,
a cq u ire d s e con d a ry t o h a llu x va lgu s or im p rop e r foot w e a r. W h e n h a m m e r t oe s
a re a s s ocia t e d w it h h yp e re xt e n s ion of t h e MTP join t s , t h e d e form it y is kn ow n
a s “cocke d -u p t oe s .” Th is m ay be s e e n in rh e u m a t oid a rt h rit is .

Me tatarsalg ia

s
Pa in a ris in g from t h e m e t a t a rs a l h e a d s , kn ow n a s m e t a t a rs a lgia , is a s ym p t om

e
m
re s u lt in g from a va rie t y of con d it ion s . Pa in on s t a n d in g a n d t e n d e rn e s s on p a l-

o
r
p a t ion of t h e m e t a t a rs a l h e a d s a re p re s e n t . Ca llu s e s ove r t h e m e t a t a rs a l h e a d s

d
n
a re u s u a lly s e e n . Th e ca u s e s of m e t a t a rs a lgia a re m a n y, in clu d in g foot s t ra in ,

y
S
u s e of h igh -h e e l s h oe s , a n eve rt e d foot , t ra u m a , s e s a m oid it is , h a llu x va lgu s ,

n
i
ch ron ic a rt h rit is , foot s u rge ry, or a foot w it h a p e s ca vu s d e form it y.

a
P
l
a
n
Me tatarsal Stre ss Fracture

o
i
Pa in , sw e llin g, t e n d e rn e s s , a n d occa s ion a l e ryt h e m a d eve lop ove r t h e m e t a t a r-

g
e
R
s a l a re a , u s u a lly w it h ou t a n y cle a r h is t ory of t ra u m a . Th e n e ck of t h e s e con d

2
m e t a t a rs a l bon e is m os t fre q u e n t ly in volve d , bu t a ll m e t a t a rs a ls ca n be s it e s of

N
fra ct u re (Fig. 5.3 ). W h ile ove ru s e s u ch a s joggin g a re com m on ca u s e s , s t re s s

O
I
T
fra ct u re s ca n be s e e n in rh e u m a t oid a rt h rit is or ge n e ra lize d os t e op oros is or t h e

C
E
e ld e rly w it h ou t a p re cip it a t in g id e n t i a ble eve n t or a ct ivit y. Th e key t o d ia gn o-

S
s is of s t re s s fra ct u re s of t h e foot is t o h a ve a h igh in d e x of s u s p icion . Th e d if-
cu lt y in m a k in g t h e d ia gn o s is is t h a t in it ia l ra d iogra p h s u s u a lly s h ow n o
a bn orm a lit ie s re q u irin g a rep e a t ra d iogra p h s eve ra l w e e ks la t e r t o d e m on s t ra t e
h e a lin g w it h ca llu s form a t ion . Bon e s ca n s ca n be h e lp fu l t o e s t a blis h a n e a rly
d ia gn os is a s t h ey s h ow a n in cre a s e in u p t a ke ove r t h e fra ct u re s it e.

Se samo id Injurie s
Le s ion s of t h e s e s a m oid bon e s of t h e big t oe m ay e xh ibit loca l p a in a n d t e n d e r-
n e s s u n d e r e it h e r t h e m e d ia l or la t e ra l s e s a m oid . Th e p a in m ay h ave a gra d u a l
on s e t or begin a bru p t ly follow in g a cu t e t ra u m a a n d is e xa ce rba t e d by d ors i e x-
ion of t h e big t oe or u p on w e igh t be a rin g. Re cogn ize d ca u s e s of s e s a m oid p a in ,
w h ich h a s loos e ly be e n ca lle d s e s a m oid it is , a re rep e t it ive s t ra in from a ct ivit ie s
s u ch a s d a n cin g or lon g-d is t a n ce ru n n in g, s t re s s fra ct u re, t ra u m a t ic fra ct u re,
bip a rt it e s e s a m oid , a n d os t e och on d rit is .

Fre ibe rg Dise ase

Fre ibe rg d is e a s e is a n os t e och on d ros is of t h e s e con d m e t a t a rs a l h e a d , p rim a rily
a ffe ct in g girls a rou n d 12 ye a rs of a ge. Pa in , t e n d e rn e s s , a n d sw e llin g of t h e m e t -
a t a rs a l a re p re s e n t . Ra d iogra p h s reve a l fra gm e n t a t ion , s cle ros is , a n d d e form it y
of t h e m e t a t a rs a l h e a d .

Achille s Te ndinitis
Ach ille s t e n d in it is u s u a lly res u lt s from t ra u m a , a t h le t ic overa ct ivit y, or im p rop -
erly t t in g s h oe s w it h a s t iff h e e l cou n t e r, bu t it ca n a ls o a ris e from in a m m a t ory
con d it ion s s u ch a s a n kylos in g s p on d ylit is , Re it e r s yn d rom e, gou t , rh e u m a t oid
 40 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
S
E
C
T
I
O
N
2
R
e
g
i
o
n
a
l
A B
P
a
i
n
S
Figure 5.3 Meta ta rsa l stress fra cture 2 weeks (A) a fter injury a nd 6 weeks (B) la ter demonstra ting ea rly periostea l rea ction a t 2 weeks a nd ca llus forma -
y
n
tion a t 6 weeks. With permission from Da ffner RH. Clinica l Ra diology: The Essentia ls , 3rd ed. Phila delphia , PA: Lippincott Willia ms & Wilkins; 2007.
d
r
o
m
e
s
a rt h rit is , a n d ca lciu m pyrop h os p h a t e d ep os it ion d is e a s e. Pa in , sw ellin g, a n d t e n -
d e rn e s s occu r over t h e Ach ille s t e n d on a t it s a t t a ch m e n t a n d in t h e a re a p roxi-
m a l t o t h e a t t a ch m e n t . Crep it u s on m ot ion a n d p a in on d ors i e xion m ay be
p re s e n t .

Achille s Te ndo n Rupture

Sp on t a n e ou s ru p t u re of t h e Ach ille s t e n d on is w e ll kn ow n a n d occu rs w it h a
s u d d e n on s e t of p a in d u rin g force d d ors i e xion . An a u d ible s n a p m ay be h e a rd ,
follow e d by d if cu lt y in w a lkin g a n d s t a n d in g on on e ' s t oe s on t h e a ffe ct e d
foot . Sw e llin g a n d e d e m a ove r t h e a re a u s u a lly d eve lop . Dia gn os is ca n be m a d e
w it h t h e Th om p s on t e s t , in w h ich t h e p a t ie n t kn e e ls on t h e ch a ir w it h t h e fe e t
e xt e n d in g ove r t h e e d ge a n d t h e e xa m in e r s q u e e ze s t h e ca lf a n d p u s h e s t ow a rd
t h e kn e e. Norm a lly, t h is p rod u ce s p la n t a r e xion , bu t in a ru p t u re d t e n d on , n o
p la n t a r e x io n o ccu r s . Ach ille s t e n d on r u p t u re is ge n e ra lly d u e t o a t h le t ic
eve n t s or t ra u m a from ju m p s or fa lls . Ma gn e t ic re s on a n ce im a gin g (MRI) ca n
a id in t h e d ia gn os is a n d ca n d is t in gu is h a com p le t e ru p t u re from a p a rt ia l on e.
Th e t e n d on is m ore p ron e t o t e a r in t h os e h avin g p re e xis t in g Ach ille s t e n d on
d is e a s e or t a kin g cort icos t e roid s .

Re tro calcane al Bursitis

Th e re t roca lca n e a l bu rs a is loca t e d be t w e e n t h e in s id e s u rfa ce of t h e Ach ille s
t e n d o n a n d t h e ca lca n e u s ; in a m m a t ion o f t h is s t r u ct u re is kn ow n a s a n
e n t h e s it is . Th e bu rs a 's a n t e rior w a ll is broca rt ila ge w h e re it a t t a ch e s t o t h e
ca lca n e u s , w h e re a s it s p os t e rior w a ll ble n d s w it h t h e s u rfa ce of t h e Ach ille s
t e n d on . Ma n ife s t a t ion s a re p a in a t t h e ba ck of t h e h e e l, t e n d e rn e s s of t h e a re a
 Ch a p te r 5 Pa in fu l Fe e t 41

a n t e rior t o t h e Ach ille s t e n d on , a n d p a in o n d o r s i e x io n . Lo ca l sw e llin g is

p re s e n t , w it h bu lgin g on t h e m e d ia l a n d la t e ra l a s p e ct s of t h e t e n d on . Re t roca l-
ca n e a l bu rs it is m ay coe xis t w it h Ach ille s t e n d in it is , a n d d is t in gu is h in g t h e t w o
is s om e t im e s d if cu lt . Th is con d it ion m ay be s e con d a ry t o rh e u m a t oid a rt h ri-
t is , s p on d ylit is , Re it e r s yn d rom e, gou t , a n d t ra u m a .

Subcutane o us Achille s Bursitis

A s u bcu t a n e ou s bu rs a p os t e rior t o t h e Ach ille s t e n d on m ay be com e sw olle n in
t h e a bs e n ce o f s ys t e m ic d is e a s e . Th is bu rs it is , kn ow n a s “p u m p -bu m p s ,” is
s e e n p re d om in a n t ly in w om e n a n d re s u lt s from p re s s u re of s h oe s , a lt h ou gh it
ca n a ls o re s u lt from bon y e xos t os e s .

Plantar Fasciitis
Pla n t a r fa s ciit is occu rs p rim a rily be t w e e n 40 a n d 60 ye a rs of a ge bu t ca n b e
s e e n in a ll a ge s . A gra d u a l on s e t of p a in in t h e p la n t a r a re a of t h e h e e l u s u a lly
occu rs bu t m a y occu r follow in g t ra u m a or from ove ru s e a ft e r a ct ivit ie s s u ch a s
t a kin g p a rt in a t h le t ics , w a lkin g for a p rolon ge d t im e, w e a rin g im p rop e rly t -
t in g s h oe s , or s t rikin g t h e h e e l w it h s om e force. Th e p a in is ch a ra ct e ris t ica lly

s
m o s t s eve re in t h e m o rn in g u p o n a ris in g e s p e cia lly w it h t h e rs t few s t e p s

e
m
from be d . Aft e r a n in it ia l im p rove m e n t , t h e p a in m a y ge t w ors e la t e r in t h e d ay

o
r
e s p e cia lly a ft e r p rolon ge d s t a n d in g or w a lkin g, or a ft e r p rolon ge d p e riod s of

d
n
in a ct ivit y a ga in . Pa lp a t ion t yp ica lly reve a ls t e n d e rn e s s a n t e rom e d ia lly on t h e

y
S
m e d ia l ca lca n e a l t u be rcle a t t h e origin of t h e p la n t a r fa s cia . Mos t p a t ie n t s w it h

n
i
h e e l p a in h ave ca lca n e a l s p u rs , bu t t h e s p u r it s e lf is n ot like ly t h e ca u s e of p a in .

a
P
l
a
n
Po ste rio r Tibial Te ndinitis and Rupture

o
i
Pa in , sw e llin g, a n d loca lize d t e n d e rn e s s ju s t p os t e rior t o t h e m e d ia l m a lle olu s

g
e
R
occu r in p os t e rior t ibia l t e n d in it is . Ext e n s ion a n d e xion m ay be n orm a l, bu t

2
p a in is p re s e n t on a ct ive in ve rs ion a ga in s t re s is t a n ce or p a s s ive eve rs ion . Th e

N
d is com fort is u s u a lly w ors e a ft e r a t h le t ic eve n t s .

O
I
T
Ru p t u re of t h e p os t e rior t ibia lis t e n d on , w h ich is n ot com m on ly re cogn ize d ,

C
E
is a ca u s e of a p rogre s s ive a t foot . It m ay be ca u s e d by t ra u m a , ch ron ic t e n d on

S
d ege n e ra t ion , or rh e u m a t oid a rt h rit is . An in s id iou s on s e t of p a in , sw e llin g, a n d
t e n d e rn e s s occu r s a lo n g t h e co u rs e of t h e t e n d on ju s t d is t a l t o t h e m e d ia l
m a lle olu s . Th e u n ila t e ra l d e form it y of h in d foot va lgu s a n d fore foot a bd u ct ion
is a n im p ort a n t n d in g. Th e fore foot a bd u ct ion ca n be s e e n be s t from be h in d ;
m ore t oe s a re s e e n from t h is p os it ion t h a n w ou ld be s e e n n orm a lly. Th e re s u lt
of t h e s in gle h e e l ris e t e s t is p os it ive w h e n t h e p a t ie n t is u n a ble t o ris e on t o t h e
ba ll of t h e a ffe ct e d foot w h ile t h e con t ra la t e ra l foot is off t h e oor. Com p u t e d
t om ogra p h y (CT) a n d MRI a re h e lp fu l in t h e d ia gn os is of t e n d on ru p t u re.

Pe ro ne al Te ndo n Dislo catio n and Pe ro ne al Te ndinitis

Dis lo ca t ion of t h e p e ro n e a l t e n d o n m a y occu r from a d ire ct blow, re p e t it ive
t ra u m a , or s u d d e n d ors i e xion w it h eve rs ion . Som e t im e s a p a in le s s s n a p p in g
n ois e is h e a rd a t t h e t im e of d is loca t ion . Ot h e r p a t ie n t s rep ort m ore s eve re p a in
a n d t e n d e rn e s s of t h e t e n d on a re a w h e re it lie s ove r t h e la t e ra l m a lle olu s . Th e
con d it ion m ay be con fu s e d w it h a n a cu t e a n kle s p ra in . Pe ron e a l t e n d in it is is
m a n ife s t e d a s loca lize d t e n d e rn e s s a n d sw e llin g ove r t h e la t e ra l m a lle olu s .

NEUROLOGICAL PROBLEMS
Th e foot is a fre q u e n t s it e of n e u rologic s ym p t om s , s om e of w h ich a re com m on
a n d ot h e rs of w h ich a re ra re. Th e u s u a l s ym p t om is n u m bn e s s of s om e p ort ion
of t h e foot , bu t t h is com p la in t is oft e n ign ore d a s be in g n on s p e ci c. Th e s ym p -
t om s of n u m bn e s s , t in glin g, p a re s t h e s ia s , bu rn in g p a in , or p in s a n d n e e d le
s e n s a t ion s h ou ld rs t p oin t t o a p os s ible n e u rologic le s ion . Th e m os t com m on
ca u s e of n u m bn e s s of t h e fe e t is p e rip h e ra l n e u rop a t h y, a lt h ou gh a n u m be r of
 42 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

o t h e r lo ca l clin ica l con d it io n s ca u s in g n u m bn e s s of t h e foo t s h ou ld a ls o be

con s id e re d .

Mo rto n Ne uro ma
Mid d le -a ge d w o m e n a re m o s t fre q u e n t ly a ffe ct e d by Mo r t o n n e u ro m a , a n
e n t ra p m e n t n e u rop a t h y of t h e in t e rd igit a l n e rve occu rrin g m os t oft e n be t w e e n
t h e t h ird a n d fou rt h t oe s . Pa re s t h e s ia s a n d a bu rn in g, a ch in g t yp e of p a in a re
u s u a lly e xp e rie n ce d in t h e fou rt h t oe. Th e s ym p t om s a re m a d e w ors e by w a lk-
in g on h a rd s u rfa ce s or w e a rin g t igh t s h oe s or h igh -h e e l s h oe s . Te n d e r n e s s
m ay be e licit e d by p a lp a t ion be t w e e n t h e t h ird a n d fou rt h m e t a t a rs a l h e a d s .
Occa s ion a lly, a n e u rom a is s e e n be t w e e n t h e s e con d a n d t h ird t oe s . Com p re s -
s ion of t h e in t e rd igit a l n e rve by t h e t ra n s ve rs e m e t a t a rs a l liga m e n t a n d p os -
s ibly by a n in t e rm e t a t a rs op h a la n ge a l bu rs a or s yn ovia l cys t m ay be re s p on s ible
for t h e e n t ra p m e n t .

Tarsal Tunne l Syndro me

In t a rs a l t u n n e l s yn d rom e, t h e p os t e rior t ibia l n e rve is com p re s s e d a t or n e a r
t h e e xor re t in a cu lu m , w h ich is loca t e d p os t e rior a n d in fe rior t o t h e m e d ia l
S
m a lle o lu s . Nu m b n e s s , b u r n in g p a in , a n d p a re s t h e s ia s o f t h e t o e s a n d s o le
E
C
e xt e n d p roxim a lly t o t h e a re a ove r t h e m e d ia l m a lle olu s w it h n oct u rn a l e xa c-
T
I
O
e rba t ion rep ort e d . Th e p a t ie n t u s u a lly ge t s s om e re lie f by leg, foot , a n d a n kle
N
m ove m e n t s . A p o s it ive Tin e l s ign is e licit e d o n p e rcu s s io n p o s t e r io r t o t h e
2
m e d ia l m a lle olu s , a n d los s of p in p rick a n d t w o-p oin t d is crim in a t ion m a y be
R
e
p re s e n t . Wom e n a re m ore oft e n a ffe ct e d , a n d t ra u m a t o t h e foot , e s p e cia lly
g
i
o
fra ct u re, va lgu s foot d e form it y, h yp e rm obilit y, occu p a t ion a l fa ct ors , a n d s yn o-
n
a
vit is , m a y con t ribu t e t o d eve lop m e n t of t h e t a rs a l t u n n e l s yn d rom e. An e le ct ro-
l
P
d ia gn os t ic t e s t m ay s h ow p rolon ge d m ot or a n d s e n s ory la t e n cie s a n d s low in g
a
i
of t h e n e rve con d u ct ion ve locit ie s . In a d d it ion , a p os it ive t ou rn iq u e t t e s t a n d
n
S
p re s s u re ove r t h e e xor re t in a cu lu m ca n in d u ce s ym p t om s .
y
n
d
r
o
Ante rio r Tarsal Tunne l Syndro me
m
Th e a n t e rior t a rs a l t u n n e l s yn d rom e (or d e e p p e ron e a l n e rve e n t ra p m e n t ) is a n
e
s
e n t ra p m e n t n e u rop a t h y of t h e d e e p p e ron e a l n e rve a t t h e leve l of t h e in fe rior
e x t e n s or re t in a cu lu m o n t h e d or s u m of t h e foot . Th e s ym p t om s con s is t of
n u m bn e s s a n d p a re s t h e s ia s ove r t h e d ors u m of t h e foot , e s p e cia lly a t t h e w e b
s p a ce. A t igh t fe e lin g m a y be d e s cribe d ove r t h e a n t e rior a s p e ct of t h e a n kle.
Th e s ym p t om s m ay a ris e follow in g t h e w e a rin g of t igh t s h oe s or h igh h e e ls .
Ot h e r ca u s e s in clu d e con t u s ion of t h e d ors u m of t h e foot , m e t a t a rs a l fra ct u re,
t a lon avicu la r os t e op h yt os is , a n d ga n glion . Sym p t om s a ls o t e n d t o occu r in be d
a t n igh t a n d a re re lieve d by s t a n d in g or w a lkin g. Hyp e s t h e s ia a n d h yp a lge s ia
m a y be p re s e n t in t h e rs t d ors a l w e b s p a ce, a n d a Tin e l s ign m a y be e licit e d
on p e rcu s s ion ju s t a n t e ros u p e rior t o t h e m e d ia l m a lle olu s . Th e e xt e n s or d igi-
t oru m brevis m a y be a t rop h ie d a n d w e a k.
A d ia gn os is of a n t e rior t a rs a l t u n n e l s yn d rom e m a y be con rm e d by e le c-
t rod ia gn os t ic s t u d ie s .

Supe r cial Pe ro ne al Ne rve Entrapme nt

Th e s u p e r cia l p e ron e a l n e rve bifu rca t e s in t o t h e in t e rm e d ia t e d ors a l cu t a n e -
ou s a n d t h e m e d ia l d ors a l cu t a n e ou s t e rm in a l n e rve s . Th e la t e ra l a s p e ct of t h e
foot is u s u a lly in n e rva t e d by a bra n ch of t h e s u ra l n e rve, t h e la t e ra l d ors a l cu t a -
n e ou s n e rve. W h e n t h is bra n ch is a bs e n t , t h e in t e rm e d ia t e bra n ch of t h e s u p e r-
cia l p e ron e a l n e rve s u p p lie s t h e in n e rva t ion t o t h e la t e ra l foot .
Th e s ym p t om s a re p a in , n u m bn e s s , or t in glin g ove r t h e la t e ra l a s p e ct o f
t h e d ors u m of t h e foot , w ors e n e d by e xe rcis e a n d oft e n be com in g m ore s eve re
a t n igh t . Th e in t e rm e d ia t e d ors a l cu t a n e ou s bra n ch , be in g ve ry s u p e r cia l, ca n
be obs e rve d a n d p a lp a t e d u p on p la n t a r e xin g a n d in ve rt in g t h e foot . If t h is
bra n ch of t h e n e rve is e n t ra p p e d , t h e n com p re s s ion a t t h is s it e w ill rep rod u ce

PATIENT ASSESSMENT
• Th e lo ca t io n o f p a in a n d
t h e p re se n ce o f ca llu se s
w ill o ffe r clu e s a s t o t h e
ca u se o f p a in .
• An a t o m ic va ria n ce s su ch
a s p e s p la n u s o r ca vu s
d e fo rm it ie s a re im p o rt a n t
clu e s t o t h e d ia g n o sis.
• Pa lp a t io n ca n o ft e n
re p ro d u ce t h e ch ie f co m -
p la in t t o id e n t ify t h e
ca u se o f p a in .
• Yo u n g a t h le t e w it h fo o t
p a in sh o u ld b e e va lu a t e d
fo r t h e p o ssib ilit y o f st re ss
fra ct u re .
NOT TO BE MISSED
• Me t a t a rsa l st re ss fra ct u re s
• Ru p t u re o f t h e Ach ille s
t e n d o n o r p o st e rio r t ib ia l
tendon
Ch a p te r 5 Pa in fu l Fe e t 43
s ym p t o m s a n d a Tin e l s ign w ill be p re s e n t . A d e cre a s e in s e n s a t io n t o ligh t
t ou ch a n d p in p rick m a y be p re s e n t in t h e cu t a n e ou s d is t ribu t ion of t h e n e rve.
Th e m o s t com m on ca u s e of t h is n e u rop a t h y is a cu t e a n d ch ron ic a n kle
s p ra in s . Ot h e r ca u s e s in clu d e o s t e o a rt h rit is o f t h e t a rs a l b o n e s a n d m u s cle
h e rn ia t ion in t h e a n t e rior com p a rt m e n t . Sin ce t h e in t e rm e d ia t e bra n ch is s o
s u p e r cia l, it is ve ry s u s cep t ible t o t ra u m a a n d m a y be t h e s ou rce of ch ron ic
t ra u m a a n kle a n d foot p a in . Ele ct rod ia gn os t ic s t u d ie s w it h a bn orm a l s e n s ory
con d u ct ion ve locit y a n d p rolon ge d d is t a l la t e n cy h e lp con rm t h e d ia gn os is .
Sural Ne rve Entrapme nt
En t ra p m e n t o f t h e s u ra l n e r ve , a lt h o u gh u n co m m o n , m a y b e ove r lo o k e d
be ca u s e of it s lim it e d cu t a n e ou s d is t ribu t ion . Th is n e rve, w h ich is form e d from
bra n ch e s of t h e p os t e rior t ibia l a n d com m on p e ron e a l n e rve s , d e s ce n d s la t e ra l
t o t h e Ach ille s t e n d on , a n d a ft e r p a s s in g t h e la t e ra l m a lle olu s , t h e n e rve t u rn s
a n t e riorly a n d con t in u e s a s t h e la t e ra l d ors a l cu t a n e ou s n e rve a lon g t h e la t e ra l
s id e of t h e foot a n d t h e ft h t oe.
Th e m a n ife s t a t ion s a re n u m bn e s s a n d a bu rn in g p a in a lon g t h e la t e ra l s id e
of t h e d ors u m of t h e foot , w h ich m a y be w ors e a t n igh t . A d e cre a s e in s e n s a t ion
s
a n d a Tin e l s ign m ay be p re s e n t . Tra u m a , s ca r t is s u e, a n d ga n glia h a ve be e n
e
m
re p ort e d a s ca u s e s of e n t ra p m e n t .
o
r
d
n
y
S
Exa mina tio n
n
i
a
P
A p rop e r p h ys ica l e xa m in a t ion of t h e foot le a d s t o t h e a n a t om ic loca liza t ion of
l
a
t h e s ou rce of t h e p a in s ym p t om s , h e lp s t o id e n t ify t h e s t a t ic a n d m e ch a n ica l
n
o
a bn orm a lit ie s of t h e foot , a n d a id s in d e t e ct in g a n u n d e rlyin g d is e a s e. Look a t
i
g
t h e s h oe s for e xce s s ive w e a r on t h e h e e ls a n d s ole s . Ext re m e la t e ra l h e e l w e a r
e
R
ca n s ign ify h in d fo o t (ca lca n e a l) va ru s . An e x a m in a t io n o f ga it is va lu a ble in
2
d ia gn os in g a n d t re a t in g m a n y foo t p ro ble m s . Th e p a t ie n t w a lks ba re foot e d
N
O
w it h t h e fe e t a n d a n kle s e xp os e d , a n d t h e h in d foot , m id foot , a n d fore foot a re
I
T
C
view e d s ep a ra t e ly.
E
S
Ob s e r ve t h e fo o t fo r s w e llin g, d e fo r m it y, a n d e ryt h e m a o r o t h e r s k in
ch a n ge s . Pa lp a t ion t o d e t e ct t e n d e rn e s s is im p ort a n t for d ia gn os is . Pa lp a t e t h e
s u bt a la r join t in t h e n e u t ra l p os it ion for t e n d e rn e s s a n d a lign m e n t . Look for
fore foo t va ru s or fo re fo ot va lgu s . Exa m in e t h e m id t a rs a l a re a for t e n d e rn e s s
a n d m obilit y. Exa m in e for ra n ge of m ot ion a n d t e n d e rn e s s or sw e llin g of t h e
MTP join t s . Ch e ck for h a m m e r t oe s , cocke d -u p t oe s , a n d t e n d e rn e s s or sw e llin g
o f t o e s . Obs e r ve t h e t oe n a ils for a bn o rm a lit ie s . Ch e ck t h e ca lca n e u s on t h e
p la n t a r s u rfa ce for t e n d e rn e s s . Exa m in e t h e Ach ille s t e n d on , re t ro ca lca n e a l
bu rs a , p os t e rior t ibia l t e n d on , a n d p e ron e a l t e n d on for sw e llin g, t e n d e rn e s s ,
s u blu xa t ion , or ru p t u re.
Id e n t ify ca llu s e s t o reve a l a re a s of e xce s s ive s t re s s e s on t h e foot . De s cribe
t h e loca t ion of ca llu s e s . Id e n t ify corn s , w h ich a re h yp e rke ra t ot ic le s ion s s e c-
on d a ry t o p re s s u re. Ha rd corn s occu r ove r bon y p rom in e n ce s a n d t yp ica lly a re
fou n d on t h e la t e ra l a s p e ct of t h e ft h t oe. Soft corn s occu r be t w e e n t h e t oe s .
Studie s
Th e s t a n d a rd p la in ra d iogra p h view s in clu d e s t a n d in g a n t e rop os t e rior, s t a n d -
in g la t e ra l, a n d obliq u e (p ron a t e d ), d ep ict in g t h e m e d ia l a s p e ct of t h e foot . It is
im p ort a n t t o obt a in t h e a n t e rop os t e rior a n d la t e ra l ra d iogra p h s in t h e s t a n d in g
p os it ion t o d e m on s t ra t e t h e a n a t om ic re la t ion s h ip s of t h e foot in t h e ir fu n c-
t ion a l p os it ion . In t h e la t e ra l view, t h e x-ra y be a m p a s s e s from la t e ra l t o m e d ia l.
Ot h e r s p e cia l view s a re t h e la t e ra l obliq u e (s u p in a t e d ) t o vis u a lize a n a cce s s ory
n a vicu la r bon e ; s e s a m oid view, w h ich is a n a xia l, obliq u e p os it ion (t ilt e d la t e ra l
of s e s a m oid s ); a n d a xia l view of t h e h e e l (Ha rris ) for ca lca n e a l fra ct u re s .
 44 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

CT s ca n n in g is h e lp fu l in im a gin g t h e h in d foot , e s p e cia lly for s u bt a la r join t

p a t h ology a n d fra ct u re s of t h e ca lca n e u s . CT is be n e cia l in t h e d ia gn os is of
brou s a n d ca rt ila gin ou s coa lit ion , ca lca n e on avicu la r bon y coa lit ion , a n d t a lo-
ca lca n e a l coa lit ion . MRI m ay be u s e d t o h e lp d ia gn os e t a rs a l coa lit ion , os t e o-
m ye lit is , o s t e o n e cro s is , t e n d in it is , t e n d o n ru p t u re , liga m e n t o u s in ju ry, a n d
os t e och on d ra l in ju rie s of t h e t a la r d om e. MRI is h e lp fu l in id e n t ifyin g s oft t is -
s u e m a s s e s , s u ch a s ga n glia , brom a t os is , Mort on n e u rom a , a n d p igm e n t e d
villon o d u la r s yn ovit is o f t h e t e n d o n s h e a t h . Te ch n e t iu m b o n e s ca n s ca n b e
u s e d t o d e t e rm in e s t re s s fra ct u re s , e s p e cia lly of t h e m e t a t a rs a ls or ca lca n e u s .
Dia gn os t ic u lt ra s on ogra p h y ca n h e lp id e n t ify t e n d in it is a n d p a rt ia l or com p le t e
t e a rs of t e n d on s of t h e foot , e s p e cia lly t h e Ach ille s t e n d on a n d t h e p os t e rior
t ibia l t e n d on .

Tre a tme nt
ORTHOSES
Ort h ot ics is t h e e ld of corre ct in g foot d e form it ie s by m e a n s of e xt e rn a l s u p -
S
p ort , a n d d evice s u s e d for t h is t a s k a re kn ow n a s ort h os e s . Th e s e ort h os e s a re
E
C
u s e d t o re lieve a n d /or cu s h ion a n a re a of p re s s u re, s u p p ort a n a re a of colla p s e,
T
I
O
or con ve rt a biom e ch a n ica lly a bn orm a l foot in t o a biom e ch a n ica lly fu n ct ion a l
N
foot d u rin g t h e s t a n ce p h a s e of ga it . In s h ort , t h e s e m e ch a n ica l d evice s h e lp
2
re s t ore los t fu n ct ion or h e lp m a in t a in op t im a l fu n ct ion by a lt e rin g biom e ch a n -
R
e
ics . Ort h os e s m ay p rovid e p a in re lie f a n d com p e n s a t e for m u s cle a n d liga m e n t
g
i
o
w e a kn e s s by d e cre a s in g force s p a s s in g t h rou gh p a in fu l w e igh t -be a rin g a re a s ,
n
a
s t a bilizin g or im m obilizin g s u blu xin g join t s , a n d rep os it ion in g t oe s .
l
P
Th e ra n ge of t h e s e ort h ot ic d evice s va rie s from s im p le in e xp e n s ive p a d s
a
i
n
ava ila ble in d ru gst ores t o com p lex, exp en sive, cu st om -m a d e orth oses . Th e im p or-
S
ta n ce a n d va lu e of foot orth os es in th e t rea tm en t of foot d isord ers is ofte n u n d er
y
n
recogn ize d . Th e p h ysicia n sh ou ld est a blis h a rela t ion sh ip w ith a p ed ort h ot ist (a n
d
r
o
ort h ot is t w h o is t ra in ed in foot d evices ), a n ort h ot ist , or a t ra in ed th era p ist w h o
m
ca n fa brica te orth os es th a t a re s p eci c for t h e p roblem .
e
s
Foot ort h os e s ca n be d ivid e d in t o t h re e t yp e s : d evice s t h a t re lieve p re s s u re
on va riou s p a rt s of t h e foot ; t h os e t h a t cu s h ion t h e foot a n d d e cre a s e im p a ct ;
a n d t h os e t h a t a re cu s t om m a d e t o corre ct a bn orm a l biom e ch a n ics a n d re s t ore
be t t e r fu n ct ion of t h e foot . Ort h os e s t h a t re lieve p re s s u re on s p e ci c a re a s of
t h e foo t a re ge n e ra lly foa m o r fe lt w it h a n a d h e s ive ba ckin g. Th e s e ca n be
s h a p e d s p e ci ca lly for p re s s u re a re a s s u ch a s u n d e r t h e rs t , s e con d , or ft h
m e t a t a rs a l h e a d s . Th e p a d is p la ce d ju s t p roxim a l t o t h e a re a of p re s s u re.
Th e s e con d t yp e of ort h os is , w h ich re d u ce s im p a ct a n d cu s h ion s t h e foot ,
is con s t ru ct e d of m a t e ria l com p os e d of m icroce llu la r ru bbe r. Th e s e a re t ra n s -
fe ra ble t o d iffe re n t s h oe s a n d a re u s e d in m ild ca s e s . Ad d it ion a l m a t e ria ls u s e d
in ort h os e s t h a t re d u ce im p a ct a n d cu s h ion t h e foot a re clos e d -ce ll t h e rm o-
p la s t ic, p olye t h yle n e foa m d evice s , a n d vis coe la s t ic m a t e ria l. Th e s e m a t e ria ls
ca n be m old e d t o t h e con t ou r of t h e foot .
Th e t h ird t yp e of ort h os is is t h e bio m e ch a n ica l cu s t o m -fa brica t e d t yp e ,
w h ich a t t e m p t s t o re s t ore t h e s u bt a la r join t t o a n e u t ra l p os it ion . Th e s e m ay be
rigid , s e m i e xible, or s oft , d ep e n d in g u p on t h e n e e d . Th e t h e rm op la s t ic m a t e ri-
a ls a re t h e s e m i e xible t yp e s . Th e rigid t yp e is u s u a lly com p os e d of a n a crylic,
rigid p olyu re t h a n e foa m , or p olyp rop yle n e. As p a rt of t h is t yp e of ort h os is , a
“p os t ,” w h ich is a w e d ge, ca n be in corp ora t e d t o s u p p ort t h e foot a n d corre ct
t h e a bn orm a lit y. If fore foot va ru s is p re s e n t , t h e n a m e d ia l p os t is u s e d ; a n d if
fore foot va lgu s is p re s e n t , t h e n a la t e ra l p os t is d evis e d . Likew is e, a m e d ia l p os t
is u s e d t o corre ct p ron a t ion (eve rs ion ) of t h e h in d foot , w h e re a s a la t e ra l p os t is
u s e d t o co r re ct h in d fo o t s u p in a t io n (in ve r s io n ). Typ ica lly, a cu s t o m -m a d e
ort h os is m a y in corp ora t e s eve ra l fe a t u re s t o a d d re s s t h e foot p roble m s , a n d if
n e e d e d , a ll t h re e t yp e s of foot ort h os e s ca n be com bin e d in t o on e ort h os is . A
 Ch a p te r 5 Pa in fu l Fe e t 45

d e p re s s ion ca n be m a d e in t h e ort h os is t o re lieve p re s s u re in a s p e ci c a re a .

La rge r-t h a n -n o r m a l o r e x t ra -d e p t h s h o e s a re n e e d e d fo r t h e o r t h o s is t o t
com fort a bly.
Liga m e n t la xit y is co m m o n in m a n y in a m m a t o ry r h e u m a t ic d is e a s e s ,
oft e n re s u lt in g in s u blu xa t ion of join t s . Su blu xa t ion of t h e MTP join t re s u lt s in
broa d e n in g of t h e fore foot , claw in g of t oe s , a n d p a in fu l w e igh t be a rin g on MTP
h e a d s . Ca llou s , a p rot e ct ive re a ct ion of t h e s kin t o s t re s s , m ay be s e e n on t h e
bot t om of t h e foot . An in t e rn a l or e xt e rn a l m e t a t a rs a l ba r or p a d ca n be p la ce d
in , or on , t h e s h oe s ju s t be h in d t h e m e t a t a rs a l h e a d s t o re d is t ribu t e t h e w e igh t
aw ay from t h is a re a t o t h e m e t a t a rs a l s h a ft s . Alt e rn a t ive ly, a m e t a t a rs a l cors e t
(a m e t a t a rs a l p a d a t t a ch e d d ire ct ly t o a t oe w it h a s t ra p , in s id e t h e s ock) m a y
be u s e d in a n y s h oe. Join t s u blu xa t ion a ls o re s u lt s in los s of foot a rch e s , u n eve n
w e igh t d is t ribu t ion , a n d p a in . Arch s u p p o rt s , s u ch a s a m e d ia l lon git u d in a l
a rch s u p p ort , p la ce d in t h e s h oe ca n re form t h e s e a rch e s . Sp a ce rs ca n be p la ce d
be t w e e n t oe s t o p reve n t ove rla p p in g a n d s e con d a ry ca llu s e s .

SHOE MODIFICATION

s
It is im p ort a n t t o h ave a ge n e ra l u n d e rs t a n d in g of s h oe con s t ru ct ion a n d ava il-

e
m
a ble s h oe m od i ca t ion s t o h e lp t re a t foot p roble m . As a s t a rt , on e ca n s im p ly

o
r
e xa m in e s h oe bot t om s for w e a r a n d t e a r t o d e t e rm in e t h e a bn orm a l force s

d
n
in volve d . A va rie t y of m od i ca t ion s ca n be m a d e. Ext ra -d e p t h s h oe s w it h a

y
S
la rge t oe box s h ou ld be u s e d t o a ccom m od a t e xe d d e form it ie s s u ch a s cla w e d

n
i
t oe s a n d t o p rovid e room for foot a n d a n kle –foot ort h os e s . Ot h e rw is e, corn s

a
P
m a y d eve lop w h e re t h e p rox im a l in t e rp h a la n ge a l join t s o f t h e t o e s or o t h e r

l
a
n
p a rt s of t h e foot ru b on t h e s u p e rior p a rt of t h e s h oe. For p a t ie n t s w it h t oe

o
i
d e fo r m it ie s , s h o e clo s u re s ca n b e m o d i e d . Tra d it io n a l s h o e la ce s ca n b e

g
e
R
ch a n ge d t o Ve lcro clos u re s . Ela s t ic la ce s ca n rep la ce regu la r la ce s , e ffe ct ive ly

2
t u rn in g t h e s h oe in t o a loa fe r t yp e. Sh oe s w it h p rop e r clos u re s a re ge n e ra lly

N
p re fe rre d ove r loa fe rs , h ow eve r, a s loa fe rs m a in t a in t h e ir p la ce on t h e foot by

O
I
T
t e n s ion .

C
E
A Th om a s h e e l, w h ich is a m e d ia l e xt e n s ion of t h e h e e l, m ay be a d d e d t o

S
s u p p o rt t h e lo n git u d in a l a rch . Re p la cin g t h e regu la r s h o e h e e l w it h a “s o lid
a n kle cu s h ion h e e l” m ay be h e lp fu l for h e e l p a in or a fu s e d a n kle, a s t h is h e e l
ca n s im u la t e a n kle p la n t a r e xion w h ile w a lkin g. A rocke r bot t om s ole m a y be
h e lp fu l for a fu s e d a n kle, h a llu x rigid u s , or ot h e r t oe d e form it ie s by s u bs t it u t -
in g for t h e p u s h -off a n d h e e l-s t rike p h a s e of w a lkin g.
Ligh t e r s h oe s a re e a s ie r t o w e a r bu t h ave le s s s t a bilit y a n d d u ra bilit y. He a v-
ie r s h oe s m a y h a ve gre a t e r s t a bilit y a n d d u ra bilit y bu t a re m o re d if cu lt t o
ca rry. Ult im a t e ly, t h e s h oe m u s t be com fort a ble, h a ve a good t , a n d be a e s -
t h e t ica lly a p p e a lin g. Ot h e r w is e , it w ill n ot b e u s e d . On e ca n a lw a ys a d vis e
p a t ie n t s t o w e a r t h e ir s p e cia l s h oe s a t h om e a n d on t h e w a y t o w ork, a n d t o
ch a n ge w h e n t h ey ge t t h e re.
In a le g le n gt h d is cre p a n cy, a lift ca n be a t t a ch e d t o t h e o u t s id e o f t h e
w h ole s h oe of t h e s h ort leg a n d n ot ju s t t o t h e s ole or h e e l. Th e s h oe ra is e
s h ou ld be on e h a lf t o t h re e fou rt h s of t h e leg le n gt h d is cre p a n cy. Th e d iffe re n ce
s h o u ld p ro b a bly b e 1 cm t o co n s id e r co rre ct in g. How eve r, if t h e leg le n gt h
d is cre p a n cy is n o t a re ce n t eve n t , a n d e s p e cia lly if it is a s ym p t om a t ic, it is
p rob a bly be s t le ft u n t re a t e d , s in ce ch a n gin g w a lkin g biom e ch a n ics a ft e r ye a rs
of com p e n s a t ion m ay re s u lt in n ew s ym p t om s .

BRACES
A p a t e lla r t e n d on –be a rin g ort h os is is h e lp fu l for t h e p roble m of p a in a n d lim i-
t a t ion in a m bu la t ion d u e t o d e s t ru ct ive ch a n ge s of t h e a n kle or s u bt a la r join t
s u bs e q u e n t t o rh e u m a t oid a rt h rit is or ot h e r in a m m a t ory a rt h rit is . Th is p a t e l-
la r t e n d on –be a rin g bra ce, w h ich p rovid e s w e igh t be a rin g on t h e p a t e lla r t e n d on
 46 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

a n d t ibia l con dyle s t h rou gh a m old e d u p p e r-ca lf ba n d , h a s a xe d a n kle a n d a

rocke r bot t om s ole. Th u s , w e igh t of t h e u p p e r body ca n be d ire ct ly t ra n s m it t e d
from t h e kn e e region a n d ca lf t o t h e oor, byp a s s in g t h e a n kle. Th is p a t e lla r
t e n d on –be a rin g bra ce is a ls o u s e d t o d e cre a s e s t re s s on t h e a n kle or s u bt a la r
join t s in ot h e r con d it ion s s u ch a s s eve re os t e oa rt h rit is , Ch a rcot join t , a n d n on -
u n it e d fra ct u re s of t h e low e r lim b.

MODALITIES
Th e m os t com m on ly u s e d m od a lit ie s a re h e a t a n d cold . Me t h od s of s u p e r cia l
h e a t in g for t h e fe e t in clu d e h ot p a cks , h e a t in g p a d s , h yd rocolla t or p a cks , h ot
w a t e r bot t le s , h e a t e d w h irlp ools , a n d in fra re d la m p s . Hyd rot h e ra p y in a w h irl-
p ool ca n p rovid e s u p e r cia l h e a t t o t h e w h ole foot . At h om e, h ot ba t h s a n d foot
s oa ks , e s p e cia lly in t h e m orn in g, ca n be u s e d for re lie f. Ult ra s ou n d m a y be u s e d
t o h e a t t e n d on s a n d d e ep e r s t ru ct u re s .
Coolin g of t is s u e s ca n be obt a in e d w it h coola n t s p rays , ice p a cks , ba s in s of
ice w a t e r, a n d froze n food p a cka ge s . Coolin g a ls o ca u s e s va s ocon s t rict ion , w it h
a re d u ct io n o f blo o d ow a n d a d e cre a s e in m e t a b o lic a ct ivit y in t h e re gio n
S
t re a t e d . In ge n e ra l, p a t ie n t s s e e m t o p re fe r h e a t ; h ow eve r, bot h h e a t a n d cold
E
C
m a y be u s e d a lt e rn a t ive ly a s a con t ra s t ba t h .
T
I
O
N
2
THERAPEUTIC EXERCISES
R
e
g
Th e ra p e u t ic e xe rcis e m ay be broa d ly cla s s i e d in t o t h re e grou p s : (a ) ra n ge of
i
o
m ot ion or s t re t ch in g, (b) s t re n gt h e n in g (re s is t ive ), a n d (c) a e robic (e n d u ra n ce ).
n
a
In m a n y ca s e s , a s im p le h om e e xe rcis e p rogra m is a d e q u a t e a n d m ay be t a u gh t
l
P
t o t h e p a t ie n t by t h e p h ys icia n . Ot h e r ca s e s re q u ire t h e p re s crip t ion of a m ore
a
i
n
form a l p h ys ica l t h e ra py p rogra m . An e xe rcis e p re s crip t ion s h ou ld in clu d e t h e
S
y
e xe rcis e fre q u e n cy, in t e n s it y, t yp e, a n d d u ra t ion .
n
d
Ra n ge -o f-m ot ion e x e rcis e s a re im p o rt a n t d u rin g t h e a ct ive p h a s e of a n
r
o
in a m m a t ory a rt h rit is t o m a in t a in m obilit y of t h e a n kle, s u bt a la r, t a rs a l, a n d
m
e
MTP join t s . An kle e xe rcis e s in clu d e foot circle s , a ct ive d ors i e xion , a n d p la n t a r
s
e xion . W rit in g t h e a lp h a be t w it h t h e t oe s a n d clot h t u gs w it h t h e t o e s a n d
foot p rovid e ra n ge of m ot ion t o t h e join t s of t h e foot . Aft e r t h e a cu t e p h a s e h a s
re s olve d , s t re n gt h e n in g e xe rcis e s a ga in s t a re s is t a n ce ca n be u s e d . Th e a n kle
m a y be s t re t ch e d w it h ru bbe r t u bin g. Pa t ie n t s ca n be a s ke d t o p u s h t h e ir fe e t
a ga in s t a bo a rd a t t a ch e d t o t h e be d . Bicycle rid in g, sw im m in g, a n d a row in g
m a ch in e a re n on –w e igh t -be a rin g e xe rcis e s t h a t ca n h e lp m a in t a in ca rd iova s -
cu la r con d it ion in g.

WHEN TO REFER
• Te n d o n ru p t u re s sh o u ld b e
re fe rre d t o a n o rt h o p e d ic
su rg e o n .
• Cu st o m o rt h o se s a re
re q u ire d .
• Wh e n a n in a m m a t o ry
a rt h rit is is id e n t i e d
re q u irin g d ise a se m o d ify-
in g a n t irh e u m a t ic d ru g s.
STEROID INJECTIONS
Loca l s t e ro id in je ct io n s ca n be h e lp fu l in ce r t a in e n t ra p m e n t n e u ro p a t h ie s
(Mort on n e u rom a , s u p e r cia l p e ron e a l n e rve, s u ra l n e rve, a n d a n t e rior t a rs a l
t u n n e l s yn d rom e s ) a n d loca l in a m m a t ory con d it ion s s u ch a s a re t roca lca n e a l
bu rs it is , p os t e rior t ibia l t e n d on it is , or p la n t a r fa s ciit is . St e roid in je ct ion s of a n
Ach ille s t e n d on it is a re t o b e a vo id e d , a s t h ey a re lin k e d w it h ru p t u re of t h e
t e n d on .
Clinica l Co urse
Th rou gh ju d iciou s u s e of n on s t e roid a l a n t i-in a m m a t ory d ru gs , re s t , ort h os e s
w h e n in d ica t e d , a n d loca l s t e roid in je ct ion s w h e n in d ica t e d , t h e s e con d it ion s
ca n be m a n a ge d e ffe ct ive ly. In ca s e s in volvin g t e n d on ru p t u re or bon y d e form -
it y t h a t co n t rib u t e s t o t h e p a in fu l co n d it io n , t h e n a s u rgica l re fe rra l is in d i-
ca t e d .
 Ch a p te r 5 Pa in fu l Fe e t 47

ICD9
727.3 Bursitis NEC
726.79 an k le
726.79 f o o t
924.9 Co ntusio n (sk in su rf ace in t act )
924.21 an k le
924.20 f o o t (w it h an k le ) (e xclu d in g t o e (s))
De rang e me nt
718.97 an k le (in t e rn al)
718.90 jo in t (in t e rn al)
718.97 an k le
718.97 f o o t
718.30 re cu rre n t
718.37 an k le
718.37 f o o t
Diso rde r
733.90 cart ilag e NEC

s
718.07 an k le

e
m
718.07 f o o t

o
r
716.60 Mo no arthritis

d
n
716.67 an k le

y
S
716.67 f o o t (an d an k le )

n
i
a
715.9 Oste o arthro sis/ Oste o arthritis (d e g e n e rat ive ) (h yp e rt ro p h ic)

P
715.97 an k le an d f o o t

l
a
n
780.96 Pain(s)

o
i
719.40 jo in t

g
e
R
719.47 an k le

2
719.47 f o o t

N
848.9 Sprain, strain (jo in t ) (lig am e n t ) (m u scle ) (t e n d o n )

O
I
T
845.00 an k le

C
E
845.00 an d f o o t

S
845.10 f o o t
782.3 Sw e lling
719.07 an k le
729.81 f o o t

Additio na l Re a ding
1. Biu n d o JJ, Ru s h PJ. Pa in fu l fe e t . In : Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of Rheu-
m atology . Ph ila d e lp h ia , PA: Lip p in cot t Willia m s a n d Wilkin s ; 2003 :48 –61 .
2. Es p in os a N , Brod s ky JW, Ma ce ira E. Me t a t a rs a lgia . J A m A cad Orthop Surg 2010 ;18 :474 –485 .
3. Ba rt on CJ, Mu n t e a n u SE, Me n z HB, e t a l . Th e e f ca cy of foot ort h os e s in t h e t re a t m e n t of in d ivid u a ls w it h
p a t e llofe m ora l p a in s yn d rom e : a s ys t e m a t ic review . Sports Med 2010 ;40 :377 –395 .
4. Sim p s on MR, How a rd TM . Te n d in op a t h ie s of t h e foot a n d a n kle . A m Fam Physician 2009 ;80 :1107 –1114 .
5. Th om a s JL, Ch ris t e n s e n JC, Kra vit z SR, e t a l. Am e rica n College of Foot a n d An kle Su rge on s h e e l p a in com -
m it t e e. Th e d ia gn os is a n d t re a t m e n t of h e e l p a in : a clin ica l p ra ct ice gu id e lin e -revis ion 2010 . J Foot A nkle
Surg 2010 ;49 :S1 –S19 .
 CHAPTER
6 Mecha nica l Disorders
of the Knee
Dennis W . Boulw are

Intro ductio n
A 25-ye ar-o ld m an p re se n t s
Me ch a n ic a l d is o r d e r s o f t h e k n e e
S
w it h a 3-d ay h ist o ry o f rig h t
E
in clu d e clin ica l co n d it io n s ca u s e d by
C
T
k n e e af t e r p layin g so cce r w it h m a lfu n ct ion , t ra u m a , or d ege n e ra t ion of
I
O
f rie n d s in t h e p ast w e e k e n d .
N
a s p e ci c in t ra -a r t icu la r a n d / o r e xt ra -
2
Despite rest and acetam inophen, a rt icu la r com p on e n t of t h e kn e e in t e r-
R
fe r in g w it h n o r m a l k n e e fu n ct io n . An
e
h e is st ill in p ain , u n ab le t o
g
in t e rn a l d e ra n ge m e n t of t h e kn e e com -
i
o
st raig h t e n h is k n e e co m p le t e ly
n
m on ly re fe rs t o a d is ord e r of t h e in t ra -
a
l
an d h is k n e e o ccasio n ally a rt icu la r com p on e n t s , m ore com m on ly
P
a
b u ck lin g . t h e a rt icu la r ca rt ila ge , m e n is cu s b ro-
i
n
ca rt ila ge, colla t e ra l liga m e n t s , or cru ci-
S
y
n
a t e liga m e n t s (Fig. 6.1 ). Dis o rd e r s o f
d
r
e xt ra -a rt icu la r com p on e n t s of t h e kn e e
o
m
join t in clu d e p a t e llofe m ora l m a la lign m e n t a n d in s u f cie n cy of t h e q u a d ricep s
e
s
or h a m s t rin g m u s cle grou p s , a n d a re con s id e re d a s m e ch a n ica l d is ord e rs t oo.
Sign i ca n t m e ch a n ica l d is ord e rs of t h e kn e e ca u s in g in s t a bilit y, if con t in -
u e d u n a ba t e d , eve n t u a lly le a d t o os t e oa rt h rit is . Exp e rim e n t a l a n im a l m od e ls of
os t e oa rt h rit is t yp ica lly in volve in it ia t in g a n in t e rn a l d e ra n ge m e n t of t h e join t ,
follow e d by con t in u e d u s e of t h e lim b. Th e m os t com m on m od e ls of e xp e ri-
m e n t a l os t e o a rt h rit is in clu d e p a rt ia l m e d ia l m e n is ce ct om y o r t ra n s e ct io n of
t h e a n t e rior cru cia t e liga m e n t . In ju rie s of t h e m e d ia l m e n is cu s a n d a n t e rior
cru cia t e liga m e n t a re com m on a n d a s ou r p op u la t ion a ge s a n d be com e s m ore
e n ga ge d in re cre a t ion a l a n d s p ort s -re la t e d a ct ivit ie s , m e ch a n ica l d is ord e rs of
t h e kn e e w ill be com e m ore p reva le n t a n d , if n ot re cogn ize d e a rly, w ill re s u lt in
CLINICAL POINTS a n in cre a s e d p reva le n ce of os t e oa rt h rit is of t h e kn e e.
• Me ch a n ica l d iso rd e rs ca n
le a d t o kn e e in st a b ilit y a n d
p re m a t u re o st e o a rt h rit is. Clinica l Pre se nta tio n
• Th e p h ysica l e xa m in a t io n Mos t kn e e p a in re s u lt s from d is ru p t ion of on e of t h e m a n y com p on e n t s t h a t
o f t h e kn e e is e sse n t ia l in
com p ris e a fu n ct ion a l kn e e join t . Th e s e com p on e n t s in clu d e t h e a rt icu la r h ya -
id e n t ifyin g t h e ca u se .
lin e ca rt ila ge, t h e s u p p ort in g m e n is ca l broca rt ila ge, a n d t h e va riou s liga m e n t s .
• Bu cklin g o f a p a in fu l kn e e An u n d e rs t a n d in g of t h e a n a t om y a n d biom e ch a n ics of t h e kn e e cou p le d w it h
is co m m o n a n d n o t a lw a ys
a fo cu s e d p h ys ica l e xa m in a t io n of va riou s com p on e n t s of t h e kn e e u s u a lly
a sso cia t e d w it h a t o rn
m e n iscu s. id e n t ify t h e ca u s e of p a in . Th is ch a p t e r focu s e s on d e ra n ge m e n t s of t h e m e n is ci,
liga m e n t s , a n d p a t e llofe m ora l a lign m e n t a s a ca u s e of kn e e p a in s in ce t h ey a re
• Ch ro n ic m e n isca l t e a rs a re
t h e m os t com m on m e ch a n ica l d is ord e rs of t h e kn e e.
co m m o n ly a sso cia t e d w it h
o st e o a rt h rit is. In ge n e ra l, p a t ie n t s com p la in of kn e e p a in p rim a rily w it h u s e a n d fu rt h e r
h is t ory is of lim it e d va lu e in id e n t ifyin g t h e m e ch a n ica l d is ord e r ot h e r t h a n t h e
48

Lateral
collateral
ligament
Ant. cruciate
ligament
Lateral
meniscus
Figure 6.1 Ana tomica l components of the knee tha t ca n ca use a
mecha nica l disorder of the knee. From Koopma n WJ, Morela nd LW, eds.
Arthritis a nd Allied Conditions: A Textbook of Rheuma tology, 15th ed.
Phila delphia : Lippincott Willia ms & Wilkins; 2005.
PATIENT ASSESSMENT
1. Wo rse p a in w it h
d e sce n d in g st a irs o r
d e clin in g su rfa ce s
su g g e st s p a t e llo fe m o ra l
d ise a se .
2. Te st in g fo r in st a b ilit y is
crit ica l in lig a m e n t o u s
le sio n s.
3. Disp la ce d m e n isca l
fra g m e n t s ca n b e co m e
e n t ra p p e d a n d lo ck t h e
kn e e .
4. Re se rve im a g in g st u d ie s
fo r re cu rre n t o r re ca lci-
t ra n t kn e e p a in .
Ch a p te r 6 Me ch a n ica l Dis ord e rs of t h e Kn e e 49
a cu it y o f t h e p a in a n d a n id e n t i a ble p re cip it a t in g
eve n t . Bu cklin g of t h e kn e e w it h w e igh t -be a r in g is
a s s o cia t e d w it h a ll t yp e s o f in t e r n a l d e ra n ge m e n t s
a n d m ore com m on ly occu r s a s a re e xive m u s cu la r
re la x a t io n t o t h e s u d d e n o n s e t o f p a in , ca u s in g t h e
Post. cruciate kn e e t o “give w a y.” Tru e lockin g of t h e kn e e, t h ou gh ,
ligament s h o u ld fo cu s t h e clin icia n o n a t or n a n d d is p la ce d
Medial collateral m e n is cu s ge t t in g e n t ra p p e d w it h in t h e join t .
ligament Acu t e in ju rie s w it h id e n t i a ble p recip it a t in g eve n t s
Medial meniscus s u ch a s t ra u m a or in ju ry com m on ly in volve m en is cu s
or liga m e n t d a m a ge w it h im m e d ia t e p a in , a n d con t in -
u e d p a in w it h w e igh t -be a rin g or u s e of t h e lim b a n d
oft en lim it e d ra n ge of m ot ion s econ d a ry t o t h e p a in . If
t h e a cu t e in ju ry re s u lt e d in a d is p la ce m e n t of t h e t orn
m e n is cu s , p a t ien t s oft en com p la in of a p a in fu l “ca t ch -
in g” or “p op p in g” s en s a t ion in t h e kn e e. La rge s u d d e n
e ffu s ion s s u gge s t a h e m a rt h ros is t h a t is m ore com -
m on ly s e en w it h t orn liga m e n t s a s op p os ed t o a t orn
s
m en is cu s . Liga m e n t s a re va s cu la rize d s t ru ct u re s , a n d
e
m
d a m a ge t o t h e liga m en t u s u a lly re s u lt s in a h e m a rt h ro-
o
r
s is . Effu s ion s t h a t occu r la t e r ca n be s e e n in e it h e r liga -
d
n
m e n t or m e n is cu s d a m a ge. An exa m in a t ion of t h e join t
y
S
w ill h e lp id e n t ify t h e s ou rce of d a m a ge.
n
i
Th e a bs e n ce of a n id e n t i a ble p re cip it a t in g eve n t s u gge s t s a d ege n e ra t ive
a
P
p roce s s t h a t eve n t u a lly re a ch e d a t ip p in g p oin t ca u s in g clin ica l s ym p t om s . Pa r-
l
a
n
t icu la rly w it h a ch ron ic t e a r of t h e m e n is cu s , t h e re is u s u a lly le s s p a in t h a n a n
o
i
a cu t e t e a r, a n d t h e re is fre q u e n t ly a la ck o f a n y re co gn iz a ble p re cip it a t in g
g
e
R
eve n t . Ch ron ic m e n is ca l t e a rs a re t yp ica lly a s s ocia t e d w it h os t e oa rt h rit is , a n d
2
a p re cip it a t in g ca u s e m ay be a s s im p le a s a s q u a t t in g a n d t w is t in g m a n e u ve r
N
or a s im p le m is s t e p . Ch ron ic p a in w it h u s e of t h e kn e e a n d ep is od ic e ffu s ion s
O
I
T
of t h e kn e e oft e n p re ce d e t h e p a t ie n t ’s eve n t u a l vis it t o s e e t h e p h ys icia n . Wit h
C
E
ch ro n ic d e ra n ge m e n t s , lim it a t io n in ra n ge o f m o t io n is le s s o f a p ro m in e n t
S
fe a t u re t h a n w it h a cu t e a n d d is p la ce d t e a rs .
Com p la in ts of p a in w ith u se a re com m on in a ll m ech a n ica l d isord ers of th e
kn ee, bu t p a in felt in th e a n terior of th e kn ee or w ith d escen d in g sta irs or in clin ed
s u rfa ce s a s op p os e d t o a s ce n d in g s t a irs or d e s ce n d in g s u rfa ce s a re com m on
com p la in ts of p a tellofem ora l com p a rtm en t p roblem s . Pa tien ts w ith p a tellofem o-
ra l p a in often com p la in of p a in a fter p rolon ged p eriod s of im m obility w ith th e
kn ee in exed p osition s su ch a s sittin g a t a d esk or rid in g in a n a u tom obile; w h en
resu m in g a ctivity a ga in , th e con d ition w ill often ca u se p a in for a brief p eriod of
tim e, su ch a s th e rst few step s a fter resu m in g a s ta n d in g p osition .
Pa in fe lt in t h e p op lit ea l a rea is t yp ica lly d u e t o e ffu s ion s d is t en d in g t h e join t
ca p s u le or d u e t o a n e ffu s ion ca u s in g a p op lit e a l cys t t o ll, ca u s in g p a in from
d is t e n t ion of t h e cys t . Pop lit e a l p a in d oe s n ot oft e n id e n t ify t h e s ou rce of t h e
m e ch a n ica l d is ord e r ca u sin g t h e in crea s ed s yn ovia l u id t o a ccu m u la t e a s m u ch
a s re e ct d is t e n t ion of t h e p op lit e a l cys t or join t ca p s u le. Pop lit e a l cys t s a re com -
m on in m a n y in d ivid u a ls a n d com m u n ica t e w it h t h e join t s p a ce, bu t t yp ica lly
a re n ot u id - lle d excep t w h en t h e p re s s u re in t h e s yn ovia l s p a ce in cre a s e s a n d
s yn ovia l u id is p u m p ed from t h e join t in t o t h e p op lit e a l cys t . Th e com m u n ica -
t ion be t w ee n t h e cys t a n d join t s p a ce d oe s n ot a lw ays a llow t h e u id t o ret u rn
t o t h e join t s p a ce, bu t w ill even t u a lly be re a bs orbed w h en t h e join t s p a ce p res -
s u re re t u rn s t o n orm a l a n d n o fu rt h e r u id is p u m p e d in t h e p op lit ea l cys t .
Physica l Finding s
Th e p h ys ica l e xa m in a t ion is t h e m os t h e lp fu l in t h e clin ica l eva lu a t ion of t h e
p a t ie n t a s va riou s m a n e u ve rs a llow t h e clin icia n t o t e s t e a ch com p on e n t of
 50 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

t h e kn e e, a llow in g id e n t i ca t ion of a d ys fu n ct ion a l com p on e n t or s ou rce

of t h e p a in . In a d d it ion t o t h e s e p rovoca t ive m a n e u ve rs , t h e e xa m in a -
t ion s h o u ld a s s e s s fo r p a s s ive ra n ge s o f m o t io n a n d t h e p re s e n ce o f
e ffu s ion s .
Pos it ion in g t h e p a t ie n t in a s u p in e p os t u re w ill a id e in ge t t in g t h e
p a t ie n t t o re la x w h ich w ill be e s s e n t ia l in m e a s u rin g t h e fu ll p a s s ive
ra n ge o f m o t ion . In m e a s u rin g p a s s ive ra n ge of m ot ion , t h e fe m u r is
u s e d a s t h e re fe re n ce a rm of t h e kn e e a n d t h e n orm a l ra n ge of e xt e n s ion
is m e a s u re d a s 0 d egre e w it h t h e kn e e e xt e n d in g t h e s a m e t ra je ct ory a s
t h e fe m u r. Th e in a bilit y of t h e kn e e t o p os it ion in t o fu ll e xt e n s ion s h ou ld
be re cord e d in d egre e s re la t ive t o t h e fe m u r. An a cu t e los s of fu ll e xt e n -
s ion m ay re e ct a d is p la ce d m e n is cu s , a la rge join t e ffu s ion d is t e n d in g
t h e kn e e join t ca p s u le, or a d is t e n d e d p op lit e a l cys t . A ch ron ic los s of fu ll
e x t e n s io n t yp ica lly re e ct s a lo n gs t a n d in g o s t e o p h yt e s u gge s t in g a
d e ge n e ra t ive p ro ce s s . W it h t h e p a t ie n t re la x e d a s m u ch a s p o s s ible ,
p a s s ive fu ll e xion in t h e p a t ie n t s h ou ld be m e a s u re d . Norm a lly, t h e
kn e e w ill h a ve 0 d egre e of e xt e n s ion a n d 140 d egre e s of e xion . As in
Figure 6.2 McMurra y test. From Berg D, m e a s u rin g e x t e n s ion , t h e a cu t e los s of fu ll e xion m a y re e ct a d is -
S
Worzala K. Atlas of Adult Physical Diagnosis . p la ce d m e n is cu s ; a la rge join t e ffu s ion d is t e n d in g t h e kn e e join t ca p s u le
E
C
Phila delphia: Lippincott Williams & Wilkins, 2006. or a d is t e n d e d p op lit e a l cys t a n d a ch ron ic los s w ill s u gge s t a n os t e o-
T
I
O
p h yt e in d ica t in g a d ege n e ra t ive p roce s s . Join t e ffu s ion s oft e n im p a ir fu ll
N
p a s s ive ra n ge of m ot ion a n d u s u a lly corre la t e w it h t h e s eve rit y of in a m m a t ion
2
w it h in t h e kn e e join t .
R
e
A t orn a n d d is p la ce d m e n is cu s ca n ca u s e lim it a t ion in p a s s ive ra n ge o f
g
i
o
m ot ion w h e n t h e d is p la ce d m e n is ca l t e a r ca u s e s e n t ra p m e n t of t h e d is p la ce d
n
a
fra gm e n t t o im p e d e t h e fu ll e xion or e xt e n s ion of t h e kn e e. Th e McMu rray t e s t
l
P
(Fig. 6.2 ) is a s p e ci c t e s t t o in d u ce e n t ra p m e n t of a m e n is ca l t e a r. W it h t h e
a
i
p a t ie n t s u p in e a n d re la xe d , t h e e xa m in e r gra s p s t h e a ffe ct e d leg a n d p a s s ive ly
n
S
e xe s t h e kn e e a n d h ip m a xim a lly t o p os it ion t h e kn e e a s clos e t o t h e ch e s t a s
y
n
p os s ible. At t h e p oin t of m a xim a l p a s s ive e xion , t h e kn e e is rot a t e d fu lly u s in g
d
r
o
th e foot a s a lever to a ttem p t im p in gem en t of th e torn la tera l or m ed ia l m en iscu s.
m
Wit h t h e kn e e h e ld in p a s s ive in t e rn a l rot a t ion in e xion , t h e kn e e is e xt e n d e d
e
s
t o d e t e ct a p a lp a ble or a u d ible s n a p in t h e join t . Th e m a n e u ve r is re p e a t e d w it h
t h e e xe d k n e e h e ld in fu ll, p a s s ive , e xt e r n a l ro t a t io n . Pa in is n o t a lw a ys
p re s e n t , p a rt icu la rly in a n old e r d ege n e ra t ive t e a r. Th e Ap ley grin d t e s t (Fig. 6.3 )
is a ls o u s e d t o d e t e ct p os s ible m e n is ca l d e ra n ge m e n t . Th is t e s t is p e rform e d
w it h t h e p a t ie n t in a p ron e p os it ion a n d t h e kn e e e xe d a t 90 d egre e s . In t h is
p os it ion t h e e xa m in e r u s e s t h e p la n t a r s u rfa ce of t h e
foot t o m a n u a lly loa d t h e kn e e join t w h ile rot a t in g
t h e kn e e in in t e rn a l a n d e xt e rn a l rot a t ion s . Te n d e r-
n e s s e licit e d d u rin g t h e Ap ley grin d t e s t is n ot s p e -
ci c fo r a m e n is ca l in ju ry, a s a n a rt icu la r ca rt ila ge
le s io n w ill a ls o p ro d u ce t e n d e rn e s s . Th e co m b in e d
p re s e n ce of a “s n a p ” a n d a n a bn orm a l Ap ley grin d
t e s t is con s is t e n t w it h a t orn m e n is cu s . Be ca u s e of
t h e a n a t om ic loca t ion of t h e m e n is ci n e a r t h e m e d ia l
a n d la t e ra l join t lin e s , join t lin e t e n d e rn e s s t o d ire ct
p a lp a t ion is t h e h a llm a rk of a m e n is ca l in ju ry. Th e
m e n is ci a re in clos e con gru it y w it h t h e p e rip h e ra l
join t ca p s u le, w h ich h a s a rich n e rve s u p p ly, a ccou n t -
in g fo r t h e lo ca liz e d t e n d e r n e s s . Jo in t lin e t e n d e r-
n e s s t o p a lp a t ion is a ls o s e e n in os t e oa rt h rit is of t h e
k n e e a n d it s p re s e n ce s h o u ld s u gge s t a m e n is ca l
le s ion on ly w h en com bin e d w it h t h e McMu rray a n d /
or Ap ley s ign s . A com bin a t ion of join t lin e t e n d e rn e s s
w it h a p os it ive McMu rray a n d /or Ap ley s ign corre la t es
Figure 6.3 Apley grind test. w e ll w it h a clin ica lly t orn m e n is cu s .
 Ch a p te r 6 Me ch a n ica l Dis ord e rs of t h e Kn e e 51

Mos t s e riou s a n d d ys fu n ct ion a l liga m e n t d is ord e rs a re d e t e ct e d by s im p le

p h ys ica l e xa m in a t ion . Th e re a re t w o s e t s of op p os in g liga m e n t s t o be e xa m -
in e d : t h e m e d ia l a n d la t e ra l colla t e ra l liga m e n t s a n d t h e a n t e rior a n d p os t e rior
cru cia t e liga m e n t s . Norm a l kn e e s t a bilit y a n d ra n ge of m ot ion d ep e n d on in t a ct
liga m e n t s t o re s t rict t h e kn e e t o p rim a ry e xion a n d e xt e n s ion . Th e colla t e ra l
liga m e n t s re s id e on t h e m e d ia l a n d la t e ra l a s p e ct of t h e kn e e a n d re s t rict t h e
kn e e from va ru s or va lgu s m ot ion . Th e a n t e rior a n d p os t e rior cru cia t e liga m e n t s
fu n ct ion t o re t a rd a n t e rior a n d p os t e rior d is p la ce m e n t of t h e t ibia re la t ive t o t h e
fe m ora l con d yle s d u rin g exion a n d e xt e n s ion .
Med ia l a n d la t e ra l colla t e ra l liga m e n t in ju ry is be s t t es t ed w h e n t h e p a t ie n t
is s ea t e d or is s u p in e a n d re la xe d . Aft e r p a s s ive ly p la cin g t h e re la xe d kn e e in
30 d egre e s of exion , t h e p a t ie n t ’s a n kle s h ou ld be gra s p e d w it h on e h a n d a n d
t h e kn e e s t a bilized w it h t h e ot h e r t o a p p ly p a s s ive s t re s s t o a t t em p t t o d is p la ce
t h e d is t a l leg in a va lgu s a n d t h e n a va ru s d ire ct ion . Norm a lly t h ere s h ou ld be n o
m otion t o d is p la ce m e n t in e it h er va lgu s or va ru s d evia t ion s of t h e kn e e. Th e a bil-
it y to d is p la ce t h e kn e e in a va lgu s d ire ct ion w ou ld in d ica t e a m e d ia l colla t e ra l
liga m e n t t e a r or in s t a bilit y. In a p a rt ia l t e a r, es p e cia lly a n a cu t e on e, t h ere w ill be
t e n d e rn e s s in t h e m ed ia l com p a rt m e n t a s s t res s is p la ced in t h e d is p la cem e n t .

s
A com p let e t e a r w ill d evia t e s ign i ca n t ly a n d m ay n ot h ave s ign i ca n t a s s oci-

e
m
a t ed t e n d e rn e s s . Sin ce t h e m e d ia l colla t e ra l liga m e n t is rm ly a t t a ch e d t o t h e

o
r
m ed ia l m e n is cu s , a n d d is ru p t ion of on e s t ru ct u re oft e n lea d s t o in ju rie s t o t h e

d
n
ot h er s t ru ct u re in t h e m e d ia l com p a rt m e n t , a t orn m e d ia l colla t e ra l liga m e n t

y
S
freq u e n t ly h a s a n a s s ocia t e d t orn m ed ia l m e n is cu s in volved . Con ve rs e ly, va ru s

n
i
force a p p lie d t o t h e d is t a l leg s t ill h e ld in t h is p os it ion ca n be u s e d t o d e t e ct

a
P
s im ila r s ign s in t h e la t e ra l com p a rt m e n t , im p lica t in g a la t e ra l colla t e ra l liga m e n t

l
a
n
in ju ry a n d ca n be follow e d by p a lp a t ion a lon g t h e la t era l join t lin e for t e n d e r-

o
i
n e s s. Mos t colla t e ra l liga m e n t a bn orm a lit ie s ca n be q u a n t i e d by t h e d egre e of

g
e
R
d is p la cem e n t . A gra d e I la xit y w ou ld rep res e n t u p t o 5 m m of a d d it ion a l m ot ion ;

2
gra d e II, 6 t o 10 m m ; gra d e III, 11 t o 15 m m ; a n d gra d e IV, 15 m m of a d d it ion a l

N
d is p la cem e n t . Ca u t ion s h ou ld be exe rcis e d in in t e rp re t in g t h is m a n eu ve r be ca u s e

O
I
T
“rela t ive” la xit y of t h e colla t e ra l liga m e n t s is oft e n s e en in kn e e s w it h los s of fu ll

C
E
a rt icu la r ca rt ila ge t h ickn e s s d u e t o ch ron ic os t e oa rt h rit is .

S
A t orn a n t e rior cru cia t e liga m e n t is be s t t e s t e d by t h e a n t e rior d raw e r s ign
or La ch m a n t e s t . Th is m a n e u ve r is p e rform e d w it h t h e p a t ie n t s e a t e d com fort -
a bly or s u p in e. Th e kn e e is p a s s ive ly e xe d t o 25 d egre e s a n d t h e foot xe d in
p la ce w it h on e h a n d a n d a n t e rior force p la ce d on t h e t ibia re la t ive t o t h e fe m -
ora l con d yle s d ra w in g t h e t ibia l p la t e a u t ow a rd t h e clin icia n . Norm a lly t h e re is
n o m ore t h a n 5 m m of d is p la ce m e n t a n d a n t e rior d is p la ce m e n t of t h e t ibia l
p la t e a u re la t ive t o t h e fe m ora l con d yle 5 m m in d ica t e s a t orn or la x a n t e rior
cru cia t e liga m e n t . Te n d e rn e s s e licit e d by t h is m a n e u ve r in t h e a bs e n ce of d is -
p la ce m e n t s u gge s t s a n in com p le t e t e a r of t h e a n t e rior cru cia t e liga m e n t . Th e
p os t e rior cru cia t e liga m e n t is be s t t e s t e d by t h e p os t e rior d raw e r s ign , w h ich is
p e rform e d w it h t h e kn e e in 90 d egre e s of e xion . Fixin g t h e p a t ie n t ’s foot w it h
on e h a n d a n d d is p la cin g t h e t ibia l p la t e a u p os t e riorly, re la t ive t o t h e fe m ora l
con d yle s s h ou ld re s u lt in n o m ore t h a n 5 m m of d is p la ce m e n t . Pos t e rior cru ci-
a t e liga m e n t p roble m s a re m u ch le s s com m on ly s e e n t h a n a n t e rior cru cia t e
liga m e n t is s u e s . Aga in , ca u t ion s h ou ld be e xe rcis e d in in t e rp re t in g t h e s e t e s t s
in p a t ie n t s w it h ch ron ic os t e oa rt h rit is a n d re la t ive la xit y of t h e liga m e n t s d u e
t o a rt icu la r ca rt ila gin ou s los s .
If t h e e xa m in a t ion h a s n ot d e t e rm in e d a ca u s e for t h e p a in t h u s fa r, t h e
clin icia n s h ou ld con s id e r p a t e llofe m ora l in volve m e n t . In p a t e llofe m ora l m a la -
lign m e n t , t h e e n d re s u lt is a d a m a ge d p a t e lla r a rt icu la r s u rfa ce ca u s in g p a in
w it h u s e. Join t e ffu s ion s a re n ot com m on ly s e e n in p a t e llofe m ora l d is e a s e, bu t
a ll e ffu s ion s corre la t e w it h t h e d egre e of in a m m a t ion a n d h is t op a t h ology of
t h e a rt icu la r ca rt ila ge a n d s eve re le s ion s of t h e p a t e lla r a rt icu la r ca rt ila ge ca n
ca u s e a n e ffu s io n . In p a t e llo fe m o ra l d is e a s e, t h e p a s s ive ra n ge o f m o t io n is
p re s e rve d , bu t m ot ion of t h e kn e e in e xion a n d e xt e n s ion fre q u e n t ly ca u s e s
 52 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

crep it u s con n e d t o t h e p a t e llofe m ora l com p a rt m e n t . Th e p a t e llofe m ora l com -

p a rt m e n t a s a s ou rce of kn e e p a in ca n be con rm e d by re p rod u cin g t h e com -
p la in t s by p a t e llofe m ora l com p re s s ion or grin d in g. Wit h t h e p a t ie n t s u p in e a n d
t h e kn e e re la xe d , com p re s s ion of t h e p a t e lla a ga in s t t h e fe m ora l in t e rcon d yla r
groove w h ile p a s s ive ly m ovin g t h e p a t e lla s u p e riorly a n d in fe riorly w it h in t h e
in t e rcon d yla r groove w ill re p rod u ce t e n d e rn e s s . Te n d e rn e s s on p a t e lla r in h ibi-
t ion is m ore s e n s it ive bu t le s s s p e ci c for p a t e llofe m ora l d is e a s e a s t h e a bs e n ce
of t e n d e rn e s s e xclu d e s t h e p a t e llofe m ora l com p a rt m e n t a s a s ou rce of p a in ,
bu t ca n ca u s e t e n d e rn e s s in t h e a bs e n ce of s ign i ca n t p a t e llofe m ora l d is e a s e.
Wit h t h e p a t ie n t s t ill s u p in e a n d t h e kn e e re la xe d , p a s s ive ly d is p la ce t h e p a t e lla
in fe riorly a n d h old it t h e re w h ile a s kin g t h e p a t ie n t t o con t ra ct t h e q u a d rice p s
m u s cle s . Th e q u a d rice p s con t ra ct ion w ill p u ll t h e p a t e lla s u p e riorly be n e a t h
t h e e xa m in e r’s n ge rs h old in g t h e p a t e lla in fe riorly a n d ca u s e t e n d e rn e s s .
An a bn orm a l d egree of p a t e lla r la xit y ca n be a ca u s e of p a t e llofem ora l m a la -
lign m en t a n d s u bs eq u e n t ly a m e ch a n ica l d is ord er of t h e kn e e. To t e s t for la xit y,
t h e p a t ie n t is s t ill s u p in e a n d t h e kn ee re la xe d . Th e exa m in e r p a s s ively d is p la ce s
t h e p a t e lla la t e ra lly w it h t h e kn e e in p a s s ive fu ll e xt e n s ion a n d t h e a bilit y t o
d is p la ce t h e p a t ella m ore t h a n h a lf of it s t ot a l w id t h s u gge s t s la xit y of t h e m e d ia l
S
re t in a cu la r re s t ra in t s . Me d ia l re t in a cu la r la xit y is a com m on ca u s e or p a t e l-
E
C
lofem ora l m a la lign m en t a n d ca n re s u lt in p a t e llofem ora l d is e a s e.
T
I
O
N
2
STUDIES
R
e
Th e la bora t ory is of n o h e lp in eva lu a t in g t h e p a t ie n t w it h kn e e p a in from a
g
i
o
m ech a n ica l d is ord e r of t h e kn e e ; t h e p h ys ica l exa m in a t ion is m ore e n ligh t en in g.
n
a
Pla in ra d iogra p h y is a p oor d ia gn os t ic m od a lit y for s oft -t is s u e in ju ry. Th e
l
P
on ly u t ilit y of p la in ra d iogra p h y w ou ld be t o a s s e s s t h e s eve rit y of coe xis t in g
a
i
os t e oa rt h rit is , a com m on com orbid fe a t u re of a d ege n e ra t ive or ch ron ic t e a r.
n
S
Cros s -s e ct ion a l im a gin g s u ch a s CT a n d /or MRI h a s h igh e r leve ls of s e n s it ivit y
y
n
for le s ion s of t h e m e n is ci or liga m e n t s , bu t s h ou ld be re s e rve d for le s ion s s u s -
d
r
o
p e ct e d of re q u irin g s u rgica l in t e rve n t ion s u ch a s h igh gra d e in s t a bilit y of t h e
m
liga m e n t s a n d d is p la ce d m e n is ci ca u s in g t ru e lockin g or in ca s e s t h a t fa il con -
e
s
se rva t ive m a n a ge m e n t a n d obs erva t ion . MRI is a n exce lle n t m od a lit y t o eva lu a t e
s oft -t is s u e in ju rie s , bu t is lim it e d by t h e d if cu lt y in d iffe re n t ia t in g a d ege n -
e ra t ive in t a ct m e n is cu s fro m a ch ro n ic o r d e ge n e ra t ive m e n is ca l t e a r. Th e
NOT TO BE MISSED grea test u tility of MRI is in a n ega tive s tu dy, beca u se of its h igh n ega tive p red ict ive
va lu e . Co m p u t e r ize d t o m ogra p h y is o f lim it e d va lu e in eva lu a t in g m e n is ca l
1. Th e p a t e llo fe m o ra l
in ju ry w h e n co m p a re d w it h t h e a b ilit y o f MRI t o d iffe re n t ia t e s o ft -t is s u e
compartment is a common
source of knee pain. le s ion s . In va s ive im a gin g, in clu d in g a r t h ros co p y a n d a rt h rogra p h y, ca rrie s a
h igh e r a ccu ra cy a n d is be t t e r le ft for t h e s u bs p e cia lis t ’s d om a in .

TREATMENT
In p rim a ry ca re t h e in it ia l t re a t m e n t con s id e ra t ion is t o d e t e rm in e t h e n e e d for
s u rgica l t re a t m e n t , p a rt icu la rly in ca s e s of liga m e n t ou s a n d m e n is ca l le s ion s .
In ge n e ra l t h e gre a t e r t h e s eve rit y gra d e t h e m ore like ly s u rgica l in t e rve n t ion
w ill be re q u ire d . Th is gu id e lin e is p a rt icu la rly t ru e for in d ivid u a ls w h o w is h t o
re s u m e a n a ct ive life s t yle, a s in t e rn a l d e ra n ge m e n t follow e d by a ct ive u s e is
t h e e xp e rim e n t a l m od e l for in d u cin g os t e oa rt h rit is . Le s ion s of t h e cru cia t e a n d
colla t e ra l liga m e n t s w it h m ore t h a n a gra d e II le s ion (ove r 10 m m of m ot ion )
a re a t gre a t e r ris k of fu t u re p re m a t u re os t e oa rt h rit is a n d s h ou ld be re fe rre d t o
ort h op e d ic s u rge ry for con s id e ra t ion of re p a ir. For m e n is ca l in ju rie s t h a t h ave
lockin g of t h e kn e e from a d is p la ce d fra gm e n t , re fe rra l t o ort h op e d ic s u rge ry is
re com m e n d e d . Me n is ca l t e a rs t h a t a re n ot d is p la ce d or d o n ot re s u lt in e n t ra p -
m e n t ca n be t re a t e d con s e rva t ive ly.
For a ll ot h e r in ju rie s a n d le s ion s t re a t e d by t h e p rim a ry ca re clin icia n , con -
s e r va t ive ge n e ra l m a n a ge m e n t s h o u ld s t a rt w it h re s t , ice, co m p re s s io n , a n d

WHEN TO REFER
1. Lig a m e n t o u s t e a rs w it h
h ig h g ra d e in st a b ilit y
re q u ire re fe rra l t o a n
o rt h o p e d ic su rg e o n .
2. Disp la ce d m e n isca l
fra g m e n t s t h a t ca u se
e n t ra p m e n t re q u ire
re fe rra l t o a n o rt h o p e d ic
su rg e o n .
Ch a p te r 6 Me ch a n ica l Dis ord e rs of t h e Kn e e 53
e leva t ion . Alt h ou gh w e ll d e s ign e d con t rolle d t ria ls a re la ckin g t o a s s e s s e f ca cy
of t h e com p on e n t s of t h is com m on re com m e n d a t ion in d ivid u a lly or in com bi-
n a t ion , t h e re com m e n d a t ion m a ke s good s e n s e a n d is u s e d w id e ly. Re s t in g t h e
a re a of p a in com bin e d w it h cyclic icin g t h e a re a of p a in for 15 t o 20 m in u t e s
follow e d by 15 t o 20 m in u t e s w it h ou t ice w ill p rovid e good a n a lge s ia . Com p re s -
s io n u s in g a n e la s t ic w ra p b a n d a ge a ro u n d t h e k n e e p rovid e s s ym p t o m a t ic
re lie f a n d h a s t h e a d va n t a ge of in h ibit in g fu ll ra n ge of m ot ion a n d re m in d in g
t h e p a t ie n t t o re s t t h e a ffe ct e d lim b. Eleva t ion is fe lt t o a s s is t in re d u cin g sw e ll-
in g, bu t h a s t h e a d d it ion a l va lu e of re in forcin g t h e p a t ie n t t o re s t t h e kn e e.
Ph a r m a co lo gic a n a lge s ia w it h n o n s t e r o id a l a n t i-in a m m a t o ry d r u gs
s h o u ld s u f ce w h e n a d d e d t o re s t , ice, co m p re s s io n , a n d e leva t io n . Ph ys ica l
t h e ra py ca n be in s t it u t e d la t e r a ft e r t h e p a in is m a n a ge d a s it s s u cce s s w ill be
d e p e n d e n t on t h e p a t ie n t ’s a bilit y t o p a rt icip a t e in t h e p re s cribe d t h e ra p y. Us e
of a n e op re n e bra ce or h in ge d s p lin t w h ich lim it s va lgu s a n d va ru s s t re s s on
t h e kn e e ca n p rovid e re lie f a n d s u p p ort , e s p e cia lly for p a t ie n t s w it h m ild in s t a -
bilit y of t h e kn e e d u rin g re h a bilit a t ion . In ca s e s of p a t e llofe m ora l d is e a s e, t h e
u s e of e xt e rn a l s u p p ort s u ch a s e la s t ic kn e e s u p p ort s a n d ort h ot ics , p a rt icu -
la rly n e op re n e s le eve s w it h a p a t e lla r w in d ow, a re oft e n h e lp fu l.
s
Su p e rvis e d re h a b ilit a t io n is a n im p or t a n t m o d a lit y of t re a t m e n t fo r a ll
e
m
k n e e in ju r ie s , bu t p a rt icu la r ly w it h cru cia t e liga m e n t ou s in ju rie s w h e re t h e
o
r
goa l of s t re n gt h e n in g t h e h a m s t rin g m u s cle re la t ive t o t h e q u a d ricep s d ep e n d s
d
n
o n t h e t yp e of liga m e n t o u s in ju ry. Aft e r a n t e rio r cr u cia t e liga m e n t in ju rie s ,
y
S
p h ys ica l t h e ra p y s h ou ld be d ire ct e d t ow a rd a ch ievin g h a m s t rin g a n d q u a d ri-
n
i
ce p s m u s cle s of re la t ive ly e q u a l s t re n gt h . Th is is u n like t h e n orm a l s it u a t ion
a
P
w h e re t h e q u a d rice p s m u s cle is rou gh ly 50% s t ron ge r t h a n t h e h a m s t rin g. In
l
a
n
p os t e rior cru cia t e liga m e n t in ju rie s , t h e q u a d ricep s m u s cle s a re s t re n gt h e n e d
o
i
m a xim a lly t o e n s u re kn e e s t a bilit y. Ea ch p a t ie n t m u s t h ave a p h ys ica l s t re n gt h -
g
e
R
e n in g regim e n s p e ci ca lly t a ilore d t o t h e in ju ry. In ca s e s of p a t e llofe m ora l d is -
2
e a s e from p a t e lla r m a la lign m e n t , s u p e rvis e d p h ys ica l t h e ra py is in d ica t e d t o
N
s t re t ch t h e la t e ra l re t in a cu lu m , h a m s t rin g, a n d iliot ibia l ba n d in con ce rt w it h
O
I
T
s t re n gt h e n in g e x e rcis e s o f t h e q u a d r ice p s m u s cle s , p a r t icu la r ly t h e va s t u s
C
E
m e d ia lis . Qu a d rice p s -s t re n gt h e n in g e xe rcis e s u t ilizin g t h e la s t 30 d egre e s o f
S
e xt e n s ion t o s t re n gt h e n t h e va s t u s m e d ia lis m u s cle a re p ivot a l in p a t e lla r la x-
it y t o e n h a n ce t h e ve ct or force of t h e q u a d ricep s m u s cle s in ke ep in g t h e p a t e lla
w it h in t h e in t e rcon d yla r groove a n d lim it in g la t e ra l m ot io n a n d d evia t ion .
He a vily loa d e d is ot on ic e xe rcis e s w it h fu ll ra n ge of m ot ion (i.e., fu ll s q u a t s w it h
w e igh t s ) s h ou ld be avoid e d in p a t e llofe m ora l d is e a s e.
Art h roce n t e s is a n d a s p ira t ion of s yn ovia l u id for la rge e ffu s ion s ca n h e lp
d e co m p re s s a la rge t e n s e e ffu s io n a n d p rovid e im m e d ia t e re lie f. In s t illin g
in t ra -a rt icu la r cort icos t e roid s ca n re lieve p a in in ca s e s a s s ocia t e d w it h os t e -
oa rt h rit is w it h p a t e llofe m ora l d is e a s e or s m a ll m e n is ca l t e a rs .
Clinica l Co urse
In ca s e s of m ild d e ra n ge m e n t w it h ou t in s t a bilit y of t h e kn e e or a d is p la ce d
m e n is ca l fra gm e n t , t h e ou t com e is good w it h a re t u rn t o fu ll a ct ivit y in w e e ks .
In p a t ie n t s w it h a s t ro n g fa m ily h is t o ry o f o s t e o a r t h r it is a n d / o r o b e s it y, a
d e ra n ge m e n t of t h e kn e e w it h in s t a bilit y m ay le a d t o a n in cre a s e d like lih ood
of os t e oa rt h rit is . Th e ris k of p re m a t u re os t e oa rt h rit is va rie s d ire ct ly w it h t h e
s eve rit y of t h e kn e e in s t a bilit y a n d s eve re le s ion s s h ou ld be re fe rre d t o ort h o-
p e d ic s u rge ry for con s id e ra t ion of s t a biliza t ion re p a ir. Pa t ie n t s w it h a n in cre a s e d
ris k from fa m ily h is t ory of os t e oa rt h rit is , obe s it y, a n d /or in s t a bilit y s h ou ld be
a d vis e d s t ron gly t o con t in u e p h ys ica l con d it ion in g of t h e kn e e a s p re s cribe d by
p h ys ica l t h e ra p y a n d t o los e w e igh t w h e n a p p rop ria t e t o id e a l bod y w e igh t a s
m u ch a s p os s ible.
In re cu r re n t kn e e p a in o r p a in fa ilin g t o im p rove a ft e r s eve ra l w e e ks of
con s e rva t ive t h e ra py, re fe rra l t o ort h op e d ic s u rge ry m a y be w a rra n t e d .
 54 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

ICD9
Bake r’s
727.51 cyst (k n e e )
727.3 Bursitis NEC
726.60 k n e e
726.61 p e s an se rin u s
726.65 p re p at e llar
924.9 Co ntusio n (sk in su rf ace in t act )
924.11 k n e e
924.5 le g
924.10 lo w e r (w it h k n e e )
Cyst (m u cu s) (re t e n t io n ) (se ro u s) (sim p le )
727.51 Bak e r’s (k n e e )
De g e ne ratio n, de g e ne rative
718.0 art icu lar cart ilag e NEC
717.5 k n e e
717.7 p at e lla
S
De rang e me nt
E
C
718.0 cart ilag e (art icu lar) NEC •
T
I
O
717.9 k n e e
N
718.36 re cu rre n t
2
718.90 jo in t (in t e rn al)
R
e
717.9 k n e e
g
i
o
718.30 re cu rre n t
n
a
718.36 k n e e
l
P
717.9 k n e e (cart ilag e ) (in t e rn al)
a
i
n
Diso rde r
S
733.90 cart ilag e NEC
y
n
d
717.9 k n e e
r
o
715.96 Oste o arthro sis/ Oste o arthritis (d e g e n e rat ive ) (h yp e rt ro p h ic) k n e e
m
780.96 Pain(s)
e
s
719.46 k n e e
848.9 Sprain, strain (jo in t ) (lig am e n t ) (m u scle ) (t e n d o n )
844.9 k n e e
844.9 an d le g
717.5 o ld
726.90 Te ndinitis, te ndo nitis
726.61 p e s an se rin u s

Additio na l Re a ding
1. Hu s n i EM , Don oh u e JP. Pa in fu l s h o u ld e r a n d re e x s ym p a t h e t ic d ys t rop h y s yn d rom e . In Koo p m a n W J,
More la n d LW, e d s . A rthritis and A llied Conditions , 15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s ;
2005 ; 2133 –2151 .
2. Bou lw a re DW. Th e p a in fu l s h ou ld e r . In Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of
Rheum atology . Ph ila d e lp h ia : Lip p in co t t Willia m s & Wilkin s ; 2003 ; 43 –47 .
3. Wood w a rd TW, Be s t TM . Th e p a in fu l s h ou ld e r : p a r t 1. Clin ica l eva lu a t io n . A m Fam Physician 2000 ;61 :
3079 –3088 .
4. Woo d w a rd TW, Be s t TM . Th e p a in fu l s h ou ld e r : p a rt 2. Acu t e a n d ch ron ic d is ord e rs . A m Fam Physician
2000 ;61 :3291 –3300 .
CHAPTER
7 Hip Pa in
in clu d in g ro t at io n . M o d e rat e t e n d e rn e ss is d e t e ct e d o n
p alp at io n o f t h e le f t g re at e r t ro ch an t e r.
CLINICAL POINTS
• Co rre ct d ia g n o sis d e p e n d s
o n u n d e rst a n d in g t h e h ip
a n a t o m y.
• Ca re fu l h ist o ry a n d
e xa m in a t io n .
• Co g n iza n ce o f p a st h ip
p a t h o lo g y in clu d in g d e ve l-
o p m e n t a l h ip d ysp la sia a n d
ch ild h o o d d ia g n o se s.
• Magnetic resonance imaging
is b e co m in g t h e st a n d a rd
fo r e va lu a t io n o f so ft t issu e
a n d ca rt ila g e st ru ct u re s
a ro u n d t h e h ip jo in t .
• Ea rly d ia g n o sis o f st ru ct u ra l
h ip d ise a se m a y p re ve n t
d e ve lo p m e n t o f se ve re
o st e o a rt h rit is a n d t h e n e e d
fo r t o t a l h ip re p la ce m e n t .
Carol Croft
Hip p a in is a com m on com p la in t in p ri-
A 45-ye ar-o ld m an is se e n m a ry ca re a n d it h a s m a n y p o s s ible
f o r le f t h ip p ain t h at h ad ca u s e s . Th e region a l a n a t om y of t h e h ip
s
e
a n d p e lvis is co m p le x , e n co m p a s s in g
m
p ro g re sse d in se ve rit y f o r t h e
o
t h e h ip a n d t h e s a croilia c (SI) join t s , d if-
r
d
last m o n t h . Th e p ain e sp e cially fe re n t grou p s of m u s cle s , t e n d on s a n d
n
y
b o t h e rs h im at n ig h t m ak in g b u r s a e , a n d t h e va r io u s va s cu la r a n d
S
n
n e u ra l s t r u ct u re s t h a t cro s s t h e h ip
i
it d if cu lt t o lie o n h is sid e ,
a
P
join t . Re fe rre d p a in ca n a ris e from t h e
w h ich is h is p re f e rre d sle e p in g
l
ilio p s oa s re gion , lu m b os a cra l s p in e , or
a
n
p o sit io n . On e xam in at io n , h e
o
re t rop e rit o n e a l s p a ce. Th u s , t h e d iffe r-
i
g
h as a n o rm al g ait w it h f u ll e n t ia l d ia gn o s is is b ro a d a n d in clu d e s
e
R
n o n t e n d e r, p assive m o t io n in t ra -a rt icu la r p a t h ology, e xt ra -a rt icu la r
2
p a t h ology, a n d m im icke r s . Th e h is t ory
N
O
a n d e xa m in a t ion a re crit ica l t o n a rrow
I
T
C
t h e broa d d iffe re n t ia l d ia gn os is .
E
S
Clinica l Pre se nta tio n
Pa tien ts freq u en tly d escribe p a in in th e groin , u p p er th igh , or bu ttock a s “h ip ” p a in .
Pa in in th e groin or m ed ia l th igh region is m ore often d u e to h ip p a th ology a n d
a rises from irrita tion of th e join t ca p su le, syn ovia l lin in g, or bot h . Lu m bosa cra l
sp in e p a th ology ca n ca u se referred p a in to th e bu ttocks , la tera l th igh , or groin .
La tera l th igh p a in is often a ttribu ted to troch a n teric bu rsitis or a d d u ctor ten d in itis.
Eva lu a t ion of t h e p a t ie n t s h ou ld begin w it h con s id e ra t ion of a ge, leve l a n d
t yp e of a ct ivit y, p a s t in ju rie s , p a s t s u rge rie s , a n d com orbid it ie s . Poin t e d q u e s -
t io n in g a b o u t ch ild h o o d h ip p r o b le m s , s u ch a s h ip d ys p la s ia , s lip p e d
ca p it a l fe m ora l e p ip h ys is (SCFE), a n d Legg-Ca lve -Pe rt h e s d is e a s e is im p ort a n t
t o d e t e rm in e t h e like lih ood of e a rly d ege n e ra t ive a rt h ros is . Dire ct e d q u e s t ion -
in g s h ou ld a d d re s s a n y lim it a t ion s of p a t ie n t fu n ct ion in clu d in g im p a irm e n t in
a ct ivit ie s of d a ily livin g, s u ch a s d on n in g s ocks , ge t t in g in a n d ou t of t h e ca r,
joggin g, w a lkin g, a n d clim bin g s t a irs . Sym p t om s t h a t re fe r t o t h e s p in e, low e r
a bd om e n , a n d n e u rop a t h ic p a in s h ou ld be q u e s t ion e d . Com orbid it ie s ca n be a n
im p ort a n t clu e t o t h e like lih ood of ava s cu la r n e cros is (AVN) in clu d in g clot t in g
d is ord e rs , h yp e rlip id e m ia , u s e of a lcoh ol a n d t oba cco, a n d p reviou s t re a t m e n t
w it h cort icos t e roid s . Th e s ocia l h is t ory in clu d in g t yp e of w ork a n d re cre a t ion a l
e xe rcis e a n d e xp os u re t o a lt it u d e ca n a ls o p rovid e gu id a n ce a s t o t h e p re t e s t
p roba bilit y of s e riou s h ip p a t h ology.
Hip p a in in ch ild re n is o ft e n a cu t e a n d a re s u lt o f o n e o f t h e t h re e co m -
m o n d is o rd e r s o f t h e h ip jo in t : a cu t e t ra n s ie n t s yn ovit is , Le gg-Ca lve -Pe r t h e s ’
d is e a s e , a n d SCFE (1 ). Th e t yp ica l p re s e n t a t io n o f h ip p a in in ch ild r e n is
55
 56 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

Figure 7.1 Legg-Calve-Perthes disease of left hip. Epiphysis is narrowed and radiodense. A subchondral fracture is
also visible. (With permission from Fleisher GR, Ludwig S, Baskin MN. Atlas of Pediatric Emergency Medicine .
Philadelphia, PA: Lippincott Williams & Wilkins; 2004.)
S
E
C
T
I
re fe r re d p a in t o t h e a n t e r io r t h igh a n d k n e e jo in t w it h lim p in g a n d re fu s in g
O
N
t o w a lk . Tra n s ie n t s yn ovit is is a s e lf-lim it e d , in a m m a t o ry co n d it io n w it h
2
e ffu s io n o f t h e h ip jo in t . In a b o u t h a lf t h e ca s e s , a h is t o ry o f p re ce d in g u p p e r
R
e
re s p ira t o r y in fe ct io n o r m ild t ra u m a ca n b e e licit e d . Pe r t h e s ’ d is e a s e is a
g
i
re s u lt o f is ch e m ic n e cro s is o f t h e fe m o ra l h e a d t h a t le a d s t o co lla p s e o f t h e
o
n
e p ip h ys is fo llow e d by re m o d e lin g. Boys a re m ore o ft e n a ffe ct e d a n d t h e a ge
a
l
P
ra n ge fo r o n s e t is b e t w e e n a ge s 2 a n d 13 ye a r s . Me d ica l t re a t m e n t s in clu d e
a
i
a n t i-in a m m a t o ry d r u gs , p h ys ica l t h e ra p y (PT), a n d b ra cin g t o a ch ieve o p t i-
n
S
m a l p o s it io n in g o f t h e fe m o ra l h e a d in t h e a ce t a bu la r cu p . Su rge ry fo r p rox i-
y
n
m a l fe m o ra l o s t e o t o m y is s o m e t im e s p e r fo r m e d . Ab o u t h a lf o f u n t re a t e d
d
r
p a t ie n t s w ill go o n t o d eve lo p e a r ly o n s e t o s t e o a r t h r it is (OA) o f t h e h ip . SCFE
o
m
is a d is e a s e of a d ole s ce n ce a n d is a ls o m ore com m on in boys . It is fe lt t o re s u lt
e
s
from s oft e n in g of t h e e p ip h ys e a l ca rt ila ge a t a d o le s ce n ce a n d is m ore com m on
in ch ild re n w it h e n d o crin o p a t h ie s , s u ch a s h yp ogo n a d is m , h yp o p it u it a r is m ,
a n d h yp o t h yro id is m . Su rgica l t re a t m e n t is w a r ra n t e d e a r ly a s o n ly a cu t e
s lip p e d e p ip h ys is ca n b e re d u ce d , a n d it is u s u a lly p e r fo r m e d b ila t e ra lly
be ca u s e of h igh ris k of re cu rre n ce on t h e u n a ffe ct e d s id e. Con ge n it a l d ys p la s ia
of t h e h ip join t is com m on a n d oft e n d e t e ct e d w it h rou t in e n ew born s cre e n in g.
W h e n d ia gn os is is d e laye d , lim p in g a n d w e a kn e s s of t h e s u rrou n d in g m u s cle s
a re t h e t yp ica l clin ica l s ign s . X-ra ys a re u s u a lly d ia gn os t ic, a n d re fe rra l t o a n
ort h op e d ic s u rge on for a ge a p p rop ria t e t re a t m e n t s is a p p rop ria t e (Fig. 7.1 ).
Hip p a in in a d ole scen t s a n d you n g a th let es m ay rep re s e n t avu ls ion fra ct u re s
a t t h e s it e of t h e bon y in s ert ion of t h e t e n d on s of t h e re ct u s fe m oris , iliop s oa s ,
s a rt oriu s , or ot h e r region a l m u s cu la t u re. Tre a t m e n t is u s u a lly re s t a n d n on s t e r-
oid a l a n t i-in a m m a t ory m e d ica t ion s (Fig. 7.2 ).

Hip Pa in in Adults
Acu t e h ip p a in loca t e d in t h e groin re gion in t h e s e t t in g of a cu t e t ra u m a in
a d u lt s is m os t oft e n d u e t o fra ct u re of t h e fe m o ra l h e a d or a ce t a bu lu m . Ot h e r
co m m o n ca u s e s in clu d e s t re s s fra ct u re s , AVN, m u s cu la r s t ra in o f t h e a d d u ct o r
o r ilio p s o a s m u s cle s a n d t e n d o n s , a n d iliop e ct in e a l b u rs it is . La bra l t e a r s , fe m -
o roa ce t a b u la r im p in ge m e n t , a n d OA ca n a ll be s ign s o f re s id u a l s e q u e la e o f
d eve lop m e n t a l d is ord e rs o f t h e h ip join t . In a m m a t ory a r t h rop a t h ie s , s u ch a s
r h e u m a t o id a r t h r it is , ca lciu m p yro p h o s p h a t e d ih yd ra t e d e p o s it io n d is e a s e ,
a n d s e p t ic a rt h rit is s h o u ld be e n t e rt a in e d in t h e corre ct clin ica l circu m s t a n ce s .
 Ch a p te r 7 Hip Pa in 57

Right Hip
(Anterior)
Iliac crest

Articular surface

Rectus femoris tendon

Posterior sup erior
Anterior
iliac spine
su perior
iliac spine Posterior inferior Acetabular labrum
iliac sp ine ( brocartilage)

Anterior inferior Ligament of femoral head

Pu bofem oral l.
iliac spine
Head of femur

Tendons (cut)
Iliofem oral l. Su perior pu bic ram u s Gluteus medius
Piriformis
Greater Pubic Obturator internus
trochanter sym p hysis Obturator externus
Iliopsoas major
Obtu rator
foram en

s
e
Inferior p ubic ram u s

m
o
r
Fem u r Ischiu m

d
n
Lesser trochanter

y
S
n
i
a
P
l
a
n
Figure 7.2 Anterior right hip liga ments. (Asset provided by Ana tomica l Cha rt Co.)

o
i
g
e
R
2
Th e ort h op e d ic lit e ra t u re h a s lon g a t t rib u t e d m u ch of t h e OA in t h e h ip

N
join t t o a n a t om ica l d e form it ie s . Os t e oa rt h rit is of t h e h ip is oft e n s e con d a ry t o

O
I
T
con ge n it a l or d eve lop m e n t a l a bn orm a lit ie s s u ch a s d eve lop m e n t a l d ys p la s ia of

C
E
t h e h ip , Pe rt h e ’s d is e a s e a n d SCFE. Prim a ry os t e oa rt h rit is w a s p re s u m e d t o be

S
id iop a t h ic (d u e t o d eve lop m e n t a l a bn orm a lit ie s of t h e a rt icu la r ca rt ila ge ), bu t
m o re re ce n t in form a t io n s u gge s t t h e m e ch a n is m in t h e s e ca s e s is fe m o ro a -
ce t a b u la r im p in ge m e n t ra t h e r t h a n e xce s s ive co n t a ct s t re s s (2 ). Ace t a b u la r
d ys p la s ia is a s h a llow n e s s of t h e a ce t a bu lu m t h a t le a d s t o u n e q u a l d is t ribu t ion
of s t re s s on t h e a ce t a bu la r ca rt ila ge, la bra l t e a rs , a n d OA. It is oft e n a com p o-
n e n t o f d eve lo p m e n t a l d ys p la s ia o f t h e h ip , w h ich p re d o m in a n t ly a ffe ct s
w om e n . Ot h e r a n a t om ica l a bn orm a lit ie s of t h e a ce t a bu lu m s u ch a s p rot ru s ion
re s u lt in ove rcove ra ge a n d re s u lt a n t im p in ge m e n t be t w e e n t h e a ce t a bu la r rim
a n d t h e fe m o ra l h e a d –n e ck ju n ct io n . Ace t a b u la r p ro t ru s io n m a y b e s e e n in
Ma rfa n s yn d rom e a n d rh e u m a t oid a rt h rit is , bu t m os t ca s e s a re id iop a t h ic.
An a t om ic va ria t ion s in t h e fe m u r ca n a ls o le a d t o s ign i ca n t a bn orm a lit ie s
in h ip join t m e ch a n ics . Th e m os t com m on ly re cogn ize d fe m ora l a bn orm a lit y is
ca lle d “a p is t ol grip d e form it y” a n d is fe lt t o be a m a jor ca u s e of OA of t h e h ip
in m e n . Th e d e form it y re s e m ble s m ild SCFE a n d m ay be a d eve lop m e n t a l va ri-
a n t t h a t is re la t e d . Te a r s o f t h e a ce t a b u la r la b r u m h a ve b e e n d e s cr ib e d in
p a t ie n t s w it h d eve lop m e n t a l h ip d ys p la s ia , Pe rt h e s ’ d is e a s e, p reviou s SCFE,
p revio u s t ra u m a , a n d in a s s o cia t io n w it h fe m o ro a ce t a b u la r im p in ge m e n t .
Pa t ie n t s w ill ge n e ra lly re p o r t gra d u a l o n s e t o f s ym p t o m s b u t o cca s io n a lly
re la t e t h e o n s e t o f p a in t o t ra u m a o f s o m e k in d . Th e p a in is ge n e ra lly b o t h
d u ll a n d s h a rp groin p a in a n d occa s ion a lly is a ls o p re s e n t in t h e bu t t ock a n d
w ors e n e d w it h a ct ivit y or p rolon ge d s it t in g (3 ).
In t ra -a rt icu la r loos e bod ie s re s u lt from va riou s ca u s e s in clu d in g OA, AVN,
p igm e n t e d villon od u la r s yn ovit is , os t eoch on d rit is d is s eca n s , a n d p rior t ra u m a t o
t h e h ip, s u ch a s d is loca t ion w it h re d u ct ion . Me ch a n ica l s ym p t om s like clickin g,
lockin g, ca t ch in g, or givin g w ay a re com m on a lon g w it h groin p a in a n d s t iffn e s s .
 58 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

Som e p a t ie n t s d e s cr ibe a p op p in g o r s n a p p in g s e n s a t io n in a s s o cia t io n

w it h p a in a rou n d t h e h ip join t . So-ca lle d “s n a p p in g h ip ” s yn d rom e p re s e n t s in
t h re e w a ys . In t ra -a rt icu la r s n a p p in g ca n re s u lt from loos e bod ie s a n d la bra l
p a t h ology. In t e rn a l s n a p p in g is ca u s e d by t h e iliop s oa s t e n d on m ovin g ove r a
bon y p rom in e n ce. Pa in or d is com fort a s s ocia t e d w it h in t e rn a l s n a p p in g in d i-
ca t e s iliop s oa s t e n d on it is . Ext e rn a l s n a p p in g h ip is le s s com m on a n d re s u lt s
from t h e iliot ib ia l (IT) ba n d o r glu t e u s m a xim u s t e n d on s n a p p in g ove r t h e
gre a t e r t roch a n t e r. Th e frict ion of t h e t e n d on m ovin g ove r s u rrou n d in g bu rs a e
ca n re s u lt in t roch a n t e ric bu rs it is .
Pa in ove rlyin g t h e t ro ch a n t e ric bu r s a is a n o t h e r com m o n fo rm o f “h ip
p a in .” Th e re ce n t lit e ra t u re p rovid e s gre a t e r u n d e rs t a n d in g of la t e ra l h ip p a in
or gre a t e r t roch a n t e ric p a in s yn d rom e a n d t h e con t ribu t in g d ia gn os e s . Gre a t e r
t roch a n t e ric p a in s yn d rom e w a s origin a lly d e n e d a s “t e n d e rn e s s t o p a lp a t ion
ove r t h e gre a t e r t roch a n t e r w it h t h e p a t ie n t in t h e s id e -lyin g p os it ion .” Th e
t yp ica l p re s e n t a t ion is p a in a n d re p rod u cible t e n d e rn e s s in t h e region of t h e
gre a t e r t roch a n t e r, bu t t ock, or la t e ra l t h igh . It a ffe ct s be t w e e n 10% a n d 25% of
t h e ge n e ra l p op u la t ion . Som e in ve s t iga t ors s u gge s t t h a t it is m ore com m on in
p a t ie n t s w it h m u s cu los ke le t a l low ba ck p a in a n d in w om e n com p a re d w it h
S
m en .
E
C
Th e a n a t om y of t h e re gion be a rs review, a s u n d e rs t a n d in g is crit ica l for
T
I
O
a ccu ra t e d ia gn os is . Th e gre a t e r t roch a n t e r a ris e s from t h e ju n ct ion of t h e fe m -
N
ora l n e ck a n d s h a ft . Five m u s cle s a t t a ch t o it , t h e glu t e u s m e d iu m a n d glu t e u s
2
m in im u s la t e ra lly a n d t h e p iriform is , obt u ra t or e xt e rn u s , a n d obt u ra t or in t e r-
R
e
n u s m ore m e d ia lly. Su p e r cia l t o t h e glu t e u s m e d iu s a n d m in im u s t e n d on s lie s
g
i
o
a brom u s cu la r s h e a t h com p os e d of t h e glu t e u s m a xim u s , t e n s or fa s cia la t a ,
n
a
a n d IT ba n d (Fig. 7.3 ) (4 ).
l
P
Tro ch a n t e r ic b u r s it is is a co m m o n ly d ia gn o s e d in a m m a t o ry co n d it io n
a
i
w it h p a in a rou n d t h e gre a t e r t roch a n t e r t h a t ra d ia t e s d ow n t h e la t e ra l t h igh or
n
S
in t o t h e b u t t o ck . It is b e lieve d t o a ris e fro m frict io n cre a t e d b e t w e e n t h e IT
y
n
ba n d a n d t h e gre a t e r t roch a n t e r w it h rep e a t e d h ip e xion a n d e xt e n s ion . It ca n
d
r
o
be a s s ocia t e d w it h ove ru s e, t ra u m a , or a bn orm a l ga it p a t t e rn s . Sch a p ira e t a l.
m
rep ort e d t h a t 91.6% of p a t ie n t s d ia gn os e d w it h t roch a n t e ric bu rs it is h a d a s s o-
e
s
cia t e d p a t h ology a ffe ct in g a d ja ce n t a re a s , s u ch a s t h e ip s ila t e ra l h ip or lu m ba r
s p in e. Previou s ly t h ou gh t t o a ffe ct p rim a rily m id d le -a ge d w om e n , t h e d ia gn os is
is n ow in cre a s in g com m on in you n ge r a ct ive p a t ie n t s of bot h s e xe s , p a rt icu -

Bursae
Iliop ectineal bu rsae
Deep trochanteric bu rsae
Trochanteric bu rsae

Obtu rator bu rsae

Iliac bu rsae

Figure 7.3 Hip bursa e. (Asset provided by Ana tomica l Cha rt Co.)
 Ch a p te r 7 Hip Pa in 59

la rly ru n n e rs . Ch a ra ct e ris t ic d e s crip t ion of t h e p a in in clu d e s a ct ivit y-re la t e d

PATIENT ASSESSMENT
1. Ga it
2. Asym m e t ric w e a kn e ss o f
m u scle s a ro u n d h ip jo in t
(Tre n d e le n b u rg sig n fo r
a d d u ct o rs, st ra ig h t le g
ra ise a g a in st re sist a n ce
fo r p so a s/h ip e xo rs)
3. Im p in g e m e n t t e st in g a n d
FABER t e st
4. Pa lp a t io n o f SI jo in t s, t ro -
ch a n t e rs, a n d e n t h e se s
a ro u n d t h e h ip a n d p e lvis.
5. Testing for IT band tightness
a n d sn a p p in g h ip
p a in a n d s ym p t om s lyin g on t h e a ffe ct e d s id e, a s w e ll a s d is com fort w it h p ro-
lo n ge d s t a n d in g o r s it t in g w it h t h e a ffe ct e d le g cro s s e d . Th e e x a m in a t io n
reve a ls t e n d e rn e s s t o p a lp a t ion a n d w ors e n e d p a in on h ip a bd u ct ion a ga in s t
re s is t a n ce t h a t ra d ia t e s d ow n t h e la t e ra l t h igh . Th e FABER a n d Obe r t e s t a re
oft e n p os it ive a s w e ll (5 ).
Exa mina tio n
Th e clin ica l e x a m in a t ion ca n begin a s t h e p a t ie n t w a lks t o t h e e xa m in a t io n
room . Th e e xa m in e r s h ou ld n ot e t h e w a lkin g s p e e d a n d evid e n ce of a n y lim p .
Aft e r t a kin g t h e h is t ory, obs e rve t h e p a t ie n t ris in g from t h e ch a ir a n d a s k h im
or h e r t o id e n t ify t h e loca t ion of t h e p a in u s in g on e n ge r. Oft e n , p a t ie n t s w it h
in t ra -a rt icu la r h ip p a in w ill d e m on s t ra t e t h e “C s ign .” Th e p a t ie n t h old s h is or
h e r h a n d in t h e s h a p e of a C a n d p la ce s it a bove t h e gre a t e r t roch a n t e r w it h t h e
t h u m b p os t e riorly a n d t h e n ge rs w ra p p in g t ow a rd t h e groin . In t ra m e d u lla ry
le s ion s of t h e fe m ora l h e a d ca n re s u lt in p a in re fe rre d t o t h e is ch ia l t u be ros it y.
Po s t e r ior –s u p e r io r p a in re q u ire s a t t e n t io n t o d iffe re n t ia t in g h ip a n d s p in e

s
e
p a t h ology.

m
Th e Mu lt ice n t e r Art h ros copy of t h e Hip Ou t com e s Re s e a rch Ne t w ork grou p

o
r
d
id e n t i e d com m on p ra ct ice a m on g s p e cia lis t s in t h e e xa m in a t ion of t h e h ip

n
y
(re fe re n ce 25, Ma r t in a r t icle ) (6 ). Be gin n in g w it h t h e s t a n d in g p o s it io n t h e

S
n
e xa m in e r s h ou ld a s s e s s t h e h e igh t o f t h e s h o u ld e rs a n d ilia c cre s t s on e a ch

i
a
s id e, obs e rve s p in a l a lign m e n t in clu d in g e xion t o d e t e ct s colios is , a n d p e r-

P
l
form s in gle leg s t a n ce t e s t in g. We a kn e s s on t h e a ffe ct e d s id e w ill re s u lt in a

a
n
d rop in t h e con t ra la t e ra l bu t t ock w h e n s t a n d in g on t h e p a in fu l leg. Ga it a bn or-

o
i
g
m a lit ie s oft e n h e lp t o d e t e ct p a t h ology ow in g t o t h e t ra n s fe r of d yn a m ic a n d

e
R
s t a t ic loa d s t o t h e liga m e n t s a n d os s e ou s s t ru ct u re s (Figs . 7.4 a n d 7.5 ).

2
N
O
I
T
C
E
S
Normal hip Weak hip
abductors abductors

Figure 7.4 Trendelenburg sign. (With permission Figure 7.5 Wea k hip a bductors. (With permission
from Bickley LS, Szilagyi P. Ba tes’ Guide to Physica l from Bickley LS, Szila gyi P. Ba tes’ Guide to Physica l
Exa mina tion a nd History Ta king , 8th ed. Examination and History Taking, 8th ed. Philadelphia,
Phila delphia , PA: Lippincott Willia ms & Wilkins.) PA: Lippincott Willia ms & Wilkins, 2003.)
 60 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

Figure 7.6 Technique for FABER ma neuver.
(With permission from Berg D, Worza la K. Atla s
of Adult Physical Diagnosis . Phila delphia, PA:
Lippincott Willia ms & Wilkins; 2006.)
Figure 7.7 Technique for Ober’s ma neuver use-
ful to a ssess for tightness in the iliotibia l ba nd.
(With permission from Berg D, Worza la K. Atla s
of Adult Physical Diagnosis . Philadelphia, PA:
Lippincott Willia ms & Wilkins; 2006.)
Figure 7.8 Technique for grea ter trocha nteric
bursa a ssessment: pa ssive hip forwa rd exion
a nd interna l rota tion. (With permission from
Berg D, Worza la K. Atla s of Adult Physica l
Diagnosis . Phila delphia , PA: Lippincott Willia ms
& Wilkins; 2006.)

Te s t in g of ra n ge of m ot ion in clu d in g e xion , e xt e n s ion , a d d u ct ion , a bd u c-

t ion , a n d in t e rn a l rot a t ion in e xt e n s ion a n d e xt e rn a l rot a t ion in e xt e n s ion is
p e rform e d in t h e s u p in e p os it ion . Hip e xion is be s t t e s t e d w it h t h e kn e e e xe d
S
E
t o re m ove t e n s ion in t h e h a m s t rin g a n d is n orm a lly 100 t o 135 d egre e s . Mot ion
C
T
is oft e n lim it e d in ca s e s of d e form it y a n d a d va n ce d OA. Hip e xion con t ra ct u re
I
O
N
ca n be q u a li e d w it h t h e Th om a s t e s t in w h ich bot h t h igh s a re brou gh t t o t h e
2
ch e s t in t h e s u p in e p os it ion . Th e n t h e a ffe ct e d leg is a llow e d t o e xt e n d t o n e u -
R
t ra l, a n d in a bilit y t o re a ch n e u t ra l d e m on s t ra t e s e xion con t ra ct u re. Th e Obe r
e
g
t e s t ca n be p e rform e d t o m e a s u re t igh t n e s s in t h e IT ba n d , a n d Ely’s t e s t is
i
o
n
p e rform e d t o d e t e ct t igh t re ct u s fe m oris m u s cle s . In t e rn a l rot a t ion a n d a bd u c-
a
l
t ion a re lim it e d e a rlie r t h a n ot h e r ra n ge of m ot ion in OA. More com p le t e t e s t -
P
a
in g o f e x t e n s io n is b e s t d o n e in t h e p ro n e o r la t e ra l p o s it io n by p a s s ive ly
i
n
e xt e n d in g t h e s t ra igh t e n e d leg (Figs . 7.6 t o 7.8 ).
S
y
n
Im p in ge m e n t t e s t in g in clu d e s s eve ra l com m on t e s t in g m a n e u ve rs . Begin
d
r
w it h a ct ive ly t h e n p a s s ive ly e xin g t h e h ip a s fa r a s p os s ible w it h t h e kn e e in
o
m
e x io n , o b s e r vin g t h e co n t ra la t e ra l h ip fo r m ove m e n t . W it h t h e le g fu lly
e
s
e xt e n d e d h old t h e con t ra la t e ra l a n t e r ior s u p e rior ilia c s p in e t o s t a biliz e t h e
p e lvis a n d t h e n p a s s ive ly a b d u ct a n d a d d u ct t h e le g. Fu r t h e r im p in ge m e n t
t e s t in g is p e rform e d w it h t h e h ip a n d kn e e e xe d t o 90 d egre e s follow e d by
in t e r n a l a n d e x t e r n a l ro t a t io n o f t h e h ip jo in t . Th e FABER o r Pa t rick ’s t e s t
in clu d e s a p p lyin g d ow n w a rd p re s s u re on t h e e xe d kn e e a n d t h e con t ra la t e ra l
a n t e rio r s u p e rio r ilia c s p in e d u rin g t h e t e s t . Pa in ra d ia t in g t o t h e b u t t o ck is
con s is t e n t w it h SI p a t h ology, w h e re a s p a in in t h e groin in d ica t e s h ip p a t h ology.
Th e St ra igh t Leg Ra is e Aga in s t Re s is t a n ce Te s t (St in ch e ld t e s t ) is a n a s s es s m en t
of h ip exor/p s oa s s t re n gt h a n d ca n e licit s ign s of in t ra -a rt icu la r p a t h ology by
in cre a s in g com p re s s ive force a cros s t h e h ip join t or p s oa s p la cin g p re s s u re on
t h e la bru m . Wit h t h e kn e e in e xt e n s ion , t h e p a t ie n t ca rrie s ou t a ct ive s t ra igh t
NOT TO BE MISSED leg ra is e u p t o 45 d egre e a t w h ich p oin t t h e e xa m in e r’s h a n d is p la ce d d is t a l t o
t h e kn e e, w h ile a p p lyin g a d ow n w a rd force. A p os it ive t e s t is n ot e d w h e n t h is
1. Fe ve r
m a n e u ve r ca u s e s p a in or d e m on s t ra t e s foca l w e a kn e s s .
2. Acu t e p a in Pa lp a t ion of t h e bon y la n d m a rks in clu d in g t h e ilia c cre s t , a n t e rior s u p e rior
3. Deform ity an d/o r inabilit y ilia c s p in e, p o s t e rio r s u p e rio r ilia c s p in e, SI jo in t s , is ch ia l t u b e ro s it y, co ccyx ,
to bea r w eig ht a n d gre a t e r t roch a n t e r s h ou ld be p e rform e d . Th e fe m ora l n e ck is loca t e d t h re e
4. Risk fa ct o rs fo r se p t ic n ge rbre a d t h s be low t h e a n t e rior s u p e rior ilia c s p in e.
a rt h rit is in clu d in g
im m u n o su p p re ssio n ,
b a ct e re m ia Studie s
5. Risk fa ct o rs fo r AVN su ch Pla in ra d iogra p h s a re t h e rs t ch oice for in it ia l im a gin g of t h e h ip join t . Th e
a s p re vio u s st e ro id u se ,
s t a n d a rd s cre e n in g s e rie s u s u a lly in clu d e s s u p in e a n t e rop os t e rior h ip view for
e xp o su re t o a lt it u d e ,
t h ro m b o p h ilia a q u a lit a t ive a s s e s s m e n t o f a ce t a b u la r cove ra ge , fe m o ra l h e a d s h a p e , a n d
e xt e n t of OA. Fu n ct ion a l ra d iogra p h s s u ch a s a frog la t e ra l view a n d cros s t a ble
 Ch a p te r 7 Hip Pa in 61

Gluteal
muscles

Anterior inferior Sacroiliac joint

iliac spine
Acetabular fossa
Acetabulum
Hip joint
Iliopectineal line
Head of femur
Neck of
femur Fovea capitis
Greater
trochanter Acetabular notch Obturator
foramen Symphysis
pubis

s
e
m
o
r
d
n
y
Intertrochanteric

S
line

n
i
a
P
l
a
Inferior ramus

n
Ischial tuberosity

o
Lesser of pubis

i
g
trochanter

e
R
2
N
O
I
T
Shaft

C
E
of femur

S
Figure 7.9 Anteroposterior radiogra ph of the hip joint. (With permission from Snell RS. Clinical Anatomy, 7th ed.
Phila delphia , PA: Lippincott Willia ms & Wilkins; 2003.)

la t e ra l view s h e lp vis u a lize t h e p roxim a l fe m u r a n d fe m ora l h e a d s p h e ricit y

a n d a s s e s s t h e p rom in e n ce in t h e a n t e rior h e a d –n e ck ju n ct ion ch a ra ct e ris t ic of
fe m oroa ce t a bu la r im p in ge m e n t (7 ). Th e s e view s a re a ls o u s e d in a s s e s s in g
a d va n ce OA. Qu a n t it a t ive a s s e s s m e n t of OA u s in g join t s p a ce w id t h s h ou ld be
d on e w it h a s t a n d in g ra d iogra p h . Not e t h a t in t roch a n t e ric bu rs it is t h e im a gin g
s t u d ie s a re fre q u e n t ly u n reve a lin g a lt h ou gh ca lci ca t ion m ay occa s ion a lly be
vis ible w it h in t h e bu rs a l s p a ce (Figs . 7.9 a n d 7.10 ).
Com p u t e d t om ogra p h y is p rim a rily u s e d for a s s e s s m e n t of a ce t a bu la r fra c-
t u re s , fe m ora l h e a d fra ct u re s , fe m ora l n e ck fra ct u re s , a n d a s s e s s m e n t of bon e
in t h e s e t t in g w h e re revis ion of t ot a l h ip a rt h rop la s t y is con s id e re d . Ma gn e t ic
re s on a n ce im a gin g (MRI) is t h e s u p e rior m od a lit y for eva lu a t in g t h e s oft t is s u e s
a rou n d t h e h ip s join t a n d t h u s h a s la rge ly re p la ce d com p u t e d t om ogra p h y for
t h is p u rp os e.
Ra d io n u clid e s cin t igra p h y w it h t e ch n e t iu m , ga lliu m , a n d in d iu m -la b e le d
w h it e blood ce lls ca n be u s e fu l in d e t e ct in g m e t a s t a t ic le s ion s , Pa ge t ’s d is e a s e,
a cu t e a n d ch ron ic os t e om ye lit is , a n d p ros t h e t ic join t in fe ct ion s .
 62 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

Subchondral Subchondral
cysts sclerosis
Nonuniform
joint space
Osteophyte
S
E
C
T
I
O
Buttressing
N
Lateral and
2
A B
superior migration
R
e
g
Figure 7.10 Degenerative joint disease: HIP. A. Diagram. B. Radiograph. Note the following fea tures: non-
i
o
uniform loss of joint spa ce (1), subchondra l sclerosis (2), subchondra l bone cysts (3), osteophytes (4 ), cortica l
n
a
buttressing (5), a nd thickened weight-bea ring tra becula e (6 ). (With permission from Yochum TR, Rowe LJ. Yochum
l
and Rowe’s Essentials of Skeletal Ra diology, 3rd ed. Phila delphia , PA: Lippincott Willia ms & Wilkins; 2004.)
P
a
i
n
Dyn a m ic s on ogra p h y of t h e bu rs a e a rou n d t h e h ip m ay be h e lp fu l, t h ou gh
S
y
MRI is m ore s e n s it ive for d e t e ct in g in a m e d bu rs a e a n d m u s cu la r t e a rs .
n
d
MRI is p a rt icu la rly e ffe ct ive a t d e t e ct in g AVN a n d is t h e gold s t a n d a rd s in ce
r
o
m
s ign i ca n t join t d e s t ru ct ion ca n occu r p rior t o evid e n ce of ra d iogra p h ic a bn or-
e
m a lit ie s on p la in ra d iogra p h s . Likew is e, MRI ca n d e t e ct s oft t is s u e a bn orm a li-
s
t ie s , s u ch a s p igm e n t e d villon od u la r s yn ovit is (Figs . 7.11 t o 7.13 ) (8 ).
Me d ica l a n d s u rgica l t re a t m e n t o p t ion s fo r OA in t h e la s t d e ca d e ca n be
o ffe re d t o p a t ie n t s b e fo re a d va n ce d jo in t in vo lve m e n t re q u ir in g t o t a l jo in t

Figure 7.11 A: Tra nsverse t1-weighted ima ge of a pa tient (supine) with hip pa in on long-term steroid thera py for
lupus erythema tosus shows nonspeci c ma rrow edema (a rrow) in the left femora l hea d (f). The loca tion a nd
clinica l context of this nding a re suggestive of a va scula r necrosis, but the ima ging a ppea ra nce is otherwise
nonspeci c. a , a ceta bulum; b , bla dder. (From Koopma n WJ, Morela nd LW. Arthritis a nd Allied Conditions: A
Textbook of Rheuma tology, 15th ed. Phila delphia , PA: Lippincott Willia ms & Wilkins; 2005.)
 Ch a p te r 7 Hip Pa in 63

a rt h rop la s t y. In p a rt icu la r, s u rgica l t e ch n iq u e s s u ch

Figure 7.12 Avascular necrosis: bite and crescent signs. AP hip. Note the
homogeneous increa se in density (snow ca p sign ) involving the upper
a spect of the hea d with a curvilinea r inferior border (bite sign ) (a rrows ).
Benea th the a rticula r cortex a subchondra l fra cture (crescent sign ) ca n be
a s p e ria ce t a bu la r o s t e ot om y, s a fe s u rgica l d is loca -
t ion of t h e h ip , a n d h ip a rt h ros cop y p rovid e s a fe a n d
e ffe ct ive t ools t o corre ct a n a t om ica l p roble m s . Th e
t re a t m e n t ou t com e in m a n y m e ch a n ica lly com p ro-
m is e d h ip s is lim it e d by t h e d egre e of ca rt ila ge d a m -
a ge t h a t o ccu rre d p rior t o t re a t m e n t . Th e ca ve a t is
d e t e ct ion of e a rly s t a ge s of t h e join t d is e a s e, w h ich
ca n be d if cu lt w it h p la in ra d iogra p h s a lon e. Th u s ,
MRI ca n h e lp id e n t ify d ia gn os e s s u ch a s fe m oroa -
ce t a b u la r im p in ge m e n t , a ce t a b u la r d ys p la s ia , a n d
la bra l in ju ry, w h ich a re fe lt t o be p re cu rs ors t o p re -
m a t u re OA. Eva lu a t io n o f t h e a rt icu la r ca rt ila ge o f
t h e h ip join t is ch a lle n gin g be ca u s e of t h e t h in ca r-
t ila ge a n d s p h e rica l ge om e t ry of t h e fe m ora l h e a d
a n d a ce t a bu lu m . Th u s , t h e in p u t of a n e xp e rie n ce d
ra d iologis t is im p ort a n t in ch oos in g t h e m os t a p p ro-
p r ia t e p ro t oco l fo r t h e MRI. MR a r t h rogra p h y h a s

s
seen (a rrowhea d ). (With permission from Yochum TR, Rowe LJ. Yochum a nd h igh e r d ia gn os t ic p e rform a n ce t h a n MRI for d e t e ct -

e
m
Rowe’s Essentia ls of Skeleta l Ra diology, 3rd ed. Phila delphia , PA: Lippincott in g la bra l t e a rs bu t h a s low e r d ia gn os t ic p e rform -

o
r
Willia ms & Wilkins; 2004.) a n ce fo r eva lu a t io n of t h e a rt icu la r ca r t ila ge . MRI

d
n
t e ch n o logy is co n t in u in g t o evo lve , a n d a d va n ce s

y
S
t h a t p rovid e h igh e r s p a t ia l re s olu t ion a n d im p rove d t is s u e con t ra s t w ill h e lp

n
i
id e n t ify t h os e p a t ie n t s for w h om e a rly in t e rve n t ion w it h a rt h ros cop y w ill be

a
P
be n e cia l.

l
a
n
o
i
g
e
R
2
N
O
I
T
C
E
S
Figure 7.13 Inguinal mass: history of right hip pain. A: Soft tissue window
computed tomogra phic (CT), a xia l pelvis. Note the cystic, low a ttenua tion
ma ss immedia tely a nterior to the right femora l hea d (a rrow). B: Proton
density–weighted ma gnetic resona nce ima ging (MRI), a xia l pelvis. The a rea
of decrea sed a ttenua tion on the CT study displa ys a homogeneous low
signa l intensity on MRI (a rrow). C: T2-weighted MRI, a xia l pelvis. Observe
the homogeneous hyperintense signa l intensity in this loca lized uid collec-
tion (a rrow). These ndings a re consistent with iliopsoa s bursitis. Comment:
This patient’s history includes an inguinal hernia and the recent onset of right
hip pain. At physical examination, a slightly pulsatile soft tissue mass was noted
on deep palpation. (With permission from Yochum TR, Rowe LJ. Yochum and
Rowe’s Essentials of Skeletal Radiology, 3rd ed. Philadelphia: Lippincott Williams
& Wilkins; 2004.)
 64 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

WHEN TO REFER Tre a tme nt a nd Clinica l Co urse

Cu rre n t t re a t m e n t s for OA of t h e h ip e n t a il a com bin a t ion of n on p h a rm a co-
• Risk fa ct o rs fo r AVN a n d
logic, p h a rm a cologic, a n d s u rgica l t h e ra p ie s . Non p h a rm a cologic t h e ra p ie s , s u ch
h ip p a in
a s w e igh t los s , la n d -ba s e d a n d w a t e r e xe rcis e, PT, a n d s e lf-m a n a ge m e n t e d u ca -
• Acu t e jo in t e ffu sio n w it h t ion p rogra m s a re ge n e ra lly s u p p ort e d by s a t is fa ct ory or good , bu t n ot e xce lle n t ,
o r w it h o u t fe ve r
evid e n ce. Th e p h a rm a cologic t h e ra p ie s t o re d u ce s ym p t om s in clu d e a ce t a m i-
• Fra ct u re s n op h e n , NSAIDs , COX 2 in h ibit ors , h ya lu ron ic a cid a n d glu cos a m in e, a ll of w h ich
• History of developmenta l a re of m od e s t be n e t . Th e ris ks a s s ocia t e d w it h lon g-t e rm u s e of NSAIDS a n d
or child hood h ip patholo gy COX 2 in h ibit ors a re a s ou rce of legit im a t e con ce rn . Cu rre n t s t u d ie s a re focu s e d
on d is cove ry a n d d eve lop m e n t of d is e a s e m od ifyin g os t e oa rt h rit is d ru gs w it h
h op e s of m od ifyin g t h e p rogre s s ion of s t ru ct u ra l ch a n ge s in OA a n d re d u cin g
t h e p reva le n ce of t h e d is e a s e (9 ).
Give n t h e d eve lop m e n t s in s u rgica l m a n a ge m e n t , e a rly re fe rra l for a d va n ce d
im a gin g s u ch a s MRI a n d s p e cia lize d eva lu a t ion by ort h op e d is t s a re re a s on a ble
s t e p s t o obvia t e p rogre s s ion t o a d va n ce d OA.
Troch a n t e ric bu rs it is is t yp ica lly s e lf-lim it e d a n d re s p on d s t o n on op e ra t ive
m a n a ge m e n t in clu d in g re s t , ice, NSAIDS, a n d PT. Th e PT in volve s s t re t ch in g,
S
e xibilit y, s t re n gt h e n in g, a n d im p rovin g ga it m e ch a n ics . In t ra bu rs a l in je ct ion
E
C
of cort icos t e roid s a n d loca l a n e s t h e t ics a re oft e n e ffe ct ive w h e n con s e rva t ive
T
I
O
s t ra t egie s a re u n s u cce s s fu l. For in t ra ct a ble s ym p t om s t h a t fa il in je ct ion s a n d
N
a re fe lt n ot t o be d u e t o a n ot h e r ca u s e, bu rs e ct om y ca n be e ffe ct ive.
2
R
e
g
i
ICD9
o
n
a
727.3 Bursitis NEC
l
P
726.5 h ip
a
i
n
726.5 t ro ch an t e ric are a
S
924.9 Co ntusio n (sk in su rf ace in t act )
y
n
924.01 h ip
d
r
o
924.00 w it h t h ig h
m
De rang e me nt
e
s
718.95 h ip (jo in t ) (in t e rn al) (o ld )
835.00 cu rre n t in ju ry
718.35 re cu rre n t
718.90 jo in t (in t e rn al)
718.95 h ip
718.30 re cu rre n t
718.35 h ip
Diso rde r
733.90 cart ilag e NEC
718.05 h ip
829.0 Fracture (ab d u ct io n ) (ad d u ct io n ) (avu lsio n ) (co m p re ssio n ) (cru sh )
(d islo cat io n ) (o b liq u e ) (se p arat io n ) (clo se d )
733.14 h ip
716.60 Mo no arthritis
716.65 p e lvic re g io n (h ip ) (t h ig h )
715.95 Oste o arthro sis/ Oste o arthritis hip (d e g e n e rat ive ) (h yp e rt ro p h ic)
780.96 Pain (s)
719.40 jo in t
719.45 h ip
848.9 Sprain, strain (jo in t ) (lig am e n t ) (m u scle ) (t e n d o n )
843.9 h ip
843.9 an d t h ig h
726.90 Te ndinitis, te ndo nitis
726.5 t ro ch an t e ric
 Ch a p te r 7 Hip Pa in 65

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m e ch a n ica l con ce p t . Clin Orthop Relat Res. 2008 Fe b ;466 (2 ):264 –72 .
3. Tibor LM , Se kiya JK. Diffe re n t ia l d ia gn os is of p a in a rou n d t h e h ip join t . A rthroscopy 2008 ;24 :1407 –1421 .
4. St ra u s s E, Nh o S, Ke lly B. Greater Trochanteric Pain Syndrom e. Sprots Med A rthrosc Rev. 2010 ;18:11.
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1986 ;67 :815 –7 .
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im p in ge m e n t a s a ca u s e of os t e o a rt h rit is . Sem in Musculoskelet Rad 2008 ;12 :334 –345 .
8. Kijow s ki R. Clin ica l ca rt ila ge im a gin g of t h e kn e e a n d h ip join t s . A m J Rad 2010 ;195 : 618 –628 .
9. Hu n t e r DJ Ph a rm a cologic t h e ra py for os t e oa rt h rit is –t h e e ra of d is e a s e m od i ca t ion . Nature Rev Rheum .
2010 ;7 (1 ):13 –22 .
10. Cu s h JJ, Lip s ky PE. Ap p roa ch t o a rt icu la r a n d m u s cu lo s ke le t a l d is ord e r s . In : Fa u ci AS, Bra u n w a ld E,
Ka s p e r DL, e t a l. Harris on ’s Prin ciples an d Pract ice of In t ern al M edicin e, 17t h e d : h t t p :/ / w w w.
a cce s s m e d icin e.com /con t e n t .a s p x?a ID = 2869993.

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 CHAPTER
8 Sports-Related Conditions
a nd Injuries
Lisa L. W illett

A 52 ye ar o ld m ale w it h t yp e
Injurie s o f the
2 d iab e t e s m e llit u s b e g an an
Ro ta to r Cuff
S
E
CLINICAL PRESENTATION
C
e xe rcise p ro g ram t o im p ro ve
T
I
O
h is d iab e t ic co n t ro l. He h as Rota tor cu ff ten d in itis is com m on in
N
a th letes w h o p a rticip a te in rep etitive
2
b e e n p layin g t e n n is t h re e
overh ea d a ctivities, s u ch a s soft ba ll,
R
e
t im e s a w e e k f o r t h e p ast ba s eba ll, te n n is , or golf. Th e rot a tor
g
i
o
m o n t h . He p re se n t s t o h is cu ff is com p rised of fou r m u scles, th e
n
a
p h ysician co m p lain in g o f s u p ra s p in a t u s , in fra s p in a t u s , t e re s
l
P
m in or, a n d su bsca p u la ris, w h ose ten -
a
rig h t sh o u ld e r p ain . Th e
i
d on s a tta ch to th e p roxim a l h u m eru s
n
p ain is w o rse in ce rt ain
S
(Fig. 8.1 ). Im p in gem en t of th e ten d on s
y
n
p o sit io n s. be t w e e n t h e h e a d of t h e h u m e ru s
d
r
o
Sp o rt in g act ivit ie s are an a n d th e a crom ion ca n lea d to in a m -
m
m a tion a n d su bseq u en t tea rs of on e
e
im p o rt an t co m p o n e n t o f a h e alt h y lif e st yle . Pat ie n t s o f all ag e s
s
or m ore of th e ten d on s. Th e su p ra sp -
are e n co u rag e d b y p h ysician s t o e xe rcise f o r h e alt h b e n e t s. in a tu s is th e m ost freq u en tly in volved .
Ho w e ve r, sp o rt s act ivit ie s can le ad t o in ju rie s. A s o u r ad u lt Sym p tom s in clu d e “a ch e-like” sh ou l-
p o p u lat io n ag e s an d a larg e r p ro p o rt io n o f t h e p o p u lat io n d er p a in , often w orse a t n igh t, exa cer-
ba ted by a bd u ction or exion of th e
e m b race s h e alt h ie r lif e st yle , sp o rt s-re lat e d co n d it io n s an d in ju rie s
a rm a s w ell a s a ctivities th a t in volve
are p re d ict e d t o in cre ase . ove rh e a d m ove m e n t of t h e a rm . If
Th e re are m an y t yp e s o f sp o rt s-re lat e d in ju rie s, ran g in g f ro m t h e t e a r is com p le t e, p a t ie n t s m ay
ch ro n ic o ve ru se t o t rau m at ic in ju rie s. Lo w e r e xt re m it y o ve ru se n ote w ea kn ess a n d d ecrea s ed ra n ge
of m otion (2 ).
in ju rie s o ccu r f ro m jo g g in g , w alk in g , ju m p in g , o r cyclin g .
Exam p le s o f ch ro n ic o ve ru se in ju rie s in clu d e p at e llo f e m o ral p ain
syn d ro m e an d A ch ille s t e n d in it is. Of t h e o ve ru se in ju rie s o f t h e EXAMINATION
Th e p h ys ica l e xa m fin d in gs va ry
u p p e r e xt re m it y, b o t h ro t at o r cu ff t e n d in it is an d lat e ral e p i-
d ep en d in g on w h ich of th e fou r ten -
co n d ylit is are t h e m o st co m m o n . In ju rie s re lat e d t o t rau m a can d on s a re in volved , a n d th e d egree of
re su lt f ro m h ig h -im p act sp o rt in g act ivit ie s, an d in clu d e lig am e n t in ju ry. If th ere is on ly in a m m a tion ,
t e ars (su ch as an an t e rio r cru ciat e lig am e n t t e ar), lig am e n t th e p a tien t w ill exp erien ce p a in ; p a r-
t ia l or fu ll-t h ickn e s s t e a rs re s u lt s in
sp rain s (lat e ral an k le sp rain ), f ract u re s, jo in t d islo cat io n s, o r h e ad
w e a kn e s s a n d d e cre a s e d ra n ge of
in ju rie s. Th e e p id e m io lo g y o f sp o rt in g in ju rie s is lim it e d . In st u d - m otion . Alth ou gh over 20 m a n eu vers
ie s (1), lo w e r e xt re m it y in ju rie s are m o re co m m o n t h an u p p e r h ave be e n d e s cribe d t o t e s t rot a t or
e xt re m it y, w it h t h e m o st co m m o n sit e s b e in g t h e k n e e an d an k le . cu ff t e a rs , t h e 3 m a n e u ve rs m os t
u s e fu l for p re d ict in g a rot a t or cu ff

66
 Ch a p te r 8 Sp orts-Rela ted Con d ition s a n d In ju rie s 67

Supraspinatus

Acromion

Suprascapular
notch

Coracoid process

Tendon of long head

of biceps brachii (cut)

Supraspinatus
Humerus
Spine of
scapula
Subscapularis
A Infraspinatus

Teres minor

s
Teres major

e
m
(cut)
B

o
r
d
Figure 8.1 Rota tor cuff muscles. A, a nterior; B, posterior. The supra spina tus (A a nd B), infra spina tus (B), teres minor (B), a nd subsca pula ris (A) ca nva s

n
y
the perimeter of the glenohumera l joint ca psule. (From Moore KL, Agur AMR. Essentia l Clinica l Ana tomy, 2nd ed. Ba ltimore: Lippincott Willia ms & Wilkins,

S
2002. Figure 7.12, p. 425.)

n
i
a
P
l
a
n
tea r a re: su p ra sp in a tu s w ea kn ess , w ea kn ess in ext ern a l rota -

o
i
tion , a n d a p ositive im p in gem en t sign (3,4). Th e test to elicit

g
e
R
s u p ra s p in a t u s w e a kn e s s (“e m p t y ca n s ign ”) in volve s h avin g

2
th e p a tien t a bd u ct h is a rm to 90 d egrees, w ith 30 d egrees for-

N
w a rd a d d u ct ion . Wit h t h e p a t ie n t ’s t h u m b p oin t in g d ow n

O
I
T
tow a rd th e oor, th e exa m in er p u sh es d ow n on th e a rm a t th e

C
E
d is t a l h u m e ru s a s t h e p a t ie n t re s is t s . To e licit w e a kn e s s in

S
extern a l rot a tion , a n d in g con sis ten t w ith in fra sp in a tu s com -
p rom is e, th e p a tien t h old s h is a rm s a ga in st h is tors o, exes
h is elbow s a t 90 d egrees w ith th e th u m bs tu rn ed u p a n d t h e
a rm rota ted in tern a lly 20 d egrees. Th e p a tien t is th en a sked to
extern a lly rota te th e a rm a ga in st th e exa m in er’s resista n ce. A
p os it ive im p in ge m e n t s ign (Fig. 8.2 ) is e licit e d w it h t h e a rm
d ow n , ext e rn a lly rot a t e d a n d t h e n p a s s ive ly e leva t e d t o a n
overh ea d p osition . Th e p a tien t w ill exp erien ce p a in w ith in ter-
n a l rot a t ion of t h e a rm . An ot h e r m a n e u ve r, t h e p a in fu l a rc
s ign (Fig. 8.3 ) ca n be h elp fu l t o exclu d e a rot a t or cu ff te a r; a
p ositive is in terp reted w h en p a in is elicited w ith a ctive ra n ge
of m otion betw een 60 a n d 100 d egrees of a bd u ction a n d it h a s
a h igh sen sitivity (97.5%) for rota tor cu ff t ea r. Th erefore, if th is
sign is absen t, th e p a t ien t is u n likely to h ave a tea r.

Figure 8.2 Impingement sign. Impingement of the grea ter
tuberosity on the cora coa cromia l liga ment occurs when the
shoulder is forwa rd exed to 90 degrees a nd interna lly rota ted,
reproducing the pa tient’s pa in. From Kova l KJ, MD a nd
Zuckerma n JD, MD. Atla s of Orthopa edic Surgery: A Multimeida l
Reference. Phila delphia : Lippincott Willia ms & Wilkins, 2004.
STUDIES
If t h e e x a m a n d h is t o ry a re co n s is t e n t w it h ro t a t o r cu ff
t e n d in it is , fu rt h e r s t u d ie s a re n ot n e ce s s a ry. How eve r, if t h e
p a in p e r s is t s , p la in ra d io gra p h s a re in d ica t e d . Su p e r io r
m igra t ion of t h e h u m e ra l h e a d ca n be s e e n if a la rge rot a t or
cu ff t e a r is p re s e n t . Ma gn e t ic re s on a n ce im a gin g (MRI) is t h e
p re fe rre d t e s t for d ia gn os in g rot a t or cu ff d is ord e rs , a lt h ou gh
u lt ra s on ogra p h y is e m e rgin g a s a cos t -e ffe ct ive a lt e rn a t ive
w it h s im ila r s e n s it ivit y a n d s p e ci cit y.
 68 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s
S
E
C
T
I
O
N
2
R
e
Figure 8.3 Pa inful a rc sign. From Moore KL, PhD, FRSM, FIAC & Da lley AF II, PhD. Clinica l Oriented Ana tomy (4th
g
i
ed.). Ba ltimore: Lippincott Willia ms & Wilkins, 1999.
o
n
a
l
P
a
i
n
TREATMENT
S
y
Mu lt ip le t h e ra p ie s a re a va ila ble t o t re a t ro t a t o r cu ff in ju r ie s . Non o p e ra t ive
n
d
t h e ra p y con s is t s of 6 w e e ks t o 3 m on t h s of n on s t e ro id a l a n t i-in a m m a t ory
r
o
m
a ge n t s (NSAIDS), in t ra -a rt icu la r s t e roid in je ct ion s , p a s s ive a n d a ct ive e xe rcis e s
e
w it h p h ys ica l t h e ra p y, p lu s h e a t , cold , or u lt ra s on ogra p h y t h e ra p y. Pa t ie n t s w h o
s
fa il n on op e ra t ive t re a t m e n t ca n be re fe rre d t o ort h op e d ics for s u rgica l rep a ir
w it h op e n , m in i-op e n , or a rt h ros cop ic t e ch n iq u e s . In a s ys t e m a t ic review of 137
s t u d ie s of n on op e ra t ive a n d op e ra t ive t re a t m e n t s (5 ), evid e n ce w a s n ot con clu -
s ive t o re com m e n d on e t h e ra py ove r a n ot h e r. Old e r a ge, in cre a s e d s ize of t h e
t e a r, a n d gre a t e r p re op e ra t ive s ym p t om s w e re a s s ocia t e d w it h re cu rre n t t e a rs .
Du ra t ion of s ym p t om s w a s n ot a s s ocia t e d w it h p oore r ou t com e s .

CLINICAL POINTS
• Ove ru se in ju rie s a re
co m m o n w h e n p a t ie n t s
b e g in e xe rcise p ro g ra m s.
• Lo w e r e xt re m it y in ju rie s
a re m o re co m m o n t h a n
u p p e r e xt re m it y, w it h t h e
m o st co m m o n sit e s b e in g
t h e kn e e a n d a n kle .
• Th e m o st co m m o n ca u se o f
kn e e p a in a m o n g st p a t ie n t s
e xe rcisin g is p a t e llo fe m o ra l
p a in syn d ro m e .
• Co n se rva t ive m a n a g e m e n t
w it h re st , ice , p h ysica l
t h e ra p y, a n d n o n st e ro id a l
a n t i-in a m m a t o ry a g e n t s is
e ffe ct ive rst lin e t h e ra p y.
CLINICAL COURSE
Rega rd le s s of t h e t re a t m e n t a p p roa ch , t h e m a jorit y of p a t ie n t s w it h rot a t or cu ff
in ju rie s im p rove.
Pa te llo fe mo ra l Pa in Syndro me
CLINICAL PRESENTATION
Pa t e llofe m ora l p a in s yn d rom e (PFPS) is on e of t h e m os t com m on s p ort s in ju -
rie s , a n d t h e m os t com m on ca u s e of kn e e p a in (1 ). It is s e e n in s p ort s in volvin g
ru n n in g, ju m p in g, q u ick s t op s , a n d t u rn in g. Th e ca u s e of p a t e llofe m ora l p a in is
d u e t o m a la lign m e n t of t h e p a t e lla a s it t ra cks in t h e t roch le a r groove of t h e
fe m u r. Sym p t om s o f PFPS in clu d e u n ila t e ra l or bila t e ra l a n t e rior kn e e p a in ,
d e s cribe d a s a d u ll a ch e in t h e p e ri- or re t ro-p a t e lla r region of t h e kn e e. It is
in it ia t e d by t h e s p ort in g a ct ivit y, bu t ca n p rogre s s t o be com e con s t a n t . Pa in is
e xa ce rba t e d by s q u a t t in g, w a lkin g u p or d ow n s t a irs , a n d p rolon ge d s it t in g. It
is a ls o kn ow n a s ch on d rom a la cia p a t e lla e or p a t e llofe m ora l join t s yn d rom e (2 ).
 Ch a p te r 8 Sp orts-Rela ted Con dition s a n d In ju rie s 69

PHYSICAL EXAMINATION
Seve ra l e xa m m a n e u ve rs h ave be e n d e s cribe d , bu t evid e n ce t o s u p p ort t h e ir
d ia gn os t ic u t ilit y is lim it e d . Th e p h ys ica l e xa m is oft e n n orm a l in p a t ie n t s w it h
PFPS, a n d t h e d ia gn os is is m a d e from t h e p a t ie n t ’s clin ica l h is t ory, a n d e xclu d -
in g o t h e r ca u s e s o f kn e e p a in . On e m a y n d a t ro p h y o f t h e va s t u s m e d ia lis
m u s cle, t igh t h a m s t rin gs , a n d p a t e lla r in s t a bilit y. To a s s e s s for t h e p re s e n ce of
p a t e lla r in s t a bilit y, t h e p a t ie n t ’s kn e e is e xe d t o 20 d egre e s . Ma n u a l p re s s u re
is a p p lie d b o t h m e d ia lly a n d la t e ra lly t o t h e p a t e lla r. Dis p la ce m e n t o f t h e
p a t e lla m ore t h a n 75% of it s w id t h s u gge s t s a n in cre a s e d ris k for s u blu xa t ion .

STUDIES
Fu rt h e r d ia gn os t ic t e s t in g is n ot w a rra n t e d on ce a clin ica l d ia gn os is of PFPS is
m a d e, a n d w h e n t ra u m a , e ffu s ion , or ot h e r con ce rn in g s ym p t om s a re a bs e n t .
Pla in ra d iogra p h s m ay d e m on s t ra t e evid e n ce of p a t e llofe m ora l m a la lign m e n t .
La t e ra l view s ca n d e m o n s t ra t e p a t e lla a lt a (a h igh -r id in g p a t e lla , w h ich
in cre a s e s ris k for s u blu xa t ion ), p a t e lla r t ilt , a n d t roch le a r d e p t h . An in fra p a t e l-
la r, or “s u n ris e view,” d e m on s t ra t e s p a t e llofe m ora l a rt icu la t ion a n d m a y be a
fu rt h e r clu e of m a la lign m e n t .

s
e
m
o
TREATMENT

r
d
n
Tre a t m e n t of PFPS is p rim a rily con s e rva t ive a n d in clu d e s NSAIDs , re s t , a n d ice.

y
S
Ph ys ica l t h e ra py is im p ort a n t t o p rovid e d yn a m ic s t a biliza t ion of t h e p a t e lla .

n
i
Th is in clu d e s e xe rcis e s t o s t re n gt h e n t h e va s t u s m e d ia lis m u s cle, a n d t h e ra p y

a
P
t o s t re t ch t h e iliot ibia l ba n d a n d h a m s t rin g m u s cle s . Pa t e lla r t a p in g a n d s t a bi-

l
a
n
liza t ion bra ce s w it h a h ole for p a t e lla r t ra ckin g a re re com m e n d e d . Pu blis h e d

o
i
d a t a a ls o s u p p ort a cu p u n ct u re a n d u lt ra s ou n d t h e ra py.

g
e
R
2
CLINICAL COURSE

N
O
It ca n t a ke s eve ra l m on t h s t o a ch ieve s ym p t om a t ic re lie f. If t h e re is n o im p rove -

I
T
m e n t a ft e r 9 m on t h s of con s e rva t ive t h e ra p y, s u rgica l re a lign m e n t of t h e p a t e l-

C
E
lofe m ora l join t ca n be con s id e re d .

S
Ilio tibia l Ba nd Syndro me
CLINICAL MANIFESTATIONS
Th e iliot ibia l ba n d con s t it u t e s con n e ct ive t is s u e t h a t con n e ct s t h e iliu m t o t h e
bu la . Tra u m a d u e t o ove ru s e, m os t com m on ly s e e n in lon g d is t a n ce ru n n e rs ,
ca n m a n ife s t it s e lf a s a d u ll a ch e u n d e rn e a t h t h e la t e ra l a s p e ct of t h e kn e e a s
t h e ba n d t rave rs e s n e xt t o t h e la t e ra l fe m ora l con d yle on it s w ay t o in s e rt on t h e
bu la . On occa s ion s t h e p a in ra d ia t e s u p t h e t h igh follow in g t h e cou rs e of t h e
ba n d u p t o it s in s e rt ion in t h e iliu m . W h ile t h is s yn d rom e is a lm os t e xclu s ive ly
s e e n on ru n n e rs , s p e ci c ris k fa ct ors in clu d e ru n n in g lon ge r d is t a n ce s t h a n t h e
p a t ie n t is a ccu s t om e d t o ru n , ru n n in g on u n eve n s u rfa ce s , or h avin g u n eve n
con t a ct w it h t h e s u rfa ce a s it h a p p e n s w h e n w e a rin g w orn s h oe s .

EXAMINATION
W h ile clin ica l s ym p t om s a re h igh ly ch a ra ct e ris t ic of t h is s yn d rom e, e s p e cia lly
in t h e righ t s u bs e t of p a t ie n t s , t h e re is on e m a n e u ve r t h a t ca n h e lp con rm t h e
d ia gn o s is . Pla cin g t h e p a t ie n t o n t h e la t e ra l d e cu b it u s p o s it io n , w it h t h e
a ffe ct e d lim b u p w a rd , t h e e x a m in e r m ove s t h e a ffe ct e d lim b fo r w a rd a n d
d ow n w a rd in a n a t t e m p t t o re p rod u ce t h e s ym p t om s in t h e a ffe ct e d a re a ; on
occa s ion s p a in is n ot re p rod u ce d bu t t igh t n e s s ca n be fe lt a lon g t h e iliot ibia l
ba n d . For com p a ris on t h e m a n e u ve r is rep e a t e d by t e s t in g t h e op p os it e ilia l-
ba n d w it h t h e p a t ie n t n ow in t h e la t e ra l d e cu bit u s p os it ion w it h t h e a ffe ct e d
s id e d ow n w a rd .
 70 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

TREATMENT
Ma n a ge m e n t for t h is co n d it io n is m o s t ly s u p p or t ive , in clu d in g re s t . Us e o f
NSAIDS is in d ica t e d for re lie f of p a in . Th e u s e of loca l cort icos t e roid s in je ct ion
s h ou ld be lim it e d t o p a t ie n t s n ot re s p on d in g t o m ore con s e rva t ive m e a s u re s ;
p a t ie n t s s h ou ld re s t ra in from ru n n in g a t le a s t for 2 t o 3 w e e ks a ft e r t h e in je c-
t ion . Ru n n in g on eve n s u r fa ce s a n d w e a rin g a p p rop ria t e ru n n in g s h oe s ca n
a ls o h e lp a llevia t e t h is p roble m .

CLINICAL COURSE
Mos t p a t ie n t s im p rove d d ra m a t ica lly w it h re s t a n d t h e u s e of NSAIDS. Occa -
s ion a l p a t ie n t s re q u ire t h e u s e of loca l cort icos t e roid s in je ct ion s . Ra re ly s u rgi-
ca l re le a s e of t h e ba n d m igh t p rove cu ra t ive for p a t ie n t s .

Achille s Te ndino pa thy

CLINICAL PRESENTATION
S
Th e Ach ille s t e n d on is o n e o f t h e m o s t com m on ly in volve d s it e s of ove ru s e
E
C
in ju rie s . It occu rs in m e n p a rt icip a t in g in ru n n in g a n d rep e t it ive ju m p in g a ct iv-
T
I
O
it ie s . Ach ille s t e n d in op a t h y re fe rs t o p a in , sw e llin g, a n d im p a ire d p e rform a n ce
N
of t h e t e n d on ; t e n d in it is or t e n d in os is is w h e n in a m m a t ion or d ege n e ra t ion
2
h a s be e n con rm e d . Th e re a re t w o t yp e s of Ach ille s t e n d in op a t h y, ba s e d on t h e
R
e
loca t ion of t h e in ju ry. In s e rt ion a l t e n d in it is occu rs w it h in 2 cm of t h e in s e rt ion
g
i
o
on t h e p os t e rior a s p e ct of t h e ca lca n e ou s . Non -in s e rt ion a l, or m id -s u bs t a n ce,
n
a
in ju rie s occu r 2 t o 6 cm p roxim a l t o t h e in s e rt ion , w h e re t h e va s cu la r d is t ribu -
l
P
t ion is lim it e d . Ach ille s t e n d on in ju rie s p rogre s s t h rou gh a s e rie s of s t a ge s . Th e
a
i
in it ia l in ju ry is lim it e d t o t h e s u rrou n d in g t e n d on s h e a t h , a n d ca n p rogre s s t o
n
S
a ffe ct t h e t e n d on it s e lf, u lt im a t e ly le a d in g t o s ca r, d ege n e ra t ion , a n d p a rt ia l or
y
n
com p le t e r u p t u re . Ru p t u re s h o u ld be co n s id e re d w h e n p a t ie n t s d e s cr ibe a
d
r
o
“p op ” or n ot e s a ch a n ge in ch ron ic p a in , or e xp e rie n ce s w e a kn e s s w it h s t a n d -
m
in g on t h e ir t oe s .
e
s
Sym p t om s of Ach ille s t en d in it is a re a n kle p a in , in it ia lly follow in g exe rcis e.
Th e p a in is loca lize d ove r t h e Ach illes t en d on , a t t h e in fe rior a s p e ct of t h e p os -
t e rior ca lf. Wit h ch ron ic in a m m a t ion , t h e p a in w ill be com e con s t a n t , a s s ocia t e d
w it h w e a kn e s s a n d m orn in g s t iffn e s s in t h e a ffe ct e d a n kle.

PHYSICAL EXAMINATION
Th e p h ys ica l e xa m n d in gs va ry w it h t h e e xt e n t of in ju ry. Pa in on p a lp a t ion is
com m on , w it h sw e llin g a n d lim it e d ra n ge of m ot ion w it h foot d ors i e xion . A
t e n d e r n od u le on t h e t e n d on t h a t m ove s w it h a n kle e xion ca n be p a lp a t e d .
If t h e p a t ie n t h a s a n Ach ille s ru p t u re, a p a lp a ble ga p m ay be n ot e d
a t t h e ru p t u re s it e, follow e d by sw e llin g, e d e m a , a n d bru is in g. Th e
Th om p s on (Fig. 8. 4 ) t e s t re lia bly p re d ict s a co m p le t e ru p t u re . Th e
p a t ie n t is p la ce d p ron e on t h e e xa m in a t ion t a ble, w it h t h e a n kle s
s u s p e n d e d off t h e t a ble ; t h e e xa m in e r t h e n s q u e e ze s t h e p os t e rior
ca lf t o e licit a n orm a l p la n t a r e xion re s p on s e. If t h e re is a bs e n ce of
p la n t a r e x io n , co n s id e re d a p o s it ive Th o m p s o n t e s t , t h e n t h e
p a t ie n t like ly h a s a t e n d on ru p t u re a n d im a gin g s h ou ld be p u rs u e d .
Ult ra s o u n d a n d MRI a re b o t h u s e fu l fo r t h e d ia gn o s is o f a n d t o
d e t e rm in e t h e e xt e n t of t h e Ach ille s t e n d on in ju ry. If a t e a r is s u s -
p e ct e d clin ica lly, a n MRI is t h e t e s t of ch oice.
Figure 8.4 The Thompson Test demonstra tes a rup-
ture of the Achilles tendon. Ada pted from Browner B, TREATMENT
Jupiter J, Levine A. S ke le ta l Tra u m a : Fra ctu re s ,
Dis lo ca tio n s , a n d Lig a m e n to u s In ju rie s , 2nd ed. Tre a t m e n t o f Ach ille s t e n d in it is is co n s e r va t ive , a n d in clu d e s
Phila delphia : WB Sa unders, 1997. NSAIDs , re s t , a n d ice. Ph ys ica l t h e ra py e xe rcis e s h ave be e n s h ow n
 Ch a p te r 8 Sp orts-Rela ted Con dition s a n d In ju rie s 71

t o be e ffe ct ive. Ecce n t ric e xe rcis e s , w h ich in volve h e e l d rop s from a s t ep s u r-

fa ce, s ign i ca n t ly im p rove p a in by 16 w e e ks a n d s h ou ld be p a rt of a p h ys ica l
t h e ra p y p ro gra m . Ex t ra co r p o re a l s h o ck w a ve t h e ra p y (ESW T), s p lin t s , a n d
in s o le s a re a ls o e ffe ct ive. Lo ca l s t e ro id in je ct io n h a s n o p rove n e f ca cy a n d
ris ks t e n d on ru p t u re . Tre a t m e n t of Ach ille s t e n d on ru p t u re is e a rly s u rgica l
rep a ir (6 ).

CLINICAL COURSE
Mos t p a t ie n t s w it h Ach ille s t e n d on it is re cove r fu lly w it h co n s e rva t ive t re a t -
m e n t ; r is k o f re cu rre n ce is u n for t u n a t e ly co m m o n o n ce ove ru s e a ct ivit y is
re in it ia t e d . Ap p rop ria t e ort h ot ics d evice s , gra d u a l re e n ga ge m e n t w it h a ct ivi-
t ie s , a n d a p p rop ria t e w a rm in g u p m a n e u ve rs a re of h e lp . Pa t ie n t s w it h a ru p -
t u re d Ach ille s t e n d on m a n a ge d in a n on s u rgica l fa s h ion h ave p oor p rogn os is
w it h h igh ra t e of re -ru p t u re a n d lon g t e rm fu n ct ion a l m orbid it y.

Ankle Spra in

s
CLINICAL PRESENTATION

e
m
o
An k le in ju r ie s a re a m o n g t h e m o s t co m m o n o f a ll m u s cu lo s k e le t a l in ju r ie s .

r
d
Th e m o s t co m m o n m e ch a n is m o f in ju ry re s u lt s fro m a la t e ra l a n k le in ve r-

n
y
S
s io n w h e re t h e a n k le jo in t is in p la n t a r e x io n , ca u s in g t h e a n k le t o “ro ll” (7 )

n
Sp o r t in g a ct ivit ie s s u ch a s b a s k e t b a ll, s o cce r, a n d ice s k a t in g a re h igh r is k

i
a
P
a ct ivit ie s fo r a n k le in ju ry, a s is a h is t o ry o f a p r io r a n k le s p ra in . Th e la t e ra l

l
a
co lla t e ra l a n k le liga m e n t s a re m o s t e a s ily in ju re d , a n d in clu d e t h e a n t e r io r

n
o
a n d p o s t e r io r t a lo b u la r liga m e n t s (ATFL a n d PTFL) a n d t h e ca lca n e o b u la r

i
g
liga m e n t (CFL) (Fig. 8. 5 ). High a n k le s p r a in s , o r s yn d e s m o t ic s p ra in s , a r e

e
R
ca u s e d by d o r s i e x io n a n d eve r s io n o f t h e a n k le w it h in t e r n a l ro t a t io n o f t h e

2
N
t ib ia , w it h in ju ry t o t h e p o s t e r io r a n d a n t e r io r t ib io b u la r liga m e n t s . An k le

O
I
T
C
E
Right foot — Lateral view

S
Fibula

Tibia

Talus

Anterior talo bular ligament

Posterior
talo bular
ligament

Cuboid bone

Calcaneo bular ligament

Figure 8.5 Ankle liga ments, right foot, la tera l view. Asset provided by Ana tomica l Cha rt Co.
 72 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

s p ra in s a r e cla s s i e d a s Gra d e 1 t h r o u gh 3 d e p e n d in g o n t h e s e ve r it y o f
in ju ry (p re s e n ce o f a t e a r, fu n ct io n a l s t a t u s , p a in a n d s w e llin g, e cch ym o s is ,
a n d w e igh t -b e a r in g a b ilit y).

PHYSICAL EXAMINATION
On p h ys ica l e xa m in a t ion , t h e a n kle s h ou ld be in s p e ct e d for sw e llin g, e cch ym o-
s is , a n d t h e loca t ion a n d d egre e of p a in on p a lp a t ion . Ma n e u ve rs , s u ch a s t h e
a n t e rior d raw e r t e s t a n d t h e t a la r t ilt t e s t eva lu a t e for join t s t a bilit y (Fig. 8.6 ).
Th e a n t e rior d raw e r t e s t eva lu a t e s for a n ATFL t e a r. Th e e xa m in e r s t a bilize s t h e
a ffe ct e d low e r leg w it h on e h a n d w h ile cu p p in g t h e h e e l w it h t h e ot h e r h a n d .
An t e rior force is a p p lie d t o t h e h e e l in a n a t t e m p t t o m ove t h e t a lu s a n t e riorly.
Th e a m ou n t of d is p la ce m e n t is t h e n com p a re d t o t h e u n a ffe ct e d a n kle. Th e
t a la r t ilt t e s t eva lu a t e s a ca lca n e o bu la r liga m e n t t e a r. In s t e a d of a n t e rior force,
a n in ve rs ion s t re s s is a p p lie d t o t h e t a lu s . Pa t ie n t s w it h a n kle in ju rie s s h ou ld
a ls o be eva lu a t e d w it h t h e Ot t a w a An kle Ru le s (8 ). Th e s e clin ica l p re d ict ion
ru le s h a ve a lm os t 100% s e n s it ivit y for a n kle fra ct u re a n d if n ega t ive, e ffe ct ive ly
ru le s ou t a fra ct u re. If p os it ive, ra d iogra p h ic im a gin g s h ou ld be obt a in e d .
S
E
C
T
TREATMENT
I
O
N
Tre a t m e n t of la t e ra l a n kle s p ra in s is con t rove rs ia l a n d lim it e d by la ck of clin i-
2
ca l t ria ls (9 ). Acu t e ly, p a t ie n t s s h ou ld a p p ly re s t , ice, com p re s s ion , a n d e leva -
R
e
t io n , a n d p ro t e ct t h e a n kle fro m fu rt h e r in ju ry for 72 h ou r s . Th e evid e n ce
g
i
o
n
a
l
P
a
i
n
S
y
n
d
r
o
m
e
s
PATIENT ASSESSMENT

• Exa m m a n e u ve rs ca n
d e t e rm in e w h e t h e r a
lig a m e n t t e a r is p re se n t .
• So m e h ig h ly se n sit ive
m a n e u ve rs (Ot t o w a ru le s)
a re e ffe ct ive a t d e cre a sin g
t h e like lih o o d o f a sig n i -
ca n t t e a r o r fra ct u re .
• Im a g in g is in d ica t e d w h e n
a lig a m e n t o r t e n d o n t e a r
is su sp e ct e d .
• Ult ra so u n d a n d MRI ca n
d e t e rm in e t h e d e g re e o f
t e n d o n in ju ry. Figure 8.6 Eva lua tion of a nkle joint sta bility. The a nterior dra wer test
(to p ) a nd the ta la r tilt test (b o tto m ).
 Ch a p te r 8 Sp orts-Rela ted Con d ition s a n d In ju rie s 73

s u p p ort s NSAIDs for p a in con t ro l a n d im p rove m e n t s in sw e llin g. Fu n ct io n a l

NOT TO BE MISSED
1. We a kn e ss o f t h e m u scle s
o f t h e ro t a t o r cu ff o r a
p o sit ive im p in g m e n t sig n
ca n im p ly a ro t a t o r cu ff
t e a r.
2. Ach ille s t e n d o n ru p t u re
p re se n t s w it h a p a lp a b le
g a p a t t h e ru p t u re sit e ,
sw e llin g , e d e m a , a n d
b ru isin g . Th is re q u ire s
im a g in g a n d su rg ica l
re fe rra l.
3. Un st a b le jo in t s sh o u ld b e
re fe rre d t o o rt h o p e d ic
su rg e ry fo r fu rt h e r
e va lu a t io n .
t re a t m e n t w it h t a p in g, ba n d a ge s , or w ra p s h a s m ore favora ble ou t com e s t h a n
im m obiliza t ion w it h a ca s t . Alt h ou gh d a t a is la ckin g on a p p rop ria t e t im in g of
s u rge ry, p a t ie n t s w it h a n u n s t a ble jo in t s h o u ld b e re fe rre d t o a n o rt h o p e d ic
s u rge on for fu rt h e r eva lu a t ion .
ICD9
726.71 Achille s bursitis o r te ndinitis
717.7 Cho ndro malacia o f pate lla
727.61 Co mple te rupture o f ro tato r cuff
844.2 Cruciate lig ame nt o f kne e
726.10 Diso rde rs o f bursae and te ndo ns in sho ulde r re g io n, unspe ci e d
829.0 Fracture (ab d u ct io n ) (ad d u ct io n ) (avu lsio n ) (co m p re ssio n ) (cru sh )
(d islo cat io n ) (o b liq u e ) (se p arat io n ) (clo se d )
733.16 an k le
733.14 f e m u r (n e ck )
733.15 sp e ci e d NEC

s
e
m
733.16 b u la

o
733.14 h ip

r
d
n
733.11 h u m e ru s

y
S
733.12 rad iu s (d ist al)

n
i
733.19 sp e ci e d sit e NEC

a
P
733.16 t ib ia

l
a
733.12 u ln a

n
o
733.12 w rist

i
g
e
780.96 Pain(s)

R
719.40 jo in t

2
N
719.46 k n e e

O
726.1 Ro tato r cuff syndro me o f sho ulde r and allie d diso rde rs

I
T
C
840.4 Ro tato r cuff (capsule )

E
S
726.32 Late ral e pico ndylitis
717.83 Old disruptio n o f ante rio r cruciate lig ame nt
Sprain, strain (jo in t ) (lig am e n t ) (m u scle )
848.9 (t e n d o n )
845.00 an k le
845.00 an d f o o t
841.9 e lb o w
845.10 f o o t
842.10 h an d
843.9 h ip
843.9 an d t h ig h
WHEN TO REFER 844.9 k n e e
844.9 an d le g
• Ph ysica l t h e ra p y re fe rra l
is im p o rt a n t fo r t re a t in g 717.5 o ld
ro t a t o r cu ff in ju rie s, p a t e l- 844.9 le g
lo fe m o ra l p a in syn d ro m e , 844.9 an d k n e e
a n d Ach ille s t e n d in it is. 846.9 lo w b ack
• Pa t ie n t s w h o fa il n o n o p - 846.0 lu m b o sacral
e ra t ive p h ysica l t h e ra p y 724.6 ch ro n ic o r o ld
a ft e r 6 t o 9 m o n t h s m a y
b e n e t fro m o rt h o p e d ic
in t e rve n t io n .
• Un st a b le jo in t s sh o u ld b e Re fe re nce s
re fe rre d fo r o rt h o p e d ic 1. Mu rray IR, Mu rra y SA, Ma cKe n zie K, Co le m a n S. How evid e n ce ba s e d is t h e m a n a ge m e n t of t w o com m on
e va lu a t io n . s p ort s in ju rie s in a s p ort s in ju ry clin ic? Br J Sports Med 2005 ;39 :912 –916 .
2. Ba rry NN , McGu ire JL. Ove ru s e s yn d rom e s in a d u lt a t h le t e s . Rheum Dis Clin North A m 1996 ;22 (3 ):515 –530 .
 74 Se ctio n 2 Sp ort -Re la t e d , Occu p a t ion a l, a n d Ot h e r Region a l Pa in Syn d rom e s

3. Ebe ll MH. Dia gn os in g rot a t o r cu ff t e a rs . A m Fam Physician 2005 ;71 (8 ):1587 –1588 .
4. Bu rba n k KM , St eve n s o n JH , Cza rn e cki GR, e t a l. Ch ron ic s h ou ld e r p a in : Pa rt I. Evaluation and Diagnosis, A m
Fam Physician 2008 ;77 (4 ):493 –497 .
5. Se id a JC, Le Bla n c C, Sch ou t e n JR, e t a l. Sys t e m a t ic Review : Non op e ra t ive a n d op e ra t ive t re a t m e n t s for
ro t a t or cu ff t e a rs . A nn Intern Med 2010 ;153 (4 ):246 –255 .
6. Ma gn u s s e n RA, Du n n W R, Th om s on AB. Non op e ra t ive t re a t m e n t of m id p ort ion Ach ille s t e n d in op a t h y: A
s ys t e m a t ic review. Clin J Sport Med 2009 ;19 :54 –64 .
7. Ivin s D. Acu t e a n kle s p ra in : An u p d a t e. A m Fam Physician 2006 ;74 :1714 –1726 .
8. Mich a e l JA, St ie ll IG. An kle In ju rie s . In Tin t in a lli JE, Ke le n GD, St a p czyn s ki JS, e d s . Em ergency Medicine: A
Com prehensiv e Study Guide, 6t h e d , McGraw Hill , 2004 .
9. Ke rkh offs GMMJ, Row e BH , As s e n d e lft W JJ, e t a l. Im m obilis a t ion a n d fu n ct ion a l t re a t m e n t for a cu t e la t e ra l
a n kle liga m e n t in ju rie s in a d u lt s . Cochrane Database of System atic Rev iew s 2002 ;(3 ):CD003762 .
S
E
C
T
I
O
N
2
R
e
g
i
o
n
a
l
P
a
i
n
S
y
n
d
r
o
m
e
s
SECTION
3

Speci c Rheuma tic Disea ses:

Dia gnosis a nd Trea tment

Chapter 9 Rh e u m atoid Arth ritis ,

In clu din g Sjögre n ’s
Syn drom e
Zachary M. Pruhs, Jam es R. O’Dell,
and Ted R. Mikuls

Chapter 10 Th e Se ron e gative

Spon dyloarth ropath ie s
Dennis W. Boulw are

Chapter 11 Sys te m ic Lu pu s
Eryth e m atos u s
Michelle A . Petri

Chapter 12 Rayn au d’s Ph e n om e n on

an d Sys te m ic Scle ros is
Laura B. Hughes and Barri Fessler

75
76 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Chapter 13 In am m atory Myopath ie s :

Polym yos itis ,
De rm atom yos itis , an d
Re late d Con dition s
Irene Z. W hitt and Frederick W. Miller

Chapter 14 Vas cu litis

Bao Quynh N. Huynh and
S. Louis Bridges, Jr

Chapter 15 Gian t Ce ll Arte ritis an d

Polym yalgia Rh e u m atica
A ngelo Gaffo

Chapter 16 Ove rlap Syn drom e s

an d Un clas s i e d or
Un diffe re n tiate d
Con n e ctive Tis s u e
Dis e as e
Iris Navarro-Millán and
Graciela S. A larcón

Chapter 17 Fibrom yalgia

Graciela S. A larcón

Chapter 18 Pre gn an cy an d
Rh e u m atic Dis e as e s
Michael Lockshin
CHAPTER
9 Rheuma toid Arthritis,
Including Sjögren’s
Syndrome
Zachary M . Pruhs, Jam es R. O’Dell, and Ted R. Mikuls

s
e
s
Intro ductio n

a
e
A 45-ye ar-o ld w o m an

s
i
D
p re se n t s w it h 4 m o n t h s o f Rh e u m a t oid a rt h rit is (RA) is a s ys -

c
i
t e m ic in a m m a t ory d is e a s e w it h

t
a
w o rse n in g p ain an d st iff -

m
it s p r im a ry m a n ife s t a t io n in t h e

u
n e ss in h e r n g e r jo in t s, s yn oviu m . Th e h a llm a rk of t h e d is -

e
h
R
w rist s, an d b alls o f t h e e a s e is a ch ron ic, s ym m e t ric p ol-

c
f e e t b ilat e rally. He r sym p - ya rt h rit is (s yn ovit is ) t h a t t yp ica lly

i
c
a ffe ct s t h e h a n d s , w ris t s , a n d fe e t

e
t o m s are w o rse in t h e

p
S
in it ia lly a n d la t e r m ay in volve a n y
m o rn in g , im p ro ve w it h

3
s yn ovia l join t . Alt h ou gh RA p rim a -

N
act ivit y, an d are asso ciat - rily in volve s t h e s yn oviu m , fe a t u re s

O
I
T
e d w it h o ccasio n al of s ys t e m ic d is e a s e a re p re s e n t in

C
E
a lm o s t a ll p a t ie n t s a n d ra n ge in
w arm t h an d sw e llin g

S
s eve rit y from fa t igu e t o s eve re m u l-
o f t h e h an d s. Han d rad io g rap h s sh o w p e riart icu lar e ro sio n s an d t is ys t e m va s cu lit is . In re ce n t ye a rs ,
o st e o p e n ia (Fig . 9.1 ). s ign ifica n t a d va n ce s in t h e ra p y
h ave occu rre d , h ow eve r, RA con t in -
u e s t o re s u lt in s u bs t a n t ia l m orbid -
it y for m os t p a t ie n t s . RA p a t ie n t s h ave a h igh e r m or-
t a lit y ra t e t h a n t h e ge n e ra l p op u la t ion t h a t is p rim a rily
re la t e d t o in cre a s e d ca rd iova s cu la r d is e a s e bu rd e n .

Figure 9.1 Ra diogra ph of ha nds a nd wrists in a pa tient with rheuma toid
a rthritis; ndings demonstra te peria rticula r osteopenia a nd erosions.
Epide mio lo g y
RA a ffe ct s a ll ra cia l grou p s w orldw id e a n d w h ile it is
s e e n m ore com m on ly in s om e p op u la t ion s , t h e p reva -
le n ce in m os t coh ort s is e s t im a t e d t o be 0.5% t o 1%. In
t h e d eve lo p e d w o r ld t h e re a p p e a r s t o b e a t re n d
t ow a rd d e cre a s in g RA in cid e n ce a n d p reva le n ce s in ce
t h e 1960s . Ove ra ll, RA is t w o t o t h re e t im e s m ore p rev-
a le n t in w o m e n t h a n in m e n . A s t u d y in Min n e s o t a
re p o r t e d a n in cid e n ce o f 50/100,000 p e r s o n -ye a r s in
m e n a n d 98/100,000 p e rs o n -ye a rs in w o m e n (1 ). Th e
p re p o n d e ra n ce o f w o m e n w it h n ew o n s e t RA w a s
m os t s t rikin g in t h e you n ge r a ge grou p s , bu t n e a r ly
e q u a l for p a t ie n t s 75 ye a rs of a ge. Th e in cid e n ce of

77
78 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
CLINICAL POINTS
• Rheumatoid arthritis (RA) is
a clinical diagnosis based pri-
marily on a thorough history
and physical exam aided by
the select use of laboratory
tests and imaging.
• Pa t ie n t s w it h RA su ffe r
fro m in cre a se d m o rb id it y
a n d m o rt a lit y, t h e la t t e r
p rim a rily d u e t o a n e xce ss
o f ca rd io va scu la r d ise a se .
• Th e co rn e rst o n e o f RA
t re a t m e n t is e a rly a g g re s-
sive t h e ra p y t re a t in g t o a
g o a l o f lo w d ise a se a ct ivit y
o r re m issio n t o p re ve n t
p e rm a n e n t d a m a g e .
• Th e u lt im a t e g o a l o f RA
t re a t m e n t is t o a ch ie ve
a n d m a in t a in co m p le t e
re m issio n .
• Lo n g -t e rm g o a ls o f RA
t re a t m e n t a lso in clu d e t h e
p re ve n t io n o f d isa b ilit y
a n d im p ro ve d su rviva l.
• Im m e d ia t e RA t re a t m e n t
g o a ls in clu d e : d e cre a sin g
p a in , p re ve n t in g jo in t d a m -
a g e a n d m a in t a in in g fu n c-
t io n , a n d co n t ro llin g o t h e r
sym p t o m s o f in a m m a t io n .
RA in cre a s e s w it h a ge, w it h fe m a le e xce s s in e a ch a ge ra n ge fou n d in m os t
s t u d ie s .
GENDER AND HORMONAL INFLUENCES
Th e gre a t e s t d iffe re n ce s in in cid e n ce ra t e s be t w e e n m e n a n d w om e n a re s e e n
in p a t ie n t s be low 50 ye a rs of a ge, w h e re RA is re la t ive ly u n com m on in m e n .
Th e re fore, h orm on a l m e ch a n is m s a re fe lt t o p lay a p a rt in RA ris k. In t h e p a s t ,
t h e u s e of ora l con t ra cep t ive p ills w e re t h ou gh t t o be p rot e ct ive in t h e d eve lop -
m e n t of RA a n d p os t p a rt u m a re s of RA a re a ls o w e ll d ocu m e n t e d in a d d it ion
t o a n a m e liora t in g im p a ct on d is e a s e d u rin g la t e -t e rm p regn a n cy. More re ce n t
s t u d ie s s u gge s t t h a t w h ile lon ge r p e riod s of bre a s t fe e d in g m a y p rot e ct fro m
RA, n e it h e r p a rit y n or u s e of ora l con t ra cep t ive p ills a p p e a rs t o d e cre a s e ris k of
d is e a s e. In a re ce n t la rge coh ort s t u d y, u s e of p os t m e n op a u s a l h orm on e t h e r-
a p y s h ow e d n o s ign i ca n t im p rove m e n t s in e it h e r ris k or s eve rit y of RA (2 ).
Som e h a ve s u gge s t e d t h a t m e n w it h RA m ay h ave m ild t e s t os t e ron e d e cie n -
cie s , a n d rep la ce m e n t m ay re s u lt in s om e d e cre a s e in s ym p t om s .
GENETIC AND ENVIRONMENTAL RISK FACTORS
Firs t -d egre e re la t ive s of t h os e w it h RA a re a t in cre a s e d ris k of d eve lop in g t h e
con d it ion , w it h s iblin gs of s eve re ly a ffe ct e d p a t ie n t s a t h igh e s t ris k. Mon ozy-
got ic t w in s h a ve a con cord a n ce ra t e of a bou t 12% t o 21%, w h e re a s d izygot ic
t w in s h a ve a ra t e a bou t on e q u a rt e r of t h is . Ge n e t ic p re d is p os it ion va rie s w id e ly
w it h e t h n icit y a n d ge ogra p h y. W h ile w o r ld w id e p reva le n ce is e s t im a t e d a t
∼0.5% t o 1%, Na t ive Am e rica n s of t h e Pim a a n d Ch ip p ew a t ribe s h a ve a n RA
p reva le n ce of 5.3% a n d 6.8% re s p e ct ive ly, a n in cre a s e d d is e a s e bu rd e n t h ou gh t
t o be m e d ia t e d by in cre a s e d ge n e t ic ris k a m on g t h e s e p op u la t ion s .
Se le ct h u m a n le u kocyt e a n t ige n s (HLA) cla s s II m ole cu le s re p re s e n t t h e
m os t im p ort a n t ge n e t ic ris k fa ct or in RA a n d t h e re la t ion s h ip e xt e n d s a cros s
e t h n ic grou p s . Th e re is e xt e n s ive evid e n ce lin kin g a h os t of HLA-DRB1 va ria n t s
(o ft e n ca lle d “s h a re d e p it o p e ” o r SE a lle le s ) w it h in cre a s e d s u s ce p t ib ilit y t o
a n t i-cyclic cit ru llin a t e d p e p t id e (a n t i-CCP) a n t ibod y p os it ive RA. Alt h ou gh n ot
a s s t ron gly a s s ocia t e d w it h d is e a s e ris k a s HLA-DRB1 SE con t a in in g a lle le s ,
s eve ra l n on -HLA ge n e t ic ris k fa ct ors for d is e a s e s u s cep t ibilit y h ave n ow be e n
d e n e d in clu d in g p olym orp h is m s in PTPN22, STAT4, CTLA4, PADI4, a n d C-re l.
How eve r, ge n e t ic t e s t in g in RA (for e it h e r d ia gn os t ic or p rogn os t ic p u rp os e s )
re m a in s la rge ly con n e d t o re s e a rch w it h ou t w id e s p re a d clin ica l a p p lica t ion .
Of t h e m a n y e n viron m e n t a l fa ct ors lin ke d t o RA ris k, ciga re t t e s m okin g is
p e rh a p s t h e be s t d ocu m e n t e d . Sm okin g h a s be e n a s s ocia t e d w it h a 50% t o 70%
in cre a s e d ris k of RA, a ris k t h a t is gre a t e s t a m on g t h os e ca rryin g HLA-DRB1 SE
con t a in in g a lle le s (a ge n e -e n viron m e n t in t e ra ct ion ). Ot h e r fa ct ors re p ort e d t o
in u e n ce RA ris k in clu d e occu p a t ion a l e xp os u re s (re la t e d t o s ilica in h a la t ion )
a n d a lcoh ol u s e, t h e la t t e r re p ort e d t o e xe rt a p rot e ct ive e ffe ct .
Clinica l Pre se nta tio n
Th e h a llm a rk s ym p t om s of RA in clu d e :
1. St iffn e s s —t yp ica lly gre a t e r in t h e m orn in g a n d re lieve d w it h a ct ivit y.
2. Pa in —oft e n a ch ie f com p la in t of t h e p a t ie n t s a n d fre q u e n t ly d if cu lt t o
q u a n t ify.
3. Te n d e rn e s s —p a lp a t ion w it h a la t e ra l join t s q u e e ze w ill e licit p a in in p a t ie n t s
w it h a ct ive s yn ovit is .
4. Sw e llin g—re s u lt s from s yn ovia l p rolife ra t ion a n d is oft e n m os t p rom in e n t a t
t h e s m a ll join t s of t h e h a n d s a n d fe e t .
5. De form it y—d eve lop s d u e t o s t re t ch in g of t e n d on s a n d liga m e n t s a lon g w it h
bon y e ros ion a n d is t yp ica lly irreve rs ible.

PATIENT ASSESSMENT
• Bila t e ra l p o lya rt icu la r
in a m m a t o ry a rt h rit is
o ft e n co n n e d t o t h e
h a n d s a n d fe e t m a y b e
ch a ra ct e rist ic e a rly in t h e
d ise a se co u rse .
• In a m m a t o ry m a rke rs
(ESR a n d CRP) m a y b e
n o rm a l a t t h e t im e o f
p re se n t a t io n in o n e t h ird
t o h a lf o f t h e p a t ie n t s.
• Rh e u m a t o id fa ct o r (RF)
is p o sit ive in ∼70% o f
p a t ie n t s b u t is n o t sp e ci c;
a n t i-CCP a n t ib o d y h a s a
sim ila r se n sit ivit y t o RF b u t
is h ig h ly sp e ci c ( 95% )
fo r RA.
Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 79
Table 9.1 Ext ra-art icular Manifest at ions of Rheumat oid Art hrit is
SYSTEM MANIFESTATIONS
Mu co cu t a n e o u s Su b cu t a n e o u s n o d u le s, p yo d e rm a g a n g re n o su m ,
Sjö g re n ’s syn d ro m e
Ca rd io p u lm o n a ry Ple u rit is, p u lm o n a ry b ro sis, in t e rst it ia l lu n g
d ise a se , b ro n ch ie ct a sis, co ro n a ry a rt e ry d ise a se /
a t h e ro scle ro sis, p e rica rd it is (ca n b e co n st rict ive )
Va scu la r Va scu lit is
Re n a l Glo m e ru lo n e p h rit is (ra re )
Op h t h a lm o lo g ic Re t in a l va scu lit is, scle rit is, e p iscle rit is
He m a t o lo g ic An e m ia o f ch ro n ic d ise a se , t h ro m b o cyt o sis, Fe lt y’s
syn d ro m e (t ria d o f le u co p e n ia , sp le n o m e g a ly, a n d
RA), la rg e g ra n u la r lym p h o cyt e (LGL) syn d ro m e
Ne u ro lo g ic Ne u ro p a t h y
s
Mu scu lo ske le t a l Ost e o p o ro sis
e
s
a
e
s
i
D
c
i
t
a
m
Th e d ia gn os is of RA s h ou ld be con s id e re d in a n y p a t ie n t w it h in a m m a -
u
e
t o ry a r t h r it is , e s p e cia lly if t h e h a n d s a n d fe e t a re in vo lve d . Th e p a t ie n t ’s
h
R
re s p on s e t o t h e q u e s t ion , “W h a t is t h e w ors t t im e of d ay for you r join t s ?” is
c
oft e n t e llin g. Pa t ie n t s w it h in a m m a t ory a rt h rit is s u ch a s RA u s u a lly re p ort
i
c
e
s ign i ca n t m o rn in g s t iffn e s s (o ft e n la s t in g 1 h o u r), w h e re a s p a t ie n t s w it h
p
S
os t e oa rt h rit is (OA) a n d ot h e r m e ch a n ica l s yn d rom e s a re u s u a lly w ors e la t e r in
3
t h e d a y a ft e r a ct ivit y. In a d d it ion , s ign i ca n t fa t igu e m a y be p re s e n t eve n in
N
O
e a rly RA.
I
T
C
E
S
EXTRA- ARTICULAR MANIFESTATIONS OF RA
Ext ra -a rt icu la r m a n ife s t a t ion s of RA (ExRA) ra n ge in s eve rit y from n od u la r s kin
le s ion s t o s ys t e m ic va s cu lit is (Ta ble 9.1 ). In a la rge coh ort s t u d y ove r a 30-ye a r
t im e s p a n , m ore t h a n 40% of RA p a t ie n t s h a d e xt ra -a rt icu la r in volve m e n t w it h
n e a rly 13% of t h os e ca t egorize d a s s eve re (3 ). Th e m os t fre q u e n t m a n ife s t a t ion s
of ExRA w e re s u bcu t a n e ou s n od u le s fou n d in 34% of p a t ie n t s . Th e m os t fre -
q u e n t s eve re m a n ife s t a t ion of ExRA w a s p e rica rd it is (5%). Pre d ict ors of s eve re
ExRA in clu d e s m okin g a t t im e of d ia gn os is , a n t i-CCP a n d RF p os it ivit y. Im p or-
t a n t ly, p a t ie n t s w it h ExRA h ave s ign i ca n t ly in cre a s e d m orbid it y a n d p a t ie n t s
w it h s eve re ExRA h ave a m a rke d ly in cre a s e d m ort a lit y.
SJÖGREN’S SYNDROME
Sjögre n ’s s yn d rom e is w e ll re cogn ize d a s a n e xt ra -a rt icu la r m a n ife s t a t ion of
RA. Sjögre n ’s is a con n e ct ive t is s u e d is e a s e a ffe ct in g t h e e xocrin e gla n d s ch a r-
a ct e rize d by d ry eye s a n d m ou t h t h a t is fre q u e n t ly a s s ocia t e d w it h ot h e r con -
n e ct ive t is s u e d is e a s e s in clu d in g RA (4 ). Sjögre n ’s s yn d rom e is oft e n cla s s i e d
by w h e t h e r it is p rim a ry (occu rrin g in is ola t ion ) or s e con d a ry (occu rrin g con -
com it a n t ly w it h a n ot h e r rh e u m a t ic con d it ion ) w it h s ign s a n d s ym p t om s t h a t
ca n be m im icke d in s e le ct vira l in fe ct ion s (e.g., He p a t it is C, HIV), lym p h op rolif-
e ra t ive m a lign a n cy, a n d s a rcoid os is . Th e re la t ion s h ip be t w e e n RA a n d Sjögre n ’s
w a s r s t n o t e d in 1933 by He n rik Sjö gre n h im s e lf. Pa t ie n t s s u ffe r in g fro m
Sjögre n ’s w ill oft e n p re s e n t w it h p a rot id a n d la crim a l gla n d sw e llin g in a d d i-
t ion t o t h e ir s ym p t om a t ic com p la in t s .
 80 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
S
E
C
T
I
O
N
3
S
p
Figure 9.2 Osteoa rthritis versus rheuma toid a rthritis joint involvement (da rker circles represent a ffected joints).
e
c
From O’Dell JR. Rheuma toid a rthritis: the clinica l picture. In: Koopma n WJ, ed. Arthritis a nd Allied Conditions: A
i
c
Textbook of Rheuma tology, 14th ed. Phila delphia : Lippincott Willia ms & Wilkins, 2001:1153–1186, with permis-
R
sion.
h
e
u
m
a
Dia gn o s is m a y be a id e d by t h e Sch irm e r’s (a s s e s s in g for ocu la r d ryn e s s )
t
i
c
a n d Ros e Be n ga l t e s t s a s w e ll a s s a liva ry gla n d or lip biop s y; p os it ive s e rologie s
D
for ANA, a n t i-SSA/SSB, a n d RF a re ch a ra ct e ris t ic of Sjögre n ’s s yn d rom e. Sjö-
i
s
e
gre n ’s m a y e xh ibit e xt ra gla n d u la r in volve m e n t in clu d in g vis ce ra l (h e a rt , lu n gs ,
a
s
e
kid n ey, ga s t roin t e s t in a l t ra ct , ce n t ra l/p e rip h e ra l n e rvou s s ys t e m ) a n d n on -vis -
s
ce ra l (s k in , m u s cle s , join t s ) m a n ife s t a t io n s . Cla s s i ca t io n of t h e d is e a s e is
gu id e d by t h e revis e d ru le s for cla s s i ca t ion from t h e Am e rica n –Eu rop e a n Con -
s e n s u s Grou p (Ta ble 9.2 ).

Exa mina tio n

Join t d is t ribu t ion is crit ica l in t h e d ia gn os is of RA. In it ia lly, RA is oft e n lim it e d
t o t h e h a n d s a n d fe e t . In t h e h a n d s , t h e p roxim a l in t e rp h a la n ge a l join t s (PIPs )
a n d m e t a ca rp a l p h a la n ge a l join t s (MCPs ) a re m os t like ly t o be in volve d e a rly in
t h e d is e a s e cou rs e . Figu re 9.2 com p a re s a n d con t ra s t s t h e join t s m os t com -
m o n ly in volve d in RA a n d OA. In t h e h a n d , t h e d is t a l in t e rp h a la n ge a l join t s
(DIPs ) a re ch a ra ct e r is t ica lly in vo lve d in OA (He b e rd e n n o d e s ) b u t s e ld o m
in volve d in RA, t h e PIPs m a y be in volve d w it h e it h e r, w h e re a s MCP in volve m e n t
is t h e ru le in RA a n d s e ld om occu rs in OA. Th e w ris t is fre q u e n t ly in volve d in
RA, w h e re a s on ly t h e rs t ca rp a l–m e t a ca rp a l join t is com m on ly in volve d in OA.
A re m a rka ble fe a t u re of RA is t h e s ym m e t ry of in volve m e n t .
If in a m m a t ion p e rs is t s ove r t im e, p e rm a n e n t d a m a ge, in clu d in g t e n d on ,
liga m e n t , ca rt ila ge, a n d s u bch on d ra l bon e d e s t ru ct ion ca n occu r, w it h re s u lt -
a n t join t d e form it y a n d d is a bilit y. Alt h ou gh in a m m a t ion a n d d e form it y a re
m o s t oft e n s e e n in it ia lly in t h e h a n d s a n d fe e t , t h e d is e a s e m a y la t e r a ffe ct
la rge r join t s . In volve m e n t of t h e kn e e s , h ip s , a n d s h ou ld e rs a ccou n t s for s ig-
n i ca n t m orbid it y in clu d in g w ork d is a bilit y in a la rge p e rce n t a ge of p a t ie n t s .
Wit h e a rly a n d e ffe ct ive t re a t m e n t s , d e form it y a n d s eve re d is a bilit y a re occu r-
rin g le s s fre q u e n t ly.
 Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 81

Table 9.2 Revised Int ernat ional Classi cat ion Crit eria for
Sjögren’s

1. Ocu la r sym p t o m s: a p o sit ive re sp o n se t o a t le a st o n e o f t h e fo llo w in g

q u e st io n s:
Ha ve yo u h a d d a ily, p e rsist e n t , t ro u b le so m e d ry e ye s fo r m o re t h a n 3 m o n t h s?
Do yo u h a ve a re cu rre n t se n sa t io n o f sa n d o r g ra ve l in t h e e ye s?
Do yo u u se t e a r su b st it u t e s m o re t h a n t h re e t im e s a d a y?
2. Ora l sym p t o m s: a p o sit ive re sp o n se t o a t le a st o n e o f t h e fo llo w in g q u e st io n s:
Ha ve yo u h a d a d a ily fe e lin g o f d ry m o u t h fo r m o re t h a n 3 m o n t h s?
Ha ve yo u h a d re cu rre n t ly o r p e rsist e n t ly sw o lle n sa liva ry g la n d s a s a n a d u lt ?
Do yo u fre q u e n t ly d rin k liq u id s t o a id in sw a llo w in g d ry fo o d ?
3. Ocu la r sig n s: o b je ct ive e vid e n ce o f o cu la r in vo lve m e n t d e n e d a s a p o sit ive
re su lt fo r a t le a st o n e o f t h e fo llo w in g t w o t e st s:
Sch irm e r’s I t e st , p e rfo rm e d w it h o u t a n e st h e sia (5 m m in 5 m in u t e s)
Ro se Be n g a l sco re o r o t h e r o cu la r d ye sco re (4 o r m o re a cco rd in g t o va n
Bijst e rve ld ’s sco rin g syst e m )
4. Hist o p a t h o lo g y: in m in o r sa liva ry g la n d s (o b t a in e d t h ro u g h n o rm a l-a p p e a rin g

s
e
m u co sa ) fo ca l lym p h o cyt ic sia lo a d e n it is, e va lu a t e d b y a n e xp e rt h ist o p a t h o lo -

s
a
g ist , w it h a fo cu s sco re o f 1 o r m o re , d e n e d a s a n u m b e r o f lym p h o cyt ic fo ci

e
s
(w h ich a re a d ja ce n t t o n o rm a l-a p p e a rin g m u co u s a cin i a n d co n t a in m o re

i
D
t h a n 50 lym p h o cyt e s) p e r 4 m m 2 o f g la n d u la r t issu e

c
i
t
a
5. Sa liva ry g la n d in vo lve m e n t : o b je ct ive e vid e n ce o f sa liva ry g la n d in vo lve m e n t

m
d e n e d b y a p o sit ive re su lt fo r a t le a st o n e o f t h e fo llo w in g d ia g n o st ic t e st s:

u
e
Un st im u la t e d w h o le sa liva ry o w ( 1.5 m L in 15 m in u t e s)

h
R
Pa ro tid sia lo gra ph y sho win g the p re se n ce o f d iffu se sia le ct asia s (p u nct at e,

c
ca vita ry, or d e st ru ctive pa tt e rn), with out e vid e n ce of ob st ructio n in th e

i
c
m a jo r d u cts

e
p
Sa liva ry scin t ig ra p h y sh o w in g d e la ye d u p t a ke , re d u ce d co n ce n t ra t io n , o r

S
d e la ye d e xcre t io n o f t ra ce r

3
N
6. Au t o a n t ib o d ie s: p re se n ce in t h e se ru m o f o n e o r b o t h o f t h e fo llo w in g

O
a u t o a n t ib o d ie s:

I
T
C
An t ib o d ie s t o Ro (Sjö g re n ’s syn d ro m e A) a n t ig e n s

E
S
An t ib o d ie s t o La (Sjö g re n ’s syn d ro m e B) a n t ig e n s
Re vise d ru le s fo r cla ssi ca t io n
Fo r p rim a ry Sjö g re n ’s syn d ro m e :
In p a t ie n t s w it h o u t a n y p o t e n t ia lly a sso cia t e d d ise a se , p rim a ry Sjö g re n ’s
syn d ro m e m a y b e d e n e d a s fo llo w s:
Th e p re se n ce o f a n y fo u r o f t h e six it e m s is in d ica t ive o f p rim a ry Sjö g re n ’s
syn d ro m e , a s lo n g a s e it h e r h ist o p a t h o lo g y o r se ro lo g y is p o sit ive
Th e p re se n ce o f a n y t h re e o f t h e fo u r o b je ct ive crit e ria it e m s (i.e ., it e m s 3, 4, 5,
a n d 6)
Fo r se co n d a ry Sjö g re n ’s syn d ro m e :
In p a t ie n t s w it h a p o t e n t ia lly a sso cia t e d d ise a se (e .g ., a n o t h e r w e ll-d e n e d
connective tissue disease), the presence of item 1 or item 2 plus any two from among
items 3, 4, and 5 may be considered as indicative of secondary Sjögren’s syndrome
Exclu sio n crit e ria :
Pa st h e a d a n d n e ck ra d ia t io n t re a t m e n t
He p a t it is C in fe ct io n
AIDS
Pre e xist in g lym p h o m a
Sa rco id o sis
Gra ft ve rsu s h o st d ise a se
Use o f a n t ich o lin e rg ic d ru g s (sin ce a t im e sh o rt e r t h a n fo u rfo ld t h e h a lf-life
o f t h e d ru g )

Ad a p t e d fro m Vit a li C, Bo m b a rd ie ri S, Jo n sso n R, e t a l. Cla ssi ca t io n crit e ria fo r Sjö g re n ’s syn d ro m e : a

re vise d ve rsio n o f t h e Eu ro p e a n crit e ria p ro p o se d b y t h e Am e rica n -Eu ro p e a n Co n se n su s Gro u p . A n n
Rh e u m Dis 2002 ;61 (6 ):557 .
 82 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
S
E
C
T
I
O
Figure 9.3 Swa n neck a nd boutonniere deformities ( fth digits) in a Figure 9.4 Arthritis mutila ns. From Koopma n WJ, Morela nd
N
pa tient with long-sta nding RA. LW, eds. Arthritis a nd Allied Conditions: A Textbook of
3
Rheuma tology, 15th ed. Phila delphia : Lippincott Willia ms &
S
Wilkins, 2005.
p
e
c
i
FINGERS
c
R
Non -re d u cible e xion con t ra ct u re s of t h e p roxim a l in t e rp h a la n ge a l (PIP) join t
h
e
w it h con com it a n t h yp e re xt e n s ion of t h e d is t a l in t e rp h a la n ge a l (DIP) join t of
u
m
t h e n ge r k n ow n a s “b o u t o n n ie re ” d e fo r m it y m a y o ccu r w it h p ro gre s s ive
a
t
d is e a s e. Hyp e re xt e n s ion a t t h e p roxim a l in t e rp h a la n ge a l join t w it h e xion of
i
c
D
t h e d is t a l in t e r p h a la n ge a l jo in t o r “sw a n -n e ck ” d e fo r m it y is a ls o s e e n in
i
s
e
RA (Fig. 9.3 ). Alt h o u gh s im ila r d e fo r m it ie s ca n b e s e e n in s ys t e m ic lu p u s
a
s
e ryt h e m a t o s u s (SLE), t h e s e a re t yp ica lly re d u cible (t h e s o -ca lle d Ja cco u d ’s
e
s
a rt h rop a t h y). “Trigge rin g” of t h e n ge r occu rs w h e n t h icke n in g or n od u le for-
m a t ion of t h e t e n d on in t e ra ct s w it h t h e con com it a n t t e n os yn ovia l p rolife ra -
t ion , t ra p p in g t h e t e n d on (s t e n os in g t e n os yn ovit is ). Te n d on ru p t u re m a y occu r
d u e t o in lt ra t ive s yn ovit is in t h e d igit or bon y e ros ion s t h a t p rod u ce s u rfa ce s
t h a t cu t t h e t e n d on a t t h e w ris t (e s p e cia lly t h e e xor p ollicis lon gu s ). Art h rit is
m u t ila n s (“op e ra gla s s h a n d s ”) re s u lt s if d e s t ru ct ion is s eve re a n d e xt e n s ive,
w it h d is s olu t ion of bon e (Fig. 9.4 ).

METACARPOPHALANGEAL JOINTS
Tw o t yp ica l d e fo r m it ie s m a y o ccu r a t t h e m e t a ca r-
p op h a la n ge a l (MCP) join t s —vola r or p a lm a r s u blu xa -
t io n o f t h e n ge r s re la t ive t o t h e m e t a ca rp a l bo n e s
a n d u ln a r d evia t ion (Fig. 9.5 ). Mos t ca s e s of u ln a r d evi-
a t ion a re a ccom p a n ie d by ra d ia l d evia t ion of t h e w ris t ,
rou gh ly p rop ort ion a l t o t h e d egre e of u ln a r d evia t ion
of t h e n ge rs . Alt h ou gh RA is t h e m os t com m on ca u s e
of u ln a r d evia t ion , ot h e r a rt h rit id e s , a s w e ll a s ce rt a in
n e u rologic d e cie n cie s , m ay re s u lt in u ln a r d evia t ion
a s w e ll.

WRISTS
Figure 9.5 Ulna r devia tion a nd subluxa tion of digits with boutonniere Th e w ris t is t h e s it e of m u lt ip le p ot e n t ia l p roble m s in
deformity of second digit. p a t ie n t s w it h RA. Th e com bin a t ion of u ln a r d rift of t h e
 Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 83

n ge rs a n d ra d ia l d evia t ion of t h e w ris t is kn ow n a s a

“z ig-z a g” d e fo r m it y. W r is t s u blu x a t io n m a y le a d t o
ru p t u re of t h e e xt e n s or t e n d on s of t h e lit t le, rin g, a n d
lon g n ge rs (Fig. 9.6 ), a s t h e e n d of t h e d is t a l u ln a m a y
be rou gh e n e d s e con d a ry t o e ros ion of bon e a n d m ay
a bra d e t h e t e n d on s a s t h ey m ove ba ck a n d fort h d u r-
in g n orm a l h a n d fu n ct ion . En t ra p m e n t of t h e m e d ia n
n e rve a s it p a s s e s t h rou gh t h e ca rp a l t u n n e l (ca rp a l
t u n n e l s yn d rom e ) le a d s t o n u m bn e s s a n d d e cre a s e d
s e n s a t ion on t h e p a lm a r a s p e ct of t h e t h u m b, in d e x,
lon g, a n d ra d ia l a s p e ct of t h e rin g n ge rs , a n d la t e r t o
w e a kn e s s a n d a t ro p h y o f t h e m u s cle s in t h e t h e n a r
e m in e n ce (Fig. 9.7 ).

ELBOW
Elbow in volve m e n t is oft e n d e t e ct e d by p a lp a ble s yn o-
via l p ro life ra t io n a t t h e ra d io h u m e ra l jo in t a n d is

s
e
com m on ly a ccom p a n ie d by a e xion d e form it y. If s yn -

s
a
ovit is o r e ffu s io n is p re s e n t in t h e e lb ow, co m p le t e

e
s
i
e xt e n s ion w ill n ot occu r; t h e re fore , com p le t e e xt e n -

D
s ion is a n e x ce lle n t s ign t h a t s ign i ca n t s yn ovit is or

c
i
t
a
e ffu s io n is a b s e n t . Ole cra n o n b u rs a l in vo lve m e n t is

m
com m on , a s a re rh e u m a t oid n od u le s in t h e bu rs a a n d

u
e
Figure 9.6 Ra diogra ph showing wrist destruction a nd subluxa tion in a a lon g t h e e xt e n s or s u rfa ce of t h e u ln a (Fig. 9.8 ). Uln a r

h
R
pa tient with RA. Willia m J. Koopma n, La rry W. Morela nd, Arthritis a nd
n e rve e n t ra p m e n t a n d corre s p on d in g n e u rop a t h y ca n

c
Allied Conditions: A Textbook of Rheumatology, 15th ed. Philadelphia:

i
occu r w it h s ign i ca n t e lbow in volve m e n t .

c
Lippincott Willia ms & Wilkins, 2005.

e
p
S
3
SHOULDERS

N
O
Sh ou ld e rs a re com m on ly in volve d , w it h n oct u rn a l p a in be in g p a rt icu la rly t rou -

I
T
blin g, a s it is oft e n d if cu lt for p a t ie n t s w it h s h ou ld e r p roble m s t o n d a com -

C
E
fort a ble p os it ion for s le ep. Sw e llin g occu rs in it ia lly a n t e riorly bu t m ay be d if -

S
cu lt t o d e t e ct a n d is p re s e n t on e xa m in a t ion in a m in orit y of p a t ie n t s a t a n y
p oin t in t im e.

FEET AND ANKLES

An kle join t in volve m e n t is s e ld om s e e n in t h e a bs e n ce of m id foot or m e t a t a r-
s op h a la n ge a l in volve m e n t . Ma jor s t ru ct u ra l ch a n ge s occu r in t h e m id foot a n d
foot d u e t o t h e com bin a t ion of ch ron ic s yn ovit is a n d w e igh t be a rin g. Pos t e rior

Figure 9.7 Thena r a trophy in a pa tient with RA a nd severe ca rpa l tunnel

syndrome.
 84 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

t ibia lis t e n d on in volve m e n t or ru p t u re m a y le a d t o

s u bt a la r s u blu xa t io n , w h ich re s u lt s in eve rs ion a n d
m igra t ion of t h e t a lu s la t e ra lly. Mid foot d is e a s e le a d s
t o los s of n orm a l a rch con t ou r w it h a t t e n in g of t h e
fe e t . Me t a t a rs op h a la n ge a l (MTP) join t in a m m a t ion
occu rs in m os t p a t ie n t s a n d is oft e n on e of t h e e a rlie s t
d is e a s e m a n ife s t a t ion s . Th e gre a t t oe t yp ica lly d eve l-
op s h a llu x va lgu s (bu n ion ). Su blu xa t ion of t h e p h a la n x
a t t h e m e t a t a rs op h a la n ge a l join t of t h e ot h e r t oe s p re -
d om in a n t ly occu r s d ors a lly (Fig. 9.9 ). Th e t oe s m a y
exh ibit com p e n s a t ory exion d u e t o a xe d le n gt h of
t h e e xor t e n d on s , re s u lt in g in “h a m m e r t oe s ” (n a m e d
be ca u s e t h ey re s e m ble p ia n o key h a m m e rs ). W h e n
d ors a l s u blu xa t ion occu rs , t h e s oft -t is s u e p a d on t h e
p la n t a r s u rfa ce of t h e m e t a t a rs a l h e a d s is d is p la ce d ,
a llow in g t h e m e t a t a rs a l h e a d s t o p rot ru d e a n d be com e
Figure 9.8 Subcuta neous nodule in a pa tient with RA. t h e p rim a ry w e igh t -be a rin g s u rfa ce. Th is is p a in fu l a n d
ca llu s e s d eve lop. Th is ca n re s u lt in p a t ie n t rep ort s of
S
E
fe e lin g like t h ey a re “w a lkin g a rou n d w it h p e bble s ” in
C
T
t h e ir s h oe s .
I
O
N
3
S
KNEES
p
e
c
La rge k n e e e ffu s io n s m a y d eve lo p in RA w it h a bu n -
i
c
d a n t p ro life ra t io n o f s yn oviu m (Fig. 9.10 ). Pe r s is t e n t
R
e ffu s io n s m a y le a d t o in h ib it io n o f q u a d rice p s fu n c-
h
e
u
t io n by s p in a l r e e x e s w it h s u b s e q u e n t m u s cu la r
m
a t ro p h y. W it h ch ro n ic e ffu s io n s t h e k n e e is m o re
a
t
i
co m fo rt a ble in t h e e xe d p o s it io n , a n d e xio n d e fo rm -
c
D
it ie s o ccu r t h a t gre a t ly in cre a s e t h e w o r k e x p e n d e d
i
s
e
t o w a lk . Ba k e r o r p o p lit e a l cys t s a re co m m o n a n d
a
s
m a y b e re s p o n s ive t o in t ra -a r t icu la r co r t ico s t e ro id
e
s
in je ct ion .
Figure 9.9 Feet with subluxa tion of digits in a pa tient with long-sta nding
RA.
HIPS
Lim it e d m ot ion or p a in w it h in t e rn a l a n d /or e xt e rn a l
rot a t ion is t h e h a llm a rk of h ip in volve m e n t w h e re a s
lo ca liz e d la t e ra l h ip p a in is m o re o ft e n d u e t o t ro -
ch a n t e ric bu rs it is . Pa t ie n t s w it h t ru e h ip join t p a t h ol-
ogy ch a ra ct e r is t ica lly re p o r t p a in in t h e m id -gro in
w it h rot a t ion or w it h w e igh t be a rin g.

Figure 9.10 Pa tient with RA a nd a la rge right knee effusion. From
Koopma n WJ, Morela nd LW, eds. Arthritis a nd Allied Conditions: A
Textbook of Rheuma tology, 15th ed. Phila delphia : Lippincott Willia ms &
Wilkins, 2005.
CERVICAL SPINE
Ne ck p a in on m ot ion a n d occip it a l h e a d a ch e a re com -
m o n m a n ife s t a t io n s o f ce r vica l s p in e in vo lve m e n t
a n d occu r in a p rop ort ion of p a t ie n t s w it h lon g-s t a n d -
in g d is e a s e . Th e a t la n t o a x ia l (C1–C2) jo in t is a s yn -
oviu m -lin e d join t a n d is s u s cep t ible t o t h e s a m e p ro-
life ra t ive s yn ovit is a n d s u bs e q u e n t in s t a bilit y t h a t a re
s e e n in t h e p e rip h e ra l join t s . Th e p os s ibilit y of s ign i -
ca n t C1–C2 in s t a bilit y s h o u ld b e co n s id e re d b e fo re a
p a t ie n t w it h RA u n d e rgo e s s u rgica l p ro ce d u re s t o
a void com p ro m is e t o t h e ce r vica l cord or bra in s t e m
d u rin g in t u ba t ion or a s t h e p a t ie n t is t ra n s fe rre d w h ile
 Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 85

a s le e p . Pa t ie n t s w it h s eve re d e s t ru ct ion in t h e h a n d s (a rt h rit is m u t ila n s ) a re

NOT TO BE MISSED ve ry like ly t o h ave s ym p t om a t ic ce rvica l s p in e a bn orm a lit ie s , a s a re t h os e t a k-
in g s ign i ca n t a m ou n t s of cort icos t e roid s .
• Th e d iffe re n t ia l d ia g n o sis
fo r RA is b ro a d a n d
in clu d e s vira l in fe ct io n s
(e .g ., He p a t it is C a n d CRICOARYTENOID JOINT
p a rvo viru s), p a ra n e o p la st ic Sin ce s yn ovia l t is s u e is p re s e n t a rou n d t h e cricoa ryt e n oid join t , in volve m e n t of
syn d ro m e s, a n d o t h e r t h is join t m a y occu r in u p t o on e fou rt h of RA p a t ie n t s . A s e n s e of “fu lln e s s ”
rh e u m a t ic d ise a se s (lu p u s,
t h a t is a ggra va t e d by s p e a kin g or sw a llow in g is u s u a lly t h e in it ia l s ym p t om .
o st e o a rt h rit is, e t c.).
Hoa rs e n e s s a n d in s p ira t ory s ym p t om s m ay d eve lop . Seve re in volve m e n t m ay
• RA is a sso cia t e d ra re ly p rod u ce e n ou gh re s t rict ion of join t m ot ion t o ca u s e a cu t e, life -t h re a t e n in g
w it h e xt ra -a rt icu la r
d ys p n e a a n d e m e rge n t t ra ch e ot om y m ay be re q u ire d .
m a n ife st a t io n s in clu d in g
su b cu t a n e o u s n o d u le s,
se ro sit is, lu n g d ise a se ,
va scu lit is, Sjö g re n ’s Studie s
syn d ro m e , in a m m a t o ry
e ye d ise a se , a n d Se le ct la bora t ory a n d im a gin g s t u d ie s m ay be h e lp fu l in t h e d ia gn os is of RA.
o st e o p o ro sis le a d in g t o Bot h rh e u m a t oid fa ct or (RF) a n d a n t i-CCP a n t ibod y a re p os it ive in 70% of
fra ct u re s. p a t ie n t s . How eve r, RF h a s on ly m od e s t d is e a s e s p e ci cit y, w h e re a s a n t i-CCP

s
e
a n t ibod y is s e e n a lm os t exclu s ive ly in RA. Oft e n re la t ive ly u n re m a rka ble e a rly in

s
• Pa t ie n t s w it h RA sh o u ld

a
t h e d is e a s e cou rs e, ra d iogra p h s of in volve d join t s m ay s h ow s oft t is s u e sw e llin g,

e
b e e va lu a t e d fo r ce rvica l

s
i
D
sp in e in vo lve m e n t p e ria rt icu la r os t e op e n ia , a n d p e ria rt icu la r e ros ion s w it h d is e a s e p rogre s s ion .

c
e sp e cia lly a s p a rt o f a n y Acu t e p h a s e re a ct a n t s (e ryt h rocyt e s e d im e n t a t ion ra t e a n d C-re a ct ive p rot e in )

i
t
a
p re o p e ra t ive a sse ssm e n t . a re e leva t e d in 50% of p a t ie n t s a t p re s e n t a t ion a n d m ay be va lu a ble in a s s e s s -

m
u
• Alt h o u g h u n co m m o n , in g re s p on s e t o t h e ra py. Ot h e r la bora t ory a bn orm a lit ie s m ay in clu d e a n e m ia of

e
h
crico a ryt e n o id jo in t ch ron ic d is e a s e a n d re a ct ive t h rom bocyt os is . Alt h ou gh n ot u n ive rs a lly e m p loye d ,

R
in vo lve m e n t m a y le a d t o

c
MRI a n d u lt ra s ou n d m ay be s e n s it ive in d e t e ct in g e a rly ch a n ge s in RA.
a irw a y o b st ru ct io n .

i
c
e
• RA is ch a ra ct e rize d b y a

p
Dia g no sis o f Rhe uma to id Arthritis

S
h ig h e r risk fo r m a lig n a n cy

3
in clu d in g lym p h o m a (n o n -

N
Ho d g kin ) a n d lu n g ca n ce r. Th e im p ort a n ce of m a kin g a n a ccu ra t e d ia gn os is of RA a s e a rly a s p os s ible ca n -

O
I
T
n ot be ove re m p h a s ize d . All m od e rn t re a t m e n t p a ra d igm s s t re s s e a rly a ggre s s ive

C
E
d is e a s e -m od ifyin g a n t irh e u m a t ic d ru g (DMARD) t h e ra py. It is crit ica l t o e n s u re

S
t h a t e ffe ct ive t re a t m e n t s a re begu n w h e n t h ey h ave t h e m a xim u m ch a n ce of
m a kin g t h e bigge s t d iffe re n ce s , w h ile a t t h e s a m e t im e p rot e ct in g p a t ie n t s w h o
d o n ot h ave RA from t h e p ot e n t ia l t oxicit ie s of u n n e ce s s a ry t h e ra p ie s .

CLASSIFICATION CRITERIA OF RHEUMATOID ARTHRITIS

In 2010 t h e Am e rica n College of Rh e u m a t ology (ACR) a n d t h e Eu rop e a n Le a gu e
Aga in s t Rh e u m a t is m (EULAR) colla bora t ive ly is s u e d n ew RA cla s s i ca t ion crit e -
ria (Ta ble 9.3 ). Th e n ew crit e ria w e re d eve lop e d t o a u gm e n t t h e 1987 ACR RA
cla s s i ca t ion crit e ria (Ta ble 9.4 ) w h ich h ave be e n crit icize d for a la ck of s e n s it iv-
it y for t h e d e t e ct ion of e a rly d is e a s e. Un d e r t h e 2010 crit e ria , a d e n it ive d ia g-
n os is of RA is a s cribe d t o p a t ie n t s w it h a s core of s ix or m ore (of a p os s ible t e n
p oin t s ) from fou r s corin g d om a in s in clu d in g n u m be r a n d loca t ion of in volve d
join t s , s e rologic a bn orm a lit y, a cu t e p h a s e re a ct a n t e leva t ion , a n d d u ra t ion of
s ym p t o m s . W h ile t h e 2010 crit e ria w ill a s s is t in id e n t ifyin g h o m oge n e o u s
grou p s of p a t ie n t s for t ria ls of e a rly in t e rve n t ion , t h e u t ilit y of t h e n ew ACR/
EULAR crit e ria in “re a l-life ” p ra ct ice is ye t t o be e s t a blis h e d .

Othe r Co nditio ns tha t Ca n Re se mble

Rhe uma to id Arthritis
W h e n p re s e n t e d w it h a p a t ie n t w h o h a s join t p a in , t h e rs t ch a lle n ge is t o d is -
ce rn if t h e p roble m is d u e t o m e ch a n ica l d e ra n ge m e n t s , OA, or in a m m a t ion .
St iffn e s s , sw e llin g, t e n d e rn e s s , w a rm t h , a n d p a in w it h m ot ion a re h a llm a rks of
 86 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 9.3 2010 American College of Rheumat ology/European

League Against Rheumat ism Classi cat ion Crit eria
for Rheumat oid Art hrit is

Ta rg e t p o p u la t io n (Wh o sh o u ld b e t e st e d ?): Pa t ie n t s Sco re

1) w h o h a ve a t le a st o n e jo in t w it h d e n it e clin ica l syn o vit is (sw e llin g )
2) w it h t h e syn o vit is n o t b e t t e r e xp la in e d b y a n o t h e r d ise a se
Cla ssi ca t io n crit e ria fo r RA (sco re -b a se d a lg o rit h m : a d d sco re o f
ca t e g o rie s A–D; a sco re o f 6/10 is n e e d e d fo r cla ssi ca t io n o f a p a t ie n t
a s h a vin g d e n it e RA)a
A. Jo in t in vo lve m e n t b
1 la rg e jo in t 0
2–10 la rg e jo in t s 1
1–3 sm a ll jo in t s (w it h o r w it h o u t in vo lve m e n t o f la rg e jo in t s)c 2
4–10 sm a ll jo in t s (w it h o r w it h o u t in vo lve m e n t o f la rg e jo in t s) 3
S
E
C
10 sm a ll jo in t s (w it h a t le a st 1 sm a ll jo in t ) 5
T
I
O
B. Se ro lo g y (a t le a st o n e t e st re su lt is n e e d e d fo r cla ssi ca t io n )
N
3
Ne g a t ive RF a n d n e g a t ive ACPA 0
S
p
Lo w -p o sit ive RF o r lo w -p o sit ive ACPA (p o sit ive b u t 3x u p p e r lim it 1
e
c
o f n o rm a l)
i
c
Hig h -p o sit ive RF o r h ig h -p o sit ive ACPA (p o sit ive , 3x u p p e r lim it 2
R
h
o f n o rm a l)
e
u
m
C. Acu t e p h a se re a ct a n t s (a t le a st o n e t e st re su lt is n e e d e d fo r
a
cla ssi ca t io n )
t
i
c
D
No rm a l CRP a n d n o rm a l ESR 0
i
s
e
Ab n o rm a l CRP o r a b n o rm a l ESR 1
a
s
e
D. Du ra t io n o f sym p t o m s
s
6 w e e ks 0
6 w e e ks 1
a
Alt h o u g h p a t ie n t s w it h a sco re o f 6/10 a re n o t cla ssi a b le a s h a vin g RA, t h e ir st a t u s ca n b e re a sse sse d
a n d t h e crit e ria m ig h t b e fu l lle d cu m u la t ive ly o ve r t im e .
b
Jo in t in vo lve m e n t re fe rs t o a n y sw o lle n o r t e n d e r jo in t o n e xa m in a t io n , w h ich m a y b e co n rm e d b y
im a g in g e vid e n ce o f syn o vit is. “ La rg e jo in t s” re fe rs t o sh o u ld e rs, e lb o w s, h ip s, kn e e s, a n d a n kle s.
c
” Sm a ll jo in t s” re fe rs t o t h e m e t a ca rp o p h a la n g e a l jo in t s, p ro xim a l in t e rp h a la n g e a l jo in t s, se co n d
t h ro u g h ft h m e t a t a rso p h a la n g e a l jo in t s, t h u m b in t e rp h a la n g e a l jo in t s, a n d w rist s.
Ad a p t e d fro m Ale t a h a , e t a l. 2010. Rh e u m a t o id a rt h rit is cla ssi ca t io n crit e ria : An Am e rica n Co lle g e o f
Rh e u m a t o lo g y/Eu ro p e a n Le a g u e Ag a in st Rh e u m a t ism co lla b o ra t ive in it ia t ive . A rt h rit is Rh e u m 2010 ;
62 (9 ):2569 –2581 .

a ct ive a rt icu la r in a m m a t io n . Th e p re s e n ce o f s eve re m o r n in g s t iffn e s s is

in d ica t ive of a n in a m m a t ory p roce s s , w h ile “ge llin g” of t h e join t s for m e re ly a
few m in u t e s in t h e m orn in g a n d a ft e r re s t is m ore con s is t e n t w it h OA a n d
m e ch a n ica l d e ra n ge m e n t s . Th e d ia gn os is of RA is m os t d if cu lt e a rly in t h e
d is e a s e cou rs e or w h e n re la t ive ly few join t s a re in volve d ; u n fort u n a t e ly, d ia g-
n os is is oft e n d e laye d s eve ra l m on t h s a ft e r t h e on s e t of s ym p t om s , p re clu d in g
t h e in it ia t ion of e a rly t re a t m e n t .
Sign s a n d s ym p t om s of in a m m a t ory a rt h rit is m ay be a s s ocia t e d w it h m a n y
s yn d rom e s ot h e r t h a n RA. A h is t ory d ire ct e d a t e licit in g t h e a s s ocia t e d fe a t u re s
of ot h e r a rt h rit id e s is e s s e n t ia l. For in s t a n ce, t h e p re s e n ce of p h ot os e n s it ivit y or
n ep h rit is s u gge s t s t h e p os s ibilit y of SLE, w h ile con ju n ct ivit is a n d d a ct ylit is m ay
s u gge s t re a ct ive a rt h rit is . Sys t e m ic va s cu lit is , s u ch a s p olya rt e rit is n od os a or
 Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 87

Table 9.4 The 1987 Revised Crit eria for t he Classi cat ion of
Rheumat oid Art hrit is

CRITERION DEFINITION
1. Mo rn in g st iffn e ss Mo rn in g st iffn e ss in a n d a ro u n d t h e jo in t s la st in g
a t le a st 1 h o u r b e fo re m a xim a l im p ro ve m e n t
2. Art h rit is o f t h re e o r At le a st t h re e jo in t a re a s sim u lt a n e o u sly h a ve h a d
m o re jo in t a re a s so ft t issu e sw e llin g o r u id (n o t b o n y o ve rg ro w t h
a lo n e ) o b se rve d b y a p h ysicia n . Th e 14 p o ssib le
a re a s a re rig h t o r le ft PIP, MCP, w rist , e lb o w,
kn e e , a n kle , a n d MTP jo in t s
3. Art h rit is o f h a n d jo in t s At le a st o n e a re a sw o lle n (a s d e n e d a b o ve ) in a
w rist , MCP, o r PIP jo in t
4. Sym m e t ric a rt h rit is Sim u lt a n e o u s in vo lve m e n t o f t h e sa m e jo in t a re a s
(a s d e n e d in 2) o n b o t h sid e s o f t h e b o d y (b ila t -
e ra l in vo lve m e n t o f PIPs, MCPs, o r MTPs is a cce p t -
a b le w it h o u t a b so lu t e sym m e t ry)

s
e
5. Rh e u m a t o id n o d u le s Su b cu t a n e o u s n o d u le s, o ve r b o n y p ro m in e n ce s,

s
a
o r e xt e n so r su rfa ce s o r in ju xt a -a rt icu la r re g io n s,

e
o b se rve d b y a p h ysicia n

s
i
D
6. Se ru m rh e u m a t o id fa ct o r De m o n st ra t io n o f a b n o rm a l a m o u n t s o f se ru m

c
i
t
rh e u m a t o id fa ct o r b y a n y m e t h o d fo r w h ich t h e

a
m
re su lt h a s b e e n p o sit ive in 5% o f n o rm a l co n t ro l

u
su b je ct s

e
h
R
7. Ra d io g ra p h ic ch a n g e s Ra d io g ra p h ic ch a n g e s t yp ica l o f rh e u m a t o id

c
a rt h rit is o n p o st e ro a n t e rio r h a n d a n d w rist

i
c
ra d io g ra p h s, w h ich m u st in clu d e e ro sio n s o r

e
p
u n e q u ivo ca l b o n y d e ca lci ca t io n lo ca lize d in o r

S
m o st m a rke d a d ja ce n t t o t h e in vo lve d jo in t s

3
(o st e o a rt h rit is ch a n g e s a lo n e d o n o t q u a lify)

N
O
I
T
Fo r cla ssi ca t io n p u rp o se s, a p a t ie n t sh a ll b e sa id t o h a ve rh e u m a t o id a rt h rit is if h e /sh e h a s sa t is e d a t

C
E
le a st 4 o f t h e se 7 crit e ria . Crit e ria 1 t h ro u g h 4 m u st h a ve b e e n p re se n t fo r a t le a st 6 w e e ks. Pa t ie n t s w it h

S
t w o clin ica l d ia g n o se s a re n o t e xclu d e d . De sig n a t io n a s cla ssic, d e n it e , o r p ro b a b le rh e u m a t o id a rt h rit is
is n o t t o b e m a d e .
Ad a p t e d fro m Arn e t t e t a l. Th e Am e rica n Rh e u m a t ism Asso cia t io n 1987 Re vise d Crit e ria fo r t h e
Cla ssi ca t io n o f Rh e u m a t o id Art h rit is. A rt h rit is Rh e u m 1988 ;31 (3 ):315 –324 .

Wege n e r gra n u lom a t os is , m ay be a s s ocia t e d w it h d is a blin g join t p a in , a lt h ou gh

o b je ct ive s ign s o f a r t h r it is a re in fre q u e n t . Hyp o t h yro id is m ca n p ro d u ce
rh e u m a t ic s ym p t om s , a n d is s e e n in in cre a s e d a s s ocia t ion w it h RA. Fin a lly, t h e
crys t a llin e a rt h rop a t h ie s in clu d in g gou t a n d ca lciu m pyrop h os p h a t e d ep os it ion
d is e a s e fre q u e n t ly p re s e n t a s in a m m a t ory a rt h rit is a n d m ay m im ic RA.

CRYSTALLINE ARTHROPATHIES
Pa t ie n t s w it h gou t d eve lop u ric a cid crys t a l d e p os it ion in t h e join t s a n d m ay
p re s e n t w it h s ym p t om s s im ila r t o RA. Cla s s ica lly, gou t p re s e n t s w it h p od a gra
(in a m m a t ion a n d p a in in t h e gre a t t oe ) or p a u cia rt icu la r join t sw e llin g w it h
e xq u is it e p a in . In con t ra s t t o RA, t h e re is a m a le p re p on d e ra n ce a n d t yp ica lly
m a le p a t ie n t s d eve lop s ym p t om s in t h e t h ird a n d fou rt h d e ca d e s of life (w it h
w om e n d eve lop in g in it ia l a re s m u ch la t e r, w e ll a ft e r m e n op a u s e ). High s e ru m
u ric a cid is s u gge s t ive bu t n ot d ia gn os t ic of gou t , h ow eve r, u ric a cid leve ls m a y
be n orm a l or eve n low d u rin g a cu t e gou t a t t a cks . De n it ive d ia gn os is is m a d e
t h ro u gh a s p ira t ion o f in t ra ce llu la r n ega t ive ly bire fr in ge n t u ric a cid crys t a ls
from t h e s yn ovia l u id , e xa m in e d u n d e r p ola rize d m icros cop y. In s e le ct ca s e s
ch ron ic gou t ca n p re s e n t in a “p s e u d o-rh e u m a t oid ” fa s h ion . Th u s , gou t s h ou ld
 88 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

be con s id e re d , p a rt icu la rly in p a t ie n t s w it h h yp e ru rice m ia w h o a re s e ron ega -

t ive for RF a n d a n t i-CCP a n t ibod y.
Pa t ie n t s w it h ca lciu m pyrop h os p h a t e crys t a l d e p os it ion (CPPD) or p s e u d o-
gou t m ay a ls o p re s e n t w it h p a u cia rt icu la r p a in a n d in a m m a t ion , e s p e cia lly in
t h e w ris t s a n d kn e e s . Pa t ie n t s w it h p s e u d ogou t m ay h ave a h is t ory of t ra u m a
t o t h e a ffe ct e d join t s . Ps e u d ogou t t yp ica lly p re s e n t s a ft e r t h e ft h d e ca d e of life
a n d h a s a s ligh t fe m a le p re p on d e ra n ce. De n it ive d ia gn os is is m a d e t h rou gh
a s p ira t io n o f w e a k ly p o s it ive b ire fr in ge n t crys t a ls fro m t h e s yn ovia l u id
(p ola rize d m icros cop y). Im p ort a n t ly, p s e u d ogou t m ay be a s s ocia t e d w it h ot h e r
u n d e r lyin g m e t a b o lic illn e s s e s in clu d in g h yp e r p a ra t h yr o id is m , h yp o t h y-
ro id is m , a n d h e m o ch ro m a t o s is . Fu r t h e r w o r k u p s h o u ld b e co n s id e re d in
p a t ie n t s d ia gn os e d w it h p s e u d ogou t . Like ch ron ic gou t , CPPD ca n clos e ly m im ic
RA in s e le ct circu m s t a n ce s .

SLE
Pa t ie n t s w it h SLE m ay p re s e n t w it h p olya rt icu la r a rt h rit is a n d a rt h ra lgia s s im -
ila r t o RA w it h a s im ila r jo in t d is t rib u t io n . How eve r, p a t ie n t s w it h SLE fre -
S
E
q u e n t ly h a ve ot h e r d is e a s e m a n ife s t a t ion s in clu d in g s kin a n d in t e rn a l orga n
C
T
in volve m e n t . Th e p re s e n ce of p h ot os e n s it ive s kin ra s h , s e ros it is , re n a l d is e a s e,
I
O
or h e m a t ologic a bn orm a lit y (e.g., cyt op e n ia s ) in a p a t ie n t w it h in a m m a t ory
N
a rt h rit is is s u gge s t ive of SLE. Ad d it ion a lly, 95% of p a t ie n t s w it h SLE w ill h a ve
3
S
a p o s it ive a n t in u cle a r a n t ibod y (ANA) t it e r a s op p os e d t o 30% t o 40% of RA
p
e
p a t ie n t s . Th e p re s e n ce of a n t i-d ou ble s t ra n d e d DNA or a n t i-Sm it h a n t ibod y is
c
i
h igh ly s p e ci c t o SLE.
c
R
h
e
u
SPONDYLOARTHROPATHIES
m
a
Th e s p o n d ylo a rt h ro p a t h ie s (re a ct ive a rt h rit is , p s o ria t ic a rt h rit is , a n d in a m -
t
i
c
m a t ory bow e l d is e a s e ) m ay a p p e a r s im ila r t o RA a t p re s e n t a t ion . Th e s p on d y-
D
i
s
loa rt h rop a t h ie s oft e n p re s e n t w it h in a m m a t ion fou n d a t e n t h e s is or s it e of
e
a
t e n d on in s e rt ion s (Ach ille s t e n d on in s e rt ion , p la n t a r fa s cia , s h a ft s of n ge rs or
s
e
t oe s ) kn ow n a s e n t h e s it is . As ym m e t ric oligoa rt h rit is (few e r t h a n fou r join t s ),
s
u s u a lly of t h e w e igh t -be a rin g join t s , is m ore com m on in t h e s e d is ord e rs t h a n
in RA. Th e p re s e n ce of con ju n ct ivit is /irit is , u re t h rit is , a n d m u cocu t a n e ou s or
in t e s t in a l m a n ife s t a t ion s in t h e s p on d yloa rt h rop a t h ie s a ls o d iffe re n t ia t e t h e s e
con d it ion s from RA. In a d d it ion , in a m m a t ory s ym p t om s of t h e a xia l s ke le t on
s t ron gly s u gge s t t h e d ia gn os is of on e of t h e s p on d yloa rt h rop a t h ie s , re cogn iz-
in g t h a t RA ca n a ffe ct t h e ce rvica l s p in e.

PALINDROMIC RHEUMATISM
Pa lin d rom ic rh e u m a t is m is a re m it t in g, re cu rrin g, n on d e s t ru ct ive, in a m m a -
t ory a rt h rit is w it h re cu rre n ce s ove r a t le a s t 6 m on t h s . At t a cks ra re ly la s t m ore
t h a n 1 w e e k a n d ge n e ra lly in volve on ly a few join t s , w it h t h e join t s u lt im a t e ly
in volve d be in g s im ila r t o t h os e in volve d in t yp ica l RA. Th e d is e a s e eve n t u a lly
evolve s in t o t yp ica l RA ove r t im e in on e q u a rt e r t o h a lf of t h e p a t ie n t s . Wom e n
w it h RF a n d /or a n t i-CCP a n t ibod y w it h e a rly h a n d in volve m e n t a re m ore like ly
t o d eve lop RA t h a n p a t ie n t s w it h ou t t h e s e fe a t u re s .

REMITTING SERONEGATIVE SYMMETRIC SYNOVITIS

WITH PITTING EDEMA
Re m it t in g s e ro n e ga t ive s ym m e t r ic s yn ovit is w it h p it t in g e d e m a (RS3PE) is
ch a ra ct e rize d by a ve ry a bru p t on s e t of m a rke d d ors a l sw e llin g of t h e h a n d s
w it h p it t in g e d e m a , w ris t s yn ovit is , a n d e xor t e n d in it is of t h e n ge rs . Sim ila r
sw e llin g a n d s yn ovit is m a y a ls o be s e e n in t h e fe e t a n d a n kle s . Pa t ie n t s ca n
 Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 89

oft e n p re cis e ly p in p oin t t h e t im e of on s e t . In ge n e ra l, t h e p rogn os is is e xce l-

le n t , a lt h o u gh RS3PE o ccu r rin g w it h a n u n d e r lyin g m a lign a n cy a s p a r t o f a
p a ra n e o p la s t ic s yn d ro m e h a s b e e n re p o r t e d . Fo r t h e m o s t p a r t , p a t ie n t s
re s p o n d d ra m a t ica lly t o low -d o s e co r t ico s t e ro id s . RF a n d a n t i-CCP a n t ib o d y
a re n ot ge n e ra lly p re s e n t a n d ra d iogra p h ic join t d e s t ru ct ion d oe s n ot t yp ica lly
occu r.

POLYMYALGIA RHEUMATICA
Polym ya lgia rh e u m a t ica (PMR) ge n e ra lly p re s e n t s w it h a n a bru p t t o s u ba cu t e
on s e t of p a in a n d s t iffn e s s in t h e s h ou ld e r a n d h ip gird le s of p a t ie n t s 50 ye a rs
of a ge. Feve r, w e igh t los s , a n d le t h a rgy ca n occu r a n d m ay be s eve re. Re s t rict ion
of s h ou ld e r m ove m e n t s e con d a ry t o p a in a n d s oft -t is s u e con t ra ct u re is com -
m o n . Th e s t iffn e s s a n d re s t rict e d m o b ilit y a re e x q u is it e ly s e n s it ive t o t re a t -
m e n t w it h m od e s t d os e p re d n is on e, w it h m a rke d clin ica l re s p on s e s t yp ica lly
obs e rve d w it h d os e s a s low a s 10 t o 15 m g/d a y. Pe rs is t e n t s m a ll join t s yn ovit is
of t h e h a n d s a n d fe e t d is t in gu is h e s RA from PMR, a lt h ou gh m orn in g s t iffn e s s
m ay ot h e rw is e be id e n t ica l. RA of a cu t e on s e t w it h PMR s ym p t om s in t h e e ld -

s
e
e rly oft e n h a s a n e xce lle n t p rogn os is .

s
a
e
s
i
D
VIRAL ARTHRITIS

c
i
t
Po lya r t h rit is m a y b e t h e p re s e n t in g fe a t u re o f vira l in fe ct io n s . Clu e s le a d in g

a
m
t o t h e e t iologic a ge n t m a y be evid e n t in t h e h is t o ry a n d e x a m in a t io n . In co n -

u
e
t ra s t t o RA, vira l a s s o cia t e d a r t h r it is is m o re o ft e n s e lf-lim it e d . Feve r a n d

h
R
cu t a n e o u s m a n ife s t a t io n s m a y s u gge s t a n in fe ct io u s p ro ce s s . Vira l in fe ct io n s

c
t h a t ca n clos e ly m im ic RA in clu d e ru be lla , p a rvovir u s B19, a n d vira l h e p a t it is

i
c
e
(p a r t icu la r ly h e p a t it is C w h ich ca n le a d t o ch ro n ic a rt h ra lgia s a n d low -t it e r

p
S
p os it ive RF).

3
N
O
I
Tre a tme nt

T
C
E
S
GOALS
Th e s t a t u s of t h e in d ivid u a l p a t ie n t a t a n y p oin t in t im e s h ou ld a lw a ys be
a s s e s s e d re la t ive t o t re a t m e n t goa ls . Sp e ci c t re a t m e n t goa ls a re w e ll a ccep t e d
a n d e a s y t o u n d e rs t a n d in s u ch con d it ion s a s h yp e rt e n s ion , h yp e rlip id e m ia , or
d ia be t e s . In RA, goa ls a re m ore d if cu lt t o q u a n t ify bu t n o le s s im p ort a n t . Wit h
im p rovin g t h e ra p ie s , re m is s ion is be com in g a m ore re a lis t ic, a lt h ou gh s t ill e lu -
s ive, goa l. No on e s in gle m e a s u re a d e q u a t e ly d e s cribe s t h e s t a t u s of a p a t ie n t
w it h RA. Ra t h e r, com bin a t ion s of a bn orm a lit ie s d e t e ct e d by la bora t ory t e s t in g,
p h ys ica l e x a m in a t io n , ra d iologic e xa m in a t ion , a n d a s s e s s m e n t of p a in a n d
fu n ct ion a l s t a t u s a re u s e d .
Th e Am e rica n College of Rh e u m a t ology (ACR) h a s re com m e n d e d a core s e t
o f com p o s it e cr it e r ia (Ta ble 9.5 ) fo r t h e o n go in g eva lu a t io n o f t h e ra p ie s in
p a t ie n t s w it h RA. Th e com p on e n t s of t h is core s e t a re e xce lle n t p a ra m e t e rs t o
follow in in d ivid u a l p a t ie n t s in clin ica l p ra ct ice, a s w e ll a s in clin ica l re s e a rch
s it u a t ion s . Fre q u e n t ly u s e d com p os it e m e a s u re s of d is e a s e a ct ivit y in clu d e t h e
Dis e a s e Act ivit y Score (DAS), t h e Rou t in e As s e s s m e n t of Pa t ie n t In d e x Da t a 3
(RAPID-3), a n d t h e Clin ica l Dis e a s e Act ivit y In d e x (CDAI). Th e la t t e r m e a s u re s
ca n be ca lcu la t e d in “re a l-t im e ” w it h s u gge s t e d t h re s h old s d e n e d corre s p on d -
in g t o low d is e a s e a ct ivit y a n d re m is s ion .

Me dica tio ns
Th e re a re fou r m a in cla s s e s of m e d ica t ion s u s e d in t h e t re a t m e n t of RA: n on -
s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs ), cort icos t e roid s , s yn t h e t ic DMARDs ,
 90 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 9.5 American College of Rheumat ology Disease Act ivit y

Measures for Rheumat oid Art hrit is Core Set

DISEASE ACTIVITY MEASURES

1. Te n d e r jo in t co u n t
2. Sw o lle n jo in t co u n t
3. Pa t ie n t ’s a sse ssm e n t o f p a in
4. Pa t ie n t ’s g lo b a l a sse ssm e n t o f d ise a se a ct ivit y
5. Ph ysicia n ’s g lo b a l a sse ssm e n t o f d ise a se a ct ivit y
6. Pa t ie n t ’s a sse ssm e n t o f p h ysica l fu n ct io n
7. Acu t e -p h a se re a ct a n t va lu e

a n d biologic DMARDs . As con t rol of RA s ym p t om s a n d p reve n t ion of lon g-t e rm

d is a bilit y from t h e d is e a s e d e p e n d s o n s t o p p in g t h e in a m m a t o ry p ro ce s s ,
t h e re is a t re n d t ow a rd e a rlie r, m ore a ggre s s ive u t iliza t ion of bot h s yn t h e t ic
a n d biologic DMARDs (5 ).
S
E
C
T
I
O
NSAIDs
N
3
NSAIDs m ay be u s e fu l e a rly on in t h e cou rs e of RA, p a rt icu la rly w h e n t h e d ia g-
S
n os is is s t ill in q u e s t ion . NSAIDs m ay re lieve p a in , sw e llin g, a n d s t iffn e s s in t h e
p
e
s h ort t e rm w h ile t h e d ia gn os t ic w orku p is com p le t e d . NSAID u s e ca rrie s ris k of
c
i
s ign i ca n t s id e e ffe ct s in clu d in g ga s t roin t e s t in a l u lce rs a n d in cre a s e d ris k of
c
R
ble e d in g. It is im p ort a n t t o re cogn ize t h a t t h e lon g t e rm u s e of NSAIDs h a s n ot
h
e
be e n s h ow n t o s low d is e a s e p rogre s s ion in RA, t h e re fore t h e ir u s e a s m on o-
u
m
t h e ra p y is n ot re com m e n d e d .
a
t
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CORTICOSTEROIDS
s
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W h ile cort icos t e roid s a re p ot e n t in h ibit ors of in a m m a t ion a n d m ay p reve n t
s
e
s
d is e a s e p rogre s s ion in RA, t h e ir u s e is a s s ocia t e d w it h a h os t of s id e e ffe ct s
in clu d in g w e igh t ga in , h yp e rt e n s ion , glu cos e in t ole ra n ce, h yp e rlip id e m ia , os t e -
op oros is , a n d ca t a ra ct s a m on g ot h e rs . Pa t ie n t s on cort icos t e roid s h ave h igh e r
ra t e s of in fe ct ion a n d a re ce n t s t u d y rep ort s a d os e d ep e n d e n t in cre a s e in ris k
of p n e u m on ia for p a t ie n t s on lon g-t e rm cort icos t e roid t h e ra p y for RA (6 ). Id e -
a lly, cort icos t e roid s s h ou ld be u s e d a s a brid ge t o DMARD t h e ra py a n d s h ou ld
ge n e ra lly n ot be e m p loye d a s m on ot h e ra p y in RA.

SYNTHETIC DMARDs
Give n t h e lo n g-t e r m go a l o f s u p p r e s s io n o f in a m m a t io n in RA, s yn t h e t ic
DMARDs h a ve b e co m e a co r n e r s t o n e o f t h e ra p y. Me t h o t r e x a t e in p a r t icu la r
h a s d e m o n s t ra t e d u t ilit y in p re ve n t in g d is e a s e p r o gre s s io n a s w e ll a s re d u c-
in g m o r t a lit y in RA p a t ie n t s (7 ). W it h a n e s t a blis h e d t ra ck re co rd , a cce p t a ble
r is k o f t o x icit y, a n d low co s t , m e t h o t re x a t e n ow co n s t it u t e s r s t -lin e t h e r-
a p y fo r RA in t h e a b s e n ce o f co n t ra in d ica t io n s t o it s u s e . Ot h e r s yn t h e t ic
DMARDs in c lu d e le u n o m id e , s u lfa s a la z in e , m in o cy c lin e , a z a t h io p r in e ,
cyclo s p o r in e , a n d h yd r o x ych lo r o q u in e . In 2008 t h e ACR is s u e d re co m m e n -
d a t io n s fo r t h e u s e o f s yn t h e t ic DMARDs in RA p a t ie n t s w h o h a d n o t p re vi-
o u s ly r e c e ive d DMARDs b a s e d o n d is e a s e d u r a t io n a n d a c t iv it y ( 8 ). Ea ch
m e d ic a t io n h a s u n iq u e s id e e ffe c t p r o le s a n d m o n it o r in g r e q u ir e m e n t s
(Ta ble 9.6 ). Syn t h e t ic DMARDs a re fre q u e n t ly u s e d in co m b in a t io n a s w e ll a s
co n co m it a n t ly w it h t h e b io lo gic DMARDs t o a ch ieve o p t im a l co n t ro l o f RA
d is e a s e a ct ivit y.
 T a b l e 9 . 6 G u i d e l i n e s f o r M o n i t o r i n g t h e T r e a t m e n t o f R h e u m a t o i d A r t h r i t i s
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M o d i e d f r o m O ’ D e l l . T h e r a p e u t i c S
t r a t e g i e s f o r R h e u m a t o i d A r t h r i t i s . N E n g l J M e d 2 0 0 4 ; 3 5 0 :
( 2 ) :5 9 1 – 6 0 2 .
91
 92 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

BIOLOGIC DMARDs
Biologic DMARDs rep re s e n t a re la t ive ly n ew cla s s of a ge n t s d e s ign e d t o in h ibit
t h e in a m m a t ory p roce s s by s e le ct ive ly t a rge t in g cyt okin e s a n d ot h e r ce llu la r
liga n d s . Th e re a re cu rre n t ly n in e biologic DMARDs a p p rove d in t h e t re a t m e n t
of RA. Sim ila r t o s yn t h e t ic DMARDs , t h e ACR h a s is s u e d re com m e n d a t ion s for
t h e u s e of biologic DMARDs in clu d in g e t a n e rcep t , in ixim a b, a d a lim u m a b, a n a -
kin ra , a ba t a cep t , a n d rit u xim a b (8 ). Biologic a ge n t s a re t yp ica lly e m p loye d a s
s e con d -lin e t h e ra py a n d a re oft e n u s e d in con ju n ct ion w it h a s yn t h e t ic DMARD,
p a rt icu la rly m e t h ot re xa t e. Us e of m u lt ip le biologics con cu rre n t ly is n ot re com -
m e n d e d d u e t o h igh e r ra t e s o f a d ve rs e eve n t s , p a rt icu la rly s e rio u s in fe ct io n
a n d la ck of a d d it ive e ffe ct . In cre a s e d ris k of s e riou s in fe ct ion s is a con ce rn w it h
t h e u s e of biologic DMARDs , a n d s cre e n in g for la t e n t t u be rcu los is p rior t o in i-
t ia t ion of t re a t m e n t is re com m e n d e d . Th e biologic DMARDs s h ou ld be a d m in -
is t e re d u n d e r t h e d ire ct ion of a rh e u m a t ologis t .

TREATMENT OF SJÖGREN’S SYNDROME

S
Tre a t m e n t of Sjögre n ’s s yn d rom e is ge a re d t ow a rd s ym p t om a t ic re lie f a n d p re -
E
C
ve n t ion of d is e a s e com p lica t ion s . Tre a t m e n t s for xe ros t om ia a n d xe rop h t h a l-
T
I
O
m ia in clu d e t op ica l a ge n t s (a rt i cia l s a liva a n d t e a rs ) a n d m u s ca rin ic a gon is t s .
N
Good ora l h ygie n e a n d regu la r d e n t a l ca re a re p a ra m ou n t t o p reve n t t oot h los s .
3
Sys t e m ic in volve m e n t a n d re fra ct ory ca s e s m a y re q u ire im m u n os u p p re s s ive
S
p
t h e ra p ie s . Ar t h ra lgia s a n d m ya lgia s m a y re s p o n d w e ll t o NSAIDs a n d / o r
e
c
i
h yd roxych loroq u in e. Vis ce ra l in volve m e n t m a y re q u ire cort icos t e roid s w h ich
c
s h ou ld be u s e d ca u t iou s ly a s s t e roid s m ay a cce le ra t e p e riod on t a l d is e a s e a n d
R
h
o ra l ca n d id ia s is in Sjö gre n ’s p a t ie n t s . In ca s e s o f life t h re a t e n in g vis ce ra l
e
u
in volve m e n t , m ycop h e n ola t e m ofe t il, a za t h iop rin e, or cyclop h os p h a m id e t h e r-
m
a
a p y m a y be re q u ire d . In ve s t iga t ion s in t o t h e p os s ible role of biologic a ge n t s
t
i
c
(rit u xim a b, a ba t a cep t ) in t re a t in g Sjögre n ’s a re on goin g.
D
i
s
e
a
s
e
Clinica l Co urse
s
NATURAL HISTORY
Th e n a t u ra l h is t ory of RA, if n ot op t im a lly m a n a ge d , in clu d e s p rogre s s ive join t
in a m m a t ion , bon y e ros ion , a n d d e form it y w it h re s u lt a n t fu n ct ion a l d is a bilit y
a s w e ll a s in cre a s e d m ort a lit y. In t h e p e riod from t h e 1950s t o t h e 1980s , RA
w a s t h ou gh t t o h a ve a “good ” ove ra ll p rogn os is w it h s ym p t om a t ic u s e of a s p i-
rin a n d NSAIDs . By t h e m id -1980s , clin icia n s bega n t o re cogn ize t h a t p a t ie n t s
w it h lon ge r d u ra t ion of RA s ym p t om s h a d m u ch w ors e ou t com e s a n d ca lle d
for t h e ra p ie s a n d s t ra t egie s t o ga in im p rove d lon g-t e rm d is e a s e co n t rol. Th e
e a rly, a ggre s s ive u s e of DMARDs a n d biologic a ge n t s h a s le d t o m u ch t igh t e r
con t rol of RA d is e a s e a ct ivit y a n d in t h e d eve lop e d w orld in p a rt icu la r, RA ou t -
com e s h a ve im p rove d s ign i ca n t ly s in ce t h e m id -1980s (9 ).

LONG TERM OUTCOMES

WHEN TO REFER
• Su sp icio n o f p o ssib le RA in
t h e a b se n ce o f a d e n it ive
d ia g n o sis.
• Kn o w n RA w it h q u e st io n s
re g a rd in g o p t im a l t re a t -
ment.
Ou t co m e s fo r RA p a t ie n t s h a ve b e e n im p rovin g in t h e p a s t few d e ca d e s . A
re ce n t a rt icle com p a rin g s im ila r coh ort s of RA p a t ie n t s re ce ivin g s t a n d a rd ca re
fro m 1985 a n d 2000, re s p e ct ive ly, fo u n d p a t ie n t s in 2000 h a d s ign i ca n t
im p rove m e n t s in n u m be r of sw olle n join t s a s w e ll a s in m e a s u re s of p h ys ica l
fu n ct ion in g a n d d is e a s e a ct ivit y s co re s . Th e coh or t from 2000 a ls o d e m o n -
s t ra t e d im p rove m e n t in obje ct ive n d in gs , in clu d in g bot h la bora t ory a n d ra d io-
gra p h ic s core s . Com p a re d t o t h e old e r coh ort , m ore con t e m p ora ry p a t ie n t s a re
a ls o fa r m ore like ly t o be on DMARD t h e ra py (66% vs . 13%) a n d m e t h ot re xa t e
in p a rt icu la r (76% vs . 10%) (10 ).
 Ch a p te r 9 Rh e u m a t oid Art h rit is , In clu d in g Sjögre n ’s Syn d rom e 93

On ce t h e d ia gn os is of RA h a s be e n e s t a blis h e d a n d a p p rop ria t e ca re is in i-

t ia t e d , p a t ie n t s t yp ica lly h a ve im p rove d o u t co m e s com p a re d t o ye a rs p a s t .
W h ile o n ly a m in o r it y o f RA p a t ie n t s is fo llow e d in p u blis h e d s t u d ie s , o u t -
com e s in t e rm s of ra d iogra p h ic ch a n ge, join t rep la ce m e n t , w ork d is a bilit y, a n d
ove ra ll clin ica l a n d fu n ct ion a l s t a t u s a p p e a r t o be im p rovin g.

ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )•
cryst als (se e also Go u t )
275.49 [712.1] d icalciu m p h o sp h at e •
275.49 [712.2] p yro p h o sp h at e •
275.49 [712.8] sp e ci e d NEC•
079.99 [711.5] d u e t o o r asso ciat e d w it h viral d ise ase NEC•
274.00 g o u t y
274.01 acu t e

s
e
s
714.30 ju ve n ile rh e u m at o id (ch ro n ic) (p o lyart icu lar)

a
e
714.31 acu t e

s
i
D
714.33 m o n o art icu lar

c
i
714.32 p au ciart icu lar

t
a
m
714.4 p o st rh e u m at ic, ch ro n ic (Jacco u d ’s)

u
696.0 p so riat ic

e
h
R
714.0 rh e u m at ic

c
acu t e o r su b acu t e – se e Fe ve r, rh e u m at ic

i
c
714.0 ch ro n ic

e
p
720.9 sp in e

S
3
714.0 rh e u m at o id (n o d u lar)

N
714.1 w it h sp le n o ad e n o m e g aly an d le u k o p e n ia

O
I
714.2 visce ral o r syst e m ic in vo lve m e n t

T
C
714.30 ju ve n ile (ch ro n ic) (p o lyart icu lar)

E
S
714.31 acu t e
714.33 m o n o art icu lar
714.32 p au ciart icu lar
716.9 Arthro pathy
136.1 [711.2]Be h çe t ’s •
714.4 p o st rh e u m at ic, ch ro n ic (Jacco u d ’s)
729.0 Fibro sitis (p e riart icu lar) (rh e u m at o id )
274.9 Go ut , g o u t y
274.00 art h rit is
274.01 acu t e
274.00 art h ro p at h y
274.01 acu t e
274.02 ch ro n ic (w it h o u t m e n t io n o f t o p h u s (t o p h i))
274.03 w it h t o p h u s (t o p h i)
274.03 t o p h i
274.81 e ar
274.82 sp e ci e d sit e NEC
710.0 Lupus
695.4 e ryt h e m at o su s (d isco id ) (lo cal)
710.0 d isse m in at e d
710.0 syst e m ic
719.3 Palindro mic, arthritis •
725 Po lymyalg ia
725 rh e u m at ica
 94 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Re fe re nce s
1. Ga brie l SE, Crow s on CS , O’Fa llon W M . Th e ep id e m iology of rh e u m a t oid a rt h rit is in Roch e s t e r, Min n e -
s ot a , 1955–1985 . A rthritis Rheum . 1999 ;42 (3 ):415 –420 .
2. Wa lit t B, Pe t t in ge r M , We in s t e in A, e t a l. Effe ct s of p os t m e n op a u s a l h orm on e t h e ra p y on rh e u m a t oid
a rt h rit is : t h e w om e n ’s h e a lt h in it ia t ive ra n d om ize d con t rolle d t ria ls . A rthritis Rheum . 2008 ;59 (3 ):302 –310 .
3. Tu re s s o n C, O’Fa llon W M , Crow s on CS, e t a l . Ext ra -a r t icu la r d is e a s e m a n ife s t a t ion s in r h e u m a t o id
a rt h rit is : in cid e n ce t re n d s a n d ris k fa ct o rs ove r 46 ye a rs . A nn Rheum Dis . 2003 ;62 (8 ):722 –727 .
4. Th e a n d e r E, Ja cobs s on LT. Re la t ion s h ip of Sjogre n ’s s yn d rom e t o ot h e r con n e ct ive t is s u e a n d a u t oim -
m u n e d is ord e rs . Rheum Dis Clin North A m . 2008 ;34 (4 ):935 –47, viii–ix . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/
q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe d &d o p t =Cit a t ion &lis t _u id s =18984413.
5. O’De ll JR. Th e ra p e u t ic s t ra t egie s for rh e u m a t oid a rt h rit is . N Engl J Med . 2004 ;350 (25 ):2591 –2602 . h t t p ://
w w w.n cbi.n lm .n ih .gov/e n t rez/q u e ry.fcgi?cm d =Re t rieve&d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s=15201416.
6. Wolfe F, Ca p la n L, Mich a u d K. Tre a t m e n t for rh e u m a t oid a rt h r it is a n d t h e ris k o f h os p it a liza t io n fo r
p n e u m on ia : a s s ocia t io n s w it h p re d n is on e, d is e a s e -m o d ifyin g a n t ir h e u m a t ic d r u gs , a n d a n t i-t u m o r
n e cros is fa ct o r t h e ra p y. A rthritis Rheum . 2006 ;54 (2 ):628 –634 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.
fcgi?cm d =Re t rieve &d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s =16447241.
7. Ch oi HK, He rn a n MA, Se ege r JD, e t a l . Me t h ot re xa t e a n d m ort a lit y in p a t ie n t s w it h rh e u m a t oid a rt h rit is :
a p ros p e ct ive s t u d y. Lancet . 2002 ;359 (9313 ):1173 –1177 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.fcgi?c
m d =Re t rieve &d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s =11955534.
8. Sa a g KG, Te n g GG, Pa t ka r NM , e t a l. Am e rica n College of Rh e u m a t ology 2008 re com m e n d a t ion s for t h e
u s e of n on biologic a n d biologic d is e a s e -m od ifyin g a n t irh e u m a t ic d ru gs in rh e u m a t oid a rt h rit is . A rthri-
tis Rheum . 2008 ;59 (6 ):762 –784 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe
d &d op t =Cit a t ion &lis t _u id s =18512708.
S
E
9. Sokka T. Lon g-t e rm ou t com e s of rh e u m a t oid a rt h rit is . Curr Opin Rheum atol. 2009 ;21 (3 ):284 –290 . h t t p ://
C
w w w.n cbi.n lm .n ih .gov/en t rez/q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe d &d op t =Cit a t ion &lis t _u id s =19342954.
T
I
10. Pin cu s T, Sokka T, Ka u t ia in e n H . Pa t ie n t s s e e n for s t a n d a rd rh e u m a t oid a rt h rit is ca re h ave s ign i ca n t ly
O
N
be t t e r a rt icu la r, ra d iogra p h ic, la bo ra t ory, a n d fu n ct ion a l s t a t u s in 2000 t h a n in 1985 . A rthritis Rheum .
2005 ;52 (4 ):1009 –1019 . h t t p ://w w w.n cbi.n lm .n ih .gov/e n t re z/q u e ry.fcgi?cm d =Re t rieve &d b=Pu bMe d &d o p t
3
=Cit a t ion &lis t _u id s =15818706.
S
p
e
c
i
c
R
h
e
u
m
a
t
i
c
D
i
s
e
a
s
e
s
CHAPTER
10 The Seronega tive
Spondyloa rthropa thies
Dennis W . Boulw are

A 22-ye ar-o ld m an
Clinica l
Pre se nta tio n

s
p re se n t s w it h a

e
s
a
3-m o n t h h ist o ry o f For m a n y ye a rs t h e s e ron ega t ive

e
s
s p o n d y lo a r t h r o p a t h ie s w e r e

i
D
lo w b ack st iff n e ss
co n fu s e d u n d e r s t a n d a bly w it h

c
i
t
w h e n h e rst arise s r h e u m a t o id a r t h r it is d u e t o

a
m
in t h e m o rn in g . co m m o n fe a t u re s o f s ign i ca n t

u
e
m o r n in g ge l a n d in a m m a t o ry

h
He n d s t h at ch an g -

R
p e r ip h e ra l a r t h r it is . Th is le d t o

c
in g h is e xe rcise
co n fu s io n in t e r m in o lo gy w it h

i
c
h ab it s an d g o in g

e
n a m e s s u ch a s r h e u m a t o id

p
S
t o t h e g ym e arly in s p o n d y lit is , r h e u m a t o id va r i-

3
a n t s , a n d s o o n . W it h b e t t e r

N
t h e m o rn in g h e lp s

O
u n d e rs t a n d in g of t h e h is t ocom -

I
re d u ce t h e d u rat io n

T
p a t ibilit y ge n e s , t h ou gh , t h ey a re

C
E
o f st iff n e ss. His f at h e r an d p at e rn al g ran d f at h e r h ave e xp e rie n ce d kn ow n n ow t o be a clin ica lly a n d

S
a lif e t im e o f b ack p ro b le m s w it h xe d st o o p e d p o st u re s an d h e is e t io lo gica lly d is t in ct clu s t e r o f
co n ce rn e d h e w ill h ave a sim ilar o u t co m e . d is e a s e s w it h s h a re d co m m o n
fe a t u re s a n d clin ica l ch a ra ct e ris -
t ics t h a t d is t in gu is h t h e m fro m
e a ch ot h e r. Th is ch a p t e r d is cu s s e s t h e fou r m a in t yp e s of s e ron ega t ive s p on d y-
loa rt h rop a t h ie s : a n kylos in g s p on d ylit is , re a ct ive a rt h rit is or Re it e r’s d is e a s e,
p s or ia t ic a rt h r it is , a n d e n t e ro p a t h ic a r t h rit is a s s o cia t e d w it h in a m m a t o ry
bow e l d is e a s e (IBD). As a grou p , t h ey a re rh e u m a t oid fa ct or n ega t ive, h e n ce t h e
n a m e s e ro n ega t ive, a n d h a ve ra d iogra p h ic a n d / or clin ica l s a cro iliit is , t yp ica l
ve rt e bra l a bn orm a lit ie s , in a m m a t ory p e rip h e ra l a rt h rit is , e n t h e s op a t h y, u ve a l
t ra ct in volve m e n t , fa m ilia l clu s t e rin g, a n d t h e fre q u e n t p re s e n ce of h u m a n le u -
kocyt e a n t ige n B27 (HLA-B27).
All of t h e s e con d it ion s a re a form of a n in a m m a t ory a rt h rit is a n d s ign i -
ca n t m orn in g ge l p h e n om e n on is e xp e ct e d d u rin g t im e s of a ct ive in a m m a -
t io n . St iffn e s s re q u ir in g ove r a n h ou r t o re s o lve a ft e r p ro lo n ge d p e r io d s of
in a ct ivit y, s u ch a s im m e d ia t e ly a ft e r a w a ke n in g in t h e m orn in g, is a com m on
fe a t u re a n d t h e d u ra t io n re q u ire d fo r re s o lu t io n o ft e n co r re la t e s w it h t h e
s eve rit y of t h e con d it ion . Morn in g ge l or m orn in g s t iffn e s s is a com m on fe a -
t u re w it h a ll in a m m a t o ry a rt h r it id e s a n d like ly le d t o t h e e a rly con fu s ion
w it h rh e u m a t o id a rt h rit is . Sim ila rly, a ct ivit y h e lp s t o im p rove t h e s e n s a t io n of
s t iffn e s s a n d p a t ie n t s w it h a n y in a m m a t o ry a rt h r it is w ill re p o rt im p rove -
m e n t w it h a ct ivit y a s o p p o s e d t o w o r s e n in g w it h a ct ivit y, a s is co m m o n in
m e ch a n ica l d is o rd e r s a n d o s t e o a r t h r it is . Th e p a t t e r n o f p e r ip h e ra l jo in t

95
 96 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

in vo lve m e n t in t h e s e ro n e ga t ive s p o n d ylo a r t h ro p a t h ie s is a s ym m e t r ic a n d

CLINICAL POINTS o ligo a rt icu la r, o r m a y h a ve n o p e r ip h e ra l jo in t in volve m e n t w it h on ly a x ia l
• Mo re co m m o n in m e n t h a n in volve m e n t a s oft e n h a p p e n s in a n kylos in g s p on d ylit is , u n like t h e s ym m e t ri-
women. ca l d is t a l s m a ll join t in volve m e n t s e e n in rh e u m a t oid a rt h rit is .
• On se t u su a lly in e a rly A s e ro n e ga t ive s p o n d ylo a r t h ro p a t h y s h o u ld b e co n s id e re d in a p e r s o n
a d u lt h o o d . w it h s ign i ca n t m o r n in g ge l p h e n o m e n o n o f ove r a n h o u r in d u ra t io n , w h o
d o e s n o t h a ve s ym m e t r ica l s m a ll jo in t p o lya r t h r it is , b u t m a y h a ve low b a ck
• As a n in a m m a t o ry
a rt h rit is, m o rn in g g e l p a in o r a s ym m e t r ic o ligo a r t h r it is , e s p e cia lly w it h in a m m a t o ry h ip o r s h o u l-
u su a lly la st s se ve ra l h o u rs. d e r in vo lve m e n t . En t h e s o p a t h ie s s u ch a s t e n d in it is o r b u r s it is a re co m m o n
in a ll t h e s e ro n e ga t ive s p o n d ylo a r t h ro p a t h ie s . At t h is p o in t , n o n a r t icu la r fe a -
• Sa cro iliit is u su a lly ca u se s
b u t t o ck p a in a n d st iffn e ss. t u re s ca n h e lp m a k e t h e co r r e ct d ia gn o s is . In a n k ylo s in g s p o n d ylit is a n d
r e a ct ive a r t h r it is , t h e m a le -t o -fe m a le ra t io is s t ro n gly m a le d o m in a n t , h e n ce
• Th e e xt ra -a rt icu la r fe a t u re s fe m a le s e x m a k e s t h o s e co n d it io n s p o s s ible , b u t s t a t is t ica lly le s s lik e ly. Th e
(skin , m u co u s m e m b ra n e s,
e ye s, a n d b o w e l) h e lp id e n - p r e s e n ce o f ce r t a in e x t ra -a r t icu la r m a n ife s t a t io n s ca n a s s is t t h e clin icia n in
t ify t h e sp e ci c d ia g n o sis. n a r r ow in g t h e d iffe re n t ia l d ia gn o s is a n d le a d t o t h e co r re ct d ia gn o s is . Sk in
le s io n s t h a t a re p a p u lo s q u a m o u s in m o r p h o lo gy, w e ll d e m a rca t e d , e ryt h e m a -
t o u s , a n d s ca ly s u gge s t ive o f p s o r ia s is w ill m a k e p s o r ia t ic a r t h r it is t h e m o s t
lik e ly d ia gn o s is , a lt h o u gh it ca n re e ct k e ra t o d e r m a ble n o r r h a gicu m s e e n in
S
E
re a ct ive a r t h r it is . Mu co u s m e m b ra n e le s io n s t h a t m a y b e p a in le s s s u ch a s
C
T
u r e t h r it is a n d o ra l u lce r s m a k e re a ct ive a r t h r it is m o s t lik e ly, b u t ca n b e s e e n
I
O
in a n kylo s in g s p o n d ylit is a n d e n t e ro p a t h ic a r t h r it is . Mu co s a l u lce r s s e e n in
N
t h e r e ct u m o r co lo n s t ro n gly s u gge s t a n e n t e ro p a t h ic a r t h r it is , bu t a re a ls o
3
S
s e e n in re a ct ive a r t h r it is a n d a n kylo s in g s p o n d ylit is . Th e ove r la p in clin ica l
p
e
p r e s e n t a t io n o f t h e s e d is e a s e s r e e ct s t h a t t h e s e co n d it io n s r e p r e s e n t a
c
i
s p e ct r u m o f d is e a s e s t h a t d iffe r p h e n o t yp ica lly, b u t h a ve a co m m o n , a lb e it
c
R
co m p le x , ge n o t yp ic p a t h o ge n ic b a s is . W h e n t h e clin icia n s u s p e ct s t h e d ia g-
h
e
n o s is o f o n e o f t h e s e ro n e ga t ive s p o n d ylo a r t h ro p a t h ie s , clo s e r e x a m in a t io n
u
m
o f t h e e x t ra -a r t icu la r fe a t u re s w ill b e m o re fr u it fu l in id e n t ifyin g t h e s p e ci c
a
d is e a s e .
t
i
c
D
i
s
e
a
Ankylo sing Spo ndylitis
s
e
s
Th e cla s s ic p a t ie n t w it h a n kylo s in g s p o n d ylit is w ill b e a m a le w it h a n o n s e t
in h is la t e t e e n s o r e a rly t w e n t ie s w it h m o r n in g s t iffn e s s , low b a ck p a in , a n d
ra d io gra p h ic b ila t e ra l s a cro iliit is . Th e d u ra t io n o f s t iffn e s s w ill b e ove r a n
h o u r a n d u s u a lly 3 t o 4 h o u rs , va ryin g d ire ct ly w it h t h e s eve r it y o f t h e d is -
e a s e . Ph ys ica l a ct ivit y w ill im p rove h is s t iffn e s s a n d b a ck p a in u n lik e t h e p a in
a n d s t iffn e s s from a m e ch a n ica l b a ck d is o rd e r o r o s t e o a r t h r it is t h a t w o r s e n s
w it h a ct ivit y. No n s t e ro id a l a n t i-in a m m a t o ry d r u gs , eve n ove r-t h e -co u n t e r
p rod u ct s w ill p rovid e re lie f a lt h o u gh it m a y be in co m p le t e re lie f o f p a in a n d
s t iffn e s s .
Pa in a n d s t iffn e s s re e ct t h e in a m m a t ory n a t u re o f t h e con d it io n a n d a n
o n s e t of p a in o r s t iffn e s s a ft e r t h e a ge o f 40 ye a rs is ve ry u n u s u a l. W h ile t h e
d is e a s e is m ore co m m o n in m e n , w o m e n a re n o t im m u n e fro m d eve lo p in g
a n kylos in g s p on d ylit is a n d oft e n h a ve le s s ba ck s ym p t om s a n d m ore p e rip h -
e ra l a s ym m e t ric oligoa rt h rit is . Th e p a in from s a croiliit is is com m on ly re p or t e d
a s low ba ck p a in by t h e p a t ie n t , bu t m a y be fe lt a s bu t t ock or glu t e a l p a in , or
p a in in t h e a n t e r io r a n d / o r la t e ra l t h igh s . Ex t ra -a r t icu la r fe a t u re s a re le s s
co m m o n in a n kylo s in g s p o n d ylit is t h a n t h e o t h e r s e ro n e ga t ive s p o n d ylo a r-
t h rop a t h ie s , bu t d o occu r in a m in or it y of p a t ie n t s . Irit is or a n t e r ior u ve it is ,
o ccu rr in g in u p t o 20% p a t ie n t s , is on e of t h e m ore co m m o n e xt ra -a rt icu la r
fe a t u re s oft e n p re d a t in g t h e d eve lop m e n t of t h e m u s cu los ke le t a l m a n ife s t a -
t ion . Ora l m u cos a l u lce ra t ion s a n d s h a llow re ct a l or colon ic u lce ra t ion s ca n be
s e e n le s s fre q u e n t ly t h a n irit is a n d u ve it is . Fin a lly, a n IgA n e p h rit is a n d le u k o -
cyt o cla s t ic cu t a n e o u s va s cu lit is re s e m blin g He n o ch –Sch ö n le in p u r p u ra h a s
be e n re p ort e d .
 Ch a p te r 10 Th e Se ron ega t ive Sp on d yloa rt h rop a t h ie s 97

Re a ctive Arthritis
Alt h ou gh com m on ly a s s ocia t e d w it h Re it e r’s s yn d rom e a n d t h e cla s s ic t ria d of
a rt h rit is , u re t h rit is , a n d u ve it is , re a ct ive a rt h rit is in clu d e s m a n y m ore e xt ra -
a r t icu la r m a n ife s t a t io n s t h a n t h e cla s s ic t r ia d , e s p e cia lly in vo lvin g t h e
s kin a n d t h e m u cos a l m e m bra n e s . Th e a rt h rit is is u s u a lly a n a cu t e, a d d it ive,
a n d a s ym m e t ric on e w it h e n t h e s it is a n d /or a xia l a rt h rit is com m on ly s e e n a n d
co m b in e d w it h k e ra t o d e r m a ble n o r rh a gicu m , d ia rrh e a , ce rvicit is , u re t h rit is ,
co n ju n ct ivit is , p a in le s s o ra l u lce r s , a n d / o r circin a t e b a la n it is . Id e n t ifyin g a
p rior re ce n t in fe ct iou s eve n t is n ot a lw a ys p o s s ible , bu t re a ct ive a rt h rit is is
kn ow n t o occu r a ft e r d ys e n t e ric t yp e illn e s s or ge n it ou rin a ry in fe ct ion s . Typ i-
ca lly, re a ct ive a rt h rit is fo llow s t h e in fe ct io n w it h in 1 t o 4 w e e k s , w it h feve r
be in g com m on a n d a rt h rit is be in g t h e la s t clin ica l fe a t u re t o p re s e n t . Re a ct ive
a rt h r it is is t h e m os t com m o n m u s cu los ke le t a l con d it ion s e e n in a ct ive HIV
in fe ct ion a n d HIV s h ou ld be con s id e re d in a n y n ew d ia gn os is of re a ct ive a rt h ri-
t is , or w ors e n in g re a ct ive a rt h rit is . Fin a lly, re a ct ive a rt h rit is is re p ort e d t o occu r
a ft e r t re a t m e n t of in fe ct ion s or im m u n iza t ion .

s
e
s
Pso ria tic Arthritis

a
e
s
i
D
Ps oria s is is a ch ron ic a u t oim m u n e s kin con d it ion t h a t h a s a h igh e r p reva le n ce

c
i
of a coe xis t in g ch ron ic in a m m a t ory a rt h rit is t h a n is s e e n in t h e ge n e ra l p op u -

t
a
m
la t ion . Th e s kin d is e a s e u s u a lly p re d a t e s t h e on s e t of a rt h rit is , a lt h ou gh t h e

u
con ve rs e re la t ion s h ip is s e e n a n d t h e con cu rre n t on s e t of p s oria s is a n d a rt h ri-

e
h
R
t is is t h e le a s t com m on m od e of p re s e n t a t ion . Th e p a t t e rn of join t in volve m e n t

c
is va ria ble bu t t yp ica lly follow s ve d iffe re n t p a t t e rn s : s ym m e t ric p olya rt h rit is ,

i
c
d is t a l in t e rp h a la n ge a l join t in volve m e n t , oligoa rt h rit is , a rt h rit is m u t ila n s , a n d

e
p
a xia l in volve m e n t .

S
3
N
O
Ente ro pa thic Arthritis Asso cia te d w ith

I
T
C
Infla mma to ry Bo w e l Dise a se

E
S
Th e in clu s ion o f IBD in t h is grou p o f d is e a s e s e m p h a s ize s t h e re la t ion s h ip
be t w e e n gu t in a m m a t ion a n d join t in a m m a t ion . Ot h e r ga s t roin t e s t in a l con -
d it ion s , s u ch a s ce lia c d is e a s e, a n d in t e s t in a l byp a s s s u rge ry a re occa s ion a lly
a ccom p a n ie d by join t in a m m a t ion , bu t t h e s e a re n ot con s id e re d a s s p on d y-
loa rt h rop a t h ie s . Croh n ’s d is e a s e a n d u lce ra t ive colit is a re d is cu s s e d t oge t h e r
s in ce t h e m u s cu los ke le t a l a n d ga s t roin t e s t in a l fe a t u re s ca n n ot be e a s ily d if-
fe re n t ia t e d . Mu s cu los ke le t a l is s u e s a re t h e m os t com m on e xt ra in t e s t in a l m a n -
ife s t a t ion s of IBD a n d a p p e a r in 2% t o 20% of p a t ie n t s w it h e it h e r u lce ra t ive
co lit is o r Cro h n ’s d is e a s e, w it h p e rip h e ra l a r t h rit is s e e n m o re fre q u e n t ly in
p a t ie n t s w it h colon ic in volve m e n t a n d m ore e xt e n s ive bow e l d is e a s e. Th e fre -
q u e n cy of p e rip h e ra l a rt h rit is in IBD ra n ge s u p t o 20% of p a t ie n t s , w it h a h igh e r
p reva le n ce in Croh n ’s d is e a s e. In bot h Croh n ’s d is e a s e a n d u lce ra t ive colit is ,
t h e a rt h r it is ge n e ra lly is p a u cia rt icu la r, a s ym m e t ric, fre q u e n t ly t ra n s ie n t or
m igra t o ry, a n d t yp ica lly n o n d e s t r u ct ive w it h co m m o n re cu r re n ce s . In fre -
q u e n t ly, t h e p e rip h e ra l a rt h rit is be com e s ch ron ic a n d d e s t ru ct ive. En t h e s op a -
t h ie s ca n ca u s e s a u s a ge d igit d e form it ie s , Ach ille s t e n d in it is , a n d p la n t a r fa s -
ciit is . Axia l in volve m e n t in volvin g t h e s a croilia c join t s or s p in e occu rs in bot h
d is e a s e s w it h p reva le n ce ra t e s of 10% t o 20% for s a croiliit is a n d 7% t o 12% for
s p on d ylit is re p ort e d , a lt h ou gh t h e a ct u a l gu re s a re p roba bly h igh e r be ca u s e of
t h e e xis t e n ce of s u bclin ica l a xia l in volve m e n t .
In m os t ca s e s of Croh n ’s d is e a s e, in t e s t in a l s ym p t om s a n t e d a t e or coin cid e
w it h t h e jo in t m a n ife s t a t io n s , w it h t h e a r t icu la r s ym p t o m s p re ce d in g t h e
in t e s t in a l s ym p t om s by ye a rs . In u lce ra t ive colit is , t h e re is a m ore d is t in ct t e m -
p ora l re la t ion s h ip be t w e e n a t t a cks of a rt h rit is a n d a re s of bow e l d is e a s e.
 98 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Ext ra in t e s t in a l a n d e xt ra -a rt icu la r m a n ife s t a t ion s a re s im ila r t o t h os e s e e n

PATIENT ASSESSMENT in IBD, in clu d in g e ryt h e m a n od os u m , pyod e rm a ga n gre n os u m , a n t e rior u ve it is ,
e p is cle rit is , a n d a p h t h ou s ora l u lce rs .
• Pre se n ce o f m o rn in g g e l.
• Evid e n ce o f syn o vit is in
p e rip h e ra l jo in t s. Exa mina tio n
• Evid e n ce o f e n t h e sit is.
Ph ys ica l e xa m in a t ion of t h e a ffe ct e d p a in fu l or d ys fu n ct ion a l p e rip h e ra l join t s
• Occu rre n ce o f skin , s h ou ld a s s e s s t h e p re s e n ce of in a m m a t ory s yn ovit is , w h ich is t h e h a llm a rk of
m u co u s m e m b ra n e , e ye , a n in a m m a t ory a rt h rop a t h y. Th e s e n d in gs in clu d e s oft t is s u e sw e llin g t h a t
a n d b o w e l in vo lve m e n t .
cou ld m a s k p a lp a t ion of bon y la n d m a rks in m ild ca s e s t o im p e d in g fu ll p a s s ive
• Im a g in g o f sa cro ilia c jo in t s ra n ge of m ot ion a n d ca u s e vis ible bu lgin g in s eve re ca s e s . Exa m in a t ion m u s t
a n d sp in e is u su a lly m o re in clu d e a xia l join t s in clu d in g t h e s a croilia c join t s a n d s p in e.
in fo rm a t ive t h a n p h ysica l
e xa m in a t io n .
Th e r e a re s eve ra l m e t h o d s fo r e x a m in a t io n o f t h e s a cro ilia c jo in t s , n o n e
o f w h ich a re ve ry s e n s it ive o r s p e ci c w h e n d o n e a lo n e . Th e s a cro ilia c jo in t s
lie in fe r io r t o t h e p o s t e r io r s u p e r io r ilia c s p in e , a n d d ire ct p a lp a t io n o f t h is
a re a (Fig. 10.1 ) u s u a lly d e t e ct s glu t e a l m u s cle t e n d e r n e s s a s o p p o s e d t o s a c-
ro ilia c jo in t t e n d e r n e s s , s in ce t h e jo in t lie s d e e p b e n e a t h t h e glu t e a l m u s -
S
cle s a n d t ra ve r s e s o bliq u e ly fro m t h e s u r fa ce m a k in g p a lp a t io n o f t h e jo in t
E
C
d ire ct ly im p o s s ib le . In d ire ct co m p r e s s io n o f t h e s a cr o ilia c jo in t ca n b e d o n e
T
I
by s e ve ra l m e t h o d s . W it h t h e p a t ie n t s u p in e , c o m p r e s s io n a n d lo a d in g o f
O
N
t h e a n t e r io r s u p e r io r ilia c s p in e s w it h t h e e x a m in e r ’s u p p e r b o d y w e igh t
3
w ill co m p r e s s t h e s a cro ilia c jo in t w it h t e n d e r n e s s fe lt in t h e s a cra l a re a (Fig.
S
p
10.2 ). Th e p a t ie n t ca n a ls o b e p o s it io n e d o n t h e ir s id e w it h co m p re s s io n a n d
e
c
lo a d in g o f t h e ilia c cre s t w it h t h e e x a m in e r ’s u p p e r b o d y w e igh t ; w it h s a c-
i
c
ro iliit is , t e n d e r n e s s m a y b e fe lt in t h e s a cra l a re a (Fig. 10.3 ). Ga e n s le n ’s t e s t
R
h
is a n o t h e r t e s t fo r s a cro iliit is w h e re o n e h ip jo in t is e x e d m a x im a lly o n o n e
e
u
s id e a n d t h e co n t ra la t e ra l h ip jo in t is e x t e n d e d . Ga e n s le n ’s t e s t ca n b e d o n e
m
w it h t h e p a t ie n t s u p in e , p a s s ive ly e x in g o n e h ip by a p p ro x im a t in g t h e k n e e
a
t
i
t o t h e p a t ie n t ’s ch e s t a n d a llow in g t h e o t h e r le g t o fa ll ove r t h e s id e o f a n
c
D
e x a m in a t io n t a b le , c a u s in g t h a t h ip t o h yp e r e x t e n d . Th e t e s t ca n a ls o b e
i
s
e
p e r fo r m e d w it h t h e p a t ie n t in t h e la t e ra l r e cu m b e n t p o s it io n w it h b o t h h ip s
a
s
e x e d a n d w it h b o t h k n e e s a p p ro x im a t in g t h e ch e s t , t h e n t a k in g t h e u p p e r
e
s
le g in t o fu ll e x t e n s io n o f t h a t t h e k n e e a n d h ip w h ile h yp e re x t e n d in g t h e h ip
(Fig. 10.4 ). Th e p a t ie n t ’s p o s it io n ca n b e re ve r s e d a n d t h e o t h e r le g t e s t e d .
Th e p re s e n ce o f s a cr o iliit is m a y ca u s e t h e p a t ie n t t o e x p e r ie n ce t e n d e r n e s s

Figure 10 .1 Exa miner a ttempting to pa lpa te directly the sa croilia c joints, Figure 10 .2 Testing for sa croiliitis by a nterior loa ding of pelvis, with weight
which lie inferior to the posterior superior ilia c spines. The sa cra l dimples on the a nterior superior ilia c spines of the pelvis.
ma rk the posterior superior ilia c spine, which is the superior end of the
sa croilia c joint.

Figure 10 .3 Testing for sa croiliitis by la tera l loa ding of pelvis, with weight
on the ilia c wings of the pelvis.
Figure 10 .4 Testing for sa croiliitis using Ga enslen’s ma neuver pla cing
leg in hypertension a nd loa ding the pelvis by torque.
Figure 10 .5 Testing for sa croiliitis using Pa trick’s test a nd loa ding the
pelvis by torque.
Ch a p te r 10 Th e Se ron ega t ive Sp on d yloa rt h rop a t h ie s 99
in t h e s a cra l a re a . Fin a lly, Pa t r ick ’s m a n e u ve r ca n b e
d o n e by p la cin g t h e p a t ie n t in a s u p in e p o s it io n a n d
e x in g o n e k n e e a n d h ip t o 90 d e gre e s , t h e n p la cin g
t h e e x e d le g’s fo o t o n t h e co n t ra la t e ra l k n e e . Th e
e x e d le g s h o u ld b e re la x e d a n d u s in g o n e h a n d o n
t h e e x e d k n e e a n d t h e o t h e r h a n d o n t h e co n t ra l-
a t e r a l a n t e r io r s u p e r io r ilia c s p in e t o s t a b iliz e t h e
p e lv is , t h e e x a m in e r w ill p u s h t h e e x e d k n e e
t ow a rd t h e e x a m in a t io n t a b le (Fig. 10.5 ). Bo t h le gs
ca n b e t e s t e d a s t h e m a n e u ve r co m p re s s e s o n e s a c-
ro ilia c jo in t w h ile d is t ra ct in g t h e o t h e r s id e . Sa cro -
iliit is c a n c a u s e d is c o m fo r t fe lt in t h e s a c r a l a r e a
d u r in g t h e t e s t . Obvio u s ly, t h e p a t ie n t m u s t h a ve
s t a b le h ip s a s t h e m a n e u ve r p la ce s gr e a t s t r e s s o n
t h e ip s ila t e ra l h ip jo in t . No n e o f t h e s e t e s t s in d ivid -
u a lly is r e lia b le a n d t h e c lin ic ia n s h o u ld p u r s u e
im a g in g s t u d ie s if s a c r o iliit is is s u s p e c t e d o r a
co n ce r n .
s
e
Sp in a l in vo lve m e n t t yp ica lly s t a r t s in t h e lu m b a r
s
a
re gio n a n d a s ce n d s u p t h e s p in e . Lo s s o f lu m b a r e x -
e
s
i
io n is a n e a r ly eve n t a n d ca n b e d e t e ct e d by u s e o f
D
c
t h e m o d i e d Sch ö b e r ’s t e s t (Fig. 10.6A, B). W it h t h e
i
t
a
p a t ie n t s t a n d in g e re ct , t h e clin icia n w ill p la ce o n e
m
m a r k b e t w e e n t h e p o s t e r io r s u p e r io r ilia c s p in e s a n d
u
e
u s e a t a p e m e a s u re , p la cin g t h e 0 e n d 10 cm a b ove
h
R
t h e o r igin a l m a r k . Th e clin icia n w ill h o ld t h e 0 e n d o f
c
i
t h e t a p e m e a s u r e in p la ce a n d a s k t h e p a t ie n t t o
c
e
b e n d fo r w a rd a t t e m p t in g t o t o u ch t h e ir t o e s a n d fu lly
p
S
e x in g t h e lu m b a r s p in e . Th e clin icia n w ill m e a s u re
3
t h e d is t a n ce o f d is p la ce m e n t w h e n t h e lu m b a r s p in e
N
O
is fu lly e x e d fro m t h e 0 e n d o f t h e t a p e m e a s u re t o
I
T
C
t h e o r igin a l m a r k b e t w e e n t h e p o s t e r io r s u p e r io r
E
S
ilia c s p in e s . A n o r m a l lu m b a r s p in e w ill in cre a s e t h e
d is t a n ce fro m 10 t o a t le a s t 15 cm . Ex a m in a t io n o f
t h e t h o ra cic a n d ce r vica l s p in e s h o u ld a ls o b e p e r-
fo r m e d w it h p a r t icu la r e m p h a s is fo r lim it e d m o t io n
in ch e s t e x cu r s io n by m e a s u r in g ch e s t circu m fe re n ce
b e t w e e n fu ll in s p ira t io n a n d e x p ira t io n . Fle x io n co n -
t ra ct u r e s o f t h e ce r vica l s p in e ca n b e d e t e ct e d by
m e a s u r in g t h e ce r vica l e ch e o r d is t a n ce fro m t h e
o ccip u t t o t h e w a ll w h e n t h e p a t ie n t s t a n d s w it h
t h e ir b a ck t o t h e w a ll w it h t h e ir h e e ls , k n e e s , b u t -
t o ck , a n d s h o u ld e r s p re s s e d a ga in s t t h e w a ll. A n o r-
m a l ce r vica l e ch e is 0 cm .
An e x a m in a t io n fo r e x t ra -a r t icu la r m a n ife s t a -
t ion s , p a rt icu la rly of t h e s kin a n d m u cou s m e m bra n e s
is e s s e n t ia l. Th e p e rip h e ra l a n d a xia l a rt icu la r in volve -
m e n t w ill n ot d iffe re n t ia t e be t w e e n t h e s e ron ega t ive
s p o n d y lo a r t h r o p a t h ie s a n d o n ly t h e p r e s e n ce o r
a b s e n ce o f t h e e x t ra -a r t icu la r fe a t u re s w ill h e lp in
id e n t ifyin g t h e corre ct d ia gn os is .
Studie s
Th e la b o ra t o r y is o f lit t le h e lp in e va lu a t in g t h e
p a t ie n t w it h a s u s p e ct e d s e r o n e ga t ive s p o n d ylo a r-
t h ro p a t h y e x ce p t t o con r m t h e p re s e n ce o f s ys t e m ic
 100 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
S
E
C
T
I
O
N
A B
3
S
p
e
Figure 10 .6 A. Sta rt of the modi ed Schöber’s test mea suring 10 cm a bove the midline between the sa cra l dimples or posterior superior
c
i
ilia c spine with the pa tient erect. B. End of the modi ed Schöber’s test mea suring the a dditiona l dista nce a bove the midline between the
c
sa cra l dimples or posterior superior ilia c spine with the pa tient ma xima lly exed a ttempting to touch their toes.
R
h
e
u
m
a
in a m m a t io n t h ro u gh a n a b n o r m a l C-re a ct ive p ro t e in o r e ryt h ro cyt e s e d i-
t
i
c
m e n t a t io n ra t e . Th e u s e o f HLA-B27 is d e b a t a ble a s it is n o t a lw a ys fo u n d in
D
t h e s e ro n e ga t ive s p o n d ylo a r t h rop a t h ie s a n d ca n b e fou n d in ce r t a in p o p u la -
i
s
e
t io n s w it h o u t a n in a m m a t o ry a r t h r o p a t h y. Sin ce low b a ck p a in is a ve ry
a
s
e
co m m o n a ilm e n t , t h e p re s e n ce o f HLA-B27 ca n re s u lt in e r ro n e o u s d ia gn o s e s
s
o f a s e ron e ga t ive s p on d ylo a r t h ro p a t h y.
Im a gin g s t u d ie s ca n be h e lp fu l in s eve ra l of t h e s e ron ega t ive s p on d yloa r-
t h rop a t h ie s . In s u s p e ct e d s a croiliit is , p la in x-ra y w ill id e n t ify s a cro iliit is or
s p o n d ylit is w it h m o re p re cis io n t h a n p h ys ica l e x a m in a t io n . In a n kylo s in g
s p o n d ylit is , t h e s a cro ilia c in vo lve m e n t is bila t e ra l a n d s t a rt s e a rly w it h e ro -
s ion s a lon g t h e s a croilia c join t , follow e d la t e r by s cle ros is a n d eve n t u a l fu s ion .
In p s oria t ic a rt h rit is , re a ct ive a rt h rit is , a n d e n t e rop a t h ic a rt h rit is , t h e s a croilia c
in volve m e n t ca n be u n ila t e ra l a n d in volve m ore e xu be ra n t s cle ros is t h a n s e e n
NOT TO BE MISSED in a n kylos in g s p on d ylit is . W h e n t h e re is s p in a l in volve m e n t , s yn d e s m op h yt e s
w ill be s e e n a n d t e n d t o be m ore e xu be ra n t a n d p rolife ra t ive in p s oria t ic a rt h ri-
• Pso ria sis t is a n d re a ct ive a rt h rit is a s op p os e d t o a n kylos in g s p on d ylit is . Ea rly s yn d e s m o-
• En t h e sit is p h yt e s com m on ly occu r in t h e t h o ra colu m ba r a re a a n d a re be s t view e d o n
• Ke ra t o d e rm a la t e ra l view s a s ca lci ca t ion of t h e a n n u lu s bros is or a n t e rior lon git u d in a l
b le n o rrh a g icu m liga m e n t s h ow s rs t on t h is view.
Ra d iogra p h ic a p p e a ra n ce of p e rip h e ra l join t s is s im ila r t o t h a t of rh e u m a -
• Circin a t e b a la n it is
t oid a rt h rit is e xcep t in t h e ca s e of p s oria t ic a rt h rit is , w h ich ca u s e s a n e ros ive
• Uve it is o r a n t e rio r irit is p a t t e rn t h a t cre a t e s a p e n cil-in -cu p a p p e a ra n ce of t h e join t . In t h e s e ca s e s , t h e
• Mu co u s m e m b ra n e p roxim a l com p on e n t of t h e join t is w h it t le d t o a p oin t a n d t h e d is t a l con ve x
in vo lve m e n t w it h o ra l s u rfa ce broa d e n s t o t a ke on t h e a p p e a ra n ce of a cu p .
u lce rs, re ct a l u lce rs, a n d
so o n
• In a m m a t o ry b o w e l Tre a tme nt
d ise a se , b o t h u lce ra t ive
co lit is a n d Cro h n ’s d ise a se Th e m a jor a im s of m a n a ge m e n t in clu d e p a t ie n t e d u ca t ion rega rd in g t h e n a tu ra l
h is t ory of t h e con d it ion , rea s on a ble rea s su ra n ce of t h e p a t ien t’s exp ecta t ion s , t h e

WHEN TO REFER
• Wh e n in d o u b t o f t h e
e xa ct d ia g n o sis.
• Wh e n t h e p e rip h e ra l
a rt h rit is is d e fo rm in g ,
e ro sive , a n d /o r d e st ru ct ive .
• Wh e n d ise a se m o d ifyin g
a n t i-rh e u m a t ic d ru g s a re
needed.
Ch a p te r 10 Th e Se ron ega t ive Sp on d yloa rt h rop a t h ie s 101
u s e of a n t i-in a m m a tory m e d ica tion s, p h ys ica l t h e ra py a n d lifes tyle m od i ca -
tion s a im e d a t re ta rd in g s p in a l a n d join t d eform ities , a n d t h e a p p rop ria te u se of
d is ea s e m od ifyin g a n ti-rh eu m a t ic d ru gs for d es tru ct ive p e rip h e ra l a rth rop a t h ie s.
Non s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs ) a re e ffe ct ive for t h e p a in
a n d s t iffn e s s a s s ocia t e d in a xia l a n d p e rip h e ra l join t in volve m e n t , bu t s h ou ld
b e u s e d ju d icio u s ly w it h a p p rop r ia t e ca u t ion fo r ga s t ro in t e s t in a l u lce ra t io n
a n d re n a l in s u f cie n cy. An e cd ot a lly, u s e of NSAIDs ca n e xa ce rba t e p s oria s is
a n d IBD.
Us e of d is e a s e m od ifyin g a n t i-rh e u m a t ic d ru gs a re in d ica t e d w h e n t h e re is
evid e n ce of d e s t ru ct ive p e rip h e ra l d is e a s e or a xia l d is e a s e re fra ct ory t o NSAIDs
a lon e. Re fe rra l t o a rh e u m a t ologis t is a d vis a ble a t t h is p oin t .
De s p it e t h e re la t ion s h ip of in fe ct ion s p re ce d in g re a ct ive a rt h rit is , t h e re a re
n o con clu s ive s t u d ie s t h a t t h e u s e of a n t ibiot ics is of a n y s ign i ca n t va lu e.
Clinica l Co urse
Th e clin ica l cou rs e for t h e s e ron ega t ive s p on d yloa rt h rop a t h ie s va rie s con s id e r-
s
e
a bly for e a ch con d it ion a n d w it h in e a ch con d it ion . In a n kylos in g s p on d ylit is ,
s
a
s a croiliit is is s e e n in virt u a lly a ll ca s e s , bu t p e rip h e ra l a rt h rit is is le s s com m on .
e
s
i
An kylos in g s p on d ylit is is m ore com m on in you n g m e n w h o h a ve t yp ica l low
D
c
ba ck p a in a n d s t iffn e s s , bu t w h e n it occu rs in w om e n a n d ch ild re n , t h ey ca n
i
t
a
h a ve a n a t yp ica l p re s e n t a t ion w it h m ore p e rip h e ra l a rt h rit is , e n t h e s it is , a n d
m
ce rvica l in volve m e n t . Th e p rogn os is in a n kylos in g s p on d ylit is is good in m os t
u
e
p a t ie n t s w h e re on ly 10% be com e s ign i ca n t ly d is a ble d a n d 90% a re a ble t o
h
R
p u rs u e fu ll-t im e e m p loym e n t . A p re d ict a ble p a t t e rn of d is e a s e u s u a lly e m e rge s
c
i
a ft e r t h e rs t 10 ye a rs w it h d e s t ru ct ive h ip in volve m e n t be in g a n in d ica t or of a
c
e
p oor fu n ct ion a l ou t com e.
p
S
In re a ct ive a rt h rit is , t h e p rogn os is a n d cou rs e of in d ivid u a l p a t ie n t s w it h
3
N
Re it e r s yn d ro m e a re va r ie d a n d u n p re d ict a ble , re ga rd le s s o f w h e t h e r t h ey
O
p re s e n t w it h t h e cla s s ic t ria d , ACR cr it e r ia , o r in com p le t e Re it e r s yn d ro m e .
I
T
C
Mo s t p a t ie n t s d e m on s t ra t e a n in it ia l e p is o d e o f a cu t e a rt h rit is w it h a m e a n
E
S
d u ra t io n of 2 t o 3 m on t h s , bu t w h ich m a y la s t u p t o a ye a r. Som e p a t ie n t s
d eve lop re cu rre n t a t t a cks w it h d is e a s e -fre e in t e rva ls . A m in orit y of p a t ie n t s
d e m on s t ra t e s a ch ron ic cou rs e of p e rip h e ra l a rt h rit is a n d t h ey h a ve a gre a t e r
p ot e n t ia l for p rogre s s ive s p on d ylit is . Pre d ict in g w h ich p a t ie n t s w ill d eve lop
re cu rre n t a t t a cks or ch ron ic re a ct ive a rt h rit is is d if cu lt a n d in e xa ct . Fa ct ors
t h a t m ay p re d ict a p oore r or m ore ch ron ic ou t com e in clu d e h ip a rt h rit is , ESR
30 m m /h ou r, p oor re s p on s e t o NSAIDs , lu m ba r s p in e in volve m e n t , s a u s a ge
d igit s , a n d /o r a n on s e t b e fore 16 ye a r s of a ge . Ye t d e s p it e t h e p ot e n t ia l fo r
ch ron ic d is e a s e, s t u d ie s h ave s h ow n t h a t p a t ie n t s w it h re a ct ive a rt h rit is t yp i-
ca lly m a in t a in a h igh e r leve l of con t in u e d e m p loym e n t t h a n in d ivid u a ls w it h
o t h e r in a m m a t o ry a r t h r it id e s . Seve re d is a b ilit y is u n co m m o n a n d is fre -
q u e n t ly s e co n d a ry t o a ggre s s ive , d e s t r u ct ive low e r-e x t re m it y in vo lve m e n t ,
a ggre s s ive a xia l in volve m e n t , or blin d n e s s .
In p s o r ia t ic a r t h r it is , t h e re ca n b e s eve ra l p a t t e r n s o f jo in t in vo lve m e n t ,
w it h t h e p o lya r t ic u la r p a t t e r n r e s e m b lin g r h e u m a t o id a r t h r it is , t h e m o s t
co m m o n fo r m . Th e p o lya r t icu la r p a t t e r n r e s p o n d s w e ll t o d is e a s e m o d ifyin g
a n t i- r h e u m a t ic d r u gs a n d c lin ic a lly h a s a go o d o u t c o m e a llo w in g fu ll
fu n ct io n in g a n d co n t in u e d e m p loym e n t . Mo r e a ggr e s s ive d is e a s e re s p o n d s
w e ll t o m o r e a ggr e s s ive d is e a s e m o d ifyin g a n t i- r h e u m a t ic d r u gs s u ch a s
m e t h o t r e x a t e a n d t h e TNF in h ib it o r s t h a t a r e u s e d fo r t re a t in g p s o r ia s is a s
w e ll.
In bot h p s oria t ic a rt h rit is a n d e n t e rop a t h ic a rt h rit is a s s ocia t e d w it h IBD,
a ggre s s ive t re a t m e n t o f t h e p s o ria s is a n d IBD is h igh ly re co m m e n d e d , a s in
s o m e ca s e s t h e s eve r it y o f t h e a rt h rit is p a ra lle ls t h e s eve rit y o f t h e s k in o r
bow e l d is e a s e.
 102 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
569.9 [713.1] d u e t o o r asso ciat e d w it h g ast ro in t e st in al co n d it io n NEC
099.3 [711.1] Re it e r’s d ise ase /Re act ive art h rit is
696.0 p so riat ic
720.9 Spo ndylitis
720.0 an k ylo sin g (ch ro n ic)

Additio na l Re a ding
1. Davis JC. An kylos in g s p on dylit is . In Koop m a n W J, More la n d LW, e d s . A rthritis and A llied Conditions . 15t h e d .
Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2005 ;1319 –1334 .
2. Kh a n MA, Siep e r J. Re a ct ive a rt h rit is . In Ko op m a n W J, More la n d LW, e d s . A rthritis and A llied Conditions .
15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2005 ;1335 –1356 .
3. Be n n e t t RM . Ps oria t ic a rt h rit is . In Koop m a n W J, More la n d LW, e d s . A rthritis and A llied Conditions . 15t h e d .
Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2005 ;1357 –1374 .
4. Mie la n t s H , Ba e t e n D, De Keys e r F, Veys EM . En t e ro p a t h ic a rt h rit is . In Koop m a n W J, More la n d LW, e d s .
S
A rthritis and A llied Conditions . 15t h e d . Ph ila d e lp h ia : Lip p in cot t W illia m s a n d Wilkin s , 2005 ;1375 –1400 .
E
C
5. Bou lw a re DW, Arn e t t FC, Cu s h JJ, Lip s ky PE, Be n n e t t RM , Mie la n t s H , De Keys e r F, Veys EM . Th e s e ron ega -
T
t ive s p on d yloa rt h rop a t h ie s . In Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Clinical Prim er of Rheum a-
I
O
tology . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s , 2003 ;127 –163 .
N
3
S
p
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c
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CHAPTER
11 Systemic Lupus
Erythema tosus
Michelle A . Petri

A 23-ye ar-o ld Cau casian w o m an

Clinica l Pre se nta tio n
EPIDEMIOLOGY

s
p re se n t s t o h e r p rim ary care d o c-

e
s
Sy s t e m ic lu p u s e r y t h e m a t o s u s

a
t o r w it h co m p lain t s o f 9 m o n t h s

e
s
(SLE) is a m u lt is ys t e m a u t oim m u n e

i
D
o f f at ig u e , p ain in m u scle s in clu d - d is e a s e . It o ccu r s p re d o m in a n t ly

c
i
t
in g t h e n e ck an d sh o u ld e r are a, in w om e n , bu t 10% of p a t ie n t s a re

a
m
an d re d ch e e k s af t e r su n e xp o - m e n . Th e o n s e t is p re d o m in a n t ly

u
e
in t h e 20s a n d 30s , bu t it ca n p re s e n t

h
su re , last in g f o r an h o u r o r so .

R
in o ld e r p a t ie n t s (it is ra re b e fo re

c
On t h e p h ysical e xam in at io n , p u be rt y). It is bot h m ore com m on

i
c
t h e ch e e k s h ave several pustules.

e
a n d m o r e s e ve r e in Afr ic a n –

p
S
Laboratory d at a are o rd e re d Am erica n s a n d Hisp a n ic–Am erica n s

3
t h a n in Ca u ca sia n s . It is e st im a ted

N
an d sh o w a p o sit ive A NA 1:80

O
th a t a bou t 300,000 Am erica n s h ave

I
(h o m o g e n e o u s p at t e rn ), n o rm al

T
SLE.

C
E
co m p le t e b lo o d co u n t , n o rm al

S
ch e m ist rie s, an d n o rm al u rin alysis. Do e s sh e h ave syst e m ic lu p u s PATHOGENESIS
e ryt h e m at o su s? Lu p u s a u t oa n t ib od ie s a re p re s e n t
for 5 t o 7 ye a rs be fore t h e clin ica l
on s e t of SLE occu rs . Th e re is a p olyge n ic ge n e t ic p r e d is p o s it io n , w it h a s
m a n y a s 100 ge n e s , m a n y a ffe ct in g in a m m a t ory p a t h w ays , s u ch a s HLA DR
a n d DQ a lle le s , in t e rfe ron , in t e rle u kin -6, a n d t h e glu cocort icoid re ce p t or p a t h -
w ay. Fe m a le h orm on e s a re a n ot h e r fa ct or in p a t h oge n e s is . Me n w it h SLE t e n d
t o be h yp oa n d roge n ic. Abn orm a l re s p on s e s t o com m on viru s e s , s u ch a s Ep s t e in
Ba rr viru s , m a y p la y a n in cit in g role (1 ). En viron m e n t a l p re cip it a n t s in clu d e
u lt raviole t ligh t , t rim e t h op rim /s u lfa , in fe ct ion s , s ilica , a n d m e rcu ry.

ORGAN MANIFESTATIONS
Be ca u s e SLE is a m u lt is ys t e m d is e a s e, m u lt ip le p re s e n t a t ion s a re p os s ible. Th e
m o s t co m m o n o rga n s in vo lve d a t p re s e n t a t io n a re cu t a n e o u s a n d m u s cu -
los ke le t a l.

Cuta ne o us Lupus
In SLE, t h e re ca n be a cu t e, s u ba cu t e, a n d ch ron ic s u bt yp e s of cu t a n e ou s lu p u s .
Acu t e cu t a n e ou s lu p u s is a p h ot os e n s it ive m a cu lop a p u la r in a m m a t ory ra s h .
Cla s s ica lly it is ca lle d a “m a la r ra s h ” if on t h e brid ge of t h e n os e a n d ch e e ks ,
bu t it ca n a ls o be on t h e “V” a re a of t h e ch e s t or on t h e fore a rm s . It is u s u a lly
103
 104 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

ra is e d a n d la s t s fo r d a ys t o m o n t h s . It m u s t b e d iffe re n t ia t e d fro m u s h e s /
CLINICAL POINTS blu s h e s , a cn e ros a ce a (w it h p u s t u le s ), s e borrh e a , s ola r u rt ica ria (w it h p ru rit u s ),
• SLE is b o t h m o re co m m o n a n d p olym orp h ou s ligh t e ru p t ion . In t h e ca s e p re s e n t a t ion , t h e re w e re p u s t u le s
a n d m o re se ve re in a n d a h is t ory of t ra n s ie n t ra s h : bot h w ou ld a rgu e a ga in s t lu p u s .
Africa n –Am e rica n s a n d Su ba cu t e cu t a n e ou s lu p u s e ryt h e m a t os u s (SCLE) ca n occu r in a n a n n u la r
Hisp a n ic–Am e rica n s t h a n form (t h a t m a y be m is t a ke n for a fu n ga l ra s h or Lym e d is e a s e ) or a p s oria form
in Ca u ca sia n s.
ra s h . SCLE ca n occu r w it h ou t SLE, a n d in m a n y ca s e s is ca u s e d or a ggrava t e d
• Mo st re d ch e e ks a re n o t by co m m o n ly u s e d m e d ica t io n s , in clu d in g h yd ro ch lo ro t h ia z id e , t e rb in a n e ,
t h e lu p u s m a la r ra sh . A s t a t in s , ca lciu m -ch a n n e l blo cke rs , ACE-in h ibit o rs , in t e rfe ron a lp h a a n d b e t a ,
lu p u s ra sh sh o u ld b e ra ise d
a n d sh o u ld p e rsist fo r d a ys
a n d TNF in h ibit ors (2 ).
t o w e e ks. Th e p re cip it a t in g Th e m os t com m on ch ron ic cu t a n e ou s lu p u s is d is coid lu p u s . It ca n occu r
u lt ra vio le t e xp o su re m a y w it h ou t SLE. On ly a bou t 5% of p a t ie n t s w it h d is coid lu p u s p rogre s s t o SLE. Dis -
h a ve b e e n d a ys b e fo re coid lu p u s is a s ca rrin g ra s h , u s u a lly on t h e s ca lp , e a rs , fa ce, a n d a rm s . It ca n
(ra t h e r t h a n im m e d ia t e ). be d is gu rin g, le a d in g t o s ca rrin g a lop e cia , a n d h yp o- a n d h yp e rp igm e n t a t ion .
SLE ca n a ls o ca u s e cu t a n e ou s va s cu lit is , p re s e n t in g a s p a lp a ble p u rp u ra or
(Co ntin u e d )
d igit a l ga n gre n e, bu t t h is is ra re.
S
MUSCULOSKELETAL LUPUS
E
C
T
Th e m a jorit y of SLE p a t ie n t s w ill h ave in a m m a t ory a rt h ra lgia s , m e a n in g join t
I
O
p a in w it h m orn in g s t iffn e s s , in t h e d is t ribu t ion of t h e s m a ll join t s of t h e h a n d s
N
(PIPs a n d MCPs ) a n d w ris t s , a n d , le s s com m on ly, la rge join t s . Th e re ca n be t ru e
3
S
s yn ovit is of t h e s e join t s . Eros ion s a re u n u s u a l. In s t e a d , SLE p a t ie n t s ca n d eve lop
p
e
Ja ccou d ’s a rt h rop a t h y, w it h re d u cible join t d e form a t ion d u e t o t e n d on a n d liga -
c
i
m e n t la xit y. Myos it is ca n occu r in SLE, bu t it is ra re. W h e n a p a t ie n t w it h SLE
c
R
h a s m u s cle p a in , t h e u s u a l ca u s e is brom ya lgia .
h
e
u
m
a
LUPUS NEPHRITIS
t
i
c
Lu p u s n ep h rit is p re s e n t s a s p rot e in u ria , h e m a t u ria , a n d s om e t im e s re d blood
D
i
s
ce ll ca s t s . It is s u bd ivid e d in t o m e s a n gia l, m e s a n gia l p rolife ra t ive, foca l, d iffu s e
e
a
p rolife ra t ive, m e m bra n ou s , a n d e n d -s t a ge s cle ros is . A re n a l biop s y is n e ce s s a ry
s
e
t o d e t e rm in e t h e In t e rn a t ion a l Socie t y of Nep h rology (ISN) cla s s , w h ich le a d s
s
t o im p or t a n t in form a t io n on p rogn o s is a n d t re a t m e n t . Diffu s e p rolife ra t ive
glom e ru lon ep h rit is (Cla s s IV) is t h e m os t like ly cla s s t o le a d t o re n a l fa ilu re.

HEMATOLOGIC LUPUS
CLINICAL POINTS (Con tin ue d )
SLE ca n a ffe ct a ll ce ll lin e s . Th e m os t com m on n d in g is le u kop e n ia a n d lym -
• SCLE m a y b e ca u se d o r
p h op e n ia . Pre d n is on e ca n ca u s e or w ors e n lym p h op e n ia . Us u a lly cyt op e n ia s
w o rse n e d b y co m m o n ly
u se d d ru g s. fro m lu p u s a re m ild a n d d o n ot re q u ire t re a t m e n t . Au t oim m u n e h e m olyt ic
a n e m ia is u s u a lly Coom bs p os it ive. Th e m os t fre q u e n t a n e m ia s fou n d in SLE
• Mu scle p a in in a n SLE
p a t ie n t s , h ow eve r, a re iron -d e cie n cy a n e m ia a n d t h e a n e m ia of ch ron ic d is -
p a t ie n t is u su a lly b ro m y-
a lg ia (n o t m yo sit is). e a s e (a ls o ca lle d t h e a n e m ia of ch ron ic in a m m a t ion ). Th rom bocyt op e n ia ca n
occu r d u e t o SLE, a s w e ll a s d u e t o a n t ip h os p h olip id a n t ibod ie s .
• Th e m o st fre q u e n t a n e m ia s
in SLE a re iro n -d e cie n cy
a n d t h e a n e m ia o f ch ro n ic
d ise a se /in a m m a t io n . SEROSITIS
SLE ca n ca u s e p le u ris y, p le u ra l e ffu s ion s , p e rica rd it is , p e rica rd ia l e ffu s ion , a n d
ra re ly, a s cit e s .

NEUROLOGIC LUPUS
SLE ca n le a d t o p s ych os is , s e izu re s , s t roke, com a , e n ce p h a lop a t h y, cra n ia l n e u -
rop a t h y, p e rip h e ra l n e u rop a t h y, m ye lit is , a n d m on on e u rit is m u lt ip le x (3 ). Th e
m os t com m on n e u rologic com p la in t , t h ou gh , is cogn it ive im p a irm e n t , t h a t ca n
occu r in 80% p a t ie n t s , 10 ye a rs a ft e r d ia gn os is (4 ).
 Ch a p te r 11 Sys t e m ic Lu p u s Eryt h e m a t os u s 105

CONSTITUTIONAL
Act ive SLE ca n le a d t o feve r, w e igh t los s , lym p h a d e n op a t h y, a n d s p le n om ega ly.
Alt h ou gh fa t igu e ca n be p a rt of a n a cu t e SLE a re, m os t ch ron ic fa t igu e in SLE
is n ot a s s ocia t e d w it h a ct ive lu p u s , bu t ra t h e r w it h brom ya lgia , d e con d it ion -
in g, d e p re s s ion , h yp ot h yroid is m , a n e m ia , a n d ot h e r com orbid it y.

Exa mina tio n

SKIN
Acu t e cu t a n e ou s lu p u s is a n e ryt h e m a t os u s m a cu lop a p u la r ra s h on t h e fa ce,
“V” a re a of t h e ch e s t , a n d fore a rm s (i.e., s u n e xp os e d a re a s ). Dis coid lu p u s (a
d e ep e r ra s h t h a t ca n ca u s e s ca rrin g) ca n be fou n d on t h e s ca lp , ju s t a bove t h e
eye brow s , in t h e e a rs , a n d on t h e p a la t e.
Ora l u lce rs ca n be fou n d on t h e bu cca l m u cos a a n d t h e t on gu e. Th ey ca n
be p a in fu l or p a in le s s . Na s a l u lce rs ca n a ls o occu r.
Th e h a ir in lu p u s is bot h t h in a n d fra gile. It t e n d s t o bre a k off a rou n d t h e
fra m e of t h e fa ce (lu p u s “frizzie s ”). Circu m s cribe d a re a s of t ot a l h a ir los s a re

s
e
m ore like ly d u e t o d is coid lu p u s (ca u s in g s ca rrin g a lop e cia ) or a lop e cia a re a t a .

s
a
SLE p a t ie n t s ca n h a ve live d o re t icu la r is , a vio la ce o u s m o t t lin g o f t h e

e
s
i
e xt re m it ie s . Th is ca n a ls o occu r from a n t ip h os p h olip id a n t ibod ie s .

D
c
i
t
a
m
HEAD

u
e
SLE p a t ie n t s w it h s e con d a ry Sjögre n ’s m a y h ave p a rot id e n la rge m e n t or eye or

h
R
m ou t h d ryn e s s .

c
i
c
e
p
S
NECK

3
SLE ca n ca u s e ce rvica l lym p h a d e n op a t h y, u s u a lly s m a ll in s ize. Th yroid e n la rge -

N
O
m e n t ca n occu r from a u t oim m u n e t h yroid d is e a s e.

I
T
C
E
S
CHEST
SLE ca n ca u s e re s t rict ive lu n g d is e a s e. Th is ca n le a d t o ba s ila r cra ckle s . Lu p u s
p le u ris y m a y ca u s e a p le u ra l ru b or p le u ra l e ffu s ion .

HEART
Pe rica rd it is ca n ca u s e a p e rica rd ia l ru b or d is t a n t h e a rt s ou n d s , if t h e re is la rge
p e rica rd ia l e ffu s io n . Pu lm on a ry h yp e r t e n s io n ca n ca u s e a n a cce n t u a t e d P2.
Act ive lu p u s ca u s e s t a ch yca rd ia . He a rt m u rm u rs a re ve ry com m on in SLE.

ABDOMEN
Ab d o m in a l s e ro s it is ca n ca u s e a s cit e s . Bu d d -Ch ia r i (fro m a n t ip h o s p h o lip id
a n t ibod ie s ) a ls o ca u s e s a s cit e s . SLE ca n ca u s e h ep a t os p le n om ega ly.

EXTREMITIES
Pe d a l e d e m a ca n be a s ign of lu p u s n e p h rit is or p u lm on a ry h yp e rt e n s ion . Ray-
n a u d ’s p h e n om e n on is com m on in SLE.

MUSCULOSKELETAL
Lu p u s ca n ca u s e t e n d e rn e s s or t ru e sw e llin g of t h e PIPs , MCPs , w ris t s , kn e e s ,
a n d a n kle s (bu t n ot t h e DIP join t s ). Te n d e rn e s s in m u s cle s is u s u a lly brom y-
a lgia , n ot lu p u s m yos it is . A p roxim a l m yop a t h y ca n occu r from cort icos t e roid s .
 106 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 11.1 ACR Classi cat ion Crit eria

Ma la r ra sh He m a t o lo g ic d iso rd e r
Disco id ra sh Im m u n o lo g ic d iso rd e r:
Ph o t o se n sit ivit y An t i-d sDNA
Ora l u lce rs An t i-Sm
Art h rit is Lu p u s a n t ico a g u la n t
Se ro sit is An t ica rd io lip in
Re n a l d iso rd e r Fa lse –p o sit ive t e st fo r syp h ilis
Ne u ro lo g ic d iso rd e r An t in u cle a r a n t ib o d y

NEUROLOGIC
SLE ca n ca u s e cra n ia l a n d p e rip h e ra l n e u rop a t h y, a n d lon git u d in a l m ye lit is .
An t ip h os p h olip id a n t ibod ie s ca n ca u s e s t roke.
S
E
C
Studie s
T
I
O
N
LABORATORY ASSESSMENT
3
S
Th e la b o ra t o ry a s s e s s m e n t t o d ia gn o s e SLE in clu d e s t h e t e s t s n e ce s s a ry t o
p
e
a s s e s s orga n in volve m e n t (com p le t e blood cou n t w it h d iffe re n t ia l, s e ru m cre -
c
i
a t in in e, u rin a lys is , u rin e p rot e in /cre a t in in e ra t io) bu t a ls o a ba t t e ry of s e rologic
c
R
t e s t s o f lu p u s a u t oa n t ib od ie s , in clu d in g ANA, a n t i-d s DNA, a n t i-Ro, a n t i-La ,
h
e
a n t i-Sm it h , a n t i-RNP, d ire ct Coom bs , a n t ip h os p h olip id a n t ibod ie s (lu p u s a n t i-
u
m
coa gu la n t a n d a n t ica rd iolip in ), C3, a n d C4.
a
t
i
c
Diag no sis o f SLE
D
i
s
Th e d ia gn os is of lu p u s is s t ill a n a rt . Th e re a re cla s s i ca t ion crit e ria for SLE,
e
a
w h ich ca n be h e lp fu l. Th e ACR Cla s s i ca t ion Crit e ria re q u ire s t h e p re s e n ce of
s
e
fou r of t h e e leve n crit e ria t o cla s s ify a p a t ie n t a s h a vin g SLE. Alt h ou gh n ot p e r-
s
fe ct , t h ey d o e m p h a s ize t h e m u lt is ys t e m n a t u re of t h e d is e a s e. ANA is n ot s u f-
cie n t t o d ia gn o s e lu p u s – m o s t p e o p le w it h a p o s it ive ANA a re n o rm a l. A
p a t ie n t w it h ANA a n d m u s cle p a in , for e xa m p le, like ly h a s brom ya lgia (n ot
lu p u s ) – a s in t h e ca s e p re s e n t a t ion (Ta ble 11.1 ).

PATIENT ASSESSMENT
• A t ru e p h o t o se n sit ive
ra sh sh o u ld b e ra ise d a n d
sh o u ld la st fo r d a ys t o
w e e ks a ft e r su n e xp o su re .
• Fib ro m ya lg ia is m u ch
m o re co m m o n t h a n lu p u s.
Are b ro m ya lg ia t e n d e r
p o in t s p re se n t ? Is t h e re
p ro lo n g e d m o rn in g
st iffn e ss in t h e sm a ll
jo in t s o f t h e h a n d s a n d
w rist s t o su g g e st in a m -
m a t o ry p o lya rt h ra lg ia ?
Clinica l Co urse
SLE is a b ou t e q u a lly d ivid e d in t o t h e “ a re p a t t e rn ”, in w h ich p a t ie n t s h a ve
e xa ce rba t ion s follow e d by im p rove m e n t , a n d “ch ron ic a ct ivit y”, in w h ich t h e re
is a lw ays s om e a ct ivit y. Re m is s ion , n ot re q u irin g p re d n is on e or im m u n os u p -
p re s s ive t re a t m e n t , is ve ry ra re.
Su rviva l in SLE h a s im p rove d s in ce t h e 1950s , bu t p la t e a u e d in t h e 1980s .
Ea rly in SLE, t h e m a jor ca u s e s of d e a t h a re a ct ive d is e a s e a n d in fe ct ion , w h e re a s ,
la t e r in SLE, t h e m a jor ca u s e of d e a t h is ca rd iova s cu la r d is e a s e (5 ).
Tre a tme nt
GENERAL MEASURES
SLE p a t ie n t s s h ou ld p ra ct ice s u n p rot e ct ion a n d u s e s u n s cre e n a s u lt raviole t
ligh t in cre a s e s SLE a re s . Be ca u s e of t h e h igh ris k of ca rd iova s cu la r d is e a s e, a
low fa t , low ch ole s t e rol d ie t is re com m e n d e d .
SLE in cre a s e s t h e ris k of in fe ct ion . Va ccin a t ion s fo r in u e n za ye a rly a n d
p n e u m o co ccu s eve ry 5 ye a r s a re re co m m e n d e d . On ly in a ct iva t e d va ccin e s
 Ch a p te r 11 Sys t e m ic Lu p u s Eryt h e m a t os u s 107

s h ou ld be u s e d if t h e SLE p a t ie n t is on p re d n is on e a n d /or im m u n os u p p re s s ive

NOT TO BE MISSED
• Hyd ro xych lo ro q u in e
sh o u ld b e p re scrib e d t o
a ll SLE p a t ie n t s, n o t ju st
t h o se w it h cu t a n e o u s
lu p u s a n d lu p u s a rt h rit is.
d ru gs .
SLE in cre a s e s t h e ris k of m a lign a n cy. Ge n e ra l gu id e lin e s s h ou ld be follow e d
in t e rm s of PAP s m e a rs , m a m m ogra m s , a n d colon os cop y.
SLE it s e lf, b u t a ls o s u n a vo id a n ce , in cre a s e s t h e r is k o f vit a m in D d e -
cie n cy. 25-h yd roxyvit a m in D leve ls s h ou ld be ch e cke d , a n d re p la ce m e n t p re -
s cribe d .
Os t e op e n ia a n d os t e op oros is a re com m on , d u e t o SLE it s e lf, bu t e s p e cia lly
d u e t o cort icos t e roid u s e. DEXA s ca n s a re re com m e n d e d eve ry 2 ye a rs , e s p e -
cia lly in SLE p a t ie n t s on cort icos t e roid s .

HYDROXYCHLOROQUINE
Hyd roxych loroq u in e s h ou ld be p re s cribe d t o a ll SLE p a t ie n t s . Th e d os e is 400
m g (200 m g t w ice d a ily) in a n a ve ra ge p e rs on , bu t t h e d os e s h ou ld n ot e xce e d
6.5 m g/kg, a n d s h ou ld be re d u ce d in re n a l in s u f cie n cy or re n a l fa ilu re. Hyd rox-
ych loroq u in e h e lp s cu t a n e ou s lu p u s a n d lu p u s a rt h rit is . It p reve n t s 50% of SLE
a re s (6 ), h e lp s t o p reve n t re n a l a n d n e u rologic lu p u s , im p rove s s u rviva l, a n d

s
e
im p rove s h yp e r lip id e m ia . Th e r is k o f re t in o p a t h y is o n e o u t o f 5,000 a ft e r

s
a
5 ye a rs of u s e.

e
s
i
D
c
NSAIDs

i
t
a
m
u
NSAIDs a re h e lp fu l for lu p u s a rt h rit is a n d s e ros it is . How eve r, t h ey s h ou ld n ot

e
h
be u s e d in p a t ie n t s w it h lu p u s n e p h rit is . Lon g-t e rm u s e m a y in cre a s e t h e ris k

R
c
of ca rd iova s cu la r d is e a s e. Ibu p rofe n m ay block t h e t h e ra p e u t ic e ffe ct of a s p irin .

i
c
e
p
S
PREDNISONE/ CORTICOSTEROIDS

3
N
Pre d n is on e le a d s t o 80% of p e rm a n e n t orga n d a m a ge a ft e r t h e d ia gn os is of SLE

O
(7 ). It s u s e s h ou ld be m in im ize d . A ch ron ic n e e d for p re d n is on e s h ou ld le a d t o

I
T
C
a re fe rra l t o a rh e u m a t ologis t , w h o ca n con s id e r t h e a d d it ion of s t e roid -s p a rin g

E
S
regim e n s . Mild /m od e ra t e lu p u s a re s m a y be t re a t e d w it h a “bu rs t ” of s t e roid s
(m e d rol d os e p a ck or on e t im e in t ra m u s cu la r t ria m cin olon e 100 m g) in s t e a d of
ch ron ic ora l s t e roid s . Seve re a re s m a y re q u ire “p u ls e ” t h e ra py w it h in t rave -
n ou s m e t h ylp re d n is olon e 1000 m g for 3 d ays , follow e d by ora l p re d n is on e. Th e
ris k of os t e on e cros is goe s u p d ra m a t ica lly w it h d os e s of ora l p re d n is on e of 20
m g or h igh e r.

IMMUNOSUPPRESSIVE DRUGS
Me tho tre xate
Me t h ot re xa t e is h e lp fu l for lu p u s a rt h rit is a n d cu t a n e ou s lu p u s . Dos e s a re u s u -
a lly be t w e e n 7.5 a n d 25 m g w e e kly, w it h d a ily fo lic a cid . Mon it or in g of t h e
com p le t e blood cou n t a n d live r fu n ct ion t e s t s is n e ce s s a ry. It ca n n ot be u s e d in
p regn a n cy.

Le uno mide
Le u n om id e is u s e d for lu p u s a rt h rit is a n d h a s s h ow n be n e t for lu p u s n e p h ri-
t is a s w e ll. Dos e s va ry from 10 t o 20 m g d a ily. Mon it orin g of t h e com p le t e blood
cou n t a n d live r fu n ct ion t e s t s is n e ce s s a ry. Mild h a ir los s ca n occu r. It ca n n ot
be u s e d in p regn a n cy.

Azathio prine
Aza t h iop rin e is a n im m u n os u p p re s s ive d ru g w it h broa d a p p lica bilit y in SLE.
Do s e s o f 1 m g t o 2 m g/ k g a re u s u a lly u s e d . Th io p u r in e m e t h ylt ra n s fe ra s e
(TPMT) t e s t in g is re com m e n d e d t o id e n t ify p a t ie n t s a t gre a t e r ris k of t oxicit y
 108 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

(cyt op e n ia s , live r fu n ct ion t e s t e leva t ion ). It ca n be u s e d in p regn a n cy w h e n

n e e d e d t o con t rol lu p u s a ct ivit y.

Myco phe no late Mo fe til

Mycop h e n ola t e m ofe t il h a s be e n w id e ly s t u d ie d in lu p u s n ep h rit is (8, 9 ), w h e re
it is e q u iva le n t t o cyclop h os p h a m id e in in d u ct ion t h e ra p y (a lt h ou gh s u p e rior
in n on -Ca u ca s ia n s ) (10 ) a n d s u p e rior t o a za t h iop rin e for m a in t e n a n ce t h e ra p y.
Mon it orin g of com p le t e blood cou n t a n d live r fu n ct ion t e s t s is n e e d e d . It ca n -
n ot be u s e d in p regn a n cy.

Cyclo pho sphamide

Cyclop h os p h a m id e w a s w id e ly u s e d for lu p u s n ep h rit is , bu t w it h a h igh p rice
in t e rm s o f t ox icit y (p re m a t u re ova ria n fa ilu re , in fe ct io n s , a n d la t e r m a lig-
n a n cy). Mycop h e n ola t e m ofe t il is n ow t h e rs t ch oice for lu p u s n e p h rit is , w it h
s o m e p o s s ible e x ce p t io n s (s u ch a s ra p id ly p rogre s s ive glo m e r u lo n e p h rit is ).
Cyclo p h o s p h a m id e is s t ill u s e d fo r re fra ct o ry lu p u s n e p h rit is a n d fo r CNS-
lu p u s . It is u s u a lly give n a s a n in t rave n ou s “p u ls e ” m on t h ly (750 m g/m 2 BSA) a s
a n in d u ct io n t h e ra p y fo r 6 m o n t h s , a n d s o m e t im e s co n t in u e d a s a m a in t e -
S
E
n a n ce t h e ra p y q u a rt e rly for u p t o 2 m ore ye a rs .
C
T
I
O
Hig h Do se Cyclo pho sphamide
N
High d os e cyclop h os p h a m id e (200 m g/kg ove r 4 d ays ) w a s n ot s u p e rior t o t h e
3
S
u s u a l m on t h ly in t ra ve n ou s cyclop h os p h a m id e regim e n in a clin ica l t ria l (11 ). It
p
e
is u s e d a s a s a lva ge t h e ra py for SLE p a t ie n t s fa ilin g a ll ot h e r t h e ra p ie s , w it h or
c
i
w it h ou t a u t ologou s s t e m ce ll t ra n s p la n t a t ion (12 ).
c
R
h
e
u
BIOLOGICS
m
a
Rituximab
t
i
c
Rit u xim a b, a m on oclon a l a n t ib od y d ire ct e d a ga in s t CD20 o n B ce lls , w a s n ot
D
i
s
s u p e rior t o s t a n d a rd of ca re for n on re n a l lu p u s or t o m ycop h e n ola t e m ofe t il for
e
a
re n a l lu p u s . How eve r, it h a s be e n e ffe ct ive in s t u d ie s of p a t ie n t s w it h h e m a t o-
s
e
logic lu p u s , CNS-lu p u s , a n d ca t a s t rop h ic a n t ip h os p h olip id a n t ibod y s yn d rom e.
s
Be limumab
Be lim u m a b is t h e rs t FDA-a p p rove d t re a t m e n t for SLE in 50 ye a rs . It t a rge t s
t h e B lym p h ocyt e s t im u la t or p rot e in (BLyS), a grow t h fa ct or for B ce lls . In Ph a s e
3 clin ica l t ria ls , it le d t o a 10% t o 14% im p rove m e n t ove r s t a n d a rd of ca re in t h e
Sys t e m ic Lu p u s Re s p on d e r In d e x, re d u ce d a re s , le d t o a gre a t e r re d u ct ion in
p re d n is on e (a n d le s s n e e d for in cre a s e d p re d n is on e ), re d u ce d a n t i-d s DNA, a n d
in cre a s e d com p le m e n t (13 ).

WHEN TO REFER
• To co n rm d ia g n o sis
• Be fo re in st it u t in g
co rt ico st e ro id s
• If t h e p a t ie n t re q u ire s
m o re t h a n 7.5 m g o f
p re d n iso n e
• To e va lu a t e p ro t e in u ria
• Fo r a ra sh n o t re sp o n sive
t o h yd ro xych lo ro q u in e
• Fo r CNS sym p t o m a t o lo g y
• Fo r d ysp n e a
ANTIPHOSPHOLIPID ANTIBODIES
Abou t 50% of SLE p a t ie n t s m ay h ave a n a n t ip h os p h olip id a n t ibod y (lu p u s a n t i-
coa gu la n t , a n t ica rd iolip in , or a n t i-be t a 2 glycop rot e in I). Th e s e a n t ibod ie s ca u s e
h yp e rco a gu la b ilit y a n d in cre a s e p re gn a n cy lo s s . Pro p h yla ct ic t h e ra p y w it h
a s p irin (81 m g) a n d h yd rox ych lo ro q u in e is re com m e n d e d . Us e of e s t roge n ,
SERMs , a n d t h a lid om id e s h ou ld be a void e d , a s t h ey in cre a s e t h e ris k of t h rom -
b os is . If a n SLE p a t ie n t w it h a n t ip h o s p h o lip id a n t ibo d ie s h a s a t h rom b ot ic
eve n t , t h e n a n t icoa gu la t ion (w it h a t a rge t INR of 2 t o 3) is re com m e n d e d life -
lon g (14 ).
SJÖGREN’S SYNDROME
Te n p e rce n t of SLE p a t ie n t s w ill d eve lop Sjögre n ’s s yn d rom e. On ly a bou t h a lf of
p a t ie n t s w it h s e con d a ry Sjögre n ’s w ill h ave Sjögre n ’s a u t oa n t ibod ie s (a n t i-Ro
 Ch a p te r 11 Sys t e m ic Lu p u s Eryt h e m a t os u s 109

or a n t i-La ). Th e d ia gn os is ca n be con rm e d w it h t h e Sch irm e r’s t e s t or e q u iva -

le n t d ocu m e n t a t ion . For eye d ryn e s s , Re s t a s is (cyclos p orin e ) eye d rop s a re re c-
om m e n d e d . For eye a n d m ou t h d ryn e s s , Evoxa c (cevim e lin e ) 30 m g t h re e t im e s
a d a y ca n be h e lp fu l.

CARDIOVASCULAR RISK FACTORS

Be ca u s e t h e m a jo r la t e ca u s e o f d e a t h in SLE is ca rd iova s cu la r d is e a s e , it
is e s s e n t ia l t o co n t r o l t ra d it io n a l ca rd iova s cu la r r is k fa ct o r s . Lu p u s it s e lf
c a n in c r e a s e h y p e r t e n s io n a n d h y p e r lip id e m ia , d u e t o lu p u s n e p h r it is .
Pr e d n is o n e in cr e a s e s h yp e r t e n s io n , h yp e r lip id e m ia , d ia b e t e s m e llit u s , a n d
o b e s it y (15 ).

ICD9

s
710.0 Lupus

e
s
695.4 d isco id (lo cal)

a
e
695.4 e ryt h e m at o d e s (d isco id ) (lo cal)

s
i
D
695.4 e ryt h e m at o su s (d isco id ) (lo cal)

c
i
710.0 d isse m in at e d

t
a
m
710.0 syst e m ic

u
710.0 [583.81] n e p h rit is

e
h
R
710.0 [580.81] acu t e

c
710.0 [582.81] ch ro n ic

i
c
583.9 Ne phritis, ne phritic (alb u m in u ric) (az o t e m ic) (co n g e n it al) (d e g e n -

e
p
e rat ive ) (d iff u se ) (d isse m in at e d ) (e p it h e lial) (f am ilial) (f o cal) (g ran u lo -

S
3
m at o u s) (h e m o rrh ag ic) (in f an t ile ) (n o n su p p u rat ive , e xcre t o ry) (u re m ic)

N
710.0 [583.81] lu p u s

O
I
T
710.0 [580.81] acu t e

C
E
710.0 [582.81] ch ro n ic

S
714.4 p o st rh e u m at ic, ch ro n ic (Jacco u d ’s)

Re fe re nce s
1. Ha rley JB, Ja m e s JA. Ep s t e in -Ba rr viru s in fe ct ion m ay be a n e n viron m e n t a l ris k fa ct or for s ys t e m ic lu p u s
e ryt h e m a t os u s in ch ild re n a n d t e e n a ge rs [le t t e r]. A rthritis Rheum 1999 ;42 (8 ):1782 –1783 .
2. Ca lle n JP. Dru g-in d u ce d s u ba cu t e cu t a n e ou s lu p u s e ryt h e m a t os u s . Lupus 19 (9 ):1107 –1011 .
3. Ha n ly JG, Urow it z MB, Su L, , e t a l. Pros p e ct ive a n a lys is of n e u rop s ych ia t ric eve n t s in a n in t e rn a t ion a l
d is e a s e in cep t ion coh ort of SLE p a t ie n t s . A nn Rheum Dis 2010;69(3):529–535 .
4. Brey RL, Hollid ay SL, Sa kla d AR, e t a l. Ne u rop s ych ia t ric s yn d rom e s in SLE: Preva le n ce u s in g s t a n d a rd ize d
d e n it ion s in t h e Sa n An t on io St u d y of Ne u rop s ych ia t ric Dis e a s e Coh ort . Neurology 2002 ;58 :1214 –1220 .
5. Urow it z MB, Gla d m a n DD, Abu -Sh a kra M , e t a l . Mor t a lit y s t u d ie s in s ys t e m ic lu p u s e ryt h e m a t os u s .
Re s u lt s from a s in gle ce n t e r. III. Im p rove d s u rviva l ove r 24 ye a rs . J Rheum atol 1997;24 (6 ):1061 –1065 .
6. Ca n a d ia n Hyd roxych loro q u in e St u d y Grou p . A ra n d om ize d s t u d y of t h e e ffe ct of w it h d raw in g h yd roxy-
ch loroq u in e s u lfa t e in s ys t e m ic lu p u s e ryt h e m a t os u s . N Engl J Med. 1991 ;324 :150 –154 .
7. Gla d m a n DD, Urow it z MB, Ra h m a n P, e t a l . Accru a l of orga n d a m a ge ove r t im e in p a t ie n t s w it h s ys t e m ic
lu p u s e ryt h e m a t os u s . J Rheum atol 2003;30 (9 ):1955 –1959 .
8. Gin zle r EM , Dooley MA, Ara n ow C, e t a l. Mycop h e n ola t e m ofe t il or in t rave n ou s cyclop h os p h a m id e fo r
lu p u s n ep h rit is . N Engl J Med 2005;353 (21 ):2219 –2228 .
9. Con t re ra s G, Pa rd o V, Le cle rcq B, e t a l. Se q u e n t ia l t h e ra p ie s for p rolife ra t ive lu p u s n ep h rit is . N Engl J Med
2004;350 (10 ):971 –980 .
10. Ap p e l GB, Con t re ra s G, Dooley MA, e t a l. Mycop h e n ola t e m ofe t il ve rs u s cyclop h os p h a m id e for in d u ct ion
t re a t m e n t of lu p u s n ep h rit is . J A m Soc Nephrol 2009 ;20 (5 ):1103 –1112 .
11. Pe t ri M , Bro d s ky RA, Jon e s RJ, Gla d s t on e D, Filliu s M , Ma gd e r LS . High d os e Cyclop h os p h a m id e ve rs u s
Mon t h ly In t ra ve n ou s Cyclop h o s p h a m id e fo r Sys t e m ic Lu p u s Eryt h e m a t os u s : A p ros p e ct ive Ra n d -
om ize d Tria l . A rthritis Rheum 2010 ;62 :1487 –1493 .
 110 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

12. Bu r t RK, Tra yn or A, St a t ku t e L, e t a l. Non m ye loa bla t ive h e m a t op oie t ic s t e m ce ll t ra n s p la n t a t ion for
s ys t e m ic lu p u s e ryt h e m a t os u s . J A m er Med A ssoc 2006 ;295 :527 –535 .
13. Nava rra SV, Gu zm á n RM , Ga lla ch e r AE, e t a l. Ef ca cy a n d s a fe t y of be lim u m a b in p a t ie n t s w it h a ct ive
s y s t e m ic lu p u s e r y t h e m a t o s u s : a ra n d o m is e d , p la ce b o -co n t r o lle d , p h a s e 3 t r ia l . Lancet 2011 ;
377 (9767):721–731 .
14. Crow t h e r MA, Gin s be rg JS, Ju lia n J, e t a l. A co m p a ris on of t w o in t e n s it ie s of w a rfa rin for t h e p reve n t ion
of re cu rre n t t h rom bos is in p a t ie n t s w it h t h e a n t ip h os p h olip id a n t ibod y s yn d rom e . N Engl J Med 2003 ;
349 (12 ):1133 –1138 .
15. Pe t ri M , La ka t t a C, Ma gd e r L, e t a l . Effe ct of p re d n is on e a n d h yd roxych loroq u in e on coron a ry a rt e ry
d is e a s e ris k fa ct ors in s ys t e m ic lu p u s e ryt h e m a t os u s : a lon git u d in a l d a t a a n a lys is . A m J Med 1994 ;96 :
254 –259 .
S
E
C
T
I
O
N
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S
p
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CHAPTER
12 Ra yna ud’s Phenomenon
a nd Systemic Sclerosis
Laura B. Hughes and Barri Fessler

A 42-ye ar-o ld m an
Ra yna ud’s
Phe no me no n

s
p re se n t s co m p lain in g

e
s
INTRODUCTION

a
o f sw o lle n h an d s.

e
s
i
Rayn a u d ’s p h en om en on (RP) is a n

D
His n g e rs t u rn b lu e

c
exa ggera t ed va s osp a s tic resp on s e

i
t
an d w h it e , an d are

a
t o cold tem p era tu re or em ot ion a l

m
asso ciat e d w it h p ain s tress . First d e scribed by Ma u rice

u
e
h
w h e n e xp o se d t o Rayn a u d in 1862 it is ch a ra ct e r-

R
ized by in term it ten t a cra l ble a ch -

c
co ld t e m p e rat u re s.

i
in g, fo llow e d by cya n o s is a n d

c
He n o t e s h e art b u rn

e
e ryt h rod erm a . Th e t yp ica l t ricolor

p
S
an d t h e se n sat io n s e q u e n ce is d rive n by va s ocon -

3
N
o f f o o d st ick in g s trict ion of d igita l a rteries (w h ite

O
p h a s e ), d e cre a s e d blood ow in

I
in h is e so p h ag u s.

T
C
ca p illa r ie s a n d ve n u le s (b lu e

E
Exam in at io n re ve als d iff u se ly e d e m at o u s h an d s w it h sk in t h ick e n in g

S
p h a s e ), fo llow e d by r e a ct ive
aff e ct in g t h e n g e rs. Nail-f o ld m icro sco p y sh o w s d ilat e d lo o p s w it h h yp e re m ia (re d p h a s e ). Po p u la -
are as o f d ro p o u t (Fig . 12.1). t ion -ba s e d s u rveys e s t im a t e t h e
p r e va le n ce o f RP in w o m e n
be t w e e n 6% a n d 20% a n d m e n
betw een 3% a n d 12.5% (1 ).

CLINICAL PRESENTATION AND EXAMINATION

Figure 12.1 Skin thickening of both ha nds. Pa llor of the 2nd, 3rd, a nd 4th
digits of the right ha nd.
Ra yn a u d ’s p h e n o m e n o n o ccu r s a s a p r im a ry (n o t
a s s ocia t e d w it h a n u n d e rlyin g d is e a s e ) or s e con d a ry
s yn d rom e (a s s ocia t e d w it h a n u n d e rlyin g d is e a s e ) (2 ).
Th e d is t in ct ion be t w e e n p rim a ry a n d s e con d a ry RP is
im p o r t a n t a s t h e ir p a t h o p h ys io logy d iffe rs , a n d t h e
p rogn os is , s eve rit y, a n d t re a t m e n t m a y a ls o d iffe r (3 ).
Prim a ry RP is ch a ra ct e rize d by t h e follow in g d ia gn os -
t ic cr it e r ia : a d e n it e h is t ory o f s ym m e t ric e p is od ic
a t ta cks of a cra l p a llor or cya n os is ; a bs en ce of p e rip h e ra l
va s cu la r d is e a s e ; a bs e n ce of t is s u e n e cros is ; n orm a l
n a il-fold ca p illa ry e xa m in a t ion ; a n ega t ive a n t in u cle a r
a n t ibod y (ANA) t e s t ; a n d a n or m a l e ryt h rocyt e s e d i-
m e n t a t ion ra t e (4 ). Pa t ie n t s w it h p rim a ry RP oft e n a re
yo u n ge r a n d h a ve m in im a l p a in w it h a t t a ck s . In
p a t ie n t s w it h s e con d a ry RP, t h e cou rs e is oft e n m ore

111
112 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
CLINICAL POINTS
• Ra yn a u d ’s p h e n o m e n o n
m a y o ccu r a s a p rim a ry
(i.e ., n o t a sso cia t e d w it h
a n u n d e rlyin g d ise a se ) o r
se co n d a ry syn d ro m e (i.e .,
a sso cia t e d w it h a n u n d e rly-
in g d ise a se ); m a kin g t h is
d ist in ct io n is im p o rt a n t
b e ca u se p ro g n o sis d iffe rs.
• Th e d ia g n o sis o f RP is
m a d e clin ica lly; n o t e st s
a re n e e d e d .
• Scle ro d e rm a m a y b e a
syst e m ic o r lo ca lize d
d ise a se . Th e m o st co m m o n
fo rm s o f SSc a re t h e d iffu se
a n d lim it e d su b t yp e s t h a t
a re d ist in g u ish e d o n t h e
b a sis o f t h e e xt e n t o f skin
t h icke n in g .
• Lim it e d scle ro d e rm a
t yp ica lly d e ve lo p s o ve r
se ve ra l d e ca d e s; d iffu se
scle ro d e rm a e vo lve s ra p id ly
o ve r 1 t o 2 ye a rs.
s eve re a n d fre q u e n t ly re s u lt s in is ch e m ic ch a n ge s a n d d igit a l u lce ra t io n (4 ).
Ma n y con n e ct ive t is s u e d is e a s e s a re a s s ocia t e d w it h s e con d a ry RP, m os t n ot a -
bly s ys t e m ic s cle ros is (SSc), w h e re it is oft e n t h e in it ia l m a n ife s t a t ion . It m a y
a ls o o ccu r in s ys t e m ic lu p u s e ryt h e m a t o s u s (SLE), m yos it is , Sjö gre n ’s s yn -
d rom e, rh e u m a t oid a rt h rit is , m ixe d con n e ct ive t is s u e d is e a s e, va s cu lit is , a n d
u n d iffe re n t ia t e d con n e ct ive t is s u e d is e a s e . Se con d a ry RP ca n a ls o o ccu r in
n on in a m m a t ory con d it ion s in clu d in g h a n d –a rm vibra t ion s yn d rom e, t h ora cic
ou t le t s yn d rom e, occlu s ive va s cu la r d is e a s e s (e.g., a rt e rios cle ros is , a t h e roe m -
boli, t h rom boa n giit is oblit e ra n s ), h e m a t ologic d is e a s e s (e.g., p a ra p rot e in e m ia ,
cryoglobu lin e m ia , cryo brin oge n e m ia , cold a gglu t in in d is e a s e, p olycyt h e m ia ),
a n d from m e d ica t ion s (e .g., a m p h e t a m in e s , be t a -blocke rs , coca in e, n icot in e,
a n t in e op la s t ic a ge n t s ) (5 ).
Clin ica l clu e s t o s u gge s t s e con d a ry RP in clu d e la t e r a ge of on s e t , a s ym m e t ric
n ge r in volve m e n t , in t e n s e p a in , t is s u e n e cros is , s ign s or s ym p t om s of a n ot h e r
d is e a s e (e.g., a lop e cia , ra s h , s icca s ym p t om s , ora l u lce rs , p h ot os e n s it ivit y, s kin
t h icke n in g, a rt h ra lgia s , d ys p n e a , ga s t roe s op h a ge a l re u x d is e a s e (GERD), m u s -
cle w e a kn e s s ), a n d a bn orm a l n a il-fold ca p illa ros copy (5 ). Na il-fold ca p illa rie s
ca n b e e x a m in e d t h ro u gh a d ro p o f o il u s in g a n o p h t h a lm o s co p e s e t a t 40
d iop t e r s . Th e p re s e n ce of e n la rge d o r t o r t u o u s ca p illa ry loo p s s u gge s t s a n
u n d e rlyin g con n e ct ive t is s u e d is e a s e , w h e re a s t h e s e n d in gs in a s s ocia t io n
w it h ca p illa ry d rop ou t a re m ore s u gge s t ive of SSc.
If a t h orou gh h is t ory a n d p h ys ica l e xa m in a t ion , in clu d in g n a il-fold ca p il-
la ros cop y, reve a ls lit t le evid e n ce for a n u n d e rlyin g d is e a s e, a clin ica l d ia gn os is
of p rim a ry RP ca n be m a d e. If t h e re is clin ica l s u s p icion of a s e con d a ry ca u s e,
or a n a bn orm a l n a il-fold ca p illa ry p a t t e rn is obs e rve d , s e rologic t e s t in g s h ou ld
be p e rform e d , in clu d in g a n ANA a n d e ryt h rocyt e s e d im e n t a t ion ra t e. An a bn or-
m a l n a il-fold ca p illa ry p a t t e rn in a p a t ie n t w it h RP h a s be e n fou n d t o be t h e
be s t p re d ict or of a n eve n t u a l d is e a s e t ra n s it ion t o s e con d a ry RP. Eleva t e d t it e rs
of ANA a n t ibod ie s in clu d in g a n t ice n t rom e re, a n t in u cle ola r, or a n t i-ScL70 a n t i-
bod ie s , in a p a t ie n t w it h RP, s u gge s t t h e p re s e n ce of—or eve n t u a l d eve lop m e n t
of—a n u n d e rlyin g con n e ct ive t is s u e d is e a s e.
STUDIES
Ra yn a u d ’s p h e n om e n on is a clin ica l d ia gn os is . If s e con d a ry ca u s e s a re s u s -
p e ct e d , a n eva lu a t ion t o a s s e s for a t h e ros cle rot ic d is e a s e is in d ica t e d a s w e ll
a s for a n u n d e rlyin g con n e ct ive t is s u e d is ord e r, in clu d in g s e rologie s for SLE,
Sjögre n ’s s yn d rom e, a n d a n a u t oim m u n e m yos it is .
TREATMENT
Tre a t m e n t ch oice s for RP d e p e n d on t h e s eve rit y of t h e con d it ion a n d t h e p re s -
e n ce of a n u n d e rlyin g d is e a s e . Th e goa ls of t h e ra p y a re t o im p rove q u a lit y of
life a n d p reve n t t is s u e in ju ry. In p a t ie n t s w it h p rim a ry RP, a con s e rva t ive , n on -
p h a r m a co lo gic a p p ro a ch is m o s t im p o r t a n t , a lt h o u gh m e d ica t io n s m a y b e
n e ce s s a ry. Ge n e ra l e d u ca t io n rega rd in g t h e d is e a s e it s e lf a s w e ll a s t h e u s e o f
n o n p h a rm a co logic life s t yle m o d i ca t io n s is re co m m e n d e d . Avo id in g u n n e c-
e s s a ry cold e xp os u re or s u d d e n t e m p e ra t u re ch a n ge s s u ch a s m ovin g from a
h o t e n viro n m e n t t o a n a ir-co n d it io n e d ro o m is e s s e n t ia l. Pa t ie n t s s h o u ld
u n d e rs t a n d t h a t t h e e n t ire bod y a n d n ot ju s t t h e d igit s s h ou ld be ke p t w a rm .
St ra t e gie s s u ch a s w e a r in g t h e r m a l u n d e r w e a r, h a t s , s ca r ve s , a n d in s u la t e d
foot w e a r h e lp ke e p t h e bod y w a rm . Th e d igit s s h ou ld be p rot e ct e d from cold
w it h glove s a n d / or h a n d w a rm e rs . Pa t ie n t s s h ou ld a void m e d ica t ion s t h a t p ro-
m o t e va s o con s t rict ion , s u ch a s d e con ge s t a n t s , a m p h e t a m in e s , be t a -blocke rs ,
a n d ca ffe in e. Sim ila rly, s m okin g ce s s a t ion is a ls o re com m e n d e d be ca u s e n ico-
t in e is va s ocon s t rict ive. Ph ys ica l m a n e u ve rs t h a t p rom ot e va s od ila t ion in t h e
d igit s ca n a ls o be t a u gh t t o le s s e n t h e s eve rit y of a n a t t a ck, in clu d in g rot a t in g
 Ch a p te r 12 Rayn a u d ’s Ph e n om e n on a n d Sys t e m ic Scle ros is 113

t h e a rm s in a w in d m ill p a t t e rn a n d p la cin g t h e h a n d s in w a rm w a t e r or in a
w a r m b o d y fo ld (s u ch a s t h e a x illa ). If t h e s e m e a s u re s fa il t o im p rove t h e
q u a n t it y a n d /or s eve rit y of a t t a cks , t h e re a re a n u m be r of p h a rm a cologic t h e r-
a p ie s t h a t ca n be in it ia t e d . Ca lciu m ch a n n e l blocke rs a re t h e m os t w id e ly u s e d
cla s s o f d ru gs fo r t h e t re a t m e n t o f RP. Am o n g t h e d iffe re n t cla s s e s of ca lciu m
ch a n n e l blo ck e rs , t h e d ih yd rop yrid in e gro u p h a s b e e n t h e m os t e ffe ct ive, w it h
d os e s of n ife d ip in e ra n gin g from 30 t o 180 m g d a ily or a m lod ip in e from 5 t o
20 m g d a ily. Th e lon g-a ct in g or s low -re le a s e p rep a ra t ion s a re ge n e ra lly p re fe rre d
a s t h ey a re be t t e r t ole ra t e d a n d a ch ieve a m ore s u s t a in e d re s p on s e. If a p a t ie n t
h a s a s u b o p t im a l re s p o n s e t o m a x im u m -d o s e ca lciu m ch a n n e l blo cke rs , t h e
a d d it io n o f a d ire ct va s o d ila t or —s u ch a s t op ica l n it roglyce r in —ca n be u s e d .
In d ire ct va s od ila t ors h a ve a ls o be e n eva lu a t e d , in clu d in g a n giot e n s in con ve rt -
in g e n zym e (ACE) in h ibit ors (e.g., e n a la p ril, ca p t op ril), a n giot e n s in II re ce p t or
a n t a go n is t s (e .g., lo s a r t a n ), a n d s e le ct ive s e rot on in re u p t a ke in h ibit or s (e .g.,
u ox e t in e ). Mo re re ce n t ly, p h o s p h o d ie s t e ra s e t yp e 5 in h ibit o rs (e.g., s ild e n a l,
t a d a la l, va rd e n a l) h a ve be e n u s e d for p a t ie n t s w it h s eve re RP w it h d igit a l
is ch e m ia . Bo s e n t a n , a n e n d o t h e lin 1 re ce p t o r a n t a go n is t , h a s d e m o n s t ra t e d
s u cce s s in t re a t in g d igit a l u lce rs in p a t ie n t s w it h s cle ro d e rm a a n d s e co n d a ry

s
e
RP. Pra zos in , a s ym p a t h olyt ic a ge n t , a n d p e n t oxyp h illin e, a p h os p h o d ie s t e ra s e

s
a
in h ib it o r, h a ve a ls o b e e n re p o r t e d t o im p rove RP s ym p t o m s . Digit a l o r t h o ra cic

e
s
i
s ym p a t h e ct o m y o r in t ra ve n o u s p ro s t a gla n d in in fu s io n s (e .g., ilo p ro s t , e p o -

D
c
p ros t e n o l) ca n be u t iliz e d in p a t ie n t s w it h RP w h o a re re fra ct o ry t o ora l m e d i-

i
t
a
ca l t h e ra p y, t yp ica lly in t h e a cu t e s e t t in g w h e re t h e re is cr it ica l d igit a l is ch e m ia .

m
Low -d o s e a s p ir in h a s a ls o b e e n r e c o m m e n d e d in p a t ie n t s w it h d igit a l

u
e
is ch e m ia .

h
R
c
i
c
CLINICAL COURSE

e
p
S
Pa t ie n t s w it h p rim a ry RP a re u n like ly t o d eve lop p rogre s s ion of t h e ir d is e a s e or

3
d a m a ge d igit a l is ch e m ia . Ed u ca t ion a bou t t h e n a t u re of RP a n d in s t ru ct ion in

N
O
n on p h a rm a cologic m e a s u re s ca n o ft e n re d u ce t h e fre q u e n cy a n d s eve rit y o f

I
T
a t t a cks a n d im p rove q u a lit y of life. Pa t ie n t s w it h s e con d a ry RP, e s p e cia lly t h os e

C
E
w it h SSc, a re m ore like ly t o d eve lop d igit a l u lce rs a n d t is s u e is ch e m ia . Re fe rra l

S
t o a rh e u m a t ologis t is re com m e n d e d for p a t ie n t s w it h s e con d a ry RP or d if cu lt -
t o-t re a t p rim a ry RP.

Syste mic Scle ro sis

INTRODUCTION
Scle rod e rm a is a ge n e ra l t e rm t h a t re fe rs t o cu t a n e ou s bros is . It m a y be s u b-
d ivid e d in t o t w o m a jor ca t egorie s : s ys t e m ic s cle ros is (SSc, a ls o re fe rre d t o a s
s ys t e m ic s cle rod e rm a ) a n d loca lize d s cle rod e rm a . Th e m os t com m on form s of
SSc a re lim ited scleroderm a a n d diffuse scleroderm a , w h ich a re d iffe re n t ia t e d by
t h e e xt e n t of s kin t h icke n in g. Lim it e d s cle rod e rm a (p reviou s ly re fe rre d t o a s
“CREST” s yn d ro m e ) is d e n e d a s s kin t h icke n in g t h a t a ffe ct s o n ly t h e e xt re m -
it ie s d is t a l t o t h e e lbow s a n d /or kn e e s . Diffu s e s cle rod e rm a is d e n e d a s s kin
t h icke n in g p roxim a l t o t h e e lbow s a n d /or kn e e s in a d d it ion t o d is t a l e xt re m it y
in vo lve m e n t a n d t r u n ca l in vo lve m e n t . Th e fa ce m a y b e in vo lve d in b o t h
lim it e d a n d d iffu s e s cle ro d e rm a . In a d d it io n t o s k in , s ys t e m ic in vo lve m e n t
a ffe ct in g t h e va s cu la t u re , ga s t ro in t e s t in a l (GI) t ra ct , lu n gs , h e a rt , join t s , a n d
kid n eys is fre q u e n t ly s e e n in bot h t h e form s of s cle rod e rm a . Cu t a n e ou s bro-
s is m a y a ls o occu r in a localiz ed form of s cle rod e rm a (n ot t o b e con fu s e d w it h
t h e lim ited form ), w h ich in clu d e s m orp h e a (on e or m o re p a t ch e s of t h icke n e d
s kin ), lin e a r s cle rod e rm a (a lin e of t h icke n e d s kin u s u a lly a ffe ct in g a n e xt re m -
it y), a n d s cle rod e rm a en cou p de sabre (lin e a r s cle rod e rm a a ffe ct in g t h e fore -
h e a d a n d fa ce ). Th e re is u s u a lly n o vis ce ra l o rga n in vo lve m e n t in p a t ie n t s w it h
lo ca liz e d s cle ro d e r m a . Fin a lly, p a t ie n t s m a y d eve lo p in t e r n a l o rga n b ro s is
 114 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

a lon g w it h s cle rod e rm a -s p e ci c a n t ibod ie s bu t in t h e a bs e n ce of s kin t h icke n -

in g; t h is s yn d rom e is re fe rre d t o a s scleroderm a sine scleroderm a a n d is ve ry ra re.
Th e e t iology of SSc is u n kn ow n , bu t be lieve d t o be m u lt ifa ct oria l, in volvin g
ge n e t ic p re d is p os it ion a n d e n viron m e n t a l e x p os u re s . Mon ozygot ic a n d d izy-
got ic t w in s t u d ie s h a ve s h ow n a low ra t e of d is e a s e con cord a n ce. On ly 1.6% of
p a t ie n t s w it h SSc h a ve a rs t -d e gre e re la t ive w it h t h e d is e a s e, s u gge s t in g a
s m a ll ge n e t ic con t ribu t ion t o d is e a s e s u s ce p t ibilit y. Th e ris k of ot h e r a u t oim -
m u n e d is e a s e s —s u ch a s SLE a n d rh e u m a t oid a rt h rit is —is in cre a s e d in rs t -
d e gre e re la t ive s of p a t ie n t s w it h SSc. Th e re is s om e evid e n ce t h a t lin ks SSc
w it h e xp os u re s t o s ilica , vin yl ch lorid e, a n d orga n ic s olve n t s ; h ow eve r, a n e n vi-
ron m e n t a l e xp os u re is n ot a p p a re n t in t h e m a jorit y of p a t ie n t s .
Th e t yp ica l a ge of o n s e t of SSc is 30 t o 50 ye a rs . It is m ore com m o n in
w om e n t h a n m e n (3–5:1). Th e in cid e n ce of SSc in t h e Un it e d St a t e s ra n ge s from
9 t o 19 ca s e s p e r m illion . Preva le n ce e s t im a t e s ra n ge from 28 t o 286 ca s e s p e r
m illion p op u la t ion .
Th e re a re t h re e fu n d a m e n t a l p a t h ologica l p roce s s e s t h a t e xp la in t h e m a jor-
it y of clin ica l a n d la bora t ory m a n ife s t a t ion s s e e n in SSc. Excessiv e deposition of
collagen in t h e s kin a n d in t e rn a l orga n s re s u lt s in s kin t h icke n in g, p u lm on a ry
S
E
bros is , a n d GI d ys m ot ilit y. A n on in a m m a t ory vasculopathy con t rib u t e s t o
C
T
Ra yn a u d ’s p h e n o m e n o n (RP), p u lm o n a ry a rt e ria l h yp e rt e n s io n (PAH), s cle ro-
I
O
d e rm a re n a l cris is (SRC), a n d ga s t ric a n t ra l va s cu la r e ct a s ia (GAVE). Fin a lly, alter-
N
ations in cellular a n d hum oral im m unity a re m a n ife s t e d by p rod u ct ion of a u t oa n -
3
S
t ibod ie s in clu d in g a n t ice n t rom e re, a n t i-SCL70 (a n t i-DNA t op ois om e ra s e 1), a n d
p
e
a n t i-RNA p olym e ra s e III a n t ibod ie s .
c
i
c
R
h
CLINICAL PRESENTATION AND EXAMINATION
e
u
m
Th e t e m p o of d is e a s e e xp re s s ion d iffe rs be t w e e n t h e t w o m a jor form s of SSc:
a
t
lim it e d SSc t yp ica lly d eve lop s ove r m a n y d e ca d e s , w h e re a s d iffu s e SSc ra p id ly
i
c
evolve s ove r 1 t o 2 ye a rs . Rayn a u d ’s p h e n om e n on , d is cu s s e d a bove, is u s u a lly
D
i
s
t h e rs t m a n ife s t a t ion of SSc, p re ce d in g t h e d eve lop m e n t of ot h e r clin ica l fe a -
e
a
t u re s by m on t h s t o ye a rs . In p a t ie n t s w it h lim it e d SSc, RP m a y be p re s e n t for 20
s
e
s
t o 30 ye a rs be fore t h e on s e t of s kin t h icke n in g. In p a t ie n t s w it h d iffu s e SSc, RP
u s u a lly d eve lop s con com it a n t ly w it h t h e s kin t h icke n in g or w it h in a ye a r of t h e
cu t a n e ou s ch a n ge s . Th e h a llm a rk of SSc is s kin in volve m e n t . In it ia lly t h e s kin
PATIENT ASSESSMENT
be com e s p ru rit ic a n d t h e e xt re m it ie s be com e d iffu s e ly sw olle n a n d e ryt h e m a -
• Na il-fo ld ca p illa ro sco p y is t ou s . As colla ge n is d e p os it e d , t h e s kin be com e s in d u ra t e d a n d t h icke n e d . Th e
h e lp fu l in d ist in g u ish in g n ge rs begin t o t a p e r a s t h ey bros e (ca lle d “s cle rod a ct yly”) a n d d igit a l e xion
p rim a ry RP fro m se co n d a ry co n t ra ct u re s m a y d eve lo p a s t h e s k in b e co m e s p rogre s s ive ly t a u t . Th e s k in
RP. t h icke n in g s t a rt s d is t a lly a ffe ct in g t h e h a n d s a n d fe e t a n d p rogre s s e s p roxi-
• If t h e re is clin ica l su sp icio n m a lly. Th e fa ce, ch e s t , a bd om e n , a n d ba ck m ay a ls o be a ffe ct e d . Are a s of s p ot t y
fo r se co n d a ry ca u se o f RP h yp op igm e n t a t ion a n d h yp e rp igm e n t a t ion (“s a lt a n d p ep p e r” a p p e a ra n ce ) m ay
o n t h e b a sis o f h ist o ry a n d / d eve lop in p a t ie n t s w it h d a rk s kin . Te la n gie ct a s ia s a re m ore com m on ly s e e n on
o r p h ysica l e xa m in a t io n ,
t h e h a n d s a n d fa ce of p a t ie n t s w it h lim it e d SSc. Ca lciu m d ep os it s (ca lcin os is
se ro lo g ic t e st in g sh o u ld b e
p e rfo rm e d . cu t is ) m ay occu r in t h e h a n d s , e lbow s , kn e e s , a n d legs , a n d a re u s u a lly a la t e
m a n ife s t a t ion of SSc, s e e n m ore fre q u e n t ly in lim it e d d is e a s e. Th e s u bcu t a n e -
• Skin b io p sie s a re n o t
ou s ca lciu m d ep os it s m a y e ru p t t h rou gh t h e s kin , le a d in g t o d ra in a ge t h a t ca n
m a n d a t o ry fo r d ia g n o sis
o f SSc, b u t t h e y m a y h e lp be m is t a ke n for in fe ct ion . Te n d on frict ion ru bs m ay be p a lp a t e d in t h e w ris t s ,
ru le o u t o t h e r d ia g n o se s. e lbow s , kn e e s , a n d a n kle s . Ulce ra t ion s ove r t h e n ge rt ip s , kn u ckle s , or e lbow s
be ca u s e of s kin t h icke n in g, va s cu la r in s u f cie n cy, a n d t ra u m a m a y d eve lop ,
• If one of the SSc-associated
autoantibodies is present ca u s in g s ign i ca n t m orbid it y.
(e.g., anticentromere, anti- Ga s t roin t e s t in a l in volve m e n t is p re s e n t in u p t o 90% of p a t ie n t s a n d is t h e
SCL70, anti-RNA polymerase s e con d m os t com m on orga n a ffe ct e d follow in g s kin in volve m e n t . Es op h a ge a l
III), it is helpful in con rm- h yp o m o t ilit y a n d in co m p e t e n ce o f t h e low e r e s o p h a ge a l s p h in ct e r ca u s in g
ing the diagnosis, but not
d ys p h a gia a n d GERD is com m on , a n d m ay re s u lt in t h e d eve lop m e n t of s t ric-
all patients with SSc have
one of these antibodies. t u re s , Ba rre t t ’s e s op h a gu s , a n d / or a s p ira t ion . Ga s t rop a re s is a n d d ys m ot ilit y,
w h ich m a y occu r t h rou gh ou t t h e GI t ra ct , a re d u e t o a t rop h y of s m oot h m u s cle
 Ch a p te r 12 Rayn a u d ’s Ph e n om e n on a n d Sys t e m ic Scle ros is 115

a n d bros is in t h e gu t w a ll. Ba ct e ria l ove rgrow t h in t h e s m a ll bow e l, m a la b-

s o rp t io n , p s e u d o -o b s t r u ct io n , a n d GAVE (w a t e rm e lo n s t o m a ch ) a re fre q u e n t
com p lica t ion s . Prim a ry bilia ry cirrh os is occu rs in 2% t o 8% of p a t ie n t s w it h SSc
w it h lim it e d d is e a s e.
Pu lm on a ry d is e a s e is n ow t h e m a jor ca u s e o f m ort a lit y in p a t ie n t s w it h
SSc. Th e t w o m a jor clin ica l m a n ife s t a t ion s a re p u lm on a ry bros is a n d p u lm o-
n a ry a rt e ria l h yp e rt e n s io n , t h e form e r t yp ica lly o ccu rrin g in 75% o f p a t ie n t s
w it h d iffu s e d is e a s e a n d t h e la t t e r in a p p roxim a t e ly 50% of p a t ie n t s w it h lim -
it e d d is e a s e. How eve r, t h e s e con d it ion s a re n ot m u t u a lly e xclu s ive. Pa t ie n t s
w it h e xt e n s ive p u lm on a ry bros is ca n d eve lop PAH, a n d p a t ie n t s w it h PAH ca n
d eve lop m ild p u lm on a ry bros is . Dys p n e a on e xe rt ion m ay be a cu t e or in s id i-
ou s . As p ira t ion p n e u m on ia a n d p u lm on a ry h e m orrh a ge m ay a ls o be s e e n . Ca r-
d ia c d is e a s e con s is t in g of a rrh yt h m ia s , p e rica rd ia l e ffu s ion s , or h e a rt fa ilu re
m ay occu r a n d is a s s ocia t e d w it h a p oor p rogn os is . (9 )
Scle rod e rm a re n a l cris is u s e d t o be t h e m o s t co m m on ca u s e of d e a t h in
p a t ie n t s w it h SSc p rior t o t h e in t rod u ct ion of ACE in h ibit ors . It t yp ica lly occu rs
in t h e s e t t in g of ra p id ly p rogre s s ive s kin t h icke n in g in a p a t ie n t w it h d iffu s e
d is e a s e ; it is a ls o a s s ocia t e d w it h a n t i-RNA p olym e ra s e III a n t ibod ie s a n d a h is -

s
e
t ory of a n t e ce d e n t h igh -d os e cort icos t e roid u s a ge. Th e m a n ife s t a t ion s in clu d e

s
a
m a lign a n t h yp e rt e n s ion p re s e n t in 90% of p a t ie n t s , a lon g w it h a ris in g cre a t i-

e
s
i
n in e a n d m icroa n giop a t h ic h e m olyt ic a n e m ia a n d t h rom bocyt op e n ia . Norm o-

D
c
t e n s ive SRC occu rs in 10% of p a t ie n t s .

i
t
a
Mu s cu lo s ke le t a l in vo lve m e n t in clu d e s a r t h ra lgia s , n o n e ro s ive a r t h r it is ,

m
join t con t ra ct u re s be ca u s e of re s t rict ion of m ot ion from s kin t h icke n in g, t e n -

u
e
d on frict ion ru bs , m yop a t h y, a n d com p re s s ion n e u rop a t h ie s . Bon e re s orp t ion of

h
R
t h e d igit a l t u ft s (ca lle d a cro-os t e olys is ) d eve lop s be ca u s e of ch ron ic va s cu la r

c
i
in s u f cie n cy a n d is ch e m ia . Ca rp a l t u n n e l s yn d rom e or u ln a r n e u rop a t h y m a y

c
e
be s e e n be ca u s e of com p re s s ion from cu t a n e ou s bros is .

p
S
3
N
O
STUDIES

I
T
C
Th e re a re s eve ra l a u t oa n t ibod ie s t h a t ca n be obs e rve d in p a t ie n t s w it h SSc;

E
S
h ow eve r, 40% t o 50% of p a t ie n t s d o not h ave on e of t h e s e a n t ibod ie s . Th e re fore
if a n a n t ibod y is p re s e n t , it is h e lp fu l in e s t a blis h in g t h e d ia gn os is a n d p re d ict -
in g t h e p rogn os is , bu t it is n ot e s s e n t ia l for t h e d ia gn os is . Th e ce n t rom e re p a t -
t e rn on ANA t e s t in g (a ls o ca lle d a n t ice n t rom e re a n t ibod ie s ) is a s s ocia t e d w it h
lim it e d SSc, PAH, a n d s eve re RP w it h is ch e m ia . Th e n u cle ola r p a t t e rn on ANA
t e s t in g is a ls o a s s ocia t e d w it h SSc. An t i-DNA t op ois om e ra s e 1 (a ls o kn ow n a s
a n t i-ScL70) a n t ibod ie s a re a s s ocia t e d w it h d iffu s e SSc a n d p u lm on a ry bros is .
An t ibod ie s t o RNA p olym e ra s e III a re a s s ocia t e d w it h a n in cre a s e d ris k of SRC
a n d d e cre a s e d in cid e n ce of lu n g d is e a s e (6 ,10 ).
In co n t ra s t t o m a n y ot h e r a u t o im m u n e d is e a s e s , a cu t e -p h a s e re a ct a n t s
(e .g., e ryt h rocyt e s e d im e n t a t ion ra t e , C-re a ct ive p rot e in ) a re n o t e leva t e d in
SSc. If t h ey a re e leva t e d , a s e a rch for a con com it a n t con d it ion —s u ch a s in fe c-
t ion , m a lign a n cy, or a n ot h e r in a m m a t ory d is e a s e —is w a rra n t e d . An e m ia of
ch ron ic d is e a s e is fre q u e n t ly s e e n in SSc; if iron -d e cie n cy a n e m ia is n ot e d , GI
eva lu a t ion for blood los s is in d ica t e d .
Th e d ia gn os is of SSc is e s t a blis h e d on t h e ba s is of a com bin a t ion of ch a r-
a ct e ris t ic s ym p t om s , p h ys ica l n d in gs , s p e ci c s e rologie s , a n d s om e t im e s s kin
biop s ie s . Th e p u blis h e d cla s s i ca t ion crit e ria (u s e d for e n rollin g p a t ie n t s in t o
clin ica l t ria ls in t h e p a s t ) con s is t of a m a jor crit e rion (p roxim a l s cle rod e rm a )
a n d t w o or m ore m in or crit e ria (s cle rod a ct yly, d igit a l p it t in g s ca rs or los s of
s u bs t a n ce from t h e n ge r p a d , a n d biba s ila r p u lm on a ry bros is ). Th e s e crit e ria
a re in a d e q u a t e be ca u s e t h ey om it t h e m a jorit y of p a t ie n t s w it h lim it e d SSc a n d
d o n o t in co rp o ra t e SSc-a s s ocia t e d a n t ibo d ie s ; t h e re fo re , t h ey a re cu r re n t ly
be in g revis e d (7 ). Cu t a n e ou s bros is is n ot s p e ci c t o SSc; t h e re a re s eve ra l ot h e r
bros in g d is ord e rs t h a t h a ve be e n d e s cribe d , in clu d in g n ep h roge n ic bros in g
116 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
NOT TO BE MISSED
• Ma le g e n d e r, o ld a g e ,
a sym m e t ric n g e r
in vo lve m e n t , t issu e
n e cro sis, a n d a b n o rm a l
n a il-fo ld m icro sco p y
a re clu e s t h a t su g g e st
se co n d a ry RP.
• Pu lm o n a ry m a n ife st a t io n s
o f SSc (i.e ., p u lm o n a ry
b ro sis a n d p u lm o n a ry
h yp e rt e n sio n ) a re a
sig n i ca n t ca u se o f
m o rt a lit y a n d m o rb id it y;
t h e re fo re , scre e n in g w it h
p u lm o n a ry fu n ct io n t e st s
(PFTs), e ch o ca rd io g ra p h y,
a n d h ig h -re so lu t io n ch e st
co m p u t e d t o m o g ra p h y
(CT; if in d ica t e d ) is ve ry
im p o rt a n t .
• Acute onset of hypertension
m a y h e ra ld SRC; p ro m p t
t re a t m e n t w it h ACE
in h ib it o rs im p ro ve s
o u t co m e .
d e r m o p a t h y, e o s in o p h ilic fa s ciit is , s cle re d e m a , a n d s cle ro m yx e d e m a , a n d
s h ou ld a lw ays be con s id e re d in t h e d iffe re n t ia l d ia gn os is . His t ory (e.g., a p a t ie n t
w it h re n a l fa ilu re w h o w a s e xp os e d t o ga d olin iu m d u rin g m a gn e t ic re s on a n ce
im a gin g), p h ys ica l e xa m in a t ion n d in gs (e.g., a bs e n ce of s kin t h icke n in g on t h e
h a n d s , a bs e n ce of RP), a n d la bora t ory t e s t in g (e.g., e leva t e d t h yroid -s t im u la t in g
h or m on e, m on o clon a l ga m m op a t h y on s e ru m p ro t e in e le ct ro p h o re s is ) m a y
h e lp t o e lu cid a t e ot h e r e t iologie s for s kin t h icke n in g.
TREATMENT
Th e m a n a ge m e n t of SSc is t a rge t e d t o s p e ci c orga n m a n ife s t a t ion s be ca u s e
t h e re is n o e ffe ct ive t h e ra p y t h a t t re a t s t h e u n d e rlyin g d is e a s e p roce s s . To d a t e,
n o m e d ica t ion h a s be e n d e m on s t ra t e d t o m a ke a s u bs t a n t ia l, clin ica lly s ign i -
ca n t im p a ct on s kin bros is ; h ow eve r, m e d ica t ion s s u ch a s m e t h ot re xa t e a n d
m ycop h e n ola t e m ofe t il a re u s e d in s e le ct p a t ie n t s be ca u s e of m od e s t e ffe ct s
d e m on s t ra t e d in s t u d ie s . In t e re s t in gly, s kin t h icke n in g in p a t ie n t s w it h d iffu s e
SSc w ill s t a rt t o s p on t a n e ou s ly regre s s a ft e r 2 t o 5 ye a rs of d is e a s e ; h ow eve r,
t h e in t e rn a l m a n ife s t a t ion s d o n ot s p on t a n e ou s ly im p rove a n d a ct u a lly m a y
con t in u e t o w ors e n ove r t im e. Give n t h e a lm os t u n ive rs a l p re s e n ce of GERD in
p a t ie n t s w it h SSc, a ll p a t ie n t s s h ou ld be t re a t e d w it h p rot on p u m p in h ibit ors
(e.g., om ep ra zole, p a n t op ra zole ) a s e s op h a ge a l d is e a s e m a y be s u bclin ica l, a n d
t re a t m e n t m a y h e lp t o p reve n t s t rict u re s , d eve lop m e n t of Ba rre t t ’s e s op h a gu s ,
a n d a s p ira t ion p n e u m on it is . Prom ot ilit y a ge n t s (e.g., e ryt h rom ycin , m e t oclo-
p ra m id e, or d om p e rid on e ) m a y be h e lp fu l in p a t ie n t s w it h ga s t rop a re s is , a n d
t re a t m e n t w it h rot a t in g a n t ibiot ics is u s e fu l in p a t ie n t s w it h ba ct e ria l ove r-
grow t h . Fre q u e n t ly, p a t ie n t s w it h SSc los e w e igh t a n d m ay re q u ire s u p p le m e n -
t a l ora l or p a re n t e ra l n u t rit ion . In p a t ie n t s fou n d t o h ave a ct ive in t e rs t it ia l lu n g
d is e a s e, cyclop h os p h a m id e is u s e d ; w h e t h e r a za t h iop rin e or m ycop h e n ola t e
m ofe t il a re u s e fu l in t h e t re a t m e n t of SSc-a s s ocia t e d in t e rs t it ia l lu n g d is e a s e
(ILD) is cu rre n t ly u n d e r in ve s t iga t ion . Scle rod e rm a re n a l cris is is t re a t e d w it h
ACE in h ibit ion a n d blood p re s s u re con t rol. Th e role of ACE in h ibit ors for p rop h -
yla xis a ga in s t SRC is u n kn ow n . Th e re is a s t ron g a s s ocia t ion of cort icos t e roid
u s a ge w it h s u b s e q u e n t d eve lo p m e n t o f SRC; t h e re fo re , s t e ro id u s e in SSc
s h o u ld b e m in im ize d o r a vo id e d co m p le t e ly. Alt h o u gh PAH u s e d t o b e u n i-
form ly fa t a l w it h in 1 t o 2 ye a rs , t h e re a re n ow n u m e rou s m e d ica t ion s t h a t h e lp
t o p rolon g s u rviva l a n d im p rove q u a lit y of life, in clu d in g e n d ot h e lin re cep t or
a n t a gon is t s (e .g., bos e n t a n , a m bris e n t a n ), p h os p h od ie s t e ra s e in h ibit ors (e.g.,
s ild e n a l, t a d a la l), a n d p ro s t a cyclin a n a lo gu e s (e .g., e p o p ro s t e n o l, t re p ro s -
t in il). An y p a t ie n t w it h SSc w it h PAH s h ou ld be follow e d by a p u lm on a ry h yp e r-
t e n s ion s p e cia lis t for op t im u m a s s e s s m e n t a n d t re a t m e n t . Pa t ie n t s w it h SSc
s h o u ld b e e n co u ra ge d t o e x e rcis e a n d / o r p a rt icip a t e in p h ys ica l t h e ra p y t o
in cre a s e e xibilit y, s t re n gt h , a n d e xe rcis e ca p a cit y. In a d d it ion , a t t e n t ion s h ou ld
be p a id t o t h e p re s e n ce of m ood d is ord e rs a s d e p re s s ion is com m on be ca u s e of
t h e a lt e re d s e lf-im a ge, fru s t ra t ion be ca u s e of los s of h a n d d e xt e rit y, m u s cle
w e a kn e s s , a n d ch ron ic p a in . Cou n s e lin g a n d p s ych ia t ric t re a t m e n t s h ou ld be
e n cou ra ge d , if in d ica t e d . In a d d it ion , s u p p ort grou p s ca n p rovid e e m ot ion a l
s u p p ort t o p a t ie n t s a n d t h e ir fa m ilie s (8 ).
CLINICAL COURSE
Scre e n in g fo r re s t r ict ive lu n g d is e a s e a n d p u lm o n a ry va s cu la r d is e a s e in
p a t ie n t s w it h SSc—con s is t in g of p u lm on a ry fu n ct ion t e s t s a n d a n e ch oca rd io-
gra m (w it h s p e cia l a t t e n t ion t o t h e righ t s id e of t h e h e a rt a n d p u lm on a ry a rt e ry
p re s s u re )—s h ou ld be p e rform e d a t d ia gn os is for ba s e lin e m e a s u re m e n t a n d a t
le a s t a n n u a lly t h e re a ft e r, m ore fre q u e n t ly (eve ry 3–6 m on t h s ) if t h e p a t ie n t h a s
ra p id ly p rogre s s ive s k in d is e a s e o r is s ym p t o m a t ic. If t h e PFTs s u gge s t a n
u n d e rlyin g re s t rict ive lu n g d is e a s e, a h igh -re s olu t ion CT of t h e lu n gs s h ou ld be

WHEN TO REFER
• If SSc is su sp e ct e d , p a t ie n t s
sh o u ld b e re fe rre d t o a
rh e u m a t o lo g ist fo r
co n rm a t io n o f d ia g n o sis,
a sse ssm e n t o f o rg a n
in vo lve m e n t , a n d t re a t -
m e n t p la n .
• Pa t ie n t s w it h SSc sh o u ld
b e re fe rre d fo r a n n u a l PFT
a n d e ch o ca rd io g ra p h y.
• If p u lm o n a ry h yp e rt e n sio n
is su sp e ct e d t h e n a ll
p a t ie n t s sh o u ld b e
re fe rre d t o a p u lm o n a ry
h yp e rt e n sio n sp e cia list fo r
co n rm a t io n b y rig h t -
h e a rt ca t h e t e riza t io n .
Ch a p te r 12 Rayn a u d ’s Ph e n om e n on a n d Sys t e m ic Scle ros is 117
p e rform e d t o d e t e rm in e if t h e re is evid e n ce of p a re n ch ym a l in a m m a t ion a n d /
or bros is ; t h e d is t in ct ion is im p ort a n t be ca u s e on ly in a m m a t ion is t re a t a ble
a n d reve rs ible. Pu lm on a ry fu n ct ion t e s t s ca n a ls o s u gge s t t h e p re s e n ce of p u l-
m on a ry va s cu la r d is e a s e if t h e re is a n is ola t e d re d u ct ion in d iffu s ion ca p a cit y
o f t h e lu n g for ca r bon m on ox id e (DLCO) w it h p re s e r va t io n of lu n g vo lu m e s
(Force d Vit a l Ca p a cit y (FVC)/DLCO ra t io .1.6). If t h e e ch oca rd iogra m a n d /or PFTs
s u gge s t p u lm on a ry va s cu la r d is e a s e, a righ t -h e a rt ca t h e t e riza t ion s h ou ld be
p e rform e d t o d e t e rm in e if PAH is p re s e n t . Tre a t m e n t for PAH s h ou ld n ot be
ba s e d on e s t im a t e d p u lm on a ry a rt e ry (PA) p re s s u re on e ch oca rd iogra m be ca u s e
t h e re a re s ign i ca n t fa ls e -n ega t ive ra t e s (in e a rly PAH) a n d fa ls e -p os it ive ra t e s
(in p u lm on a ry bros is ). Se ru m cre a t in in e a n d u rin a lys is s h ou ld be m on it ore d
q u a rt e rly. Pa t ie n t s s h ou ld be e n cou ra ge d t o ch e ck t h e ir blood p re s s u re s eve ra l
t im e s a w e e k a t h om e e s p e cia lly if t h ey h ave ra p id ly p rogre s s ive d iffu s e s kin
d is e a s e or a re a n t i-RNA p olym e ra s e III p os it ive.
ICD9
s
e
Raynaud’s
s
a
443.0 d ise ase o r syn d ro m e (p aro xysm al d ig it al cyan o sis)
e
s
Scle ro sis, scle ro tic
i
D
710.1 syst e m ic (p ro g re ssive )
c
i
t
a
Scle ro de rma, scle ro de rmia (acro scle ro t ic)
m
(d iff u se ) (g e n e raliz e d ) (p ro g re ssive )
u
e
710.1 (p u lm o n ary)
h
R
701.0 circu m scrib e d
c
701.0 lin e ar
i
c
e
701.0 lo caliz e d (lin e ar)
p
S
778.1 n e w b o rn
3
N
O
I
T
C
E
Re fe re nce s
S
1. Fra e n k e l L. Ra yn a u d ’s p h e n o m e n o n : Ep id e m io logy a n d r is k fa ct o r s . Cu rr Rheum atol Rep 2002 ;4 (2 ):
123 –128 .
2. Rich t e r JG, Sa n d e r O, Sch n e id e r M , e t a l . Dia gn os t ic a lgorit h m for Rayn a u d ’s p h e n om e n on a n d va s cu la r
s kin le s ion s in s ys t e m ic lu p u s e ryt h e m a t os u s . Lupus 2010 ;19 (9 ):1087 –1095 .
3. Ba ks t R, Me rola JF, Fra n ks AGJ, e t a l. Rayn a u d ’s p h e n om e n on : Pa t h oge n e s is a n d m a n a ge m e n t . J A m A cad
Derm atol 2008 ;59 (4 ):633 –653 .
4. Le Roy EC, Me d s ge r TA, Jr . Ra yn a u d ’s p h e n om e n o n : A p rop o s a l fo r cla s s i ca t io n . Clin Ex p Rheum atol
1992 ;10 (5 ):485 –488 .
5. Block JA, Se q u e ira W. Rayn a u d ’s p h e n om e n on . Lancet 2001 ;357 (9273 ):2042 –2048 .
6. Pe re ra A, Fe rt ig N , Lu ca s M , Me d s ge r TA, Jr . Clin ica l s u bs e t s , s kin t h ickn e s s p rogre s s ion ra t e a n d s e ru m
a n t ibo d y leve ls in s ys t e m ic s cle ro s is p a t ie n t s w it h a n t i-t o p o is o m e ra s e I a n t ib od y. A rthritis Rheu m
2007 ;56 :2740 –2746 .
7. Hu d s on M , Frit zle r MJ, Ba ron M ; Ca n a d ia n Scle rod e rm a Re s e a rch Grou p . Sys t e m ic s cle ros is ; e s t a blis h in g
d ia gn os t ic crit e ria . Medicine (Baltim ore) 2010 ;89 (3 ):159 –165.
8. Kh a n n a D, De n t on CP. Evid e n ce -ba s e d m a n a ge m e n t of ra p id ly p rogre s s ive s ys t e m ic s cle ros is . Best Pract
Res Clin Rheum atol 2010 ;24 (3 ):387 –400 .
9. Tyn d a ll AJ, Ba n n e rt B, Von k M , e t a l. Ca u s e s a n d ris k fa ct ors for d e a t h in s ys t e m ic s cle ros is : A s t u d y from
t h e EULAR Scle rod e rm a Tria ls a n d Re s e a rch (EUSTAR) d a t a ba s e . A nn Rheum Dis 2010 ;69 (10 ):1809 –1815.
10. Glid d on AE, Dore CJ, Du n p h y J, e t a l . An t in u cle a r a n t ibod ie s a n d clin ica l a s s ocia t ion s in a Brit is h Coh ort
w it h lim it e d cu t a n e ou s s ys t e m ic s cle ros is . J Rheum atol, 2011 :38 (4 ):702 –705 .
 CHAPTER
13 In ammatory
Myopathies: Polymyositis,
Derma tomyositis, a nd
Rela ted Conditions
Irene Z . W hitt and Frederick W . Miller
S
E
C
T
I
O
N
3
Clinica l Pre se nta tio n
S
p
A p re vio u sly h e alt h y
e
c
In a m m a t o ry m yop a t h ie s a re d is -
54-ye ar-old librarian com es
i
c
e a s e s ch a ra ct e r iz e d by a cq u ire d
R
t o t h e clin ic co m p lain in g m u s cle in a m m a t io n . Th is t e r m
h
e
o f “t ire d an d so re arm s e n co m p a s s e s a la rge n u m b e r o f
u
m
an d le g s” f o r t h e p re vio u s d is ord e rs t h a t in clu d e vira l, fu n ga l,
a
t
i
a n d p a ra s it ic in fe ct ion s of m u s cle,
c
7 w e e k s. Th is cam e o n
D
t oxic m yop a t h ie s , a n d ot h e r ca u s e s
i
s
g rad u ally af t e r a cru ise
e
o f m u s c le d a m a g e . W h e n t h e
a
t o t h e Carib b e an , w h ile
s
a p p r o p r ia t e c lin ic a l, la b o r a t o r y,
e
s
p layin g g o lf in t h e su n a n d p a t h o logic s t u d ie s e lim in a t e
k n ow n ca u s e s o f m u s cle in a m -
all d ay, b u t sh e h as co n -
m a t io n , a d ia gn o s is o f id io p a t h ic
t in u e d t o g e t w e ak e r, t o t h e p o in t t h at sh e n e e d s h e lp g e t t in g in a m m a t o ry m yo p a t h y (IIM) ca n
in an d o u t o f h e r b at h t u b an d h as d if cu lt y re ach in g h ig h sh e lve s be m a d e (1 ). Id iop a t h ic in a m m a -
at w o rk . De sp it e avo id in g t h e su n sin ce t h e cru ise e n d e d , sh e h as t ory m yop a t h y is ve ry ra re, w it h a n
in cid e n ce o f a p p ro x im a t e ly 9 t o
a f ain t , p e rsist e n t “su n b u rn ” o n h e r h an d s an d k n e e s. Sh e is
12 ca s e s / m illio n / ye a r. It t yp ica lly
f at ig u e d an d h as d if cu lt y w it h b re at h in g w h ile g o in g u p st airs. m a n ife s t s e it h e r in you n g ch ild re n
Sh e h as n o t ice d m o re h e art b u rn t h an u su al, an d so m e t im e s so lid or in a d u lt s in t h e ft h d e ca d e of
f o o d “co m e s b ack u p .” Sh e d e n ie s t ak in g an y illicit d ru g s, h as h ad life , t h o u gh it ca n p re s e n t a t a n y
a ge. Wom e n a re m ore a ffe ct e d t h a n
n o m e d icat io n ch an g e s re ce n t ly, an d d rin k s w in e o n ly o ccasio n ally.
m e n (2 ).
Lo o k in g at h e r ch art , yo u n o t e t h at sh e h as h ad a n o rm al t h yro id - Th e t h re e m o s t co m m o n
st im u lat in g h o rm o n e an d e le ct ro lyt e p an e l in t h e p ast 1 ye ar, fo r m s o f IIM a r e p o ly m yo s it is
b u t sh e d id n o t g e t t h e m am m o g ram , Pap an ico lao u sm e ar, o r (PM) a n d in clu s io n b o d y m yo s it is
(IBM), w h e r e in fla m m a t io n is
co lo n o sco p y yo u h ad re co m m e n d e d .
fo u n d in m u lt ip le m u s c le s , a n d
d e r m a t o m yo s it is (DM), in w h ich
in a m m a t o ry ch a n ge s o ccu r in t h e s k in a s w e ll a s m u s cle s . In PM a n d DM,
in a m m a t io n is a ls o fr e q u e n t ly s ys t e m ic, a n d o ccu r s in o t h e r o rga n s s u ch
a s t h e jo in t s , lu n gs , h e a r t , o r ga s t r o in t e s t in a l (GI) t ra ct . Th is in a m m a t io n
m a n ife s t s a s d ire ct o rga n in lt ra t io n by m o n o n u cle a r ce lls , fr e q u e n t im m u n e
a b n o r m a lit ie s , a n d t h e p r o d u ct io n o f a u t o a n t ib o d ie s . Th is , in a d d it io n t o a
118
 Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s
CLINICAL POINTS
• Id io p a t h ic in a m m a t o ry
m yo p a t h y is a d ia g n o sis
o f e xclu sio n , a n d t h e
d iffe re n t ia l d ia g n o sis
ca n b e ch a lle n g in g .
• Sym m e t ric p ro xim a l m u scle
w e a kn e ss p re d o m in a t e s; a
g o o d fu n ct io n a l a sse ssm e n t
o f t h e p a t ie n t is re q u ire d
in o rd e r t o d ist in g u ish t ru e
w e a kn e ss fro m p a in t h a t
lim it s fu n ct io n .
• Ra sh e s in DM ca n b e
su b t le , a n d m o st a re n o t
p a t h o g n o m o n ic.
• Pa t ie n t s m a y h a ve clin ica l
w e a kn e ss b e fo re o r in t h e
a b se n ce o f e le va t e d m u scle
e n zym e s; a m u scle b io p sy
is re q u ire d in m o st ca se s
fo r d e n it ive d ia g n o sis,
e sp e cia lly in p a t ie n t s w it h -
o u t t h e p a t h o g n o m o n ic
ra sh o f DM.
• Ca n ce r h a s b e e n a sso cia t e d
w it h IIM, e sp e cia lly DM;
a g e -a p p ro p ria t e ca n ce r
scre e n in g sh o u ld b e
p e rfo rm e d . Wo m e n w it h
IIM sh o u ld b e e va lu a t e d
fo r o va ria n ca n ce r.
NOT TO BE MISSED
A Diffe re ntial Diag no sis o f
Muscle We akne ss o r Pain
Nonin ammatory
Myopathies
• En d o crin e (h yp o - a n d
h yp e rt h yro id ism ,
a cro m e g a ly, d ia b e t e s,
Cu sh in g ’s syn d ro m e ,
Ad d iso n ’s d ise a se , h yp o -
a n d h yp e rp a ra t h yro id ism ,
hypocalcemia, hypokalemia)
• To xic (e t h a n o l,
co rt ico st e ro id s, co ca in e ,
st a t in s, b ra t e s)
• Me t a b o lic (a cid m a lt a se
d e cie n cy, ca rn it in e
d e cie n cy, u re m ia )
• Co n g e n it a l
• Mit o ch o n d ria l
(Co n t in u e d )
119
d e m o n s t ra t e d r e s p o n s e t o t h e ra p ie s t h a t d e cr e a s e in a m m a t io n , h a s le d t o
t h e cla s s i ca t io n o f IIM a s a u t o im m u n e d is e a s e s . Ye t , t h e IIM t h e m s e lve s
a r e a h e t e r o ge n e o u s gr o u p o f r a r e s yn d r o m e s t h a t d iffe r c o n s id e r a b ly in
t h e ir clin ica l p re s e n t a t io n s , p a t h o lo gic n d in gs , d is e a s e co u r s e s , a n d p ro g-
n o s e s (3 ).
Mos t p a t ie n t s w it h DM p re s e n t w it h ch a ra ct e ris t ic ra s h e s ove r t h e kn u ckle s
(Got t ron ’s p a p u le s ; s e e Fig. 13.1A) or a rou n d t h e eye s (h e liot rop e ra s h ; Fig. 13.1B)
a n d p rogre s s ive, s ym m e t ric p roxim a l m u s cle w e a kn e s s , m ore p ron ou n ce d in
t h e le gs t h a n t h e a r m s , evo lvin g ove r w e e k s t o m o n t h s . Pa t ie n t s w it h PM
p re s e n t w it h t h e w e a kn e s s , bu t n ot t h e ra s h . Th ey u s u a lly h a ve h ip m u s cle
w e a kn e s s , a n d n ot ice in cre a s in g d if cu lt y ge t t in g u p from a ch a ir or clim bin g
s t a irs . Th e s h ou ld e r m u s cle s oft e n be com e s ym p t om a t ic la t e r, re s u lt in g in d if-
cu lt y com bin g t h e h a ir or re a ch in g obje ct s on h igh s h e lve s . Im p ort a n t ly, on ly
on e q u a rt e r of p a t ie n t s w it h DM or PM h ave s ign i ca n t m u s cle p a in or t e n d e r-
n e s s . In t h e a bs e n ce of obje ct ive w e a kn e s s , h ip or s h ou ld e r gird le p a in a s t h e
on ly p re s e n t in g com p la in t s u gge s t s a n a lt e rn a t ive d ia gn os is , s u ch a s p olym y-
a lgia rh e u m a t ica .
Ot h e r s ke le t a l m u s cle s ca n be a ffe ct e d , a n d 20% of p a t ie n t s h a ve d ys p h a gia
s
e
(w it h n a s a l regu rgit a t ion of liq u id s s ign ifyin g gre a t e r s eve rit y), w h ile a s m a lle r
s
a
s u bs e t e xp e rie n ce s re s p ira t ory in s u f cie n cy from re s p ira t ory m u s cle w e a kn e s s .
e
s
i
Su bt le s ign s of e xt ra m u s cu la r in a m m a t ion m a y a ls o be p re s e n t if ca re fu lly
D
c
s ou gh t . Pa t ie n t s m ay h ave p rofou n d fa t igu e, p e rs is t e n t u n e xp la in e d low -gra d e
i
t
a
feve rs , s ym m e t ric s m a ll-join t a rt h ra lgia s or a rt h rit is , a bd om in a l p a in , d ys p n e a
m
on e xe rt ion from in t e rs t it ia l lu n g d is e a s e, or p a lp it a t ion s (from ca rd ia c con d u c-
u
e
t io n a bn o r m a lit ie s ) a n d h e a r t fa ilu re re la t e d t o d ire ct in a m m a t io n o f t h e
h
R
ca rd ia c m u s cle.
c
i
c
e
p
S
DIFFERENTIAL DIAGNOSIS
3
N
Th e IIM a re s ys t e m ic con n e ct ive t is s u e d is e a s e s , a n d m a n y o t h e r o rga n s ys -
O
I
T
t e m s ca n b e in vo lve d , re s u lt in g in a w id e ra n ge o f p o s s ible p re s e n t a t ion s a n d
C
E
s ym p t o m s t h a t ca n m im ic m a n y o t h e r d is o rd e r s . Th u s , t h e d iffe re n t ia l d ia g-
S
n o s is o f IIM in clu d e s t h e m a n y d is o rd e rs a s s o cia t e d w it h m u s cle com p la in t s
a n d is co n s id e ra bly ch a lle n gin g, n o t o n ly b e ca u s e o f t h e p le t h o ra o f co n d i-
t io n s t o b e co n s id e re d , b u t a ls o b e ca u s e IIM a re s o ra re t h a t few clin icia n s a re
t h o ro u gh ly fa m ilia r w it h t h e s e d is e a s e s . On e be gin s w it h cle a rly d e n in g t h e
p a t ie n t ’s p r im a ry p ro ble m s . Sin ce p a t ie n t s m a y u s e “w e a k n e s s ” a n d “p a in ”
in t e rch a n ge a bly, q u e s t io n s s h o u ld fo cu s o n (1 ) d is t in gu is h in g m ya lgia s fro m
t r u e w e a k n e s s , w h ich is o ft e n p a in le s s , by fo cu s in g o n t h e p a t ie n t s ’ fu n c-
t io n a l a b ilit ie s (w h a t t h ey ca n a n d ca n n o t d o in t h e ir d a ily ro u t in e ) (2 ); t h e
lo ca t io n o f w e a k n e s s (p rox im a l m u s cle s in PM a n d DM vs . d is t a l m u s cle s in
IBM a n d o t h e r d is o rd e r s ; s ym m e t r ic w e a k n e s s in PM a n d DM vs . a s ym m e t r ic
m u s cle in vo lve m e n t in IBM a n d o t h e r d is o rd e r s ) (3 ); t h e t im e fra m e a n d
t e m p o o f s ym p t o m p rogre s s io n a n d w h e t h e r a t ro p h y is p re s e n t , s ign ifyin g a
ch ro n ic co u r s e m o s t co n s is t e n t w it h d ys t ro p h ie s (4 ); a n d a n y a s s o cia t e d n o n -
m u s cu la r s ym p t o m s s u ch a s fa t igu e , low -gra d e feve r s , ra s h e s , b re a t h in g o r
sw a llow in g d if cu lt ie s , a rt h r it is o r a r t h ra lgia s , w h ich s u gge s t a s ys t e m ic d is -
e a s e , s u ch a s IIM.
Ne x t , o n e n e e d s t o co n s id e r p o s s ible ca u s e s . Ha s t h e in d ivid u a l b e e n
exp osed to a n y m yotoxin s , licit or illicit d ru gs, bota n ica l or ot h er over-th e-cou n ter
p r e p a ra t io n s t h a t co u ld r e s u lt in m yo p a t h y, o r a m e t a b o lic a b n o r m a lit y
s u ch a s h yp o ka le m ia ? Ha s t h e p a t ie n t h a d a n y re ce n t u n u s u a l e xp os u re, in fe c-
t io n , or t ra ve l? Are t h e re a n y s ym p t o m s o r n d in gs t h a t s u gge s t t h yro id or
p a ra t h yroid d is e a s e, d ia be t e s , or a n u n d e rlyin g m a lign a n cy? Is t h e re a fa m ily
h is t o ry o f a s im ila r d is o rd e r t h a t w o u ld s u gge s t a d ys t ro p h y o r in h e r it e d
m yo p a t h y?
 120 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

A B
S
E
C
T
I
O
N
3
S
p
e
c
i
c
R
h
e
u
C D
m
a
t
i
c
D
i
s
e
a
s
e
s
E F

Figure 13.1 Skin cha nges seen in derma tomyositis. A: Gottron’s pa pules a re sca ly pa pules overlying the extensor surfa ces of the ha nds (over the meta -
ca rpopha la ngea l a nd proxima l interpha la ngea l joints in this ca se), elbows, knees, or ma lleoli. This pa tient a lso ha s scleroda ctyly a nd a rthritis of the
meta ca rpopha la ngea l a nd proxima l interpha la ngea l joints. B: The heliotrope ra sh is a purplish discolora tion a round the eyes, especia lly on the upper
lids. C: Linea r extensor erythema overlies the extensor surfa ce of the ha nds beyond the usua l loca tion of Gottron’s pa pules or sign. D: Periungua l va s-
culitic cha nges a nd cuticula r overgrowth. E: Photosensitive diffuse erythroderma with a ccentua ted erythema in the V of the neck (V sign) in a pa tient with
ca ncer-a ssocia ted derma tomyositis. F: Drying a nd cra cking of the skin over the la tera l a nd pa lma r surfa ces of the ngers, known a s “mecha nic’s ha nds,”
is seen frequently in pa tients with both DM a nd PM with one type of myositis-speci c a ntibodies, the a utoa ntibodies to a minoa cyl-tRNA syntheta ses (the
a ntisyntheta se syndrome). With permission from Miller W. Frederick in a mma tory myopa thies: Polymyositis, derma tomyositis, a nd rela ted conditions.
In: Koopma n WJ, Morela nd LW, eds. Arthritis a nd Allied Conditions: A Textbook of Rheuma tology. 15th ed. Ba ltimore: Lippincott Willia ms & Wilkins;
2005:6–7.
 Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s
NOT TO BE MISSED (Co n t in u e d )
Muscular Dystro phie s
• Myo t o n ia
• Ne u rop a t hie s [am yo t ro ph ic
la t e ra l scle ro sis (ALS),
Guilla in –Ba rre syn drom e ,
d ia b e t ic p le xop a th y]
• Ne u ro m u scu la r ju n ct io n
d iso rd e rs (Ea t o n –La m b e rt
syn d ro m e a n d m ya st h e n ia
g ra vis)
• Ove ru se syn d ro m e s
• Pa ra n e o p la st ic
(carcinomatous neuropathy,
ca ch e xia , m yo n e cro sis)
• Rh a b d o m yo lysis
• Te n d o n it is–fa sciit is
In ammato ry Myo pathie s
In fe ct io u s
• Ba ct e ria l (St ap h ylo co ccu s,
St re p t o co ccu s, Clo st rid ia ,
Mycobacterium tuberculosis)
• Vira l (in u e n za ,
a d e n o viru s, Ep st e in –Ba rr
viru s, co xsa ckie viru s,
h e p a t it is B a n d C, h u m a n
im m u n o d e cie n cy viru s
(HIV), human T-lymphotropic
virus 1 (HTLV-1))
• Fu n g a l (Can d id a ,
co ccid io m yco sis)
• Pa ra sit ic (t rich in o sis,
t o xo ca ria sis, cyst ice rco sis,
t ryp a n o so m ia sis,
t o xo p la sm o sis)
• To xic (L-t ryp t o p h a n ,
e o sin o p h ilia m ya lg ia
syn d ro m e )
• Gra ft -ve rsu s-h o st d ise a se
• Rh e u m a t ic co n d it io n s
(g ia n t ce ll a rt e rit is,
p o lya rt e rit is n o d o su m ,
o ve rla p syn d ro m e s w it h
lu p u s a n d scle ro d e rm a )
• Ma cro p h a g ic o r
e o sin o p h ilic m yo fa scit is
• Idiopathic In ammatory
Myopathies (see Table 13.1 )
121
DIAGNOSTIC CRITERIA
Crit e ria t o d e n e t h e IIM s yn d rom e s a n d d is t in gu is h t h e m from ot h e r m yop a -
t h ie s w e re p rop os e d m ore t h a n 30 ye a rs a go (4 ) a n d re m a in u s e fu l t od ay. Sin ce
t h e s e a re d ia gn os e s of e xclu s ion , on e m u s t rs t d o a n eva lu a t ion d ire ct e d by t h e
h is t ory a n d p h ys ica l e xa m in a t ion n d in gs t o e xclu d e t h e m a n y ot h e r ca u s e s of
m yop a t h y. On ce t h is h a s be e n a ccom p lis h e d , a d ia gn os is of IIM ca n be m a d e
u s in g t h e n d in gs of a cu t e or s u ba cu t e s ym m e t ric p roxim a l m u s cle w e a kn e s s ,
s ign i ca n t e leva t ion of m u s cle e n zym e s , ch a ra ct e ris t ic EMG a bn orm a lit ie s , a n d
m u s cle biop s y n d in gs or ra s h e s con s is t e n t w it h IIM (Ta ble 13.1 ). In u n cle a r
ca s e s , a d d it ion a l clu e s t h a t ca n a s s is t in m a kin g t h e d ia gn os is of IIM in clu d e
t h e p re s e n ce of a n t in u cle a r a n t ibod ie s (ANA) or m yos it is a u t oa n t ibod ie s (5 ), a
fa m ily h is t ory of a u t oim m u n e d is e a s e, d e t e ct ion of in a m m a t ory ch a n ge s in
m u s cle s by m a gn e t ic re s on a n ce im a gin g (MRI) (6 ), or a clin ica l re s p o n s e t o
im m u n os u p p re s s ive t h e ra p y (Ta ble 13.2 ).
In clu s ion b o d y m yo s it is is t h e m o s t co m m on IIM o ccu rr in g in p a t ie n t s
old e r t h a n 50 ye a rs . Pa t ie n t s w it h IBM u s u a lly fu l ll t h e IIM crit e ria , bu t in con -
t ra s t , h a ve m ore s low ly p rogre s s ive w e a k n e s s o f t h e q u a d r ice p s a n d d is t a l
m u s cle s of t h e a rm s , in a s om ew h a t a s ym m e t ric fa s h ion ; low e r e leva t ion s of
s
e
s
s e ru m CK leve ls ; a n d ch a ra ct e ris t ic a m ylo id d e p o s it s a n d rim m e d va cu o le s
a
e
w it h in m yocyt e s s e e n on ligh t m icros cop y. Som e in a m m a t ory ch a n ge s m ay
s
i
D
be p re s e n t , bu t a m yloid d ep os it ion p re d om in a t e s . Alt h ou gh s om e p a t ie n t s m a y
c
i
in it ia lly im p rove w it h im m u n o s u p p re s s ive t re a t m e n t s , m o s t h a ve a gra d u a l
t
a
m
a n d re le n t le s s p rogre s s ion of m u s cle w e a kn e s s .
u
e
h
R
c
i
Table 13.1 Bohan and Pet er Crit eria for t he Diagnosis of
c
e
Dermat omyosit is (DM) and Polymyosit is (PM)a
p
S
3
N
1. Sym m e t ric w e a kn e ss, u su a lly p ro g re ssive , o f t h e p ro xim a l lim b -g ird le m u scle s
O
I
T
2. Ele va t io n o f se ru m le ve ls o f m u scle -a sso cia t e d e n zym e s
C
E
S
– CK, a ld o la se , LDH, AST/SGOT, ALT/SGPT
3. EMG t ria d o f m yo p a t h y
– Sh o rt , sm a ll, lo w -a m p lit u d e p o lyp h a sic m o t o r u n it p o t e n t ia l
– Fib rilla t io n p o t e n t ia ls, e ve n a t re st
– Biza rre h ig h -fre q u e n cy re p e t it ive d isch a rg e s
4. Mu scle b io p sy e vid e n ce o f ch ro n ic in a m m a t io n w it h o u t o t h e r ca u se s
– Ne cro sis o f t yp e I o r t yp e II m u scle b e rs
– De g e n e ra t io n a n d re g e n e ra t io n o f m yo b e rs w it h va ria t io n in m yo b e r
size
– Fo ca l co lle ct io n s o f e n d o m ysia l, p e rim ysia l, p e riva scu la r, o r in t e rst it ia l
m o n o n u cle a r ce lls
5. Ch a ra ct e rist ic ra sh e s o f d e rm a t o m yo sit is
– He lio t ro p e ra sh , Go t t ro n ’s p a p u le s, Go t t ro n ’s sig n
CK, creatine kinase; LDH, lactate dehyrogenase; AST/SGOT, aminotransferase/serum glutamic oxaloacetic trans-
aminase; ALT/SGPT, alanine aminotransferase/serum glutamic pyruvic transaminase; EMG, electromyography.
a
In p a t ie n t s in w h o m a ll kn o w n ca u se s o f m yo p a t h y h a ve b e e n e xclu d e d :
De n it e IIM Fo r PM, a ll o f t h e rst fo u r crit e ria
Fo r DM, a n y t h re e o f t h e rst fo u r crit e ria p lu s t h e ra sh
Pro b a b le IIM Fo r PM, a n y t h re e o f t h e rst fo u r crit e ria
Fo r DM, a n y t w o o f t h e rst fo u r crit e ria p lu s t h e ra sh
Po ssib le IIM Fo r PM, a n y t w o o f t h e rst fo u r crit e ria
Fo r DM, a n y o n e o f t h e rst fo u r crit e ria p lu s t h e ra sh
122 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
PATIENT ASSESSMENT
• Su b a cu t e p ro g re ssive
p ro xim a l m u scle w e a kn e ss
w it h o u t o t h e r n e u ro lo g ic
a b n o rm a lit y.
• Mya lg ia s a re n o t
p ro m in e n t .
• Syst e m ic sym p t o m s su ch a s
fatigue, arthritis, dysphagia,
GI, lu n g , a n d ca rd ia c
a b n o rm a lit ie s.
• Cre a t in e kin a se (CK)
e le va t io n s 10 upper
lim it o f n o rm a l.
• Ele ct ro m yo g ra p h y (EMG)
sh o w in g b rilla t io n s o r
p o sit ive sh a rp w a ve s.
• Mu scle b io p sy a n d /o r skin
b io p sy co m p a t ib le w it h
in a m m a t io n .
• Exclu d e t h e m a n y o t h e r
ca u se s o f m u scle w e a kn e ss.
• Se rio u s co m p lica t io n s:
d ysp h a g ia fro m o ro p h a -
ryn g e a l m u scle w e a kn e ss
ca n le a d t o a sp ira t io n ;
in t e rst it ia l lu n g d ise a se
ca n b e ra p id ly p ro g re ssive
a n d se ve re ; a n d ca rd ia c
in vo lve m e n t ca n le a d t o
co n d u ct io n a b n o rm a lit ie s
n e ce ssit a t in g p a ce m a ke r
in t e rve n t io n .
Table 13.2 Useful Discriminat ors for Myosit is in Confusing
Cases of Myopat hy
FEATURES LEADING TOWARD IIM FEATURES LEADING AWAY FROM IIM
Fa m ily h ist o ry o f a n y a u t o im m u n e Fa m ily h ist o ry o f m u scu la r syn d ro m e
d ise a se sim ila r t o t h e p a t ie n t ’s (i.e ., h e re d it a ry
m u scle d ise a se )
Sym m e t ric, ch ro n ic, p ro xim a l We a kn e ss re la t e d t o e xe rcise o r in vo lvin g
d ist a l w e a kn e ss t h e fa ce
Mu scle a t ro p h y a ft e r ch ro n ic Mu scle a t ro p h y e a rly o r h yp e rt ro p h y a t
sym p t o m s a n y p o in t
Ab se n ce o f n e u ro p a t h y b y Pre se n ce o f n e u ro p a t h y
e xa m in a t io n o r EMG
La ck o f fa scicu la t io n s a n d lit t le Fa scicu la t io n s o r p ro m in e n t m u scle
m u scle cra m p in g cra m p in g
Ch a ra ct e rist ic ra sh o f DM No ra sh o r va scu lit is
Fe a t u re s o f CTD—fa t ig u e , fe ve rs, No CTD sym p t o m s
a rt h rit is, ILD, e t c.
CK, AST, ALT, LDH, a ld o la se le ve ls En zym e s 2 n o rm a l ra n g e o r 100
2–100 n o rm a l n o rm a l
Po sit ive ANA, ENA, o r m yo sit is Ne g a t ive a u t o a n t ib o d ie s
a n t ib o d ie sa
Mu scle b io p sy e vid e n ce o f m yo b e r Myo b e r va cu o le s, ra g g e d re d b e rs,
d e g e n e ra t io n /re g e n e ra t io n w it h p a ra sit e s; n o in a m m a t io n o r a lka lin e
in a m m a t io n , st ro n g a lka lin e p h o s- p h o sp h a t a se st a in in g o f t h e in t e rst it iu m
p h a t a se st a in in g in t h e in t e rst it iu m
MRI—sp o t t y b rig h t sym m e t ric a re a s MRI n o rm a l o r o n ly sh o w s a t ro p h y
in m u scle b y STIR
Clin ica l re sp o n se t o im m u n o su p - No clin ica l re sp o n se t o im m u n o su p p re ssio n
p re ssio n
EMG, e le ct rom yo g ra p h y; IIM, idio p a t h ic in a m m a t o ry m yop a t h y; DM, d e rm a t om yo sit is; CK, cre a t in e
kina se ; LDH, la ct a t e d e h yrog e n a se ; AST, a m ino t ra n sfe ra se ; ALT, a la nin e a m ino t ra n sfe ra se ; MRI, m a g n e t ic
re son a n ce im a g ing ; STIR, sho rt t a u in ve rsio n re p e a t ; ANA, a n t inu cle a r a n t ib o d y; ENA, a n t ie xt ra ct a b le
n u cle a r a n t ig e n a nt ib o dy p a n e l; CTD, co n ne ct ive t issue d ise a se ; ILD, in t e rst it ia l lu ng d ise a se ; o n sp e ci c
t e st in g , t his in clu d e s t he fo llo wing a n t ib o die s: d o ub le -st ra nd e d DNA (d sDNA), SSA (a nt i-Ro ), SSB (a nt i-La ),
an t i-U1RNP, a n t i-Sm it h, a n d a nt i-scl70.
a
Myo sit is a u t o a n t ib o d ie s. Th e se in clu d e a n t isyn t h e t a se a n t ib o d ie s (t h e m o st co m m o n o f w h ich is
an t i-Jo -1), a n t i-SRP, a n t i-Mi-2, a n d o t h e rs. Va lid a t e d im m u n o p re cip it a t io n a ssa ys fo r t h e se a re a va ila b le
co m m e rcia lly.
Ca n ce r-a s s o cia t e d m yo s it is is a n o t h e r IIM d is o rd e r, a n d o n t h e b a s is o f
p op u la t ion s t u d ie s (7 ), ca n be con s id e re d if bot h d ia gn os e s a re m a d e w it h in
2 ye a rs of on e a n ot h e r. Tre a t in g t h e u n d e rlyin g ca n ce r ge n e ra lly a ls o t re a t s t h e
m yos it is . Alt h ou gh m ole cu la r ge n e t ic s t u d ie s h ave id e n t i e d ge n e s re s p on s ible
for m a n y d ys t rop h ie s , m e t a bolic, a n d m it och on d ria l m yop a t h ie s , s om e p a t ie n t s
con t in u e t o d e fy d ia gn os t ic eva lu a t ion s a n d re m a in e n igm a s .
Physica l Finding s
Th e p h ys ica l e xa m in a t ion be gin s w it h m a n u a l s t re n gt h t e s t in g of p roxim a l
ve rs u s d is t a l lim b m u s cle s a n d n e ck e x o rs . Ca re fu lly d is t in gu is h w e a k n e s s
from fa t iga bilit y or p a in t h a t lim it s fu n ct ion by a s kin g t h e p a t ie n t t o give a fu ll
e ffort on t h e e xa m in a t ion . Not e if a p a t ie n t is a ble t o ris e from a s q u a t t in g or
s it t in g p os it ion w it h ou t t h e u s e of h is or h e r h a n d s , h ow ra p id ly t h e p a t ie n t is
a ble t o d re s s or u n d re s s , w h e t h e r a w a d d lin g ga it is p re s e n t (d e m on s t ra t in g h ip
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 123

e xt e n s or w e a kn e s s ), a n d n ot e w h a t t h e p a t ie n t ca n a n d ca n n ot d o com p a re d t o
a p reviou s t im e p oin t . A s im p le a ct ivit ie s -of-d a ily-livin g q u e s t ion n a ire t h a t ca n
be e a s ily s core d is oft e n u s e fu l. Th e re m a in d e r of t h e n e u rologic e xa m in a t ion ,
in clu d in g s e n s ory t e s t in g, s h ou ld be n orm a l; n ot e t h a t m u s cle t e n d on re e xe s
a re p re s e rve d u n t il t h e w e a kn e s s is a d va n ce d . On e s h ou ld eva lu a t e t h e fu n c-
t ion of ot h e r m u s cle s a n d orga n s , in clu d in g t h e h e a rt (is t h e p u ls e irregu la r,
s u gge s t in g co n d u ct io n a bn o r m a lit ie s , o r a re t h e re s ign s o f h e a r t fa ilu re ?);
orop h a ryn x (is sw a llow in g n orm a l?); re s p ira t ory m u s cle s a n d lu n gs (n ot e t h e
p a t ie n t ’s ove ra ll re s p ira t ory e ffort in a d d it ion t o a ca re fu l lu n g e xa m in a t ion
lis t e n in g for Ve lcro cra ckle s t h a t h e ra ld in t e rs t it ia l lu n g d is e a s e or coa rs e cra ck-
le s s ign ifyin g a s p ira t ion p n e u m on ia ). An y d e t e ct e d a bn orm a lit ie s s h ou ld be
p u r s u e d w it h a p p ro p ria t e t e s t s , a s in d ica t e d , s u ch a s a n e le ct roca rd iogra m
(EKG), Ho lt e r m o n it o r in g, o r e ch o ca rd io gra m , sw a llow in g s t u d y, ch e s t x -ra y
a n d /or com p u t e d t om ogra p h ic (CT) s ca n of t h e ch e s t , a n d p u lm on a ry fu n ct ion
t e s t s w it h in s p ira t ory a n d e xp ira t ory p re s s u re s (Ta ble 13.3 ).
Ma n y o f t h e s kin le s io n s d e s cr ib e d in p a t ie n t s w it h DM a re s u b t le , a n d
be ca u s e t h ey a re oft e n m in im ize d by t h e p a t ie n t s t h e m s e lve s , t h ey m u s t be
a ct ive ly s o u gh t d u r in g t h e e x a m in a t io n . No n e o f t h e m is p a t h ogn o m o n ic,

s
e
e xce p t Got t ron ’s p a p u le s . Th e s e a re p a lp a ble le s ion s ove rlyin g t h e e xt e n s or

s
a
s u rfa ce s of t h e h a n d join t s , e lbow s , kn e e s , or m a lle oli w it h a n e ryt h e m a t ou s

e
s
i
b a s e (Fig. 13.1A ). Ot h e r ra s h e s ch a ra ct e r is t ic for DM in clu d e Got t ro n ’s s ign ,

D
c
w h ich is a s ca lin g e ryt h e m a w it h o u t p a p u le s in t h e s a m e d is t r ib u t io n a s

i
t
a
Go t t ro n ’s p a p u le s , a n d t h e h e lio t ro p e ra s h , a s u b t le , p u r p lis h d is co lo ra t io n

m
a rou n d t h e eye s (Fig. 13.1B). In t h e a b s e n ce o f a p ro m in e n t h e lio t ro p e ra s h ,

u
e
p a t ie n t s m ay h ave s u bt le p e riorbit a l e d e m a . Ot h e r com m on ra s h e s in clu d e a

h
R
s ca lin g s ca lp ra s h re s e m blin g p s o ria s is (p s e u d op s oria s is ), s om e t im e s a s s oci-

c
i
a t e d w it h p a t ch y a lo p e cia if s eve re ; lin e a r e x t e n s o r e ryt h e m a (Fig. 13.1C );

c
e
p e riu n gu a l va s cu lit ic ch a n ge s a n d cu t icu la r ove rgrow t h (Fig. 13.1D ); p h ot os e n -

p
S
s it ive e ryt h ro d e r m a ; a cce n t u a t e d e ryt h e m a in t h e V o f t h e n e ck (V s ign ;

3
Fig. 13.1E) or a rou n d t h e s h ou ld e rs (s h aw l s ign ); a n d a d ryin g a n d cra ckin g of

N
O
t h e s kin ove r t h e la t e ra l a n d p a lm a r s u rfa ce s of t h e n ge rs , kn ow n a s “m e ch a n -

I
T
C
ic’s h a n d s ” (Fig. 13.1F). In p a t ie n t s w it h ch ro n ic or s eve re s k in ra s h e s a n d in

E
S
ch ild re n , s u bcu t a n e ou s ca lciu m d ep os it s , or ca lcin os is , d eve lop ove r t im e.
Mo s t im p ort a n t ly, if IIM (a n d DM in p a rt icu la r ) is s u s p e ct e d , t h e clin ica l
eva lu a t ion is n ot com p le t e w it h ou t a t h orou gh a ge -a p p rop ria t e ca n ce r s cre e n -
in g. Mu lt ip le p op u la t ion -ba s e d s t u d ie s a n d regis t rie s h a ve fou n d a n in cre a s e d
in cid e n ce of m a lign a n cie s in p a t ie n t s w it h DM (s t a n d a rd ize d in cid e n ce ra t io
(SIR) 3.0:12.6) (7 ) a n d t o a le s s e r d egre e in p a t ie n t s w it h PM (SIR 1.9) com p a re d
t o t h e ge n e ra l p op u la t ion . Alt h ou gh t h e t yp e of m a lign a n cy va rie s a n d is oft e n
a ge s p e ci c, t h e s t ron ge s t a s s ocia t ion s w e re w it h ova ria n , lu n g, p a n cre a t ic, GI,
a n d n on -Hod gkin lym p h om a . Of s p e cia l n ot e, ova ria n ca n ce r w a s ove rre p re -
s e n t e d in s om e s e rie s a n d s h ou ld be s p e ci ca lly s cre e n e d for in w om e n w it h
IIM, e s p e cia lly DM.

Pa tho g e ne sis
W h ile t h e ca u s e s of t h e IIM a re by d e n it ion u n kn ow n , evid e n ce s u gge s t s t h a t
t h ey like ly re s u lt from on e or m ore e n viron m e n t a l s t im u li a ct in g on ge n e t ica lly
s u s ce p t ible in d ivid u a ls t o in d u ce ch ron ic im m u n e a ct iva t ion a n d s u bs e q u e n t
m yos it is . Som e e n viron m e n t a l t rigge rs a re be t t e r u n d e rs t ood t h a n ot h e rs . As
w it h t h e ca s e a t t h e begin n in g of t h is ch a p t e r, e xce s s ive e xp os u re t o u lt raviole t
ligh t h a s be e n s h ow n t o in d u ce a n d e xa ce rba t e t h e ra s h of DM. In con t ra s t , HIV
a n d HTLV-1 in fe ct ion s h ave be e n a s s ocia t e d w it h PM.
Ma n y lin e s of in d ire ct evid e n ce s u gge s t t h a t in a p p rop ria t e ce llu la r im m u n e
a ct iva t ion is re s p on s ible for t h e p a t h ologic e ffe ct s s e e n in m yos it is a n d t h a t t h e
p a t t e rn s of im m u n e a ct iva t ion a re d is t in ct be t w e e n t h e d iffe re n t IIMs , in volv-
in g d iffe re n t ce lls a n d p roce s s e s . In DM, a va s cu lop a t h y m a y be t h e p rim a ry
 124 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 13.3 Syst emic Manifest at ions of IIM and Suggest ed Furt her Invest igat ions

ORGAN SYSTEM INVESTIGATIONS TO CONSIDER

Ge n e ra l Diff e re n t ial d iag n o sis: ESR, CRP, a g e -a p p ro p ria t e m a lig n a n cy
Fa t ig u e scre e n in g
Fe ve rs
We ig h t lo ss A u t o an t ib o d ie s: ANA, ENA, m yo sit is a u t o a n t ib o d ie s

Mu scu lo ske le t a l
Mu scle w e a kn e ss, p ro xim a l d ist a l, u p p e r Ot h e r cau se s: fa st in g g lu co se , Ca , Ph o s, K, TSH, GGT (if a lco h o l)
a n d lo w e r limb s, n eck, ra re ly fa cia l mu scle s
La b o ra t o ry t e st s o f m u scle e n zym e s (se e t e xt )
Ne u ro lo g ic e xa m in a t io n , EMG, m u scle b io p sy o f t h e m u scle m o st
in vo lve d ; co n sid e r MRI o f m u scle if u n cle a r sit e fo r b io p sy
Art h ra lg ia s o r a rt h rit is X-ra ys o f a ffe ct e d jo in t s
Re sp ira t o ry
Dysp n e a a t re st a n d /o r o n e xe rt io n , d ry Ch e st x-ra y
co u g h , w h e e zin g , ra le s
S
Pn e u m o n ia d u e t o a sp ira t io n o r Ch e st x-ra y, CT ch e st a s n e e d e d
E
C
im m u n o su p p re ssio n
T
In t e rst it ia l lu n g d ise a se CT ch e st w it h p ro n e p o sit io n in g ; p u lm o n a ry fu n ct io n t e st s
I
O
N
Ca rd ia c
3
Co n g e st ive h e a rt fa ilu re Ech o ca rd io g ra m
S
Arrh yt h m ia s EKG, Ho lt e r m o n it o rin g
p
e
Myo ca rd it is Rig h t ve n t ricu la r h e a rt b io p sy; ca rd ia c MRI
c
i
c
Ga st ro in t e st in a l
R
Dysa rt h ria —p o o r t o n g u e p ro p u lsio n s Fo rm a l sw a llo w in g e va lu a t io n
h
e
Dysp h a g ia —u p p e r a n d lo w e r e so p h a g e a l
u
d ysm o t ilit y
m
a
Re u x e so p h a g it is Em p iric t h e ra p y; co n sid e r EGD if p ro lo n g e d , se ve re d ysp h a g ia
t
i
c
Skin
D
i
De rm a t o m yo sit is-sp e ci c ra sh e s Clin ica l p h o t o g ra p h y (a s b a se lin e ) a n d skin b io p sy
s
e
De rm a t o m yo sit is-a sso cia t e d ra sh e s
a
s
Pa n n icu lit is
e
s
Ca lcin o sis cu t is Ca n b e se e n o n x-ra ys
Pe riu n g u a l ca p illa ry ch a n g e s Exa m in e w it h o p h t h a lm o sco p e (o n 40-d io p t e r se t t in g )
Ra yn a u d ’s p h e n o m e n o n N/A
Asso cia t io n w it h m a lig n a n cy Ag e -a p p ro p ria t e ca n ce r scre e n in g
Ova ria n ca n ce r scre e n in g in w o m e n w it h IIM

ESR, e ryt h ro cyt e se d im e n t a t io n ra t e ; CRP, c-re a ct ive p ro t e in ; ANA, a n t in u cle a r a n t ib o d y; ENA, a n t ie xt ra ct a b le n u cle a r a n t ig e n a n t ib o d y p a n e l; se e
Ta b le 13.2 fo r sp e ci cs.
Ca , se ru m ca lciu m le ve l; Ph o s, se ru m p h o sp h o ru s le ve l; K, se ru m p o t a ssiu m le ve l; TSH, t h yro id -st im u la t in g h o rm o n e ; GGT, g a m m a -g lu t a m yl
t ra n sp e p t id a se , o ft e n h e lp fu l in d ist in g u ish in g a lco h o l-re la t e d ve rsu s m yo sit is-re la t e d t ra n sa m in a se e le va t io n .
EMG, electromyography; CT, computed tomography; EKG, electrocardiogram, MRI, magnetic resonance imaging; EGD, esophagogastroduodenoscopy.

eve n t re s p on s ible for t h e la t e r m u s cle d a m a ge. Ge n e e xp re s s ion a n a lys is h a s

s h ow n t h a t in t e rfe ron -a lp h a ge n e s a re ove re xp re s s e d , p rod u cin g a n “in t e rfe ron
s ign a t u re ” t h a t is m ore p rom in e n t w h e n com p a re d t o PM/IBM or ot h e r a u t oim -
m u n e d is e a s e s . Th u s , on e m od e l of p a t h oge n e s is (8 ) s u gge s t s t h a t p la s m a cy-
t oid d e n d rit ic ce lls , p re s e n t in t h e p e riva s cu la r s p a ce, be com e a ct iva t e d t h rou gh
a n e n vir o n m e n t s t im u lu s –ge n e t ic s u s ce p t ib ilit y in t e ra ct io n a n d s e cre t e
in t e rfe ron -a lp h a . Th is in t u rn le a d s t o s p e ci c p rot e in e xp re s s ion , a ct iva t ion
of CD4 ce lls a n d B ce lls t h a t s e cre t e a n t ibo d ie s . Th e re s u lt is com p le m e n t
d e p os it ion , ca p illa ry in ju ry, a n d p a t h ologic ch a n ge s of m u s cle in fa rct ion of t h e
s u rrou n d in g m yocyt e s .
In con t ra s t , it is im m u n oglobu lin -re la t e d ge n e s t h a t a re ove re xp re s s e d in
blo o d s a m p le s fro m p a t ie n t s w it h PM a n d IBM (8 ). Th is le a d t o a h yp o t h e s is
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 125

t h a t it is t h e m ye loid d e n d rit ic ce lls , w h ich a re p re s e n t in t h e e n d om ys iu m s u r-

rou n d in g t h e m yocyt e s , t h a t be com e a ct iva t e d t h rou gh a n u n kn ow n e n viron -
m e n t a l t rigge r. Th ey in t u rn a ct iva t e CD8 cyt ot oxic T ce lls , w h ich d ire ct ly
d e s t roy in d ivid u a l m yocyt e s . Mye loid d e n d rit ic ce lls a ls o s t im u la t e p la s m a ce lls
in m u s cle t o ove rp rod u ce im m u n oglobu lin s , w h ich a s ye t h ave a n ill-d e n ed role
in p a t h oge n e s is .

Studie s (La bo ra to ry, EMG, Muscle

Bio psy, Ima g ing )
CLINICAL CHEMISTRY
On e of t h e p rim a ry la bora t ory clu e s t o a m yop a t h y is t h e d e t e ct ion of e leva t e d
s e ru m leve ls o f e n zym e s o rigin a t in g fro m t h e cyt o p la s m o f t h e m u s cle ce ll
(s a rcop la s m ). Th e m os t fre q u e n t ly m e a s u re d e n zym e is CK be ca u s e of it s h igh
s e n s it ivit y, m u s cle s p e ci cit y, a n d re la t ive ly go o d co r re la t io n w it h d is e a s e
a ct ivit y a n d m u s cle s t re n gt h . At t h e o n s e t o f illn e s s , s e ru m CK leve ls m a y
be e leva t e d a s m u ch a s 10 t o 100 t im e s t h e u p p e r lim it of n orm a l. Mos t of t h e

s
e
e leva t ion of s e ru m CK leve ls in IIM is d u e t o in cre a s e s in t h e MM is oe n zym e

s
a
fra ct ion , w h ich is re le a s e d from s ke le t a l m u s cle . Eleva t ion of t h e MB is oe n -

e
s
i
zym e, fou n d p rim a rily in t h e m yoca rd iu m , m a y a ls o occu r n ot on ly a s a re s u lt

D
c
o f m yo ca rd it is bu t a ls o a s a n in d ica t o r o f s ke le t a l m u s cle rege n e ra t io n a n d

i
t
a
m yo bla s t a ct iva t io n . In p a t ie n t s w it h IIM, m yobla s t a ct iva t ion a ls o re s u lt s in

m
e leva t io n o f o t h e r e n z ym e s t h a t co r re la t e w it h CK leve ls , in clu d in g la ct a t e

u
e
d e h yd roge n a s e (LDH), a ld o la s e , s e r u m glu t a m ic ox a lo a ce t ic t ra n s a m in a s e /

h
R
a s p a rt a t e a m in ot ra n s fe ra s e (SGOT/AST), a n d s e ru m glu t a m ic pyru vic t ra n s a m -

c
i
in a s e /a la n in e a m in ot ra n s fe ra s e (SGPT/ALT). Eleva t ion s of t h e la t t e r t w o h a ve

c
e
s om e t im e s le d t o u n n e ce s s a ry live r biop s ie s .

p
S
Alt h ou gh t h e s e ru m leve ls of CK a n d ot h e r m u s cle -d e rive d e n zym e s a re

3
N
ge n e ra lly u s e fu l in follow in g m yos it is a ct ivit y a n d re s p on s e s t o t h e ra p y, t h ey

O
ca n n o t s u b s t it u t e fo r a t h o ro u gh eva lu a t io n o f t h e p a t ie n t , w h ich in clu d e s

I
T
C
fu n ct ion a l a s s e s s m e n t . Firs t , t h e re is a d e la y be t w e e n t h e m a gn it u d e of t h e

E
S
e n zym e e leva t ion a n d globa l d is e a s e a ct ivit y; t h e CK leve ls t e n d t o n orm a lize 3
t o 8 w e e k s b e fore m u s cle s t re n gt h im p rove s a n d con ve rs e ly m a y r is e 5 t o
6 w e e ks a ft e r a clin ica l re la p s e is d e t e ct e d . Th e re fore, clin ica l im p rove m e n t or
w ors e n in g in t h e p a t ie n t m u s t be corre la t e d w it h CK leve ls , n ot t h e reve rs e.
Se con d , a p a t ie n t w it h IIM m a y h a ve a n orm a l CK leve l in t h e fa ce of clin ica lly
a ct ive d is e a s e , a s d e m o n s t ra t e d by m u s cle w e a k n e s s a n d a cco m p a n ie d by
in a m m a t ion on m u s cle biop s y or MRI. Th is m ay be d u e t o s u p p re s s ion of CK
by cort icos t e roid s , t h e p re s e n ce of s e ru m in h ibit ors of CK e n zym e a ct ivit y, or
e xt e n s ive m u s cle a t rop h y be ca u s e of ch ron ic d is e a s e. In a d d it ion , p a t ie n t s w it h
s ys t e m ic lu p u s e ryt h e m a t os u s , rh e u m a t oid a rt h rit is , a n d ot h e r con n e ct ive t is -
s u e d is e a s e s t e n d t o h ave a bn orm a lly low CK leve ls ; t h u s , a n orm a l CK leve l in
t h e s e p a t ie n t s m a y in d ica t e a ct ive m yos it is . In con t ra s t , ra cia l a n d ot h e r d iffe r-
e n ce s n ot t a ke n in t o a ccou n t by t h e t e s t in g la bora t ory m a y re s u lt in fa ls e ly
h igh CK leve ls . Be ca u s e CK leve ls corre la t e w it h m u s cle m a s s , Africa n Am e rica n s
h a ve s ign i ca n t ly h igh e r ba s e lin e CK leve ls t h a n Ca u ca s ia n s , a s d o m u s cu la r
a t h le t e s a n d m a ra t h on ru n n e rs .
Abn orm a lit ie s of n on s p e ci c m a rke rs of in a m m a t ion —s u ch a s le u kocyt o-
s is , e leva t e d p la t e le t cou n t s , h igh C-re a ct ive p rot e in , a n d e ryt h rocyt e s e d im e n -
t a t ion ra t e s —m a y be fou n d in p a t ie n t s w it h m yos it is . Th e s e m ay be u s e fu l in
a s s e s s in g IIM a ct ivit y, a ft e r be in g s u re t o e xclu d e ot h e r coe xis t in g p roce s s e s
s u ch a s in fe ct io n o r m a lign a n cy, w h ich ca n a ls o ca u s e t h e s e a b n o rm a lit ie s .
Tw e n t y-fo u r-h o u r u rin a ry cre a t in in e e x cre t io n , w h ich re e ct s m u s cle m a s s
a n d d a m a ge, is e leva t e d in m a n y p a t ie n t s w it h m u s cle d is e a s e s . Ad d it ion a lly,
a b n o rm a lly low s e ru m cre a t in in e leve ls m a y b e t h e re s u lt o f lo s s o f m u s cle
m a s s a n d s h ou ld a le rt on e t o t h e p re s e n ce of ch ron ic m yos it is .
 126 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

IMMUNOLOGY
Im m u n ologic a bn orm a lit ie s a re s om e t im e s t h e rs t clu e t h a t a p a t ie n t h a s IIM.
Th e m os t fre q u e n t a bn orm a lit ie s a re h yp e rga m m a globu lin e m ia or t h e p re s e n ce
of a n a u t oa n t ibod y. An t in u cle a r a u t oa n t ibod ie s (ANAs ) a re t h e m os t com m on
a u t oa n t ibod ie s , bu t occu r on ly in 25% of p a t ie n t s (9 ). Th e ANA u s u a lly d is p lays
a s p e ckle d p a t t e rn , a lt h ou gh a n y ot h e r p a t t e rn ca n a ls o be p re s e n t . Ot h e r
im m u n e a bn or m a lit ie s in clu d e h yp oga m m a globu lin e m ia , m on oclon a l ga m -
m op a t h y, cryoglobu lin e m ia , a n d a va rie t y of a u t oa n t ibod ie s , s om e of w h ich a re
s t ron gly a s s ocia t e d w it h m yos it is (m yos it is a u t oa n t ibod ie s ) (Ta ble 13.2 ).

ELECTROMYOGRAPHY AND OTHER TESTS

Ele ct rom yogra p h y a n d n e rve con d u ct ion ve locit y m e a s u re m e n t s a re oft e n p e r-
form e d t o d is t in gu is h n e u rop a t h ie s from m yop a t h ie s . Th ey a ls o ca n a d d t o t h e
p roba bilit y t h a t t h e p a t ie n t h a s a n in a m m a t ory m yop a t h y w h e n ch a ra ct e ris -
t ic a bn orm a lit ie s , s u ch a s brilla t ion s or p os it ive s h a rp w ave s a t re s t a n d m yo-
p a t h ic m ot or u n it p ot e n t ia ls , a re p re s e n t (Ta ble 13.1 ). How eve r, t h e s e n d in gs
a re n ot p a t h ogn om on ic for IIM a n d ca n a ls o be s e e n in ot h e r ca s e s , s u ch a s
S
E
d ru g-in d u ce d m yop a t h ie s . Th u s , a m u s cle biop s y is u s u a lly n e e d e d t o fu rt h e r
C
T
n a rrow t h e d iffe re n t ia l.
I
O
N
In a d d it ion , ra d iogra p h s , EKGs , a n d ot h e r la bora t ory s t u d ie s s h ou ld be p e r-
3
form e d on t h e ba s is of t h e n a t u re of t h e s ym p t om s a n d n d in gs , a n d con ce rn
S
for t h e p re s e n ce of ca n ce r, w h ich is a s s ocia t e d w it h IIM (Ta ble 13.3 ). Th is la s t
p
e
is s u e is a d if cu lt on e, s in ce t h e re a re n o cu rre n t gu id e lin e s on t h e n u m be r or
c
i
s p e ci c t e s t s for m a lign a n cy t h a t s h ou ld be p e rform e d . A p ru d e n t a p p roa ch
c
R
w ou ld be t o s t a rt w it h t h e p a t ie n t h is t ory a n d fa m ily h is t ory a n d p u rs u e re a -
h
e
s o n a ble a ve n u e s in a d d it io n t o a ge -a p p ro p r ia t e s cre e n in g. Fo r e x a m p le , a
u
m
s m o k e r s h o u ld p ro b a bly h a ve a ch e s t x -ra y a n d CT ch e s t t o e x clu d e m a lig-
a
t
n a n cy; a 40-ye a r-o ld w it h a fa m ily h is t o ry of co lon ca n ce r s h ou ld p roba bly
i
c
D
u n d e rgo a colon os cop y d e s p it e t h e you n g a ge ; a n d a p a t ie n t w it h re cu rre n t
i
s
h igh feve r s s h ou ld p ro b a bly b e in ve s t iga t e d fo r lym p h o m a . In a d d it ion , a ll
e
a
w om e n w it h DM in p a rt icu la r s h ou ld be ca re fu lly s cre e n e d for ova ria n ca n ce r
s
e
s
a n d follow e d u p t h orou gh ly if t h ey h a ve p e rs is t e n t va gu e a bd om in a l p a in . A
s cre e n in g p e lvic a n d va gin a l u lt ra s ou n d is p roba bly a good s t a rt in g p oin t , t o be
p u rs u e d by ot h e r t e s t in g.

MUSCLE BIOPSY
Alt h o u gh p h ys icia n s m a y b e re lu ct a n t t o p e rfo r m a m u s cle b io p s y in w h a t
w ou ld a p p e a r t o be s t ra igh t forw a rd ca s e s of DM o r PM, a biop s y s h o u ld be
in clu d e d e a rly in t h e eva lu a t ion of m os t p a t ie n t s , give n t h e m a n y ot h e r con d i-
t ion s t h a t ca n clos e ly m im ic t h e IIM. Th e biop s y m a y reve a l a n u n e xp e ct e d
d is e a s e, s om e t im e s w it h im p o rt a n t t h e ra p e u t ic, p rogn o s t ic, or re p rod u ct ive
im p lica t io n s . It s h ou ld be obt a in e d in t h e m u s cle ju d ge d t o be t h e w e a ke s t
(u s u a lly t h e d e lt o id o r q u a d rice p s m u s cle s ), a n d o n t h e s id e o p p o s it e fro m
w h e re t h e EMG w a s p e rform e d , t o a vo id a fa ls e -p o s it ive re s u lt . No n e t h e le s s ,
t h e biop s y m ay n ot a lw a ys be d ia gn os t ic. W h e n a m u s cle ce ll d ie s for a n y re a -
s on , a s e con d a ry in a m m a t ory p roce s s m ay occu r. Th e re fore, m u s cle in a m -
m a t io n ca n b e p re s e n t in s o m e d ys t ro p h ie s , e s p e cia lly fa cio s ca p u lo h u m e ra l
a n d d ys fe rlin d ys t rop h ie s , a n d in s om e t oxic m yop a t h ie s . In a d d it ion , in a m -
m a t ion in t yp ica l m yos it is m ay be m is s e d be ca u s e of it s s p ot t y n a t u re or a s a
re s u lt of t h e ra p y. Th e yie ld ca n be im p rove d by p e rform in g a n MRI of t h e m os t
clin ica lly a ffe ct e d m u s cle s , w h ich ca n d e t e ct m u s cle in a m m a t ion a n d d a m -
a ge a n d t h u s d ire ct t h e s it e of biop s y.
W h e n it is d e t e ct e d , m u s cle in a m m a t ion in IIM con s is t s of a p re p on d e r-
a n ce of lym p h ocyt e s , w h ich a re oft e n in d ire ct con t a ct w it h a d yin g m yocyt e
(e n d o m ys ia l), a s in t h e ca s e o f cyt o t ox ic CD8 T ce lls in PM (Fig. 13.2A); o r
 Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 127

A B

s
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C D

S
3
N
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S
E F

Figure 13.2 Biopsy ndings in Myositis. A: Muscle biopsies from pa tients with polymyositis tend to show foca l endomysia l in ltra tion by mononuclea r
cells (hema toxylin a nd eosin sta in). B: Muscle biopsies from pa tients with derma tomyositis show more periva scula r a nd interstitia l in a mma tion with
perifa scicula r myo ber a trophy (modi ed trichrome sta in). C: Tra nsverse fresh-frozen section of muscle from a pa tient with inclusion body myositis dis-
pla ying purplish gra nula r ma teria l lining the multiple va cuoles in severa l myo bers a nd the presence of a ngula ted myo bers (modi ed trichrome sta in).
D: Strong a lka line phospha ta se sta ining of the interstitium is common in the IIM a nd ca n help distinguish this condition from other myopa thies, even in
the a bsence of in a mma tion. E: Trichinosis pa ra sites in a myo ber surrounded by mononuclea r in a mma tory cells in a pa tient origina lly misdia gnosed
with polymyositis (Courtesy Dr. Lori A. Love ). F: Intensely in a mma tory gra nuloma tous myositis is cha ra cterized by the presence of gra nuloma ta a nd
endomysia l in a mma tion in this pa tient with sa rcoidosis (hema toxylin a nd eosin sta in). With permission from Miller W. Frederick. In a mma tory myopa -
thies: Polymyositis, derma tomyositis, a nd rela ted conditions. In: Koopma n WJ, Morela nd LW, eds. Arthritis a nd Allied Conditions: A Textbook of
Rheuma tology. 15th ed. Ba ltimore: Lippincott Willia ms & Wilkins; 2005:6–7.
128 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
WHEN TO REFER
• In it ia l d ia g n o sis o f IIM.
• Pa t ie n t w it h IIM n o t
re sp o n d in g t o m a xim a l
d o se s o f p re d n iso n e .
• Pa t ie n t w it h IIM w it h
su sp e ct e d in t e rst it ia l
lu n g d ise a se , ca rd ia c
in vo lve m e n t , o r se ve re
GI in vo lve m e n t .
• Pa t ie n t w it h ch ro n ic
IIM w it h n e w w e a kn e ss,
su sp e ct e d t o h a ve a re d .
• Pa t ie n t w it h DM w it h skin
in vo lve m e n t o n ly, n o t
re sp o n d in g t o st a n d a rd
t h e ra p y.
• Fo r p a t ie n t s w it h IIM
w it h a n e w ly d isco ve re d
ma ligna ncy, re fe r promptly
t o a n o n co lo g ist , a s
t re a t m e n t o f t h e m a lig -
n a n cy w ill u su a lly a lso
t re a t t h e IIM.
be t w e e n u n a ffe ct e d ce lls a n d fa s cicle s (p e rim ys ia l); or in t h e a d ja ce n t in t e rs t i-
t ia l t is s u e , a s in t h e ca s e o f CD4 T ce lls in DM (Fig. 13.2B). Th e n d in g of
s m a lle r m yocyt e s a t t h e p e rip h e ry of t h e fa s cicle, ca lle d p e rifa s cicu la r a t rop h y,
is a ls o h e lp fu l in d ia gn os in g DM. In a d d it io n , s t ron g a ct ivit y of t h e a lka lin e
p h os p h a t a s e s t a in in t h e in t e rs t it iu m , re e ct in g rege n e ra t in g m u s cle be rs a n d
in a m m a t ion , s u gge s t s a n IIM eve n if o t h e r evid e n ce of in a m m a t ion is n o t
p rom in e n t (Fig. 13.2D ).
Pre d om in a n ce of n e u t rop h ils or p e rin e u ra l in a m m a t ion u s u a lly p oin t s t o
a p roce s s ot h e r t h a n IIM, w h e re a s p re d om in a n t p la s m a ce lls , e os in op h ils , or
gra n u lom a t a in a n ot h e rw is e t yp ica l m yos it is s u gge s t t h e t yp e of IIM p re s e n t
(i.e ., e o s in o p h ilic m yo s it is o r s a rco id o s is ; Fig. 13.2F). Ir re gu la r re d -r im m e d
in clu s ion s on t rich rom e s t a in ca n id e n t ify IBM (Fig. 13.2C). Th e n d in g of p rom -
in e n t glycoge n (by p e riod ic a cid –Sch iff s t a in ), fa t (by oil re d O s t a in ), a bn orm a l
m it och on d ria (t h e ra gge d re d be r on h e m a t oxylin a n d e os in s t a in ), or ot h e r
in clu s ion s s h ou ld m ove on e a w a y from t h e d ia gn os is of IIM t o t h a t of ot h e r
s yn d rom e s . Th e m u s cle biop s y ca n oft e n a ls o be h e lp fu l in id e n t ifyin g in fe c-
t iou s e t iologie s , s u ch a s t rich in os is (Fig. 13.2E).
IMAGING STUDIES
Ra d iogra p h ic s t u d ies a re u s e fu l in s cre en in g for a n d a s s e s s in g ga s t roin t e s t in a l,
ca rd ia c, a n d p u lm on a ry d is e a s e, eros ive a rt h rop a t h y, or ca lci ca t ion s (Ta ble 13.3 ).
Th e re is in cre a s in g in t e re s t in u s in g MRI, a n d a re la t e d t e ch n iq u e ca lle d m a g-
n e t ic re s o n a n ce s p e ct ro s co p y, t o a s s e s s m u s cle d is e a s e b e ca u s e t h e s e t e ch -
n iq u e s a re n on in va s ive a n d ca n s a m p le la rge r vo lu m e s o f m u s cle t h a n EMG
a n d m u s cle b iop s y. St u d ie s s u gge s t t h a t a co m bin a t ion of t h e T1-w e igh t e d
im a ge a n d t h e STIR (s h ort t a u in ve rs ion rep e a t ) or ot h e r fa t -s u p p re s s e d im a ge
s h ou ld be com bin e d t o a s s e s s m u s cle d is e a s e in IIM. Mu lt ip le cros s -s e ct ion s of
t h e t h igh s a re u s u a lly u s e fu l view s , bu t t h e loca t ion t o be eva lu a t e d s h ou ld be
d ict a t e d by t h e lo ca t ion of t h e m os t s eve re t h e s ign s a n d s ym p t om s of t h e
in d ivid u a l. De s p it e t h e e xp e n s e of MRI, it m ay be a cos t -e ffe ct ive a d ju n ct for
d ia gn os in g a n d a s s e s s in g s e le ct e d p a t ie n t s by d ire ct in g t h e biop s y s it e. Of n ot e,
p a t ie n t s s h ou ld be in s t ru ct e d t o re s t for a t le a s t a n h ou r p rior t o t h e s t u d y.
Act ive e xe rcis e ca n ca u s e m u s cle ch a n ge s t h a t re s u lt in t ra n s ie n t e leva t ion s in
s e ru m CK leve ls a n d in a m m a t ory ch a n ge s s e e n on MRI.
Tre a tme nt
GENERAL CONSIDERATIONS
Fo r t h e p r im a ry ca re p h ys icia n , t h e r s t s t e p in t re a t m e n t is t o con s id e r e a r ly
re fe r ra l t o a s p e cia lis t fa m ilia r w it h m u s cle d is e a s e s (a r h e u m a t o lo gis t , o r
n e u ro logis t , w it h t h e a s s is t a n ce of a d e r m a t ologis t , d e p e n d in g o n t h e ca s e ).
Th e re a re m a n y re a s o n s for e a r ly re fe r ra l, in clu d in g t h e fa ct t h a t a d e la y in
d ia gn o s is is a s s o cia t e d w it h in cr e a s e d m o r b id it y a n d m o r t a lit y (2 ); t h a t
m yos it is a u t o a n t ibo d y t e s t in g a s w e ll a s s p e ci c s t a in s a n d in t e r p re t a t io n o f
m u s cle b io p s ie s fre q u e n t ly re q u ire e x p e r t is e fro m t e r t ia ry re fe r ra l ce n t e r s ;
t h a t t h e IIM a re m u lt io rga n d is e a s e s t h a t u s u a lly n e ce s s it a t e m u lt is p e cia lt y
eva lu a t io n a n d co o rd in a t io n o f ca re ; a n d t h a t d e d ica t e d t e r t ia ry re fe r ra l ce n t -
e r s h a ve o n go in g re s e a rch e ffo r t s t h a t a re in va lu a ble fo r p a t ie n t s w it h t h e s e
ve ry ra re d is e a s e s .
Th e ra py s h ou ld be in d ivid u a lize d on t h e ba s is of p rogn os t ic fa ct ors , s eve rit y
o f d is e a s e , a n d ris k fa ct ors for a d ve rs e eve n t s a s s ocia t e d w it h t h e ra p e u t ic
a ge n t s . Th e p a s t d e ca d e h a s s e e n a s h ift from t h e t ra d it ion a l a p p roa ch of s t ep p e d
t h e ra p y—in w h ich a s t ru ct u re d s e rie s of rs t -lin e, s e con d -lin e, a n d t h ird -lin e
a ge n t s a re p re s cribe d in ch ron ologic ord e r a s d is e a s e s eve rit y in cre a s e s —t o
m ore in d ivid u a lize d , a n d oft e n m ore a ggre s s ive, form s of t h e ra py.
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 129

How eve r, a s s e s s in g d is e a s e s eve rit y re m a in s a m a jor ch a lle n ge, e s p e cia lly

in ch ro n ic ca s e s . It is o ft e n d if cu lt t o d is t in gu is h m yo s it is d is e a s e a ct ivit y
(d e n e d a s in a m m a t o ry ch a n ge s t h a t m a y re s p o n d t o im m u n o s u p p re s s ive
t h e ra p y) fro m d is e a s e d a m a ge (d e n e d a s ir reve r s ible ch a n ge s t h a t h a ve
re s u lt e d from p rior d is e a s e a ct ivit y), s in ce bot h m a n ife s t p rim a rily a s m u s cle
w e a kn e s s . To t h is e n d , t h e In t e r n a t io n a l Myos it is As s e s s m e n t a n d Clin ica l
St u d ie s Grou p (IMACS), a n in t e rn a t ion a l con s ort iu m of m yos it is e xp e rt s , h a s
d eve lo p e d d is e a s e a ct ivit y a n d d is e a s e d a m a ge in d ice s , w h ich in co r p ora t e
p h ys ica l e xa m in a t ion n d in gs a s w e ll a s la bora t ory va lu e s in ord e r t o be t t e r
q u a n t ify a n d d is t in gu is h a ct ive d is e a s e from d a m a ge, a n d t h u s be t t e r t a ilor
t h e ra py (10 ).

REHABILITATION
Th e goa l of a ll t h e ra p y is t o op t im ize t h e fu n ct ion a l leve ls of p a t ie n t s a n d , if
p os s ible, t o re t u rn t h e m t o n orm a l. In t h is rega rd , p h ys ica l a n d occu p a t ion a l
t h e ra p y re m a in u n d e ru t ilize d m od a lit ie s . Gra d e d re h a bilit a t ion t h a t t a ke s in t o
a ccou n t t h e s t a ge a n d s eve rit y of t h e p a t ie n t ’s m yos it is is t h e be s t a p p roa ch .

s
e
Alt h ou gh be d re s t is oft e n n e ce s s a ry d u rin g p e riod s of s eve re d is e a s e, p a s s ive

s
a
ra n ge of m ot ion e xe rcis e s a n d s t re t ch in g s h ou ld be in it ia t e d e a rly, e s p e cia lly in

e
s
i
ve ry d e bilit a t e d , h os p it a lize d p a t ie n t s t o p reve n t t h e form a t ion of con t ra ct u re s .

D
As t h e d e gre e o f m yo s it is d e cre a s e s , p a t ie n t s s h o u ld in cre a s e t h e ir a ct ivit y

c
i
t
a
t h rou gh s t a ge s : a ct ive -a s s is t e d ra n ge of m ot ion , follow e d by is om e t ric, t h e n

m
is ot on ic, a n d n a lly, a e robic e xe rcis e.

u
e
h
R
c
THERAPEUTIC APPROACHES FOR MYOSITIS

i
c
e
Cort icos t e roid s re m a in t h e p rim a ry t h e ra p y for t h e IIM a n d s h ou ld be in it ia t e d

p
S
a s e a rly a s p os s ible in n e a rly a ll p a t ie n t s , w it h t h e re cogn it ion t h a t t h ey t e n d

3
N
t o re q u ire h igh d os e s for lon g p e riod s of t im e. Im p ort a n t con s id e ra t ion s in clu d e

O
a n a d e q u a t e in it ia l d os e (in m os t ca s e s a t le a s t 1 m g/kg/d a y) (1 ), con t in u a t ion

I
T
C
of p re d n is on e a t a h igh d os e u n t il or a ft e r t h e s e ru m CK be com e s n orm a l (2 ),

E
S
w h ich m a y la s t s eve ra l m on t h s , a n d a s low ra t e of p re d n is on e t a p e rin g (3 , 11 ).
Ta p e rin g p re d n is on e t oo q u ickly le a d s t o re la p s e. Th e role of p u ls e cort icos t e r-
o id s a s t re a t m e n t re m a in s u n cle a r. In d ivid u a ls w it h p o or p rogn o s t ic fa ct o rs
s h ou ld be con s id e re d for m ore a ggre s s ive t h e ra py u s in g cort icos t e roid s w it h a n
a d d e d cyt ot oxic a ge n t from t h e begin n in g of t h e ir d is e a s e.
Du rin g t h is t re a t m e n t p h a s e, bot h t h e p rim a ry ca re p h ys icia n a n d t h e s p e -
cia lis t n e e d t o a ggre s s ive ly s cre e n for, p reve n t , a n d m a n a ge com m on s id e e ffe ct s
of h igh d os e s of p re d n is on e, s u ch a s in fe ct ion s , GI u lce rs , d ia be t e s , h yp e rt e n -
s io n , h yp e rlip id e m ia , w a t e r re t e n t ion , o s t e op e n ia /os t e op oros is , a n xie t y, a n d
p s ych os is , t o n a m e a few. Ca re fu l con s id e ra t ion s h ou ld be give n t o in it ia t ion of
Pneum ocystis jirov ecii p n e u m on ia p rop h yla xis , e s p e cia lly in t h e e ld e rly or t h os e
w it h d e cre a s e d re n a l cle a ra n ce, s in ce t rim e t h op rim s u lfa m e t h oxa zole (Ba ct rim )
in t e ra ct s w it h m e t h ot re xa t e (on e of t h e cyt ot oxic a ge n t s fre q u e n t ly u s e d for
IIM), ca u s in g t oxic leve ls of m e t h ot re xa t e a n d bon e m a rrow s u p p re s s ion .
Th e t re a t m e n t of IBM re m a in s con t rove rs ia l a n d m os t p a t ie n t s w it h IBM d o
n ot re s p on d t o t h e ra p y a t t h e leve l s e e n in p a t ie n t s w it h m yos it is in t h e ot h e r
clin ica l grou p s . Pa t ie n t s w it h IBM a n d evid e n ce of a ct ive in a m m a t ion , h ow -
eve r, m ay be n e t from cort icos t e roid a n d cyt ot oxic t h e ra p y in t e rm s of s low in g
t h e ra t e of p rogre s s ion of d is e a s e. Re t ros p e ct ive review s of cort icos t e roid a n d
cyt ot oxic t h e ra py, a p ros p e ct ive op e n t ria l of in t ra ve n ou s ga m m a globu lin (IVIg),
a n d a ra n d om ize d t ria l of com bin a t ion ora l m e t h ot re xa t e p lu s a za t h iop rin e
ve rs u s h igh -d os e m e t h ot re xa t e w it h le u covorin re s cu e, a ll s u gge s t t h a t t h e ra t e
of d e t e riora t ion m ay be d e cre a s e d or s t a bilize d in t h os e p a t ie n t s .
Alt h ou gh m os t p a t ie n t s w it h DM or PM h ave a t le a s t a p a rt ia l re s p on s e t o
cort icos t e roid s , s om e d o n ot re s p on d a d e q u a t e ly, m a n y m ore exp e rie n ce d is e a s e
 130 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

a ct ivit y in cre a s e s d u r in g s t e roid t a p e rin g, a n d m os t eve n t u a lly s u ffe r fro m

t h e t o x icit ie s o f co r t ico s t e ro id s . Lit t le is k n ow n a b o u t o p t im a l t h e ra p y in
corticosteroid -resista n t p a tien ts. Ora l m eth otrexa te, a t d oses of 7.5 to 25 m g/w eek,
a n d a za t h iop rin e, a t 50 t o 150 m g/d a y, a re t h e m a jor t h e ra p e u t ic op t ion s for
p a t ie n t s w h o a re cort icos t e roid re s is t a n t a n d p a t ie n t s w it h in it ia lly m od e ra t e
t o h igh d is e a s e a ct ivit y. A com bin a t ion of m e t h ot re xa t e a n d a za t h iop rin e le a d s
to im p rovem en t in som e p a tien ts w h o h ave h a d in a d eq u a te resp on ses to eith er
agen t given a lon e. In traven ou s ga m m aglobu lin , cyclop h osp h a m id e, m ycop h en o-
la te m ofetil, FK506, or oth er com bin a tion s of cytotoxic agen ts m ay be ben e cia l in
som e p a tien ts a n d w a rra n t fu rth er eva lu a tion . A d ou ble-blin d , p la cebo-con trolled
t ria l h a s s h ow n t h a t IVIg a t le a s t t ra n s ie n t ly in cre a s e s s t re n gt h a n d d e cre a s e s
CK, ra s h , a n d m u s cle in a m m a t ion in s om e p a t ie n t s w it h DM. Th e n ove l bio-
logic a n t i-in a m m a t ory a ge n t rit u xim a b h a s be e n s t u d ie d in on e m u lt ice n t e r,
p la ce bo-co n t rolle d ra n d om iz e d clin ica l t r ia l t h a t is n e a r in g com p le t io n a n d
s h ow s e a rly p rom is in g re s u lt s in s om e p a t ie n t s .
Ma n y orga n s ys t e m s m ay be a ffe ct e d in IIM a n d ca u s e s ign i ca n t m orbid it y
a n d m o r t a lit y. Ge n e ra l s ym p t o m s o f fa t igu e , feve r, a n d w e igh t lo s s o ft e n
re s p o n d t o co r t ico s t e ro id o r cyt o t ox ic t h e ra p y fo r t h e u n d e r lyin g m yo s it is .
S
E
Ra yn a u d ’s p h e n om e n on m a y re s p on d t o cold a void a n ce or ca lciu m ch a n n e l
C
T
blocke rs . Th e ra s h of DM m ay be a ve ry t rou ble s om e p roble m for t h e p a t ie n t
I
O
a n d m a y p e rs is t lon g a ft e r t h e m yos it is h a s re s olve d . Avoid a n ce of s u n a n d
N
p h ot os e n s it ize rs —a s w e ll a s t op ica l s u n s cre e n s a n d s t e roid s —m a y be h e lp fu l,
3
S
bu t oft e n t h e u s e of h yd roxych loroq u in e or m e t h ot re xa t e is re q u ire d . Som e
p
e
a u t h ors h ave u s e d q u in a crin e s u cce s s fu lly, a n d is ot re t in oin , d e s p it e t e ra t oge n ic
c
i
con ce rn s , m ay be u se fu l in th e t rea tm en t of IIM ra s h es . Su bcu ta n eou s ca lci ca -
c
R
tion s, m ore com m on in ch ild ren t h a n a d u lts , ca n be very t rou blin g. No trea tm en t ,
h
e
ot h e r t h a n t h e ra p y for t h e u n d e rlyin g m yos it is , h a s be e n s h ow n t o im p rove
u
m
ca lci ca t ion s .
a
Pu lm on a ry bros is is a w orris om e com p lica t ion in p a t ie n t s w it h IIM, ca n
t
i
c
d eve lop ra p id ly, a n d in s om e p a t ie n t s d oe s n ot im p rove w it h a n y t h e ra p y. Nev-
D
i
s
e rt h e le s s , p u ls e cort icos t e roid s , cyclos p orin e A w it h ca re fu l d ru g leve l m on it or-
e
a
in g, t a crolim u s , a n d cyclop h os p h a m id e a re oft e n t rie d in a n a t t e m p t t o t re a t
s
e
t h is ca u s e of gre a t m orbid it y a n d m ort a lit y. Th e role of p u lm on a ry t ra n s p la n t a -
s
t ion in p u lm on a ry d ys fu n ct ion a s s ocia t e d w it h s ys t e m ic a u t oim m u n e d is e a s e
re m a in s u n cle a r, bu t a n e cd ot a l rep ort s s u gge s t s u cce s s fu l ou t com e s in s om e
p a t ie n t s . Sym p t om a t ic h e a rt fa ilu re s h ou ld be t re a t e d in t h e s t a n d a rd m a n n e r,
a n d if con d u ct ion s ys t e m a bn orm a lit ie s a re p re s e n t , a n t ia rrh yt h m ics a n d /or
p a ce m a ke r im p la n t a t ion s h ou ld be con s id e re d . If m yoca rd it is is p re s e n t , cort i-
cos t e roid s a n d cyt ot oxic a ge n t s s h ou ld be u s e d .
Som e p a t ie n t s h a ve s u ch s eve re d ys p h a gia a n d a re a t s u ch h igh ris k o f
a s p ira t ion t h a t t u be fe e d in gs a re n e ce s s a ry. Re u x e s op h a git is is com m on (a s
in t h e clin ica l ca s e a bove ) a n d s h ou ld be t re a t e d by t h e u s u a l a p p roa ch e s of
e leva t in g t h e h e a d of t h e be d , p re s cribin g a n t a cid s , or H2-re ce p t or a n t a gon is t s .
Cr ico p h a ryn ge a l d ys fu n ct io n ca n b e t h e ca u s e o f s ign i ca n t d ys p h a gia a n d
od yn op h a gia , a n d m ay im p rove w it h m yot om y.

Clinica l Co urse
Th e IIM a re s e r io u s a n d s o m e t im e s life -t h re a t e n in g d is e a s e s . Su r viva l o f
p a t ie n t s w it h m yos it is h a s be e n in cre a s in g d u rin g t h e p a s t few d e ca d e s from
50% p rior t o t h e in t rod u ct ion of cort icos t e roid t h e ra py, t o 5-ye a r s u rviva l ra t e s
of 65% in 1947 t o 1968, t o a p p roxim a t e ly 80% m ore re ce n t ly (12 ). La rge coh ort
s e rie s w it h lon g follow -u p h ave s h ow n t h a t , in ge n e ra l, a p p roxim a t e ly 20% t o
30% of p a t ie n t s w it h IIM h ave a m on op h a s ic illn e s s (a n d n o lon ge r re q u ire a n y
t h e ra p y a ft e r 2 ye a rs of t re a t m e n t ), 20% t o 30% h a ve a p olyp h a s ic illn e s s ch a r-
a ct e rize d by a re s p u n ct u a t e d w it h p e riod s of re m is s ion , w h ile t h e re s t h ave a
ch ron ic p rogre s s ive cou rs e a n d re q u ire s u s t a in e d t re a t m e n t (13 ).
Ch a p te r 13 In a m m a t ory Myop a t h ie s : Polym yos it is , De rm a t om yos it is , a n d Re la t e d Con d it ion s 131

Th e ra rit y a n d h e t e roge n e it y of m yos it is h a s lim it e d t h e colle ct ion of s u ch

d a t a , ye t a n u m be r of s t u d ie s h a ve a t t e m p t e d t o d e n e p rogn os t ic fa ct ors in
t h e IIM. Ad ve rs e p rogn os t ic fa ct ors in clu d e PM a s op p os e d t o DM, old e r a ge,
a s s ocia t e d m a lign a n cy, ca rd io p u lm o n a ry d is e a s e , s eve re w e a k n e s s , lo n ge r
d u ra t ion of w e a kn e s s p rior t o d ia gn os is , feve r, d ys p h a gia , IBM, or t h e p re s e n ce
of a n t is yn t h e t a s e or a n t is ign a l re cogn it ion p a rt icle a u t oa n t ibod ie s . Som e s e ro-
logic n d in gs p re d ict a m ore be n ign m yos it is cou rs e. Th e s e in clu d e a n t i-Mi-2,
a n t i-PM-Scl, a n d a n t i-U1RNP a u t oa n t ibod ie s (3 ).

Ackno w le dg me nts
We t h a n k Dr. St eve n Yt t e rbe rg for m a n y u s e fu l d is cu s s ion s a bou t m yos it is . Th is
w ork w a s s u p p ort e d by t h e in t ra m u ra l p rogra m o f t h e Na t ion a l In s t it u t e of
En viron m e n t a l He a lt h Scie n ce s , NIH.

Re fe r to Patie nt Education

s
ICD9

e
s
a
710.3 De rmato myo sitis (acu t e ) (ch ro n ic)

e
s
729.1 Myo sitis

i
D
729.1 rh e u m at ic

c
i
t
729.1 rh e u m at o id

a
m
729.1 t rau m at ic (o ld )

u
e
Po lymyo sitis (acu t e ) (ch ro n ic)

h
R
710.4 (h e m o rrh ag ic)

c
w it h in vo lve m e n t o f

i
c
e
710.4 [517.8] lu n g

p
S
710.3 sk in

3
N
O
I
T
C
E
Re fe re nce s

S
1. Plot z PH , Da la ka s M , Le ff RL, e t a l. Cu rre n t con cep t s in t h e id iop a t h ic in a m m a t ory m yop a t h ie s : p oly-
m yos it is , d e rm a t om yos it is , a n d re la t e d d is ord e rs . A nn Intern Med 1989 ;111 :143 –157 .
2. Airio A, Ka u t ia in e n H , Ha ka la M . Progn os is a n d m ort a lit y of p olym yos it is a n d d e rm a t om yos it is p a t ie n t s .
Clin Rheum atol 2006 ;25 :234 –239 .
3. Ta rgoff IN . De rm a t om yos it is a n d p olym yos it is . Curr Probl Derm atol 1991 ;3 :131 –180 .
4. Boh a n A, Pe t e r JB. Polym yo s it is a n d d e r m a t om yos it is (p a rt s 1 a n d 2). N Engl J Med 1975 ;292 :344 –347 ,
403 –407 .
5. Mille r FW . Myos it is -s p e ci c a u t oa n t ibod ie s . Tou ch s t on e s for u n d e rs t a n d in g t h e in a m m a t ory m yop a -
t h ie s . JA MA 1993 ;270 :1846 –1849 .
6. Fra s e r DD, Fra n k JA, Da la ka s M , e t a l. Ma gn e t ic re s on a n ce im a gin g in t h e id iop a t h ic in a m m a t ory
m yop a t h ie s . J Rheum atol 1991 ;18 :1693 –1700 .
7. Hill CL, Zh a n g Y, Sigu rge irs s on B, e t a l. Fre q u e n cy of s p e ci c ca n ce r t yp e s in d e rm a t om yos it is a n d p oly-
m yos it is : A p op u la t ion -ba s e d s t u d y. Lancet 2001 ;357 :96 –100 .
8. Gre e n be rg SA. Prop os e d im m u n ologic m od e ls of t h e in a m m a t ory m yop a t h ie s a n d p ot e n t ia l t h e ra p e u -
t ic im p lica t ion s . Neurology 2007 ;69 :1966 –1967 .
9. Va n cs a A, Ge rge ly L, Pon yi A, e t a l. Myo s it is -s p e ci c a n d m yo s it is -a s s ocia t e d a n t ibod ie s in ove r la p
m yos it is in com p a ris on t o p r im a ry d e rm a t op olym yos it is : Re leva n ce for clin ica l cla s s i ca t ion : re t ro-
s p e ct ive s t u d y of 169 p a t ie n t s . Joint Bone Spine 2010 ;77 :125 –130 .
10. Is e n be rg DA, Alle n E, Fa rew e ll V, e t a l., for t h e In t e rn a t ion a l Myos it is a n d Clin ica l St u d ie s Grou p (IMACS).
In t e rn a t ion a l con s e n s u s ou t com e m e a s u re s fo r p a t ie n t s w it h id iop a t h ic in a m m a t ory m yop a t h ie s .
Deve lop m e n t a n d in it ia l va lid a t ion of m yos it is a ct ivit y a n d d a m a ge in d ice s in p a t ie n t s w it h a d u lt on s e t
d is e a s e . Rheum atology 2004 ;43 :49 –54 .
11. He n gs t m a n GJD, Va n De n Ho oge n FHJ, va n En ge le n BGM . Tre a t m e n t of t h e in a m m a t ory m yop a t h ie s :
Up d a t e a n d p ra ct ica l re com m e n d a t ion s . Expert Opin Pharm acother 2009 ;10 :1183 –1190 .
12. Lu n d b e rg IE, Fo r b e s s CJ. Mo r t a lit y in id io p a t h ic in a m m a t o r y m yo p a t h ie s . Clin Ex p Rheu m atol
2008 ;26 :S109 –S114 .
13. Bron n e r IM , Va n De r Me u le n MFG, d e Vis s e r M , e t a l. Lon g-t e rm ou t com e in p olym yos it is a n d d e rm a t o-
m yos it is . A nn Rheum Dis 2006 ;65 :1456 –1461 .
 CHAPTER
14 Va sculitis
Bao Quynh N. Huynh and S. Louis Bridges , Jr

A 39-ye ar-old fe m ale w it h an

Clinica l
ant inu cle ar ant ib ody tite r of
Pre se nta tio n
1:320, spe ck le d p att e rn is Va s cu lit is is a h e t e r o ge n e o u s
grou p of d is ord e rs ch a ra ct e rize d
re f e rre d to a rhe um atologist
S
by in a m m a t io n o f blo o d ve s -
E
C
for painf ul e ryt h e m atous s e ls . On e s ys t e m of cla s s i ca t ion
T
I
O
le sions on he r low e r e xt re m i- o f va s cu lit id e s is b a s e d o n t h e
N
tie s. De spite be ing on antibi- s ize o f t h e p re d om in a n t ve s s e ls
3
in volve d (Ta ble 14.1 ). Fo r e x a m -
S
otics for pre sum e d ce llulitis,
p
p le , gia n t ce ll a r t e r it is (GCA)
e
c
her sym pt om s progre sse d,
i
in vo lve s la rge -s iz e d blo o d ve s -
c
w it h addit ional sim ilar le sions s e ls s u ch a s t h e a o r t a a n d it s
R
h
b ra n ch e s , w h e re a s p o lya r t e r it is
e
de ve lo ping ove r t he le f t ank le , le ft calf , right foot , and right low e r
u
n o d o s a in vo lve s m e d iu m -s iz e d
m
le g. He r physical e xam inat ion w as re m ark able f or m ult iple 0.3- to 1-cm
a
ve s s e ls co n t a in in g a n in t e r n a l
t
i
c
raise d, palpable , te nde r purpuric le sions ove r t he ank le and post e rior e la s t ic m e m b r a n e , m u s c u la r
D
i
aspe ct of t he calve s (Fig. 14.1 ). The re m ainde r of the e xam inat ion w as m e d ia , a n d a d ve n t it ia . Sm a ll-
s
e
ve s s e l va s cu lit is in volve s ca p il-
a
w it hin norm al lim its. Laboratory e valuation including com ple t e blood
s
e
la rie s , a n d p os t ca p illa ry ve n u le s
s
count (CBC), che m ist ry p ro le , se dim e nt ation rat e , live r f unction te sts,
a n d a rt e riole s . Prior t o t h e 1990s ,
he patitis se rologie s, and se rum cryoglobulins w as norm al or ne gative . a form a l cla s s i ca t ion s ys t e m of
A sk in biopsy of an active le sion w as consist e nt w it h le uk ocyt oclastic va s cu lit ic s y n d r o m e s d id n o t
vasculit is. She w as t re at e d w ith pre dnisone , but had an incom ple te e xis t be ca u s e of a la ck of con s e n -
s u s in evid e n ce -ba s e d cla s s i ca -
re sp onse , so az at hioprin e w as adde d. Ove r a course of se ve ral m onths,
t ion of in d ivid u a l p a t ie n t s w it h
he r le sions re solve d com ple t e ly, le aving only scarring (Fig . 14.1 ). va s cu lit ic s yn d r o m e s (1 ). Th is
w a s a d d re s s e d by t h e Am e rica n

A B

Figure 14 .1 Skin lesions a t presenta tion (A) a nd a fter resolution (B). By permission of Devore AE a nd Jorizzo JL.
Cha pter 39: Cuta neous sma ll vessel va sculitis. In: Va sculitis , 2nd ed. Ba ll GV a nd Bridges SLJr., eds. New York:
132 Oxford University Press, Inc.; 2008.
 Ch a p te r 14 Va s cu lit is 133

Table 14.1 Classi cat ion of More Common Forms of Vasculit is,
Emphasizing t he Predominant Size of Involved Vessels

Larg e ve sse l
Gia n t ce ll (t e m p o ra l) a rt e rit is
Ta ka ya su ’s a rt e rit is
Me dium ve sse l
Po lya rt e rit is n o d o sa
He p a t it is B viru s re la t e d
Fa m ilia l Me d it e rra n e a n fe ve r
Cu t a n e o u s p o lya rt e rit is n o d o sa
Ka w a sa ki’s d ise a se
Me dium- to small ve sse l
We g e n e r’s g ra n u lo m a t o sis
Ch u rg –St ra u ss syn d ro m e
Micro sco p ic p o lya n g iit is (p o lya rt e rit is)
Va scu lit is o f co n n e ct ive t issu e d ise a se s
Be h çe t ’s syn d ro m e (m a y b e la rg e )
Small ve sse l

s
Cu t a n e o u s le u ko cyt o cla st ic a n g iit is

e
s
He n o ch –Sch ö n le in p u rp u ra

a
e
Cryo g lo b u lin e m ic va scu lit is

s
i
D
c
i
Ad a p t e d fro m Re fe re n ce (4).

t
a
m
u
e
h
R
College of Rh e u m a t ology (ACR) in 1990, w h ich p rop os e d crit e ria for t h e cla s s i -

c
i
ca t ion of s eve n d iffe re n t va s cu lit id e s (2 ). Th e s e crit e ria a re n ot m e a n t a s d ia g-

c
e
n os t ic crit e ria , a s t h ey com p a re d p a t ie n t s w it h d iffe re n t t yp e s of va s cu lit is , bu t

p
S
n ot p a t ie n t s w it h ot h e r s ys t e m ic or con n e ct ive t is s u e d is e a s e s .

3
Th e ACR cla s s i ca t io n cr it e r ia d o n o t in clu d e m icro s co p ic p o lya n giit is

N
O
(MPA) or con s id e r a n t in e u t rop h il cyt op la s m ic a n t ibod ie s (ANCA) a s d ia gn os t ic

I
T
C
crit e ria . In 1994, t h e Ch a p e l Hill Con s e n s u s Con fe re n ce (CHCC) p rod u ce d d e -

E
S
n it ion s for va s cu lit is (3 ) a n d in clu d e d MPA in it s cla s s i ca t ion crit e ria . Th ey a ls o
re cogn ize d t h a t h is t ologica l d a t a w ou ld n ot be ava ila ble for a ll p a t ie n t s , e s p e -
cia lly w h e n t h e clin ica l co n d it io n o f t h e p a t ie n t m igh t p re clu d e o b t a in in g
a p p rop ria t e biop s ie s . Fu rt h e rm ore, t h e s a m p le m igh t n ot be rep re s e n t a t ive or
t h e s a lie n t h is t ologica l fe a t u re s m ay n ot be fou n d be ca u s e of s a m p lin g e rror.
Th e cla s s i ca t ion s ch e m e in Ta ble 14.1 e m bo d ie s fe a t u re s o f bo t h ACR a n d
CHCC crit e ria , a n d is n ow w id e ly u s e d for ep id e m iologica l s t u d ie s .

Epide mio lo g y o f Va sculitis

Th e va s cu lit id e s a ffe ct in d ivid u a ls of a ll a ge s , bu t a re p re d om in a t e ly s e e n in
t h e e xt re m e s of a ge grou p s . Fu rt h e rm ore, t h e e xa ct e t iology is u n kn ow n , bu t it
h a s be e n d e m o n s t ra t e d t o b e m u lt ifa ct or ia l w it h fa ct o rs s u ch a s e t h n icit y,
ge n e s , ge n d e r a n d u lt raviole t ligh t , in fe ct ion s , t oxin s , d ru gs , s m okin g, a n d s u r-
ge ry in u e n cin g d is e a s e e xp re s s ion (1 ).

La rg e - Ve sse l Va sculitis
GIANT CELL ARTERITIS
Th e re is a n in cre a s in g in cid e n ce w it h a ge, w it h ve ry few ca s e s occu rrin g in t h os e
you n ge r t h a n 50 ye a rs of a ge. Th e re is a gre a t e r in cid e n ce in w om e n , w it h a
fe m a le -t o-m a le ra t io of a rou n d 2:1 (1 ). Gia n t ce ll a rt e rit is is m ore com m on in
Ca u ca s ia n s t h a n in Africa n -Am e rica n s a n d His p a n ics . In t e re s t in gly, t h e in ci-
d e n ce of GCA va rie s w it h la t it u d e w it h in cre a s in g in cid e n ce w it h h igh e r la t it u d e.
 134 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

De s p it e in t e n s ive in ve s t iga t ion , n o s p e ci c in fe ct iou s a ge n t h a s be e n id e n t i-

e d . As t h e im m u n e s ys t e m a ge s it b e co m e s m ore vu ln e ra ble t o in fe ct ion s .
Re in fe ct ion w it h t h e h u m a n p a ra in u e n za viru s (HPIV) w a s a s s ocia t e d w it h t h e
on s e t of GCA. Viru s e s s u ch a s h ep a t it is B, h e rp e s zos t e r, Ep s t e in –Ba rr viru s (EBV),
h e rp e s s im p lex viru s (HSV 1 a n d 2), re s p ira t ory s yn cyt ia l viru s , a n d a d e n oviru s
h ave be e n t h ou gh t t o ca u s e GCA; h ow eve r, t h e re h a s be e n n o evid e n ce s u p p ort -
in g t h e a s s ocia t ion be t w e e n t h e s e orga n is m s a n d t h e d eve lop m e n t of GCA (1 ).

TAKAYASU’S ARTERITIS
Th is form of va s cu lit is occu rs w orld w id e, bu t it is m ore com m on in As ia . Th e
a n n u a l in cid e n ce in m os t p op u la t ion s is 1 t o 3 p e r m illion , w it h t h e p e a k a ge
of t h e on s e t of d is e a s e in t h e t h ird d e ca d e. Th e d is e a s e is m ore com m on in
w om e n (1 ).

Me dium- Ve sse l Va sculitis

S
Th e a n n u a l in cid e n ce of p olya rt e rit is n od os a (PAN) is 2 t o 9 p er m illion , w it h t h e
E
C
h igh es t in cid e n ce of 16 p er m illion in Ku w a it a n d 14.8 p e r m illion in Ja p a n . W h ere
T
I
O
th e re h a s bee n m ore a t t en t ion to h ep a tit is B va ccin a t ion , t h e p reva le n ce of PAN
N
h a s d ecre a s ed .
3
Th e p reva le n ce of Be h çe t ’s s yn d rom e is h igh e s t in t h e region s e xt e n d in g
S
p
from Ea s t e rn As ia t o t h e Me d it e rra n e a n ba s in a n d low e s t in We s t e rn cou n t rie s .
e
c
Th e h igh e s t p reva le n ce is s e e n in Tu rkey w it h 80 t o 370 ca s e s p e r 100,000 p e o-
i
c
p le. In As ia n cou n t rie s s u ch a s Ja p a n , Kore a , Ch in a , a n d Mid d le Ea s t e rn cou n -
R
h
t rie s s u ch a s Ira n a n d Sa u d i Ara bia , t h e p reva le n ce is be t w e e n 13.5 a n d 20 ca s e s
e
u
p e r 100,000 p e op le . Be h çe t ’s s yn d rom e is m o re com m on a m o n g fe m a le s in
m
a
As ia n cou n t rie s a n d a m on g m a le s in Mid d le Ea s t e rn cou n t rie s . It occu rs fre -
t
i
c
q u e n t ly in t h ird a n d fou rt h d e ca d e of life.
D
i
s
e
a
Me dium- to Sma ll- Ve sse l Va sculitis
s
e
s
Th e in cid en ce of a n tin eu trop h il cytop la sm a n tibody (ANCA)-a ssocia ted (Wegen er’s
gra n u lom a t os is (W G), Ch u rg–St ra u s s s yn d rom e , a n d MPA) is a p p roxim a t e ly
10 t o 20 p e r m illion p e r ye a r, w it h on s e t p e a kin g be t w e e n a ge s 65 a n d 74 ye a rs
(5 ). Wege n e r’s gra n u lom a t os is —a d is e a s e w it h n e crot izin g gra n u lom a t a of re s -
p ira t ory t ra ct , n e crot izin g va s cu lit is , a n d foca l glom e ru lon e p h rit is —is m ore
com m on in m e n a n d is ra re ly s e e n in ch ild re n (0.3 p e r m illion p e r ye a r). Va riou s
s t u d ie s h ave d e m on s t ra t e d t h a t W G is n ot a s com m on a s m icros cop ic a n giit is
in n on -Eu rop e a n p op u la t ion s , t h a t is , Ja p a n e s e a n d Ch in e s e. Fa m ilia l ca s e s of
W G h ave be e n rep ort e d , a lbe it ra re. HLA DPB1*0401 h a s be e n a s s ocia t e d w it h
W G. En viron m e n t a l fa ct ors s u ch a s s e a s on a lit y a n d d ru gs h ave be e n p reviou s ly
t h ou gh t t o con t ribu t e t o t h e d eve lop m e n t of W G. How eve r, s t u d ie s con d u ct e d by
La n e e t a l. d id n ot con rm t h e s e a s on a l e ffe ct on d eve lop in g t h is d is e a s e. No
s in gle d ru g h a s be e n s h ow n t o le a d t o t h e d eve lop m e n t of W G; h ow eve r, ce rt a in
d r u gs —in clu d in g co ca in e —ca n re s u lt in ANCA-a s s o cia t e d co n d it io n s t h a t
m im ic p rim a ry ANCA-a s s o cia t e d va s cu lit is . Staphylococcu s au reu s in fe ct io n s
h ave be e n a s s ocia t e d w it h W G a n d a h igh e r ris k of re la p s e (5 ).
Th e in cid e n ce of MPA is h igh e s t in Ku w a it , w it h a n in cid e n ce o f 24 p e r m il-
lion . Th e a n n u a l in cid e n ce of MPA is a ls o h igh in t h e Ja p a n e s e p op u la t ion , w it h
a n in cid e n ce of 14.8 p e r m illion from 2000 t o 2004. W it h in Eu rop e, MPA is m ore
com m on in Sou t h e rn Eu rop e, w h e re a s W G is m ore com m on in t h e n ort h e rn
p a r t o f t h e co n t in e n t . Ch u rg–St ra u s s s yn d ro m e , t h e le a s t co m m o n o f t h e
ANCA-a s s ocia t e d va s cu lit id e s , h a s a n a n n u a l in cid e n ce of 1 t o 3 p e r m illion
a n d is m ore com m on in fe m a le s t h a n m a le s . It h a s a p e a k a ge of on s e t of 65 t o
75 ye a rs (5 ).

CLINICAL POINTS
• Th e re is n o t a sp e ci c se t
o f g u id e lin e s t o h e lp t h e
g e n e ra l clin icia n in t h e
e va lu a t io n o f a p a t ie n t
w it h su sp e ct e d va scu lit is.
• Th e cu rre n t cla ssi ca t io n
crit e ria a re in t e n d e d m a in ly
fo r re se a rch p u rpo se s.
Wh ile t h e y a re h e lp fu l fo r
fra m in g t h e d ia g n ost ic
a p p ro a ch in t h e g e n e ra l
p ra ct ice se t t in g , n o t e ve ry
p a t ie n t w it h a g ive n d ise a se
w ill sa t isfy t h e se crit e ria .
• Th e p ra ct it io n e r o ft e n
re lie s o n t h e clin ica l h ist o ry
a n d o t h e r m o d a lit ie s,
in clu d in g la b o ra t o ry d a t a ,
ra d io g ra p h s, a n d h ist o p a -
t h o lo g y in t h e d ia g n o sis
o f va scu lit is.
PATIENT ASSESSMENT
• A d e t a ile d h ist o ry a n d
p h ysica l e xa m in a t io n is
ke y in t h e e va lu a t io n o f
a p a t ie n t w it h su sp e ct e d
va scu lit is.
• La b o ra t o ry t e st s a re o ft e n
h e lp fu l in t h e w o rku p o f
va scu lit is.
• Im a g in g m o d a lit ie s in t h e
d ia g n o st ic p ro ce ss in clu d e
ch e st ra d io g ra p h s (CXR),
co m p u t e d t o m o g ra p h y
(CT), m a g n e t ic re so n a n ce
im a g in g (MRI), a n g io g ra -
p h y, a n d u lt ra so u n d .
• Tissu e b io p sy re m a in s t h e
g o ld st a n d a rd o f d ia g n o sis.
Ch a p te r 14 Va s cu lit is 135
Sma ll- Ve sse l Va sculitis
HENOCH–SCHONLEIN PURPURA
He n och –Sch on le in p u rp u ra is m ore com m on ly s e e n in ch ild re n a n d le s s s e e n
in a d u lt s w it h a n in cid e n ce of 3 t o 10 p e r m illion (1 ).
CUTANEOUS SMALL- VESSEL VASCULITIS
Ou r p a t ie n t w a s d ia gn os e d w it h cu t a n e ou s s m a ll-ve s s e l va s cu lit is , a ls o re fe rre d
t o a s le u kocyt ocla s t ic va s cu lit is (a h is t ologic d e s crip t ion ) a n d h yp e rs e n s it ivit y
va s cu lit is . Th is is m ore com m on t h a n m a n y ot h e r form s of va s cu lit is . In Nor-
w ich from 1990 t o 1994, t h e a n n u a l in cid e n ce of biop s y-p rove n cu t a n e ou s le u -
kocyt ocla s t ic va s cu lit is w a s 15.4 p e r m illion , w it h a h igh e r in cid e n ce in fe m a le s .
Th e Ge rm a n s t u d y rep ort e d t h a t t h e in cid e n ce of CHCC-d e n e d cu t a n e ou s le u -
kocyt ocla s t ic a n giit is w a s 4 t o 9 p e r m illion be t w e e n 1998 a n d 2002.
Clinica l Histo ry
s
e
At p re s e n t , t h e re is n ot a s p e ci c s e t of gu id e lin e s t o h e lp t h e clin icia n in t h e
s
a
eva lu a t ion of a p a t ie n t w it h s u s p e ct e d va s cu lit is . Th e cu rre n t cla s s i ca t ion cri-
e
s
i
t e ria a re in t e n d e d m a in ly for re s e a rch p u rp os e s . W h ile t h ey a re h e lp fu l for
D
fra m in g t h e d ia gn os t ic a p p ro a ch in t h e ge n e ra l p ra ct ice s e t t in g, n o t eve ry
c
i
t
a
p a t ie n t w it h a give n d is e a s e w ill s a t is fy t h e s e crit e ria (6 ). Th u s , t h e p ra ct it ion e r
m
oft e n re lie s on t h e clin ica l h is t ory a n d ot h e r m od a lit ie s , in clu d in g la bora t ory
u
e
d a t a , ra d iogra p h s , a n d h is t op a t h ology in t h e d ia gn os is of a va s cu lit ic con d it ion .
h
R
Th e in it ia l a s s e s s m e n t in clu d e s a t h orou gh h is t ory a n d p h ys ica l e xa m in a -
c
i
t io n o f t h e p a t ie n t , w h o m a y p re s e n t o n ly w it h n o n s p e ci c co n s t it u t io n a l
c
e
s ym p t om s . Th is m a ke s t h e w orku p of s ys t e m ic va s cu lit id e s q u it e ch a lle n gin g;
p
S
h ow eve r, p a t t e rn re cogn it ion of s ign s a n d s ym p t om s t h a t h ave be e n d e m on -
3
s t ra t e d in va riou s va s cu lit ic con d it ion s ca n p rovid e t h e clin icia n a good s t a rt in g
N
O
p oin t in t h e d ia gn os t ic p roce s s (6 ).
I
T
C
A d e t a ile d h is t ory of t h e n a t u re of t h e con d it ion p rovid e s clu e s t h a t a id in
E
t h e n a l d ia gn os is of t h e u n d e rlyin g va s cu lit is . For e xa m p le, a p a t ie n t w it h
S
MPA m ay p re s e n t w it h n on s p e ci c u like s ym p t om s a n d a rt h ra lgia t h a t ca n be
p re s e n t m on t h s t o ye a rs be fore a d ia gn os is ca n be m a d e. Micros cop ic p oly-
a n giit is ca n a ls o p re s e n t a cu t e ly, w it h t h e on s e t of s ym p t om s w it h in d ays t o
w e e k s . Pa t ie n t s w it h a lve o la r h e m or r h a ge w it h p u lm o n a ry in vo lve m e n t in
ANCA-a s s o cia t e d va s cu lit is m a y re p o rt d ys p n e a , h e m o p t ys is , a n d p le u r it ic
ch e s t p a in (7 ). A h is t ory of ch ron ic s in u s it is , h e m op t ys is , a n d h e m a t u ria s u g-
ge s t s W G, a p u lm on a ry–re n a l s yn d rom e w it h m e d iu m - t o s m a ll-ve s s e l in volve -
m e n t . Sim ila rly, a com p la in t of h e a rin g los s w a rra n t s fu rt h e r eva lu a t ion for W G
a s t h e m u cos a of t h e m id d le e a r or of t h e n a s op h a ryn x m ay be in volve d in t h is
con d it ion (8 ). A rep ort of h e a d a ch e s , jaw cla u d ica t ion , los s of vis ion , a n d m u s cle
s t iffn e s s m a y s u gge s t GCA w it h or w it h ou t p olym ya lgia rh e u m a t ica .
Age a n d ot h e r ris k fa ct ors s u ch a s s m okin g h is t ory s h ou ld a ls o be kep t in
m in d in t h e eva lu a t ion p roce s s . For e xa m p le, Kaw a s a ki’s d is e a s e is m ore com -
m on in ch ild re n , w h e re a s GCA is s e e n m ore fre q u e n t ly in t h e old e r p op u la t ion ,
u s u a lly old e r t h a n 50 ye a rs (6 ).
Physica l Exa mina tio n o f the Pa tie nt
Ce rt a in p h ys ica l e xa m in a t ion n d in gs m ay a ls o h e lp t h e clin icia n a rrive a t a
d ia gn os is of va s cu lit is . Fu rt h e rm ore, t h ey p rovid e a n id e a of t h e d egre e of m u l-
t is ys t e m in volve m e n t , s u ch a s lu n gs , kid n eys , a n d t yp e of blood ve s s e ls , t h a t is ,
a ort a . Th e p re s e n ce of bru it s m a y p oin t t ow a rd Ta ka ya s u ’s a rt e rit is , GCA, or
Be h çe t ’s s yn d rom e. Abd om in a l p a in in t h e s e t t in g of n ew -on s e t h igh blo od
p re s s u re a n d p e r ip h e ra l n e u ro p a t h y ra is e s t h e p o s s ib ilit y o f p o lya r t e r it is
 136 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

NOT TO BE MISSED
• Ru le o u t m im icke rs o f
va scu lit is.
• Fo r visu a l sym p t o m s a n d
h ig h ESR in p a t ie n t s o ld e r
t h a n 50 ye a rs, h a ve a
h ig h clin ica l su sp icio n fo r
GCA.
• Re co g n ize life -t h re a t e n in g
p u lm o n a ry, re n a l,
n e u ro lo g ic, o r o cu la r
m a n ife st a t io n s.
n od os a . Th e p re s e n ce of blood p re s s u re d iffe re n ce or la ck of p u ls e in t h e a rm s
s u gge s t s Ta kaya s u ’s a rt e rit is .
Ch u rg–St ra u s s s yn d rom e is a n ot h e r p u lm on a ry–re n a l s yn d rom e in w h ich a
p a t ie n t w it h a s t h m a m ay p re s e n t w it h e os in op h ilia . Cert a in vira l in fe ct ion s h ave
be e n a s s ocia t e d w it h s ys t e m ic va s cu lit id e s . For exa m p le, h ep a t it is C in fe ct ion
h a s be en d e m on s t ra te d in cryoglobu lin e m ic va scu lit is , es p ecia lly w h en a ss oci-
a t ed w ith Rayn a u d ’s p h en om en on a n d p a lp a ble p u rp u ra . Moreover, h ep a t it is B
in fe ct ion h a s be en lin ked to p olya rte ritis n od os a . Beh cet ’s syn d rom e is ch a ra cte r-
ized by recu rren t ora l a p h t h ou s a n d gen ita l u lcers , e ryth em a n od osu m , a rth ritis,
a n d u ve it is . Recu rren t ocu la r ep is od es of u veitis ca n lea d to ret in a l d a m a ge a n d
blin d n es s. Th e m u cos a l u lcers in Be h ce t’s s yn d rom e a re rou n d , p a in fu l le sion s
w it h eryt h e m a t ou s m a rgin s a n d a re cove red w it h a yellow p s e u d om em bra n e.

Dia g no stic Studie s

Aft e r p e rfo rm in g a co m p le t e h is t o ry a n d p h ys ica l e xa m in a t ion , t h e clin icia n
s h ou ld con s id e r ord e rin g a few ba s ic la bora t ory t e s t s , s u ch a s com p le t e blood
ce ll co u n t w it h d iffe re n t ia l, ch e m is t ry p ro le —in clu d in g t ra n s a m in a s e s a n d
S
E
cre a t in in e, e ryt h rocyt e s e d im e n t a t ion ra t e (ESR), a n d u rin a lys is —t o ga in a be t -
C
T
t e r id e a of w h ich orga n s ys t e m s m ay be in volve d . An e m ia of ch ron ic d is e a s e
I
O
a n d t h rom bocyt os is a re com m on ly s e e n in va s cu lit is , w h e re a s t h rom bocyt op e -
N
3
n ia a n d le u cop e n ia a re s u gge s t ive of a d is e a s e p roce s s ot h e r t h a n va s cu lit is (6 ).
S
Ab n o r m a l a s p a r t a t e a m in o t ra n s fe ra s e (AST) a n d a la n in e a m in o t ra n s fe ra s e
p
e
(ALT) s u gge s t live r in volve m e n t , p os s ibly h e p a t it is B or C in fe ct ion s t h a t p oin t
c
i
t ow a rd a m e d iu m -ve s s e l va s cu lit is s u ch a s p olya rt e rit is n od os a or s m a ll-ve s s e l
c
R
cryoglobu lin e m ic va s cu lit is , re s p e ct ive ly. How eve r, e leva t e d t ra n s a m in a s e s a re
h
e
n ot s p e ci c t o t h e live r a n d ca n be s e e n in ot h e r in a m m a t ory con d it ion s s u ch
u
m
a s m yos it is . Se ru m cre a t in in e m ay give a n id e a of t h e e xa m in e d p a t ie n t ’s re n a l
a
t
fu n ct io n . Th e p re s e n ce o f h e m a t u r ia o r p ro t e in u r ia s u gge s t s glo m e r u la r
i
c
in volve m e n t a n d ra is e s t h e p o s s ibilit y of va s cu lit ic s yn d rom e s , t h a t is , W G.
D
i
s
Micro s co p ic e xa m in a t ion of a u rin e s a m p le s h ou ld be p e rform e d t o loo k fo r
e
a
ce llu la r ca s t s . For e xa m p le, t h e p re s e n ce of re d blood ce ll (RBC) ca s t s or d ys -
s
e
m orp h ic RBCs is h igh ly s u gge s t ive of glom e ru la r in ju ry.
s
An eleva ted ESR is n ot sp eci c to va scu litis. Fu rth erm ore, a n orm a l ESR d oes
n ot ru le ou t a d iagn osis of va scu litis, a s a p a tien t w ith GCA ca n h ave a n orm a l
ESR. Th e p resen ce of cytop la sm ic a n d p erin u clea r ANCA (c-ANCA a n d p -ANCA) by
in d irect im m u n o u orescen ce su ggests W G a n d m icroscop ic a n giitis, resp ectively.
An t ibod ie s t o s e rin e p rot e in a s e 3 a n d m ye lop e roxid a s e ca n be d e t e ct e d w it h
en zym e-lin ked im m u n osorben t a ssays w ith h igh er p ositive p red ictive va lu e a n d
a re h igh ly su ggestive of W G a n d m icroscop ic a n giitis, resp ectively. How ever, th ere
is ove rla p a s t h e p re s e n ce of c-ANCA ca n be s e e n in m icros cop ic a n giit is a n d
Ch u rg–Stra u ss syn d rom e, w h erea s p -ANCA ca n be a ssocia ted w ith W G (6 ). Oth er
rh eu m a t ologic la bora t ory t es t s com m on ly ord ere d in clu d e s e ru m com p le m e n t
levels. C3 a n d C4 a re u su a lly n orm a l in th e system ic va scu litid es. Alth ou gh a n ti-
n u clea r a n tibod ies a n d rh eu m a toid fa ctor m ay be u sefu l in screen in g for oth er
in a m m a tory con d ition s su ch a s system ic lu p u s eryth em a tosu s a n d rh eu m a toid
a rth ritis, th ey a re n ot u sefu l in th e eva lu a tion of va scu litis a s th ey a re n on sp eci c
a n d ca n be a ssocia ted w ith both va scu litis a n d its m im ickers, th a t is, en d oca rd itis.
Us e d in con ju n ct ion w it h la bora t ory d a t a , im a gin g is a u s e fu l t ool in t h e
eva lu a t ion of s u s p e ct e d va s cu lit is . Cavit a ry n od u le s on ch e s t x-ray lm s m igh t
s u gge s t W G. High -re s olu t ion ch e s t CT is m ore s e n s it ive t h a n ch e s t ra d iogra p h y
a n d oft e n u s e d if t h e ch e s t ra d iogra p h s a re n orm a l w h ile t h e clin ica l s u s p icion
for va s cu lit is is h igh . Ot h e r im a gin g m od a lit ie s t o be u s e d a t t h e clin icia n ’s
d is cre t ion in clu d e bra in MRI, h e a d CT, a n giogra p h y, color d u p le x u lt ra s ou n d ,
a n d p os it ron e m is s ion t om ogra p h y.
La bora t ory t e s t s a n d im a gin g m od a lit ie s a re s u gge s t ive on ly of a va s cu lit ic
s yn d rom e ; t h ey a re n ot d ia gn os t ic. Tis s u e biop s y re m a in s t h e gold s t a n d a rd of
d ia gn os is (6 ). Th e biop s y s it e s a re la rge ly d e t e rm in e d by t h e orga n s in volve d .

RESOURCES FOR PATIENTS
• h t t p s://w w w.
va scu lit isfo u n d a t io n .o rg
• h t t p ://w w w.cks.n h s.u k/
p a t ie n t _in fo rm a t io n _
le a e t /va scu lit is_a rc#
• h t t p ://w w w.a rt h rit is.o rg
• h t t p ://w w w.w e b m d .co m /
rh e u m a t o id -a rt h rit is/
g u id e /va scu lit is-t re a t m e n t
• h t t p ://w w w.m a yo clin ic.
co m /h e a lt h /va scu lit is/
DS00513/DSECTION=
sym p t o m s
Ch a p te r 14 Va s cu lit is 137
For e xa m p le, if t h e p u lm on a ry or re n a l s ys t e m s a re in volve d a s in p u lm on a ry–
re n a l s yn d rom e s , t is s u e s from lu n gs or kid n eys w ou ld be t h e n e xt logica l s t e p s .
How eve r, if GCA is s u s p e ct e d , a t e m p ora l a rt e ry biop s y is in d ica t e d . If t h e re is
cu t a n e o u s in vo lve m e n t a s in t h e p a t ie n t p re s e n t e d a t t h e b egin n in g o f t h is
ch a p t e r, t h e n a s k in b io p s y is n e ce s s a ry. Fo r t h e p a t ie n t w h o p re s e n t s w it h
n e u ro p a t h y o r m yo p a t h y, n e rve co n d u ct io n s t u d y o r e le ct ro m yogra p h y w it h
m u s cle biop s y s h ou ld be p e rform e d .
Tre a tme nt
Sin ce va s cu lit is h a s h igh m orbid it y a n d m ort a lit y, it is im p ort a n t t o d ia gn os e
a ccu ra t e ly a n d e a rly s o t h a t a p p rop ria t e t re a t m e n t s a re in s t it u t e d . Dru gs u s ed t o
t re a t va s cu lit is va ry from cort icos t e roid s t o im m u n os u p p res s ive a ge n t s , s u ch a s
a za t h iop rin e (Im u ra n ) in ou r d e s cribe d p a t ie n t , t o cyt ot oxic a ge n t s , s u ch a s
cyclop h os p h a m id e (Cyt oxa n ). New e r a ge n t s s u ch a s rit u xim a b (Rit u xa n ) a re
ava ila ble, w h ich w a s re cen t ly d e m on s t ra t e d t o be n on in fe rior t o cyclop h os p h a -
m id e, a s d e m on s t ra t ed in t h e Rit u xim a b for ANCA-As s ocia t ed Va s cu lit is (RAVE)
s
t ria l (9 ). Th e t re a t m e n t of va s cu lit is s h ou ld in clu d e p a t ie n t e d u ca t ion . Wit h
e
s
kn ow led ge of t h eir d is e a s e s , p a t ie n t s a re m ore like ly t o m a ke in form e d d ecis ion s
a
e
a n d com p ly w it h t re a t m e n t p la n s a n d follow -u p a s t h e m ed ica t ion s u s e d in t h e
s
i
D
t re a t m e n t of va s cu lit is a re n ot h a rm les s . Nu m e rou s on lin e re s ou rces a re ava il-
c
i
a ble t o t h e p a t ie n t ; a few a re p rovid e d h e re (s e e box t o le ft ) a s a s t a rt in g p oin t .
t
a
m
u
e
h
Clinica l Co urse
R
c
i
Th e d iffe re n t ia l d ia gn os is of va s cu lit is is broa d , in clu d in g m a n y con d it ion s t h a t
c
e
m ay m im ic t ru e va s cu lit is . In fe ct ion s , t h rom boe m bolic p h e n om e n a , a n d m a lig-
p
S
n a n cie s ca u s e in a m m a t ion a n d d a m a ge t o blood ve s s e ls , le a d in g t o clin ica l
3
N
p re s e n t a t ion s im ila rly s e e n in va s cu lit is (10 ). Th e va riou s d is e a s e s t h a t ca u s e
O
in ju ry t o blood ve s s e ls , in cit e a n in a m m a t ory p roce s s , a n d m im ic a va s cu lit ic
I
T
C
p roce s s a re p rovid e d in Ta ble 14.2 .
E
S
Fu rt h e rm ore, cu t a n e ou s m a n ife s t a t ion s a s s e e n in ou r p a t ie n t p re s e n t e d a t
t h e begin n in g of t h is ch a p t e r ca n be m is d ia gn os e d in it ia lly a s in fe ct ion s s u ch
a s ce llu lit is . Th e clin icia n s h ou ld be a r in m in d t h a t im it a t ors of va s cu lit is e xis t ,
ord e r a n y n e ce s s a ry t e s t s t o ru le ou t m im icke rs of va s cu lit is , a n d re fe r t o rh e u -
m a t ology for fu rt h e r eva lu a t ion if a d ia gn os is is s t ill in q u e s t ion .
In fectiou s orga n ism s su ch a s ba cteria , viru ses, a n d fu n gi often lea d to con d i-
tion s th a t im ita te va scu litis by eith er ca u sin g d irect va scu la r in ju ry or in d irectly
a lterin g th e va scu la r stru ctu re via im m u n e-m ed ia ted or toxic m ech a n ism s, resu lt-
in g in ch a n ges sim ila rly seen in va scu litis. For exa m p le, Salm onella h a s been im p li-
ca ted in a ortitis. Often , cen tra l n ervou s system va scu litis is secon d a ry to ba cteria l
or vira l m en in gitis or d u e to ba cteria l en d oca rd itis. Cu ta n eou s in fection s su ch a s
p a n n icu litis a n d cellu litis ca n p resen t clin ica lly, very sim ila r to tru e va scu litis.
Ma lign a n cie s ca n cre a t e a clin ica l p ict u re s im ila r t o va s cu lit is via d iffe re n t
m e ch a n is m s : (a ) in d u ct ion of im m u n e -m e d ia t e d in a m m a t ion , (b) occlu s ion of
blood ve s s e ls by e it h e r ca n ce r ce lls or cre a t ion of a h yp e rcoa gu la ble s t a t e, or
(c) in va s ion of n erves in n erva t in g blood ves s els , p rod u cin g a n eu rop a t h y m im ick-
in g tru e va scu litis. Oth er n on m a lign a n t occlu sive p rocesses su ch a s a th eroem boli
a n d a n t ip h o s p h o lip id a n t ibod y s yn d ro m e s h o u ld a ls o be con s id e re d in t h e
eva lu a t ion of s u s p e ct e d va s cu lit is (10 ).
On ce m im ickers of va scu litis h ave been ru led ou t a n d trea tm en ts h ave been
in stitu ted for tru e va scu litis, th e clin ica l cou rse of d isea se va ries from com p lete
rem ission to rela p se to refra ctorin ess to d ea th . Now a d ays, th e ra tes of rem ission
in ANCA-a ssocia ted va scu litis trea ted w ith m od ern th era py a re grea ter th a n or
eq u a l to 90%. Ou tcom e m ea su res in ANCA-a ssocia ted va scu litis in clu d e va riou s
a s se ss m en t tools su ch a s Va s cu litis Da m a ge In d ex a n d Birm in gh a m Va s cu lit is
Activity Score (BVAS), w ith th e BVAS bein g th e sta n d a rd .
 138 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 14.2 Nonin ammat ory Causes of Vascular Damage

Occlusive pro ce sse s At h e ro e m b o lic d ise a se

Th ro m b o t ic d iso rd e rs
An t ip h o sp h o lip id a n t ib o d y syn d ro m e
Th ro m b o t ic t h ro m b o cyt o p e n ic p u rp u ra
Sickle ce ll a n e m ia
Th ro m b o e m b o lism
Ab n o rm a l p ro t e in s
Cryo g lo b u lin s
Cryo b rin o g e n s
Pa ra p ro t e in s
Ne o plasia Ca rd ia c m yxo m a
Ot h e r n e o p la sm s
Exte rnal injury Exp o su re t o co ld
Ra d ia t io n e xp o su re
Inte rnal injury Hyp e rt e n sio n , a rt e ria l d isse ct io n
Infe ctio n Ba ct e ria l
Fu n g a l
S
E
Myco b a ct e ria l
C
Vira l
T
I
O
Sp iro ch e t a l/Ricke t t sia l
N
Pa ra sit ic
3
Co ng e nital o r inhe rite d Pse u d o xa n t h o m a e la st icu m
S
p
abno rmalitie s Eh le rs–Da n lo s syn d ro m e
e
Ne u ro b ro m a t o sis
c
i
Fib ro m u scu la r d ysp la sia
c
R
Misce llane o us co nditio ns Dru g e ffe ct s
h
e
Mo ya m o ya d ise a se
u
m
No n va scu la r
a
t
i
c
Ad a p t e d fro m Re fe re n ce (10).
D
i
s
e
a
s
Du rin g t h e co u rs e o f t re a t m e n t o f va s cu lit is w it h d iffe re n t im m u n o s u p -
e
s
p re s s ive d r u gs a n d glu co r t ico id s , d r u g t ox icit y re m a in s a co n ce rn . Ad ve rs e
eve n t s s u ch a s a cu t e a lle rgic re a ct ion s , le u kop e n ia , in fe ct ion s , m a lign a n cy, d ia -
be t e s , a n d os t e op oros is h ave be e n obs e rve d .
WHEN TO REFER Va s cu lit is is a h e t e roge n e ou s gro u p o f d is ord e rs in volvin g blo od ve s s e ls
t h a t ca n a ffe ct m u lt ip le orga n s w it h d ire con s e q u e n ce s . How eve r, t h e p rogn os is
• Th e d ia g n o sis is u n cle a r. of t h e s e con d it ion s , w h e n d ia gn os e d a n d t re a t e d e a rly, is ge n e ra lly p os it ive.
• Tre a t m e n t w it h im m u n o -
su p p re ssive d ru g s a n d
cyt o t o xic d ru g s m a y b e
in d ica t e d . ICD9
447.6 Arte ritis
446.5 g ian t ce ll
446.0 n e cro sin g o r n e cro t iz in g
446.5 t e m p o ral
446.1 Kaw asak i
716.9 Arthro pathy •
136.1 [711.2] Be h çe t ’s•
686.1 Granulo mato sis NEC
446.4 W e g e n e r’s (n e cro t iz in g re sp irat o ry)
446.0 Po lyarte ritis (n o d o sa) (re n al)
Purpura
287.0 Sch ö n le in (-He n o ch ) (alle rg ic)
Takayasu (-Onishi) dise ase o r syndro me
446.7 (p u lse le ss d ise ase )
447.6 Vasculitis
 Ch a p te r 14 Va s cu lit is 139

Re fe re nce s
1. Wa t t s R, Scot t DGI. Ep id e m iology of va s cu lit is . In : Ba ll G, Brid ge s S, Jr , e d s . Vasculitis . 2n d e d . New York :
Oxford Un ive rs it y Pre s s , In c ; 2008 :7 –22 .
2. Frie s JF, Hu n d e r GG, Blo ch DA, e t a l. Th e Am e rica n College of Rh e u m a t ology 1990 crit e ria fo r t h e cla s -
s i ca t ion of va s cu lit is . Su m m a ry. A rthritis Rheum 1990 ;33 (8 ):1135 –1136 .
3. Je n n e t t e JC, Fa lk RJ, An d ra s s y K, e t a l. Nom e n cla t u re o f s ys t e m ic va s cu lit id e s . Prop os a l of a n in t e rn a -
t ion a l con s e n s u s con fe re n ce . A rthritis Rheum 1994 ;37 (2 ):187 –192 .
4. Ba ll G, Brid ge s S, Jr . Cla s s i ca t ion of Va s cu lit is . In : Ba ll G, Brid ge s S, Jr , e d s . Vasculitis. 2n d e d . New York :
Oxford Un ive rs it y Pre s s , In c ; 2008 :3 –6 .
5. Nt a t s a ki E, Wa t t s RA, Scot t DG. Ep id e m iology of ANCA-a s s ocia t e d va s cu lit is . Rheum Dis Clin North A m
2010 ;36 (3 ):447 –461 .
6. Fe s s le r B. Ap p roa ch t o t h e d ia gn os is of va s cu lit is in a d u lt p a t ie n t s . In : Ba ll G, Brid ge s S, Jr , e d s . Vasculitis .
2n d e d . New York : Oxford Un ive rs it y Pre s s , In c ; 2008 :277 –285 .
7. Ch u n g SA, Se o P. Micros co p ic p olya n giit is . Rheum Dis Clin North A m 2010 ;36 (3 ):545 –558 .
8. Holle JU, La u d ie n M , Gros s W L. Clin ica l m a n ife s t a t ion s a n d t re a t m e n t o f Wege n e r’s gra n u lom a t o s is .
Rheum Dis Clin North A m 2010 ;36 (3 ):507 –526 .
9. St on e JH , Me rke l PA, Sp ie ra R, e t a l. Rit u xim a b ve rs u s cyclop h os p h a m id e for ANCA-a s s ocia t e d va s cu lit is .
N Engl J Med 2010 ;363 (3 ):221 –232 .
10. Ch u n g S, Sa ck K. Im it a t ors of va s cu lit is . In : Ba ll G, Brid ge s SL, Jr , e d s . Vasculitis . 2n d e d . New York : Oxford
Un ive rs it y Pre s s , In c ; 2008 :599 –621 .

s
e
s
a
e
s
i
D
c
i
t
a
m
u
e
h
R
c
i
c
e
p
S
3
N
O
I
T
C
E
S
 CHAPTER
15 Gia nt Cell Arteritis a nd
Polymya lgia Rheuma tica
A ngelo Gaffo

A 76-ye ar-o ld w h it e w o m an
Clinica l
Pre se nta tio n
S
E
p re se n t s t o h e r p rim ary care
C
T
Po lym ya lgia r h e u m a t ica (PMR)
I
p h ysician w it h a 3-m o n t h
O
a n d gia n t ce ll a rt e rit is (GCA) a re
N
h ist o ry o f p ro g re ssive
3
t w o clin ica l con d it ion s t h a t s h a re
f at ig u e , m alaise , p o o r ap p e -
S
m u lt ip le p a t h o p h ys io lo gic a n d
p
e
t it e , an d a 10-lb w e ig h t lo ss. c lin ic a l ch a r a c t e r is t ic s . Bo t h
c
i
a lm os t e xclu s ive ly a ffe ct in d ivid -
c
Sh e also re p o rt s b ilat e ral
R
u a ls o ld e r t h a n 50 ye a r s , a r e
h
sh o u ld e r an d h an d p ain . No
e
ch a ra ct e r iz e d by m u s cu lo s k e le -
u
m
visu al co m p lain t s are re p o rt - t a l p a in a n d s t iffn e s s , a n d a re
a
t
e d , an d o n e xam in at io n , sh e u s u a lly a ccom p a n ie d by p rom i-
i
c
D
is n o t ice d t o h ave m ild b ilat - n e n t co n s t it u t io n a l s ym p t o m s
i
s
s u ch a s m a la is e, w e igh t los s , a n d
e
e ral m e t acarp o p h alan g e al sw e llin g an d p ain w it h p alp at io n .
a
e leva t e d in a m m a t o ry m a rk e rs .
s
e
Lab o rat o ry n d in g s in clu d e a n o rm o ch ro m ic, n o rm o cyt ic an e m ia
s
In a d d it io n , b o t h t h e d is e a s e s
(h e m at o crit o f 28% ) an d in cre ase d in am m at o ry m ark e rs w it h an h ave a good re s p on s e t o d iffe re n t
e ryt h ro cyt e se d im e n t at io n rat e (ESR) o f 60 m m /h o u r. No e ro sio n s d o s a ge s o f glu co co r t ico id t h e r-
a p y. W h e r e a s PMR lim it s it s
are n o t e d o n h an d rad io g rap h s, an d a t e n t at ive d iag n o sis o f
in volve m e n t t o t h e m u s cu los ke l-
se ro n e g at ive rh e u m at o id art h rit is is m ad e . W h ile t h e p at ie n t w ait s e t a l s ys t e m , GCA is a p a n -a rt e ri-
f o r a rh e u m at o lo g y re f e rral sh e is p lace d o n a 10-m g d o se o f o ral t is t h a t a ffe ct s t h e a ort a a n d it s
p re d n iso n e . m a in b ra n ch e s w it h a s p e cia l,
b u t n o t e x clu s ive , p re d ile ct io n
Tw o w e e k s lat e r w h e n sh e is se e n b y a rh e u m at o lo g ist , t h e
for t h e e xt ra cra n ia l bra n ch e s of
f at ig u e , m alaise , p o o r ap p e t it e , an d art h rit is are m ild ly im p ro ve d , t h e ca ro t id a r t e ry. As a co n s e -
b u t st ill p re se n t . No visu al co m p lain t s are re p o rt e d , b u t t h e p at ie n t q u e n ce, e a rly re cogn it ion of GCA
h as d e ve lo p e d p e rsist e n t jaw d isco m f o rt an d w e ak n e ss w h ile ch e w - is e s s e n t ia l t o a vo id it s m o r e
fe a re d is ch e m ic co n s e q u e n ce s ,
in g as w e ll as h e ad ach e s, w it h scalp t e n d e rn e ss n o t e d w h ile layin g
in clu d in g irreve rs ible vis ion los s .
o n a p illo w o r w e arin g g lasse s. On p h ysical e xam in at io n t h e re is a Po ly m ya lg ia r h e u m a t ic a c a n
p alp ab le t e m p o ral art e ry (Fig . 15.1 ) an d sig n i can t scalp t e n d e rn e ss. evolve in t o GCA, w it h t h is clin i-
A d d it io n al n d in g s in clu d e co n t in u e d sh o u ld e r an d p e lvic g ird le c a l c o n t in u u m le a d in g m a n y
a u t h ors t o con s id e r PMR a form e
p ain o n p alp at io n . Lab o rat o ry n d in g s are larg e ly u n ch an g e d ,
fru s t e of GCA in w h ich ove rt va s -
w it h an ESR at 56 m m /h o u r. cu lit is h a s n ot d eve lop e d .
A t e m p o ral art e ry b io p sy is sch e d u le d in t h e n e xt d ays an d is Bot h PMR a n d GCA a p p e a r t o
sh o w n in Fig u re 15.2 . b e m o re co m m o n in w h it e s o f
n ort h e rn Eu rop e a n d e s ce n t t h a n
140
 Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 141

s
e
s
a
e
s
i
D
Figure 15.1 A prominent, tender tempora l a rtery. Figure 15.2 Temporal artery biopsy in giant cell arteritis reveals a chroni-

c
i
t
Reproduced with permission from Gold DH, Weingeist cally in amed artery with marked narrowing of the lumen. Hematoxylin and

a
m
TA. Color Atla s of the Eye in Systemic Disea se . Ba ltimore: eosin stain; original magni cation 310. With permission from Tasman W,

u
Lippincott Willia ms & Wilkins; 2001. Jaeger E. The Wills Eye Hospital Atlas of Clinical Ophthalmology. 2nd ed.

e
h
Philadelphia: Lippincott Williams & Wilkins; 2001.

R
c
i
c
e
p
S
in ot h e r ra cia l grou p s . Th e in cid e n ce ra t e of GCA in w h it e s of n ort h e rn Eu ro-

3
p e a n d e s ce n t h a s be e n e s t im a t e d a t a ro u n d 20 t o 30/ 100,000. Re p ort s fro m

N
O
ot h e r grou p s in clu d in g s ou t h e rn Eu rop e a n s , Africa n Am e rica n s , As ia n s , a n d

I
T
Ara b s d e s crib e a m u ch low e r in cid e n ce ra t e a t 1 t o 11/100,000. Po lym ya lgia

C
E
rh e u m a t ica is a p p roxim a t e ly t h re e t im e s m ore com m on t h a n GCA, w h ich in

S
t u rn h a s be e n re p ort e d a s t h e m os t com m on form of va s cu lit is in t h e old e r
t h a n 50 ye a rs a ge grou p a n d t h e in cid e n ce in cre a s e s w it h a ge u n t il t h e n in t h
d e ca d e of life. Th e s e con d it ion s a re e xce e d in gly ra re in in d ivid u a ls you n ge r
t h a n 50 ye a rs . Wom e n h ave a n in cre a s e d fre q u e n cy of bot h PMR a n d GCA w h e n
com p a re d t o m e n (1.7:1 for PMR a n d 3.5:1 for GCA).
Th e ce n t ra l h is t ologic fe a t u re of GCA is t h e p re s e n ce of a n in a m m a t ory
in lt ra t e w it h p re d om in a n ce of CD4 T ce lls a n d m a crop h a ge s t h a t ca n e xt e n d
a cros s t h e w h ole e la s t ic a rt e ry ve s s e l w a ll, bu t u s u a lly con ce n t ra t e s a rou n d t h e
in t e rn a l e la s t ic la m in a (Fig. 15.2 ) (1 ). De s t ru ct ion of t h e in t e rn a l e la s t ic la m in a
is a p a t h ogn om on ic fe a t u re of GCA. Gia n t ce lls ca n be p re s e n t , bu t a re a n in con -
s is t e n t fe a t u re of t h e d is e a s e, re p ort e d in a bou t 50% o f biop s y-p rove n ca s e s .
La rge n u m be rs of gia n t ce lls in t h e biop s y s p e cim e n h ave be e n a s s ocia t e d w it h
a h igh e r ris k of is ch e m ic com p lica t ion s . Alt h ou gh brin oid n e cros is cou ld be
s e e n in ra re ca s e s , it s p re s e n ce is s o u n u s u a l t h a t it s h ou ld ra is e s u s p icion for
a lt e rn a t ive d ia gn o s e s . No ch a ra ct e r is t ic h is t op a t h ologic fe a t u re s h a ve be e n
re p ort e d for PMR, a n d t h e m a in role of biop s y is w orku p of s u s p e ct e d a ccom -
p a n yin g GCA.
Polym ya lgia rh e u m a t ica a n d gia n t ce ll a rt e rit is , ve ry like ly be in g p a rt of a
com m on p a t h op h ys iologic s yn d rom e, s h a re m a n y clin ica l ch a ra ct e ris t ics . Poly-
m ya lgia rh e u m a t ica it s e lf is con s id e re d a clin ica l m a n ife s t a t ion of GCA. Neve r-
t h e le s s , a m a jorit y of p a t ie n t s w it h PMR n eve r d eve lop ot h e r m a n ife s t a t ion s of
GCA a n d PMR is s t ill w id e ly co n s id e re d a s t a n d -a lo n e co n d it io n . Gia n t ce ll
a r t e r it is is m o s t ly re co gn iz e d by it s cra n ia l a r t e r it is a n d m u s cu lo s k e le t a l
 142 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 15.1 Clinical Feat ures of Giant Cell Art erit is Syndromes a

Cra n ia l a rt e rit is • He a d a ch e a n d sca lp t e n d e rn e ss

• Ja w cla u d ica t io n
• Op h t h a lm ic isch e m ia : visio n lo ss, b lu rre d visio n ,
visu a l h a llu cin a t io n s, d ip lo p ia
• Trismus, facial pain, tongue claudication or infarction,
ca ro t id yn ia , d ysp h a g ia
• Po st e rio r circu la t io n t ra n sie n t isch e m ic a t t a cks o r
st ro ke s: co n fu sio n , co rt ica l b lin d n e ss, a t a xia
Po lym ya lg ia rh e u m a t ica • Pa in a n d st iffn e ss a ro u n d t h e sh o u ld e rs, n e ck,
a n d /o r h ip s
• Fa t ig u e
• Pe rip h e ra l a rt h rit is
Wa st in g a n d ca ch e xia • Fe ve r o r n ig h t sw e a t s
• Ma la ise o r a n o re xia
• We ig h t lo ss
• De p re ssio n
S
Ao rt it is a n d p e rip h e ra l • Lim b cla u d ica t io n
E
C
a rt e ry o cclu sio n • Bru it s o r d e cre a se d p u lse s
T
• Ra yn a u d ’s p h e n o m e n o n
I
O
• Dry co u g h
N
• Ch e st p a in o r d ysp n e a
3
• Su d d e n d e a t h
S
p
e
c
a
In clu d in g p o lym ya lg ia rh e u m a t ica .
i
c
R
h
e
u
m
m a n ife s t a t io n s . How eve r, o t h e r m a n ife s t a t io n s o f t h e d is e a s e ca n e a s ily go
a
t
i
u n n ot ice d , in clu d in g t h os e s e con d a ry t o a ort it is (lim b cla u d ica t ion , a n e u rys m s ,
c
D
Rayn a u d ’s p h e n om e n on ) a n d w a s t in g w it h ca ch e xia (feve r, n igh t sw e a t s , w e igh t
i
s
e
los s , a n ore xia ; Ta ble 15.1 ) (2 ). It is ve ry im p ort a n t t o n ot e t h a t t h e s e clin ica l
a
s
s u bs e t s a re n ot m u t u a lly e xclu s ive, a n d t h e clin ica l p re s e n t a t ion ca n h a ve con -
e
s
s id e ra ble ove rla p .

Exa mina tio n

CRANIAL ARTERITIS
Cra n ia l a rt e rit is is a re s u lt of t h e in a m m a t ory in volve m e n t of t h e e xt ra cra n ia l
bra n ch e s of t h e ca rot id a rt e ry. He a d a ch e is t h e m os t com m on m a n ife s t a t ion .
Th e s p e ci c ch a ra ct e ris t ics of t h is h e a d a ch e a re va ria ble, w it h ou t a s p e ci c
t yp e (cou ld be d u ll, s h a rp , or t h robbin g), loca t ion (bila t e ra l or u n ila t e ra l, t e m p o-
ra l, o ccip it a l, or d iffu s e ), or in t e n s it y (fro m m ild t o s eve re ). It is u s u a lly t h e
p e rs is t e n ce of t h is com p la in t t h a t brin gs it t o t h e a t t e n t ion of t h e clin icia n .
An ot h e r fe a t u re t h a t s h ou ld ra is e a a g is t h e in cre a s e d s e n s it ivit y of t h e s ca lp
t o t a ct ile s t im u li: s u d d e n ly t h e p a t ie n t h a s d is com fort w it h rou t in e a ct ivit ie s
s u ch a s w e a rin g gla s s e s , com bin g t h e ir h a ir, or la yin g t h e ir h e a d on a p illow.
Th e corre la t ion of t h is on p h ys ica l e xa m in a t ion is t e m p ora l t e n d e rn e s s on p a l-
p a t ion , w it h t h e a d d it ion a l n d in g of a p u ls a t in g, e n la rge d , or n od u la r t e m p o-
ra l a rt e ry in a few ca s e s . Jaw cla u d ica t ion is on e of t h e m os t s p e ci c s ym p t om s
of t h e d is e a s e. It is be lieve d t o be ca u s e d by d e m a n d is ch e m ia in t h e m a s s e t e r
m u s cle s . Neve rt h e le s s , t h e on s e t of p a in ca n s om e t im e s h a p p e n sw ift ly a ft e r
t h e in it ia t ion of m a s t ica t ion . Tris m u s , fa cia l p a in , t on gu e cla u d ica t ion or in fa rc-
t ion , s ca lp n e cros is , a n d ca rot id yn ia a re a d d it ion a l m a n ife s t a t ion s of is ch e m ia
in t h is circu la t ory be d .
Th e m os t fe a re d com p lica t ion of GCA is t h e vis ion los s ca u s e d by is ch e m ic
co m p ro m is e o f t h e o p t ic n e rve a n d t h e ch o ro id in d u ce d by p o s t e rio r cilia ry
 Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 143

a rt e ry occlu s ion (a bra n ch of t h e op h t h a lm ic, w h ich is it s e lf a bra n ch of t h e

in t e rn a l ca rot id a rt e ry). In h a lf of t h e p a t ie n t s t h e on s e t of vis ion los s is s u d d e n
a n d , in a lm os t a ll ca s e s , p a in le s s . An im p ort a n t p rop ort ion of p a t ie n t s ca n h a ve
p re m on it ory s ym p t om s , in clu d in g blu rre d vis ion , t ra n s ie n t m on ocu la r vis u a l
los s (am aurosis fugax ), vis u a l h a llu cin a t ion s , a n d d ip lop ia . Vis u a l los s ca u s e d by
GCA is ve ry oft e n irreve rs ible, a n d it s p re m on it ory s ym p t om s ca n be con s id -
e re d a t r u e m e d ica l e m e rge n cy. On fu n d o s co p ic e x a m in a t io n , d is k e d e m a
follow e d by d is k p a llor is p rom in e n t .
Ce n t ra l n e rvou s s ys t e m is ch e m ia in t h e form of t ra n s ie n t is ch e m ic a t t a cks
or s t roke s ca n occu r a s a con s e q u e n ce of GCA a n d , p re fe re n t ia lly, a ffe ct t h e
p os t e rior circu la t ion . Th e s e a re be lieve d t o be s e con d a ry t o t h rom boe m bolic
d is e a s e, n a rrow in g or occlu s ion of t h e ca rot id or ve rt e broba s ila r a rt e rie s .

POLYMYALGIA RHEUMATICA
Th e m a in clin ica l ch a ra ct e ris t ic of PMR is p a in a n d s t iffn e s s a rou n d t h e m u s -
cle s o f t h e s h ou ld e r a n d p e lvic gird le . Us u a lly t h e on s e t is s u d d e n a n d t h e
s h ou ld e r gird le is a ffe ct e d rs t . Nigh t t im e p a in is com m on , bu t in t h e m orn in gs ,

s
e
t h e s ym p t om s cou ld be s o p ron ou n ce d t h a t t h e p a t ie n t h a s m a rke d d if cu lt y

s
a
ca rin g for t h e m s e lve s a n d ca n e n d u p con n e d t o be d . Th e re is evid e n ce t h a t

e
s
i
t h e p roxim a l p a in fu l m a n ife s t a t ion s of PMR in t h e s h ou ld e r a n d p e lvic gird le

D
c
a re con s e q u e n ce of in a m m a t ion of m u lt ip le p e ria rt icu la r s h ou ld e r a n d h ip

i
t
a
bu rs a s . Pe rip h e ra l join t sw e llin g t h a t ca n p rogre s s t o in volve t h e w h ole h a n d is

m
com m on ly d e s cribe d . Tru e p e rip h e ra l a rt h rit is h e ra ld s m ore re s is t a n t d is e a s e.

u
e
Dis u s e m u s cle a t rop h y ca n d eve lop in lon g-s t a n d in g u n t re a t e d p a t ie n t s .

h
R
c
i
c
e
WASTING AND CACHEXIA

p
S
A p rom in e n t s ys t e m ic in a m m a t ory re s p on s e le a d in g t o a p re s e n t a t ion w it h

3
N
feve r, m a la is e, a n d w e igh t los s re s e m blin g a feve r of u n kn ow n origin ca n occu r.

O
It is im p ort a n t t o e m p h a s ize t h a t GCA a ccou n t s for a bou t 20% of ca s e s of feve r

I
T
C
of u n kn ow n origin in in d ivid u a ls old e r t h a n 65 ye a rs . Feve r is u s u a lly low gra d e,

E
S
bu t s p ike s of u p t o 39 C or 40 C a re n ot u n com m on . Pa ra d oxica lly, a p re s e n t a t ion
w it h t h e s e fe a t u re s a ccom p a n ie d w it h con com it a n t h igh leve ls of in a m m a t ory
m a rke rs s e e m s t o be p rot e ct ive a ga in s t t h e d eve lop m e n t of cra n ia l a rt e rit is , bu t
it is u n cle a r if t h is is be ca u s e of a n e a rlie r d ia gn os is w it h con cu rre n t e a rlie r
e xp os u re t o glu cocort icoid t h e ra p y or t h e p re d om in a n ce of in a m m a t ory fa c-
t ors t h a t m ay p rot e ct a ga in s t a rt e ria l occlu s ion .

AORTITIS AND PERIPHERAL ARTERIAL OCCLUSION

Th is is by fa r t h e m os t u n d e r-re cogn ize d m a n ife s t a t ion of GCA, bu t it a ffe ct s
a p p roxim a t ely 10% of p a t ie n t s . Ma n y m ore m ay be a ffe ct e d s u bclin ica lly. Pe rip h -
e ra l a rt e ria l occlu s ion s a ffe ct va s cu la r be d s in a m a n n e r s im ila r t o Ta kaya s u ’s
a rt e rit is , w it h a p re fe re n ce for t h e s u bclavia n , a xilla ry, a n d bra ch ia l a rt e rie s .
Gia n t ce ll a rt e rit is ra re ly in volve s ot h e r ve s s e ls s u ch a s t h e fe m ora l, coron a ry, or
m e s e n t e ric a rt e rie s . Pre s e n t a t ion in clu d e s lim b cla u d ica t ion , Rayn a u d ’s p h e -
n om e n on , d e cre a s e d p u ls e s , a n d bru it s ove r t h e in volve d ve s s e ls . An a d d it ion a l
s ym p t om t h a t ca n be a t t ribu t e d t o p e rip h era l a rt e ria l in volve m e n t , in t h is ca s e
of t h e re s p ira t ory t ra ct , is a p e rs is t e n t d ry cou gh . Pa t ie n t s w it h p e rip h e ra l a rt eria l
com p rom is e a re u s u a lly n ot a ffe ct e d by con com it a n t cra n ia l a rt e rit is .
Aort it is t e n d s t o p re fe re n t ia lly a ffe ct t h e t h ora cic a ort a , le a d in g t o a n e u -
rys m form a t ion , d is s e ct ion , a n d a ort ic in com p e t e n ce. Com m on clin ica l p re s e n -
t a t ion s in clu d e d ys p n e a a n d ch e s t p a in (ca u s e d by a ort ic in s u f cie n cy, le a d in g
t o d e m a n d coron a ry is ch e m ia ), a lon g w it h t h e n d in g on rou t in e ch e s t ra d io-
gra p h s of a n e n la rge d a ort ic s h a d ow. Su d d e n d e a t h ca n a ls o occu r, u s u a lly a s a
con s e q u e n ce of a ort ic d is s e ct ion .
 144 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Studie s
In bot h PMR a n d GCA, t h e clin ica l a s s e s s m e n t p rovid e s m os t of t h e e le m e n t s
n e ce s s a ry fo r t h e d ia gn o s is , w it h s om e s u p p ort p rovid e d by la bo ra t ory d a t a ,
h is t o p a t h o logy fro m a t e m p o ra l a r t e ry b io p s y, a n d ve ry u n co m m o n ly ra d io -
logic s t u d ie s .
Gia n t ce ll a rt e rit is s h ou ld be s u s p e ct e d in a n y p a t ie n t old e r t h a n 50 ye a rs
w it h s ym p t om s of PMR or t is s u e is ch e m ia in t h e h e a d , n e ck, or u p p e r t h ora x.
A h igh e ryt h rocyt e s e d im e n t a t ion ra t e (ESR) or C-re a ct ive p rot e in (CRP) t it e r a re
s u p p ort ive of t h e d ia gn os is , bu t it is ve ry im p ort a n t t o n ot e t h a t a rou n d 25% of
biop s y-p rove n ca s e s d o n ot h a ve a bn orm a l va lu e s of e it h e r a t p re s e n t a t ion .
Eleva t e d leve ls of in t e rle u kin 6 a re p rom is in g m a rke rs of d is e a s e a ct ivit y, a s
t h ey a re p a rt of t h e p a t h op h ys iologic p a t h w ay of t h e d is e a s e. How eve r, t h e ir
u s e h a s n ot be e n s t a n d a rd ize d ye t . Ot h e r com m on la bora t ory n d in gs in clu d e
m icrocyt ic a n e m ia , t h rom bocyt os is , le u kocyt os is , a bn orm a lit ie s in bioch e m ica l
live r t e s t (a lka lin e p h os p h a t a s e a n d t ra n s a m in a s e s ), a n d low leve ls of a lbu m in .
Th e role of im a gin g in t h e d ia gn os is of GCA is s t ill la rge ly u n d e t e rm in e d .
Pa t ie n t s w h o p re s e n t w it h cra n ia l a rt e rit is cou ld be con s id e re d for a Dop p le r
S
E
u lt ra s o u n d e x a m in a t io n o f t h e t e m p o ra l a r t e r ie s , w h e re a h yp o e ch oic r im
C
T
a rou n d t h e ve s s e l lu m e n (kn ow n a s t h e “h yp oe ch oic h a lo”) cou ld be a u s e fu l
I
O
n d in g in t h e p re d ict ion of ve s s e l in a m m a t ion a n d in n d in g a n a d e q u a t e s it e
N
fo r bio p s y. How eve r, t h e p ro ce d u re is h igh ly o p e ra t o r d e p e n d e n t , a n d s u bs e -
3
S
q u e n t s t u d ie s h ave n ot p rove d it s u s e fu ln e s s for d ia gn os t ic p u rp os e s . Dop p le r
p
e
u lt ra s ou n d t e ch n iq u e s cou ld be u s e fu l for t h e a s s e s s m e n t of s t e n os is in ot h e r
c
i
va s cu la r b e d s , s u ch a s t h e ve rt e b ra l o r s u b cla via n a r t e rie s . In p a t ie n t s w h o
c
R
p re s e n t w it h lim b cla u d ica t ion or s ign s of a ort ic com p rom is e (a ort ic in s u f -
h
e
cie n cy o r a n e u rys m a l d ila t a t io n ), a n a n giogra m o r a le s s in va s ive m a gn e t ic
u
m
re s on a n ce im a gin g a n giogra p h y (MRA) cou ld be con s id e re d . A s m oot h , u n iform
a
t a p e rin g in t h e a ffe ct e d p e rip h e ra l ve s s e l lu m e n is t h e ch a ra ct e ris t ic n d in g in
t
i
c
GCA. Ma gn e t ic re s o n a n ce im a gin g a n giogra p h y h a s t h e a d d it io n a l b e n e t o f
D
i
s
a llow in g t h e a s s e s s m e n t of t h e ve s s e l w a ll for t h icke n in g a n d e d e m a t h a t ca n
e
a
p re ce d e occlu s ion . Pos it ron e m is s ion t om ogra p h y w it h F18 - u orod e oxyglu cos e
s
e
ca n d e m on s t ra t e in cre a s e d u p t a ke in a ffe ct e d ve s s e ls a n d is a p rom is in g, bu t
s
s t ill n ot w id e ly a d op t e d , t e ch n iq u e for a s s e s s m e n t of d is e a s e a ct ivit y.
Th e m a in s t a y of t h e d ia gn os is of GCA is t h e h is t op a t h ologic e xa m in a t ion
of t h e t e m p ora l a rt e ry. It is im p ort a n t t o n ot e t h a t s om e p a t ie n t s d o n ot h ave
a n y t e m p ora l a rt e ry in volve m e n t , m a in ly t h e s u bs e t of p a t ie n t s w h o p re s e n t a s
a ort it is or p e rip h e ra l a rt e ria l occlu s ion , a n d m a y n ot be n e t from t h e p roce -
d u re. How eve r, t h e biop s y o f t h e t e m p ora l a rt e ry re m a in s a s a t im e -h on ore d
con rm a t ory t e s t in a gre a t m a jorit y of ca s e s a n d s h ou ld be p u rs u e d w h e n eve r
p os s ible. Ma n y m is con cep t ion s e xis t a bou t t h e t im in g a n d t e ch n ica l a s p e ct s of
t h e p roce d u re (Ta ble 15.2 ) (3, 4 ). Th e in a m m a t ory com p rom is e in d u ce d by GCA
is oft e n p a t ch y a n d cou ld be m is s e d eve n in p rop e rly p e rform e d biop s ie s . Th e
w a y t o m in im ize t h is p o s s ib ilit y is by o b t a in in g a ge n e ro u s s e gm e n t o f t h e
a rt e ry for s t u d y. At t h e ve ry le a s t 1 cm is re q u ire d , bu t s egm e n t s of 3 cm or
m ore a re p re fe rre d . Bila t e ra l s a m p le s , a lt h ou gh n ot u s u a lly fe a s ible, h ave be e n
s h ow n t o im p rove t h e d ia gn os t ic yie ld by 20% t o 40%. Mu lt ip le cu t s of t h e a rt e ry
s p e cim e n s h ou ld be p e rform e d a n d s t u d ie d . Te m p ora l a rt e ry biop s ie s a re u s e fu l
eve n 4 w e e ks in t o h igh -d o s e glu cocort ico id t h e ra p y. Th e n d in g m os t com -
m on ly a ffe ct e d by t h is t h e ra py is t h e d is a p p e a ra n ce of t h e in a m m a t ory in l-
t ra t e s from t h e ve s s e l w a ll, bu t fra gm e n t a t ion of t h e e la s t ic la m in a , e n d ot h e lia l
p rolife ra t ion , a n d eve n t h e e m p t y “n e s t s ” w h e re gia n t ce lls w e re loca t e d (in
ca s e s t h a t p re s e n t w it h gia n t ce lls ) ca n s t ill be u s e fu l a n d s u p p o rt ive o f t h e
d ia gn os is . As a con s e q u e n ce, la ck of p rom p t a cce s s t o a p h ys icia n w h o cou ld
p e rform t h e p roce d u re s h ou ld n ot be a d e t e rre n t for s t a rt in g a p p rop ria t e h igh -
d os e t h e ra p y in re a s on a bly h igh s u s p icion ca s e s . Eve n in p rop e rly p e rform e d
a n d p roce s s e d t e m p ora l a rt e ry biop s ie s , t h e re s u lt ca n be n ega t ive in u p t o 15%

CLINICAL POINTS
• Po lym ya lg ia rh e u m a t ica
is a clin ica l d ia g n o sis,
a n d t h e re fo re , t h e re is
n o co n rm a t o ry t e st .
• Cra n ia l a rt e rit is is t h e
b e t t e r re co g n ize d fo rm o f
GCA. Ho w e ve r, o t h e r clin i-
ca l p re se n t a t io n s in clu d e
w a st in g syn d ro m e s, PMR,
a o rt it is, a n d p e rip h e ra l
a rt e ria l o cclu sio n s. Th e se
a re o ft e n m isse d , a n d
clin icia n s sh o u ld m a in t a in
a h ig h in d e x o f su sp icio n .
• Te m p o ra l a rt e ry b io p sy is
t h e g o ld st a n d a rd fo r t h e
d ia g n o sis in m o st ca se s o f
GCA. It sh o u ld b e p u rsu e d
w h e n e ve r p o ssib le , e ve n
a ft e r t h e p a t ie n t h a s b e e n
e xp o se d t o g lu co co rt ico id s.
• Wh e n t h e re is su sp icio n
o f visu a l sym p t o m s re la t e d
t o GCA, h ig h -d o se g lu co -
co rt ico id t h e ra p y sh o u ld
b e in it ia t e d a s so o n a s
p o ssib le . Th is sh o u ld n o t b e
d e la ye d w h ile w a it in g fo r
a t e m p o ra l a rt e ry b io p sy.
• Pa t ie n t s o n h ig h -d o se
g lu co co rt ico id t h e ra p y
fo r GCA sh o u ld b e clo se ly
m o n it o re d a n d t re a t e d fo r
e xp e ct e d co m p lica t io n s o f
t h e ra p y, m o st n o t a b ly b o n e
m a ss lo ss, h yp e rg lyce m ia ,
a n d h yp e rt e n sio n .
Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 145
Table 15.2 Import ant Considerat ions Regarding Temporal Art ery
Biopsies for Giant Cell Art erit is
• Th e le n g t h o f t h e a rt e ry se g m e n t o b t a in e d sh o u ld b e a t le a st 1 cm , b u t le n g t h s
o f 3–4 cm a re p re fe rre d
• Bila t e ra l t e m p o ra l a rt e ry b io p sie s in cre a se t h e d ia g n o st ic yie ld b y 20% –40%
• Process and cut the entire arterial segment, as the disease has a patchy distribution
• Do n o t st rip t h e a rt e ria l sa m p le o ff it s p e ria rt e ria l co n n e ct ive t issu e . Se ve ra l
t im e s t h e d ia g n o sis ca n b e fo u n d in p e ria rt e ria l ve sse ls ra t h e r t h a n t h e
t e m p o ra l a rt e ry b io p sie d
• De sp it e b e in g t h e p re fe rre d d ia g n o st ic t e st , fa lse n e g a t ive s in t e m p o ra l a rt e ry
b io p sie s a re co m m o n (a b o u t 15% o f ca se s)
• Te m p o ra l a rt e ry b io p sie s sh o u ld b e p e rfo rm e d a s so o n a s p o ssib le . Ho w e ve r,
t h e y ca n b e u se fu l e ve n a ft e r 4 w e e ks o f g lu co co rt ico id t h e ra p y
ca s e s of con rm e d GCA. Ph ys icia n s e n cou n t e rin g t h is d if cu lt s ce n a rio s h ou ld
con s id e r p rom p t ly e n rollin g t h e h e lp of a rh e u m a t ologis t , a s s e s s in g t h e com -
s
p rom is e of ot h e r va s cu la r be d s t h rou gh im a gin g, a n d gu id in g t re a t m e n t d e ci-
e
s
a
s ion s on t h e ba s is of clin ica l s ym p t om s a n d t h e ove ra ll leve l of s u s p icion for
e
s
GCA.
i
D
Po ly m ya lgia r h e u m a t ic a h a s n o s p e c i c d ia gn o s t ic m a r k e r s a n d t h e
c
i
t
a p p r o a ch is e s s e n t ia lly clin ica l. Sim ila r t o GCA, t h e in a m m a t o ry m a r k e r s
a
m
a r e u s u a lly e le va t e d , b u t t h e re is n o t h r e s h o ld t h a t ca n d iffe r e n t ia t e t h e t w o
u
e
co n d it io n s . Th e u s e o f u lt ra s o u n d o r m a gn e t ic re s o n a n ce im a gin g t o id e n -
h
R
t ify t h e p e r ia r t icu la r b u r s it is o f t h e s h o u ld e r a n d h ip s t h a t a re ch a ra ct e r is t ic
c
o f t h e co n d it io n h a s b e e n a d vo ca t e d . How e ve r, t h e s e p r o ce d u re s h a ve fa ile d
i
c
e
t o d e m o n s t ra t e a cle a r d iffe re n t ia t io n w it h o t h e r co n d it io n s t h a t ca n re s e m -
p
S
b le PMR.
3
N
O
I
DIFFERENTIAL DIAGNOSES
T
C
E
Th e Am e r ica n Co lle ge o f Rh e u m a t o logy d eve lo p e d cla s s i ca t io n cr it e r ia fo r
S
GCA in 1990 (Ta ble 15.3 ) (5 ). As m o s t cla s s i ca t io n crit e ria , t h e s e w e re cre a t e d
in ord e r t o h e lp t o in clu d e p a t ie n t s in s t u d ie s in a u n iform fa s h ion a n d s h ou ld
n o t be a p p lie d t o t h e d ia gn o s is o f in d ivid u a l p a t ie n t s . Th e s e crit e ria p e rfo rm
re a s on a bly w e ll in d iffe re n t ia t in g GCA from ot h e r va s cu lit id e s , bu t t h e ir u s e -
fu ln e s s is d im in is h e d w h e n t ryin g t o d iffe re n t ia t e it fro m co n d it io n s o t h e r
t h a n va s cu lit id e s . Th e s e crit e ria focu s h e a vily on t h e cra n ia l a rt e rit is p re s e n t a -
t ion p a t t e rn , a n d ot h e r p re s e n t a t ion p a t t e rn s cou ld be m is s e d w h e n t h e s e a re
u t ilize d .
Table 15.3 Tradit ional Format of t he 1990 American College
of Rheumat ology Crit eria for t he Classi cat ion
of Giant Cell Art erit is a
• Ag e a t d ise a se o n se t e q u a l t o o r o ld e r t h a n 50 ye a rs
• Ne w o n se t o f o r n e w t yp e o f h e a d a ch e
• Te m p o ra l a rt e ry t e n d e rn e ss t o p a lp a t io n o r d e cre a se d p u lsa t io n (u n re la t e d t o
a t h e ro scle ro sis)
• Eryt h ro cyt e se d im e n t a t io n ra t e g re a t e r t h a n 50 m m /h
• Bio p sy o f t h e t e m p o ra l a rt e ry sh o w in g va scu lit is co n sist e n t w it h g ia n t ce ll
a rt e rit is
Ad a p t e d fro m re fe re n ce 5.
a
Th e p re se n ce o f t h re e o r m o re crit e ria yie ld s a se n sit ivit y o f 93.5% a n d a sp e ci cit y o f 91.2% .
 146 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 15.4 Different ial Diagnosis of Polymyalgia Rheumat ica

and Giant Cell Art erit is

POLYMYALGIA RHEUMATICA GIANT CELL ARTERITIS

Se ro n e g a t ive rh e u m a t o id Va scu lit id e s in clu d in g We g e n e r’s
a rt h rit is g ra n u lo m a t o sis, m icro sco p ic p o lya n g iit is,
p o lya rt e rit is n o d o sa
Ce rvica l a n d h ip o st e o a rt h rit is At h e ro scle ro sis
Fib ro m ya lg ia Te m p o ra l–m a n d ib u la r jo in t d ise a se a n d
o d o n t o g e n ic p ro b le m s
In a m m a t o ry m u scle d ise a se , Trig e m in a l n e u ra lg ia
in clu d in g in clu sio n b o d y m yo sit is
a n d p o lym yo sit is
Am ylo id o sis Am ylo id o sis
Ma lig n a n cy Ma lig n a n cy, in clu d in g m u lt ip le m ye lo m a ,
Wa ld ë n st ro m ’s m a cro g lo b u lin e m ia , a n d
S
m ye lo d ysp la st ic syn d ro m e s
E
C
In fe ct io n s in clu d in g ch ro n ic vira l In fe ct io n s in clu d in g o t it is m e d ia , sin u sit is,
T
I
O
co n d it io n s o r e n d o ca rd it is p h a ryn g it is, e n d o ca rd it is, a n d o st e o m ye lit is
N
Hyp o t h yro id ism Su b a cu t e t h yro id it is
3
S
p
De p re ssio n Nonarteritic anterior ischemic optic neuropathy
e
c
i
Pa rkin so n ’s d ise a se Ch ro n ic kid n e y d ise a se w it h u re m ia o r
c
ca lcip h yla xis
R
h
La t e -o n se t syst e m ic lu p u s
e
u
e ryt h e m a t o su s
m
a
Dru g re a ct io n s, e .g ., m yo sit is fro m
t
i
c
st a t in s, Pa rkin so n ia n sym p t o m s
D
fro m n e u ro le p t ics
i
s
e
a
Lu m b a r sp in a l st e n o sis
s
e
s
Cryst a l a rt h ro p a t h ie s, in clu d in g
p o lya rt icu la r g o u t a n d ca lciu m
p yro p h o sp h a t e d e p o sit io n d ise a se

Th e d iffe re n t ia l d ia gn os is of bot h GCA a n d PMR is e xt e n s ive a n d s h ou ld be

w e igh e d ca re fu lly be fore com m it t in g p a t ie n t s t o lon g-t e rm glu cocort icoid t h e r-
a p y (Ta ble 15.4 ). Of a ll t h e s ign s a n d s ym p t om s d is cu s s e d for GCA, on ly ja w
cla u d ica t io n a n d a bn orm a l t e m p o ra l a rt e rie s o n p a lp a t ion h e lp e d t o re lia bly
d is t in gu is h GCA from ot h e r it e m s in t h e d iffe re n t ia l d ia gn os is .
Th e m a in co n s id e ra t io n in t h e d iffe re n t ia l d ia gn o s is o f PMR is u s u a lly
s e ron ega t ive rh e u m a t oid a rt h rit is . Bot h t h e d is e a s e s ca n be ve ry d if cu lt t o d if-
fe re n t ia t e , give n t h a t PMR ca n s om e t im e s ca u s e p e r ip h e ra l join t sw e llin g.
Re s p on s e t o glu co cor t ico id t h e ra p y is n o t a re lia ble w a y of d iffe re n t ia t in g
b e t w e e n t h e t w o co n d it ion s . Th e p re d om in a n ce of d is com fort a ffe ct in g t h e
s h ou ld e r a n d p e lvic gird le is t h e be t t e r w ay t o d iffe re n t ia t e t h e t w o in favor of
PMR, a lt h ou gh t h e s e e le m e n t s of t h e h is t ory cou ld oft e n be d if cu lt t o obt a in
from ce rt a in p a t ie n t s . Fibrom ya lgia a n d re la t e d m yofa s cia l p a in d is ord e rs t e n d
t o occu r in you n ge r in d ivid u a ls , bu t cou ld be e xt re m e ly d if cu lt t o d iffe re n t ia t e
from PMR w h e n t h e in a m m a t ory m a rke rs a re n ot e leva t e d . Th e p re fe re n t ia l
loca t ion of t h e d is com fort in t h e s h ou ld e rs a n d h ip gird le, a lon g w it h a ra p id
re s p on s e t o a low d os e of glu cocort icoid s , cou ld be clu e s in d iffe re n t ia t in g PMR
from brom ya lgia . Polym ya lgia rh e u m a t ica la cks t h e m u s cle e n zym e e leva t ion s
of t h e in a m m a t ory m yop a t h ie s , a n d if t h e p a t ie n t ’s s ym p t om s a llow a p rop e r
m u s cle s t re n gt h e xa m in a t ion , t h e re s u lt s s h ou ld be ve ry clos e t o n orm a l.

PATIENT ASSESSMENT
• Po lym ya lg ia rh e u m a t ica
a n d g ia n t ce ll a rt e rit is a re
se e n in p e o p le o ld e r t h a n
50 ye a rs.
• Ele va t e d se d im e n t a t io n
ra t e s a n d /o r C-re a ct ive
p ro t e in le ve ls a re fo u n d in
a la rg e m a jo rit y b u t n o t
a ll ca se s.
• Ot h e r a b n o rm a l, b u t
le ss sp e ci c, la b o ra t o ry
n d in g s a re m icro cyt ic
a n e m ia , t h ro m b o cyt o sis,
le u ko cyt o sis, e le va t e d
a lka lin e p h o sp h a t a se a n d
t ra n sa m in a se , a n d
h yp o a lb u m in e m ia .
• Te m p o ra l a rt e ry b io p sy
sp e cim e n s m u st b e o f
su f cie n t le n g t h , a t le a st
1 cm a n d p re fe ra b ly 3 cm ,
t o a vo id sa m p lin g e rro r.
Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 147
A co n d it io n t h a t co u ld clo s e ly re s e m ble b o t h PMR a n d GCA is a m ylo id o s is .
Pa t ie n t s c o u ld p r e s e n t w it h p r o x im a l p a in , fa t igu e , w e a k n e s s , ve r y h igh
in a m m a t o r y m a r k e r s , a n d h a rd e n e d t e m p o ra l a r t e r ie s . A t e m p o ra l a r t e r y
b io p s y is ve ry o ft e n t h e t e s t t h a t p rovid e s t h e d ia gn o s is , s h ow in g t h e ch a r-
a c t e r is t ic Co n go r e d s t a in in t h e a ffe c t e d ve s s e l w a ll. Ot h e r va s c u lit id e s
s u ch a s We ge n e r ’s gra n u lo m a t o s is , m icro s co p ic p o lya n giit is , a n d p o lya r t e r i-
t is n o d o s a c o u ld m im ic GCA in t h e ir p r e s e n t a t io n . It is ve r y im p o r t a n t
t o n o t e t h a t a ll o f t h e s e va s c u lit id e s c a n a ls o a ffe c t t h e t e m p o r a l a r t e r y
a n d p r e s e n t w it h in a m m a t o ry in lt ra t e s , le a d in g in e x p e r ie n ce d p a t h o lo -
gis t s t o d ia gn o s e GCA w h e n t h is is t h e m a in co n d it io n s u s p e ct e d . Ab s e n ce
o f b r in o id n e c r o s is a n d fr a gm e n t a t io n o f t h e e la s t ic la m in a a r e n d in gs
e x p e ct e d fro m b io p s ie s in p a t ie n t s w it h GCA. At h e ro s cle r o s is a n d gia n t ce ll
a r t e r it is co u ld b e d iffe r e n t ia t e d by t h e ir a n gio gr a p h ic p a t t e r n s in c a s e o f
a va s c u la r o b s t r u c t io n . Sm o o t h t a p e r in g o f t h e b lo o d ve s s e l lu m e n is
e x p e c t e d in GCA, a s o p p o s e d t o s u d d e n b lo ck s in b r a n ch in g p o in t s in
a t h e r o s cle r o s is .
s
e
Tre a tme nt
s
a
e
s
i
To d a t e, glu cocort icoid t h e ra py is t h e on ly a p p roa ch t h a t h a s be e n p rove d t o be
D
c
e ffe ct ive in bot h PMR a n d GCA. Th e in it ia l d os e of glu cocort icoid s in GCA w it h -
i
t
a
ou t cu rre n t or re ce n t n d in gs s u gge s t ive of vis ion los s is of 40 t o 60 m g/d ay of
m
p re d n is on e or it s glu cocort icoid e q u iva le n t . In ca s e s of im p e n d in g vis ion los s ,
u
e
h igh d o s e s of in t ra ve n ou s glu cocort icoid s (1,000 m g of in t ra ve n o u s m e t h yl-
h
R
p re d n is olon e for 3 d a ys follow e d by 60 m g a d a y of p re d n is on e ) is a com m on
c
i
a p p roa ch a lt h ou gh cle a r evid e n ce of it s be n e t ove r p re d n is on e 40 t o 60 m g/
c
e
d a y is la ckin g. Eve n t h is a ggre s s ive a p p roa ch ve ry ra re ly s a lva ge s vis ion w h e n
p
S
m o re t h a n 24 h ou rs h a ve e la p s e d s in ce t h e vis ion los s . For t h is re a s o n , it is
3
N
im p o r t a n t t o e m p h a s iz e t h e e m e rge n t n a t u re o f t h is a ggre s s ive t re a t m e n t
O
w h e n p re m on it ory s ign s of vis ion los s a re p re s e n t . If a t e m p ora l a rt e ry biop s y
I
T
C
ca n n ot be obt a in e d w it h in a few h ou rs , glu cocort icoid t h e ra py s h ou ld be s t a rt e d
E
S
a n d follow e d by a biop s y a s s oon a s p os s ible. Ap a rt from vis ion los s , s ym p t om s
of GCA u s u a lly re s p on d d ra m a t ica lly w it h in 48 h ou rs , bu t it m a y t a ke u p t o
5 d ays in s om e ca s e s .
Th e t r e a t m e n t o f PMR s h o u ld b e in it ia t e d a t a d o s e o f 10 t o 20 m g o f
p r e d n is o n e o r it s glu c o c o r t ic o id e q u iva le n t p e r d a y. As w it h GCA, t h e
re s p o n s e is u s u a lly s o d ra m a t ic t h a t s o m e u s e it a s a co n r m a t o ry d ia gn o s -
t ic e le m e n t . In b o t h PMR a n d GCA, t a p e r in g o f glu c o co r t ic o id s s h o u ld b e
s lo w, s t a r t in g s o m e w h e r e b e t w e e n 2 a n d 4 w e e k s a ft e r t h e in it ia t io n o f
t r e a t m e n t , a n d o n ly a ft e r t h e r eve r s ib le m a n ife s t a t io n s o f t h e d is e a s e h a ve
re s p o n d e d a n d in a m m a t o ry m a r k e r t it e r s h a ve n o r m a liz e d . Re co m m e n d a -
t io n s fo r glu co co r t ico id t a p e r in g ca n b e fo u n d in Ta b le 15.5 (3 ). Th e r o le o f
in a m m a t o r y m a r k e r s in t h e t a p e r in g o f glu co co r t ico id s is s u p p o r t ive , a n d
t r e a t m e n t d e cis io n s a r e p r im a r ily b a s e d o n t h e p re s e n ce o r a b s e n ce o f clin -
ica l m a n ife s t a t io n s . Pa t ie n t s w h o a re a s ym p t o m a t ic b u t s e e t h e ir ESR o r CRP
t it e r s in cre a s e s h o u ld h a ve t h e ir glu co co r t ico id t a p e r s low e d d ow n , b u t m a y
n o t n e e d t o h a ve t h e ir glu co co r t ico id d o s a ge in cre a s e d a ga in . On t h e o t h e r
h a n d , p a t ie n t s w it h n o r m a l ESR o r CRP b u t w it h clin ica l m a n ife s t a t io n s o f
re la p s e n e e d t o h a ve t h e ir glu co co r t ico id d o s e in cr e a s e d a ga in . Pa t ie n t s t yp -
ica lly s t a y o n glu co co r t ico id s a n a ve ra ge o f 2 ye a r s , a n d m o s t o f t h a t p e r io d
s h o u ld b e a t low d o s e s . Ca r e give r s s h o u ld m o n it o r a n d a ggr e s s ive ly t r e a t
c o m p lic a t io n s o f glu c o c o r t ic o id t h e r a p y, in c lu d in g b u t n o t lim it e d t o
glu co co r t ico id -in d u ce d o s t e o p o r o s is , d ia b e t e s , h yp e r lip id e m ia , d e p re s s io n ,
a n d p e p t ic u lce r d is e a s e . La rge d o s e s o f in t ra ve n o u s glu co co r t ico id s a s a
s t a n d a rd in d u ct io n t h e ra p y in p a t ie n t s w it h GCA co u ld le a d t o a m o re ra p id
re s p o n s e a n d d e cre a s e t h e fu t u re n e e d fo r o ra l glu co co r t ico id s t o t re a t t h e
148 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Table 15.5 Recommendat ions for Glucocort icoid Tapering in Polymyalgia Rheumat ica
and Giant Cell Art erit is

GIANT CELL ARTERITIS POLYMYALGIA RHEUMATICA

In it ia l d o se in m illig ra m s 1 m g /kg /d 10–20 m g /d
o f p re d n iso n e a
Wh e n t o st a rt t a p e rin g Aft e r a t le a st 2 w e e ks o f t re a t m e n t , a n d o n ly w h e n sym p t o m s h a ve re so lve d a n d
in a m m a t o ry m a rke rs h a ve n o rm a lize d
Tapering recommendationsb • Re d u ce d a ily d o sa g e b y 5–10 m g e ve ry • Re duce da ily dosa g e by 2.5–5 m g eve ry
2–4 w e e ks u n t il re a ch in g 20 m g /d ; t h e n 2–4 w e e ks u n til re a ch in g 10 m g /d ; t h e n
• Re d u ce d a ily d o sa g e b y 2.5–5 m g e ve ry • Re d u ce d a ily d o sa g e by 1–2.5 m g e ve ry
2–4 w e e ks u n t il re a ch in g 10 m g /d ; t h e n 1–2 m o n t h s u n t il d isco n t in u a t io n
• Re d u ce d a ily d o sa g e b y 1–2.5 m g e ve ry
1–2 m o n t h s u n t il d isco n t in u a t io n

Ad a p t e d fro m re fe re n ce 3.
a
Do e s n o t a p p ly t o o p t ic isch e m ia , w h e re h ig h d o se s o f in t ra ve n o u s g lu co co rt ico id s a re p re fe rre d .
b
Pro ce e d a n d co n t in u e t a p e rin g o n ly if t h e p a t ie n t re m a in s a sym p t o m a t ic. Dise a se re la p se s a re co m m o n fo r b o t h g ia n t ce ll a rt e rit is a n d p o lym ya lg ia
rh e u m a t ica d u rin g t h is p h a se .

NOT TO BE MISSED
• Eld e rly p a t ie n t s w it h
m a rke d fu n ct io n a l d e clin e
a n d d if cu lt y ca rin g fo r
t h e m se lve s m a y h a ve PMR
o r GCA a s t h e u n d e rlyin g
d ia g n o sis.
• Ja w cla u d ica t io n is a
re la t ive ly sp e ci c sym p t o m
o f t h e d ise a se a n d sh o u ld
b e a ske d a b o u t d u rin g
t h e e va lu a t io n o f p a t ie n t s
su sp e ct e d o f h a vin g GCA.
• Visio n lo ss is t h e m o st
fe a re d co m p lica t io n o f
GCA. Sym p t o m s su g g e st ive
of o ph t h a lm ic co m prom ise
sh ould a lwa ys be e xplo re d;
th e se m a inly inclu de blu rry
vision, tra nsie nt visua l loss,
visua l ha llucina tion s, a nd
diplo pia .
• A t h o ro u g h p e rip h e ra l
va scu la r e xa m in a t io n
(p u lse s a n d b lo o d
p re ssu re ) sh o u ld a lw a ys
b e p e rfo rm e d in p a t ie n t s
su sp e ct e d o f h a vin g PMR
o r GCA a s t h is m a y re ve a l
n d in g s in d ica t ive o f
a o rt it is o r p e rip h e ra l
a rt e ria l o cclu sio n s.
• The p re sen ce of n orma l
in a mma tory ma rke rs (ESR
a n d/o r CRP), w h ile u nlike ly,
does no t e xclu de th e
diagn osis o f PMR or GCA.
c o n d it io n . Fa ilu r e t o r e s p o n d t o glu c o c o r t ic o id t h e r a p y s h o u ld p r o m p t a
re a s s e s s m e n t o f t h e d ia gn o s is .
Ace t yls a licylic a cid (a s p irin ), a t a d os e be t w e e n 81 a n d 325 m g/d a y, is a n
im p ort a n t a d ju va n t t h e ra p y in p a t ie n t s w it h GCA w h o d o n ot h a ve con t ra in d i-
ca t io n s t o it . St u d ie s s u p p o rt it s ro le in p reve n t in g vis u a l lo s s a n d is ch e m ic
com p lica t ion s , bu t it s m e ch a n is m of a ct ion is u n cle a r a s t h rom bos is d oe s n ot
p lay a big role in va s cu la r occlu s ion s ca u s e d by GCA. Tria ls of glu cocort icoid -
s p a r in g a ge n t s h a ve b e e n u n s u cce s s fu l. Az a t h io p r in e , a n t im a la r ia ls , cyclo -
p h os p h a m id e, d a p s on e, a n d s t a t in s a ll h a d d is a p p oin t in g re s u lt s in ke e p in g
t h e d is e a s e in re m is s ion a n d in t h e ir glu cocort icoid -s p a rin g e ffe ct . De s p it e in i-
t ia l e n t h u s ia s m w it h m e t h ot re xa t e, it s e f ca cy in m a in t a in in g re m is s ion a n d
a s a glu cocort icoid -s p a rin g a ge n t cou ld n ot be con rm e d in a la rge ra n d om ize d
con t rolle d t ria l (6 ). A s im ila r d is a p p oin t in g re s u lt w a s obt a in e d w it h t h e t u m or
n e cro s is fa ct o r re ce p t o r a n t ib o d y in ix im a b, w h ich s h ow e d n o e ffe ct a s a
glu cocort icoid -s p a rin g a ge n t (7 ). In con clu s ion , t h e cu rre n t a p p roa ch re m a in s
t o ke e p t h e low e s t d os e of glu cocort icoid s for t h e s h ort e s t p e riod of t im e, in
ord e r t o avoid s id e e ffe ct s .
Clinica l Co urse a nd Co nclusio ns
Th e p rogn os is for t h e gre a t m a jorit y of p a t ie n t w it h PMR is good , a s t h e d is e a s e
is u s u a lly t re a t m e n t re s p on s ive a n d m os t p a t ie n t s d is con t in u e glu cocort icoid s
a ft e r 1 t o 2 ye a rs . A s u bs e t of p a t ie n t s cou ld d eve lop a s e ron ega t ive in a m m a -
t ory p olya rt h rit is re q u irin g a t re a t m e n t a p p roa ch s im ila r t o rh e u m a t oid a rt h ri-
t is , bu t t h is a rt h rit is is n ot a ggre s s ive or e ros ive.
Th e m os t om in ou s m a n ife s t a t ion s of GCA a re t h e d eve lop m e n t of vis io n
lo s s o r o t h e r cra n ia l is ch e m ic m a n ife s t a t io n s , p rin cip a lly s t ro k e s . If t h is is
avoid e d , p a t ie n t s re s p on d w e ll t o h igh -d os e glu cocort icoid t h e ra p y. Th e m a in
lon g-t e rm m orbid it y is s e con d a ry t o a p rolon ge d e xp os u re t o glu cocort icoid s . A
m a jorit y of p a t ie n t s h ave a t le a s t on e re la p s e of d is e a s e, u s u a lly in t h e form of
PMR. No cle a r p ict u re a bou t life e xp e ct a n cy in GCA h a s be e n obt a in e d , w it h
con t ra d ict in g s t u d ie s s u p p ort in g bot h a p re m a t u re m ort a lit y a n d a n orm a l life
e xp e ct a n cy.
 Ch a p te r 15 Gia n t Ce ll Art e rit is a n d Polym ya lgia Rh e u m a t ica 149

WHEN TO REFER ICD9

• All p a t ie n t s su sp e ct e d
o f h a vin g GCA sh o u ld
b e re fe rre d t o a rh e u m a -
t o lo g ist .
• If t h e in it ia l sym p t o m s o f
GCA a re su g g e st ive o f
im p e n d in g visio n lo ss,
p a t ie n t s sh o u ld b e st a rt e d
im m e d ia t e ly o n h ig h d o se s
o f g lu co co rt ico id s w h ile
u rg e n t ly re q u e st in g a
co n su lt a t io n fro m a rh e u -
m a t o lo g ist a n d a su rg ica l
sp e cia list ca p a b le o f p e r-
fo rm in g a t e m p o ra l a rt e ry
b io p sy. Th e se a re u su a lly
o p h t h a lm o lo g ist s, ENT
su rg e o n s, o r g e n e ra l
447.6 Arte ritis
446.5 g ian t ce ll
725 Po lymyalg ia
725 rh e u m at ica
Re fe re nce s
1. As h t on -Key M, Ga lla gh e r PJ. Su rgica l p a t h ology of cra n ia l a rt e rit is a n d p olym ya lgia rh e u m a t ica . Baillieres
Clin Rheum atol 1991 ;5 (3 ):387 –404 .
2. Weya n d CM, Goron zy JJ. Gia n t -ce ll a r t e rit is a n d p olym ya lgia rh e u m a t ica . A nn Intern Med 2003 ;139 (6 ):
505 –515 .
3. Ne s h e r G, Ne s h e r R. Polym ya lgia rh e u m a t ica a n d gia n t ce ll a rt e rit is . In : Ba ll V, Brid ge s SL, e d s . Vasculitis .
New York: Oxfo rd Un ive rs it y Pre s s ; 2008 :xviii, 629, 16 p p . of p la t e s .
4. Se o P, Ton e JH. La rge -ve s s e l va s cu lit is . A rthritis Rheum 2004 ;51 (1 ):128 –139 .
5. Hu n d e r GG, Bloch DA, Mich e l BA, e t a l. Th e Am e rica n College of Rh e u m a t ology 1990 crit e ria for t h e cla s -
s i ca t ion of gia n t ce ll a rt e rit is . A rthritis Rheum 1990 ;33 (8 ):1122 –1128 .
6. Hoffm a n GS, Cid MC, Re n d t -Za ga r KE, e t a l. A m u lt ice n t e r, ra n d om ize d , d ou ble -blin d , p la ce bo-con t rolle d
t ria l of a d ju va n t m e t h ot re xa t e t re a t m e n t for gia n t ce ll a rt e rit is . A rthritis Rheum 2002 ;46 (5 ):1309 –1318 .

s
e
su rg e o n s. Sp e ci ca t io n s 7. Hoffm a n GS, Cid MC, He llm a n n DB, e t a l. In ixim a b for m a in t e n a n ce of glu cocort icos t e roid -in d u ce d

s
a
re m is s io n of gia n t ce ll a rt e rit is : A ra n d om ize d t ria l . A nn Intern Med 2007 ;146 (9 ):621 –630 .
a b o u t t h e b io p sy sp e cim e n

e
s
m a n a g e m e n t sh o u ld b e

i
D
p ro vid e d .

c
i
t
a
• Pa tie nt suspe cte d of havin g

m
GCA w it h visio n sym p t o m s

u
e
should se e an ophtha lmol-

h
R
ogist a s so on as po ssib le for

c
a fu n d o sco p ic e xa m in a t io n

i
a n d t o ru le o u t o t h e r

c
e
re ve rsib le ca u se s o f visio n

p
S
lo ss.

3
N
• Pa t ie n t s w it h PMR w h o

O
h a ve sym p t o m re cu rre n ce

I
T
a ft e r a n a p p ro p ria t e

C
E
g lu co co rt ico id co u rse a n d

S
t a p e r sh o u ld b e re fe rre d
t o a rh e u m a t o lo g ist .
CHAPTER
16 Overla p Syndromes
a nd Uncla ssi ed or
Undifferentia ted
Connective Tissue
Disea se
Iris Navarro-Millán and Graciela S. A larcón

A 48-ye ar-o ld Hisp an ic w o m an

Intro ductio n
De s p it e s ign i ca n t ga in s in t h e
w it h sym m e t ric p o lyart h rit is, an e -
u n d ersta n d in g of th e im m u n op a th o-
m ia, m yalg ias, an d p ro xim al m u s- ge n e s is of t h e d iffe re n t con n e ct ive
cle w e ak n e ss. Ove r t im e sh e tissu e d isea ses (CTDs), th eir etiology
d e ve lo p e d scle ro d act yly an d sk in re m a in s e lu s ive . Th e d ia gn o s is o f
t h e d iffere n t CTDs is th u s a m a tt er
t h ick e n in g o ve r arm s, h an d s, an d
o f clin ica l ju d gm e n t a s p a t ie n t s
f ace . Sh e w as f o u n d t o b e an t in u - p r e s e n t w it h co n s t e lla t io n s o f
cle ar an t ib o d y (A NA ), an t i-d o u b le s ym p t om s , p h ys ica l n d in gs , a n d
st ran d e d DNA (an t i-d sDNA ), an t i- labora tory fea tu res th a t p erm it th eir
re cogn it ion (1 ). Oft e n t im e s , h ow -
Sm it h , an t i-Sjo g re n ’s syn d ro m e A
ever, p a tien ts p resen t w ith m a n ifes-
(SSA ), Sjo g re n ’s syn d ro m e B (SSB), t a tion s of m ore th a n on e d iffe ren t
an d an t icard io lip in Ig G an d Ig M CTD or w it h m a n ife s t a t ion s t h a t
an t ib o d ie s p o sit ive , w it h o u t a h is- d efea t cla ssi ca tion . Th e term “over-
la p ” is u sed in t h is ch a p t er for t h e
t o ry o f t h ro m b o sis o r m iscarriag e s. Rh e u m at o id f act o r (RF) an d
rst grou p of p a tien ts, w h erea s th e
an t i-CCP an t ib o d ie s w e re n e g at ive ; h o w e ve r, rad io g rap h s o f t h e term s “u n cla ssi ed ” or “u n d ifferen -
h an d s an d f e e t sh o w e d larg e e ro sio n s o n b o t h h an d s an d f e e t . t ia t e d ” a re u s e d for t h e s e con d
He r CK w as e le vat e d an d a m u scle b io p sy w as co n sist e n t w it h an grou p ; t h e t e rm m ixed (M) CTD is
reserved for p a tien ts w ith a d e n ed
in am m at o ry m yo p at h y. Be cau se o f p ro g re ssive d ysp n e a, a h ig h -
overla p syn d rom e (vide infra ). As ou r
re so lu t io n co m p u t e d t o m o g rap h y w as p e rf o rm e d , w h ich d e m o n - u n d ersta n d in g of th e etiop a th ogen -
st rat e d in t e rst it ial lu n g d ise ase (ILD). esis of th e CTDs im p roves, m ore p re-
cise labels w ill certa in ly be u sed .
Th e t e rm a t yp ica l (A) CTD h a s
a ris e n from t h e con s e n s u s re a ch e d by n on p h ys icia n s w orkin g w it h p a t ie n t s
w it h s ilicon e bre a s t im p la n t s ; t h e “lega l” d e n it ion of ACTD is s u ch t h a t a lm os t
a n y in d ivid u a l p re s e n t in g w it h s om e (su bjective, for th e m ost p a rt) n eu rop sy-
ch ologic or m u scu loskeleta l m a n ifesta tion m a y be d ia gn os e d w it h t h is “e n t it y.”
150
 Ch a p te r 16 Ove rla p Syn d ro m e s a n d Un cla s s i e d or Un d iffe re n t ia t e d Con n e ct ive Tis s u e Dis e a s e
CLINICAL POINTS
• Wh ile t h e re a re p a t ie n t s
w it h a n a u t o im m u n e rh e u -
m a t ic d ise a se w h o m a y
d e ve lo p m a n ife st a t io n s o f
a n o t h e r, t h e re a re so m e
p a t ie n t s w h o fu lly d e ve lo p
t w o o r m o re d ise a se s sim u l-
t a n e o u sly o r se q u e n t ia lly.
• Th e se p a t ie n t s m a y b e
cla ssi e d a s h a vin g a n
o ve rla p syn d ro m e .
• Co m m o n o ve rla p syn -
d ro m e s in clu d e rh u p u s,
scle ro d e rm a t o m yo sit is o r
scle ro m yo sit is, a n d MCTD.
• Mixe d co n n e ct ive t issu e
d ise a se is a t e rm co in e d
n e a rly 40 ye a rs a g o t o re fe r
t o p a t ie n t s w it h fe a t u re s
o f m o re t h a n o n e d ise a se
(a rt h rit is, scle ro d e rm a ,
lu p u s, m yo sit is) w it h h ig h
a n t i-U1RNP a n t ib o d ie s;
w it h t im e , h o w e ve r, t h e se
p a t ie n t s u su a lly e vo lve in t o
a m o re d e n e d CTD.
• Th e re is n o co n se n su s o n
h o w t o d ia g n o se u n cla ssi-
e d o r u n d iffe re n t ia t e d
CTD; su ch a la b e l m a y re p -
re se n t t h e p ro d ro m e o f
lu p u s; h o w e ve r, so m e o f
t h e se p a t ie n t s m a y re m a in
u n d iffe re n t ia t e d o r in co m -
p le t e o r e vo lve in t o a b ro -
m ya lg ia -like syn d ro m e w it h
ANA p o sit ivit y.
151
Table 16.1 Terminology or Nomenclat ure
ACR Am e rica n Co lle g e o f Rh e u m a t o lo g y
CTD Co n n e ct ive t issu e d ise a se
De n e d CTD Cle a r-cu t d ia g n o sis o f syst e m ic lu p u s e ryt h e m a t o su s,
rh e u m a t o id a rt h rit is, p o lyd e rm a t o m yo sit is, o r
scle ro d e rm a
Ove rla p syn d ro m e Pre se n ce o f t w o d e n e d CTDs (se e Ta b le 16.2)
Un d iffe re n t ia t e d CTD Pa t ie n t s w it h clin ica l fe a t u re s o f CTDs w h o d o n o t
m e e t crit e ria fo r a d e n e d CTD
Mixe d CTD A p a rt icu la r fo rm o f o ve rla p syn d ro m e (se e Ta b le 16.2)
At yp ica l CTD Te rm u se d in t h e silico n e b re a st im p la n t lit ig a t io n (n o t
sa n ct io n e d b y t h e ACR)
s
Th e rh e u m a t ologic com m u n it y h a s n ot va lid a t e d t h e e xis t e n ce of s u ch d is or-
e
s
a
d e r; t h u s , ACTD is n ot d is cu s s e d .
e
s
Th e t e rm in ology or n om e n cla t u re u s e d in t h is ch a p t e r is s u m m a rize d in
i
D
Ta ble 16.1 .
c
i
t
a
m
u
The Ove rla p Syndro me s
e
h
R
Th e follow in g ove rla p s yn d rom e s h a ve be e n d e s cribe d in t h e lit e ra t u re : rh u p u s
c
i
o r t h e ove r la p b e t w e e n r h e u m a t o id a r t h r it is (RA) a n d s ys t e m ic lu p u s e ry-
c
e
p
t h e m a t o s u s (SLE); s cle ro d e r m a t o m yo s it is (o r s cle ro m yo s it is ) o r t h e ove rla p
S
be t w e e n s cle rod e rm a a n d m yos it is ; a n d MCTD or t h e ove rla p be t w e e n p oly/
3
N
d e rm a t om yos it is , s cle rod e rm a , SLE, a n d RA in t h e p re s e n ce of a n t i-U1RNP a n t i-
O
bod ie s a n d HLA-DR4. Ot h e r “ove rla p s ” a re con s id e re d s u bs e t s of d e n e d CTDs
I
T
C
ra t h e r t h a n ove rla p s ; s u ch is t h e ca s e for p a t ie n t s w it h SLE or RA w h o a ls o h ave
E
S
m yos it is or va s cu lit is , a s w e ll a s for p a t ie n t s w it h SLE w h o h ave clin ica l a n d
la bora t ory fe a t u re s of t h e a n t ip h os p h olip id a n t ibod y s yn d rom e (APS). Ot h e r
p a t ie n t s w it h a d e n e d CTD p re s e n t ove rla p p in g m a n ife s t a t ion s w it h n on -CTD
d is ord e rs ; s u ch is t h e ca s e of p a t ie n t s w it h lu p os cle ros is a s t h e ove rla p p in g
clin ica l s yn d rom e of SLE, a n d m u lt ip le s cle ros is h a s be e n ca lle d . Fin a lly, p a t ie n t s
w it h p rim a ry APS m ay a ls o p re s e n t w it h m a n ife s t a t ion of m u lt ip le s cle ros is .
Ta ble 16.2 s u m m a rize s t h e s e d iffe re n t con d it ion s by ca t egorie s .
Th e rs t t h re e ove rla p s yn d rom e s a re n ow d e s cribe d in s om e d e t a il.
RHUPUS
Art h ra lgia s a n d a rt h rit is a re ra t h e r com m on in p a t ie n t s w it h SLE; h ow eve r, in
s om e p a t ie n t s w it h SLE, t h e m os t p rom in e n t clin ica l m a n ife s t a t ion is a s ym -
m e t ric p olya rt h rit is . Th e s e p a t ie n t s m a y o r m a y n ot h a ve a p os it ive RF. Th a t
w a s t h e ca s e o f o u r p a t ie n t w h o s e clin ica l p re s e n t a t io n w a s a s ym m e t r ic
in a m m a t ory a rt h rit is w it h ra d iogra p h ic evid e n ce of e ros ion s t h a t re s e m ble
RA, ye t h e r s e ro logie s w e re m ore s u gge s t ive o f SLE. Pa t ie n t s w it h RA m a y
p re s e n t s om e e xt ra -a rt icu la r fe a t u re s a n d a p os it ive ANA t e s t t h a t m ay s u gge s t
t h e d ia gn os is of SLE. Th e t e rm rh u p u s , h ow eve r, is re s e rve d for t h os e p a t ie n t s
w h o cle a rly m e e t crit e ria for bot h SLE a n d RA, a n d w h o p re s e n t ch a ra ct e ris t ic
clin ica l fe a t u re s of bot h t h e d is ord e rs . Th e s e p a t ie n t s u s u a lly h ave a s e rop os i-
t ive, e ros ive, s ym m e t ric p olya rt h rit is , w h ich a n t e d a t e s t h e on s e t of u n e q u ivo-
ca l clin ica l fe a t u re s of SLE. Th ey a ls o p re s e n t a u t oa n t ibod ie s ch a ra ct e ris t ic of
bot h t h e d is ord e rs ; t h e s e in clu d e IgM-RF, ANA, a n t i-d s DNA, a n d in a bou t h a lf
t h e p a t ie n t s , a n t ibod ie s t o Ro. Mos t re ce n t ly h igh ly s p e ci c a n t ibod ie s for RA
152 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

PATIENT ASSESSMENT
• Ou r p a t ie n t h a d sym m e t ric
p o lya rt h rit is in a rh e u m a -
t o id -like d ist rib u t io n w it h
se ro lo g ie s t h a t w e re m o re
co n sist e n t w it h SLE ra t h e r
t h a n w it h RA.
• Ha n d s a n d fe e t ra d io -
g ra p h s d e m o n st ra t e d a n
e ro sive a rt h rit is h ig h ly
su g g e st ive o f RA.
• Th e re w a s b io p sy-p ro ve n
p o lym yo sit is.
• Scle ro d a ct yly a n d ILD
su g g e st e d t h e d ia g n o sis o f
syst e m ic scle ro sis (SSc).
• Th e se n d in g s re p re se n t
t h e o ve rla p o f fo u r rh e u -
m a t ic d ise a se s: RA, SLE,
SSc, a n d p o lym yo sit is;
h o w e ve r, sh e la cke d a n t i-
U1RNP a n t ib o d ie s, t h e
h a llm a rk o f MCTD.
Table 16.2 Overlap Connect ive Tissue Diseases and
Relat ed Syndromes
Re co g nize d o ve rlap CTDs
SLE/RA : Rh u p u s
M yo sit is/scle ro d e rm a: Scle ro d e rm at o m yo sit is o r scle ro m yo sit is
M yo sit is/scle ro d e rm a/RA /SLE: M CTD
Subse ts w ithin de ne d CTDs
SLE/m yo sit is
RA /m yo sit is
SLE/A PS
RA /vascu lit is
SLE/vascu lit is
Ove rlap CTD and a no nrhe umatic diso rde r
SLE/m u lt ip le scle ro sis
Ove rlap CTD-like and a no nrhe umatic diso rde r
A PS/m u lt ip le scle ro sis
CTD, co n n e ct ive t issu e d ise a se ; SLE, syst e m ic lu p u s e ryt h e m a t o su s; RA, rh e u m a t o id a rt h rit is; APS,
a n t ip h o sp h o lip id a n t ib o d y syn d ro m e .

s u ch a s a n t icyclic cit ru llin a t e d p ep t id e a n t ibod ie s h ave a ls o be e n d e s cribe d in

p a t ie n t s w it h rh u p u s (2 ). Som e of t h e e xt ra -a rt icu la r fe a t u re s t h e s e p a t ie n t s
p re s e n t m ay be re la t e d t o t h e p re s e n ce of rh e u m a t oid n od u le s ra t h e r t h a n t o
SLE; t h is d is t in ct ion m ay h ave t h e ra p e u t ic im p lica t ion s .
In p a t ie n t s w it h rh u p u s , RA u s u a lly p re s e n t s rs t a n d is n ot u n t il a n ave r-
a ge o f 15 t o 18 ye a rs t h a t s ym p t o m s a n d s e ro logie s fo r SLE m a y e n s u e (3 ).
Pa t ie n t s w it h rh u p u s s h ou ld be d is t in gu is h e d from t h os e p a t ie n t s w it h SLE
w h o d eve lop d e form in g n on e ros ive a rt h rop a t h y w h ich re s e m ble s t h a t occu r-
rin g in p a t ie n t s w it h re cu rre n t rh e u m a t ic feve r (Ja ccou d ’s a rt h rop a t h y). Th e s e
p a t ie n t s in it ia lly p re s e n t w it h corre ct a ble s u blu xa t ion of t h e m e t a ca rp op h a la n -
ge a l join t s w it h u ln a r d evia t ion , a s w e ll a s sw a n -n e ck a n d bou t on n ie re n ge rs
a n d Z-t h u m b d e form it ie s . Th e s e a bn orm a lit ie s a p p e a r t o be t h e re s u lt of liga -
m e n t ou s la xit y a n d com p re s s ion of h a n d m u s cu la t u re ra t h e r t h a n re s u lt from
t h e p re s e n ce of p a n n u s . Th e m a gn it u d e of t h e a bove -d e s cribe d fe a t u re s w a s
t h e ba s is for t h e d eve lop m e n t of a n in d e x t o
a id in t h e d ia gn os is of Ja ccou d ’s a rt h rop a t h y.
RA-like hand deformities in SLE patients (as per Va n Vu gt e t a l. h ave d eve lop e d a n a lgorit h m t o
ACR criteria)
cla s s ify t h e d e fo r m in g h a n d a r t h ro p a t h y o f
p a t ie n t s w it h lu p u s ; a revis ion o f t h is a lgo -
Erosive disease rit h m is p re s e n t e d in Figu re 16.1 .
Th e fre q u e n cy of rh u p u s a t t h e p op u la t ion
No Yes leve l is u n kn ow n . Sin ce m o s t o f t h e s e ca s e s
Jaccoud’s index Criteria for RA h ave be e n re cogn ize d a t t e rt ia ry ca re ce n t e rs ,
greater than 5 (per ACR) t h is p roba bly re e ct s t h e d egre e of aw a re n e s s
a bo u t t h is co n d it io n , ra t h e r t h a n it s t ru e fre -
No Yes Yes No q u e n cy. Th e la ck of clin ica l crit e ria cre a t e s con -
fu s ion in t h e ch a ra ct e riza t ion of t h is s yn d rom e
Mild deforming Jaccoud’s
arthropathy arthropathy
“Rhupus” Undefined (4 ). It is a ls o u n cle a r w h e t h e r t h e coe xis t e n ce
of SLE a n d RA is t h e re s u lt of t h e ra n d om a s s o-
Figure 16.1 Flow dia gra m for the dia gnosis of the deforming a rthropa thies of SLE.
cia t io n o f t h e s e d is o rd e r s o r t h e re s u lt o f
RA, rheuma toid a rthritis; SLE, systemic lupus erythema tosus; ACR, America n ge n e t ic p re d is p os it ion for bot h , a s p os t u la t e d
College of Rheuma tology. Modi ed from Va n Vugt et a l. (1). by Bra n d e t a l.
Ch a p te r 16 Ove rla p Syn d ro m e s a n d Un cla s s i e d or Un d iffe re n t ia t e d Con n e ct ive Tis s u e Dis e a s e 153

From t h e p ra ct ica l p oin t of view, p a t ie n t s w it h rh u p u s s h ou ld be t re a t e d

a ccord in g t o t h e ir clin ica l m a n ife s t a t io n s (a n d t h e ir s eve rit y), u t ilizin g co m -
p ou n d s p rove d t o be e ffe ct ive in bot h RA a n d SLE. Th u s , a n t im a la ria l d ru gs m ay
b e n e e d e d t o p reve n t SLE a re s , b u t m e t h o t re x a t e o r le u n o m id e m a y b e
n e e d e d t o p reve n t join t d a m a ge. An t it u m or n e cros is fa ct or (TNF- ) t h e ra p y
h a s be e n a s s ocia t e d w it h t h e d eve lop m e n t a n d e xa ce rba t ion of SLE a s w e ll a s
e xa ce rba t ion of t h e SLE com p on e n t of t h is ove rla p s yn d rom e (5, 6 ). Th is t h e r-
a py s h ou ld , t h e re fore, be u s e d ve ry ca re fu lly in p a t ie n t s w h e re t h e “a rt h rit is ” is
re fra ct ory t o d is e a s e -m od ifyin g a n t irh e u m a t ic d ru gs (DMARDs ), ye t t h e re a re
fe a t u re s t h a t s u gge s t t h e p re s e n ce of a m ore s ys t e m ic CTD (s e e RA Ch a p t e r 9).

SCLERODERMATOMYOSITIS OR SCLEROMYOSITIS
Th ese a re p a tien ts w ith m a n ifesta tion s of sclerod erm a a n d p oly/d erm a tom yositis
t h a t e xh ibit va ria ble cu t a n e ou s , m u s cu la r, a n d orga n s ys t e m m a n ife s t a t ion s ;
a lt h ou gh t h is ove rla p s yn d rom e w a s origin a lly d e s cribe d in a d u lt s , p e d ia t ric
ca s e s h a ve a ls o be e n rep ort e d . Com m on m a n ife s t a t ion s ch a ra ct e ris t ic of SSc
a re a ls o fre q u e n t ly fou n d in s cle rod e rm a t om yos it is or s cle rom yos it is , in clu d -

s
e
in g Rayn a u d ’s p h e n om e n on , m ya lgia s or a rt h ra lgia s , d ys p h a gia , a n d in a bou t

s
a
30% of t h e p a t ie n t s , ILD. Fe a t u re s of d e rm a t om yos it is s u ch a s p e riorbit a l e d e m a

e
s
i
a n d e ryt h e m a , Go t t ro n ’s p a p u le s , a n d e ryt h e m a t o u s a n d p o ik ilo d e r m a t ou s

D
c
le s ion s on t h e t ru n k a n d a rm s or t h e “s h a w l s ign ” m ay occu r ove r t h e cou rs e of

i
t
a
t h e d is e a s e (7 ). W h ile t h e re a re a u t h ors w h o s t re s s t h e im p ort a n ce of t h e p re s -

m
e n ce of “m e ch a n ic’s h a n d s ” (h yp e rke ra t ot ic ch ron ic e cze m a of t h e h a n d s ) (8 ),

u
e
h
ot h e rs s u gge s t t h a t t h is m igh t be p re s e n t in a ll t yp e s of m yop a t h ie s a n d t h u s

R
t h is n d in g is n ot s p e ci c for s cle rod e rm a t om yos is t is or s cle rom yos it is . Ou r

c
i
ow n e xp e rie n ce w it h t h is ra re d is ord e r, h ow eve r, is q u it e d iffe re n t ; t h e p a t ie n t s

c
e
(ch ild re n a n d a d u lt s ) w e h ave follow e d h ave h a d s eve re a n d ge n e ra lize d s kin

p
S
in volvem e n t w it h t h e con s eq u en t occu rren ce of exion con t ra ctu res . Pu lm on a ry,

3
N
ga s t roin t e s t in a l, a n d re n a l in volve m en t , a s t h e on e d e scribe d in s clerod e rm a , is

O
ch a ra ct e r is t ica lly m ild , b u t s eve re m e ga co lo n a n d re s t r ict ive lu n g fu n ct io n

I
T
C
h a ve be e n d e s cribe d .

E
S
Pa t ie n t s w it h s cle rod e rm a t om yos it is u s u a lly e xh ibit h igh ANA t it e rs in a
h om oge n e ou s p a t t e rn , w h ich corre s p on d t o t h e p re s e n ce of t h e PM-Scl a n t ige n
(a n u cle ola r a n t ige n ic com p le x of 11 t o 16 p olyp ep t id e s ); a n t i-U1RNP a n t ibod ie s
a re ch a ra ct e ris t ica lly a bs e n t . PM-Scl a n t ibod ie s a re n ot , h ow eve r, s p e ci c for
s cle rom yos is t is , bu t in d iffe re n t ca s e s e rie s , t h ey h ave be e n t h e m os t fre q u e n t ly
fou n d a n t ibod ie s ; in fa ct , t h ey h a ve be e n d e s cribe d in u p t o 83% of p a t ie n t s
w it h t h is d is e a s e, bu t on ly in 10% t o 17% w it h ot h e r CTDs (9 ). From t h e im m u -
n oge n e t ic p oin t of view, p a t ie n t s w it h s cle rod e rm a t om yos it is a re e it h e r HLA-
DR3 h om ozygou s or HLA-DR3/DR4 h e t e rozygou s . Th ey a re t h u s q u it e d iffe re n t
from p a t ie n t s w it h MCTD.
Th e freq u en cy of th is d isord er is la rgely u n kn ow n ; a s w ith rh u p u s, m ost p u b-
lica tion s on sclerod erm a tom yositis com e from tertia ry ca re fa cilities a n d in clu d e
sm a ll ca se series a n d ca se rep orts; th u s, p op u la tion -ba sed gu res a re u n ava ilable.
Th e t re a t m e n t of t h e s e p a t ie n t s s h ou ld be a im e d a t con t rollin g t h e in a m -
m a t ory p ro ce s s in m u s cle s a n d ot h e r t is s u e s in volve d . W h ile SSc a s s o cia t e d
w it h m yos it is is u s u a lly a ve ry s eve re form of t h e d is e a s e, s cle rom yos it is h a s ,
in ge n e ra l, a p rot ra ct e d a n d ra t h e r be n ign cou rs e . Th e d iffe re n ce lie s on it s
vis ce ra l in volve m e n t a n d n ot in fre q u e n t ly by t h e vis u a l s ign s of d e rm a t om y-
os it is (7 ). Mu s cle in a m m a t ion is u s u a lly m ild a n d s t e roid re s p on s ive. Aggre s -
s ive t re a t m e n t s u ch a s t h e on e u s e d in SSc a n d d e rm a t om yos it is cou ld be m ore
h a rm fu l t h a n t h e d is e a s e it s e lf, a n d is ra re ly re q u ire d (7 ). Th is is a n im p ort a n t
re a s on for re cogn izin g p a t ie n t s w it h t h is ove rla p s yn d rom e. Th e p rogn os is of
p a t ie n t s w it h t h is ove rla p s yn d rom e d ep e n d s on t h e d egre e of orga n s ys t e m
in volve m e n t t h ey h a ve, bu t ove ra ll, t h e p rogn os is is m ore favora ble t h a n SSc or
d e rm a t om yos it is by t h e m s e lve s (9 ).
 154 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

MIXED CONNECTIVE TISSUE DISEASE

Th e r s t d e s cr ip t io n o f MCTD d a t e s b a ck t o 1972 w h e n Sh a r p d e s cr ib e d
25 p a t ie n t s w it h ove rla p p in g clin ica l m a n ife s t a t ion s of RA, SLE, m yos it is , a n d
s cle rod e rm a occu rrin g p re d om in a n t ly in a d u lt w om e n ; s im ila r ca s e s h ave be e n
d e s cr ib e d in ch ild re n a n d o ld e r a d u lt s (1 ). Th e s e p a t ie n t s a ls o e x h ib it e d
e xt re m e ly h igh t it e rs of a n t ibod ie s t o e xt ra ct a ble n u cle a r a n t ige n (ENA), la t e r
id e n t i e d a s a n t ibod ie s t o U1RNP a n d HLA-DR4 p os it ivit y. Sin ce t h e n , t o d a t e,
t h is s yn d rom e h a s be e n a t t h e ce n t e r of d is cu s s ion , w it h s om e rh e u m a t ologis t s
favorin g it s re cogn it ion a n d ot h e rs n ot . Th e re a re t h os e w h o a rgu e t h a t p a t ie n t s
w it h MCTD, in clu d in g t h e o n e s o rigin a lly d e s cribe d by Sh a rp , t e n d t o evo lve
in t o on e of t h e m ore d e n e d CTDs , s u ch a s SLE, m yos it is , or s cle rod e rm a , a n d
s h ou ld n ot be con s id e re d t o h a ve a d e n e d s yn d rom e. Th e re a re ot h e rs , h ow -
eve r, w h o p rop os e t h a t p a t ie n t s w it h a n t i-U1RNP a n t ibod ie s , bu t n o cle a r-cu t
m a n ife s t a t ion s of MCTD, re p re s e n t e a rly or u n d e n e d MCTD a n d t h a t a s t im e
goe s on t h ey evolve in t o t h e fu ll-blow n MCTD s yn d rom e. So t h e p re s e n ce of
a n t ibod ie s t o U1RNP, a lt h ou gh ch a ra ct e ris t ic of MCTD, d oe s n ot , in t h e a bs e n ce
o f o t h e r clin ica l fe a t u re s , s u f ce t o m a ke t h is d ia gn os is . Th e fa ct t h a t s o m e
S
p a t ie n t s evolve in t o a m ore d e n e d CTD h a s be e n p os t u la t e d t o h ave ge n e t ic
E
C
ba s is . Pa t ie n t s w h o s t a rt a s MCTD a n d a re HLA-DR3 or HLA-DR5 evolve in t o SLE
T
I
or s cle rod e rm a , w h e re a s t h os e w h o a re HLA-DR4 re m a in a s MCTD.
O
N
Ta ble 16.3 s h ow s t h e d is t in ct clin ica l fe a t u re s of MCTD: Ra yn a u d ’s p h e -
3
n om en on , s clerod a ctyly, sa u sa ge d igit s, lym p h oa d en op a th y, m a la r ra s h , m yosit is ,
S
p
p u lm on a ry in volve m e n t , e s op h a ge a l d ys m ot ilit y, s ym m e t ric p olya rt h rit is (in
e
c
a n RA-like d is t ribu t ion ), a n d s e ros it is . Orga n s ys t e m in volve m e n t , p a rt icu la rly
i
c
ga s t roin t e s t in a l a n d p u lm on a ry, occu rs w it h va ria ble fre q u e n cy, bu t re n a l a n d
R
h
ce n t ra l n e r vo u s s ys t e m in vo lve m e n t s a re co n s p icu o u s ly a b s e n t . Ra yn a u d ’s
e
u
p h e n om e n on s eve re e n ou gh t o p rod u ce s eve re d igit a l is ch e m ia a n d n e cros is ,
m
s a u s a ge d igit s , sw olle n h a n d s , p o lya rt h rit is , a n d ra s h a re t h e m ore com m on
a
t
i
p re s e n t in g m a n ife s t a t ion s of MCTD. Crit e ria for t h e d ia gn os is of MCTD h ave
c
D
be e n p rop os e d by Sh a rp a n d s u bs e q u e n t ly by ot h e r in ve s t iga t ors ; t h ey in clu d e,
i
s
e
in a d d it ion t o t h e clin ica l m a n ife s t a t ion s d e s cribe d , t h e p re s e n ce of a n t ibod ie s
a
s
t o ENA (a n t i-U1RNP) a t ve ry h igh t it e rs (in t h e m illion s ) in t h e a bs e n ce of a n t i-
e
s
Sm it h a n t ibod ie s . A p a t h oge n ic role for a n t i-U1RNP a n t ibod ie s h a s n ot be e n
d e t e rm in e d t o d a t e ; it is q u it e p os s ible (a n d in fa ct h a s be e n p rop os e d ) t h a t
t h e s e a n t ibod ie s m od ify t h e clin ica l e xp re s s ion of a CTD.
Tre a t m e n t in p a t ie n t s w it h MCTD is d ire ct e d t ow a rd t h e clin ica l m a n ife s t a -
t ion s p re s e n t , a n d t o t h e p reve n t ion of s t ru ct u ra l d a m a ge in a ffe ct e d orga n s ,
u s in g s t a n d a rd p h a rm a cologic com p ou n d s com m on ly u s e d in t h e m ore d e n e d
CTDs , s u ch a s co r t ico s t e ro id s , m e t h o t re x a t e , a n d o t h e r im m u n o s u p p re s s ive
d ru gs . Th e p rogn os is in p a t ie n t s w it h MCTD is va ria ble ; p a t ie n t s w h o evolve
in t o a d e n e d CTD a d op t t h e clin ica l cou rs e a n d ou t com e of t h e n ew e n t it y,
w h e re a s t h o s e w h o re m a in a s a n ove r la p m a y d eve lo p p ro m in e n t d igit a l

Table 16.3 Clinical and Laborat ory Feat ures of Mixed Connect ive
Tissue Disease

MAJOR MINOR
Sw o lle n n g e rs a n d /o r h a n d s Art h rit is
Ra yn a u d ’s p h e n o m e n o n Alo p e cia
Eso p h a g e a l d ysm o t ilit y Myo sit is
Scle ro d a ct yly Trig e m in a l n e u ro p a t h y
Myo sit is Cyt o p e n ia s
Se ro sit is
Pu lm o n a ry in vo lve m e n t
An t i-U1RNP a n t ib o d ie s
Ne g a t ive a n t i-Sm a n t ib o d ie s
 Ch a p te r 16 Ove rla p Syn d ro m e s a n d Un cla s s i e d or Un d iffe re n t ia t e d Con n e ct ive Tis s u e Dis e a s e
NOT TO BE MISSED
• No t a ll p a t ie n t s w it h
sym p t o m s o f m o re t h a n
o n e rh e u m a t ic d ise a se
re p re se n t a n o ve rla p .
• Sym p t o m s su ch a s
Ra yn a u d ’s p h e n o m e n o n ,
a rt h rit is, scle ro d a ct yly, a n d
a lve o lit is m a y b e p re se n t
in p a t ie n t s w it h d iffe re n t
rh e u m a t ic d ise a se s a n d
a re st ill m o re co m m o n ly
e xp la in e d b y o n e e n t it y
(o n e d ise a se ) t h a n se ve ra l
o ccu rrin g sim u lt a n e o u sly.
155
is ch e m ic or n e crot ic eve n t s , a s w e ll a s p u lm on a ry h yp e rt e n s ion or s ign i ca n t
ga s t roe s op h a ge a l re u x.
THE UNCLASSIFIED OR UNDIFFERENTIATED CONNECTIVE
TISSUE DISEASES
Th e re is n o con s e n s u s on h ow e xa ct ly t o d ia gn os e t h e s e p a t ie n t s . Som e a u t h ors
con s id e r t h e s e p a t ie n t s t o be t h e p re a m ble of MCTD, ot h e rs of lu p u s (p re lu p u s ,
la t e n t lu p u s , in co m p le t e lu p u s ); o t h e rs , in clu d in g o u r gro u p , m a y co n s id e r
t h e s e p a t ie n t s a s h a vin g a n ANA-p os it ive , brom ya lgia -like s yn d ro m e (s e e
Fibrom ya lgia ch a p t e r). Ot h e rs p re fe r t o ca ll t h e s e p a t ie n t s u n cla s s i e d or u n d if-
fe re n t ia t e d CTDs on ly t o in d ica t e t h e fa ct t h a t t h e s e p a t ie n t s t e n d t o evolve in t o
a d e n e d CTD. In d e e d a la rge e ffort by rh e u m a t ologis t s a t d iffe re n t U.S. a ca -
d e m ic ce n t e rs t ook p la ce be t w e e n 1982 a n d 1995; t h ey con s t it u t e d t h e la rge s t
coh ort of “u n cla s s i e d ” p a t ie n t s w it h d is e a s e m a n ife s t a t ion s of u p t o 12 m on t h s
in d u ra t ion a n d follow e d t h e s e p a t ie n t s ove r t im e. Th e a im w a s t o id e n t ify
a m on g t h e s e p a t ie n t s t h e p re d ict ors of a give n ou t com e. Th re e s u bgrou p s of
p a t ie n t s w e re re cogn ize d w it h in t h is coh ort of u n cla s s i e d p a t ie n t s : (a ) t h os e
s
e
w it h is ola t e d Rayn a u d ’s p h e n om e n on , (b) t h os e w it h u n e xp la in e d p olya rt h rit is
s
a
(p a t ie n t s q u it e n ot m e e t in g crit e ria for t h e d ia gn os is of RA), a n d (c) t h os e w it h
e
s
i
t ru ly u n d e n e d m a n ife s t a t ion s (a s p rovid e d in Ta ble 16.4 ). It ca n be a rgu e d t h a t
D
c
n ot a ll p a t ie n t s e n t e rin g t h e u n d e n e d ca t egory w ou ld h ave be e n in clu d e d a s
i
t
a
s u ch t o d a t e ; in d e e d s om e of t h e s e p a t ie n t s p roba bly cou ld h ave be e n con s id -
m
e re d a s h a vin g a n ANA-p os it ive, brom ya lgia -like s yn d rom e a s d e s cribe d by
u
e
ou r grou p s eve ra l ye a rs a go. Th is m u lt ice n t ric grou p a ls o con s t it u t e d a s e con d
h
R
coh ort of p a t ie n t s w it h w e ll-d e n e d CTDs t h a t s e rve d a s a com p a ris on for t h e
c
i
u n cla s s i e d p a t ie n t s .
c
e
Pa t ie n t s in t h is s t u d y w e re follow e d lon git u d in a lly in a n e ffort t o d e t e rm in e
p
S
t h e p a t ie n t s ’ n a l d ia gn os is . Ye a rly vis it s w e re d on e d u rin g t h e rs t 5 ye a rs ; a n
3
N
a d d it ion a l vis it w a s con d u ct e d a t 10 ye a rs . Th e p rot ocol re q u ire d on ly a n u p d a t e
O
in t e rva l h is t o ry, a p h ys ica l e x a m in a t io n , a n d a co re o f la b o ra t o ry t e s t s . An y
I
T
C
ot h e r la bora t ory t e s t or m ore s op h is t ica t e d a n cilla ry p roce d u re re q u ire d t h e
E
S
p re s e n ce of clin ica l m a n ife s t a t ion s t h a t cou ld ju s t ify ord e rin g or p e rform in g
t h e m . Th e re s u lt s of t h is s t u d y a re w ort h d is cu s s in g. Firs t , t h e ove rw h e lm in g
m a jorit y of p a t ie n t s e n t e rin g t h e s t u dy a s d e n e d CTDs kep t t h e s a m e d ia gn os is
a t a la t e r t im e p oin t ; t h is con t ra s t s w it h le s s t h a n 50% for t h os e w it h u n d iffe r-
e n t ia t e d d is e a s e t h a t kep t t h e s a m e d ia gn os is . Am on g t h os e w it h u n cla s s i e d
d is e a s e s , t h e re w e re s o m e d iffe re n ce s d e p e n d in g o n t h e s u b gro u p w it h in
t h is coh ort a t e n rollm e n t . Of t h os e w h o s t a rt e d a s u n e xp la in e d p olya rt h rit is ,
Table 16.4 Clinical Feat ures of Pat ient s wit h Unclassi ed or
Undifferent iat ed Connect ive Tissue Disease
Art h ra lg ia s/a rt h rit is
Mya lg ia s
Ra sh e s
Sicca
Pe rica rd it is/p le u rit is
Pu lm o n a ry in vo lve m e n t
Pe rip h e ra l n e u ro p a t h y
Ele va t e d a cu t e -p h a se re a ct a n t (s)
Po sit ive se ro lo g ic t e st fo r syp h ilis
 156 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

Unclassified or
undifferentiated
CTD
n = 213

UPA Remission Remission

n = 67 n= 41a n = 13(1) n = 29(1)

Defined CTDs Defined CTDs

n = 12(2) n = 33(4)
NA
n = 26
Undefined CTDs Undefined
n = 15(1) CTDs n = 58(7)
S
E
C
T
I
O
RP n = 15 Remission
N
n = 31 n =5
3
S
p
e
c
i
NA Defined CTDs
c
n=2
R
n = 16
h
e
u
m
a
Undefined CTDs
t
i
c
n=8
D
i
s
e
a
s
e
s
Undefined CTDs Remission
n = 15 n = 68b n = 11

Defined CTDs
n = 19(2)
NA
n = 47

Undefined CTDs
n = 35(6)

Figure 16.2 Ten-yea r follow-up dia gnoses of pa tients with uncla ssi ed or undifferentia ted connective tissue disea se
(CTD); UPA, unexpla ined polya rthritis; NA, nona va ila ble; RP, Ra yna ud’s phenomenon. a One pa tient developed psoria tic
a rthritis; b one pa tient ea ch developed psoria tic a rthritis, sa rcoidosis, a nd mya sthenia gra vis. Modi ed from Ala rcón (1).

a bou t on e t h ird re m a in e d u n d iffe re n t ia t e d , on e t h ird w e n t in t o re m is s ion , a n d

t h e ot h e r t h ird evolve d in t o a d e n e d CTD. In con t ra s t , of t h os e p a t ie n t s w h o
e n t e re d t h e coh ort a s is ola t e d Ra yn a u d ’s p h e n om e n on or a s u n d e n e d m a n i-
fe s t a t ion s of a CTD, a bou t on e h a lf re m a in e d a s u n d iffe re n t ia t e d ; p a t ie n t s w it h
Rayn a u d ’s p h e n om e n on w e re m ore like ly t o go in t o re m is s ion , w h e re a s t h os e
w it h u n d e n e d m a n ife s t a t ion s w e re m ore like ly t o evolve in t o a d e n e d CTD.
Figu re 16.2 s u m m a rize s t h e in it ia l a n d n a l d ia gn os e s of p a t ie n t s from t h is
u n d iffe re n t ia t e d CTD coh ort .
 Ch a p te r 16 Ove rla p Syn d ro m e s a n d Un cla s s i e d or Un d iffe re n t ia t e d Con n e ct ive Tis s u e Dis e a s e
WHEN TO REFER
• In a m m a t o ry a rt h rit is.
• Skin ch a n g e s ch a ra ct e rize d
b y t h icke n in g , scle ro d a ct y-
ly, a n d Ra yn a u d ’s p h e n o m -
enon.
• Po sit ive se ro lo g ie s fo r CTD
in t h e se t t in g o f a p p ro p ri-
a t e clin ica l m a n ife st a t io n s.
• Re fe rra l a llo w s t h e rh e u -
m a t o lo g ist t o d e n e t h e
d ia g n o sis (a s m u ch a s p o s-
sib le ) a n d re co m m e n d
p ro p e r m a n a g e m e n t ; t h is
is o f p a ra m o u n t im p o r-
t a n ce if t h e p o ssib le d e le -
t e rio u s im p a ct o f t h e CTD
is t o b e le sse n e d .
157
Th e e xa m in a t ion of s ocioe con om ic–d e m ogra p h ic a n d clin ica l p a ra m e t e rs
for p re d ict ors of a give n ou t com e a m on g p a t ie n t s from t h e e n t ire u n d iffe re n t i-
a t e d coh ort re n d e re d s om e in t e re s t in g d a t a . You n g p a t ie n t s of Africa n -Am e rica n
e t h n icit y w it h a lop e cia , s e ros it is , d is coid lu p u s , p os it ive ANAs , a n d a n t i-Sm it h
a n t ibod ie s w e re m ore like ly t o evolve in t o SLE; t h os e w it h s m a ll h a n d join t s
in volve m e n t w e re m ore like ly t o evolve in t o RA. Of cou rs e it ca n be a rgu e d t h a t
in bot h t h e s e ca s e s p a t ie n t s cou ld h ave be e n d ia gn os e d a s h avin g SLE a n d RA,
re s p e ct ive ly, bu t follow in g t h e s t rict gu id e lin e s e s t a blis h e d a p riori for t h is s t u d y
t h ey cou ld n ot , s in ce t h ey d id n ot m e e t crit e ria for e it h e r d is ord e r.
Re ce n t ly, few s t u d ie s h ave s h ow n t h a t low leve ls of vit a m in D in p a t ie n t s
w it h UCTD m ay p lay a role in t h e s u bs e q u e n t p rogre s s ion in t o a w e ll-d e n e d
CTD. Su p p le m e n t a t ion of t h e s e p a t ie n t s w it h vit a m in D a s w e ll a s m e a s u re -
m e n t of vit a m in D leve ls m igh t be con s id e re d (10 ).
In s u m m a ry, m ore t h a n a p re cis e d ia gn os is , t h e ge n e ra lis t s h o u ld follow
p a t ie n t s w it h m a n ife s t a t ion s s u gge s t ive, bu t n ot d ia gn os t ic, of a CTD w it h a
ve ry op e n m in d a n d be re a d y t o d ia gn os e a n d t re a t a CTD if cle a r-cu t m a n ife s -
t a t ion s of s u ch evolve. Pa t ie n t s s h ou ld be t re a t e d a ccord in g t o t h e ir clin ica l
m a n ife s t a t ion s , t ryin g t o m in im ize t h e im p a ct of t h e d is ord e r a s w e ll a s t h a t of
s
e
t h e t h e ra p ie s u t ilize d .
s
a
e
Re fe r to Patie nt Education
s
i
D
c
i
t
a
ICD9
m
u
710.9 Co nne ctive tissue , diffuse
e
h
R
c
i
c
Re fe re nce s
e
p
S
1. Ala rcon G. Un cla s s i e d o r u n d iffe re n t ia t e d con n e ct ive t is s u e d is e a s e . In : Koop m a n W J, Bou lw a re DW,
3
He u d e be rt GR, e d s . Clinical Prim er of Rheum atology. Lip p in cot t Willia m s a n d W ilkin s . 2003 :213 –219 .
N
2. Am e zcu a -Gu e rra LM , Sp rin ga ll R, Ma rq u e z-Ve la s co R, e t a l. Pre s e n ce of a n t ibod ie s a ga in s t cyclic cit -
O
I
ru llin a t e d p e p t id e s in p a t ie n t s w it h “rh u p u s ”: A cros s -s e ct ion a l s t u d y. A rthritis Res Ther 2006 ;8 (5 ):R144 .
T
C
3. Ro d r igu e z-Reyn a TS, Ala rcon -Segovia D. Ove rla p s yn d rom e s in t h e con t e xt of s h a re d a u t oim m u n it y.
E
Autoim m unity 2005 ;38 (3 ):219 –223 .
S
4. Pip ili C, Sfrit ze ri A, Ch olon git a s E. De fo rm in g a rt h rop a t h y in SLE: Review in t h e lit e ra t u re a p rop os of on e
ca s e . Rheum atol Int 2009 ;29 (10 ):1219 –1221 .
5. Levin e D, Sw it lyk SA, Got t lie b A. Cu t a n e ou s lu p u s e ryt h e m a t os u s a n d a n t i-TNF-a lp h a t h e ra py: A ca s e
re p ort w it h review of t h e lit e ra t u re . J Drugs Derm atol 2010 ;9 (10 ):1283 –1287 .
6. Soforo E, Ba u m ga rt e r M , Fra n cis L, e t a l. In d u ct ion of s ys t e m ic lu p u s e ryt h e m a t os u s w it h t u m or n e cro-
s is fa ct or blocke rs . J Rheum atol 2010 ;37 (1 ):204 –205 .
7. Ja blon s ka S, Bla s zyk M . Scle rom yos it is (s cle rod e rm a /p olim yos it is ove rla p ) is a n e n t it y. J Eur A cad Derm atol
Venereol 2004 ;18 (3 ):265 –266 .
8. Torok L, Da kó K, Cs e rin G, e t a l. PM-SCL a u t oa n t ibod y p os it ive s cle rod e rm a w it h p olym yos it is (m e ch a n -
ic’s h a n d : clin ica l a id in t h e d ia gn os is ). J Eur A cad Derm atol Venereol 2004 ;18 (3 ):356 –359 .
9. Ja blon s ka S, Bla s zczyk M . Scle rom yos it is : A s cle rod e rm a /p olym yos it is ove rla p s yn d rom e . Clin Rheum atol
1998 ;17 (6 ):465 –467 .
10. Zold E, Szod oray P, Ka p p e lm a ye r J, e t a l. Im p a ire d regu la t ory T-ce ll h om e os t a s is d u e t o vit a m in D d e -
cie n cy in u n d iffe re n t ia t e d con n e ct ive t is s u e d is e a s e . Scand J Rheum atol 2010 ;39 :490 –497 .
 CHAPTER
17 Fibromya lgia
Graciela S . A larcón

Intro ductio n
A 40-ye ar-o ld o b e se , se d e n -
Fib ro m ya lgia (FM) is a co n d it io n
S
t ary, Cau casian w o m an
E
C
a ffe c t in g p r e fe r e n t ia lly m id d le -
T
p re se n t s t o a rh e u m at o lo g ist
I
a ge d w h it e w om e n ; m e n , ch ild re n
O
N
w it h a 6-m o n t h h ist o ry o f of e it h e r ge n d e r, a n d old e r a d u lt s
3
g e n e raliz e d m yalg ias, ca n be a ffe ct e d , h ow eve r (1 ). Fibro-
S
p
m ya lgia h a s be e n re cogn iz e d p r i-
e
art h ralg ias, sw e llin g o f sm all
c
m a r ily in t h e m id d le a n d u p p e r
i
h an d jo in t s, an d m o rn in g
c
s ocioe con om ic s t ra t a . W h e t h e r t h is
R
st iff n e ss o f u n sp e ci e d d u ra- re e ct s on ly a cce s s t o h e a lt h ca re
h
e
u
t io n . He r p rim ary care p h ysi- or t ru e d iffe re n ce s in t h e in cid e n ce
m
a n d p r e va le n ce o f t h e d is o rd e r
a
cian h ad ru n so m e t e st s an d
t
i
a m on g d is a d va n t a ge d p op u la t ion s
c
re f e rre d h e r f o r p o ssib le
D
h a s n ot be e n d e t e rm in e d .
i
s
e
rh e u m at o id art h rit is (RA ). Th e tru e in cid en ce a n d p reva -
a
s
(Ig M rh e u m at o id f act o r w as len ce of FM is u n kn ow n . Pop u la tion -
e
s
ba sed stu d ies a re d if cu lt to in ter-
p o sit ive at 24 u n it s.) Ot h e r
pret; issu es su ch a s th e criteria u sed
sym p t o m s e licit e d b y t h e t o d ia gn os e FM, w h e t h e r p rim a ry
rh e u m at o lo g ist in clu d e d a n d secon d a ry ca ses a re in clu d e d ,
f at ig u e , u n re f re sh e d sle e p , a n d th e d em ogra p h ic ch a ra cteristics
of th e p op u la tion th a t is bein g su r-
in t e rm it t e n t ab d o m in al
veyed n eed to be con sid ered . Stu d ies
p ain , an d in cre ase d u rin ary from Nort h Am e rica a n d Eu rop e,
f re q u e n cy. M o rn in g st iff n e ss last e d ab o u t 30 m in u t e s. Ph ysical im p e rfe ct a s t h ey m ay be, reve a l
e xam in at io n re ve ale d an o b e se w h it e w o m an in n o d ist re ss. Th e re overa ll p reva len ce ra tes betw een 1%
a n d 5%, bu t gu res a s h igh a s 13%
w e re m u lt ip le t e n d e r are as o ve r t h e u p p e r an d lo w e r b ack , an d
h ave been rep orted . Th es e p op u la -
aro u n d t h e sh o u ld e r an d p e lvic g ird le s. Th e h an d s w e re p u ff y tion -ba sed stu d ies con rm th e gen -
(f at ), b u t n o syn o vit is w as d e t e ct e d in an y o f t h e jo in t s. A co m - d e r d is t r ib u t io n (p re d o m in a n t ly
p le t e b lo o d co u n t an d a u rin alysis w e re n o rm al. Rad io g rap h s o f fem a le) of th e FM syn d rom e. In th e
clin ica l settin g, th e freq u en cy of FM
t h e aff e ct e d are as w e re n o t o b t ain e d .
d ep en d s, to a certa in exten t, on th e
degree of aw a ren ess abou t th is con -
d ition . Figu res betw een 2% a n d 4% h ave been rep orted in th e p rim a ry ca re settin g.
In rh eu m a tology clin ics, th e freq u en cy of FM u ctu a tes betw een 3% a n d 20%. Th ese
gu res p robably re ect th e rh eu m a tologists’ in terest in FM a n d th e level of aw a re-
n ess abou t th is con d ition a m on g com m u n ity ph ysicia n s a n d th e p u blic a t la rge (1 ).
Like m a n y ot h e r rh e u m a t ic d is ord e rs , t h e e t iop a t h oge n e s is of FM is p rob-
a bly m u lt ifa ct oria l (1 ). Su s cep t ible in d ivid u a ls m a y d eve lop FM a s a re s u lt of t h e
158

CLINICAL POINTS
• Fib ro m ya lg ia is p ro b a b ly
m o re co m m o n t h a n rh e u -
m a t o id a rt h rit is. In t h e
a b se n ce o f syn o vit is, a p o si-
t ive rh e u m a t o id fa ct o r t e st
sh o u ld n o t b e co n sid e re d
t o d ia g n o se RA.
• Wo m e n a re m o re co m m o n -
ly a ffe ct e d . It o ccu rs m a in ly
in a d u lt s, b u t ca n a ffe ct
ch ild re n a n d t h e e ld e rly.
• Ne w e r crit e ria d e ve lo p e d
b y t h e Am e rica n Co lle g e o f
Rh e u m a t o lo g y (ACR) d o
n o t in clu d e t h e cla ssica l
t e n d e r p o in t s.
PATIENT ASSESSMENT
• Th e d ia g n o sis is clin ica l. A
co m p le t e h ist o ry a n d a
p h ysica l e xa m in a t io n a re
n e ce ssa ry. Mu lt ip le t e n d e r
p o in t s a re u su a lly p re se n t ,
w h e re a s jo in t sw e llin g is
co n sp icu o u sly a b se n t .
• Ext e n sive (a n d e xp e n sive )
a n cilla ry t e st s a re n o t
re co m m e n d e d .
• Tre a t m e n t is m u lt id iscip li-
n a ry w it h m e d ica t io n s
b e in g o n ly o n e e le m e n t .
Ch a p te r 17 Fibrom ya lgia 159
in t e ra ct ion of p e rip h e ra l a n d ce n t ra l fa ct ors . Fa m ilia l a ggrega t ion of FM d oe s
n ot it s e lf p rove ge n e t ic s u s ce p t ibilit y; in fa ct , it ca n be a rgu e d t h a t fa m ilia l
a ggrega t ion re e ct s on ly le a rn e d be h avior a m on g t h e offs p rin g of a d u lt p a t ie n t s
w it h FM. How eve r, t h e fa m ilia l p a t t e rn of FM (a ffe ct in g p rim a rily t h e fe m a le
ge n d e r) s u gge s t s a n a u t os om a l-d om in a n t t ra n s m is s ion (1 ). An im a l d a t a in d e e d
s u gge s t t h a t ge n e t ic fa ct ors m ay in u e n ce p a in s e n s it ivit y a n d p a in m od u la -
t ion ; h u m a n d a t a a re ju s t e m e rgin g (1 ).
In s om e p a t ie n t s , FM evo lve s in a n in s id io u s m a n n e r. It is im p o s s ible t o
d e t e rm in e p re cis e ly w h e n s ym p t om s re a lly s t a rt e d . Ot h e r p a t ie n t s , h ow eve r,
ca n t im e t h e on s e t of t h e ir s ym p t om s t o a t ra u m a t ic eve n t (p h ys ica l or e m o-
t io n a l) or t o a w e ll-d e n e d in fe ct iou s p ro ce s s . In fa ct , t h e s e p os t in fe ct io u s
ca s e s w e re ca lle d in t h e p a s t “re a ct ive FM” (com p a rin g t h e m t o ot h e r p os t in fe c-
t iou s rh e u m a t ic d is ord e rs (re a ct ive a rt h rit is )) (1 ), bu t t h is t e r m is n o lon ge r
u s e d . Wit h rega rd t o t ra u m a , t h e n a t u re of t h e t ra u m a d oe s n ot re a lly m a t t e r
(s eve rit y of in ju ry or eve n if t h e eve n t w a s p re d om in a n t ly p h ys ica l, bu t p e r-
ce ive d a s e m o t ion a l by t h e p a t ie n t ) (1 ). Nu m e rou s in fe ct iou s p ro ce s s e s h a ve
be e n d e s cribe d a s ca p a ble of p re cip it a t in g FM. Th ey in clu d e in fe ct ion s w it h t h e
h u m a n im m u n od e cie n cy viru s , h e p a t it is C viru s , Coxs a ckie viru s , a n d Pa rvo-
s
e
viru s B19 (1 ). In fe ct ion s w it h Borrelia burgdorferi (Lym e d is e a s e ) h ave a ls o be e n
s
a
re cogn iz e d a s ca p a ble o f p re cip it a t in g FM. It s h ou ld be n ot e d t h a t , u n fo rt u -
e
s
i
n a t e ly, m a n y ca s e s of p os t -Lym e FM a re e rron e ou s ly d ia gn os e d a s ch ron ic Lym e
D
c
d is e a s e a n d p a t ie n t s a re s u bje ct e d t o cos t ly, u n n e ce s s a ry, a n d le n gt h y t re a t -
i
t
a
m e n t s (s e e Ch a p t e rs 27 t o 30).
m
u
e
h
R
Clinica l Pre se nta tio n
c
i
c
Fibrom ya lgia is a ch ron ic m u s cu los ke le t a l d is ord e r ch a ra ct e rize d by ge n e ra l-
e
p
S
ize d p a in a n d t e n d e rn e s s a t s p e ci c a n a t om ic s it e s , ca lle d tender points (1 ).
3
Fibrom ya lgia ca n occu r in is ola t ion or in t h e s e t t in g of ot h e r m u s cu los ke le t a l
N
O
or rh e u m a t ic d is ord e r (p rim a ry vs . s e con d a ry FM) (1 ). In fa ct , in s om e p a t ie n t s
I
T
w it h rh e u m a t oid a rt h rit is (RA) or s ys t e m ic lu p u s e ryt h e m a t os u s (SLE), t h e ove r-
C
E
w h e lm in g clin ica l m a n ife s t a t ion s a re t h os e of FM, a n d n ot t h e on e s w e t yp ica lly
S
a t t ribu t e t o e it h e r RA or SLE. Th es e FM s ym p t om s a re, by a n d la rge, u n re s p on s ive
t o t h e ra p ies com m on ly u s e d for t h e t re a t m e n t of t h e u n d e rlyin g con d it ion .
MUSCULOSKELETAL MANIFESTATIONS
Pa t ie n t s w it h FM o ft e n p r e s e n t t o t h e ir p h ys icia n s co m p la in in g o f d iffu s e
a r t h ra lgia s a n d m ya lgia s a s w e ll a s o f jo in t s w e llin g, p a r t icu la r ly in t h e s m a ll
jo in t s o f t h e h a n d s a n d fe e t (1 ). So m e p a t ie n t s a ls o co m p la in o f m o r n in g
s t iffn e s s , la s t in g fro m m in u t e s t o h o u r s ; o t h e r s e x h ib it jo in t h yp e r m o b ilit y.
It s h o u ld b e n o t e d , h ow e ve r, t h a t jo in t s w e llin g is n o t p r e s e n t in t h e s e
p a t ie n t s .
OTHER CLINICAL MANIFESTATIONS
Pa t ie n t s w it h FM m ay e xp e rie n ce n u m e rou s ot h e r clin ica l m a n ife s t a t ion s . In
fa ct , t h e s e ot h e r m a n ife s t a t ion s m ay be t h e on e s t h a t brin g t h e s e p a t ie n t s t o
s e e k m e d ica l h e lp . Sym p t om s re fe rre d t o a ll orga n s ys t e m s h ave be e n d e s cribe d .
In s om e ca s e s , t h e s e ot h e r m a n ife s t a t ion s , ra t h e r t h a n p a in , m a y be t h e p re -
d om in a n t on e s .
Fatig ue
Pa t ie n t s w it h FM oft e n com p la in of s om e d egre e of fa t igu e ; ra re ly, h ow eve r, is
fa t igu e s o in t e n s e a s t o be t h e fa ct or d e t e rm in in g in ca p a cit a t ion , u n like t h e
s it u a t ion of p a t ie n t s w it h ch ron ic fa t igu e s yn d rom e (CFS) (1 ). In t u rn , p a t ie n t s
 160 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

w it h CFS m ay e xp e rie n ce a rt h ra lgia s a n d m ya lgia s , a n d m a y e xh ibit s om e t e n -

d e r p oin t s . Ra re ly, t h e p a t ie n t s m ay m e e t crit e ria for bot h t h e d is ord e rs . Like
p a in , fa t igu e is a s u bje ct ive m a n ife s t a t ion , w h ich ca n on ly be q u a n t i e d by
s e lf-rep ort .

Sle e p Disturbance s
Pa t ie n t s w it h FM, rega rd le s s of t h e in t e n s it y of t h e ir p a in , u s u a lly com p la in of
p oor s le e p ; t h ey m ay h a ve d if cu lt y fa llin g a s le ep or m ay w a ke u p t h rou gh ou t
t h e n igh t . As a re s u lt , t h ey aw a ke in t h e m orn in g u n re fre s h e d a n d t ire d . Som e
in ve s t iga t ors h a ve p os t u la t e d t h a t t h e m u s cu los ke le t a l p a in in FM re s u lt s from
s le e p d e p riva t io n . Sle e p s t u d ie s co n d u ct e d in p a t ie n t s w it h FM h a ve in d e e d
s h ow n a bn orm a l re cord in gs d u rin g d e ep s le e p . Th is p a t t e rn , ca lle d “n on –ra p id
eye m ove m e n t a n o m a ly,” is ch a ra ct e rize d by a re la t ive fa s t fre q u e n cy (a lp h a
w a ve s ) s u p e rim p o s e d in a s low e r d e lt a fre q u e n cy (1 ). Sim ila r n d in gs h a ve
b e e n o b t a in e d in n o r m a l in d ivid u a ls s u b je ct e d t o s le e p d e p r iva t io n ; t h e s e
a bn orm a lit ie s a re n e it h e r s p e ci c n or s e n s it ive for FM. An o t h e r a bn orm a lit y,
s le ep a p n e a , d e s cribe d in s om e p a t ie n t s w it h FM, p rim a rily ove rw e igh t m e n ,
S
ca n be con s id e re d a m a rke r for t h is d is ord e r. How eve r, on ly a ca re fu l a s s e s s -
E
C
m e n t of s le ep (in clu d in g t h e s p ou s e or be d p a rt n e r) m a y u n cove r t h e p re s e n ce
T
I
O
a n d s eve rit y of s le ep a p n e a .
N
3
S
Othe r Manife statio ns
p
e
Ta ble 17.1 p rovid e s ot h e r clin ica l m a n ife s t a t ion s d e s cribe d in p a t ie n t s w it h FM.
c
i
Th e s e p a t ie n t s m ay be u n d e r t h e ca re of d iffe re n t p h ys icia n s for t h e ir va riou s
c
R
s ym p t om s a n d m a y be s u bje ct e d t o e xt e n s ive, e xp e n s ive, a n d eve n in va s ive
h
e
t e s t s a n d p roce d u re s in ord e r t o ru le ou t m ore s e riou s or d iffe re n t d is ord e rs .
u
m
Im a gin g a n d n u cle a r m e d icin e s t u d ie s , e n d os cop ie s , a n d e xp lora t ory s u rge rie s
a
t
a re, u n fort u n a t e ly, n ot u n com m on ly p e rform e d . Ta ble 17.1 p rovid e s p roce d u re s
i
c
a n d t e s t s com m on ly obt a in e d in p a t ie n t s w it h FM.
D
i
s
Rh e u m a t o logis t s s e e p a t ie n t s w it h p o s s ible FM in con s u lt a t ion in d iffe r-
e
a
e n t s it u a t io n s . On e s ce n a r io is t h a t o f p a t ie n t s w it h FM w h o h a ve fa ile d
s
e
n u m e ro u s t re a t m e n t s a n d w h o co m e s e e k in g a cu re fo r t h e ir a ilm e n t . A s e c-
s
o n d s ce n a r io is t h a t o f p a t ie n t s w h o w a n t t o le git im iz e t h e ir d ia gn o s is fo r
le ga l p u r p o s e s (e .g., w o r k m a n ’s co m p e n s a t io n o r d is a b ilit y d e t e r m in a t io n ) (1 ).
St ill o t h e r s a re p a t ie n t s w it h d iffe re n t m u s cu lo s k e le t a l d is o rd e r s , w h o h a d
b e e n d ia gn o s e d a s h a vin g FM b u t w h o s e d ia gn o s e s h a ve b e e n ove r lo o k e d .
Ex a m p le s in clu d e s p in a l s t e n o s is , p e r ip h e ra l n e u ro p a t h ie s , s ys t e m ic va s cu li-
t is , m yo s it is , a n d p o lym ya lgia r h e u m a t ica , a m o n g o t h e r s . A fo u r t h s ce n a r io is
t h a t o f p a t ie n t s w h o h a ve b e e n d ia gn o s e d a s h a vin g “re fra ct o ry RA” a n d h a ve
re ce ive d m u lt ip le m e d ica t io n s , b u t h a ve s ign i ca n t jo in t co m p la in t s (p a in
p r im a r ily). If p a t ie n t s a re o b e s e , t h e d iffe re n t ia t io n b e t w e e n p u ffy o r fa t t y
h a n d s a n d t r u e a rt h r it is m a y n o t be re a d ily evid e n t t o t h e n o n r h e u m a t o logis t .
La s t ly, o t h e r p a t ie n t s h a ve b e e n d ia gn o s e d a s h a vin g SLE o r re fe rre d fo r eva l-
u a t io n o f p o s s ible SLE. Th ey p re s e n t FM-lik e m a n ife s t a t io n s a n d a p o s it ive
t e s t fo r a n t in u cle a r a n t ibo d ie s (ANA). Th ey m a y a ls o h a ve s u bje ct ive , b u t n o t
o b je ct ive , clin ica l m a n ife s t a t io n s t h a t re n d e r t h e d ia gn os is o f SLE p la u s ible ,
u n t il t h e h is t o ry is e xa m in e d m o re cr it ica lly (1 ). Fo r e x a m p le , p a t ie n t s m a y
p re s e n t a ft e r h a vin g h a d ora l or n a s a l u lce r s , p h o t os e n s it ivit y, a n d p h o t o s e n -
s it ive ra s h e s . Sim ila r ly, t h ey m a y co m p la in o f Ra yn a u d ’s p h e n o m e n o n –lik e
m a n ife s t a t io n s , a lo p e cia , ch e s t p a in (w h ich w o r s e n s in in s p ira t io n ), a n d o f
co u r s e , a r t h ra lgia s a n d m ya lgia s . A p o s it ive ANA in t h is s e t t in g re in fo rce s t h e
d ia gn o s is of SLE a n d , u n fo rt u n a t e ly, m a y p ro m p t t h e in it ia t io n o f p o t e n t ia lly
t o x ic p h a r m a co lo gic co m p o u n d s . Alt h o u gh it is n eve r p o s s ib le t o b e s u re
w h e t h e r s u ch p a t ie n t s m a y eve n t u a lly d eve lo p SLE, it is p re fe ra ble t o w a it
u n t il o b je ct ive e vid e n ce o f SLE b e co m e s e vid e n t a n d t o n o t a la r m t h e s e
p a t ie n t s u n d u ly.
 Ch a p te r 17 Fibrom ya lgia 161

Table 17.1 Sympt oms, Diagnost ic Test s or Procedures, and Diagnoses in Pat ient s wit h
Fibromyalgia Seeking Healt h Care

REASONS FOR POTENTIAL TESTS/

SPECIALIST CONSULTATION PROCEDURES POSSIBLE DIAGNOSESa
In t e rn ist Ma la ise , fa t ig u e , w e a kn e ss Va rio u s Va rio u s
Ca rd io lo g ist Pa lp it a t io n s, ch e st p a in , ECG, e xe rcise t e st , e ch o ca rd io - Mit ra l va lve p ro la p se ,
syn co p e , h yp o t e n sio n g ra m , co n ve n t io n a l a n d MR a t yp ica l a n g in a ,
a n g io g ra m s, ca rd ia c ca t h e t e r- d ysa u t o n o m ia
iza t io n , t ilt -t a b le e va lu a t io n
Pu lm o n o lo g ist Dysp n e a , sn o rin g Pu lm o n a ry fu n ct io n t e st s, Ast h m a , sle e p a p n e a
a rt e ria l b lo o d g a se s,
p o lyso m n o g ra m
Ga st ro e n t e ro lo g ist Dysp h a g ia , d ysp e p sia , Up p e r a n d lo w e r GI t ra ct No n ca rd ia c ch e st p a in ,
a b d o m in a l p a in , b lo a t in g , e n d o sco p ie s, ra d io g ra p h s irrit a b le b o w e l syn d ro m e ,
co n st ip a t io n , d ia rrh e a a n d /o r b io p sie s, a b d o m in a l CT g a st ro e so p h a g e a l re u x
a n d /o r u lt ra so u n d , a b d o m in a l
a n g io g ra m

s
e
s
En d o crin o lo g ist We a kn e ss, fa in t n e ss Fa st in g b lo o d su g a rs, se ru m Hyp o g lyce m ia

a
e
h o rm o n e le ve ls

s
i
D
Rh e u m a t o lo g ist Mya lg ia s, a rt h ra lg ia s, Se ro lo g ic t e st s, e le ct ro p h ysio - “ La t e n t ,” “ va ria n t ,”

c
i
t
Ra yn a u d ’s p h e n o m e n o n , lo g ic st u d ie s o r “ p re lu p u s” ; co st o ch o n -

a
m
w e a kn e ss, n e ck a n d /o r b a ck d rit is; p o lym ya lg ia

u
p a in , fa t ig u e rh e u m a t ica ; “ u n d iffe re n t i-

e
h
a t e d ” CTD

R
c
De rm a t o lo g ist Pru rit u s, h ive s, skin ra sh e s, Skin b io p sie s De rm a t it is

i
c
“ p h o t o se n sit ivit y”

e
p
S
Alle rg ist “ Alle rg ie s” Skin t e st s, su p p re ssio n t e st s Alle rg ie s

3
Mu lt ip le ch e m ica l

N
O
se n sit ivit ie s

I
T
C
Ne u ro lo g ist Dizzin e ss, d yse st h e sia s, CT sca n s a n d /o r MRIs, MR Mig ra in e , re st le ss le g

E
ve rt ig o , h e a d a ch e , syn co p e , a n g io g ra m s, e le ct ro p h ysio lo g - syn d ro m e , d ysa u t o n o m ia ,

S
se izu re s ic st u d ie s, lu m b a r p u n ct u re , a n xie t y
b io p sie s
Gyn e co lo g ist Polyuria, dysuria, dyspareunia, Cyst o sco p ie s, co lp o sco p ie s UTI, cyst it is, va g in it is,
“ va g in it is,” p e lvic p a in e n d o m e t rio sis
Ot o rh in o la ryn g o lo g ist Tin n it u s, co u g h , h e a d a ch e , Au d io g ra m s, CT sca n s o r MRIs, Rh in it is, sin u sit is, Me n iè rie ,
h o a rse n e ss, sn o rin g , ve rt ig o , p o lyso m n o g ra m sle e p a p n e a
d izzin e ss
Ort h o p e d ist Ne ck a n d /o r b a ck p a in Ra d io g ra p h s, MRIs, a n d /o r CT “ Art h rit is”
sca n s
Ne u ro su rg e o n He a d a ch e , n e ck a n d /o r CT sca n s a n d /o r MRIs, e le ct ro - Sp in a l st e n o sis, ra d icu lo -
b a ck p a in , d yse st h e sia s p h ysio lo g ic st u d ie s pathy
Op h t h a lm o lo g ist Dry e ye s, b lu rre d visio n , Sch irm e r t e st , u o re sce in t e st Sicca syn d ro m e
d o u b le visio n
Psych ia t rist Anxiety, depression, insomnia, MMPI, n e u ro co g n it ive e va lu a - An xie t y, d e p re ssio n , a b u se
d e cre a se d m e m o ry, se xu a l t io n , o t h e r p sych o lo g ic t e st s (se xu a l a n d /o r p h ysica l)
a n d /o r p h ysica l a b u se
De n t ist Dry m o u t h Sa liva ry g la n d b io p sy Sicca syn d ro m e

Mo d i e d fro m Ala rcó n GS. Fib ro m ya lg ia : Disp e llin g d ia g n o st ic a n d t re a t m e n t m yt h s. W m n He alt h Pri Care (Ort h Ed ) 1999 ;2 :11 –22 .
CT, co m p u t e rize d t o m o g ra p h y; CTD, co n n e ct ive t issu e d ise a se ; ECG, e le ct ro ca rd io g ra m s; GI, g a st ro in t e st in a l; MMPI, Min n e so t a Mu lt ip h a sic
Pe rso n a lit y In ve n t o ry; MR, m a g n e t ic re so n a n ce ; MRI, MR im a g in g ; UTI, u rin a ry t ra ct in fe ct io n .
a
So m e o f t h e se d ia g n o se s re p re se n t t ru e a sso cia t io n s. Ot h e rs, u n fo rt u n a t e ly, a re g ive n t o p a t ie n t s in a n e ffo rt t o e xp la in t h e ir sym p t o m s, b u t la ck
org a n ic b a sis.
 162 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

NOT TO BE MISSED Exa mina tio n

A ca re fu l h is t o ry (m u lt it u d e o f s o m a t ic co m p la in t s , fa t igu e , p o o r s le e p , a n d
• Sle e p a p n e a
im p a ire d cogn it ion ) a n d a com p le t e p h ys ica l e xa m in a t ion (n ot lim it e d t o t e n -
• Syst e m ic lu p u s d e r p oin t s ) s h ou ld p oin t t o t h e corre ct d ia gn os is . Th e e xa m in a t ion t yp ica lly
e ryt h e m a t o su s d oe s n ot id e n t ify a n y orga n ic m u s cu los ke le t a l ca u s e of p a in a n d t yp ica lly on ly
• Rh e u m a t o id a rt h rit is t e n d e rn e s s in t yp ica l t e n d e r p oin t s a n d h yp e ra lge s ia a t t im e s .
• Po lym ya lg ia rh e u m a t ica
• Pe rip h e ra l n e u ro p a t h y Studie s
• Sp in a l st e n o sis
At t h is t im e, t h e in clu s ion of e it h e r im a gin g bra in s t u d ie s (p a rt icu la rly SPECT)
• De p re ssio n or t h e s t u d y of s e ru m a n d CSF leve ls of n e u rop ep t id e s in a ll p a t ie n t s w it h FM
is n ot re com m e n d e d (Fig. 17.2). As u s e fu l a s t h e s e s t u d ie s h ave be e n a n d con -
t in u e t o be in cla rifyin g t h e n a t u re of t h is m ys t e riou s con d it ion , t h e ir d ia gn os -
t ic p rop e rt ie s (s e n s it ivit y, s p e ci cit y, a n d n ega t ive, p os it ive, a n d ove ra ll p re d ic-
t ive va lu e ) h a ve n o t be e n d e t e r m in e d , a n d t h e ir r is k a n d cos t m a k e t h e m
cu rre n t ly u n ju s t i a ble. Ot h e r a n cilla ry s t u d ie s in clu d in g la bora t ory t e s t s s h ou ld
S
b e o rd e re d o n ly a s clin ica lly in d ica t e d o r t o e xclu d e ot h e r co n d it io n s t h a t
E
C
p re s e n t w it h clin ica l fe a t u re s s im ila r t o FM, s u ch a s s le e p s t u d ie s t o e xclu d e
T
I
O
s le ep a p n e a or t h yroid fu n ct ion t e s t s t o e xclu d e h yp ot h yroid is m .
N
Alt h ou gh t h e con d it ion h a d be e n re cogn ize d for d e ca d e s u n d e r ot h e r n a m e s
3
(nonarticular rheum atism , psychogenic rheum atism , a n d brositis ), it w a s n ot u n t il
S
p
1990 t h a t t h e ACR d e n e d crit e ria for t h e cla s s i ca t ion of t h e s e p a t ie n t s a n d FM
e
c
w a s “of cia lly” born e. Ge n e ra lis t s , h ow eve r, n eve r fe lt q u it e com fort a ble w it h
i
c
t h e e xa m in a t ion of t e n d e r p oin t s (Fig. 17.1 ); t h e ACR h a s re ce n t ly p u blis h e d
R
h
revis e d d ia gn os t ic crit e ria t h a t e n com p a s s a m e a s u re of s ym p t om s eve rit y,
e
u
re e ct in g t h e n on a rt icu la r m a n ife s t a t ion s of FM (2 ). Accord in g t o t h e n ew d ia g-
m
a
t
i
c
D
i
s
e
Genetic Susceptibility: 5HTT & COM genes
a
s
e
s
Emotional
Trauma/Stress Physical Trauma
Infections
Sleep Abnormalities Muscle
Homeostasis/
Microtrauma Structural
Abnormalities
Neuroendocrine
GH Axis
Abnormalities
↑ Dorsal Horn
Peripheral Excitability:
↑ NGF ↑ Neurotransmitters
Nociceptive Central Sensi-
HPT, HPG
Transmission tization (NMDA,
HPA Axes
AMPA & NK1,
NK2 Receptors)
Excitatory Mediators:
Sympathetic NS Glutamate, GABA, Subs. P
Altered rCBF to
Altered Pain Threshold : Brain Structures:
Allodynia and Hyperalgesia Pain Dysregulation
Health Care Seeking
Figure 17.1 Tender point loca tions for
Altered Physical and Psychosocial and
the 1990 America n College of
Mental Function Abnormal Pain Behaviors Cultural Factors
Rheuma tology cla ssi ca tion criteria
for bromya lgia . Ada pted from Wolfe Altered Social Relations
F, Smythe HA, Yunus MB, et a l. The
America n College of Rheuma tology Figure 17.2 Model of a bnorma l pa in perception in bromya lgia . Broken lines a re proposed mecha nisms; solid
1990 criteria for the cla ssi ca tion of lines , de ned mecha nisms. HPT, hypotha la mic–pituita ry–thyroid a xis; HPG, hypotha la mic–pituita ry–gona da l
bromya lgia : Report of the multicent- a xis; HPA, hypotha la mic–pituita ry–a drena l a xis; GH, growth hormone a xis; NGF, nerve growth fa ctor; NS, nerv-
er criteria committee. Arthritis Rheum ous system; NO, nitric oxide; rCBF, regiona l cerebra l blood ow. Modi ed from Weigent DA, Bra dley LA, Bla lock
1990;33:160–172, by permission. JE, et a l. Fibromya lgia ; Dispelling dia gnostic a nd trea tment myths. Am J Med Sci 1998;315:405–412.
 Ch a p te r 17 Fibrom ya lgia 163

Table 17.2 Crit eria and Ascert ainment of Fibromyalgia

Crite ria
A p a t ie n t sa t is e s d ia g n o st ic crit e ria fo r b ro m ya lg ia if t h e fo llo w in g t h re e co n d it io n s a re m e t :
1. Wid e sp re ad Pa in In d e x (WPI) 7 a n d Sym pt o m Se ve rit y (SS) sca le sco re 5 o r WPI 3–6 a nd SS sca le sco re 9
2. Sym p t o m s h a ve b e e n p re se n t a t a sim ila r le ve l fo r a t le a st 3 m o n t h s
3. Th e p a t ie n t d o e s n o t h a ve a d iso rd e r t h a t w o u ld o t h e rw ise e xp la in t h e p a in
Asce rtainme nt
1. If WPI: n o t e t h e n u m b e r o f a re a s in w h ich t h e p a t ie n t h a s h a d p a in o ve r t h e la st w e e k. In h o w m a n y a re a s
h a s t h e p a t ie n t h a d p a in ? Sco re w ill b e b e t w e e n 0 a n d 19
Sh o u ld e r g ird le , le ft Hip (b u t t o ck, t ro ch a n t e r), le ft Ja w, le ft Up p e r b a ck
Sh o u ld e r g ird le , rig h t Hip (b u t t o ck, t ro ch a n t e r), rig h t Ja w, rig h t Lo w e r b a ck
Up p e r a rm , le ft Up p e r le g , le ft Ch e st Ne ck
Up p e r a rm , rig h t Up p e r le g , rig h t Ab d o m e n
Lo w e r a rm , le ft Lo w e r le g , le ft
Lo w e r a rm , rig h t Lo w e r le g , rig h t
2. SS sca le sco re :

s
e
Fa t ig u e

s
a
Wa kin g u n re fre sh e d

e
Co g n it ive sym p t o m s

s
i
D
Fo r t h e e a ch o f t h e t h re e sym p t o m s a b o ve , in d ica t e t h e le ve l o f se ve rit y o ve r t h e p a st w e e k u sin g t h e fo llo w in g

c
i
t
sca le :

a
m
0—n o p ro b le m

u
1—slig h t o r m ild p ro b le m s, g e n e ra lly m ild o r in t e rm it t e n t

e
h
2—m o d e ra t e , co n sid e ra b le p ro b le m s, o ft e n p re se n t a n d /o r a t a m o d e ra t e le ve l

R
3—se ve re : p e rva sive , co n t in u o u s, life -d ist u rb in g p ro b le m s

c
i
c
Co n sid e rin g so m a t ic sym p t o m s in g e n e ra l, in d ica t e w h e t h e r t h e p a t ie n t h a s:

e
p
0—n o sym p t o m s

S
1—fe w sym p t o m s

3
2—a m o d e ra t e n u m b e r o f sym p t o m s

N
O
3—a g re a t d e a l o f sym p t o m s

I
T
C
Th e SS sca le sco re is t h e su m o f t h e se ve rit y o f t h e t h re e sym p t o m s (fa t ig u e , w a kin g u n re fre sh e d , co g n it ive

E
S
sym p t o m s) p lu s t h e e xt e n t (se ve rit y) o f so m a t ic sym p t o m s in g e n e ra l. Th e n a l sco re is b e t w e e n 0 a n d 12

Wit h p e rm issio n fro m re fe re n ce 2.

n os t ic crit e ria , FM is p re s e n t if t h e follow in g con d it ion s a re m e t : (a ) Wid e s p re a d

Pa in In d e x (W PI) 7 a n d s ym p t om s eve rit y (SS) s ca le 5 or W PI be t w e e n 3 a n d
6 a n d SS 9; (b) s ym p t om s h ave be e n p re s e n t for a t le a s t 3 m on t h s ; a n d (c) t h e
p a t ie n t d oe s n ot h a ve ot h e r d is ord e r t o e xp la in h is or h e r s ym p t om s . Wid e -
s p re a d Pa in In d e x is d e n e d by p oin t s give n t o d iffe re n t bod y region s (ra n ge : 0
t o 19) a n d SS com p ris e s fou r d om a in s : fa t igu e, u n re fre s h e d s le e p , cogn it ive
im p a irm e n t , a n d s om a t ic com p la in t s —e a ch on e m e a s u re d in a s ca le from 0 t o
3 for a t ot a l of 12 p os s ible p oin t s (Ta ble 17.2 ). Th e s e crit e ria corre ct ly cla s s i e d
be t w e e n 89% a n d 95% of p a t ie n t s w it h FM. Eit h e r t h e 1990 or 2010 crit e rion ca n
be u s e d in t h e clin ica l a n d re s e a rch s e t t in gs .

Tre a tme nt
Give n t h a t w e a re ju s t be gin n in g t o u n d e rs t a n d t h is d is ord e r, it s h ou ld n o t
com e a s a s u rp ris e t h a t w e h ave lim it e d e ffe ct ive t h e ra p ie s t o m a n a ge t h e s e
p a t ie n t s . Prim a ry ca re p h ys icia n s h a ve t h e t re m e n d ou s re s p on s ibilit y of s t e e r-
in g p a t ie n t s a w a y from u n p rove d (a n d oft e n ris ky) t re a t m e n t s . Pa t ie n t s w it h
FM n e e d t o rs t be lieve t h a t w e, t h e ir h e a lt h ca re p rovid e rs , a ckn ow le d ge t h a t
 164 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

t h e ir p a in is re a l a n d ca u s e s s u ffe rin g (1 ). Se co n d , re a lis t ic goa ls s h ou ld be

e s t a blis h e d from t h e ou t s e t . Th ird , it s h ou ld be e m p h a s ize d t h a t p h a rm a co-
logic com p ou n d s con s t it u t e on ly on e e le m e n t of t h e ove ra ll t re a t m e n t p la n .
Ot h e r e le m e n t s in clu d e a ba la n ce be t w e e n e xe rcis e a n d re s t ; a d ie t a im e d a t
a ch ievin g or m a in t a in in g a n id e a l bod y w e igh t ; avoid a n ce of a lcoh ol, ca ffe in e,
n icot in e, a n d re cre a t ion a l d ru gs ; a n d m od i ca t ion of a bn orm a l s le ep be h a viors
or h a bit s (3 ).
Pa t ie n t s w it h FM a r e s o o ft e n ove r w e igh t a n d d e co n d it io n e d t h a t t h e y
h a ve t o s t a r t a n e x e rcis e p r o gra m ve r y gra d u a lly. Aq u a t ic e x e rcis e s ra t h e r
t h a n la n d e x e rcis e s a re b e t t e r t o le ra t e d ; u n fo r t u n a t e ly, ye a r-ro u n d a q u a t ic
p rogra m s e xis t o n ly in u r b a n a re a s a n d a re n o t a cce s s ible t o a ll p a t ie n t s . If
t h e s e fa cilit ie s e x is t , h ow eve r, p a t ie n t s s h o u ld b e s t ro n gly a d vis e d t o e n t e r
a q u a t ic e x e rcis e p rogra m s u n d e r p ro p e r s u p e r vis io n . Low -im p a ct a e ro b ics is
a n a lt e r n a t ive fo r p a t ie n t s la ck in g a q u a t ic fa cilit ie s . Re ce n t ly, fa vo ra ble re s u lt s
in t e r m s o f t h e Fib ro m ya lgia Im p a ct Qu e s t io n n a ire a n d t h e SF-36 h a ve b e e n
re p o r t e d w it h cla s s ic Yo u n g-s t yle Ta i Ch i in a s m a ll 12-w e e k s in gle -blin d e d
s t u d y; a lt h o u gh a la rge r a n d lo n ge r co n r m a t o ry s t u d y is n e e d e d , t h e s e d a t a
a re ce r t a in ly re leva n t (4 ).
S
E
Un fort u n a t e ly, m a n y p a t ie n t s w it h FM p re s e n t t o rh e u m a t ologis t s w it h a
C
T
(s om e t im e s ve ry la rge ) s a c or box, w h ich in clu d e s cu rre n t a n d p a s t m e d ica -
I
O
t ion s (in a d d it ion t o a bin d e r w it h m e d ica l re cord s a n d a s t a ck of ra d iogra p h s
N
a n d im a gin g s t u d ie s ). On ce p a t ie n t s h a ve re a ch e d t h is leve l of p olyp h a rm a cy,
3
S
it is e x t re m e ly d if cu lt t o s im p lify t h e ir t h e ra p e u t ic re gim e n . Mo re ove r, t h e
p
e
ra t io n a le fo r t h e u s e o f s o m e co m p o u n d s is virt u a lly la ck in g. Th a t is t h e ca s e,
c
i
fo r e x a m p le , fo r n o n s t e ro id a l a n t i-in a m m a t o r y d r u gs (NSAIDs ) u s u a lly
c
R
d e t a ile d t o ge n e ra lis t s a n d s p e cia lis t s a like a s t h e p a n a ce a for “a rt h rit is ” a n d
h
e
p re s cribe d q u it e oft e n t o p a t ie n t s w it h FM (5 ). Ot h e r t h a n t h e ir p os s ible ce n t ra l
u
m
e ffe ct (p u re ly a n a lge s ic), t h e re is n o re a s on t o u s e t h e m . Na rcot ic a n a lge s ics
a
(o f d iffe re n t s t re n gt h a n d q u a lit y) a re , u n fo r t u n a t e ly, a ls o co m m o n ly u s e d ,
t
i
c
eve n in ch ild re n a n d yo u n g a d u lt s . It is m y e x p e rie n ce t h a t o n ce p a t ie n t s w it h
D
i
s
FM s t a rt t h is t yp e of a n a lge s ic, t h ey ra re ly a re a ble t o d is con t in u e it . Mu s cle
e
a
re la x a n t s a re a ls o co m m o n ly u s e d fo r a p ro lo n ge d t im e . No n s t e ro id a l a n t i-
s
e
in a m m a t ory d ru gs , n a rcot ic a n a lge s ics , a n d m u s cle re la xa n t s , if u s e d , n e e d
s
t o be p re s cribe d ju d iciou s ly a n d for lim it e d t im e p e riod s (e.g., d u rin g e xa ce r-
ba t ion of ba ckgrou n d p a in or a ft e r t ra u m a in p a t ie n t s w it h join t h yp e rm obil-
it y). Th is s h o u ld b e d is cu s s e d w it h t h e p a t ie n t fro m t h e o u t s e t (1 ). Pa t ie n t s
n e e d t o u n d e rs t a n d t h a t FM p e r s e d o e s n o t p ro d u ce p h ys ica l d e fo rm it ie s a n d
t h a t d e s p it e p a in , a re la t ive ly n orm a l life —in clu d in g w ork, fa m ily, a n d re cre a -
t io n a l a ct ivit ie s —is p o s s ible . Livin g w it h p a in ca n , h ow eve r, e x e r t a t o ll o n
p a t ie n t s a n d fa m ilie s w it h s t u d ie s s u gge s t in g t h a t FM is a ris k fa ct or for s e lf-
in ict e d d e a t h (6, 7 ).
Ph a r m a cologic co m p o u n d s fou n d t o be be n e cia l in p a t ie n t s w it h FM
in clu d e t h e t ricyclic a n t id ep re s s a n t s (TCAs ) a s w e ll a s t h e s e le ct ive s e rot on in
re u p t a ke in h ibit ors (SSRIs ), in d ep e n d e n t of w h e t h e r p a t ie n t s a re d ep re s s e d (1 ).
Am on g t h e TCAs , a m it rip t ylin e is t h e m os t com m on ly u s e d (1 ). Th e s t a rt in g
d os e va rie s be t w e e n 10 a n d 25 m g/d ay a n d ca n be e s ca la t e d t o 50 t o 75 m g/d ay.
In t e rm s of t h e SSRIs , t h e m os t com m on ly u s e d is u oxe t in e ; t h e m os t fre q u e n t
d os e is 20 m g/d ay, bu t h igh e r d os e s h ave be e n u s e d . Ot h e r SSRIs in clu d in g cit a -
lop ra m , s e rt ra lin e h yd roch lorid e, a n d h a ve a ls o be e n u s e d . Dou ble re u p t a ke
in h ibit ors s u ch a s m iln a cip ra n ve n la fa xin e a n d d u loxe t in e h a ve a ls o be e n
s h ow n t o be of be n e t in p a t ie n t s w it h FM (8 ). Fin a lly, a m e t a -a n a lys is of t h e
e ffe ct ive n e s s of a n t id ep re s s a n t s in FM for t h e ou t com e of p a in h a s s h ow n t h e m
t o be be n e cia l (9 ). Th e n ew e s t “kid on t h e block” is p rega ba lin (10 ). In t h e la n d -
m a rk 2005 s t u d y of Crofford e t a l., 529 p a t ie n t s w it h FM w e re ra n d om ize d t o
e it h e r 150, 300, 450 m g or p la ce bo, w it h t h e 450 m g grou p d e m on s t ra t in g
im p rove m e n t in t e rm s of p a in , fa t igu e, a n d s le ep . A n u m be r of ot h e r p rega ba lin
s t u d ie s h ave n ow be e n p e rform e d w it h on e of t h e m be in g of lon ge r d u ra t ion

Figure 17.3 Single-photon-emission computerized tomogra phy of the
bra in in a norma l individua l a nd one with bromya lgia . There is
decrea sed regiona l cerebra l ow to the tha la mus a nd ca uda te nuclei in
the pa tient with bromya lgia . Modi ed from Ala rcón GS. Fibromya lgia :
Dispelling dia gnostic a nd trea tment myths. Wmn Hea lth Pri Ca re (Orth Ed) ra t io n a lit y fo r p e r for m in g p e r io d ic s oft -t is s u e in je c-
1999;2:11–22.
WHEN TO REFER
• Wh e n t h e d ia g n o sis is in
d o u b t a n d a m o re se rio u s
rh e u m a t ic d iso rd e r is
b e in g co n sid e re d .
• Wh e n t h e p a t ie n t w o u ld
like t o h a ve a se co n d
o p in io n t o co n rm
d ia g n o sis.
Ch a p te r 17 Fibrom ya lgia 165
(11 ); ove ra ll, t h e s e s t u d ie s s u p p ort t h e origin a l rep ort
of Crofford e t a l. An xiolyt ics a n d ot h e r p s ych op h a rm a -
ce u t ica l d ru gs s h o u ld b e re s t rict e d t o p a t ie n t s w it h
cle a r-cu t in d ica t io n s fo r t h e ir u s e (con com it a n t p s y-
ch op a t h ology).
Th e ro le of lin im e n t s a n d o t h e r t o p ica l p re p a ra -
t ion s (s u bs t a n ce P a n t a gon is t s , s u ch a s ca p s a icin ) in
t h e t re a t m e n t of FM is p roba bly lim it e d t o t h os e cir-
cu m s t a n ce s in w h ich t h e re is d e n it e a d d e d lo ca l
p a t h ology t o a region or a re a of t h e m u s cu los ke le t a l
s ys t e m (e.g., a s h ou ld e r, e lbow, t roch a n t e ric or a n s e r-
in e b u r s a ). In t h e p a s t , r h e u m a t o lo gis t s fre q u e n t ly
in je ct e d s eve ra l t e n d e r p o in t s w it h co r t ico s t e ro id s
a n d a n e s t h e t ics eve ry s o oft e n . Som e p a t ie n t s in d e e d
re p ort e d t h e s e in je ct ion s t o be be n e cia l. Th is e ffe ct
p roba bly re la t e s t o t h e u s e of s t e roid s a n d t h e ir s ys -
t e m ic a bs orp t ion , ra t h e r t h a n t o t h e ir loca l e ffe ct . Th e
s
e
t io n s in a ll p a t ie n t s w it h FM is n o n e x is t e n t , o t h e r
s
a
t h a n p e r h a p s “n e e d lin g” t h e s e p a t ie n t s in m u ch t h e
e
s
i
s a m e w a y a s is d on e w it h a cu p u n ct u re , n ow a re cogn iz e d a lt e rn a t ive t re a t -
D
c
m e n t fo r FM (1 ). Th e ro le o f s o ft -t is s u e m a s s a ge s , h yp n o t h e ra p y, re la x a t io n ,
i
t
a
a n d s p in a l m a n ip u la t ion s for t h e t re a t m e n t of FM is u n d e t e rm in e d for n ow.
m
Cla im s h a ve a p p e a re d on t h e In t e rn e t of t h e s u cce s s fu l t re a t m e n t of FM
u
e
w it h d e com p re s s ive s u rge ry of t h e cra n ioce rvica l ju n ct ion (1 ). Th is s u rge ry is
h
R
b a s e d on t h e re p o rt e d p os s ible a s s o cia t ion of FM w it h Ch ia ri m a lfo rm a t io n
c
i
(p rot ru s ion of t h e t on s ils be low t h e leve l of t h e fora m e n m a gn u m ). Alt h ou gh w e
c
e
re cogn ize t h a t p a t ie n t s w it h ce rvica l s p in a l s t e n os is m ay e xh ibit s om e FM-like
p
S
m a n ife s t a t ion s , s e a rch in g fo r t h is a s s o cia t io n s h ou ld be d on e on ly if clin ica l
3
m a n ife s t a t ion s a re in d ica t ive of ca n a l s t e n os is a n d com p re s s ive m ye lop a t h y,
N
O
bu t n ot ot h e rw is e (1 ). Un fort u n a t e ly, t h e In t e rn e t h a s favore d t h e d is s e m in a t ion
I
T
C
of u n lt e re d in form a t ion ca p a ble of d ire ct ly re a ch in g m a n y m ore p a t ie n t s t h a n
E
S
w it h m e t h od s u s e d in t h e p a s t . (Million s of We b s it e s a re fou n d .) PCPs s h ou ld
be p rop e rly in form e d s o t h a t p a t ie n t s re ce ive a d e q u a t e cou n s e lin g a n d u n n e c-
e s s a ry a n d ris ky s u rgica l p roce d u re s a re avoid e d .
Clinica l Co urse
Alt h o u gh p a t ie n t s w it h FM d o n o t d eve lo p o bvio u s p h ys ica l d e fo r m it ie s o r
im p a irm e n t s , t h is d is ord e r ca n a ffe ct s eve ra l d om a in s of t h e ir live s (p a in , ia t ro-
ge n e s is , e m p loym e n t , a n d n a n cia l a n d fa m ily s t a bilit y) (1, 6, 7 ). Pa t ie n t s w h o
re m a in e m p loye d , p h ys ica lly a ct ive, a n d t rim ; t a ke few m e d ica t ion s ; a n d h ave
a d e q u a t e cop in g s kills a n d a s u p p ort ive fa m ily t e n d t o d o be t t e r t h a n t h os e
w h o a re p h ys ica lly in a ct ive, u n e m p loye d , ove rw e igh t , a n d a lre a d y t a kin g m a n y
m e d ica t ion s .
Co nclusio ns
Alth ou gh w e d o n ot com p letely u n d ersta n d a ll th e m ech a n ism s in volved in th e
m u s cu los ke let a l p a in p a t ien t s w it h FM h ave, w e h ave m a d e s ign i ca n t st rid e s
tow a rd u n d ersta n d in g th em . Draw in g from ou r stu d ies a n d th ose of oth er in ves-
tiga tors, w e h ave p u t togeth er a testa ble p a in m od el. Th e con tribu tion s of p erip h -
era l a n d cen tra l fa ctors to th e p a th ogen esis of p a in in FM a re sh ow n in Figu re 17.3 ,
w h ich is a n itera tion of th e m od el ou r grou p h a s p u blish ed before (1 ). Th is m od el
sh ou ld be m od i ed a s n ew evid e n ce e m erge s from re s ea rch con d u ct e d w orld -
w id e. Figu re 17.4 su m m a rizes th e m a in p oin ts d iscu ssed in th is ch a p ter.
 166 Se ctio n 3 Sp e ci c Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

*Fibromyalgia is not a psychiatric disorder. The misconception that fibromyalgia may be an affective
disorder arose from the fact that patients seen in tertiary care centers (patients included in most clinical
trials and studies) often have a concomitant psychiatric illness. However, they are not typical of all
persons with fibromyalgia.

*Criteria for the classification of fibromyalgia (2000) patients include widespread and persistent
musculoskeletal pain and the presence of soft tissue tender points in at least 11 of 18 anatomic sites
called “tender points” (See Figure 20.1). However, these criteria were developed for research and not so
much for clinical practice. In fact, a new set of criteria have been proposed (2010) which do not include
these tender points but, in addition to widespread pain, include a symptom severity scale (See Table
20.1).
*The following findings help support the diagnosis of fibromyalgia (and some of them are considered in
the symptom severity scale of the 2010 preliminary diagnostic criteria, as noted in Table 20.1): fatigue,
difficulty sleeping, arthralgias, headache, chest, abdominal, pelvic and/or perineal pain, cognitive
impairment, weakness, and dysesthesias.
*Why patients with fibromyalgia experience chronic pain remains unknown, although evidence points
out to aberrations in CNS processing of stimuli. Abnormalities of the endocrine system, sleep
disturbances, altered cerebral blood flow to the thalamus and caudate nucleus, bilateral activation of
the somatosensory cortices on painful stimulation, increase resting brain activity within multiple brain
networks and altered neuropeptide serum and CSF levels are seen in these patients (See Fig. 17.3 for
a model of fibromyalgia etiopathogenesis).
*Although the etiology of fibromyalgia remains unknown, several triggers have been identified: bacterial
S
E
(i.e., Borrelia  Burgdorferi) or viral (i.e., Parvovirus) infections, physical and/or emotional trauma, and
C
sleep deprivation. However, in some patients the onset of fibromyalgia is insidious, and no triggers can
T
I
be identified. A genetic predisposition is supported by studies in twins and siblings.
O
N
*Managing patients with fibromyalgia is challenging. A combination of pharmacological and non-
3
pharmacological options is recommended. Non-pharmacological options include cognitive-behavioral
S
therapy, exercise (combined with periods of rest). Newer pharmacological options including the double
p
e
reuptake inhibitors and pregabalin have been shown to be beneficial. Antidepressants, in general, have
c
shown to be beneficial as well.
i
c
*NSAIDs and glucocorticoids are not indicated for the treatment of patients with fibromyalgia except
R
under specific circumstances (localized area of pain of clear inflammatory nature). However, NSAIDs can
h
e
be used sporadically for their analgesic effects. Narcotic analgesics and other psychotropic drugs should
u
m
be avoided if at all possible.
a
t
i
c
Figure 17.4 Importa nt pra ctica l issues in bromya lgia . Modi ed from Ala rcón GS. Wmn Hea lth Pri Ca re (Orth
D
Ed) 1999;2:11–22.
i
s
e
a
s
e
ICD9
s
729.1 Fibro myalg ia

Re fe re nce s
1. Ala rcon G. Fibrom ya lgia . In : Koop m a n W J, Bou lw a re DW, He u d e be rt GR, e d s . Lip p in cot t Willia m s a n d
Wilkin s ; 2003 :226 –235 .
2. Wolfe F, Cla u w DJ, Fit zch a rle s MA, e t a l . Th e Am e rica n College of Rh e u m a t ology p re lim in a ry d ia gn os t ic
crit e ria fo r brom ya lgia a n d m e a s u re m e n t of s ym p t om s eve rit y. A rthritis Care Res 2010 ;62 :600 –610 .
3. Be rn a rdy K, Fü be r N , Kölln e r V, e t a l. Ef ca cy of cogn it ive -be h aviora l t h e ra p ie s in brom ya lgia s yn d rom e —
a s ys t e m a t ic review a n d m e t a -a n a lys is of ra n d om ize d con t rolle d t ria ls . J Rheum atol 2010 ;37 :1991 –2005 .
4. Wa n g C , Sch m id CH , Ro n e s R, e t a l . A ra n d o m ize d t r ia l o f t a i ch i fo r b ro m ya lgia . N Engl J Med
2010 ;363 (8 ):743 –754 .
5. Be n n e t t RM , Jon e s J, Tu rk DC, e t a l . An in t e rn e t s u rvey of 2,596 p e op le w it h brom ya lgia . BMC Muscu-
loskelet Disord 2007 ;8 :27 .
6. Wolfe F, Ha s s e t t AL, Wa lit t B, e t a l . Mort a lit y in brom ya lgia : An 8,186 p a t ie n t s t u dy ove r 35 ye a rs . A rthri-
tis Care Res 2011 ;63 :94 –101 .
7. Dreye r L, Ke n d a ll S, Da n n e s kiold -Sa m s ø e B, e t a l . Mort a lit y in a coh ort of Da n is h p a t ie n t s w it h brom y-
a lgia : In cre a s e d fre q u e n cy of s u icid e . A rthritis Rheum 2010 ;62 :3101 –3108 .
8. Gold e n be rg DL, Cla u w DJ, Pa lm e r RH , e t a l . Du ra bilit y o f t h e ra p e u t ic re s p on s e t o m iln a cip ra n t re a t m e n t
fo r bro m ya lgia . Re s u lt s o f a ra n d om ize d , d o u ble -blin d , m o n o t h e ra p y 6-m on t h e xt e n s io n s t u d y. Pain
Med 2010 ;11 :180 –194.
9. Hä u s e r W, Be rn a rd y K, Uçeyle r N , e t a l . Tre a t m e n t of brom ya lgia s yn d rom e w it h a n t id ep re s s a n t s : A
m e t a -a n a lys is . JA MA 2009 ;301 :198 –209 .
10. Crofford LJ, Row bot h a m MC, Me a s e PJ, e t a l . Prega ba lin for t h e t re a t m e n t of brom ya lgia s yn d rom e :
Re s u lt s of a ra n d om ize d , d ou ble -blin d , p la ce bo-con t rolle d t ria l . A rthritis Rheum 2005 ;52 :1264 –1273 .
11. Cro fford LJ, Me a s e PJ, Sim p s on SL, e t a l . Fibrom ya lgia re la p s e eva lu a t ion a n d e f ca cy for d u ra bilit y of
m e a n in gfu l re lie f (FREEDOM): A 6-m o n t h , d ou ble -blin d , p la ce bo -con t ro lle d t ria l w it h p rega b a lin . Pain
2008 ;136 :419 –431 .
CHAPTER
18 Pregna ncy a nd
Rheuma tic Disea ses
Michael Lockshin

A 39-year-old w om an w ith long-stand-

Clinica l Pre se nta tio n

s
Th a t t h e p a t ie n t h a s n o t be e n in

e
ing rheum atoid arthritis, w hich she

s
m e d ica l co n t a ct d e s p it e o n go in g

a
e
believes is now quiescent, consults you

s
d is e a s e is a m a t t e r of con ce rn . He r

i
D
because she is planning a pregnancy. ch oice m ay re e ct m is u n d e rs t a n d -

c
i
t
She has not been under regular m edical in g a bou t h e r illn e s s , con ict s w it h

a
m
h e r p h ys icia n s , s o cia l o r n a n cia l

u
care, but instead has taken ibuprofen

e
is s u e s , d e n ia l, o r o t h e r is s u e s .

h
or naproxen on an as-needed basis for

R
W h a t eve r t h e re a s o n , h e r e a r lie r

c
joint pain. A prior pregnancy 3 years ch oice t o avoid m e d ica l ca re ra is e s

i
c
e
earlier w as successfully delivered at a gs fo r m a n a ge m e n t of a fu t u re

p
S
p regn a n cy.
term . She com es now at the insistence of her colleague. She asks for

3
N
your advice regarding risks to her and her potential child, particular-

O
I
EXAMINATION

T
ly those im parted by treatm ent. You point out that anti-in am m ato-

C
E
ry m edications interfere w ith cilial m otion that transports the ovum Im m e d ia t e t h in gs t o a s s e s s in clu d e

S
ca re fu l join t e xa m in a t ion , focu s in g
through the Fallopian tube and, thus, m odestly inhibits fertility.
e s p e c ia lly o n jo in t in s t a b ilit y,
Yo u r e valu at io n sh o w s m o d e rat e ly act ive syn o vit is in h e r w rist s be ca u s e of p ot e n t ia l w ors e n in g a s
(w it h sig n s o f e arly carp al t u n n e l syn d ro m e ), e lb o w s, an d k n e e s. p regn a n cy-a s s ocia t e d re la xin loos -
He r lab o rat o ry st u d ie s sh o w st ro n g p o sit ive rh e u m at o id f act o r, e n s liga m e n t s in la t e p re gn a n cy.
Ce r v ica l s p in e s u b lu x a t io n a n d
an t icyclic cit ru llin at e d p e p t id e , an d an t i-Sjo g re n ’s syn d ro m e A
C1 t o C2 in s t a b ilit y a re e s p e cia lly
(SSA ), also k n o w n as an t i-Ro . A n t i-Sjo g re n ’s syn d ro m e B (SSB) an t i- im p o r t a n t b e ca u s e o f p o t e n t ia l
b o d ie s, also k n o w n as an t i-La, an t icard io lip in , an t i- 2 -g lyco p ro t e in cord in ju ry. It m ay be n e ce s s a ry t o
I, an d lu p u s an t ico ag u lan t t e st s are n e g at ive . Lat e ral ce rvical sp in e p rovid e t h e p a t ie n t w it h a rigid col-
la r d u rin g la t e p regn a n cy a n d d u r-
x-ray in e xio n an d e xt e n sio n sh o w s 11-m m d isp lace m e n t o f t h e
in g d e live ry, w h e n in t u ba t ion is a
o d o n t o id p ro ce ss f ro m t h e an t e rio r arch o f t h e at las in e xio n . p os s ib ilit y. Liga m e n t lo o s e n in g a t
t h e h ip a n d kn e e m a y ca u s e ga it
p roble m s a s p regn a n cy p rogre s s e s .
Ca rp a l t u n n e l s ym p t om s t yp ica lly w ors e n in la t e p regn a n cy.

STUDIES AND TREATMENT

In fa n t s of m ot h e rs w it h a n t i-SSA a n d a n t i-SSB a n t ibod ie s a re a t ris k for n e on a -
t a l lu p u s (ra s h , a bou t 20%; con ge n it a l h e a rt block, a bou t 3%) (1 ). Pregn a n cie s
ch a ra ct e rize d by t h e s e a u t oa n t ibod ie s re q u ire s p e cia l m on it orin g of fe t a l ca rd ia c
s t a t u s (by fe t a l e ch o ca rd iogra m lo o k in g fo r ve n t ricu la r co n t ra ct io n s t re n gt h ,
p erica rd itis, a n d a tria l–ven tricu la r con d u ction d elay) betw een w eeks 15 a n d 26 (2 ).
167
168 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t
CLINICAL POINTS
• An t i-in a m m a t o ry a g e n t s
in h ib it fe rt ilit y.
• Lig a m e n t lo o se n in g m a y
t e m p o ra rily in cre a se d isa -
b ilit y d u rin g p re g n a n cy; in
t h e ce rvica l sp in e , it ca n
t h re a t e n co rd in ju ry.
• All p re g n a n t p a t ie n t s w it h
rh e u m a t ic d ise a se sh o u ld
b e e va lu a t e d fo r a n t i-SSA,
a n t i-SSB, a n d a n t ip h o sp h o l-
ip id a n t ib o d ie s.
• Pre d n iso n e is sa fe t o u se in
p re g n a n cy; TNF-α in h ib it o rs
a re p ro b a b ly sa fe ; m e t h -
o t re xa t e , le u n o m id e , m yc-
o p h e n o la t e , a n d o t h e r
m e d ica t io n s a re co n t ra in d i-
ca t e d .
• De live ry ro o m st a ff m u st
b e p re sch o o le d a b o u t t h e
p a t ie n t ’s lim it a t io n s.
PATIENT ASSESSMENT
• It is im p o rt a n t t o t h e
p sych o so cia l st a t e o f a
p re g n a n t p a t ie n t w it h
rh e u m a t ic d ise a se .
• Pa t ie n t s w it h a rt h rit is
sh o u ld b e w a rn e d o f
in cre a se d jo in t in st a b ilit y;
t h o se w it h n e ck d ise a se
may need to wear a
h a rd co lla r.
• Pa t ie n t s w it h a n t i-SSA a n d
a n t i-SSB a n t ib o d ie s sh o u ld
u n d e rg o fe t a l ca rd ia c
m o n it o rin g , a n d t h e
ch ild ’s n e o n a t o lo g ist s a n d
p e d ia t ricia n s sh o u ld b e
a le rt e d t o t h e p o ssib ilit y
o f n e o n a t a l lu p u s ra sh .
• Pa t ie n t s w it h h ig h -t it e r
Ig G a n t ica rd io lip in o r
lu p u s a n t ico a g u la n t m a y
b e n e t fro m h e p a rin
t h e ra p y.
How eve r, e ffe ct ive t re a t m e n t for in u t e ro h e a rt block is n ot a va ila ble (3 ); e a rly
d e live ry m a y be re q u ire d . Ne on a t a l lu p u s ra s h , if it occu rs , w ill a p p e a r a ft e r
d e live ry. Hyd roxych loroq u in e m ay be p rot e ct ive (4 ).
Pa t ie n t s w it h a n y rh e u m a t ic illn e s s m a y h ave a n t ip h os p h olip id a n t ibod ie s .
Low -t it e r a n t ip h os p h olip id a n t ibod ie s d o n ot a p p e a r t o im p a rt ris k a n d n e e d
n ot be t re a t e d ; lu p u s a n t icoa gu la n t a n d p os s ibly h igh -t it e r IgG a n t ica rd iolip in
m a y le a d t o e a rly, s eve re p re e cla m p s ia , p re m a t u re d e live ry, a n d fe t a l grow t h
re s t rict ion or d e a t h (5 ). For t h is p a t ie n t , t h e n ega t ive t e s t s a n d t h e p rior s u c-
ce s s fu l p re gn a n cy a re re a s s u r in g t h a t s h e is n o t a t ris k . Evid e n ce is u n cle a r
w h e t h e r p regn a n t p a t ie n t s w ith lupus anticoagulant w h o h a ve not h a d a p rior
t h rom bos is or fe t a l los s s h ou ld be p rop h yla ct ica lly t re a t e d w it h h ep a rin (p ro-
p h yla ct ic d os e s , u s u a lly 1 m g/kg e n oxa p a rin p e r d ay or it s e q u iva le n t ). Evid e n ce
is w e a k t h a t it is n e ce s s a ry t o t re a t p a t ie n t s w h o h ave a n t ica rd iolip in a n t ibod y
w it h ou t lu p u s a n t icoa gu la n t , bu t n ot p rior t h rom bos is or fe t a l los s . Pa t ie n t s
w it h p rior fe t a l los s e s a n d h igh -t it e r a n t ica rd iolip in or lu p u s a n t icoa gu la n t bu t
n o p rior t h ro m bo s e s s h ou ld re ce ive p rop h yla ct ic d os e t re a t m e n t ; t h o s e w it h
p rior t h rom bos e s s h ou ld re ce ive t h e ra p e u t ic d os e t re a t m e n t (1 m g/kg e n oxa -
p a rin eve ry 12 h ou rs or it s e q u iva le n t ).
CLINICAL COURSE
Yo u r p a t ie n t a ch ieve s p re gn a n cy t h ro u gh ova r ia n s t im u la t io n , ovu m re t r ieva l,
in vit ro fe r t iliz a t io n , a n d e m b ryo im p la n t a t io n . Th is p ro ce s s in vo lve s d a ily
in je ct io n s o f fo llicle - s t im u la t in g h o r m o n e fo llow e d by h u m a n ch o r io n ic
go n a d o t r o p in , la p a r o s co p ic r e m ova l o f m a t u r e ova , fe r t iliz a t io n in vit r o,
e x a m in a t io n o f t h e gr ow in g e m b r yo fo r ch r o m o s o m a l a b n o r m a lit ie s , a n d
im p la n t a t io n in t o t h e u t e r in e ca vit y. Du r in g t h is p ro ce d u re , t h e p a t ie n t is a t
r is k fo r ova r ia n h yp e r s t im u la t io n s yn d ro m e , in w h ich m u lt ip le ova m a t u re
s im u lt a n e o u s ly. In m ild ca s e s , t h is re s u lt s in a b d o m in a l p a in ; in s eve re ca s e s ,
u id re t e n t io n , cyt o k in e s t o r m , a n d re n a l fa ilu re . Ot h e r t h a n h yp e r s t im u la -
t io n s yn d ro m e , t h e r is k s o f a s s is t e d re p ro d u ct ive t e ch n iq u e s a re n o t u n d u ly
h igh fo r p a t ie n t s w it h r h e u m a t ic d is e a s e , eve n t h o s e w it h a n t ip h o s p h o lip id
a n t ib o d ie s (6 ).
Du r in g h e r p r e gn a n cy, b e ca u s e s h e h a s a n t i-SSA a n t ib o d ie s , h e r fe t u s
s h o u ld b e m o n it o re d , by fe t a l e ch o ca rd iogra p h y, b e t w e e n w e e k s 15 a n d 26 fo r
s ign s o f t h e ca rd it is a s s o cia t e d w it h n e o n a t a l lu p u s . If s u ch o ccu r s , t re a t m e n t
o f t h e fe t u s w it h d e x a m e t h a s o n e o r b e t a m e t h a s o n e o r in t ra ve n o u s im m u -
n oglo bu lin m a y be a t t e m p t e d , bu t s u cce s s ra t e s a re low (3 ); d e live ry m a y b e
in d ica t e d t o p reve n t p rogre s s io n . Alt h o u gh n o t re leva n t fo r t h is p a t ie n t , p re g-
n a n cie s of w om e n w it h a n t ip h os p h olip id a n t ib od ie s m u s t a ls o b e m o n it o re d
fo r fe t a l grow t h ra t e , p la ce n t a l s iz e a n d h e a lt h , a n d a m n io t ic u id vo lu m e .
Wo m e n a t h igh e s t r is k a re t h o s e w it h lu p u s a n t ico a gu la n t , ve ry h igh t it e r
a n t ica rd iolip in a n t ib od y, or s ys t e m ic lu p u s e ryt h e m a t o s u s . Pa t ie n t s w it h low -
t it e r a n t ib o d y w h o la ck lu p u s a n t ico a gu la n t a re lik e ly n o t a t r is k , n o r a re
t h os e w it h is ola t e d ot h e r a u t o a n t ibo d ie s , s u ch a s a n t ibo d y t o β2 -glycop ro t e in
I o r a n t ip h o s p h a t id yls e r in e . Pa t ie n t s w it h h igh -t it e r a n t ip h o s p h o lip id a n t i-
bo d ie s w h o h a ve h a d p r io r p re gn a n cy los s s h o u ld b e p ro p h yla ct ica lly t re a t e d
w it h h e p a r in , p rop h yla ct ic d o s e s , for e xa m p le , 1 m g/ kg e n oxa p a rin p lu s 81 m g
a s p ir in d a ily, fro m co n ce p t io n t o d e live ry; p a t ie n t s w it h p r io r t h ro m b o s is
s h o u ld r e ce ive t h e ra p e u t ic d o s e s , fo r e x a m p le , 1 m g/ k g e n o x a p a r in eve ry
12 h o u r s . Th e n e e d t o t re a t p a t ie n t s w it h h igh -t it e r a n t ica rd io lip in o r lu p u s
a n t ico a gu la n t w it h n o p r io r p re gn a n cy lo s s e s is n o t e s t a blis h e d ; b e ca u s e
s o m e p h ys icia n s m a y a d vis e t re a t m e n t a n d o t h e r s n o t , n ego t ia t io n w it h t h e
p a t ie n t , h e r obs t e t ricia n , a n d o t h e r co n ce r n e d fa m ily m e m be rs is n e ce s s a ry.
So m e t im e s a cce d in g t o t re a t m e n t re q u e s t s o f o ld e r o r in fe r t ile w om e n w h o
m a y n o t m e e t t re a t m e n t cr it e r ia , b u t w h o h a ve lim it e d o p p o rt u n it y fo r fu t u re
p re gn a n cie s , is re q u ire d .

NOT TO BE MISSED
• All p re g n a n t p a t ie n t s
w it h rh e u m a t ic d ise a se
sh o u ld b e t e st e d fo r
a n t ip h o sp h o lip id a n d
a n t i-SSA a n d a n t i-SSB
a n t ib o d ie s.
• All p re g n a n t p a t ie n t s
w it h rh e u m a t ic d ise a se
sh o u ld u n d e rg o a
ca re fu l m u scu lo ske le t a l
e xa m in a t io n t o id e n t ify
p o t e n t ia l p ro b le m s
b e ca u se o f lig a m e n t
lo o se n in g a n d d e live ry
ro o m co m p lica t io n s.
• All p re g n a n t p a t ie n t s
w it h rh e u m a t ic d ise a se
sh o u ld b e fo llo w e d b y
a n e xp e rie n ce d t e a m o f
h ig h -risk o b st e t ricia n s a n d
t h e p h ysicia n t re a t in g t h e
rh e u m a t ic d ise a se .
• Po st p a rt u m co m p lica t io n s
sh o u ld b e a n t icip a t e d ,
p a rt icu la rly t h o se
co n ce rn in g t h e m o t h e r’s
a b ilit y t o ca re fo r h e r
ch ild .
WHEN TO REFER
• All p a t ie n t s w it h rh e u m a t -
ic d ise a se o u g h t t o co n su lt
a n e xp e rt a t le a st o n ce fo r
e va lu a t io n o f risk fa ct o rs
t o t h e m o t h e r o r ch ild .
• Pa t ie n t s w it h se ro lo g ic
m a rke rs o f risk (a n t ip h o s-
p h o lip id o r a n t i-SSA/Ro
a n d a n t i-SSB/La a n t ib o d -
ie s).
• Pa t ie n t s w it h se ve re jo in t
d ise a se , ca rd io p u lm o n a ry
o r re n a l d ise a se , o r t h ro m -
b o cyt o p e n ia .
• Pa t ie n t s w it h p rio r p re g -
n a n cy co m p lica t io n s.
• Pa t ie n t re q u irin g t re a t -
m e n t w it h p o t e n t ia lly
fe t o t o xic m e d ica t io n s.
Ch a p te r 18 Pregn a n cy a n d Rh e u m a t ic Dis e a s e s 169
Pa t ie n t s w it h h igh -t it e r a n t ip h os p h olip id a n t ibod ie s a re a d d it ion a lly a t ris k
for e a r ly, s eve re p re e cla m p s ia . In rh e u m a t oid a rt h r it is a n d o t h e r rh e u m a t ic
d is e a s e s , d iffe re n t ia l d ia gn os is is n ot d if cu lt , bu t p rot e in u ria , t h rom bocyt op e -
n ia , a n d h yp e rt e n s ion clos e ly re s e m ble s ys t e m ic lu p u s e ryt h e m a t os u s a re (7 ).
Dis t in gu is h in g fe a t u re s b e t w e e n lu p u s a n d p re e cla m p s ia a re a s fo llow s : u ri-
n a ry e ryt h rocyt e ca s t s occu r in lu p u s n ep h rit is , bu t n ot p re e cla m p s ia ; n orm o-
co m p le m e n t e m ia is u n u s u a l in lu p u s n e p h r it is , b u t h yp o co m p le m e n t e m ia
m a y occu r in bot h . Lu p u s ra s h , a rt h rit is , feve r, a n d lym p h a d e n op a t h y d o n ot
occu r in p re e cla m p s ia . How eve r, p a in fu l p a lm a r e ryt h e m a (“va s cu lit is ”) occu rs
in bot h .
For p a t ie n t s w it h d e s t ru ct ive a rt h rit is , d e live ry m e rit s s p e cia l ca re. Ce rvica l
s p in e d is e a s e a n d t e m p orom a n d ibu la r d is e a s e m ay com p lica t e in t u ba t ion or
ot h e r h a n d lin g on t h e d e live ry t a ble. Sh ou ld e r a n d e lbow d is e a s e m ay com p li-
ca t e e m e rge n cy p la ce m e n t of in t ra ve n ou s lin e s ; h a n d a n d w ris t d is e a s e m ay
in t e r fe re w it h t igh t gr ip p in g o f h a n d le s d u r in g t h e “p u s h ” s t a ge o f va gin a l
d e live ry. Norm a l va gin a l d e live ry re q u ire s fu ll h ip e xion a n d a bd u ct ion , a n d
fu ll kn e e e xion . In t h e h e a t of d e live ry, obs t e t ric s t a ff m ay ove re s t im a t e m obil-
it y a n d d is lo ca t e o r fra ct u re jo in t s w it h lim it e d ra n ge o f m o t io n . Th e ris k is
s
e
e s p e cia lly h igh for p a t ie n t s w it h h ip rep la ce m e n t s .
s
a
A n orm a l la bor m ay t a ke 18 or m ore h ou rs , d u rin g w h ich t h e p a t ie n t m a y
e
s
i
n ot be a ble t o t a ke h e r n orm a l m e d ica t ion s . Es p e cia lly for m a in t e n a n ce cort i-
D
c
cos t e roid s , t h e rh e u m a t ologis t s h ou ld re m in d t h e obs t e t ric s t a ff t o give t h e s e
i
t
a
m e d ica t ion s in t rave n ou s ly.
m
u
e
h
R
CONCLUSIONS
c
i
c
Po s t p a rt u m is s u e s in clu d e re la t ive ly s low re cove ry b e ca u s e o f t h e m o t h e r ’s
e
p
ch ron ic illn e s s . (Th e con t e m p ora ry “in -a n d -ou t in 1 d a y” p ra ct ice for d e live ry
S
s h ou ld be avoid e d .) Me d ica t ion s s h ou ld be re s u m e d q u ickly, w it h a t t e n t ion t o
3
N
t h os e m e d ica t ion s a ccep t a ble for bre a s t -fe e d in g if t h e m ot h e r ch oos e s t o d o
O
I
t h is . (Seve ra l s ou rce s of in form a t ion a bou t a ccep t a ble m e d ica t ion s a re a va ila -
T
C
ble ; 8, 9 .) Mot h e rs w it h u p p e r e xt re m it y a rt h rit is m ay be u n a ble t o cra d le a ba by
E
S
for n u rs in g. Mot h e rs w it h a n y ch ron ic illn e s s m ay be u n a ble t o bre a s t -fe e d or
ca re for t h e ir in fa n t s in t h e w ay t h ey w is h , p ot e n t ia lly le a d in g t o d ep re s s ion or
fa m ily con ict or bot h .
Be ca u s e fa m ilia rit y w it h t h e m a n y p ot e n t ia l com p lica t ion s of rh e u m a t ic
d is e a s e p regn a n cy is n ot w id e s p re a d , re fe rra l t o a n e xp e rt in t h e e ld for con -
s u lt a t ion a t le a s t on ce is a d vis a ble. Som e p a t ie n t s , for in s t a n ce t h os e w it h n o
s e ro logic w a r n in g s ign s o r a n a t o m ic r is k s , m a y b e co n s id e re d low r is k a n d
n e e d n o fu rt h e r eva lu a t ion . Th os e w it h a n t ip h os p h olip id a n t ibod ie s , a n t i-SSA/
Ro a n d a n t i-SSB/La a n t ibod ie s , w it h p rior fe t a l los s or com p lica t e d p regn a n cie s ,
a n a t o m ic d is a bilit ie s , re n a l or ca rd iop u lm on a ry d is e a s e , t h ro m bo cyt o p e n ia ,
a n d re q u irin g p ot e n t ia lly t oxic m e d ica t ion s s h ou ld a ll re ce ive s p e cia lize d ca re.
Re fe re nce s
1. Bru ca t o A, Cim a z R, Ca p ora li R, e t a l. Pregn a n cy ou t com e s in p a t ie n t s w it h a u t oim m u n e d is e a s e s a n d
a n t i-Ro/SSA a n t ibod ie s . Clin Rev A llergy Im m unol 2011;40 (1 ):27 –41 .
2. Bu yon JP, Cla n cy RM , Frie d m a n DM . Ca rd ia c m a n ife s t a t ion s of n e on a t a l lu p u s e ryt h e m a t o s u s : Gu id e lin e s
t o m a n a ge m e n t , in t egra t in g clu e s from t h e be n ch a n d be d s id e . Nat Clin Pract Rheum atol 2009 ;5 (3 ):139 –148 .
[Review ]
3. Frie d m a n DM , Lla n os C, Izm irly PM , e t a l. Eva lu a t ion of fe t u s e s in a s t u d y of in t rave n ou s im m u n oglobu -
lin a s p reve n t ive t h e ra p y fo r co n ge n it a l h e a r t block : Re s u lt s of a m u lt ice n t e r, p ro s p e ct ive, o p e n -la b e l
clin ica l t ria l . A rthritis Rheum 2010 ;62 (4 ):1138 –1146 .
4. Izm irly PM , Kim MY, Lla n os C, e t a l. Eva lu a t ion of t h e ris k of a n t i-SSA/Ro-SSB/La a n t ibod y-a s s ocia t e d
ca rd ia c m a n ife s t a t io n s o f n e o n a t a l lu p u s in fe t u s e s o f m o t h e r s w it h s ys t e m ic lu p u s e ryt h e m a t o s u s
e xp os e d t o h yd roxych loroq u in e . A nn Rheum Dis 2010 ;69 (10 ):1827 –1830, e p u b May 6, 2010 .
5. Sa lm on J, Gira rd i G, Locks h in MD . Th e a n t ip h os p h olip id s yn d rom e —a d is ord e r in it ia t e d by in a m m a t ion :
Im p lica t ion s for t h e ra py of p regn a n t p a t ie n t s . Nat Clin Pract Rheum atol 2007 ;3 (3 ):140 –147 .
 170 Se ctio n 3 Sp e cific Rh e u m a t ic Dis e a s e s : Dia gn os is a n d Tre a t m e n t

6. Gu ba lla N , Sa m m a rit a n o L, Sch w a rt zm a n S, e t a l. Ovu la t ion in d u ct io n a n d in vit ro fe rt iliza t ion in lu p u s

a n d a n t ip h os p h olip id a n t ibod y s yn d rom e . A rthritis Rheum 2000 ;43 :550 –556 .
7. Ru iz-Ira s t orza G, Kh a m a sh t a M, Gord on C, et a l. Me a su rin g s yst e m ic lu p u s eryt h em a t osu s a ct ivit y d u rin g
p regn a n cy: Va lid a t ion of t h e s ca le Lu p u s Act ivit y In d ex in Pregn a n cy (LAI-P). A rthritis Care Res 2004 ;51 :78 –82 .
8. Os t e n s e n M , Locks h in M , Do ria A, e t a l. Up d a t e on s a fe t y d u rin g p regn a n cy of biologica l a ge n t s a n d s om e
im m u n os u p p re s s ive a n t i-rh e u m a t ic d ru gs . In : Cu t olo M , Ma t u cci-Ce rin ic M , Locks h in MD, Os t e n s e n M ,
co-e d s . Pregnancy in the Rheum atic Diseases. Rheum atology 2008 ;47(Su p p l 3):28 –31.
9. Øs t e n s e n M , Kh a m a s h t a M , Locks h in M , e t a l. An t irh e u m a t ic d ru g t h e ra py a n d rep rod u ct ion . A rthritis Res
Ther 2006 ;8 :209.
S
E
C
T
I
O
N
3
S
p
e
c
i
c
R
h
e
u
m
a
t
i
c
D
i
s
e
a
s
e
s
SECTION
4

Osteoa rthritis a nd Meta bolic

Bone a nd Joint Disea se

Chapter 19 Os te oarth ritis

Mary S. W alton, Carlos J. Loz ada, and
Seth M. Berney

Chapter 20 Gou t an d Crys tal-In du ce d

Arth ropath ie s
A ngelo Gaffo

Chapter 21 Os te ope n ic Bon e Dis e as e s

an d Os te on e cros is
Kenneth G. Saag, Gregory A . Clines, and
Sarah L. Morgan

Chapter 22 Arth ropath ie s As s ociate d

w ith Sys te m ic Dis e as e s
Leann Maska and A m y C. Cannella

171
CHAPTER
19 Osteoa rthritis
Mary S. W alton , Carlos J. Loz ada, and Seth M. Berney

Intro ductio n

e
A 60-ye ar-o ld m ale f o rm e r

n
o
Os t e o a r t h rit is (OA), a ls o re fe r re d t o a s

B
p ro f e ssio n al f o o t b all p laye r

c
d e ge n e ra t ive join t d is e a s e (DJD), is t h e

i
l
w it h a h ist o ry o f m u lt ip le k n e e

o
m o s t com m on fo rm of join t d is e a s e in

b
in ju rie s co m p lain s o f b ilat e ral

a
h u m a n s . Be ca u s e o f p h ys icia n vis it s ,

t
e
M
k n e e p ain f o r 10 ye ars. Th e m e d ica t ion s , s u rgica l in t e rve n t ion , a n d
t im e m is s e d from w ork, OA a p p e a rs t o

d
p at ie n t also co m p lain s o f

n
co s t a s m u ch a s 30 t im e s m o re t h a n

a
b ilat e ral w rist p ain an d 15 t o

s
rh e u m a t oid a rt h rit is (RA) (1 ).

i
t
i
r
20 m in u t e s o f m o rn in g st iff - Os t e oa rt h rit is w a s on ce t h ou gh t t o

h
t
r
n e ss. He d e n ie s jo in t sw e llin g , be t h e re s u lt of a gin g. How eve r, w e n ow

a
o
b e lie ve t h a t it d e ve lo p s a s a co n s e -

e
Rayn au d ’s p h e n o m e n a, sicca sym p t o m s, f e ve r, o r ch ills.

t
s
q u e n ce o f m u lt ip le fa ct o r s , in clu d in g

O
On p h ysical e xam in at io n , h e is a n o n –ill-ap p e arin g m ale bioch e m ica l a n d biom e ch a n ica l a bn or-

4
w it h a n o n t e n d e r n o d u le o n t h e rig h t in d e x d ist al in t e r-

N
m a lit ie s , a s w e ll a s ge n e t ic p re d is p os i-

O
t ion s m a n ife s t in g clin ica lly a s OA.

I
p h alan g e al (DIP) jo in t an d b o n y e n larg e m e n t o f rig h t lo n g

T
C
E
an d le f t rin g p ro xim al in t e rp h alan g e al (PIP) an d DIP jo in t s.

S
He also h as t e n d e rn e ss o n p alp at io n at t h e b ase o f b ilat e ral EPIDEMIOLOGY
t h u m b s’ carp o m e t acarp al (CM C) jo in t s an d e n larg e m e n t o f Os t e o a r t h r it is ca n b e d e n e d ra d io -
h is b ilat e ral k n e e s w it h p ain an d cre p it u s o n p assive ran g e gra p h ica lly o r clin ica lly (ra d io gra p h s
p lu s clin ica l s ym p t om s or s ign s ). Ut iliz-
o f m o t io n . His w rist s, m e t acarp o p h alan g e al (M CP) jo in t s,
in g ra d iogra p h ic crit e ria , 30% of in d ivid -
e lb o w s, h ip s, an d an k le s are n o rm al (Fig . 19.1 ). u a ls be t w e e n t h e a ge s of 45 a n d 65 a re
a ffe ct e d , a n d m ore t h a n 80% a re a ffe ct e d
by t h e ir e igh t h d e ca d e of life.
Th e p reva le n ce of OA in cre a s e s in bot h m e n a n d w om e n a s t h ey a ge, bu t
ge n d e r d iffe re n ce s e xis t . Os t e oa rt h rit is a ffe ct s m e n m ore com m on ly a m on g
p a t ie n t s you n ge r t h a n 45 ye a rs a n d w om e n m ore com m on ly a m on g p a t ie n t s
o ld e r t h a n 55 ye a rs . Ad d it ion a lly, DIP OA is t e n t im e s m ore like ly in w om e n
t h a n in m e n . Mot h e rs a n d s is t e rs of w om e n w it h DIP OA a re t w o t o t h re e t im e s
m ore like ly t o be a ffe ct e d by it (2 ).
Obe s it y in w om e n h a s be e n lin ke d t o OA of t h e kn e e s a n d h ip (3 ) a n d is
p roba bly a ls o a ris k fa ct or for kn e e OA in m e n Obe s it y is a ls o a ris k fa ct or for
h a n d OA in bot h ge n d e rs . Th e m e ch a n is m s for t h is h ave n ot be e n cle a rly e lu -
cid a t e d a n d m a y in clu d e in cre a s e in bod y m a s s , a lt e re d biom e ch a n ics of ga it ,
ge n e t ic p re d is p os it ion , a n d /or a lt e re d m e t a bolis m . We a ls o ca n n ot a d e q u a t e ly
e xp la in t h e a s s ocia t ion be t w e e n obe s it y a n d OA of n on –w e igh t -be a rin g join t s
s u ch a s t h e s t e rn oclavicu la r a n d DIP join t s .

173
 174 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

PATHOGENESIS
In it ia lly t h ou gh t of a s a d is e a s e on ly of a rt icu la r ca rt i-
la ge , OA in vo lve s t h e e n t ir e jo in t , in clu d in g t h e
s u b ch o n d ra l b o n e. Be ca u s e t h e ro le o f in a m m a t io n
in OA w it h in cre a s e d e xp re s s ion of cyt okin e s a n d m e t -
a llop rot e in a s e s in s yn oviu m a n d ca rt ila ge is be com in g
m ore re cogn ize d , t h e t e rm degenerativ e joint disease is
n o lon ge r a p p rop ria t e w h e n re fe rrin g t o OA. Fu rt h e r-
m ore, t h e con t e n t ion t h a t OA is “n on in a m m a t ory” is
in co r re ct , w h ile “m ild ly in a m m a t o ry” w o u ld b e a
m ore a ccu ra t e d e s crip t ion .
Th e e t iop a t h oge n e s is of OA h a s be e n d ivid e d in t o
t h re e s t a ge s (5 ). Du rin g s t a ge 1, in cre a s e d p rod u ct ion
of p ro t e olyt ic e n z ym e s s u ch a s m e t a llo p rot e in a s e s
(e.g., colla ge n a s e a n d s t rom e lys in ) d e s t roys t h e ca rt i-
la ge m a t rix. Du rin g s t a ge 2, t h e ca rt ila ge s u rfa ce e rod e s
S
a n d brilla t e s , re le a s in g p rot e oglyca n s a n d colla ge n
E
Figure 19.1 Sta nding (weight-bea ring) view of the knees indica tes
C
signi ca nt bila tera l media l joint spa ce na rrowing, modera te bila tera l fra gm e n t s in t o t h e s yn ovia l u id . Fin a lly, in s t a ge 3,
T
I
O
la tera l compa rtment joint spa ce na rrowing, a nd media l a nd la tera l joint t h e s e ca rt ila ge bre a kd ow n p rod u ct s in d u ce a ch ron ic
N
osteophyte forma tion. in a m m a t ory re s p on s e in t h e s yn oviu m , ch a ra ct e rize d
4
by m a crop h a ge p rod u ct ion of in t e rle u kin 1 (IL-1), t u m or
O
s
n e cros is fa ct or (TNF- α), a n d m e t a llop rot e in a s e s . Th e s e
t
e
s u bs t a n ce s p ro ba bly in cre a s e t h e ca r t ila ge u lce ra t io n s a n d m a y s t im u la t e
o
a
ch on d rocyt e s t o p rod u ce m ore m e t a llop rot e in a s e s , re s u lt in g in ca rt ila ge los s
r
t
h
a n d bon y ebu rn a t ion a n d u lt im a t e ly s u bch on d ra l bon e os t e op h yt e form a t ion .
r
i
t
i
s
a
n
d
Clinica l Pre se nta tio n
M
e
t
Th e in it ia l goa l of t h e h e a lt h ca re p rofe s s ion a l w h e n s e e in g a p a t ie n t w it h join t
a
b
p a in is t o d iffe re n t ia t e OA from m ore in a m m a t ory a rt h rit id e s , s u ch a s RA.
o
l
i
In con t ra s t t o OA, RA p rim a rily a ffe ct s t h e w ris t s , MCP join t s , a n d PIP join t s
c
B
(PIP), a n d s p a re s t h e DIP join t s a n d t h ora cic a n d lu m bos a cra l s p in e. Rh e u m a -
o
n
t oid a rt h rit is is a ls o t yp ica lly a s s ocia t e d w it h in a m m a t ory m orn in g s t iffn e s s
e
(m ore t h a n 1 h ou r) a n d ra d iogra p h ic n d in gs of bon e los s (p e ria rt icu la r os t e o-
p e n ia ; m a rgin a l e ros ion s of bon e ) ra t h e r t h a n bon e form a t ion .
Sym p t om a t ic h ip OA is u s u a lly in s id iou s in on s e t a n d m ay ca u s e d im in is h e d
in t e rn a l rot a t ion , a lim p, a n d groin or bu t t ock p a in . How eve r, n ot u n com m on ly,
p a t ie n t s m ay exp e rie n ce low ba ck p a in or m e d ia l kn e e p a in , rep re s e n t in g p a in
re fe rre d from t h e h ip . Pa in in t h e la t e ra l a s p e ct of t h e t h igh , a rou n d t h e gre a t e r
t roch a n t e r t h a t is u s u a lly rep rod u cible on p a lp a t ion , u s u a lly rep re s e n t s gre a t e r
t roch a n t e ric bu rs it is , n ot OA.
CLINICAL POINTS
Os t e oa rt h rit is of t h e lu m ba r s p in e ca n ca u s e s p in a l s t e n os is . Th e s e s ym p -
• Wh a t Diffe re n t ia t e s OA t om s m a y in clu d e p s e u d ocla u d ica t ion w it h in t e rm it t e n t or con s t a n t p a in in
Fro m RA t h e legs w ors e n e d by e xe rt ion (p a rt icu la rly w h e n t h e p a t ie n t s t a n d s s t ra igh t u p
• Asym m e t ric jo in t or h yp e re xt e n d s t h e ba ck, s u ch a s d e s ce n d in g s t a irs ) a n d re lieve d by e xin g t h e
in vo lve m e n t ba ck, s it t in g, or w a lkin g u p s t a irs .
• Bo n y jo in t e n la rg e m e n t Eros ive OA, a d is ord e r occu rrin g p rim a rily in w om e n , ca u s e s in a m m a t ion
(n o t jo in t sw e llin g ) of t h e DIP or PIP join t s , re s u lt in g in a ce n t ra l join t e ros ion (d e s cribe d a s “s e a gu lls ”
• Ne w b o n e fo rm a t io n on ra d iogra p h ).
(o st e o p h yt e s) Mu lt ip le ca u s e s of s e con d a ry OA e xis t , in clu d in g join t t ra u m a (fra ct u re s or
s u rge rie s ), p rior in a m m a t ory a rt h rop a t h y, Pa ge t d is e a s e, h e m op h ilia , m u lt ip le
• Mo rn in g st iffn e ss 45 t o
60 m in u t e s e n d ocrin op a t h ie s , n e u rop a t h ic or Ch a rcot join t s , a n d con ge n it a l or h yp e rm o-
bilit y d is ord e rs .
• In vo lve m e n t o f DIP jo in t s, Th e d is e a s e p rogre s s ion is ch a ra ct e ris t ica lly s low, ove r ye a rs or d e ca d e s .
PIP jo in t s, a n d /o r sp in e ;
sp a rin g MCP jo in t s Eve n t u a lly, t h e s e eve n t s a lt e r t h e join t a rch it e ct u re, a n d a d d it ion a l bon e grow s
a s it re m od e ls t o s t a bilize t h e join t .
 Ch a p te r 19 Os t e o a rt h rit is 175

PATIENT ASSESSMENT

• Hist o ry: p a in w it h o u t
sw e llin g (syn o vit is) a n d
m o rn in g st iffn e ss 45
m in u t e s
• Ph ysica l e xa m in a t io n
ndings: bony enlargement
without synovitis commonly
involving DIP, PIP, rst CMC
joints, AC joint of shoulder,
h ip s, kn e e s, rst MTP
jo in t s, fa ce t jo in t s o f t h e
ce rvica l a n d lu m b a r sp in e
• La b o ra t o ry: No rm a l
la b o ra t o ry st u d ie s;
jo in t e ffu sio n w ill b e
n o n in a m m a t o ry w it h Figure 19.2 Bony joint enla rgement of the right thumb interpha la ngea l

e
n
2,000 WBC/m m 3 joint, bila tera l index a nd long nger proxima l interpha la ngea l (PIP) joints,

o
B
a nd multiple dista l interpha la ngea l (DIP) joints with a ngula tions a t the
• Ra d io g ra p h ic: Asym m e t ric

c
right ring nger DIP, long nger PIP a nd DIP, index nger PIP a nd DIP, a nd

i
l
jo in t sp a ce n a rro w in g ;

o
the left index nger PIP a nd DIP joints.

b
a sym m e t ric jo in t

a
t
in vo lve m e n t ; o st e o p h yt e s

e
M
d
n
a
Exa mina tio n

s
i
t
i
r
h
Th e p h ys ica l e xa m in a t ion n d in gs a re lim it e d t o t h e a ffe ct e d join t s . On in s p e c-

t
r
a
t ion , t h e re m ay be bon y e n la rge m e n t a n d m a la lign m e n t (s u ch a s a n gu la t ion of

o
e
t h e PIP, DIP, or kn e e join t s ) d ep e n d in g on d is e a s e s eve rit y. He be rd e n ’s a n d /or

t
s
O
Bou ch a rd ’s n od e s (com p re s s e d broge la t in ou s cys t s ) ove rlyin g t h e DIP a n d PIP

4
join t s , re s p e ct ive ly, m ay d eve lop a n d in a m e (Fig. 19.2 ).

N
A n on in a m m a t ory join t e ffu s ion (d e n e d a s a W BC cou n t of 200 t o 2,000

O
I
W BC/m m 3 ) m ay occu r, u s u a lly w it h ou t s ign i ca n t join t e ryt h e m a or w a rm t h .

T
C
E
Pa t ie n t s h ave p a in on a ct ive or p a s s ive ra n ge of m ot ion of t h e a ffe ct e d join t s .

S
Cre p it u s (a gra t in g or grin d in g s e n s a t ion t h a t occu rs a s t h e join t is m ovin g) is
ch a ra ct e ris t ic of la rge r join t s , s u ch a s t h e kn e e s . Lim it a t ion of join t m ot ion m ay
b e p re s e n t in m ore a d va n ce d ca s e s , a s w e ll a s p e ria rt icu la r m u s cle a t rop h y
s e con d a ry t o d is u s e.

Dia g no stic Studie s

Os t e oa rt h rit is t yp ica lly d oe s n ot ca u s e a n y con ve n t ion a l la bora t ory a bn orm a l-
it ie s o t h e r t h a n a n o n in a m m a t o ry s yn ovia l u id a n a lys is (a le u k o cyt e ce ll
co u n t o f 200 t o 2,000/m m 3 , w it h a m on on u cle a r p re d om in a n ce ). In co n t ra s t ,
t h e la bora t ory n d in gs in RA corre la t e w it h s ys t e m ic in a m m a t ion a n d com -
m on ly in clu d e e leva t e d a cu t e -p h a s e re a ct a n t s (e ryt h rocyt e s e d im e n t a t ion ra t e
a n d C-re a ct ive p rot e in ) a n d t h e “a n e m ia of ch ron ic d is e a s e.” Eigh t y p e rce n t of
p a t ie n t s eve n t u a lly h a ve a p o s it ive s e r u m r h e u m a t o id fa ct o r. In a m m a t o ry
jo in t u id (W BC 2,000 ce lls / m m 3 w it h a p o lym o r p h o n u cle a r ce ll p re d o m i-
n a n ce ) fu rt h e r d iffe re n t ia t e s t h e t w o d is e a s e s .
Radiographic ndings m os t in d ica t ive of OA a re bon y grow t h s a t t h e jo in t
m a rgin s k n ow n a s o s t e o p h yt e s (co llo q u ia lly k n ow n a s “b o n e s p u rs ”). Ot h e r
n d in gs in clu d e a s ym m e t ric join t s p a ce n a rrow in g, s u bch on d ra l s cle ros is , a n d
s u b ch o n d ra l cys t fo r m a t io n . Th e s eve r it y o f t h e ra d iogra p h ic n d in gs o ft e n
fa ils t o corre la t e w it h s ym p t om s u n t il t h e join t s p a ce is oblit e ra t e d . W h e n ra d i-
ogra p h in g kn e e s a n d h ip s , w e igh t -be a rin g (or u p righ t ) view s re s u lt in a m ore
re a lis t ic im a ge of t h e join t .
176 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
NOT TO BE MISSED
Diffe re ntial Diag no se s to
Co nside r
• In a m m a t o ry ve rsu s
n o n in a m m a t o ry
• Syn o vit is (jo in t
in a m m a t io n ) ve rsu s
b o n y e n la rg e m e n t
Diffe re ntial Diag no se s
• No n in a m m a t o ry (OA)
• In a m m a t o ry (RA,
se ro n e g a t ive
sp o n d ylo a rt h ro p a t h ie s)
• Cryst a llin e a rt h ro p a t h ie s
• In fe ct io n
• Fra ct u re
Tre a tme nt
Th e m a n a ge m e n t of OA in clu d e s p reve n t ive a n d t h e ra p e u t ic (n on p h a rm a co-
logic a n d p h a rm a cologic) com ponents .
PREVENTIVE THERAPY
Alt h ou gh m a n y of t h e p re s e n t ly e s t a blis h e d ris k fa ct ors , s u ch a s in cre a s in g a ge
a n d ge n e t ics , ca n n ot be a lt e re d , t h e s in gle m os t im p ort a n t m od i a ble fa ct or
e m e rgin g from e p id e m iologic t ria ls is obe s it y.
We igh t los s s h ou ld be a goa l in p a t ie n t s w h o a re obe s e be ca u s e eve n m od -
e s t w e igh t los s h a s be e n a ccom p a n ie d by, a t t im e s , a d ra m a t ic im p rove m e n t in
ba ck a n d low e r e xt re m it y s ym p t om s .
SYMPTOMATIC THERAPY OF OA
Th e m o s t e ffe ct ive s ym p t o m a t ic t h e ra p y co m b in e s s eve ra l s im u lt a n e o u s
a p p roa ch e s a n d m ay be m ore e ffe ct ive if a m u lt id is cip lin a ry a p p roa ch is u s e d
(e.g., t h e rh e u m a t ologis t , p h ys ia t ris t , ort h op e d is t , p h ys ica l t h e ra p is t , occu p a -
t ion a l t h e ra p is t , p s ych ologis t , p s ych ia t ris t , n u rs e /n u rs e coord in a t or, d ie t it ia n ,
a n d s ocia l w orke r).
Physical Me asure s
A va rie t y of p h ys ica l m od a lit ie s a re va lu a ble for im p rovin g t h e s ym p t om s of
OA, a n d in clu d e e xe rcis e, s u p p ort ive d evice s , a lt e ra t ion s in a ct ivit ie s of d a ily
livin g, a n d t h e rm a l m od a lit ie s (Ta ble 19.1 ).
Table 19.1 Physical Measures in t he Management of
Ost eoart hrit is
Exe rcise
Pa ssive ra n g e o f m o t io n
Re st p e rio d s
Act ive : ra n g e o f m o t io n , iso m e t ric, iso t o n ic, iso kin e t ic
Su p p o rt a n d o rt h o t ic d e vice s
Ca n e s
Cru t ch e s
Co lla rs
Sh o e in so le s
Me d ia l t a p in g o f t h e p a t e lla
Kn e e b ra ce s
Mo d i e d a ct ivit ie s o f d a ily livin g
Pro p e r p o sit io n in g a n d su p p o rt w h e n sit t in g , sle e p in g , o r d rivin g a ca r
Ad ju st in g w a ys o f p e rfo rm in g su ch a ct ivit ie s a s g e t t in g d re sse d , e t c.
Ad ju st in g fu rn ish in g s a ro u n d t h e h o u se o r a t w o rk (e .g ., ra isin g t h e le ve l o f a
ch a ir o r t o ile t se a t )
Th e rm a l m o d a lit ie s
Su p e r cia l h e a t (e .g ., h o t p a cks a n d p a ra f n b a t h s)
De e p h e a t (e .g ., u lt ra so u n d )
Co ld a p p lica t io n s (e .g ., co ld p a cks a n d va p o co o la n t sp ra ys)
Misce lla n e o u s
Pu lse d e le ct ro m a g n e t ic e ld s
Tra n scu t a n e o u s n e u ra l st im u la t io n
Acu p u n ct u re
Ch iro p ra ct ic
Sp a , m a ssa g e , a n d yo g a t h e ra p y
Fro m Lo za d a CJ, Alt m a n RD. In : Ko o p m a n WJ, e d . A rt h rit is an d A llie d Co n d it io n s: A Te xt b o o k o f
Rh e u m at o lo g y . 14t h e d . Ph ila d e lp h ia : Lip p in co t t Willia m s & Wilkin s, 2001 :2246 –2263 , w it h p e rm issio n .
 Ch a p te r 19 Os t e o a rt h rit is 177

Ex e rcis e m a y re d u ce p a in a n d im p rove fu n ct io n in p a t ie n t s w it h OA.

Alt h ou gh p h ys ica l a n d occu p a t ion a l t h e ra p y gu id a n ce a re re q u ire d in s om e
p a t ie n t s , in m os t in s t a n ce s , t h e e xe rcis e s ca n be p e rform e d by t h e p a t ie n t a t
h om e a ft e r m in im a l in s t ru ct ion .
Im p roved stren gth of th e p a ra -a rticu la r stru ctu re a d d s sta bility a n d su p p ort
t o th e join t a n d a p p ea rs to red u ce sym p tom s. Stren gth en in g of th e q u a d ricep s
m u scles in a p a tien t w ith kn ee OA ca n im p rove fu n ction a n d d ecrea se p a in for u p
to 8 m on th s (6 ). Moreover, a su p ervised p rogra m of tn ess w a lkin g a n d ed u ca tion
im p rove s t h e p a t ie n t ’s fu n ct ion a l s t a t u s . Hea lt h ca re p rovid e rs s h ou ld a ct ive ly
d isp el th e m yth th a t a n y exercise w orsen s a rth ritis a n d th u s sh ou ld en cou ra ge
p a t ien t s w it h OA t o gra d u a lly in crea s e t h e ir a ct ivit y. How ever, in cre a s in g p a in
m ay be a w a rn in g sign th a t th ey h ave exceed ed th eir exercise tolera n ce.
Exercises th a t m a xim ize m u scle stren gth en in g w h ile m in im izin g stress on th e
a ffected join ts a re p referable. Sw im m in g is p a rticu la rly effective beca u se it ca u ses
m in im a l join t im p a ct a n d s tren gth en s m u ltip le m u scle grou p s. Un fort u n a te ly,
ce rt a in e xe rcis e s m a y a ct u a lly w ors e n s ym p t om s (e.g., ch on d rom a la cia p a t e lla
m a y be w ors e n e d by bicycle rid in g; lu m ba r fa ce t OA m a y be w ors e n e d by h yp e r-

e
n
e xt e n s ion of t h e s p in e , a s in sw im m in g). Ad d it ion a lly, w e n o lon ge r re co m -

o
B
m e n d be d re s t for p a t ie n t s w it h a cu t e or ch ron ic low ba ck p a in .

c
i
l
Supportiv e dev ices a re a ls o h e lp fu l be ca u s e t h ey p a rt ia lly u n loa d t h e w e igh t

o
b
from join t s , a n d m ay d e cre a s e p a in a n d im p rove ba la n ce a n d m obilit y. Th e s e

a
t
e
d evice s in clu d e ca n e s , cru t ch e s , w a lke rs , cors e t s , colla rs , a n d ort h ot ic d evice s

M
for s h oe s . Ca n e s , w h e n p rop e rly u s e d , ca n in cre a s e t h e ba s e of s u p p ort , d e cre a s e

d
n
loa d in g, a n d re d u ce d e m a n d s on t h e low e r lim b a n d it s join t s . Th e t ot a l le n gt h

a
o f a p ro p e rly m e a s u re d ca n e s h o u ld e q u a l t h e d is t a n ce b e t w e e n t h e u p p e r

s
i
t
i
bord e r of t h e gre a t e r t roch a n t e r of t h e fe m u r a n d t h e bot t om of t h e h e e l of t h e

r
h
t
s h oe. Th is s h ou ld re s u lt in e lbow e xion of a bou t 20 d egre e s a n d be h e ld in t h e

r
a
o
h a n d con t ra la t e ra l t o a n d m ove d t oge t h e r w it h t h e a ffe ct e d lim b.

e
t
Prop e r foot w e a r a n d ort h ot ic s h oe s ca n be of gre a t va lu e. A s h ort leg t h a t

s
O
a cce n t u a t e s lu m ba r s colios is m ay be h e lp e d t h rou gh a u n ila t e ra l h e e l or a s ole

4
lift . An ort h ot ic d evice, or s h oe in s e rt , m a y h e lp t h e p a t ie n t w it h s u blu xe d m e t -

N
O
a t a rs o p h a la n ge a l jo in t s . A p a t ie n t ’s w a lk in g a b ilit y a n d p a in in t h e m e d ia l

I
T
com p a rt m e n t of t h e kn e e m a y im p rove w it h a la t e ra l h e e l-w e d ge d in s ole. At h -

C
E
le t ic s h oe s w it h good m e d ia l a n d la t e ra l s u p p ort , a s w e ll a s good m e d ia l a rch

S
s u p p ort , a n d ca lca n e a l cu s h ion ca n be of be n e t .
Kn e e bra ce s m ay be of u s e in s om e p a t ie n t s w it h t ibiofe m ora l d is e a s e, e s p e -
cia lly t h os e w it h la t e ra l in s t a bilit y a n d a t e n d e n cy for t h e kn e e t o “give ou t .”
Join t s u p p ort s a n d ort h ot ic d evice s a llow t h e p a t ie n t t o p a rt icip a t e in m ore
a ct ivit ie s , im p rove co m p lia n ce , a n d re t a in fu n ct io n a l in d e p e n d e n ce . Th e s e
d evice s s h o u ld b e fre q u e n t ly m o n it o re d t o e n s u re p ro p e r u s e , s u ch a s t h e
p rop e r s izin g a n d orie n t a t ion of t h e ce rvica l colla r. Ca n e a n d cru t ch t ip s s h ou ld
be ch a n ge d w h e n w orn in ord e r t o avoid s lip p in g on s m oot h or w e t s u rfa ce s .
Pa t ie n t s m ay n eed t o a lt er s om e of t h e ir activities of daily living be ca u se s im p le
a d ju st m en ts m ay d ecrea s e t h eir s ym p t om s . For exa m p le, p a tien t s w it h ba ck p a in
s h ou ld avoid s it t in g on s oft cou ch e s or re clin e rs , or lyin g in be d w it h a p illow
u n d er th e kn ee s. In s t ea d th ey s h ou ld s it in s t ra igh t -ba ck ch a irs w it h good st ru c-
t u ra l s u p p ort (cu s h ion s a llow ed ). Ra is in g t h e leve l of a ch a ir or t oilet s ea t ca n be
h elp fu l, beca u s e th e h ip a n d kn ee s a re s u bject ed to t h e h igh e st p res s u res d u rin g
t h e in it ia l p h a se of ris in g from t h e s ea t ed p os it ion . How eve r, lift ch a irs a re very
ra rely h elp fu l or n eces sa ry. Th e p a t ie n t s h ou ld a lso u s e a rm m a t tres s, p erh a p s
w ith a bed boa rd , a n d avoid s lou ch in g, even w h e n d rivin g. Th e ca r s ea t sh ou ld be
p la ce d forw a rd s o t h a t t h e kn ees a re exed d u rin g d rivin g.
Therm al m odalities ca n h e lp d e cre a s e a p a t ie n t ’s p a in . Th e u s e of h e a t , cold ,
or a lt e rn a t in g h e a t a n d cold is ba s e d on t h e p a t ie n t ’s p re fe re n ce. Tra d it ion a lly,
t h e m ore a cu t e t h e p roce s s , t h e m ore like ly cold a p p lica t ion s w ill be of be n e t .
He a t ca n be s u bd ivid e d in t o s u p e r cia l a n d d e e p , w it h n o p rove n a d va n t a ge of
on e ove r t h e ot h e r. Th e t h e ra p e u t ic va lu e of a p p lyin g h e a t in clu d e s d e cre a s in g
 178 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

join t s t iffn e s s , a llevia t in g p a in , re lievin g m u s cle s p a s m , a n d p reve n t in g con -

t ra ct u re s . Th e t e m p e ra t u re s u s e d ra n ge from 40 ° t o 45 °C (104 ° t o 113 °F) for 3 t o
30 m in u t e s . Hot p a cks , p a ra f n ba t h s , h yd rot h e ra py, a n d ra d ia n t h e a t p rovid e
s u p e r cia l h e a t . De e p h e a t ca n be p rovid e d by u s in g u lt ra s o u n d , u s u a lly fo r
la rge r jo in t s , s u ch a s h ip s . How eve r, h e a t s h o u ld b e u s e d w it h ca u t io n in
p a t ie n t s w h o a re a n e s t h e t ize d , s om n ole n t , or obt u n d e d a n d is con t ra in d ica t e d
ove r t is s u e s w it h in a d e q u a t e va s cu la r s u p p ly, ble e d in g, or ca n ce r a s w e ll a s
a re a s clos e t o t h e t e s t icle s or n e a r d eve lop in g fe t u s e s . Cold is t yp ica lly u s e d in
t h e form of cold p a cks or va p ocoola n t s p ra ys t o re lieve m u s cle s p a s m , d e cre a s e
sw e llin g in a cu t e t ra u m a , a n d re lieve p a in from in a m m a t ion .
Seve ra l m iscellaneous p h ys ica l m od a lit ie s t h a t a re a ls o u t ilize d in clu d e m a s -
s a ge, yoga t h e ra py, a cu p re s s u re, a cu p u n ct u re, m a gn e t s , p u ls e d e le ct rom a gn e t ic
e ld s , t ra n s cu t a n e o u s n e u ra l s t im u la t io n , a n d s p a t h e ra p y (b a ln e o t h e ra p y).
Bu t, m any of th e s e program s are of u n prove n valu e .

Psycho so cial Me asure s

Pa in a n d d isa bility a re n ot solely rela ted to p h ys ica l im p a irm en t, bu t a p p e a r a s s o-
S
E
cia t ed w it h th e p a t ie n t’s p s ych os ocia l con d it ion s . Old er a ge, low er e d u ca tion a l
C
T
leve l, low e r in com e, a n d u n m a rrie d s t a t u s h ave be e n lin ke d t o d is a bilit y in
I
O
N
p a t ie n t s w it h m u s cu los ke le t a l com p la in t s (7 ). Fu rt h e rm ore, p a t ie n t d ep re s s ion
4
m ay w orsen t h eir p ercep t ion of p a in a n d th u s t h e effectiven es s of th e t h era py.
O
Re a s s u ra n ce, cou n s e lin g, a n d e d u ca t ion by t h e h e a lt h ca re p rovid e r a re
s
t
e
im p o rt a n t t o m it iga t e t h e n ega t ive e ffe ct s o f a d ve r s e p s ych o s o cia l fa ct o r s .
o
a
Pa t ie n t s m u s t p a rt icip a t e in t h e ir ca re, w h ich m ay le a d t o be t t e r p a t ie n t com p li-
r
t
h
a n ce a n d ou t com e s . Pe riod ic t e lep h on e s u p p ort h a s be e n fou n d t o be be n e cia l
r
i
t
a n d t o p rom ot e s e lf-ca re a m on g p a t ie n t s w it h OA (8 ).
i
s
a
n
d
Me dicatio n-Base d Sympto matic The rapy
M
Me d ica t ion s u s e d t o t re a t s ym p t om s in OA ca n be d ivid e d in t o ca t egorie s of
e
t
t op ica l a ge n t s , s ys t e m ic ora l a ge n t s , a d ju va n t t h e ra p ie s (e.g., a n t is p a s m od ic a n d
a
b
p s ych oa ct ive d ru gs ), in t ra -a rt icu la r a ge n t s , a n d s t ru ct u re - or d is e a s e -m od ifyin g
o
l
i
d ru gs (n o a ge n t s ye t p rove d t o be lon g in t h is la t t e r ca t egory; Ta ble 19.2 ). Th e
c
B
o
n
e
Table 19.2 Pharmacologic Therapy for Patients with Osteoarthritis a
Ora l a ce t a m in o p h e n
COX-2–sp e ci c in h ib it o r
No n se le ct ive NSAID p lu s m iso p ro st o l o r a p ro t o n p u m p in h ib it o r b
No n a ce t yla t e d sa licyla t e
Ot h e r p u re a n a lg e sics
Tra m a d o l
Op io id s
In t ra -a rt icu la r
Glu co co rt ico id s
Hya lu ro n a n
To p ica l ca p sa icin
Me t h ylsa licyla t e

COX-2, cyclo o xyg e n a se -2; NSAID, n o n st e ro id a l a n t i-in a m m a t o ry d ru g .

a
Th e ch o ice o f a g e n t (s) sh o u ld b e in d ivid u a lize d fo r e a ch p a t ie n t .
b
Miso p ro st o l a n d p ro t o n p u m p in h ib it o rs a re re co m m e n d e d in p a t ie n t s w h o a re a t in cre a se d risk fo r u p p e r
ga st ro in t e st in a l a d ve rse e ve n t s.
Fro m re fe re n ce 11.
 Ch a p te r 19 Os t e o a rt h rit is 179

t re a t m e n t regim e n s h ou ld be in d ivid u a lize d for e a ch p a t ie n t a n d t h e s e m e d ica -

t ion s a re oft e n u s e d in com bin a t ion s .
Pa t ie n t s fre q u e n t ly in q u ire a bou t t h e be n e t s of d ie t s , vit a m in s , m in e ra ls ,
a n d s u p p le m e n t s . How eve r, n o con clu s ive evid e n ce e xis t s t h a t a n y of t h e s e
im p rove t h e s ym p t om s or t h e u n d e rlyin g d is e a s e. Th e re fore in ge s t ion of s p e -
cia l fo o d s , vit a m in s , z in c, co p p e r, a n d h o m e re m e d ie s b eyo n d t h e re co m -
m e n d e d d a ily re q u ire m e n t s s h ou ld be d is cou ra ge d .

To pical Ag e nts
Top ica l a ge n t s ca n be u s e fu l a d ju n ct s in t h e t re a t m e n t of OA. Ca p s a icin , d e rive d
from ca p s icu m , t h e com m on p e p p e r p la n t , is ava ila ble w it h ou t p re s crip t ion . It
in t e rfe re s w it h s u bs t a n ce P–m e d ia t e d p a in t ra n s m is s ion by reve rs ibly d ep le t -
in g s t ore s of s u bs t a n ce P in u n m ye lin a t e d C- be r a ffe re n t n e u ron s . Un t il t h e
n e rve e n d in gs a re d ep le t e d of s u bs t a n ce P, ca p s a icin (a p p lie d t w o t o fou r t im e s
d a ily) m a y ca u s e a bu rn in g s e n s a t ion w h e re it is a p p lie d . If n ot u s e d con t in u -
ou s ly, t h e n e rve e n d in gs re n ew t h e ir s u p p ly of a n d s e n s it ivit y t o s u bs t a n ce P.
Wa rn p a t ie n t s t o a vo id in a d ve rt e n t ly ge t t in g ca p s a icin in t h e eye s , b e ca u s e

e
n
t h e ir eye s w ill bu rn t re m e n d ou s ly.

o
B
A va rie t y of ot h e r t o p ica l a n a lge s ics e x is t of q u e s t io n a ble be n e t . Th e s e

c
i
l
in clu d e m e n t h ol- a n d s a licyla t e -ba s e d ove r-t h e -cou n t e r t op ica l p rep a ra t ion s ,

o
b
a s w e ll a s t op ica l n on s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs ).

a
t
e
M
Syste mic Oral Ag e nts

d
n
No n –a n t i-in a m m a t o r y analgesics in clu d e d r u gs s u ch a s a ce t a m in o p h e n .

a
De s p it e m a n y ye a rs of re s e a rch , t h e m e ch a n is m s of a ct ion of a ce t a m in op h e n

s
i
t
i
a re s t ill n ot a d e q u a t e ly u n d e rs t ood . In a n im a ls , t h e a ct ion s a p p e a r t o a ct a t t h e

r
h
t
s p in a l co rd a n d ce re bra l leve ls a n d in t e rfe re w it h a t le a s t cyclooxyge n a s e -3.

r
a
o
Neve rt h e le s s , a ce t a m in op h e n m a y be a s e ffe ct ive a s ibu p rofe n for t h e t re a t -

e
t
m e n t o f kn e e OA p a in (9 ). Fu r t h e r m o re , a ce t a m in o p h e n is s a fe r t h a n NSAIDs

s
O
b e ca u s e it d o e s n o t a p p e a r t o ca u s e ga s t ro p a t h y o r n e p h ro p a t h y a t co n ve n -

4
t io n a l d o s e s , b u t h e p a t o t o x icit y ca n o ccu r w h e n in ge s t e d a t h igh d o s e s .

N
O
Tra m a d ol is a ls o a n e ffe ct ive a n a lge s ic by m ild ly s u p p re s s in g t h e µ-op ioid

I
T
re ce p t o r a n d in h ib it in g t h e u p t a k e o f n o re p in e p h r in e a n d s e ro t o n in . It ca n

C
E
ca u s e n a u s e a a n d ce n t ra l n e rvou s s ys t e m s id e e ffe ct s t h a t ca n be re d u ce d by

S
s t a rt in g w it h 50 m g t w ice d a ily for 3 d ays a n d s low ly e s ca la t in g t h e d os e t o t h e
m a xim u m re com m e n d e d d os e of 50 m g QID or u n t il t h e d e s ire d p a in re lie f is
a ch ieve d .
Th e OA p a in is ge n e ra lly re s p on s ive t o n a rcot ic a n a lge s ics . Mild ly p ot e n t
a n d m in im a lly a d d ict ive n a rcot ic a n a lge s ics , s u ch a s cod e in e, h ave be e n e ffe c-
t ive in p a t ie n t s w it h OA, e s p e cia lly in com bin a t ion w it h n on n a rcot ic a n a lge s ics
(e.g., a ce t a m in op h e n a n d /or NSAIDs ). Be ca u s e of t h e a d d ict ive p ot e n t ia l of t h e
s t ron ge r op ia t e s a n d op ioid s , t h e ris ks of oxycod on e a n d h yd rocod on e s h ou ld
b e com p a re d w it h t h e b e n e t s of t h e p a in re lie f a ch ieve d . A nti-in am m atory
drugs , of w h ich NSAIDs a re t h e m os t com m on ly p re s cribe d , a re u s e d for t re a t in g
bot h p a in a n d m ild in a m m a t ion in OA. Wit h m os t t ra d it ion a l NSAIDs , a n a lge -
s ia ca n be a ch ieve d a t s m a lle r d os e s t h a n a re n e e d e d fo r a n t i-in a m m a t ory
e ffe ct s . How eve r, for m os t NSAIDs , t h e gre a t e r t h e d os e, t h e gre a t e r t h e a n t i-
in a m m a t ory e ffe ct (a ls o t h e gre a t e r ris k of a n a d ve rs e re a ct ion ). Mos t rh e u -
m a t o logis t s re cogn ize t h a t a t t h e ra p e u t ic d o s e s , a ll NSAIDs a p p e a r e q u a lly
e ffe ct ive a t p rovid in g a n a lge s ia .
Th e m a jor p ot e n t ia l a d ve rs e e ffe ct s of n on s e le ct ive NSAIDs a re ga s t rop a -
t h y (p e p t ic u lce r d is e a s e a n d ga s t r it is ) a n d re n a l d ys fu n ct io n (in t e r s t it ia l
n e p h r it is a n d p ro s t a gla n d in -in h ib it io n –re la t e d re n a l in s u f cie n cy). Th e s e
a d ve rs e e ffe ct s a re m ore p reva le n t in t h e e ld e rly.
Effe ct ive s t ra t egie s h a ve be e n d eve lop e d t o m it iga t e t h e ga s t ro in t e s t in a l
(GI) t oxicit y of t h e NSAIDs : u s e of low e r d os e s , n on a ce t yla t e d s a licyla t e, con -
com it a n t u s e of m is op ros t ol (200 µg BID t o QID), or a p rot on p u m p in h ibit or, u s e
 180 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

of a s p e ci c cyclooxyge n a s e (COX)-2 in h ibit or, t op ica l a n a lge s ics , in t ra -a rt icu la r

t h e ra p y w it h a d ep ocort icos t e roid or h ya lu ron a t e, avoid in g con com it a n t u s e of
m u lt ip le NSAIDs , glu cocort icoid s , or s ys t e m ic a n t icoa gu la n t s . How eve r, a n t a c-
id s a n d H 2 - blocke rs h ave n ot be e n a s e ffe ct ive (10 ). We fre q u e n t ly in s t ru ct ou r
p a t ie n t s t o t a ke a ce t a m in op h e n 1 g BID or TID w it h t h e ir NSAID. An e cd ot a lly,
t h is re s u lt s in im p rove d p a in re lie f com p a re d w it h e it h e r a ge n t in d ivid u a lly.
Glucosam ine sulfate a n d ch on d roitin su lfa te h ave been both tes ted in d ivid u a lly
a n d in com bin a t ion . Des p ite t h eir p op u la r u s e, th e ava ila ble d a ta a re in con clu sive
rega rd in g th eir ben e t on p a in or d is ea s e.
S-adenosy lm ethionine (SAM-e ) a n d m ethy lsulfony lm ethane (MSM) h a ve a ls o
be e n u s e d w it h ou t con clu s ive evid e n ce of t h e ir e f ca cy.

Adjuvant Ag e nts
An y a n a lge s ic p rogra m ca n be s u p p le m e n t e d w it h tricyclic antidepressants o r
selectiv e serotonin reuptake inhibitors. Not on ly t h ey m ay a cce n t u a t e t h e e ffe ct of
t h e ot h e r a n a lge s ics , t h ey m ay e xe rt p a rt of t h e ir be n e t in t h os e p a t ie n t s h a v-
in g s le e p d is t u rba n ce s be ca u s e of n oct u rn a l m yoclon u s a n d brom ya lgia -like
S
E
com p la in t s .
C
T
A ntispasm odics a re u s e fu l in re d u cin g m u s cle p a in a n d s p a s m in OA. Pa in
I
O
N
a s s ocia t e d w it h m u s cle s p a s m m a y be re d u ce d w it h a n in je ct ion of lid oca in e,
4
w it h or w it h ou t a d ep ocort icos t e roid .
O
s
t
e
Intra-Articular The rapy
o
a
Ora l cort icos t e roid s a re n ot in d ica t e d for t h e t re a t m e n t of OA. How eve r, intra-
r
t
h
articular corticosteroids m ay re lieve t h e p a t ie n t ’s p a in . Th ey h ave n ot be e n con -
r
i
t
s is t e n t ly h e lp fu l in fa ce t join t s for t re a t m e n t of ch ron ic low ba ck p a in , bu t h ave
i
s
a
b e e n u s e fu l in m a n y p a t ie n t s a s e p id u ra l in je ct ion s fo r s ym p t om a t ic s p in a l
n
d
s t e n os is . De s p it e t h e clin ica l im p re s s ion t h a t t h ey m ay be of va lu e, n o con s is t -
M
e n t clin ica l p re d ict ors of re s p on s e t o in t ra -a rt icu la r d e p ocort icos t e roid s h ave
e
t
be e n fou n d t o a id in p a t ie n t s e le ct ion for t h is t h e ra py.
a
b
In ge n e ra l, d e p ocort icos t e ro id in je ct ion s s h ou ld be lim it e d t o fou r in je c-
o
l
i
t ion s t o a n y s in gle join t p e r ye a r (t yp ica lly n o m ore fre q u e n t ly t h a n a t 3-m on t h
c
B
in t e rva ls ). How eve r, if p a t ie n t s re q u ire m u lt ip le in je ct ion s , t h ey p roba bly re q u ire
o
n
ort h op e d ic s u rgica l in t e rve n t ion .
e
Com p lica t ion s of in t ra -a rt icu la r d e p ocort icos t e roid s , s u ch a s s ep t ic a rt h ri-
t is , a re ra re if p rop e r a s e p t ic t e ch n iq u e is e m p loye d . Dep ocort icos t e roid s a re
crys t a llin e a n d ca n in d u ce a t ra n s ie n t s yn ovit is or “p os t in je ct ion in a m m a t ory
re a ct ion .” Th is re a ct ion occu rs w it h in s eve ra l h ou rs of t h e in je ct ion , in con t ra s t
t o a join t in fe ct ion , w h ich m os t oft e n h a p p e n s 24 t o 72 h ou rs a ft e r t h e p roce -
d u re . Th e a p p lica t io n o f co ld co m p re s s e s o ft e n re d u ce s t h e p a in u n t il t h e
in a m m a t ion re s o lve s . Th e s u s p icion o f in fe ct ion s h ou ld p ro m p t im m e d ia t e
a s p ira t io n w it h s u b s e q u e n t Gra m s t a in a n d cu lt u re s . Fu r t h e rm o re , fre q u e n t
in t ra -a rt icu la r cort icos t e roid s m ay d a m a ge ca rt ila ge a n d bon e, a n d m ay eve n
con t ribu t e t o t h e d eve lop m e n t of ava s cu la r n e cros is .
Syn t h e t ic a n d n a t u ra lly occu rrin g hyaluronic acid derivativ es a re a d m in is t e re d
in t ra -a rt icu la rly. Th e s e v iscosupplem ents a re p rep a re d in a va rie t y of m ole cu la r
w e igh t s (ra n ge 100,000 t o 1,000,000 Sve d be rg u n it s ) a n d m ay re d u ce p a in a n d
im p rove m obilit y for p rolon ge d p e riod s of t im e. Th e m e ch a n is m (s ) of a ct ion is
u n kn ow n . How eve r, s om e evid e n ce e xis t s , s u gge s t in g a n a n t i-in a m m a t ory
e ffe ct (p a rt icu la rly t h e h igh -m ole cu la r-w e igh t p rep a ra t ion ), a s h ort -t e rm lu bri-
ca n t e ffe ct , a n a n a lge s ic e ffe ct by d ire ct ly bu ffe rin g s yn ovia l n e rve e n d in gs , a n d
a s t im u la t in g e ffe ct on s yn ovia l lin in g ce lls in t o p rod u cin g n orm a l h ya lu ron ic
a cid , p e rh a p s t h rou gh bin d in g t o t h e s yn ovia l ce ll CD44H re cep t ors .
Th e vis co s u p p le m e n t s in clu d e Syn vis c (HYLAN GF 20) a d m in is t e re d a s
t h re e w e e kly in je ct ion s , Hya lga n (h ya lu ron a t e s od iu m ) a d m in is t e re d a s t h re e
t o ve w e e kly in je ct io n s , a n d Or t h ovis c (h ya lu ro n a n ) a d m in is t e re d a s t h re e
w e e kly in je ct ion s .
 Ch a p te r 19 Os t e o a rt h rit is 181

Surg ical Inte rve ntio n

WHEN TO REFER
• If u n ce rt a in a b o u t t h e
d ia g n o sis
• If p a in u n re sp o n sive t o
a ce t a m in o p h e n o r NSAIDs
• If t h e p a t ie n t h a s a n
in a m m a t o ry a rt h ro p a t h y
• If t h e clin icia n su sp e ct s
t h a t t h e p a t ie n t n e e d s
jo in t re p la ce m e n t
Th e p rim a ry re a s on for e le ct ive ort h op e d ic s u rge ry is in t ra ct a ble p a in . Th e s e c-
on d a ry re a s on for s u rge ry is re s t ora t ion of com p rom is e d join t fu n ct ion . In t e r-
ve n t ion s in clu d e re m ova l of loos e bod ie s , s t a biliza t ion of join t s , re d is t ribu t ion
of join t force s (e.g., os t e ot om y), re lie f of n e u ra l im p in ge m e n t (e.g., s p in a l s t e n o-
s is a n d h e rn ia t e d d is c), a n d join t rep la ce m e n t (e.g., t ot a l kn e e re p la ce m e n t ).
Os t e o t om ie s m a y s e rve a s a lt e rn a t ive s t o a rt h rop la s t y in yo u n ge r, ove r-
w e igh t p a t ie n t s a n d in u n icom p a rt m e n t a l d is e a s e of t h e kn e e. Th is m a y d e lay
p rogre s s ion of d is e a s e (h e n ce t h e n e e d for t ot a l join t rep la ce m e n t ).
Art h ros cop ic in t e rve n t ion s h ou ld be lim it e d t o p a t ie n t s in w h om a n a d d i-
t ion a l d ia gn os is is s u s p e ct e d , s u ch a s ca rt ila gin ou s or liga m e n t ou s d a m a ge.

Clinica l Co urse
W it h a d e q u a t e p a in re lie f, p a t ie n t s s h ou ld h a ve a n u n co m p lica t e d clin ica l
cou rs e. Th e re is n o good ep id e m iologic d a t a t h a t OA s h ort e n s life exp e ct a n cy a s

e
n
RA a n d s ys t e m ic lu p u s e ryt h e m a t a s u s (SLE) h ave cle a rly be e n d e m on s t ra t e d t o

o
B
d o. W h ile ove ra ll s u rviva l is n ot a ffe ct e d by t h is con d it ion , t h e d is e a s e t e n d s t o

c
i
h ave a s low, p rogre s s ive cou rs e oft e n cu lm in a t in g in t h e n e e d for in va s ive ort h o-

l
o
b
p e d ic p roce d u re s t o a ch ieve p a in con t rol. As s u ch , a ggre s s ive m a n a ge m e n t of

a
t
m od i a ble ris k fa ct ors , s u ch a s w e igh t con t rol a n d s u p e rvis e d exe rcis e p rogra m s ,

e
M
a re of p a ra m ou n t im p ort a n ce t o le n gt h en t h e t im e for a n ort h op e d ic p roce d u re.

d
n
a
s
ICD9

i
t
i
r
h
715.9 Oste o athritis – (se e also Ost e o a rt h ro sis) •

t
r
a
Use t h e f o llo w in g f t h -d ig it

o
e
su b classi cat io n w it h cat e g o rie s 715:

t
s
O
0 sit e u n sp e ci e d

4
1 sh o u ld e r re g io n

N
2 u p p e r arm

O
I
T
3 f o re arm

C
E
4 h an d

S
5 p e lvic re g io n an d t h ig h
6 lo w e r le g
7 an k le an d f o o t
8 o t h e r sp e ci e d sit e s e xce p t sp in e
9 m u lt ip le sit e s
715.9 Oste o arthro sis (d e g e n e rat ive ) (h yp e rt ro p h ic) •
715.0 [0,4,9] g e n e raliz e d
715.3 lo caliz e d •
715.1 id io p at h ic •
715.1 p rim ary •
715.2 se co n d ary •
715.89 m u lt ip le sit e s, (n o t g e n e raliz e d )
715.09 p o lyart icu lar
721.90 sp in e (se e also Sp o n d ylo sis)
524.6 t e m p o ro m an d ib u lar jo in t

Re fe re nce s
1. Kra m e r JS, Ye lin EH , Ep s t e in W V. Socia l a n d e con om ic im p a ct s of fou r m u s cu los ke le t a l con d it ion s : A
s t u d y u s in g n a t ion a l com m u n it y-ba s e d d a t a . J Rheum atol 1983 ;26 :901 –907 .
2. Law re n ce JS. Ge n e ra lize d os t e oa rt h ros is in a p op u la t ion s a m p le . A m J Epidem iol 1969 ;90 :381 –389 .
3. Fe ls on DT. Th e ep id e m iology of kn e e os t e oa rt h rit is : Re s u lt s from t h e Fra m in gh a m os t e oa rt h rit is s t u d y.
Sem in A rthritis Rheum 1990 ;20 :42 –50 .
4. Pe lle t ie r JP, Ma rt e l-Pe lle t ie r J, How e ll DS. Et iop a t h oge n e s is of os t e oa rt h rit is . In : Koop m a n W J, e d . A rthritis
and A llied Conditions: A Textbook of Rheum atology. 13t h e d . Ba lt im ore : Willia m s & Wilkin s , 1997 :1969 –1984 .
 182 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

5. Fis h e r NM , Pe n d e rga s t DR, Gre s h a m GE, e t a l. Mu s cle re h a bilit a t ion : It s e ffe ct s on m u s cu la r a n d fu n c-

t ion a l p e rform a n ce of p a t ie n t s w it h kn e e os t e oa rt h rit is . A rch Phys Med 1991 ;72 :367 –374 .
6. Cu n n in gh a m LS , Ke ls y JL. Ep id e m iology of m u s cu los ke le t a l im p a irm e n t s a n d a s s ocia t e d d is a bilit y. A m
J Pub Health 1984 ;74 :574 –579 .
7. Re n e J, We in be rge r M , Ma zzu ca SA, e t a l. Re d u ct ion of join t p a in in p a t ie n t s w it h kn e e os t e oa rt h rit is
w h o h ave re ce ive d m on t h ly t e lep h o n e ca lls from la y p e rs on n e l a n d w h os e m e d ica l t re a t m e n t regim e n s
h ave re m a in e d s t a ble . A rthritis Rheum 1992 ;35 :511 –515 .
8. Bra d ley JD, Bra n d t KD, Ka t z BP, e t a l. Com p a ris on of a n a n t iin a m m a t ory d os e of ibu p rofe n , a n a n a lge s ic
d o s e of ibu p rofe n , a n d a ce t a m in op h e n in t h e t re a t m e n t of p a t ie n t s w it h o s t e oa rt h rit is of t h e kn e e .
N Engl J Med 1991 ;325 :87 –91 .
9. Ye om a n s ND, Tu la s s ay Z , Ju h a s z L, e t a l. A com p a ris on of om ep ra zole w it h ra n it id in e for u lce rs a s s oci-
a t e d w it h n on s t e roid a l a n t iin a m m a t ory d ru gs . Acid Su p p re s s ion Tria l: Ra n it id in e ve rs u s Om ep ra zole
for NSAID-a s s ocia t e d Ulce r Tre a t m e n t (ASTRONAUT) St u d y Grou p . N Engl J Med 1998 ;338 :719 –726 .
10. Alt m a n RD , Hoch be rg MC, Mos kow it z RW, Sch n it ze r TJ. Re com m e n d a t ion s for t h e m e d ica l m a n a ge m e n t
of os t e oa rt h rit is of t h e h ip a n d kn e e : 2000 u p d a t e . A rthritis Rheum 43 :1905 –1915 .
11. Loza d a CJ, Alt m a n RD, In Koop m a n W J, ed . Art h rit is a n d Allie d Con d it ion s : A t e xt book of Rh e u m a t o logy.
14t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s & Wilkin s , 2001 :2246 –2263 .
S
E
C
T
I
O
N
4
O
s
t
e
o
a
r
t
h
r
i
t
i
s
a
n
d
M
e
t
a
b
o
l
i
c
B
o
n
e
CHAPTER
20 Gout a nd Crysta l-
Induced Arthropa thies
A ngelo Gaffo

Clinica l Pre se nta tio n

e
A 65-ye ar-o ld p at ie n t w it h

n
o
Gou t is t h e clin ica l m a n ife s t a t ion from

B
p o o rly co n t ro lle d d iab e t e s,

c
t h e t is s u e d e p os it ion of m on os od iu m

i
l
h yp e rt e n sio n , h e art f ailu re ,

o
u ra t e (MSU) crys t a ls . Th e d is e a s e h a s

b
an d a p rio r d iag n o sis o f g o u t

a
becom e m ore p reva le n t in Wes te rn p op -

t
e
M
is h o sp it aliz e d b e cau se o f an u la t ion s , s p e ci ca lly in ce rt a in p a t ie n t
grou p s s u ch a s tra n sp la n t recip ien ts . It is

d
e xace rb at io n o f h e art f ailu re

n
on e of t h e few m e d ica l con d it ion s for

a
w it h w o rse n in g e d e m a an d

s
w h ich p h ys icia n s h ave a n ea rly com p lete

i
t
i
r
p ro g re ssive d ysp n e a. On h o s- u n d e rs t a n d in g of t h e ca u s a t ive a n d n e c-

h
t
r
p it al st ay d ay n u m b e r 2, sym p - es sa ry fa ctor for its d evelop m e n t , in t h is

a
o
ca se a s eru m u ra te con ce n t ra tion a bove

e
t o m s le ad in g t o ad m issio n

t
s
t h e s a t u ra t ion t h re s h old , or h yp e ru ri-

O
w e re sig n i can t ly im p ro ve d . Ho w e ve r in t h e p rio r 12 h o u rs, ce m ia . Th is u n d e rs t a n d in g of t h e e t iol-

4
h e h as d e ve lo p e d a re d , w arm , sw o lle n , an d e xt re m e ly

N
ogy a n d t h era p eu t ic t a rge t of t h e d is ea se

O
h a s n ot t ra n s la t e d in t o a d e q u a t e m a n -

I
t e n d e r rig h t an k le .

T
C
a ge m e n t fo r t h e m a jo rit y o f p a t ie n t s

E
A n art h ro ce n t e sis o f t h e aff e ct e d jo in t yie ld s clo u d y u id

S
w it h gou t be ca u s e of a com bin a t ion of
t h at is p o sit ive f o r t h e p re se n ce o f n e g at ive ly b ire f rin g e n t fa ctors, in clu d in g in com p le te kn ow le d ge
n e e d le -sh ap e d cryst als (Fig . 20.1 ). A jo in t g lu co co rt ico id of th e ba s ic t h era p e u tic p rin cip les of t h e
in je ct io n w as d e laye d an d o n ly an alg e sic t re at m e n t alo n g d is e a s e a n d t h e grow in g com p le xit y of
p a t ie n t s w it h gou t , d rive n by m u lt ip le
w it h lo w -d o se o ral co lch icin e w as p ro vid e d . A t 48 h o u rs t h e
co m o rb id it ie s o r p o lyp h a r m a cy. Un t il
syn o vial u id cu lt u re w as re p o rt e d p o sit ive f o r g ro w t h o f recen t ly, a s ca rcity of th era p eu tic op tion s
Kle b sie lla sp p . Th e p at ie n t im p ro ve d w it h an t ib io t ic for gou t a d d e d t o t h e s e ch a lle n ge s , bu t
t h e rap y, re p e at e d jo in t asp irat io n s, lo w -d o se co lch icin e , th a t p a n ora m a h a s s t a rt ed t o ch a n ge.
an d an alg e sics.
EPIDEMIOLOGY
Go u t is t h e m o s t co m m o n in a m m a -
t ory a rt h rit is in t h e Un it e d St a t e s : a ccord in g t o t h e m os t re ce n t e s t im a t e by t h e
Na t ion a l Art h rit is Da t a Wo rkgrou p , u s in g 1996 d a t a from t h e Na t io n a l He a lt h
In t e rview Su rvey (NHIS) a n d Na t io n a l He a lt h a n d Nu t rit ion Exa m in a t io n Su r-
vey (NHANES), 3.0 m illio n a d u lt s old e r t h a n 18 ye a rs h a d go u t in t h e p revio u s
ye a r a n d 6.1 m illion a d u lt s old e r t h a n 20 ye a rs h a d gou t a t s om e p o in t of t h e ir
live s . Th e fre q u e n cy ra t e s h a ve cle a r ly b e e n in cre a s in g in t h e la s t d e ca d e s ,
w it h a cu rre n t e s t im a t e d p reva le n ce a t 940 p e r 100,000 a d u lt s old e r t h a n 18
ye a rs (1 ).

183
184 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
Figure 20 .1 Needle-shaped monosodium urate crystals showing charac-
teristic negative birefringence. (Axis of the polarizer points at four O’clock
and crystals are predominantly yellow at that direction; perpendicular crys-
tals are predominantly blue.) Courtesy of H. Ralph Schumacher, Jr., M.D.,
and Janet Dinnella, University of Pennsylvania (http:/ / www.med.upenn.
edu/ synovium. Accessed June 6, 2011).
CLINICAL POINTS
• Ea rly in t h e d ise a se co u rse ,
g o u t is ch a ra ct e rize d b y
a cu t e a t t a cks o f a rt h rit is
( a re s) a n d a sym p t o m a t ic
in t e rva ls. If t h e d ise a se
g o e s u n t re a t e d , it m o rp h s
in t o a ch ro n ic d e fo rm in g
a rt h rit is w it h t o p h i.
• Common precipitants of
gout ares include acute
illnesses, alcohol intake, star-
vation, excessive intake of
purines, and use of certain
medications (allopurinol,
diuretics, cyclosporine).
• Go u t a re s in it ia lly in vo lve
t h e lo w e r e xt re m it y jo in t s
a n d p e a k in in t e n sit y
w it h in 24 h o u rs.
• When starting urate-lowering
t h e ra p y fo r g o u t , it sh o u ld
a lw a ys b e a cco m p a n ie d b y
p ro p h yla ct ic t h e ra p y fo r
g o u t a re s (n o n st e ro id a l
a n t i-in a m m a t o ry d ru g s
(NSAIDs), g lu co co rt ico id s,
o r lo w -d o se co lch icin e ).
• Ca lciu m p yro p h o sp h a t e
d e p o sit io n d ise a se ca n
p re se n t a s a cu t e a rt h rit is
(p se u d o g o u t ), a n in a m -
m a t o ry su b a cu t e p o lya r-
t h rit is (p se u d o rh e u m at o id
art h rit is), d e g e n e ra t ive
jo in t d ise a se (p se u d o -
o st e o art h rit is), sp in a l
d ise a se , a n d a d e st ru ct ive
a rt h rit is re se m b lin g a
n e u ro p a t h ic a rt h rit is.
World w id e, d a t a a bou t m e a s u re s of d is e a s e fre -
q u e n cy a n d t im e t re n d s a re h e t e roge n e ou s . It is u n cle a r
if t h e s e va ria t ion s a re be ca u s e of t ru e d iffe re n ce s in
fre q u e n cie s or h e t e roge n e o u s go u t d e n it io n s a n d
m e t h od s of d a t a colle ct ion . Th e p reva le n ce of gou t in
t h e Un it e d Kin gd om in 1993 s e e m e d t o h a ve t rip le d
w h e n com p a re d w it h t h a t in t h e 1970s . Ot h e r gou t
h igh -p reva le n ce p op u la t ion s a re t h e Ma la yo -Polyn e -
s ia n s a n d New Ze a la n d Ma oris (clos e t o 10%). On t h e
ot h e r h a n d , re la t ive ly low d is e a s e fre q u e n cie s h a ve
be e n rep ort e d in Ch in a .
HYPERURICEMIA
Uric a cid , fou n d in s e ru m a s u ra t e , is t h e e n d p ro d u ct
of p u r in e m e t a bo lis m in h u m a n s . Th e a ccu m u la t io n
o f u ra t e b e yo n d it s s o lu b ilit y p o in t o f 6.8 m g/ d L
d e n e s h yp e r u rice m ia , a n e ce s s a ry bu t n ot s u f cie n t
fa ct o r for t h e d eve lop m e n t o f gou t . Gou t is t h e clin i-
ca l m a n ife s t a t io n o f t h e d e p o s it io n o f MSU crys t a ls in
t is s u e s .
Th e im p ort a n ce of h yp e ru rice m ia a s a ca u s a t ive fa ct or for gou t h a s be e n
corrobo ra t e d in p ro s p e ct ive s t u d ie s . As p a rt of t h e Norm a t ive Agin g St u d y, a
coh ort of 2,046 m e n w a s follow e d for 15 ye a rs (2 ). Th e ris k for gou t follow e d a
gra d ie n t d ep e n d in g on t h e in it ia l u ra t e leve l: w it h a n in it ia l leve l of m ore t h a n
9 m g/d L, t h e a n n u a l in cid e n ce ra t e w a s 4.9%. W h e n t h e in it ia l leve l w a s be t w e e n
7.0 a n d 8.9 m g/d L, t h e a n n u a l in cid e n ce ra t e w a s 0.5%, a n d n a lly, it w a s 0.1%
w it h u ra t e leve ls le s s t h a n 7.0 m g/d L. Th e im p ort a n ce of h yp e ru rice m ia in p re -
d ict in g gou t a t t a cks is lim it e d n ot on ly t o t h e in it ia l d ia gn os is , bu t a ls o t o t h e
m a n a ge m e n t , a s it h a s be e n d e m on s t ra t e d t h a t low s e ru m u ra t e leve ls p re d ict
fre e d om from re cu rre n ce of gou t a re s .
Uric a cid is s yn t h e s ize d in t h e live r from p u rin e com p ou n d s p rovid e d by
d ie t a n d t h e e n d o ge n o u s p a t h w a y o f p u r in e s yn t h e s is d e n ovo. It is t h e n
re le a s e d in t o t h e circu la t ion a lm os t e xclu s ive ly in it s s olu ble -form MSU, w h ich
is re a d ily a va ila ble fo r lt ra t io n in t h e p rox im a l t u b u le s o f t h e k id n ey. Tw o
m e ch a n is m s e xis t t h rou gh w h ich a n in d ivid u a l cou ld d eve lop h yp e ru rice m ia :
ove rp rod u ct ion (e xcre t ion of m ore t h a n 600 m g/d a y in t h e u rin e w h ile on a
p u rin e -fre e d ie t , a ccou n t in g for 10% t o 15% of ca s e s ) a n d u n d e re xcre t ion (e xcre -
t ion of le s s t h a n 400 m g/d a y, a ccou n t in g for 85% t o 90% of ca s e s ). In bot h ca s e s
t h e p roble m cou ld be p rim a ry (s e con d a ry t o e n zym a t ic in h e rit e d d is ord e rs of
u ra t e p rod u ct ion or d e fe ct s in re n a l e xcre t ion ) or s e con d a ry t o e xce s s ive p u rin e
t u rn ove r (d ie t , m a lign a n cie s ), m e d ica t ion s , or t oxin s . For a n e xp a n d e d ove r-
view of ca u s e s of h yp e ru rice m ia , s e e Ta ble 20.1 .
Aft e r a n e a rly com p le t e lt ra t io n in t h e glom e ru lu s , u ra t e u n d e rgoe s a n
e xt e n s ive re a bs orp t ion in t h e p roxim a l t u bu le la rge ly m e d ia t e d by a s p e ci c
orga n ic a n ion t ra n s p ort e r. Aft e r t h e rs t rou n d of re a bs orp t ion , a s e con d cycle
of s e cre t ion a n d fu rt h e r re a bs orp t ion occu rs in t h e d is t a l p ort ion s of t h e p rox-
im a l t u bu le s . Th e s e n a l s t ep s d e t e rm in e t h e n e t u ra t e e xcre t ion , t yp ica lly 8%
t o 12% of t h e in it ia lly lt e re d loa d .
On ce h yp e ru rice m ia e n s u e s , t h e p roba bilit y of d eve lop in g gou t d e p e n d s on
t h e con ce n t ra t ion of u ra t e in t h e t is s u e or join t a n d ot h e r p re d is p os in g fa ct ors
s u ch a s a low p H, low t e m p e ra t u re, p reviou s t ra u m a t o t h e join t , a n d la ck of
m obilit y (e.g., d u rin g s le ep , w h e n t h e re is a n in cre a s e d w a t e r re a bs orp t ion , a n d
con ce n t ra t ion of u ra t e ). Re ce n t a d va n ce s in u n d e rs t a n d in g h ow MSU crys t a ls
ca u s e t h e ch a ra ct e ris t ic gou t in a m m a t o ry re s p o n s e h ave be e n m a d e. Alon g
w it h ot h e r crys t a ls , s u ch a s ca lciu m pyrop h os p h a t e, s ilica , a n d a s be s t os , MSU
is in t e rn a lize d in t o p h a gocyt e s a n d s e n s e d by t h e in n a t e im m u n e s ys t e m a s a
 Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 185

Table 20.1 Causes of Hyperuricemia

INCREASED URIC ACID

PRODUCTION IMPAIRED URIC ACID EXCRETION
Primary
Id io p a t h ic Id io p a t h ic o r g e n e t ica lly d e t e rm in e d re n a l
h yp e ru rice m ia
En zym e d e cie n cie s le a d in g t o
a cce le ra t e d p u rin e n u cle o t id e
syn t h e sis: h yp o xa n t h in e -g u a n in e
p h o sp h o rib o sylt ra n sfe ra se (ca u se
o f Le sch –Nyh a n syn d ro m e ),
p h o sp h o rib o sylp yro p h o sp h a t e
syn t h e t a se (PRPP) o ve ra ct ivit y
Se co ndary
Exce ssive p u rin e d ie t in t a ke Re d u ce d re n a l fu n ct io n a l m a ss b e ca u se

e
n
o f ch ro n ic kid n e y d ise a se

o
B
Increased purine nucleotide turnover: In h ib it io n o f t u b u la r u ra t e se cre t io n

c
i
l
myeloproliferative and lymphoprolif- (o rg a n ic a cid o sis): la ct ic a cid o sis, ke t o -

o
b
erative diseases, psoriasis a cid o sis, e t h a n o l, p re e cla m p sia

a
t
e
Acce le ra t e d a d e n o sin e t rip h o sp h a t e In h ib it io n o f t u b u la r u ra t e se cre t io n

M
(ATP) d e g ra d a t io n : e t h a n o l in t a ke , (d ru g s): sa licyla t e s, t h ia zid e s,

d
t issu e h yp o xia , g lyco g e n st o ra g e cyclo sp o rin e , e t c.

n
a
d ise a se s En h a n ce d t u b u la r u ra t e re a b so rp t io n :

s
i
d e h yd ra t io n , d iu re t ic u se , in su lin

t
i
r
re sist a n ce

h
t
r
Un kn o w n m e ch a n ism : ch ro n ic le a d

a
o
e xp o su re , h yp e rt e n sio n , h yp e rp a ra t h y-

e
t
ro id ism , sa rco id o sis, b e ryllio sis

s
O
4
N
O
I
T
d a n ge r s ign a l in d ica t ive of t is s u e d a m a ge a n d re cogn ize d by a s e rie s of s op h is -

C
E
t ica t e d cyt os olic re cep t ors (3 ).

S
Th e e ffe ct o f d ie t a s a ris k fa ct o r fo r h yp e r u r ice m ia a n d go u t h a s b e e n
cla ri e d by ep id e m iologic evid e n ce. Cros s -s e ct ion a l a n a lys e s reve a l t h a t t ot a l
b e e r, liq u o r, m e a t , a n d s e a fo o d co n s u m p t io n w e re a s s o cia t e d w it h h igh e r
s e ru m u ric a cid leve ls . How eve r, t h e m a gn it u d e of t h e in cre a s e in s e ru m u ra t e
in m os t in d ivid u a ls p e r u n it o f in t a ke is re la t ive ly s m a ll. W in e, t ot a l p rot e in ,
a n d d a iry in t a ke h ave n ot be e n fou n d t o be a s s ocia t e d w it h h igh e r s e ru m u ra t e
leve ls . Th e e ffe ct of a lcoh ol in t a ke in in d u cin g a re s in p a t ie n t s w it h e s t a b-
lis h e d gou t is s ign i ca n t .
Fru ct os e in t a ke h a s ga t h e re d m u ch a t t e n t ion a s a fa ct or a s s ocia t e d w it h
h igh e r leve ls of s e ru m u ra t e, re n a l d is e a s e, a n d t h e d eve lop m e n t of h yp e rt e n -
s ion . Fru ct os e m a y in d u ce h yp e ru rice m ia t h rou gh d ep le t ion of a d e n os in e t ri-
p h os p h a t e a n d it s ra p id con ve rs ion in t o a d e n os in e m on op h os p h a t e, w h ich w ill
be la t e r ca t a bolize d in t o u ric a cid . Ep id e m iologic s t u d ie s h a ve e s t a blis h e d a n
a s s ocia t ion be t w e e n fru ct os e in t a ke a n d h yp e ru rice m ia a n d gou t .
Th e re a re s eve ra l m e d ica t ion s a n d t oxin s t h a t in u e n ce t h e re n a l h a n d lin g
of u ric a cid . As p irin h a s a d u a l e ffe ct on s e ru m u ric a cid leve ls , w it h h igh leve ls
of in t a ke (m ore t h a n 3 g/d ay) be in g u ricos u ric a n d low e r leve ls of in t a ke (75 t o
2,000 m g/d a y) p rom ot in g u ric a cid re t e n t ion . Diu re t ics (bot h loop a n d t h ia zid e s )
a re w e ll k n ow n t o b e a s s o cia t e d w it h h igh e r s e r u m u ra t e leve ls , p o s s ibly
t h rou gh volu m e con t ra ct ion a n d con cu rre n t s t im u la t ion of u ra t e re a bs orp t ion
a t t h e leve l of t h e u ra t e a bs orp t ion re ce p t or in t h e p roxim a l t u bu le s . Cyclos p orin e
a n d t a crolim u s a re w id e ly u s e d d ru gs for p os t t ra n s p la n t im m u n os u p p re s s ion
a n d a re s t ron gly a s s ocia t e d w it h t h e d eve lop m e n t of h yp e ru rice m ia a n d gou t ;
186 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e
PATIENT ASSESSMENT
• When approaching patients
in w h ich a cryst a l a rt h rit is
is in t h e d iffe re n t ia l, a
jo in t a sp ira t io n w it h
m icro sco p ic e xa m in a t io n
u n d e r p o la rize d lig h t
sh o u ld b e p e rfo rm e d
w h e n e ve r p o ssib le .
• Se ru m u ra t e le ve ls sh o u ld
n o t b e u t ilize d fo r t h e
e va lu a t io n o r a sse ssm e n t
o f su sp e ct e d g o u t a re s.
• As se p t ic a rt h rit is is
u su a lly in t h e d iffe re n t ia l
o f cryst a l a rt h rit id e s, g ra m
st a in a n d cu lt u re o f u id
a sp ira t e s sh o u ld u su a lly
b e p e rfo rm e d , e ve n in
ca se s in w h ich cryst a ls
a re re a d ily id e n t i e d .
• Th e d ia g n o sis o f ca lciu m
p yro p h o sp h a t e d e p o sit io n
d ise a se ca n b e su p p o rt e d
b y t h e n d in g o f n e
ca rt ila g e ca lci ca t io n
(ch o n d ro ca lcin o sis) in
ra d io g ra p h s o f t h e
a ffe ct e d jo in t s.
ot h e r ch e m ica ls a s s ocia t e d w it h h yp e ru rice m ia a n d gou t in clu d e le a d , p yra zi-
n a m id e, e t h a m bu t ol, a n d n ia cin .
Exa mina tio n
Go u t is a ch ro n ic d is e a s e t h a t , if u n t re a t e d , t yp ica lly p ro gre s s e s ove r fo u r
p h a s e s : (a ) a s ym p t om a t ic h yp e r u r ice m ia , (b ) gou t a re s , (c) in t e rcrit ica l p e r i-
o d s , a n d (d ) ch ro n ic, u s u a lly t o p h a ce o u s go u t . Th is p rogre s s io n is illu s t ra t e d
in Figu re 20.2 . Typ ica lly, go u t a re s p re s e n t a s w a r m t h , s w e llin g, e ryt h e m a ,
a n d p a in o f a br u p t o n s e t in t h e in vo lve d jo in t , w it h s ym p t om s p e a kin g ove r 8
t o 12 h o u rs . Pa t ie n t s u s u a lly d e s cribe t h e p a in a s e x cr u cia t in g, a n d eve n t h e
s ligh t e s t p h ys ica l co n t a ct w it h t h e a ffe ct e d a re a (lik e t h a t p ro d u ce d by a b e d -
s h e e t ) ca n in d u ce m a rk e d s u ffe r in g. Nigh t t im e o n s e t o f s ym p t o m s is fre q u e n t .
Feve r, ch ills , a n d m a la is e a re co m m o n ly p a r t of t h e p re s e n t a t io n in p a t ie n t s
w it h p o lya r t icu la r a re s . In t h e e ld e r ly, a t yp ica l p re s e n t a t io n s t h a t in clu d e
d e lir iu m a re fre q u e n t . Co m m o n ly, t h e in vo lve d jo in t s a re in t h e fe e t (w it h t h e
r s t m e t a t a r s o p h a la n ge a l b e in g e ve n t u a lly in vo lve d in m o re t h a n 90% o f
ca s e s ), a n k le s , k n e e s , e lb ow s , w r is t s , a n d n ge r s . Th e p re d ile ct io n fo r t h e
low e r e x t re m it ie s is b e ca u s e o f low e r t e m p e ra t u re s in t h e s e jo in t s t h a t fa vo r
t h e p r e cip it a t io n o f MSU crys t a ls . Ex t ra -a r t icu la r s it e s a re a ls o in vo lve d ,
in clu d in g t h e b u rs a s (m a in ly t h e o le cra n o n a n d p re p a t e lla r b u r s a s ) a n d t e n -
d on s . Th e r s t a t t a ck is u s u a lly m on oa r t icu la r, a n d loca t e s a t t h e rs t m e t a -
t a r s o p h a la n ge a l join t in 50% o f t h e ca s e s . Pre cip it a n t s o f gou t a re s in clu d e
a cu t e illn e s s (t ra u m a , s e p s is , s u rge ry), a lco h o l in t a k e , s t a r va t io n , e x ce s s ive
in t a k e o f ce rt a in fo o d gro u p s (m a in ly p u r in e s ), a n d m e d ica t io n s . Dru gs s u ch
a s a llop u rin o l, t h ia z id e s , a n d cyclo s p or in e —w h ich a ffe ct s e r u m u ra t e leve ls
o r ca u s e bo d y u id s h ift s —h a ve b e e n a s s o cia t e d w it h gou t a re s . Un t re a t e d
a t t a cks fre q u e n t ly re s olve ove r 3 t o 10 d a ys , s o m e t im e s w it h e xfo lia t io n of t h e
ove r lyin g s k in .
Th e clin ica l cou rs e of gou t is ch a ra ct e rize d by a n a m e liora t ion or com p le t e
d is a p p e a ra n ce o f s ym p t o m s d u r in g t h e in t e rcrit ica l p e r io d . How eve r, if t h e
d is e a s e p rogre s s e s in t o ch ron ic gou t , t h e le n gt h of t h e s e in t e rcrit ica l p e riod s
s h ort e n s a n d ch ron ic join t p a in p e rs is t s eve n d u rin g t h e s e in t e rcrit ica l p e riod s
(Fig. 20.2 ). It is n ot in fre q u e n t t o re cove r MSU crys t a ls from a s p ira t e s of a p revi-
ou s ly a ffe ct e d join t d u rin g t h e in t e rcrit ica l p e riod .
Ch ron ic gou t is ch a ra ct e rize d by t h e u n re m it t in g n a t u re of t h e s ym p t om s ,
d e s t ru ct ive a rt h rit is , a n d t h e id e n t i a ble d ep os it ion of s olid u ric a cid in t is s u e s
Over time, untreated, chronic hyperuricemia increases
body urate stores, advancing the severity of the disease
Painful
Painless Intercritical
Intercritical
Segments
Segments
Flares last longer
Flares occur
more often
n
i
a
P
Intercritical
segments decrease
Persistent pain
and stiffness
Asymptomatic Acute Flares Advanced
Hyperuricemia Time Gout
Adapted from Klippel et al, eds. In: P rim e r o n th e Rh e u m a tic Dis e a s e s . 12th ed.
Arthritis Foundation; 2001:313.
Figure 20 .2 Evolution of hyperuricemia a nd gout.
 Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 187

(t op h i). At t h is s t a ge t h e in volve d join t s re m a in p e r s is t e n t ly u n com for t a ble,

s t iff, a n d sw o lle n . Th e con d it ion m a y m im ic ot h e r in a m m a t ory a rt h rit id e s ,
s u ch a s rh e u m a t o id a rt h r it is . Su p e r im p o s e d a cu t e a re s , w h ich a re u s u a lly
p olya rt icu la r a n d a d d it ive, s t ill occu r. Top h i a p p e a r a s a fu n ct ion of t h e d egre e
a n d d u ra t ion of u n t re a t e d h yp e ru rice m ia , u s u a lly ove r e xt e n s or s u rfa ce s (fore -
a rm s a n d t h e Ach ille s t e n d on ) a n d p re s s u re p oin t s , t yp ica lly in t h e n ge rs ,
w ris t s , kn e e s , a n d ole cra n on bu rs a s .

Studie s
Th e d ia gn os is of gou t is s t ron gly s u p p ort e d by t h e com bin a t ion of a cla s s ica l
clin ica l p re s e n t a t ion (m on oa rt h rit is a n d t op h i) a lon g w it h evid e n ce of h yp e ru ri-
ce m ia a n d clin ica l re s p on s e t o colch icin e, NSAIDs , or glu cocort icoid s . How eve r,
it is ve ry im p ort a n t t o e m p h a s ize t h a t e a ch on e of t h e s e d ia gn os t ic con s id e ra -
t ion s a re im p e rfe ct a n d t h a t t h e d ia gn os is ca n on ly be re lia bly e s t a blis h e d by t h e
id e n t i ca t ion of n ega t ive ly bire frin ge n t n e e d le -s h a p e d MSU crys t a ls from a n

e
a ffe ct e d join t or t is s u e.

n
o
Th e m os t com m on w ay of id e n t ifyin g MSU crys t a ls in p a t ie n t s s u s p e ct e d

B
c
of h a vin g a gou t a re is t h rou gh s yn ovia l u id a s p ira t ion from a n a ffe ct e d join t .

i
l
o
Th e u id obt a in e d from join t s a ffe ct e d by gou t is u s u a lly t u rbid w it h a ye llow

b
a
t in ge, bu t in e xt re m e ca s e s , it is t h ick a n d ch a lky, w it h a w h it e colora t ion . Th e

t
e
M
ce ll cou n t s a re u s u a lly in t h e in a m m a t ory ra n ge from 3,000/m m 3 u p t o gre a t e r
t h a n 50,000/ m m 3 , m o re t h a n 90% o f t h e s e ce lls b e in g p o lym o r p h o n u cle a r.

d
n
Oft e n , n e e d le -s h a p e d MSU crys t a ls ca n be id e n t i e d u n d e r s t a n d a rd ligh t

a
s
m icros cop y. How eve r, t h e op t im a l w a y t o vis u a lize MSU is t h rou gh p o la rize d

i
t
i
r
ligh t m icro s co p y, in w h ich n e e d le -s h a p e d MSU crys t a ls w ill a p p e a r w it h a

h
t
r
b righ t -ye llow or blu e co lo ra t ion (d e p e n d in g on if t h e a xis of t h e p o la rize r is

a
o
p a ra lle l or p e rp e n d icu la r t o t h e crys t a l) a ga in s t a p u rp le ba ckgrou n d (Fig. 20.1 ).

e
t
s
Ma n y t im e s t h e MSU crys t a ls a re fou n d in s id e a le u kocyt e t h a t is a t t e m p t in g

O
p h a gocyt os is . De s p it e be in g t h e s t a n d a rd w ay of d e t e rm in in g t h e p re s e n ce of a

4
N
go u t a re , s yn ovia l u id a n a lys is w it h crys t a l id e n t i ca t io n h a s s o m e d ra w -

O
I
ba cks . For e xa m p le, p a t ie n t s w it h gou t a n d h yp e ru rice m ia t h a t a re n ot h a vin g

T
C
a gou t a re cou ld h a ve MSU crys t a ls in t h e ir join t s yn ovia l u id (u s u a lly in t h e

E
S
con t e xt of a n on in a m m a t ory ce ll cou n t ). Als o, t h e a s p ira t ion of s m a ll join t s
co u ld be t e ch n ica lly ch a lle n gin g a n d t h e p ro ce d u re cou ld be d if cu lt t o p e r-
form for u n t ra in e d p ra ct it ion e rs . An ot h e r p ot e n t ia l is s u e is t h a t s yn ovia l u id
h a s t o be p ro m p t ly a n a lyze d a s ce lls co u n t s d e clin e a n d crys t a ls d ege n e ra t e
w h e n s a m p le p roce s s in g is d e laye d . Fin a lly, t h e id e n t i ca t ion of MSU crys t a ls
in p a rt ia lly t re a t e d p a t ie n t s or t h os e in w h ich t h e gou t a re is re s olvin g ca n be
ch a lle n gin g a n d re q u ire s lot s of p a t ie n ce on p a rt of t h e e xa m in e r. Bu rs a l u id ,
t op h i a s p ira t e s , a n d t is s u e s a m p le s ca n a ls o be a n a lyze d w it h t h e p u rp os e of
id e n t ifyin g MSU crys t a ls .
Me a s u re m e n t of s e ru m u ra t e is a n u n re lia ble p re d ict or of gou t a re s a n d
s h ou ld n o t be u s e d w it h d ia gn o s t ic p u rp o s e s a s u p t o 40% o f ca s e s o f a cu t e
gou t occu r in t h e s e t t in g of n orm ou rice m ia . On t h e ot h e r h a n d , h yp e ru rice m ia
is fre q u e n t in t h e ge n e ra l p op u la t ion a n d cou ld be p re s e n t in t h e s e t t in g of a n
a cu t e a rt h rit is s e con d a ry t o rh e u m a t oid d is e a s e, p s oria s is , in fe ct ion , a n d s o on .
Ot h e r a n cilla ry in ve s t iga t ion s s u ch a s t h e m e a s u re m e n t of u rin e u ra t e e xcre -
t ion a n d p la in ra d iogra p h s h ave a lim it e d role in d ia gn os t ic a n d m a n a ge m e n t
d e cis ion s .
Th e Am e rica n College of Rh e u m a t ology (form e rly Am e rica n Rh e u m a t is m
As s o cia t io n ) p ro p o s e d p re lim in a ry cr it e r ia fo r t h e d ia gn o s is o f a cu t e go u t y
a rt h rit is in 1977 (Ta ble 20.2 ; 4 ). De s p it e t h e ir w id e ly a d op t e d u s e a n d cit a t ion ,
t h os e w e re n eve r va lid a t e d , a n d im p or t a n t lim it a t io n s in t h e ir p e rform a n ce
h a ve be e n re cogn ize d . More re ce n t ly, t h e Eu rop e a n Le a gu e Aga in s t Rh e u m a -
t is m h a s p rop os e d re com m e n d a t ion s for t h e d ia gn os is of gou t t h a t t ra n s la t e
 188 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Table 20.2 Rules for t he Classi cat ion and Diagnosis of Gout

ARA PRELIMINARY
CLASSIFICATION CRITERIA EULAR EVIDENCE-BASED DIAGNOSIS OF GOUT IN
FOR ACUTE GOUTY RECOMMENDATIONS FOR PATIENTS WITH ACUTE
ARTHRITIS (1977) GOUT DIAGNOSIS (2006) MONOARTHRITIS (2010)
Co n t e xt Acu t e a rt h rit is ( a re s) An y g o u t Community-based undiagnosed
monoa rthritis
Ru le o r 1. Mo n o so d iu m u ra t e cryst a ls 1. Ra p id (6–12 h o u rs) 1. Ma le se x (2 p o in t s)
recommendations in t h e jo in t u id ; o r d e ve lo p m e n t o f se ve re 2. Pre vio u s p a t ie n t
2. To p h u s p ro ve n t o co n t a in p a in , sw e llin g , e ryt h e m a re p o rt e d —a t t a ck (2 p o in t s)
u ra t e cryst a ls; o r is h ig h ly su g g e st ive , b u t 3. On se t w it h in 1 d a y
3. Six o f t h e fo llo w in g : n o t sp e ci c fo r g o u t (0.5 p o in t s)
• Mo re t h a n o n e a t t a ck o f 2. Fo r t yp ica l p re se n t a tio n s, 4. Jo in t re d n e ss (1 p o in t )
a cu t e a rt h rit is clin ica l d ia g n o sis is 5. First MTP in vo lve m e n t
• Ma xim a l in a m m a t io n re a so n a b ly a ccu ra t e (2.5 p o in t s)
d e ve lo p e d w it h in 1 d a y 3. MSU cryst a ls in syn o via l 6. Hyp e rt e n sio n o r 1 cardio-
• At t a ck o f m o n o a rt icu la r u id o f t o p h u s co n rm s vascular diseasesa (1.5 points)
S
E
a rt h rit is gout 7. Se ru m u ra t e 5.88 m g /d L
C
T
• Jo in t re d n e ss 4. Ro u t in e se a rch fo r MSU (3.5 p o in t s)
I
O
• First MTP jo in t p a in fu l cryst a ls in d ia g n o se d • Le ss t h a n 4 p o in t s: g o u t
N
o r sw o lle n jo in t s is re co m m e n d e d p re va le n ce 2.8%
4
• Un ila t e ra l a t t a ck in vo lv- 5. Id e n t i ca t io n o f MSU • More t ha n 4 t o 8 p oin t s:
O
in g rst MTP jo in t crystals from asymptomatic go ut pre va len ce 27%
s
t
e
• Su sp e ct e d t o p h u s joints allows diagnosis in • Mo re t h a n 8 p o in t s: g o u t
o
• Hyp e ru rice m ia intercritical periods p re va le n ce 80.4%
a
r
• Asym m e t ric sw e llin g 6. Gra m st a in a n d cu lt u re
t
h
r
w it h in a jo in t (ra d io - sh o u ld b e d o n e in jo in t s
i
t
i
g ra p h s) su sp e ct e d t o h a ve g o u t
s
a
• Su b co rt ica l cyst s w it h o u t 7. Se ru m u ra t e d o n o t
n
e ro sio n s (ra d io g ra p h s) co n rm o r e xclu d e g o u t
d
M
• Ne g a t ive cu lt u re s d u rin g 8. Re n a l u ra t e e xcre t io n
e
a cu t e e p iso d e sh o u ld b e co n sid e re d in
t
a
ce rt a in p a t ie n t s
b
o
9. Ra d io g ra p h s se ld o m a re
l
i
c
n o t u se fu l in a cu t e g o u t
B
10. Risk fa ct o rs a n d co m o rb id -
o
n
it ie s sh o u ld b e a sse sse d
e
Pe rfo rm a n ce Se n sit ivit y 88% No t p ro vid e d Are a u n d e r t h e cu rve 0.87
Sp e ci cit y 80%

ARA, Am e rica n Rh e u m a t ism Asso cia t io n (cu rre n t ly Am e rica n Co lle g e o f Rh e u m a t o lo g y); EULAR, Eu ro p e a n Le a g u e Ag a in st Rh e u m a t ism ; MSU,
m o n o so d iu m u ra t e ; MTP, m e t a t a rso p h a la n g e a l.
a
An g in a p e ct o ris, m yo ca rd ia l in fa rct io n , h e a rt fa ilu re , ce re b ro va scu la r a ccid e n t , t ra n sie n t isch e m ic a t t a ck, o r p e rip h e ra l va scu la r d ise a se .
Ta b le a d a p t e d fro m re fe re n ce s 4 –6 .

in t o a d ia gn os t ic ru le (5 ). In a d d it ion , a Du t ch p rim a ry ca re grou p d eve lop e d a

d ia gn os t ic ru le for id e n t i ca t ion of gou t in p a t ie n t s w it h m on oa rt h rit is w it h -
o u t t h e n e e d of a n a rt h roce n t e s is t h a t cou ld be of gre a t u s e fu ln e s s t o clin i-
cia n s in co m m u n it ie s w it h ou t a cce s s t o p ro m p t s yn ovia l u id a n a lys is (Ta ble
20.2 ; 6 ).

DIFFERENTIAL DIAGNOSIS
Gou t a re s ca n be m im icke d by ot h e r in a m m a t ory a n d in fe ct iou s con d it ion s ,
m a in ly s e p t ic a rt h rit is (Ta ble 20.3 ). Th e clin ica l d iffe re n t ia t ion be t w e e n t h e s e
con d it ion s ca n be d if cu lt in t h e im m u n e -s u p p re s s e d , e ld e rly, or s u bje ct s w it h
m u lt ip le com orbid it ie s . In t h e s e s e t t in gs , bot h con d it ion s ca n be p olya rt icu la r
a n d a s s ocia t e d w it h p rom in e n t s ys t e m ic m a n ife s t a t ion s s u ch a s feve r, ch ills ,
 Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 189

NOT TO BE MISSED Table 20.3 Different ial Diagnosis of Gout

• To p h i a re MSU t issu e GOUT FLARES CHRONIC GOUT

d e p o sit s t h a t u su a lly
lo ca t e su b cu t a n e o u sly Se p t ic a rt h rit is Rh e u m a t o id a rt h rit is
o ve r e xt e n so r su rfa ce s Pse u d o g o u t a n d o t h e r cryst a l a rt h rit id e s Ost e o a rt h rit is
(a rm s a n d Ach ille s
t e n d o n s), a n d p re ssu re Tra u m a Ca lciu m p yro p h o sp h a t e d e p o sit io n
p o in t s in t h e h a n d s, d ise a se (p se u d o rh e u m a t o id a rt h rit is)
w rist s, kn e e s, a n d Rh e u m a t o id a rt h rit is Pso ria t ic a rt h rit is
o le cra n o n b u rsa s.
Acu t e se ro n e g a t ive a rt h rit is Po lym ya lg ia rh e u m a t ica
• In p a t ie n t s w h o a re
e ld e rly, ch ro n ica lly ill, Ne u ro p a t h ic a rt h rit is
a n d h o sp it a lize d , g o u t
a re s fre q u e n t ly a re
p o lya rt icu la r a n d ca n
b e a cco m p a n ie d b y
p ro m in e n t syst e m ic a n d con fu s ion . It is im p ort a n t t o n ot ice t h a t bot h e n t it ie s ca n coe xis t in t h e

e
sym p t o m s, in clu d in g

n
s a m e p a t ie n t , a s join t a s p ira t e s con t a in in g gou t or p s e u d ogou t crys t a ls h a ve

o
fe ve r a n d ch ills.

B
a ls o b e e n re p o r t e d p o s it ive fo r b a ct e r ia l cu lt u re s . Se p t ic a r t h r it is ca n a ls o

c
• Medica tio n nonco mpliance

i
p re s e n t in p a t ie n t s w it h e s t a blis h e d gou t , m im ickin g a n ew a re of t h e d is e a s e.

l
o
is a very frequ ent ca use of

b
For t h is re a s on , gra m s t a in a n d cu lt u re s a re re com m e n d e d a s p a rt of t h e rou -

a
gou t that is re sistan t to

t
t in e la bora t o ry w ork-u p o f s yn ovia l u id a s p ira t e d from a p a t ie n t in w h om

e
ura te -low ering the rap y.

M
gou t is s u s p e ct e d .

d
Ot h e r con d it ion s t h a t ca n m im ic gou t a re s in clu d e t ra u m a , p s e u d ogou t

n
a
a n d ot h e r crys t a l a rt h rit id e s , or a re s of ot h e r in a m m a t ory a rt h rit id e s , s u ch

s
i
t
a s s e ron ega t ive s p on d yloa rt h rop a t h ie s a n d rh e u m a t oid a rt h rit is . Ch ron ic gou t

i
r
h
co u ld b e d if cu lt t o d iffe re n t ia t e fro m o t h e r in a m m a t o ry a rt h rit id e s , m o s t

t
r
a
n ot a bly rh e u m a t oid a rt h rit is . Top h i cou ld be m is t a ke n a s rh e u m a t oid n od u le s

o
e
in t h a t s a m e co n t e x t . In e ld e r ly p a t ie n t s w it h e x t re m e d is a b ilit y ca u s e d by

t
s
O
ch ron ic p olya rt icu la r gou t , t h e clin ica l p ict u re cou ld be con fu s e d w it h p olym y-

4
a lgia rh e u m a t ica , s e ron ega t ive a rt h rit is , or d ep re s s ion .

N
O
I
T
C
Tre a tme nt

E
S
Th e m a n a ge m e n t goa ls in gou t d iffe r d ep e n d in g on t h e s e t t in g. In a cu t e gou t t h e
t re a t m e n t is a im e d a t re s olvin g t h e a re s of p rom in e n t p a in a n d in a m m a t ion .
In t h e in t e rcrit ica l p e riod s t h e goa ls a re t o m a in t a in u ric a cid a t s u bs a t u ra t ion
leve ls , p reve n t in g t h e occu rre n ce of n ew a re s a n d t h e d eve lop m e n t of ch ron ic
t op h a ce ou s gou t . A lis t of t h e a ge n t s ava ila ble for m a n a ge m e n t of gou t is p re -
s e n t e d in Ta ble 20.4 .

MANAGEMENT OF GOUT FLARES

Su cce s s in p rom p t ly a n d com p le t e ly a bort in g gou t a re s d e p e n d s on h ow e a rly
t h e p h a rm a cologic m a n a ge m e n t is in it ia t e d a n d con t in u in g it for a n a p p rop ri-
a t e a m ou n t of t im e. As a ge n e ra l ru le, lon g-t e rm u ra t e -low e rin g t h e ra py s h ou ld
n o t be in it ia t e d u n t il jo in t in a m m a t io n h a s co m p le t e ly re s o lve d . Pa t ie n t s
s h ou ld be in form e d a bou t re s olu t ion of a a re n ot be in g a cu re for t h e d is e a s e.
Mu lt ip le ora l a n d p a re n t e ra l n on s e le ct ive NSAIDs h a ve p rove d t o be e ffe c-
t ive t h e ra p ie s for gou t a re s . High d os a ge s a re u s e d in t h e rs t 3 t o 4 d a ys , fol-
low e d by a low e r m a in t e n a n ce d os e for a t ot a l of 7 t o 10 d a ys . Th e s e low e r
d os e s ca n a ls o be u s e d t o p reve n t re cu rre n ce of a t t a cks , a lt h ou gh t h e re is n o
co n t ro lle d evid e n ce t o s u p p o r t t h is a p p ro a ch . Ca u t io n s h o u ld b e e x e rcis e d
b e ca u s e of t h e w e ll-k n ow n ga s t ric, re n a l, ca rd ia c, h e m a t ologic, a n d h e p a t ic
t oxicit ie s of NSAIDs . Clos e m on it orin g or com p le t e avoid a n ce of NSAIDs is re c-
om m e n d e d in e ld e rly p a t ie n t s , u s e rs of w a rfa rin , a n d t h os e w it h ca rd ia c, re n a l,
or h e p a t ic d ys fu n ct ion .
 190 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Table 20.4 Therapeut ic Agent s for Management of Gout

MANAGEMENT OF ACUTE GOUT FLARES

• No n st e ro id a l a n t i-in a m m a t o ry d ru g s
• Ora l co lch icin e
• Ora l o r in t ra ve n o u s g lu co co rt ico id s
• Co syn t ro p in (ACTH)
PROPHYLAXIS DURING INITIATION OF URATE-LOWERING THERAPY
• No n st e ro id a l a n t i-in a m m a t o ry d ru g s
• Ora l co lch icin e
• Ora l g lu co co rt ico id s
URATE-LOWERING THERAPY
• Xa n t h in e o xid a se in h ib it o rs: a llo p u rin o l, fe b u xo st a t
• Urico su rics: p ro b e n e cid , su l n p yra zo n e
• Urica se s: p e g lo t ica se
IN DEVELOPMENT
• In t e rle u kin 1 in h ib it o rs fo r g o u t a re s a n d u ra t e -lo w e rin g p ro p h yla xis:
S
rilo n a ce p t , ca n a kin u m a b
E
C
• Se le ct ive u rico su rics: RDEA 594 (URAT-1)
T
I
O
N
4
O
Am o n g t h e s e le ct ive COX-2 in h ib it o rs , e t o rico x ib a n d lu m ira co x ib h a ve
s
t
e
be e n fou n d t o be e f ca ciou s a n d w e ll t ole ra t e d for m a n a ge m e n t of gou t a re
o
a
e p is od e s . Ne it h e r a ge n t is ava ila ble in t h e Un it e d St a t e s , bu t it s u gge s t s t h a t
r
t
h
a ge n t s in t h is ca t egory, s u ch a s ce le coxib, cou ld be u s e fu l for t h e t re a t m e n t of
r
i
t
gou t a re s . Sch e d u le d m a in t e n a n ce d os e s of NSAIDs ca n be u s e d a s p rop h yla ct ic
i
s
a
t h e ra py d u rin g in it ia t ion of u ra t e -low e rin g t h e ra py.
n
d
Colch icin e in t e rfe re s w it h m icrot u bu le a s s e m bly a n d t h rou gh t h is m e ch a -
M
n is m w it h p h a gocyt os is a n d ch e m ot a xis . It is m os t e ffe ct ive in con t rollin g gou t
e
t
a re s w h e n t a ke n w it h in t h e r s t 24 h ou rs a ft e r s ym p t om on s e t . Th e com -
a
b
m on ly a d voca t e d d os a ge of 0.6 m g ora lly eve ry h ou r u n t il “s ym p t om re s olu t ion
o
l
i
o r d ia rrh e a ” (t o a m a x im u m o f 6.0 m g in 12 h o u rs ) is ve ry o ft e n lim it e d by
c
B
p rom in e n t ga s t roin t e s t in a l s id e e ffe ct s , w it h n a u s e a , vom it in g, a n d d ia rrh e a
o
n
le a d in g t o d e h yd ra t ion a n d a n in com p le t e re s olu t ion of t h e a re. Th is a p p roa ch
e
t o m a n a ge m e n t of gou t a re s h a s be e n p rogre s s ive ly fa llin g ou t of favor.
Th e is s u e of colch icin e d os in g for gou t a re s h a s be e n cla ri e d by a ra n d -
o m ize d con t rolle d t ria l w h ich e s t a blis h e d t h a t a “low -d os e ” a p p roa ch o f col-
ch icin e (1.2 m g by m ou t h follow e d by 0.6 m g 1 h ou r la t e r) a ch ieve d com p a ra ble
s e ru m con ce n t ra t ion s of t h e d ru g a n d e f ca cy in t h e re s olu t ion of gou t a re
s ym p t o m s w h e n co n t ra s t e d w it h t h e “h igh -d o s e ” a p p ro a ch d e s cribe d a b ove.
Th is “low -d os e ” a p p roa ch h a d a s ign i ca n t ly low e r ra t e of ga s t roin t e s t in a l a n d
t ot a l a d ve rs e eve n t s (7 ). In t ra ve n ou s colch icin e h a s be e n lin ke d t o m u lt ip le
fa t a lit ie s a n d it s u s e is s t ron gly d is cou ra ge d .
Colch icin e is com m on ly u s e d a s a p rop h yla ct ic a ge n t t o p reve n t a re s . Th e
d o s a ge s u s e d in t h is s e t t in g a re b e t w e e n 0.6 t o 1.2 m g/ d a y o ra lly, b u t d o s e
re d u ct ion s m u s t be p e rform e d if t h e d ru g n e e d s t o be u s e d in t h e s e t t in g of
k id n ey d ys fu n ct ion . Ga s t roin t e s t in a l s id e e ffe ct s in clu d in g d ia rrh e a , n a u s e a ,
a n d vo m it in g ca n a ls o be p re s e n t a t t h e s e low e r d o s e s . W it h lo n g-t e rm u s e ,
n e u t rop e n ia , n e u rop a t h y, a n d a va cu ola r m yop a t h y ca n d eve lop . Th e s e s id e
e ffe ct s t e n d t o re s olve w it h d is con t in u a t ion of t h e d ru g.
In view of t h e in cre a s in g com p le xit y of t h e p a t ie n t s w it h gou t a re s , glu co-
cort icoid s a re be com in g m ore fre q u e n t ly u s e d w h e n NSAIDs or colch icin e a re
con t ra in d ica t e d . W h e n p a t ie n t s p re s e n t w it h a con rm e d m on o- or oligoa rt ic-
u la r gou t a re, a s p ira t ion of s yn ovia l u id follow e d by a n in t ra -a rt icu la r in je c-
t ion of a lon g-a ct in g glu cocort icoid m ay be a ll t h a t is n e ce s s a ry t o re s olve t h e
a re. It is ve ry im p ort a n t t o e m p h a s ize, h ow eve r, t h a t clin ica l ju d gm e n t s h ou ld
be e xe rcis e d in d e cid in g w h ich p a t ie n t s a re good ca n d id a t e s for t h is a p p roa ch ,
 Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 191

n a m e ly t h os e in w h om t h e clin ica l p re s e n t a t ion , m e d ica l h is t ory, a n d la bora -

t ory s t u d ie s m a ke t h e p os s ibilit y of s ep t ic a rt h rit is m in im a l.
Ora l co u r s e s o f t h e ra p y a re co m m o n ly d o n e w it h p re d n is o n e o r it s glu co -
co r t ico id e q u iva le n t a t d o s e s o f 30 t o 60 m g/ d a y. Ta p e r in g s h o u ld b e p e r fo r m e d
ove r t h e cou r s e of 10 t o 14 d a ys , a co m m on m is t a k e be in g t o a d m in is t e r ve ry
s h o r t co u r s e s o f glu co co r t ico id s (7 d a ys o r le s s ) w it h in co m p le t e re s o lu t io n
o r re cu r re n ce o f t h e go u t a re . Glu co co r t ico id -b a s e d re gim e n s a re e q u iva le n t
in e ffe ct ive n e s s t o t h o s e b a s e d o n NSAIDs , a n d p o s s ibly a s s o cia t e d w it h
fe w e r s h o r t - t e r m a d ve r s e e ve n t s (m a in ly u id r e t e n t io n , h y p e r t e n s io n ,
h yp e rglyce m ia , a n x ie t y, a n d in s o m n ia ). Th e co n ce r n a b o u t a d ve r s e e ffe ct s
fro m glu co co r t ico id s , a lb e it va lid , is o f le s s im p o r t a n ce give n t h e s h o r t -t e r m
co u r s e s t h e p a t ie n t s a re s u p p o s e d t o re ce ive . Th is is n o t t h e ca s e in p a t ie n t s
w it h re cu r re n t a cu t e a re s o r ch ro n ic go u t m a n a ge d w it h fre q u e n t d o s e s o f
glu co co r t ico id s .
Pa ra d oxica lly, t h e in je ct ion of d ep os it glu cocort icoid s t o re lieve in a m m a -
t ion on ra re occa s ion ca n in d u ce a n a cu t e ep is od e of s eve re p a in , in a m m a t ion ,
a n d sw e llin g s e con d a ry t o crys t a lliza t ion of t h e glu cocort icoid . Th e con d it ion

e
n
u s u a lly p re s e n t s w it h in 8 t o 12 h ou rs a ft e r t h e in je ct ion a n d h a s be e n d e s cribe d

o
B
m ore fre q u e n t ly in a s s ocia t ion w it h t ria m cin olon e h e xa ce t on id e p rep a ra t ion s .

c
i
l
Th e d ia gn os is ca n be s u p p ort e d by a s p ira t ion of s yn ovia l u id a n d vis u a liza t ion

o
b
of la rge, irregu la r, in t e n s e ly bire frin ge n t , irregu la r crys t a ls . Th e con d it ion is s e lf-

a
t
e
lim it e d , u s u a lly s u bs id in g w it h in 24 t o 48 h ou rs a ft e r t h e in je ct ion . An a lge s ics ,

M
NSAIDs , a n d ice p a cks cou ld be u s e d a s s ym p t om a t ic t h e ra p y.

d
n
Co r t ico t ro p in (ACTH) s h a re s t h e s a m e p ro le o f in d ica t io n s a s s ys t e m ic

a
glu co co r t ico id s , n a m e ly p o lya r t icu la r a re s in w h ich NSAIDs a re n o t e ffe ct ive

s
i
t
i
o r co n t ra in d ica t e d . How eve r, ACTH is co s t ly co m p a re d w it h glu co co r t ico id s

r
h
t
a n d n o t w id e ly a va ila ble . It s m e ch a n is m o f a ct io n s e e m s t o b e t h ro u gh s t im -

r
a
o
u la t io n o f e n d o ge n o u s a d r e n a l h o r m o n e s , b u t d ir e ct a n t i- in a m m a t o r y

e
t
e ffe ct s a t t h e a ffe ct e d s it e co u ld a ls o b e im p lica t e d . Th e d r u g is a va ila ble fo r

s
O
s u b cu t a n e o u s o r in t ra m u s cu la r a d m in is t ra t io n , a n d a s in gle d o s e o f 40 IU h a s

4
b e e n fo u n d t o b e ra p id , e f cie n t , a n d w e ll t o le ra t e d eve n in p a t ie n t s t h a t a re

N
O
t a k in g m o d e r a t e d o s e s o f glu c o c o r t ic o id s . Ad ve r s e e ffe c t s in c lu d e m ild

I
T
h yp o k a le m ia , u id re t e n t io n , h yp e rglyce m ia , a n d t h e d eve lo p m e n t o f re b o u n d

C
E
go u t a re s , t h e la t t e r b e in g co n t ro lle d by t h e a d m in is t ra t io n o f o t h e r p ro p h y-

S
la ct ic t h e ra p y.

URATE- LOWERING THERAPY FOR HYPERURICEMIA AND GOUT

Th e d e cis io n o f in it ia t in g ch ro n ic t h e ra p y fo r h yp e r u r ice m ia ca u s in g go u t
s h o u ld b e in d ivid u a liz e d fo r e a ch ca s e a s t h e re is n o evid e n ce t o t h is d a t e
rega rd in g a be n e t of t re a t in g a s ym p t om a t ic h yp e ru rice m ia a lon e. How eve r,
p a t ie n t s n e e d t o u n d e rs t a n d t h a t ve ry h igh leve ls of s e ru m u ra t e p la ce t h e m
a t a ve ry h igh ris k for in cid e n t gou t a n d p os s ibly ca rd iova s cu la r eve n t s , a n d a t
le a s t life s t yle ch a n ge s (re d u ct io n in a lco h o l in t a k e , d ie t a ry ch a n ge s , w e igh t
los s ) s h ou ld be con s id e re d . Aft e r a n in it ia l gou t a re, u ra t e -low e rin g t h e ra py
cou ld b e w it h h e ld give n t h a t jo in t d a m a ge is u n lik e ly t o o ccu r in p a t ie n t s w h o
re m a in a s ym p t om a t ic, bu t s u ch t h e ra p y is a d voca t e d in p a t ie n t s w it h t w o or
m o re a re s , o n e a re in t h e s e t t in g of ve ry h igh s e ru m u ra t e ( 8.0 m g/d L), or
t op h i.
Th e con com it a n t in it ia t ion of p rop h yla ct ic t h e ra p y w it h colch icin e, glu co-
cort icoid s , or NSAIDs a lon g w it h u ra t e -low e rin g t h e ra py is s t ron gly a d voca t e d
t o p reve n t a re s . Prop h yla ct ic t h e ra p y s h ou ld be m a in t a in e d for a m in im u m of
6 m on t h s a ft e r u ra t e -low e rin g t h e ra py in it ia t ion or t h e occu rre n ce of t h e la s t
gou t a re. Ura t e -low e rin g t h e ra py s h ou ld be in t e n s i e d u n t il t h e goa l of a s u b-
s a t u ra t io n con ce n t ra t io n of u ric a cid a t 6 m g/d L is re a ch e d . Mo re a ggre s s ive
goa ls m igh t be n e ce s s a ry for p a t ie n t s w it h la rge t is s u e d e p os it s of u ra t e, s u ch
a s t h os e w it h t op h i or m u lt ip le ra d iogra p h ic e ros ion s .
 192 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

ATP GTP Allop u rin ol is t h e m os t w id e ly u s e d u ra t e -low e rin g

a ge n t in view o f it s e f ca cy in ove r p ro d u ce r s a n d
O
u n d e re xcre t ors of u ric a cid , e a s y d os in g regim e n , low
O O
cos t , a n d a ccep t a ble s a fe t y p ro le. Allop u rin ol a n d it s
Xanthine N Xanthine H
HN
N
oxidase HN oxidase HN N m e t a bolit e oxyp u rin ol a re s u bs t ra t e s of xa n t h in e oxi-
N O N N
O
d a s e, a n d a ct by in h ibit in g xa n t h in e oxid a s e, blockin g
N H N
H H O N
H H t h e con ve rs ion of h yp oxa n t h in e t o xa n t h in e a n d s u b-
Hypoxanthine Xanthine Uric acid s e q u e n t ly t h e la t t e r t o u ric a cid (Fig. 20.3 ). In it ia l d os e s
of a llop u rin ol ra n ge be t w e e n 100 a n d 300 m g/d a y, w it h
low e r d o s e s p re fe r re d b e ca u s e o f a p e rce ive d low e r
in cid e n ce o f a re s a n d h yp e r s e n s it ivit y r e a ct io n s .
OH OH Be s id e s , s o m e p a t ie n t s m a y re a ch s e ru m u ra t e goa ls
Xanthine w it h low d os e s of 100 t o 200 m g/d a y. Eve n low e r s t a rt -
N N
N
oxidase
N in g d os e s of 50 t o 100 m g/d a y s h ou ld be u s e d in e ld e rly
N N
H
HO N N
H
p a t ie n t s a n d t h os e w it h im p a ire d kid n ey fu n ct ion . It is
im p o r t a n t t o m o n it o r s e r u m u ra t e leve ls eve ry 2 t o
Allopurinol Oxypurinol
4 w e e ks for d os a ge a d ju s t m e n t s u n t il t h e t a rge t con -
S
E
Figure 20 .3 Xa nthine oxida se inhibitors mecha nism of a ction. ce n t ra t ion is re a ch e d . Th e m os t com m on ly u s e d d os a ge
C
T
Allopurinol is a structura l a na logue of hypoxa nthine. (Simila rity is high- of 300 m g/d ay a ch ieve s t a rge t s e ru m u ra t e con ce n t ra -
I
O
lighted in blue.) Oxida tion of a llopurinol yields oxypurinol, a noncom-
N
t ion s in on ly h a lf t h e p a t ie n t s a n d d os a ge s a s h igh a s
petitive inhibitor of xa nthine oxida se. (At low doses, a llopurinol is a
4
competitive inhibitor of xa nthine oxida se.) Inhibition of xa nthine oxida se
900 m g/d a y a re n e ce s s a ry in m a n y p a t ie n t s , a lt h ou gh
O
t h is d o s e e x ce e d s t h e FDA-a p p rove d d a ily d o s e o f
s
decrea ses the production of uric a cid by inhibiting two steps in its syn-
t
e
thesis. The increa sed pla sma levels of xa nthine a nd hypoxa nthine a re 800 m g/ d a y. How eve r, b e fo re e s ca la t in g t h e d o s e t o
o
a
tolera ted beca use these meta bolites a re more soluble tha n uric a cid. ve ry h igh leve ls , a d h e re n ce s h ou ld be a s s e s s e d be ca u s e
r
t
(With permission from Gola n DE, Ta shjia n AH, Armstrong EJ. Principles of a s m a n y a s 50% of p a t ie n t s a re n on a d h e re n t w it h t h e
h
r
Pha rma cology: The Pa thophysiologic Ba sis of Drug Therapy. 2nd ed.
i
t
m e d ica t io n , e s p e cia lly if t h ey a re h a vin g re cu r re n t
i
s
Ba ltimore: Wolters Kluwer Hea lth; 2008.)
a
gou t a re s .
n
d
Ad ve rs e re a ct ion s from a llop u rin ol a re u n com m on
M
a n d m ild . Th e m os t fre q u e n t t oxicit ie s a re ra s h , ga s t roin t e s t in a l in t ole ra n ce or
e
t
d ia rr h e a , h e a d a ch e, a n d le u cop e n ia . Ra s h e s ca n re cu r on re e xp os u re t o t h e
a
b
d ru g a n d a re a n im p ort a n t ca u s e of in t ole ra n ce. Allop u rin ol d e s e n s it iza t ion
o
l
i
p rot ocols a re a va ila ble bu t in fre q u e n t ly u s e d s in ce a lt e rn a t ive s t o a llop u rin ol
c
B
a re n ow ava ila ble. Th e a llop u rin ol h yp e rs e n s it ivit y s yn d rom e is a n u n com m on
o
n
im m u n e -m e d ia t e d s eve re re a ct ion w it h a m ort a lit y of u p t o 20%. It is ch a ra c-
e
t e rize d by feve r, ra s h , a cu t e re n a l in s u f cie n cy, e os in op h ilia , h ep a t ic in ju ry, a n d
va s cu lit is . Th e m os t com m on ly id e n t i e d ris k fa ct or for it s occu rre n ce is kid -
n ey d ys fu n ct ion . Mu lt ip le d ru g in t e ra ct ion s cou ld be a n a d d it ion a l lim it in g fa c-
t or for t h e u s e of a llop u rin ol; n ot a ble a m on g t h e s e a re in cre a s e d leve ls of t h e o-
p h yllin e, w a rfa rin , a n d a za t h iop rin e. Th ia zid e d iu re t ics ca n in h ibit t h e e xcre t ion
of a llop u rin ol a n d p ot e n t ia t e t oxicit y. Fin a lly, a h igh in cid e n ce of s kin ra s h e s
h a s be e n d e s cr ibe d w it h t h e co m b in a t io n o f a m p icillin o r a m oxicillin a n d
a llop u rin ol.
Fe bu xos t a t is a n ora lly a d m in is t e re d , n on p u rin e s e le ct ive in h ibit or of xa n -
t h in e oxid a s e. Th e d r u g a ct s t h rou gh a ve ry s t a ble a n d lon g-live d e n zym e ’s
in h ibit ory in t e ra ct ion w it h bot h t h e oxid ize d a n d re d u ce d form s of t h e e n zym e
a n d a s t ron g in h ibit ion of s u bs t ra t e bin d in g. Fe bu xo s t a t , a t a p p rove d d os e s
ra n gin g from 40 t o 80 m g/d ay, is e f ca ciou s in re d u cin g s e ru m u ra t e in p a t ie n t s
w it h h yp e ru rice m ia a n d gou t , com p a rin g favora bly w it h xe d d os e s of a llop u -
rin ol in t h a t re s p e ct (8 ). Ea rly s a fe t y s ign a ls w it h re s p e ct t o live r t e s t a bn or-
m a lit ie s a n d ca rd iova s cu la r ou t com e s h a ve n ot be e n con rm e d in re ce n t la rge
p ros p e ct ive t ria ls , bu t n e e d t o be fu rt h e r m on it ore d . Give n cos t con s id e ra t ion s ,
fe bu xos t a t w ill like ly n d a n ich e in p a t ie n t s w it h gou t w h o a re u n a ble t o u s e
a llop u rin ol be ca u s e of in t ole ra n ce s , a d ve rs e re a ct ion s , or d ru g–d ru g in t e ra c-
t ion s . In a d d it ion , p a t ie n t s w it h t op h a ce ou s gou t or w it h ve ry h igh s e ru m u ra t e
(SUA) leve ls (m ore t h a n 10 m g/d L) m a y a ls o be n e t from t h e h igh e r p ot e n cy of
fe bu xos t a t ve rs u s a llop u rin ol a t t h e xe d d os a ge s t e s t e d . Pa t ie n t s w it h ch ron ic
k id n ey d is e a s e a n d o rga n t ra n s p la n t a t io n s a re goo d fe b u xo s t a t ca n d id a t e s .
 Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 193

How eve r, a llop u rin ol give n it s cos t a n d e xp e rie n ce w it h u s e w ill like ly re m a in

a s t h e rs t -lin e d ru g for t h e m a n a ge m e n t of gou t in m os t p a t ie n t s .
Uricos u ric d ru gs a t t e m p t t o reve rt t h e m os t com m on p h ys iologic a bn orm a l-
it y in gou t , w h ich is u n d e re xcre t ion of u ric a cid . Probe n e cid a n d s u l n pyra zon e
a re u s e d in t e rn a t ion a lly. Ot h e r d ru gs w it h m ild u ricos u ric e ffe ct s in clu d e los a -
rt a n a n d fe n o bra t e. Mos t u ricos u ric a ge n t s a ct a t t h e leve l of t h e t ra n s p ort e r in
t h e p roxim a l t u bu le in a n on s e le ct ive m a n n e r. W h e n u s e d on id e a l ca n d id a t e s ,
p robe n e cid a n d s u l n pyra zon e a llow a m a jorit y of p a t ie n t s t o a ch ieve s e ru m
u ra t e goa ls . How eve r, s eve ra l lim it a t ion s a re e n cou n t e re d w h e n t ryin g t o u s e
u ricos u ric a ge n t s in p ra ct ice. Firs t , t h ey ra p id ly los e e ffe ct ive n e s s a s t h e glom e r-
u la r lt ra t ion ra t e (GFR) d rop s t o le s s t h a n 50 m L/m in u t e. Se con d , t h e ir u s e is
s t ron gly d is cou ra ge d in p a t ie n t s w it h h is t ory of re n a l ca lcu li, a s t h e u ricos u ric
a ge n t s m a y fu rt h e r p ro m o t e n e p h ro lit h ia s is . La s t ly, t h e ir u s e is n o t re co m -
m e n d e d in e ld e rly p a t ie n t s , t h os e on m u lt ip le m e d ica t ion s (be ca u s e of m u lt ip le
d ru g in t e ra ct ion s ), a n d t h os e w h o h ave t rou ble com p lyin g w it h m u lt ip le d a ily
d os e s . For e xa m p le , p robe n e cid h a s kn ow n in t e ra ct ion s w it h a za t h iop rin e ,
rifa m p in , s a licyla t e s , p e n icillin s , in d om e t h a cin , a n d h ep a rin . Probe n e cid is t h e

e
n
m os t w id e ly u s e d u ricos u ric; u s u a lly in it ia t e d a t a d os e of 500 m g ora lly t w ice a

o
B
d ay, t h e d os a ge ca n be s low ly in cre a s e d u p t o 3 g/d ay. Ad ve rs e e ffe ct s in clu d e

c
i
l
ga s t roin t e s t in a l in t o le ra n ce, ra s h , h e p a t ot oxicit y, gou t a re s , n e p h ro lit h ia s is ,

o
b
a n d n ep h rot ic s yn d rom e.

a
t
e
Ura t e ox id a s e (u rica s e ) is a p o t e n t e n z ym e p re s e n t in a ll m a m m a ls b u t

M
h igh e r p rim a t e s a n d h u m a n s , w h ich con ve rt s s e ru m u ra t e in t o m ore s o lu ble

d
n
a lla n t oin . Non re com bin a n t (obt a in e d from A spergillus av us ) a n d re com bin a n t

a
fo rm s (o bt a in e d from Saccharom y ces cerev isiae) h a ve be e n u s e d e ffe ct ive ly a s

s
i
t
i
in t ra ve n o u s in fu s io n s in t h e p reve n t io n a n d t re a t m e n t o f t u m o r lys is s yn -

r
h
t
d ro m e. How eve r, t h e ir com p lica t e d d os in g s ch e m e s , s eve re a d ve rs e re a ct ion s ,

r
a
o
a n d s e co n d a ry lo s s o f e f ca cy s eve re ly re s t r ict e d t h e ir u s e fo r t re a t m e n t -

e
t
re fra ct ory ca s e s of gou t .

s
O
A p olye t h yle n e glycol (PEG)–lin ke d u rica s e (p eglot ica s e ) h a s be e n a p p rove d

4
a s s e con d -lin e t re a t m e n t for gou t . Th e d ru g is a d m in is t e re d a s a n in t rave n ou s

N
O
in fu s ion of 8 m g eve ry 2 w e e ks , a n d re q u ire s p re m e d ica t ion w it h a n t ih is t a -

I
T
m in e s a n d glu cocort icoid s . In clin ica l t ria ls it p rove d t o be h igh ly e ffe ct ive a n d

C
E
p ot e n t in a ch ievin g m a rke d s e ru m u ra t e re d u ct ion s . It is im p ort a n t t o n ot e t h a t

S
a b o u t 40% o f p a t ie n t s d id n o t re s p o n d t o t h e d ru g p rim a rily o r d eve lo p e d a
s e con d a ry los s of re s p on s e. Ma n y p a t ie n t s h a d p a rt ia l or com p le t e re s olu t ion
of t h e ir t op h i bu rd e n . Us e of t h e m e d ica t ion w a s lim it e d by in cre a s e in t h e
fre q u e n cy o f go u t a re s a n d in fu s ion re a ct ion s (in clu d in g ca s e s o f a n a p h y-
la xis ). It s ca rd iova s cu la r s a fe t y w a s ca lle d in t o q u e s t ion , bu t s h ort -t e rm clin ica l
t ria ls d id n ot ra is e a n y cle a r s a fe t y s ign a ls . Cle a rly, p os t m a rke t in g s u rve illa n ce
s t u d ie s a re n e ce s s a ry.

THERAPEUTIC APPROACHES IN DEVELOPMENT

Th e role of in t e rle u kin 1β (IL-1β) a s a n im p ort a n t p rod u ct of in a m m a s om e -
m e d ia t e d re s p on s e t o MSU le d t o t h e a t t e m p t e d u s e of blocke rs of t h is cyt okin e
t o t re a t gou t a re s . An a kin ra , a n IL-1β blocke r a p p rove d for t h e t re a t m e n t of
rh e u m a t oid a rt h rit is on ly, w a s in it ia lly t e s t e d , a n d a lt h ou gh e ffe ct ive, it s loca l
a d ve rs e re a ct ion s a n d h igh fre q u e n cy of a d m in is t ra t ion m a d e it a n in con ve n -
ie n t op t ion . Lon ge r a ct in g IL-1β blocke rs (rilon a ce p t a n d ca n a kin u m a b) a re in
a d va n ce d s t a ge s of d eve lop m e n t a n d t e s t in g, s h ow in g p rom is e for m a n a ge -
m e n t of gou t a re s a n d p rop h yla xis of gou t a re s in p a t ie n t s re ce ivin g u ra t e -
low e rin g t h e ra p y.

SPECIAL THERAPEUTIC CONSIDERATIONS

Seve ra l obs e rva t ion a l s t u d ie s h ave d e s cribe d a n a s s ocia t ion be t w e e n in cre a s e d
s e ru m u ra t e a n d h yp e rt e n s ion , d e cre a s e d GFR, a n d p rogre s s ion t o e n d -s t a ge
 194 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

re n a l d is e a s e. Exp e rim e n t a l m od e ls of h yp e ru rice m ia in ra t s h ave s h ow n t h a t

t h ey d eve lop re n in -d ep e n d e n t h yp e rt e n s ion , in t e rs t it ia l re n a l d is e a s e, glom e r-
u la r h yp e r t e n s io n , a r t e r iolop a t h y, a n d a n e n d ot h e lia l d ys fu n ct io n p a r t ia lly
reve rs ible by t h e a d m in is t ra t ion of a llop u rin ol. In a d d it ion , a llop u rin ol h a s be e n
fo u n d t o reve rs e h yp e rt e n s ion in h yp e ru rice m ic a n d ove rw e igh t a d o le s ce n t s
w it h h yp e rt e n s ion a n d t o d e cre a s e t h e p rop ort ion of p a t ie n t s w it h d e t e riora -
t io n o f re n a l fu n ct io n in p a t ie n t s w it h h yp e r u r ice m ia a n d ch ron ic k id n ey
d isea se. All th ese d a ta su ggest th a t a sym p tom a tic h yp eru ricem ia , w h ich cu rren tly
h a s n o in d ica t ion for t re a t m en t , m ay lea d to a dvers e ren a l a n d ca rd iova s cu la r
ou tcom es (9 ).

Ca lcium Pyro pho spha te Dihydra te

De po sitio n Dise a se
Ca lciu m p yro p h o s p h a t e d ih yd ra t e d e p o s it io n d is e a s e (CPPD) is t h e re s u lt o f
S
a r t icu la r d e p o s it io n o f ca lciu m p yro p h o s p h a t e crys t a ls . Ove r p ro d u ct io n o f
E
C
e xt ra ce llu la r p yrop h os p h a t e le a d s t o CPPD crys t a l form a t ion a n d d e p os it ion , a
T
I
p roce s s t h a t is u biq u it ou s a n d e s s e n t ia lly in evit a ble w it h a gin g. Th e con d it ion
O
N
h a s t h e ch a ra ct e ris t ic of clos e ly s im u la t in g ot h e r a u t oim m u n e a n d d ege n e ra -
4
t ive co n d it io n s , re q u ir in g a ca re fu l co m b in e d in t e r p re t a t io n o f clin ica l a n d
O
ra d iologic d a t a , a lon g w it h m icros cop ica l a n a lys is of s yn ovia l u id for t h e ch a r-
s
t
e
a ct e r is t ic crys t a ls . Un fo r t u n a t e ly, t re a t m e n t s d o n o t a im a t co r re ct in g t h e
o
a
u n d e rlyin g m e t a bolic d e fe ct , bu t a t d e cre a s in g t h e p a in , in a m m a t ion , a n d
r
t
h
d is a bilit y ca u s e d by t h e d is e a s e.
r
i
t
i
In cre a s e d p rod u ct ion of p yrop h os p h a t e by a rt icu la r ch on d rocyt e s in a n
s
a
e n viron m e n t e n rich e d in e xt ra ce llu la r ca lciu m s e e m s t o be t h e n e ce s s a ry con d i-
n
d
t ion for t h e form a t ion of CPPD crys t a ls . Th e s e crys t a ls e licit a n in a m m a t ory
M
re s p on s e t h rou gh s im ila r m e ch a n is m s a s MSU crys t a ls . Th e p e rp e t u a t ion of t h is
e
t
a
in a m m a t ory re s p on s e le a d s t o ce ll p rolife ra t ion a n d ge n e ra t ion of m e t a llop ro-
b
t e in a s e s t h a t con t ribu t e t o t h e s t ru ct u ra l colla p s e ch a ra ct e ris t ic of join t d ege n -
o
l
i
c
e ra t ion .
B
Th e p roce s s e s le a d in g t o CPPD a re a s s ocia t e d w it h d iffe re n t p h ys io logic
o
n
a n d p a t h oge n ic con t ribu t in g fa ct ors (Ta ble 20.5 ). Th e m a in a s s ocia t e d fa ct or is
e
a gin g, w it h s eve ra l a u t op s y a n d ra d iogra p h ic s t u d ie s con rm in g a n in cre a s e d
p reva le n ce of ch on d roca lcin os is w it h a d va n cin g a ge. We ll-kn ow n p a t h oge n ic
a s s o cia t io n s in clu d e h e m o ch r o m a t o s is , h yp e r p a ra t h yr o id is m , h yp o m a g-
n e s e m ia , h yp op h os p h a t e m ia , p reviou s t ra u m a , os t e oa rt h rit is , a n d gou t . Ot h e r
ge n e t ic a n d m e t a b olic fa ct o rs h a ve a ls o be e n p o s t u la t e d in a s s ocia t io n w it h
t h e d is e a s e . Kn ow le d ge o f t h e s e a s s ocia t io n s is im p or t a n t for t w o re a s o n s :
s om e of t h e s e con d it ion s (e.g., h e m och rom a t os is , h yp e rp a ra t h yroid is m ) cou ld
be s u s p e ct e d be ca u s e of t h e ir p re s e n t a t ion a s CPPD, a n d corre ct ion of t h e s e
con d it ion s cou ld s low t h e p rogre s s ion of CPPD.

Clinica l Pre se nta tio n

Ca lc iu m p y r o p h o s p h a t e d ih y d r a t e d e p o s it io n d is e a s e c a n m im ic s e ve r a l
o t h e r r h e u m a t o lo gic co n d it io n s . Th e b e s t k n ow n o f t h e s e is t h e a cu t e a r t h r i-
t is fo r m k n ow n a s pseu dogou t . Ap p r o x im a t e ly 25% o f p a t ie n t s p r e s e n t t h is
w a y a t s o m e p o in t in t h e ir d is e a s e , a n d a s it s n a m e im p lie s , c lin ic a lly it
clo s e ly re s e m ble s a go u t a r e . Th e m o s t co m m o n ly a ffe ct e d jo in t s a r e t h e
k n e e s , w r is t s , a n k le s , e lb ow s , s h o u ld e r s , a n d fe e t . It is im p o r t a n t t o e m p h a -
s iz e t h a t in vo lve m e n t o f t h e r s t m e t a t a r s o p h a la n ge a l jo in t d o e s n o t r u le
o u t p s e u d o go u t , w h ich ca n a ls o a ffe ct t h is ch a ra ct e r is t ic go u t in vo lve m e n t
s it e . As w it h go u t , a t t a ck s o f p s e u d o go u t a re p re cip it a t e d by t ra u m a , s u rge ry,
h o s p it a liz a t io n s , a n d a c u t e illn e s s e s . N o t a b le a m o n g t h e s e p r e d is p o s in g
 Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 195

Table 20.5 Condit ions Predisposing t o t he Format ion of Calcium

Pyrophosphat e Cryst als

PHYSIOLOGIC
• Ag in g
INJURY-RELATED
• Tra u m a
• Prio r su rg e ry t o a ffe ct e d jo in t
• Po st su rg ica l st a t e a
RHEUMATOLOGIC
• Ost e o a rt h rit is
• Go u t
• Ne u ro p a t h ic a rt h rit is
ENDOCRINE
• Hyp e rp a ra t h yro id ism a
• He m o ch ro m a t o sis
• Hyp o t h yro id ism

e
n
• Acro m e g a ly

o
B
METABOLIC

c
i
l
• Hyp o m a g n e se m ia

o
b
• Hyp o p h o sp h a t e m ia

a
t
e
MISCELLANEOUS

M
• Wilso n ’s d ise a se

d
• Och ro n o sis

n
a
s
i
a

t
Hyp e rp a ra t h yro id e ct o m y su rg e ry is a co m m o n p re d isp o sin g fa ct o r.

i
r
h
t
r
a
o
e
t
s
O
4
fa ct o r s , o n e p re cip it a n t is p a ra t h yro id e ct o m y s u rge ry. In a d d it io n

N
O
t o go u t , t h e p s e u d o go u t fo r m o f CPPD n e e d s t o b e d iffe r e n t ia t e d

I
T
fr o m s e p t ic a r t h r it is t h r o u gh s y n ovia l u id a n a ly s e s . Go u t a n d

C
E
p s e u d o go u t ca n co e x is t in t h e s a m e jo in t .

Figure 20 .4 Synovial uid showing rectangular and
irregularly sha ped calcium pyrophosphate dihydrate
crystals at a magni cation of 400×. (Courtesy of H. Ralph
Schumacher, Jr., M.D., and Janet Dinnella, University of
Pennsylvania (http:/ / www.med.upenn.edu/ synovium)).
S
Ca lciu m pyrop h os p h a t e d ih yd ra t e d ep os it ion d is e a s e ca n a ls o
p re s e n t w it h a d va n ce d d ege n e ra t ive join t d is e a s e, in a form kn ow n
a s pseu do-osteoarthritis . As w it h p r im a ry o s t e o a rt h rit is , t h is fo rm
in volve s p a in , p rogre s s ive s t iffn e s s , a n d fu n ct ion a l lim it a t ion . Th e
p a t t e rn of join t in volve m e n t ca n be a t yp ica l for p rim a ry os t e oa r-
t h rit is , a s it u s u a lly a ffe ct s , in a d d it ion t o t h e t yp ica l join t s s u ch a s
t h e kn e e s , n on –w e igh t -be a rin g join t s s u ch a s t h e w ris t s , e lbow s ,
a n d s h o u ld e r s . A va lgu s k n e e d e fo rm it y is h igh ly s u gge s t ive of
CPPD. Th e d iffe re n t ia t io n fro m p r im a ry o s t e o a r t h r it is is o ft e n
d if cu lt .
A p r e s e n t a t io n clo s e ly r e s e m b lin g r h e u m a t o id a r t h r it is is
k n ow n a s pseu dorheu m atoid arthritis . It in vo lve s p a in , s t iffn e s s ,
sw e llin g, a n d m ild e leva t io n in in a m m a t o ry m a r k e rs in a s ym -
m e t r ic fa s h io n a n d u s u a lly in vo lvin g s m a ll jo in t s . Mild s yn ovia l
p ro life ra t io n a n d e ro s io n s co u ld m a k e t h e d iffe re n t ia t io n w it h
r h e u m a t o id a r t h r it is eve n m o re ch a lle n gin g. In e ld e r ly p a t ie n t s ,
p o lym ya lgia r h e u m a t ica w it h p e r ip h e ra l a r t h r it is ca n p re s e n t in a
s im ila r w a y.
Ad d it io n a l p re s e n t a t io n s o f CPPD in clu d e s eve re d e s t r u ct ive
a r t h rit id e s re s e m blin g n e u ro p a t h ic a r t h ro p a t h ie s a n d a x ia l s k e l-
e t o n d is e a s e w it h low b a ck o r n e ck p a in . Th e la t t e r co u ld b e a cu t e
a n d s e ve r e , e ve n m im ick in g m e n in git is o r in a m m a t o r y b a ck
p a in s .
 196 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Studie s
Th e d ia gn os is of CPPD ca n be re in force d w h e n in t h e
righ t clin ica l con t e xt , a n a lys is of s yn ovia l u id d e m on -
s t ra t e s t h e p re s e n ce of s m a ll, w e a kly p os it ive bire frin -
ge n t crys t a ls on a p ola rizin g ligh t m icros cop ic e xa m i-
n a t ion (blu e w h e n t h e la rge r a xis of t h e crys t a l is
p a ra lle l t o t h e a xis of t h e p ola rize r; s e e Fig. 20.4 ). Th e s e
a re u s u a lly re ct a n gu la r, bu t cou ld a ls o be s q u a re d ,
oblon g, or h ave ot h e r irregu la r s h a p e s . An in a m m a -
t ory s yn ovia l u id a ls o s u p p ort s t h e role of t h e crys t a ls
in t h e in a m m a t ory a rt h rit is . An a d d it ion a l im p ort a n t
re a s on t o e xa m in e s yn ovia l u id , m a in ly in p a t ie n t s
w it h a cu t e a rt h rit is in w h ich p s e u d ogou t is in t h e d if-
fe re n t ia l, is t o ru le ou t s ep t ic a rt h rit is a n d gou t . Lim it a -
t ion s of s yn ovia l u id a n a lys is t o e s t a blis h a d ia gn os is
of p s e u d o go u t in clu d e t h e t e ch n ica l ch a lle n ge s t o
S
E
id e n t ify t h e crys t a ls (t h e s e a re oft e n s m a ll a n d ca n e a s -
C
T
ily be m is s e d ) a n d t h e fa ct t h a t ca lciu m pyrop h os p h a t e
I
O
N
crys t a ls ca n be p re s e n t in join t s n ot a ffe ct e d by CPPD.
4
An ot h e r u s e fu l a p p roa ch in t h e w ork-u p of CPPD
O
is t h rou gh ra d iologic s t u d ie s d e m on s t ra t in g t h e p re s -
s
t
e
Figure 20 .5 Anteroposterior ra diogra ph of the wrist, showing ca lci ca tion e n ce of ch on d roca lcin os is in s u s p iciou s join t s . Ch on -
o
a
of the ca rtila ginous a rticula r disc a nd a ne line of ca lci ca tion pa ra llel to d roca lcin os is a p p e a rs a s a n e, p u n ct a t e, d is cre t e, or
r
t
h
the radiodensity of the underlying bone, indica tive of a rticula r cartilage lin e a r ra d io -o p a cit y in ca rt ila gin o u s a re a s (Fig. 20.5 ).
r
i
calci cation (arrow ). (Reproduced with permission from Koopma n WJ,
t
Com m on ly in volve d a re t h e kn e e s , w ris t s , a n d h ip s a t
i
s
Morela nd LW, eds. Arthritis a nd Allied Conditions: A Textbook of
t h e leve ls of t h e s ym p h ys is p u bis . Ch on d roca lcin os is
a
Rheumatology. 15th ed. Phila delphia : Lippincott Willia ms & Wilkins; 2005.)
n
is a co m m o n n d in g in ra d io logic s t u d ie s in e ld e rly
d
M
in d ivid u a ls , s o it s n d in g s h o u ld b e in t e r p re t e d a s
e
s u p p o rt ive o f t h e d ia gn o s is o f CPPD in t h e righ t clin ica l co n t e x t . Dia gn o s t ic
t
a
b
crit e ria for CPPD h ave be e n p u blis h e d a n d a re p re s e n t e d in Ta ble 20.6 .
o
l
i
c
B
o
n
Table 20.6 Diagnost ic Crit eria and Cat egories for Calcium Pyrophosphat e Dihydrat e
e
Cryst al Deposit ion Disease (Revised Version)

1. De m o n st ra t io n o f ca lciu m p yro p h o sp h a t e d ih yd ra t e cryst a ls in t issu e o r syn o via l u id b y d e n it ive m e a n s

(e .g ., ch a ra ct e rist ic x-ra y d iffra ct io n o f ch e m ica l a n a lysis)
2. a . Id e n t i ca t io n o f m o n o clin ic o r t riclin ic cryst a ls sh o w in g w e a kly p o sit ive o r n o b ire frin g e n ce b y
co m p e n sa t e d p o la rize d lig h t m icro sco p y
b . Pre se n ce o f t yp ica l ra d io g ra p h ic ca lci ca t io n
3. a . Acu t e a rt h rit is, e sp e cia lly o f kn e e s o r o t h e r la rg e jo in t s
b . Ch ro n ic a rt h rit is, e sp e cia lly o f kn e e , h ip , w rist , ca rp u s, e lb o w, sh o u ld e r, o r m e t a ca rp o p h a la n g e a l jo in t ,
e sp e cia lly if a cco m p a n ie d b y a cu t e e xa ce rb a t io n s. Th e fo llo w in g fe a t u re s h e lp in d iffe re n t ia t in g fro m
o st e o a rt h rit is:
i. Un co m m o n sit e fo r p rim a ry o st e o a rt h rit is: w rist , m e t a ca rp o p h a la n g e a l, e lb o w, a n d sh o u ld e r
ii. Ra d io g ra p h ic a p p e a ra n ce ; e .g ., ra d io ca rp a l o r iso la t e d p a t e llo fe m o ra l jo in t sp a ce n a rro w in g
iii. Su b ch o n d ra l cyst fo rm a t io n
iv. Se ve re p ro g ressive de g en erat io n , w it h sub cho nd ra l bo ny co lla p se (micro fra ct ure s), a nd frag m e n t a t ion
w it h fo rm a t io n o f in t ra -a rt icu la r ra d io d e n se b o d ie s
v. Va ria b le a n d in co n st a n t o st e o p h yt e fo rm a t io n
vi. Te n d o n ca lci ca t io n s, e sp e cia lly o f Ach ille s, t rice p s, a n d o b t u ra t o r t e n d o n s
vii. In vo lve m e n t o f t h e a xia l ske le t o n a n d su b ch o n d ra l cyst s o f a p o p h yse a l a n d sa cro ilia c jo in t s, m u lt ip le
le ve ls o f d isc ca lci ca t io n a n d va cu u m p h e n o m e n o n , a n d sa cro ilia c va cu u m p h e n o m e n o n
Cate g o rie s
A. De n it e : Crit e ria 1 o r 2(a ) a n d 2(b ) m u st b e fu l lle d
B. Pro b a b le : Crit e ria 2(a ) o r 2(b ) m u st b e fu l lle d
C. Po ssib le : Crit e ria 3(a ) o r 3(b ) sh o u ld a le rt t h e clin icia n t o t h e p o ssib ilit y o f u n d e rlyin g CPPD d e p o sit io n
 Ch a p te r 20 Gou t a n d Crys t a l-In d u ce d Art h rop a t h ie s 197

WHEN TO REFER Tre a tme nt

• Pa t ie n t s w it h g o u t w h o d o
n o t a ch ie ve a t a rg e t se ru m
u ra t e o f 6 m g /d L o r le ss
d e sp it e co m p lia n t t h e ra p y
w it h m o re t h a n 300 m g /
d a y o f a llo p u rin o l.
• Pa t ie n t s w it h g o u t a n d
t ra n sp la n t e d o rg a n s,
m u lt ip le m e d ica l p ro b le m s,
o r a d va n ce d ch ro n ic
kid n e y d ise a se .
• Patients with tophaceous
gout or destructive arthritis.
Th e t h e ra p e u t ic a p p roa ch t o CPPD w ill d e p e n d on t h e s p e ci c p re s e n t a t ion of
t h e d is e a s e . Th e m a n a ge m e n t is o n ly s ym p t o m a t ic, a s t h e re is n o w a y t o
re m ove ca lciu m p yrop h os p h a t e d e p os it s from s yn ovia l t is s u e. Th e id e n t i ca -
t ion a n d s u cce s s fu l m a n a ge m e n t of con d it ion s t h a t p re d is p os e t o CPPD ca n
p reve n t fu rt h e r d ep os it ion of ca lciu m p yrop h os p h a t e in join t s , bu t w ill n ot le a d
t o re s orp t ion of e xis t in g ca lciu m p yrop h os p h a t e d e p os it s .
Th e m a n a ge m e n t of a cu t e a t t a cks of p s e u d ogou t is s im ila r t o t h a t of gou t
a re s w it h NSAIDs , loca l o r s ys t e m ic glu co cort icoid s , a n d colch icin e. Colch i-
cin e is rega rd e d a s e ffe ct ive in m o s t ca s e s o f CPPD, b u t in re a lit y, it is m ore
e ffe ct ive re la t ive t o t h e a cu it y a n d in a m m a t ion of t h e p re s e n t a t ion of CPPD
(p s e u d ogo u t p s e u d o rh e u m a t o id p s e u d o -o s t e o a r t h r it is ). Co lch icin e ca n
a ls o be u s e d for p rop h yla xis of a cu t e a t t a cks in p a t ie n t s w h o s u ffe r from t h os e
fre q u e n t ly. For CPPD a s s ocia t e d on ly w it h join t d ege n e ra t ion , a n a p p roa ch s im -
ila r t o p rim a ry os t e oa rt h rit is (a n a lge s ic a ge n t s , p h ys ica l t h e ra p y, bra cin g, loca l-
ize d in je ct ion s ) is p re fe rre d .

e
n
o
B
c
Clinica l Co urse

i
l
o
b
a
Acu t e a re s o f go u t a n d CPPD ca n b e s e lf-lim it e d ; u s e o f a n t i-in a m m a t o ry

t
e
M
a ge n t s ca n h a s t e n re cove ry. A s m a ll n u m be r of p a t ie n t s w it h gou t ca n con t in u e
t o h ave s om e d is com fort d u rin g t h e in t e rcrit ica l p e riod s . Th e ch ron ic form of

d
n
gou t ca n be d e form in g a n d ca u s e s ign i ca n t d is a bilit y. Un like gou t , CPPD ca n

a
s
fre q u e n t ly p re s e n t a s a p o lya r t icu la r a r t h ro p a t h y re s e m blin g r h e u m a t o id

i
t
i
r
a rt h rit is a n d os t e oa rt h rit is re s p e ct ive ly; t h e s e form s of CPPD t e n d t o h a ve a

h
t
r
le s s e ros ive a n d d e s t ru ct ive cou rs e t h a n t h a t of rh e u m a t oid a rt h rit is . Ep id e -

a
o
m io logic evid e n ce lin k in g h yp e ru r ice m ia t o a n a d ve r s e ca rd iova s cu la r o u t -

e
t
s
com e s is in t rigu in g a n d m e rit s fu rt h e r eva lu a t ion .

O
4
N
O
I
T
C
E
ICD9

S
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
d u e t o o r asso ciat e d w it h cryst als
275.49 [712.1] d icalciu m p h o sp h at e
275.49 [712.2] p yro p h o sp h at e
275.49 [712.8] sp e ci e d NEC
274.00 g o u t y
274.01 acu t e
275.49 [712.3] Cho ndrocalcino sis (art icu lar) (cryst al de p o sit io n ) (d ih yd rat e )
due to
275.49 [712.2] calciu m p yro p h o sp h at e
275.49 [712.1] d icalciu m p h o sp h at e cryst als
275.49 [712.2] p yro p h o sp h at e cryst als
274.9 Go ut , g o u t y
274.00 art h rit is
274.01 acu t e
274.00 art h ro p at h y
274.01 acu t e
274.02 ch ro n ic (w it h o u t m e n t io n o f t o p h u s (t o p h i))
274.03 w it h t o p h u s (t o p h i)
274.03 t o p h i
274.81 e ar
274.82 sp e ci e d sit e NEC
 198 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Re fe re nce s
1. La w re n ce RC, Fe ls on DT, He lm ick CG, e t a l. Es t im a t e s of t h e p reva le n ce of a rt h rit is a n d ot h e r rh e u m a t ic
con d it ion s in t h e Un it e d St a t e s . Pa rt II. A rthritis Rheum 2008 ;58 26 –5835 .
2. Ca m p ion EW, Glyn n RJ, De La bry LO . As ym p t om a t ic h yp e ru rice m ia . Ris ks a n d con s e q u e n ce s in t h e Nor-
m a t ive Agin g St u d y. A m J Med 1987 ;82 :421 –426 .
3. Ma rt in on F. Me ch a n is m s of u ric a cid crys t a l-m e d ia t e d a u t oin a m m a t ion . Im m unol Rev 233 :218 –232 .
4. Wa lla ce SL, Robin s on H , Ma s i AT, e t a l. Pre lim in a ry crit e ria for t h e cla s s i ca t ion of t h e a cu t e a rt h rit is of
p rim a ry gou t . A rthritis Rheum 1977 ;20 :895 –900.
5. Zh a n g W, Doh e rt y M , Pa s cu a l E, e t a l. EULAR evid e n ce ba s e d re com m e n d a t ion s for go u t . Pa rt I: Dia gn os is .
Rep ort of a t a s k force of t h e St a n d in g Com m it t e e for In t e rn a t ion a l Clin ica l St u d ie s In clu d in g Th e ra p e u -
t ics (ESCISIT). A nn Rheum Dis 2006 ;65 :1301 –1311 .
6. Ja n s s e n s HJ, Fra n s e n J, va n d e Lis d on k EH , e t a l. A d ia gn os t ic ru le for a cu t e go u t y a rt h rit is in p rim a ry ca re
w it h ou t join t u id a n a lys is . A rch Intern Med 2010 ;170 :1120 –1126.
7. Te rke lt a u b RA, Fu rs t DE, Be n n e t t K, e t a l. High ve rs u s low d os in g of ora l colch icin e for e a rly a cu t e gou t
a re : Tw e n t y-fou r-h ou r ou t com e of t h e rs t m u lt ice n t e r, ra n d o m ize d , d ou ble -blin d , p la ce bo-con t rolle d ,
p a ra lle l-grou p , d os e -com p a ris on colch icin e s t u d y. A rthritis Rheum 2010 ;62 :1060 –1068.
8. Be cke r MA, Sch u m a ch e r HR, Jr., Wo rt m a n n RL, e t a l. Fe bu xo s t a t com p a re d w it h a llop u rin ol in p a t ie n t s
w it h h yp e ru rice m ia a n d gou t . N Engl J Med 2005 ;353 :2450 –2461.
9. Fe ig DI, Ka n g DH, Joh n s on RJ. Uric a cid a n d ca rd iova s cu la r ris k . N Engl J Med 2008 ;359 :1811 –1821.
S
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I
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t
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o
a
r
t
h
r
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e
CHAPTER
21 Osteopenic Bone
Disea ses a nd
Osteonecrosis
Kenneth G. Saag, Gregory A . Clines, and Sarah L. Morgan

e
n
A 75-year-old m ale seen for com pression fractures. He relates a strong

o
B
fam ily history of m etabolic bone disease or fractures; his m other had

c
i
l
o
severe osteoporosis, tw o sisters have osteoporosis, and his father had

b
a
t
com pression fractures, w hich com plicated his em physem a. He presents

e
M
w ith records docum enting com pressions fractures at thoracic vertebra

d
n
11 (T11), T12 and lum bar vertebra 4 (L4) and L5. He has undergone a

a
s
i
kyphoplasty at L5. All com pression fractures occurred w ithout know n

t
i
r
h
traum a. He w as initially treated w ith injectable calcitonin and has

t
r
a
o
been on alendronate for approxim ately 10 years. He is referred because of concern for future fractures and

e
t
s
w orsening restrictive long disease in the setting of glucocorticoid-dependent obstructive lung disease.

O
He in dicat e s t hat he has a hist ory of in f e rt ilit y and p ro ble m s w it h im po t e nce . He has a lon g h ist o ry o f

4
N
in hale d glu co cort ico id use . Th e re is no hist ory o f an abo lic st e roid use an d n o hist ory of t h yro id d ise ase .

O
I
T
He g re w u p d rin k in g m ilk , b u t cu rre n t ly d rin k s n o m ilk an d e at s 2 o z o f ch e e se p e r w e e k . He co n -

C
E
S
su m e s n o calciu m -f o rt i e d f o o d s. He g e n e rally d o e s n o t g e t an y sig n i can t su n e xp o su re . He co n su m e s
15 g lasse s o f w in e p e r w e e k an d 2 o z o f h ard liq u o r p e r w e e k .
His p ast m e d ical h ist o ry is re m ark ab le f o r at h e ro scle ro t ic h e art d ise ase , e m p h yse m a, h yp e rlip id e m ia,
an d o st e o art h rit is. His cu rre n t m e d icat io n s in clu d e ale n d ro n at e 70 m g /w e e k , calciu m carb o n at e p lu s
vit am in D t w ice a d ay, ib u p ro f e n t w o t ab le t s d aily f o r b ack p ain , m o n t e lu k ast 10 m g o rally d aily, ip rat -
ro p iu m b ro m id e an d alb u t e ro l su lf at e in h ale r t w o p u ff s f o u r t im e s a d ay, in h ale d .
On p h ysical e xam in at io n , h e is 68 in . t all (d rive r’s lice n se h e ig h t is 74 in .), h is w e ig h t is 238 lb , vit al
sig n s are n o rm al. M P’s p o st u re is n o t ab le , h e ad b o w e d f o rw ard w it h a slig h t ly p ro t u b e ran t ab d o m e n .
He is w e arin g an e xt e n sio n b race . Eye s, n o b lu e scle ra. M o u t h , n o e xp o se d b o n e . Th e t h yro id is p alp ab le
w it h o u t m asse s.
Lo w e r t h o racic k yp h o sis, n o p o in t p ain t o p alp at io n . Ch e st , cle ar an d card iac e xam in at io n m u rm u r.
A b d o m e n , n o o rg an o m e g aly o r p ain . Ne u ro lo g ic, n o n f o cal.
Laboratory data. Chem istry pro le norm al, calcium = 8.7, alkaline phosphatase = 99, PTH = 67 (nl 12 to 90).
CBC, IFE, PSA all norm al. Anti tissue transglutam inase (TTG) 5. 25-OH vitam in D total = 43. Calcium /creatinine
ratio on a spot urine = 0.10.
Th e p at ie n t is st art e d o n t e rip arat id e as an an ab o lic ag e n t f o r h is b o n e . Th e re w as n o h ist o ry o f
b o n e t u m o rs, rad iat io n t h e rap y, an d im p lan t ab le rad iat io n t o p o se an ab so lu t e co n t rain d icat io n . Th e
b ase lin e alk alin e p h o sp h at e s an d b ase lin e b o n e -sp e ci c alk alin e p h o sp h at ase w e re n o rm al.

199
 200 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Table 21.1 World Health Organization (WHO) Criteria for the

Diagnosis of Osteopenic Bone Disease Based on T-score

CATEGORY DEFINITION
No rm a l BMD b e t t e r t h a n 1 SD b e lo w t h e m e a n va lu e
o f p e a k b o n e m a ss in yo u n g w h it e w o m e n
Ost e o p e n ia (lo w b o n e m a ss) BMD b e t w e e n 1.0 a n d 2.5 SD b e lo w t h e
m e a n p e a k va lu e
Ost e o p o ro sis BMD m o re t h a n 2.5 SD b e lo w t h e p e a k va lu e
Se ve re o st e o p o ro sis BMD crit e ria fo r o st e o p o ro sis a n d fra ct u re

BMD, b o n e m in e ra l d e n sit y; SD, st a n d a rd d e via t io n .

Intro ductio n
S
E
C
Os te op oros is is a syst em ic s kelet a l d ise a s e ch a ra ct erized by low bon e m a ss a n d
T
I
m icroa rch it e ct u ra l d e t e riora t ion of bon e t is s u e w it h a con s e q u e n t in cre a s e in
O
N
bon e fra gilit y a n d s u s cep t ibility t o fra ctu re. Th e World Hea lt h Orga n iza tion (W HO)
4
d e n it ion s of ost eop oros is a re ba s ed on ep id em iologic d a ta t h a t rela t e fra ct u re
O
s
in cid en ce to bon e m in era l d en s it y (BMD) in Ca u ca s ia n w om en (Ta ble 21.1 ).
t
e
By a ge 60 t o 70 ye a rs , o n e of t h re e n on -His p a n ic Ca u ca s ia n w om e n w ill
o
a
h ave os t e op oros is a n d t h e re m a in d e r, os t e op e n ia (a s t a t e of low bon e m a s s in
r
t
h
be t w e e n n orm a l a n d os t e op orot ic BMD); by a ge 80 ye a rs , 70% w ill h ave os t e -
r
i
t
i
op oros is . Figu re 21.1 s h ow s t h e p reva le n ce of os t e op oros is a n d os t e op e n ia in
s
a
Am e rica n w om e n bot h n ow a n d in t o t h e fu t u re.
n
d
Th e e s t im a t e d n u m be r of fra ct u re s a m on g Nort h Am e rica n w om e n w a s
M
200,000 in 1990 a n d is e s t im a t e d t o in cre a s e t o n e a rly 500,000 in 2025. Th e
e
t
a
p rop ort ion of fra ct u re s a t t ribu t a ble t o os t e op oros is is le s s for n on w h it e s t h a n
b
o
w h it e s a n d le s s for m e n t h a n w om e n . Th e in cid e n ce ra t e for h ip fra ct u re s is
l
i
c
a p p roxim a t e ly 2 p e r 1,000 p a t ie n t -ye a rs a t a ge 65 t o 69 in Ca u ca s ia n a n d n on -
B
o
Ca u ca s ia n w om e n , a n d in cre a s e s t o a bou t 26 p e r 1,000 p a t ie n t -ye a rs a t a ge 80
n
e
t o 84. Th e in cid e n ce a n d p reva le n ce of ve rt e bra l fra ct u re s is low p rior t o a ge
50 yea rs a n d ris e s a lm os t e xp on e n t ia lly t h e re a ft e r (Ta ble 21.2 ). Am on g Am e rica n
w om e n , t h e in cid e n ce of w ris t fra ct u re s in cre a s e s ra p id ly a t t h e t im e of m e n o-
p a u s e a n d p la t e a u s a t a bou t 700 p e r 100,000 p e rs on -ye a rs a ft e r a ge 60.
Th e life t im e ris k of a n y fra ct u re in t h e h ip , s p in e, or d is t a l fore a rm is a bou t
50% in Ca u ca s ia n w om e n of a ge 50 a n d 20% in Ca u ca s ia n m e n of s im ila r a ge.
Th e re a re s p e cia l p op u la t ion s , s u ch a s a p op u la t ion of in d ivid u a ls w it h h u m a n

60 Low bone mass

Osteoporosis
50
40.9
40
n
35.1
s)
e
m
n
o
o
29.6
i
w
30
l
l
i
m
f
o
30.4
n
.
o
i
26
(
20
N
21.8

10

7.8 9.1 10.5

0
2002 2010 2020

Figure 21.1 Preva lence of low bone mass and osteoporosis in women a ged 50 yea rs a nd older.
(Na tiona l Osteoporosis Founda tion, a va ila ble a t: http:/ / www.nof.org/ a dvoca cy/ preva lence.)
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 201

CLINICAL POINTS Table 21.2 Est imat ed Lifet ime Fract ure Risk in 50-Year-Old
Whit e Women and Men a
• Lifetime risk of osteoporotic
fracture in Caucasian males
is 20% . WOMEN %, (95% MEN %, (95%
SITE CONFIDENCE INTERVAL ) CONFIDENCE INTERVALb )
b

• Ob t a in in fo rm a t io n o f
h e ig h t lo ss o ve r t im e fro m Pro xim a l fe m u r 17.5 (16.8, 18.2) 6.0 (5.6, 6.5)
a d rive r’s lice n se . Ve rt e b ra l fra ct u re 15.6 (14.8, 16.3) 5.0 (4.6, 5.4)
• Un u su a l z-sco re s o n DEXA Dist a l fo re a rm fra ct u re 16.0 (15.2, 16.7) 2.5 (2.2, 3.1)
sca n ca n re p re se n t b o n e
m in e ra l d iso rd e r o t h e r An y fra ct u re 39.7 (38.7, 40.6) 13.1 (12.4, 13.7)
t h a n o st e o p o ro sis.
a
Ag e 50 ye a rs w a s ch o se n b e ca u se t h is is a b o u t t h e a ve ra g e o f m e n o p a u se in w o m e n .
• Ost e o n e cro sis o f t h e ja w is b
Usin g in cid e n ce o f clin ica lly d ia g n o se d fra ct u re s o n ly.
a d e va st a t in g co m p lica t io n Fro m Me lt o n LJ, Ch risch ille s EA, Co o p e r C, e t a l. Ho w m a n y w o m e n h a ve o st e o p o ro sis? J Bo n e M in e r
from use of bisphosphonates Re s 1992 ;7 :1005 –1010 , w it h p e rm issio n .
a n d is a sso cia t e d w it h
d e n t a l p ro ce d u re s.

e
n
• Diffu se b o n e p a in ca n

o
im m u n o d e cie n cy vir u s (HIV) w h e re a h igh p reva le n ce a n d p rogre s s io n o f

B
b e a m a n ife st a t io n o f
o s t e op o ros is o r os t e o p e n ia h a s b e e n d ocu m e n t e d . It is a n t icip a t e d t h a t t h e

c
o st e o m a la cia .

i
l
o
p reva le n ce of os t e op oros is a n d like ly fra ct u re s w ill grow in t h is p op u la t ion .

b
• Ost e o n e cro sis ca n b e

a
a sso cia t e d w it h a lco h o l Osteoporosis a n d con seq u en t fra ctu res a re m a jor p u blic h ea lth con cern s in th e

t
e
Un ited Sta tes. Th e econ om ic costs of osteop orotic fra ctu res a re la rge a n d som ew h a t

M
a b u se , p ro lo n g e d u se
o f co rt ico st e ro id s, a n d d if cu lt to a ssess beca u se th e tota l in clu des expen ses for su rgery a n d h osp ita liza -

d
n
m a n y m e d ica l co n d it io n s tion , reh a bilita tion , lon g-term ca re costs, loss of p rod u ctivity, a n d m ed ica tion s.

a
in clu d in g sickle ce ll d ise a se

s
Oth er bu rd en s a ssocia ted w ith fra ctu re in clu d e p oor resu lta n t fu n ction a l sta tu s,

i
t
a n d syst e m ic lu p u s e ry-

i
r
p a in , a d im in ish ed qu a lity of life, loss of in d ep en d en ce, fea r, a n d d ep ression .

h
t h e m a t o sis (SLE).

t
r
Hip fra ct u re s re s u lt in m ore t h a n 7 m illion d ays of re s t rict e d a ct ivit y a n d

a
o
6,000 a d m is s ion s t o n u rs in g h om e s a n n u a lly in t h e Un it e d St a t e s ; n e a rly t h re e

e
t
s
q u a rt e rs of a ll n u rs in g h om e a d m is s ion s a re re la t e d t o os t e op oros is . For h ip

O
fra ct u re s , a bo u t h a lf o f t h e h e a lt h ca re co s t s re e ct n u rs in g h om e e xp e n s e s .

4
N
Th e re is a n a p p roxim a t e ly 20% m ort a lit y w it h in 1 ye a r of h ip fra ct u re, a n d 50%

O
of s u rvivors n eve r fu lly re cove r. Th e m ort a lit y a s s ocia t e d w it h ve rt e bra l fra c-

I
T
C
t u re s is a ls o gre a t e r t h a n e xp e ct e d in t h e ge n e ra l p op u la t ion , w h e re a s t h e m or-

E
S
t a lit y of p a t ie n t s w it h w ris t fra ct u re s is s im ila r.
Figu re 21.2 sh ow s t h e lifet im e a ccru a l a n d los s of BMD in m e n a n d w om en .
Pea k BMD is t h e m a xim u m p os s ible w ith n orm a l grow t h a n d rep res en ts a gen et -
ica lly a n d e n viron m e n t a lly d e t e rm in e d a p ex from w h ich fu t u re los s e s occu r.
Mos t s ke let a l d e n s it y (bot h tra becu la r a n d cort ica l) is a ccu m u la t ed by a ge 18. In
1,600 cort ica l bon e, a s low p h a s e of loss begin s a t a ge
40, ra n gin g from 0.3 t o 0.5% p e r ye a r in m e n
a n d w om en . At m e n op a u s e in w om en n ot t a k-
in g h orm on e rep la cem en t t h e ra py, los s es aver-
y
1,200
t
si
a ge a bou t 1% p er yea r, bu t m ay a p p roa ch 3% t o
n
e
D
5% p e r ye a r. Aft e r t h is a cce le ra t e d los s for
l
a
800 a bo u t 8 t o 10 ye a rs , t h e ra t e d e cre a s e s in
r
e
n
a n ot h e r s low p h a s e. Th e cu m u la t ive life t im e
i
M
Men Women
e
loss es of bon e m ay be a s m u ch a s 30% t o 40%
n
o
400 of p ea k BMD in w om e n a n d 20% t o 30% in m en .
B
0
0 10 20 30 40 50 60 70 80 Clinica l Pre se nta tio n
Years of Age
Th e clin ica l eva lu a tion of osteop orosis sh ou ld
Figure 21.2 Age-rela ted bone minera l density for men and women. From Christenson id en tify lifestyle risk fa ctors a n d p ertin en t p h ys-
RH. Biochemica l ma rkers of bone meta bolism: An overview. Clin Biochem 1997;30:573–
593, with permission. (Reprinted in Sa a g KG, Morga n SL, Ca o X, et al. Bone in hea lth
ica l n d in gs, a n d a ss es s s econ d a ry ca u se s of
and disea se. In: Koopma n WJ, ed. Arthritis a nd Allied Condition: A Textbook of osteop en ia . Table 21.3 p rovid es con d ition s a sso-
Rheuma tology. 15th ed. Phila delphia : Lippincott Willia ms & Wilkins; 2005:2449–2541.) cia ted w ith osteop en ia or osteop orosis.
 202 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Table 21.3 Diseases and Drug Therapies Associat ed wit h Ost eopenia and Fract ure

Un iq u e t o w o m e n Exce ssive p ro t e in in t a ke
Na t u ra l m e n o p a u se Im m o b iliza t io n o r m icro g ra vit y
Pre g n a n cy Lo w ca lciu m o r vit a m in D in t a ke
Hyp o g o n a d ism Se d e n t a ry life st yle
Ag o n ist fo r g o n a d o t ro p in -re le a sin g h o rm o n e o r Sm o kin g
De p o - Pro ve ra
Ma lig n a n cy
Go n a d a l d ysg e n e sis (e .g ., Tu rn e r’s syn d ro m e )
En d o m e t rio sis Lym p h o p ro life ra t ive a n d m ye lo p ro life ra t ive
d ise a se s (lym p h o m a a n d le u ke m ia )
Un iq u e t o m e n
Mu lt ip le m ye lo m a
Hyp o g o n a d ism
Syst e m ic m a st o cyt o sis
Co n st it u t io n a l d e la y o f p u b e rt y
Tu m o r se cre t io n o f p a ra t h yro id h o rm o n e –re la t e d
He m o ch ro m a t o sis (d u e t o e it h e r in lt ra t io n
p e p t id e
o f t e st e s (h yp e rg o n a d o t ro p ic) o r p it u it a ry
(h yp o g o n a d o t ro p ic) Nu t rit io n a l d iso rd e rs
Kallman’s syndrome (isolated gonadotropin
de ciency) Ea t in g d iso rd e rs, su ch a s a n o re xia n e rvo sa
S
Klin e fe lt e r’s syn d ro m e (g e n o t yp e XXY) Ost e o m a la cia
E
Ma la b so rp t io n syn d ro m e s
C
Orch it is, vira l
T
Pa re n t e ra l n u t rit io n
I
O
M e n an d w o m e n Pe rn icio u s a n e m ia
N
Ag e -re la t e d b o n e lo ss Ba ria t ric su rg e ry (e sp e cia lly Ro u x-e n -Y b yp a ss)
4
Co n n e ct ive t issu e d ise a se s
O
An kylo sin g sp o n d ylit is Ot h e r d ise a se s
s
t
Ch ro n ic o b st ru ct ive p u lm o n a ry d ise a se (o ft e n
e
Ost e o g e n e sis im p e rfe ct a
o
Rh e u m a t o id a rt h rit is se co n d a ry t o g lu co co rt ico id u sa g e )
a
Ch ro n ic re n a l fa ilu re
r
Sp in a l co rd in ju ry
t
h
Co n g e n it a l p o rp h yria
r
i
t
En d o crin e ca u se s He m o ch ro m a t o sis
i
s
Acro m e g a ly He m o p h ilia
a
n
Ad re n a l t ro p h y a n d Ad d iso n ’s d ise a se Ho m o cyst in u ria
d
Cu sh in g ’s syn d ro m e Hyp o p h o sp h a t a sia
M
Dia b e t e s m e llit u s t yp e 1 Th a la sse m ia
e
t
Glu co co rticoid e xce ss (e n do g e n o us a n d e xo g e n o us)
a
M e d icat io n s
b
Go n a d o t ro p h ce ll a d e n o m a
o
Alu m in u m
l
Hyp e rp a ra t h yro id ism (p rim a ry a n d se co n d a ry)
i
c
Hyp e rp ro la ct in e m ia (a s a ca u se o f h yp o g o n a d ism ) An t ie p ile p t ics (so m e )
B
Ch e m o t h e ra p e u t ic a g e n t s t h a t ca u se ch e m ica l
o
Hyp e rt h yro id ism
n
ca st ra t io n
e
Hyp e rca lcit o n in e m ia ?
Hyp o g o n a d ism (p rim a ry, se co n d a ry, o r su rg ica l) Cyclo sp o rin e A a n d t a cro lim u s
Pa n h yp o p it u it a rism Cyt o t o xic d ru g s
Th yro t o xico sis Glu co co rt ico id s a n d a d re n o co rt ico t ro p in
He p a rin (p e rh a p s le ss se ve re w it h lo w -m o le cu la r-
Ga st ro in t e st in a l d ise a se s w e ig h t co m p o u n d s)
Ch o le st a t ic live r d ise a se (e sp e cia lly p rim a ry b ilia ry Lit h iu m
cirrh o sis) Me t h o t re xa t e
Ga st re ct o m y Ta m o xife n (p re m e n o p a u sa l u se )
In a m m a t o ry b o w e l d ise a se (e sp e cia lly re g io n a l Th yro id h o rm o n e (in e xce ss)
e n t e rit is) Se le ct ive se ro t o n in re u p t a ke in h ib it o rs
Po st g a st re ct o m y Pro t o n p u m p in h ib it o rs
Th io g lit a zo n e s
Life st yle /g e n e t ic fa ct o rs
Exce ssive a lco h o l
Exce ssive ca ffe in e ?
Exce ssive e xe rcise (im p a irm e n t o f h yp o t h a la m ic–
p it u it a ry a xis)

Fro m Mo rg a n SL, Sa a g KG, Ca o X, e t a l. Bo n e in h e a lt h a nd dise a se . In: Koo pm a n WJ, e d . A rt h rit is an d A llie d Co n d it io n : A Te xt b o o k o f Rh e u m at o lo g y .

15t h e d . Ph ila d e lp h ia : Lip p in co t t Willia m s & Wilkin s; 2005 :2449 –2541 .

PATIENT ASSESSMENT
• Fa m ily h ist o ry o f
m e t a b o lic b o n e d ise a se .
• Life st yle risk fa ct o rs
(e xe rcise , sm o kin g , a lco h o l
u se , fa ll risk, e t c.) fo r
o st e o p o ro sis.
• Lo ss in h e ig h t .
• Hist o ry o f fra ct u re s o f a ll
ca u se s.
• Life t im e a n d cu rre n t
co n su m p t io n o f ca lciu m ,
vit a m in D, so d iu m , a n d
ca ffe in e .
• Me d ica t io n u se .
Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 203
A ca re fu l eva lu a t ion of os t e op oros is in clu d e s identi cation of a fa m ily h is -
t ory of m e t a bolic bon e d is e a s e, life s t yle ris k fa ct ors , h is t ory of ch a n ge in h e igh t
a n d w e igh t , h is t o ry of p revio u s fra ct u re s , re p rod u ct ive h is t o ry (evid e n ce o f
h yp ogon a d is m ), e n d ocrin e h is t ory, d ie t a ry fa ct ors (in clu d in g life t im e a n d cu r-
re n t con s u m p t ion of ca lciu m , vit a m in D, s od iu m , a n d ca ffe in e ), a s m okin g h is -
t ory, a lcoh ol in t a ke, e xe rcis e, h is t ory of re n a l or h ep a t ic fa ilu re, a n d p a s t a n d
cu rre n t m e d ica t io n s a n d s u p p le m e n t s . In a d d it ion , fa ct o rs t h a t in cre a s e t h e
r is k of fa lls , s u ch a s n e u ro m u s cu la r d is e a s e a n d u n s a fe livin g co n d it io n s ,
s h ou ld a ls o be s ou gh t . A h is t ory of bon e p a in is u s e fu l; h ow eve r, os t e op oros is
is n ot p a in fu l u n le s s fra ct u re s d eve lop . Fu rt h e r, a la rge p rop ort ion of ve rt e bra l
fra ct u re s m ay occu r w it h ou t ove rt s ym p t om s .
Exa mina tio n
He igh t m e a s u re m e n t is a vit a l p a rt of t h e p h ys ica l e xa m in a t ion a t e a ch vis it .
Com p a ris on of cu rre n t h e igh t w it h t h a t on a d rive r’s lice n s e is h e lp fu l in u n cov-
e
e rin g h e igh t los s . Los s of 2 in . or m ore is a fa irly s e n s it ive in d ica t or of ve rt e bra l
n
o
com p re s s ion . Th e s p in e s h ou ld be e xa m in e d for con form a t ion a n d s p in a l a n d
B
c
p a ra s p in ou s t e n d e rn e s s . If kyp h os is is p re s e n t , t h e p os s ibilit y of p u lm on a ry
i
l
o
co m p ro m is e s h o u ld b e co n s id e re d . A “b u ffa lo h u m p ,” e a s y b ru is a b ilit y, a n d
b
a
s t r ia e s u gge s t Cu s h in g’s s yn d ro m e . Blu e s cle ra e m a y in d ica t e o s t e oge n e s is
t
e
M
im p e rfe ct a . Th e n u m be r of m is s in g t e e t h h a s be e n corre la t e d t o t h e s eve rit y of
d
los s in BMD. A join t a s s e s s m e n t m ay s u gge s t rh e u m a t ologic ca u s e s of low BMD.
n
Th e n e u rologic e xa m in a t ion is im p ort a n t be ca u s e m u s cu la r w e a kn e s s p re d is -
a
s
p os e s t o fa lls a n d a n u n d e rlyin g n e u rologic p roble m m ay be d is cove re d .
i
t
i
r
h
t
r
a
Studie s
o
e
t
s
O
LABORATORY EVALUATION
4
Ro utine Labo rato ry Te sting
N
O
Th e la b ora t ory a s s e s s m e n t s e e k s p os s ible s e con d a ry ca u s e s o f los s o f BMD.
I
T
Ta ble 21.4 p rovid e s t e s t s t h a t m a y be a p p rop ria t e. Ma n y a re n ot cos t -e ffe ct ive
C
E
if obt a in e d for eve ry p a t ie n t . In t a ct PTH con ce n t ra t ion , for e xa m p le, s h ou ld be
S
Table 21.4 Laborat ory Evaluat ion of Decreased Bone Mass
TEST DIAGNOSIS RULED IN OR RULED OUT
Se ru m p ro t e in e le ct ro p h o re sis/ Mu lt ip le m ye lo m a
co m p le t e b lo o d co u n t
Se ru m ca lciu m a n d p h o sp h o ru s Hyp e rp a ra t h yro id ism
Se ru m in t a ct p a ra t h yro id h o rm o n e Hyp e rp a ra t h yro id ism
Se ru m cre a t in in e Re n a l fa ilu re
Live r e n zym e s Live r fa ilu re
24-h o u r u rin e -fre e co rt iso l o r Cu sh in g ’s syn d ro m e
d e xa m e t h a so n e su p p re ssio n t e st
Th yro id -st im u la t in g h o rm o n e Hyp e rt h yro id ism
Fo llicle -st im u la t in g h o rm o n e Me n o p a u se
Fre e t e st o st e ro n e Ma le h yp o g o n a d ism
Urin e ca lciu m /cre a t in in e ra t io Hyp e rca lciu ria
25-m o n o h yd ro xy vit a m in D3 a n d Vit a m in D d e cie n cy o r o st e o m a la cia
a lka lin e p h o sp h a t a se
 204 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Table 21.5 Biochemical Markers of Bone Turnover

FORMATION
Fro m o st e o b last s, in se ru m
Bo n e a lka lin e p h o sp h a t a se
Ost e o ca lcin
Fro m b o n e m at rix, in se ru m
Pro co lla g e n I C-t e rm in a l p ro p e p t id e
Pro co lla g e n I N-t e rm in a l p ro p e p t id e
Fro m b o n e m at rix, in u rin e
RESORPTION
Fro m o st e o clast s
Ta rt ra t e -re sist a n t a cid p h o sp h a t a se
N-te rm in al t elopep tide o f type I collagen
C-termina l te lop e pt id e o f t yp e I collage n
Pyrid in o lin e a n d d e o xyp yrid in o lin e
cro ss-lin ks
N-terminal telopeptide of type I collagen
Hyd ro xyp ro lin e fro m co lla g e n
d e g ra d a t io n

Fro m Ro sa lki SB. Bio ch e m ica l m a rke rs o f b o n e t u rn o ve r. In t J Clin Pract 1998 ;52 :256 , w it h p e rm issio n .
S
E
C
T
I
O
N
m e a s u re d if t h e ca lciu m con ce n t ra t ion is e leva t e d a n d t h e p h os p h oru s con ce n -
4
O
t ra t ion is low or if clin ica l s u s p icion is h igh for h yp e rp a ra t h yroid is m .
s
t
e
o
Spe ci c Bo ne Turno ve r Marke rs
a
r
Bio ch e m ica l m a r ke r s o f bo n e t u r n ove r a re s o m e t im e s u s e d in t h e m a n a ge -
t
h
r
m e n t of o s t e o p o ro s is . W h ile bo n e fo r m a t io n a n d re s or p t io n a re u s u a lly “co u -
i
t
i
s
p le d ,” n e t im b a la n ce s ca n be eva lu a t e d w it h t h e s e a s s a ys . Ta ble 21.5 p rovid e s
a
n
b o n e t u r n ove r m a r k e r s t h a t ca n be cla s s i e d a s in d ice s o f b o n e fo r m a t io n o r
d
r e s o r p t io n . “Bo n e b a la n ce ” is t h e n e t d iffe r e n ce b e t w e e n fo r m a t io n a n d
M
e
re s o r p t io n .
t
a
b
o
l
i
Ima g ing
c
B
o
n
Du a l-e n e rgy x -ra y a b s o r p t io m e t ry (DXA) is cu r re n t ly t h e “go ld s t a n d a rd ” fo r
e
p a t ie n t ca re a n d clin ica l in ve s t iga t io n fo r o s t e o p o ro s is . On DXA, b o n e m a s s
is r e p o r t e d a s a n a b s o lu t e va lu e in g/ cm 2 , a co m p a r is o n t o a ge - a n d s e x -
m a t ch e d re fe re n ce ra n ge (t h e Z-s co re ), a n d a co m p a r is o n t o m e a n b o n e m a s s
o f yo u n g a d u lt n o r m a l in d ivid u a ls (t h e T-s co re o r yo u n g-a d u lt Z-s co re ; s e e
Fig. 21.3 ). T-s co re s a re u s e d t o p re d ict fra ct u re r is k a n d cla s s ify d is e a s e s t a -
t u s . A ch a n ge o f o n e s t a n d a rd d evia t io n in t h e T- o r Z-s co re co r re la t e s t o a
ch a n ge o f a p p r o x im a t e ly 0.06 g/ cm 2 , o r a b o u t 10% o f BMD. Alt h o u gh t h e
Z-s co re is o f le s s clin ica l va lu e t h a n t h e T-s co re , Z-s co re s s ign i ca n t ly d evia t -
in g fro m n o r m a l m a y in d ica t e a lt e r n a t ive ca u s e s o f m e t a b o lic b o n e d is e a s e .
Du a l-e n e rgy x -ra y a b s o r p t io m e t ry s ca n s a ls o p ro d u ce a d e n s it y-b a s e d im a ge
u s e fu l in in t e r p re t in g s ca n q u a lit y (s e e Fig. 21.3 a n d b e low ). Th e s e re a d in gs
a r e co m p a r e d t o t h e Na t io n a l He a lt h a n d Nu t r it io n Ex a m in a t io n Su r ve y
(NHANES) III d a t a b a s e .
Du a l-e n e rgy x-ray a bs orp t iom e t ry m e a s u re s BMD a t ce n t ra l a n d p e rip h e ra l
s it e s . Th e ch oice of s it e (s ) s ca n n e d s h ou ld d e p e n d on t h e a n t icip a t e d ra t e s of
ch a n ge in bon e m a s s w it h in t h e s e s ke le t a l loca t ion s a n d p re cis ion of t h e t e s t -
in g d evice a t t h e s e s it e s . Th e ce n t ra l DXA s it e s of t h e h ip a n d s p in e, follow e d
by p e rip h e ra l s it e s o f t h e w ris t a n d h e e l, a re t h e m os t d e s ire d im a gin g loca -
t ion s . Ce n t ra l DXA of t h e s p in e a n d h ip h a s e xce lle n t p re cis ion a n d good a ccu -
ra cy. Ce n t ra l DXA is ge n e ra lly p re fe rre d be ca u s e t h e q u a n t it y of ca n ce llou s
bon e of ce n t ra l s it e s is h igh ly in d ica t ive of t h e os t e op oros is bu rd e n a n d fra c-
t u re ris k. In os t e op oros is , t h e e a rlie s t bon e los s begin s in ca n ce llou s bon e. A
h igh e r p rop ort ion of e a rly p os t m e n op a u s a l w om e n h ave low e r ca n ce llou s BMD
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 205

e
B

n
o
C

B
c
Figure 21.3 Dua l-energy x-ra y a bsorptiometry (DXA) printout. For a 70-yea r-old white woma n. A: DXA of this pa tient’s lumba r spine

i
l
o
showing ima ging windows for vertebra e L1 to L4. Estima ted vertebra l a rea s, bone minera l content (BMC), a nd bone minera l density

b
(BMD) a re shown (middle ). Bone minera l density is plotted a ga inst a lumba r spine reference da ta ba se showing the pa tient’s current

a
t
e
va lue a s well a s previous rea dings indica ted by crosses (right, top ). The da rk (top ) ba r of the gra ph indica ted 2 sta nda rd devia tions

M
a bove norma l a nd the lighter (bottom ) ba r 2 sta nda rd devia tions below pea k bone ma ss. T-scores (pea k bone ma ss ma tched) show

d
tha t the pa tient is well below the World Hea lth Orga niza tion’s de nition of osteoporosis (T-score −2.5) a t ea ch vertebra l level a nd for

n
a
the lumba r spine overa ll. The Z-score is a n a ge-ma tched mea surement. B: Simila r pa ra meters a re shown for the left hip, a nd ba sed

s
on T-scores , there is osteoporosis a t both the femora l neck a nd the tota l hip. C: At both the hip a nd lumba r spine, there ha s been

i
t
i
r
signi ca nt 3-yea r improvement in BMD. The seria l plot (left ) a nd ta ble show a nea rly 12% increa se a t the left hip. The a sterisk signi es

h
t
a signi ca nt increa se of decline between two va lues. An 18.4% increa se in BMD wa s a lso seen a t the lumba r spine (da ta not shown).

r
a
(From Sa a g KG, Morga n SL, Ca o X, et a l. Bone in hea lth a nd disea se. In: Koopma n WJ, ed. Arthritis a nd Allied Condition: A Textbook of

o
e
Rheuma tology. 15th ed. Phila delphia : Lippincott Willia ms & Wilkins; 2005:2449–2541.)

t
s
O
4
N
O
t h a n cort ica l BMD. Ap p roxim a t e ly a t h ird of t h e s p on gy t ra be cu la r bon e of t h e

I
T
h ip a n d s p in e re m od e ls e a ch ye a r a s op p os e d t o on ly 3% t u rn ove r of com p a ct

C
E
co rt ica l b o n e co m p ris in g a gre a t e r p ro p o rt io n o f p e rip h e ra l s k e le t o n . At t h e

S
s p in e, DXA re p ort s m e a s u re m e n t s of a n in d ivid u a l ve rt e bra a s w e ll a s ave ra ge
BMD of t h e L1 t o L4 (s e e Fig. 21.3 ). At t h e h ip , fe m ora l n e ck, a n d t h e t ot a l h ip
a re t h e t h re e m e a s u re m e n t s it e s of gre a t e s t clin ica l in t e re s t . Ce n t ra l m e a s u re -
m e n t s a re u s e d t o d ia gn os e os t e op oros is , a s s e s s fra ct u re ris k, a n d follow u p t h e
re s p on s e t o a n t ios t e op orot ic t h e ra p ie s .
Pe rip h e ra l DXA of t h e fore a rm is m od e ra t e ly corre la t e d w it h ce n t ra l DXA
re s u lt s a n d ca n , t h u s , be u s e d a s a n a lt e rn a t ive t o p re d ict fra ct u re ris k. He e l
DXA corre la t e s w e ll w it h ot h e r h e e l im a gin g t e ch n ologie s a n d a d e q u a t e ly d is -
cr im in a t e s o s t e o p o ro t ic fro m n o r m a l yo u n g s u b je ct s . How eve r, t h e m u ch
s low e r ra t e of bon e re m od e lin g a t s it e s s u ch a s t h e h e e l lim it s t h is t e ch n ology
for m on it orin g t h e re s p on s e t o t h e ra p y. Th e e n h a n ce d p ort a bilit y of d e d ica t e d
p e rip h e ra l bon e m a s s m e a s u re m e n t in s t ru m e n t s a n d t h e ir low e r cos t re n d e rs
t h e m in cre a s in gly a t t ra ct ive for com m u n it y os t e op oros is s cre e n in g.
Ve rt e bra l fra ct u re a n a lys is (VFA) is a p oin t of s e rvice e xa m in a t ion t h a t ca n
be p e rform e d on m a n y DXA s ca n n e rs . Ve rt e bra l fra ct u re a n a lys is con ce n t ra t e s
on t h e m orp h om e t ry of in d ivid u a l ve rt e bra l bod ie s for t h e p u rp os e of id e n t ify-
in g ve rt e bra l com p re s s ion fra ct u re s .
Bon e m in e ra l d e n s it y m e a s u re d by DXA is a good p re d ict or of t h e ris k of
h ip a n d s p in a l fra ct u re s . Sp in a l fra ct u re is in ve rs e ly p rop ort ion a l t o bon e m in -
e ra l con t e n t . For e a ch d e clin e of a bou t 1 s t a n d a rd d evia t ion of bon e m a s s , t h e re
is a 1.3- t o 2.5-fold in cre a s e in fra ct u re ris k of a n y s it e. Alt h ou gh fra ct u re ris k
a t a n y s it e ca n be a ccu ra t e ly a s s e s s e d u s in g a va rie t y of n on in va s ive bon e m a s s
m e a s u re m e n t s d on e a t a n y s it e, BMD a t t h e fe m ora l n e ck is be t t e r t h a n BMD a t
 206 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Country : United States Name / ID : About the risk factors i

Questionnaire: 10. Secondary osteoporosis No Yes

1. Age (between 40-90 years) or Date of birth 11. Alcohol 3 more units per day No Yes
Age: Date of birth: 12. Femoral neck BMD
Y: M: D: Select
2. Sex Male Female Clear Calculate
S
3. Weight (kg)
E
C
4. Height (cm)
T
I
5. Previous fracture No Yes
O
N
6. Parent fractured hip No Yes
4
7. Current smoking No Yes
O
8. Glucocorticoids No Yes
s
t
9. Rheumatoid arthritis No Yes
e
o
a
r
t
h
r
i
t
i
s
Figure 21.4 The FRAX WHO Fra cture Risk Assessment Tool. Ca lcula tes the 10-yea r proba bility of hip a nd ma jor osteoporotic* fra cture in previously
a
untrea ted pa tients. Ma jor osteoporotic fra cture is de ned a s vertebra l, hip, forea rm, or humerus fra cture. (Na tiona l Osteoporosis Founda tion. Clinicia n’s
n
Guide to Prevention a nd Trea tment of Osteoporosis . Wa shington, DC: Na tiona l Osteoporosis Founda tion; 2008. FRAX® WHO Fra cture Risk Assessment
d
M
Tool. Ava ila ble a t: www.shef.a c.uk/ FRAX/ tool.jsp.)
e
t
a
b
o
l
i
c
t h e s p in e, ra d iu s , a n d ca lca n e u s t o p re d ict h ip fra ct u re. De cre a s e s of 2 s t a n d a rd
B
d evia t ion s in ra d ia l a n d ca lca n e a l bon e m a s s a re a s s ocia t e d w it h 4- t o 6-fold
o
n
in cre a s e s in ris k for ve rt e bra l fra ct u re. In cre a s in g a ge a n d d e cre a s in g BMD of
e
t h e ra d iu s p re d ict s u b s e q u e n t n o n s p in a l fra ct u re s . It is e s t im a t e d t h a t a
50-ye a r-old w om a n h a s a 19% life t im e ris k of fra ct u re if ra d ia l bon e m a s s is in
t h e 10t h p e rce n t ile com p a re d w it h a n 11% life t im e ris k if t h e m e a s u re m e n t is
in t h e 90t h p e rce n t ile. Abs olu t e fra ct u re ris k for t h e n e xt 10 ye a rs ca n be ca l-
cu la t e d by in co rp o ra t in g clin ica l in fo rm a t io n o n fra ct u re ris k w it h BMD a n d
u s in g t h e FRAX t o ol a va ila ble on t h e We b (h t t p ://w w w.s h e f e ld .a c.u k /FRAX/;
s e e Fig. 21.4 ).

Pre ve ntio n a nd The ra py

Alt h ou gh d e cre m e n t s in BMD m ay a ccu ra t e ly p re d ict fra ct u re ris k, w h e n eva lu -
a t in g p reve n t ion a n d t re a t m e n t s t u d ie s , t h e e ffe ct of a n in t e rve n t ion on fra c-
t u re in cid e n ce is t h e m os t crit ica l ou t com e.
Nu m e ro u s ge n e ra l m e d ica l a n d s p e cia lt y s o cie t ie s h a ve p ro m u lga t e d
gu id e lin e s fo r o s t e o p o ro s is p reve n t io n a n d t re a t m e n t . In 2009 t h e Na t io n a l
Os t e op oros is Fou n d a t ion (NOF) is s u e d gu id e lin e s in colla bora t ion w it h 10 m e d -
ica l orga n iza t ion s . Th e s e re com m e n d a t ion s a re ba s e d on a ge, BMD T-s core, a n d
w h e t h e r or n ot t h e re a re a ccom p a n yin g ris k fa ct ors . Th e NOF gu id e lin e s a d vo-
ca t e p h a rm a cologic in t e rve n t ion t o re d u ce t h e ris k of fra ct u re s in :
• a h ip or ve rt e bra l (clin ica l or m orp h om e t ric) fra ct u re ;
• T-s core −2.5 a t t h e fe m ora l n e ck or s p in e a ft e r a p p rop ria t e eva lu a t ion t o
e xclu d e s e con d a ry ca u s e s ;
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 207

• low bon e m a s s (T-s core be t w e e n −1.0 a n d −2.5 a t t h e fe m ora l n e ck or s p in e )

and a 10-ye a r p roba bilit y of a h ip fra ct u re 3% or a 10-ye a r p roba bilit y of a
m a jor os t e op oros is -re la t e d fra ct u re 20% u s in g t h e US-a d a p t e d W HO a lgo-
rit h m (s e e FRAX, Fig. 21.2 );
• Clin icia n ’s ju d gm e n t a n d /or p a t ie n t p re fe re n ce s m a y in d ica t e t re a t m e n t for
p e op le w it h 10-ye a r fra ct u re p roba bilit ie s a bove or be low t h e s e leve ls .

NONPHARMACOLOGIC PREVENTION
Exe rcise
Mod era t e t o in ten s ive w eigh t-bea rin g exercise ca n lea d to m od est in crea ses of
abou t 1% to 3% in BMD. For a n exercise to be effective in a lterin g BMD, it m u st
stra in th e skeleta l site bein g eva lu a ted . For exa m p le, bon e m a ss ga in s a re p a rticu -
la rly n otable in th e tibia in ru n n ers a n d in th e sp in e a m on g w eigh t lifters. Old er
w om en m ay d em on stra te lu m ba r BMD ga in s w ith regu la r vigorou s w eigh t-bea rin g
exe rcis e p e rform e d m u lt ip le t im e s p e r w e e k. Con t in u e d p h ys ica l a ct ivit y is
req u ired to m a in ta in observed BMD ga in s. Sp in a l exten sion exercises a re p referred

e
n
over exion m a n eu vers, w h ich m ay lea d to sp in a l com p ression d eform ities.

o
B
c
i
l
Hip Pro te cto rs

o
b
Protective h ip p a d s w orn in sp ecia lized u n d erga rm en ts h ave effectively red u ced

a
t
e
fra ct u re ra t e s in n u rs in g h om e p a t ie n t s in s om e s t u d ie s . Ad h e re n ce t o t h e s e

M
d evices is p roblem a tic a n d oth er stu d ies h ave n ot been su p p ortive of th eir ef ca cy.

d
n
a
s
i
PHARMACOLOGIC PREVENTION

t
i
r
h
t
Calcium and Vitamin D

r
a
o
Ca lciu m a lo n e m a y s o m ew h a t re d u ce, b u t n o t fu lly p reve n t , b o n e lo s s e a rly

e
t
a ft e r m e n o p a u s e . In p o s t m e n o p a u s a l w o m e n , s u f cie n t ca lciu m p rovid e d

s
O
t h rou gh d ie t a ry a n d e xoge n ou s s ou rce s d e cre a s e s a p p e n d icu la r s ke le t a l bon e

4
los s by 1% t o 3% com p a re d t o w om e n w h o d o n ot con s u m e a d e q u a t e ca lciu m .

N
O
Ca lciu m m a y be m os t be n e cia l for w om e n la t e r a ft e r m e n op a u s e. How eve r,

I
T
eve n a m on g you n ge r w om e n a n d m e n , ca lciu m s u p p le m e n t a t io n p reve n t s

C
E
bon e los s a t va riou s s ke le t a l s it e s .

S
Va ryin g a m ou n t s of e le m e n t a l ca lciu m a re fou n d in d iffe re n t food grou p s
a n d n u t rit ion a l s u p p le m e n t s . Ca lciu m is e q u a lly w e ll a bs orbe d (25% t o 30%)
from e it h e r m ilk p rod u ct s or ca lciu m ca rbon a t e. Alt h ou gh s om e s t u d ie s s u g-
ge s t t h a t ca lciu m cit ra t e h a s s ligh t ly h igh e r a bs or p t ion t h a n ot h e r p re p a ra -
t ion s , ot h e r in ve s t iga t ion s in d ica t e t h a t t h ey a re e q u a lly w e ll a bs orbe d .
On e a re a o f co n t rove r s y co n ce r n s t h e u s e o f ca lciu m s u p p le m e n t s in
p a t ie n t s w it h a h is t o ry o f n e p h ro lit h ia s is . High in t a k e o f d ie t a ry ca lciu m
a p p e a rs t o d e cre a s e t h e ris k of s t on e s , w h e re a s in t a ke of h igh d os e s of s u p -
p le m e n t a l ca lciu m m a y m od e s t ly in cre a s e ris k. Die t a ry ca lciu m m a y be n e -
cia lly bin d oxa la t e, t h e p rim a ry com p on e n t in m os t re n a l s t on e s .
Alt h ou gh ca lciu m s u p p le m e n t s a re w e ll t ole ra t e d by m a n y, con s t ip a t ion (in
a bou t 10% of u s e rs ) a n d d ys p ep s ia lim it lon g-t e rm a d h e re n ce. In d ivid u a l t ria ls
of d iffe re n t p rep a ra t ion s a n d t im e s of a d m in is t ra t ion m a y m a xim ize p a t ie n t
s a t is fa ct ion . In s t it u t e of Me d icin e 2010 Con s e n s u s re com m e n d a t ion s for d a ily
d os e s of e le m e n t a l ca lciu m a re p rovid e d in Ta ble 21.6. Th e in cre a s in g va rie t ie s
of food a n d beve ra ge p rod u ct s a va ila ble in t h e Un it e d St a t e s t h a t a re ca lciu m
fort i e d h ave re d u ce d t h e re lia n ce on e xoge n ou s ca lciu m s a lt s u p p le m e n t s t o
a ch ieve d a ily re q u ire m e n t s . Th e re is evid e n ce from s om e, bu t n ot ot h e r, s t u d ie s
t h a t e xce s s ive ca lciu m s u p p le m e n t a t ion m a y in cre a s e ca rd iova s cu la r eve n t s ,
s u ch a s m yoca rd ia l in fa rct ion , in ce rt a in p op u la t ion s .
Vit a m in D is a grou p of fa t -s olu ble s t e rols t h a t in clu d e s e rgoca lcife rol (vit a -
m in D 2 ) a n d ch ole ca lcife rol (vit a m in D 3 ); vit a m in D 3 is m ore p ot e n t t h a n vit a -
m in D 2 . Th e s e in a ct ive p roh orm on e s a re h yd roxyla t e d in t h e live r a n d kid n ey
 208 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Table 21.6 Calcium and Vit amin D Recommended Daily

Allowances from t he Inst it ut e of Medicine

AGE RANGE (YEARS) CALCIUM (MG/ DAY) VITAMIN D (IU/ DAY)

9–18 1,300 600
19–50 1,000 600
51–70 (m e n )
51–70 (w o m e n ) 1,200 600
70 1,200 800

t o p rod u ce t h e a ct ive vit a m in D m e t a bolit e ca lcit riol or 1,25-d ih yd roxyvit a m in

D. Ca lcit riol in cre a s e s ca lciu m a bs orp t ion a n d m a y p reve n t s p in a l bon e los s ,
p a rt icu la rly a m on g old e r w om e n . De s p it e BMD ga in s , s eve ra l s t u d ie s h ave n ot
s h ow n a be n e cia l e ffe ct of a ct ive vit a m in D m e t a bolit e s on fra ct u re ra t e. Re ce n t
S
E
C
evid e n ce s u gge s t s t h a t t h e im p ort a n t biologica l e ffe ct s of vit a m in D in bon e a re
T
I
n ot d ep e n d e n t on circu la t in g ca lcit riol, bu t on loca l con ce n t ra t ion s of t h is a ct ive
O
N
h orm on e ge n e ra t e d t h rou gh con ve rs ion from t h e in a ct ive vit a m in D. Th e p ot e n -
4
t ia l for h yp e rca lciu ria a n d h yp e rca lce m ia w it h a ct ive vit a m in D p rep a ra t ion s
O
lim it s t h e ir rou t in e u s e a n d re q u ire s ca re fu l s e ru m a n d u rin e m on it orin g. If
s
t
e
ca lcit riol is u s e d , it is im p ort a n t t o m od e ra t e ca lciu m s u p p le m e n t a t ion .
o
a
In a ct iva t e d vit a m in D a n a logu e s a ls o h ave be n e cia l e ffe ct s on bon e. Vit a -
r
t
h
m in D low e r s t h e r is k o f h ip a n d o t h e r n o n ve rt e b ra l fra ct u re s a m o n g o ld e r
r
i
t
w om e n a n d m e n in s om e, bu t n ot a ll, s t u d ie s . Vit a m in D m ay a ls o low e r fa ll
i
s
a
ris k. Ta ble 21.6 p rovid e s gu id e lin e s for vit a m in D d a ily re q u ire m e n t s of old e r
n
d
a d u lt s . In in d ivid u a ls w it h d ocu m e n t e d vit a m in D d e cie n cy or ca lciu m m a l-
M
a bs orp t ion , m ore vit a m in D s u p p le m e n t a t ion is n e e d e d .
e
t
a
b
Estro g e n
o
l
i
Be ca u s e of t h e a cce le ra t e d ra t e of bon e los s a t m e n op a u s e, e s t roge n rep la ce -
c
B
m e n t t h e ra py (ERT) h a s be e n u s e d in p os t m e n op a u s a l w om e n for os t e op oros is
o
n
p reve n t ion . Es t roge n re p la ce m e n t t h e ra p y is m os t e ffe ct ive in d e cre a s in g bon e
e
m a s s w h e n in it ia t e d s oon a ft e r m e n op a u s e a n d u s e d con t in u ou s ly. Es t roge n in
com bin a t ion w it h p roge s t in s ign i ca n t ly re d u ce d t h e ris k of h ip fra ct u re s on
t h e ba s is of t h e la rge Wom e n ’s He a lt h In it ia t ive (W HI). How eve r, t h is com bin a -
t ion in W HI w a s a ls o a s s ocia t e d w it h a n in cre a s e in ca rd iova s cu la r a d ve rs e
o u t co m e s a n d bre a s t ca n ce r in cid e n ce . Ve n o u s t h rom b oe m b olic eve n t s a re
t h re e t o fou r t im e s m ore com m on a m on g e s t roge n u s e rs t h a n n on u s e rs . Da ily
a d m in is t ra t ion of e s t roge n w it h con t in u ou s low -d os e p roge s t in (e.g., m e d roxy-
p roge s t e ron e 2.5 m g/d a y) is ge n e ra lly w e ll t ole ra t e d w it h ra re bre a kt h rou gh
ble e d in g a n d n o d o cu m e n t e d in cre a s e in t h e e n d o m e t r ia l t h ick n e s s . Low e r
d os e s a d m in is t e re d t h rou gh t ra n s d e rm a l p re p a ra t ion s h a ve be n e t s in bon e
w it h ou t p rod u cin g e xce s s ive t h rom boe m bolic ris k.
Ult im a t e ly, t h e d e cis ion t o in it ia t e ERT n e e d s t o be in d ivid u a lize d a n d is
b a s e d o n a b a la n ce d a s s e s s m e n t of ris k a n d b e n e t s by t h e p h ys icia n a n d
p a t ie n t . Th e p re s e n ce of d e n it ive fra ct u re ris k re d u ct ion d a t a , a s m a ll in cre a s e d
ris k for bre a s t ca n ce r, p ot e n t ia l for h yp e rcoa gu la bilit y, a n in cre a s in g con ce rn
a bou t a n ca rd iova s cu la r ris k, a n d t h e u s e of a lt e rn a t ive bon e -p rot e ct ive a ge n t s
h a ve a t t e n u a t e d e n t h u s ia s m for e s t roge n s a s a n t ios t e op orot ic a ge n t s , beyon d
t h e p e riod im m e d ia t e ly follow in g m e n op a u s e.

Se le ctive Estro g e n Re ce pto r Mo dulato rs

Se le ct ive e s t roge n re ce p t or m o d u la t o r s (SERMs ) a re n o n s t e ro id a l s yn t h e t ic
com p ou n d s t h a t h ave e s t roge n -like p rop e rt ie s in t h e bon e a n d ca rd iova s cu la r
s ys t e m s , ye t a re e s t roge n a n t a go n is t s t o t h e b re a s t a n d , in s o m e ca s e s , t h e
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 209

e n d om e t r iu m . Ra loxife n e is t h e on ly SERM cu r re n t ly lice n s e d in t h e Un it e d

St a t e s fo r os t e o p oros is . It s ign i ca n t ly low e r s bio ch e m ica l m a r ke r s o f b o n e
re m od e lin g t o leve ls e q u iva le n t t o con ju ga t e d e s t roge n s . In p os t m e n op a u s a l
w om e n , a ft e r 6 m on t h s of ra loxife n e 60 m g/d a y, bon e m a s s in t h e lu m ba r s p in e
a n d a t t h e t ot a l h ip in cre a s e d s ign i ca n t ly. Low -d e n s it y lip op rot e in s , t ot a l ch o-
le s t e rol, a n d t riglyce rid e s a ll d e clin e d a n d h igh -d e n s it y lip op rot e in s in cre a s e d .
In a la rge m u lt ice n t e r t ria l, ra loxife n e s ligh t ly bu t s ign i ca n t ly in cre a s e d BMD
of t h e s p in e a n d fe m ora l n e ck BMD, a n d re d u ce d ve rt e bra l fra ct u re ris k by 30%.
It h a s n ot be e n p rove d t o p reve n t fra ct u re s a t n on ve rt e bra l s it e s . Th e ris k of
in va s ive bre a s t ca n ce r a ls o w a s d e cre a s e d by ra loxife n e. In con t ra s t t o e s t roge n ,
h ot a s h e s a n d ot h e r m e n op a u s a l s ym p t om s m ay re cu r w it h ra loxife n e. Sim ila r
t o e s t roge n , w it h ra loxife n e t h e re is a n in cre a s e in low e r e xt re m it y e d e m a a n d
a t h re e fold in cre a s e d ris k of d e ep ve n ou s t h rom bos is .

Calcito nin
W h e n u s e d for p reve n t ion or t re a t m e n t of os t e op oros is , s yn t h e t ic ca lcit on in
(d e rive d from s a lm on ) is a d m in is t e re d e it h e r s u bcu t a n e ou s ly (u p t o 100 IU d a ily

e
n
for os t e op oros is ) or m ore com m on ly in t ra n a s a lly (200 IU d a ily). Ca lcit on in s h ou ld

o
B
be give n w it h a d e q u a t e ca lciu m (a t le a s t 1 g) a n d vit a m in D (400 IU d a ily). Ra n -

c
i
l
d om ize d con t rolle d t ria ls of in je ct a ble a n d in t ra n a s a l ca lcit on in for t re a t m e n t of

o
b
e s t a blis h e d p os t m e n op a u s a l os t e op oros is h ave con s is t e n t ly s h ow n e it h e r s t a bi-

a
t
e
liza t ion of BMD or s m a ll, bu t s ign i ca n t , in cre a s e s in ve rt ebra l BMD. Be n e cia l

M
BMD e ffe ct s a t t h e h ip h ave n ot ye t be e n rep ort e d . A 5-ye a r m u lt ice n t e r s t u d y of

d
n
ca lcit on in n a s a l s p ra y s h ow e d a 36% re d u ct ion in ve rt e bra l fra ct u re s in t h e

a
200 IU, bu t n ot in t h e 100 or 400 IU grou p s . In t e rp re t a t ion of s t u d y w a s lim it e d

s
i
t
i
by a n a p p roxim a t e ly 50% d rop ou t ra t e. Na s a l ca lcit on in is ge n e ra lly w e ll t ole r-

r
h
t
a t e d , ot h e r t h a n occa s ion a l rh in it is m in im ize d by a lt e rn a t in g n os t rils e a ch d ay.

r
a
o
He a d a ch e, u s h in g, n a u s e a , a n d d ia rrh e a h ave be e n rep ort e d m ore com m on ly

e
t
w it h s u bcu t a n e ou s t h a n w it h in t ra n a s a l ca lcit on in . On t h e ba s is of it s w e a k

s
O
a n t ire s orp t ive e ffe ct s a n d t h e ava ila bilit y of a grow in g a rm a m e n t a riu m of ot h e r

4
a n t ios t e op oros is a ge n t s , t h e u s e of ca lcit on in h a s d e clin e d ove r t im e a n d is cu r-

N
O
re n t ly re lega t e d t o a s e con d - or t h ird -lin e op t ion .

I
T
C
E
Bispho spho nate s

S
Bis p h os p h on a t e s com p ris e a cla s s of a n t ire s orp t ive a ge n t s ch a ra ct e rize d by a
p h os p h oru s –ca rbon –p h os p h oru s bon d . Th ey a re re cogn ize d a s p ot e n t in h ibi-
t ors of bon e re s orp t ion a n d re d u ce ris ks for fra ct u re s w h e n a d m in is t e re d ora lly
o r by in t ra ve n o u s in fu s io n . Va r ia t io n s in t h e s t r u ct u re o f t h e ir a m in o s id e
ch a in s a lt e r t h e p h a r m a co lo gic a ct ivit y. Bis p h o s p h o n a t e s va r ia bly s u p p re s s
o s t e o cla s t s a n d / o r le a d t o p re m a t u re d e a t h of o s t e o cla s t s a s t h e ir p rim a ry
m e ch a n is m of a ct ion . Ora l bis p h os p h on a t e s a re p oorly a bs orbe d w it h bioava il-
a bilit y of le s s t h a n 1% a n d a re bou n d by d iva le n t ca t ion s . Th u s , w it h t h e e xcep -
t ion of on e p rep a ra t ion of ris e d ron a t e t h a t is d e e m e d a cce p t a ble t o t a ke w it h
foo d , t h ey s h o u ld be t a ke n o n a n e m p t y s t o m a ch t o m a xim iz e a bs or p t io n .
Bisp h osp h on a tes tigh tly bin d to h yd roxya p a tite crysta ls in th e resorp tion la cu n a e
of bon e w h ere th ey h ave a lon g s keleta l reten tion (a bou t 10 yea rs for a len d ron a te).
Th is p rop e rt y re s u lt s in p rot ra ct e d p a rt ia l s u p p re s s ion of bon e re m od e lin g for
m on th s to yea rs a fter t h e m ed ica tion s a re d iscon tin u ed .
Fou r bis p h os p h on a t e s a le n d ron a t e, ris e d ron a t e, iba n d ron a t e, a n d zole d ron ic
a cid a re lice n s e d in t h e Un it e d St a t e s for t re a t m e n t of os t e op oros is . Pot e n t ia l
m od e s of a d m in is t ra t ion of t h e s e a ge n t s va ry s om ew h a t a s give n in Ta ble 21.7 .
Ale n d ron a t e in h ibit s bon e re s orp t ion w it h ou t d e t rim en t a l e ffect s on m in e r-
a liza t ion ove r t h e s h ort t o m od e ra t e t e rm . St u d ie s of p os t m e n op a u s a l w om e n
re ceivin g 10 m g/d ay s h ow e d t h a t lu m ba r s p in e BMD in cre a s e d u p t o 9% ove r a
2-ye a r p e riod . In a la rge US s t u dy of old er w om en w it h a t le a s t on e p rior ve rt ebra l
fra ct u re a n d low fe m ora l n eck BMD, a le n d ron a t e s ign i ca n t ly re d u ce d ve rt ebra l
a n d h ip fra ct u re s by 47% a n d 51%, re s p e ct ive ly. In s u bje ct s w it h ou t p reva le n t
 210 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Table 21.7 Prescript ion Drug Therapy for Ost eoporosis

EFFECT ON FRACTURE RISK

MOST COMMON
AGENT DOSE ROUTE FREQUENCY VERTEBRAL NONVERTEBRAL HIP
Est ro g e n Va ria b le Pill/p a t ch Da ily/w e e kly
Ra lo xife n e 60 m g Pill Da ily √ — —
Ca lcit o n in 200 IU Na sa l sp ra y Da ily √ — —
Ale n d ro n a t e 70 m g Pill We e kly √ √ √
Rise d ro n a t e 35 m g /140 m g Pill We e kly/m o n t h ly √ √ √
Ib a n d ro n a t e 150 m g /3 m g Pill/IV Mo n t h ly/3 √ — —
months
Zo le d ro n ic 5 mg IV Ye a rly √ √ √
a cid
S
De n o su m a b 60 m g Su b c in je ct io n 6 months √ √ √
E
C
T
Te rip a ra t id e 20 µg Su b c in je ct io n Da ily √ √ —
I
O
N
IV, in t ra ve n o u s; Su b c, su b cu t a n e o u s.
4
O
s
t
e
o
a
r
t
h
ve rt e bra l fra ct u re s , a le n d ron a t e 10 m g/d ay d e cre a s e d ra d iogra p h ic ve rt e bra l
r
i
t
fra ct u re s by 44%. A s im ila r m u lt in a t ion a l s t u dy of a le n d ron a t e s im ila rly id e n t i-
i
s
a
e d a 47% ris k re d u ct ion for n on ve rt ebra l fra ct u re s . Lon g-t e rm ext e n s ion s t o t h is
n
d
origin a l s t u dy s u gge s t t h a t a len d ron a t e effe ct s on BMD p e rs is t for u p t o 10 ye a rs
M
a n d BMD ga in s a re on ly m od e s t ly los t , a t t h e h ip s it e s m ore s o t h a n t h e s p in e,
e
t
w h en t h e m e d icin e is w it h d raw n . On t h e ba s is of con ve n ie n ce a n d p ot en t ia lly
a
b
be t t e r a d h e re n ce, cou p le d w it h n e a r-e q u iva le n t BMD d a t a com p a re d t o d a ily
o
l
i
a d m in is t ra t ion , a len d ron a t e is a lm os t exclu s ively give n a s a w ee kly p rep a ra t ion .
c
B
Trea tm en t w ith 5 m g/d ay of rised ron a te sign i ca n tly low ered th e risk of n ew
o
n
vertebra l (41% red u ction ) a n d n on vertebra l (39% red u ction ) over a 3-yea r p eriod in
e
w om en w ith a t lea st on e p rior vertebra l fra ctu re. A ben e cia l effect of ea ch trea t-
m en t on h ip fra ctu res a m on g w om en w ith very low bon e m a ss h a s a lso been d em -
on stra ted . Rised ron a te is gen era lly w ell tolera ted w ith n o sign i ca n t d ifferen ces in
u p p er ga stroin testin a l (GI) a dverse even ts com p a red to th ose receivin g p la cebo.
In la rge clin ica l t ria ls of iba n d ron a t e, BMD a t bot h t h e s p in e a n d t h e h ip
w e re in cre a s e d s ign i ca n t ly a bove p la ce bo a n d fra ct u re ris k re d u ct ion w a s 52%
a t t h e s p in e. Iba n d ron a t e is t h e on ly bis p h os p h on a t e in t h e Un it e d St a t e s t h a t
ca n be a d m in is t e re d e it h e r ora lly or in t ra ve n ou s ly.
Zole d ron ic a cid is a on ce -ye a rly in t rave n ou s bis p h os p h on a t e. In p h a s e III
clin ica l t ria ls it s ign i ca n t ly in cre a s e d BMD a t t h e s p in e a n d h ip a n d re s u lt ed in
a s ign i ca n t re d u ct ion in s p in e (70%) a n d ve rt ebra l fra ct u re s (25%). An ot h e r la rge
clin ica l t ria l d em on s t ra t e d t h a t a m on g m e n a n d w om e n w it h p rior h ip fra ct u re s ,
it s ign i ca n t ly re d u ce d t h e ir ris k of a s u bs e q u e n t clin ica l fra ct u re by 35%. An
u n exp la in e d re d u ct ion in a ll-ca u s e m ort a lit y w a s a ls o obs e rve d in t h a t s t u dy.
Ora l bisp h osp h on a tes m ay ca u se GI in tolera n ce, p a rticu la rly a t low ga stric p H.
Recom m en d a tion s to red u ce GI a n d m a xim ize absorp tion in clu d e in gestin g p ills
w ith 8 oz w a ter, rem a in in g u p righ t for a t lea st 30 m in u tes a fter sw a llow in g th e
tablet, a n d h avin g n oth in g to ea t or d rin k for 30 to 60 m in u tes before a n d a fter
in gestin g ea ch p ill. Ach a la sia a n d esop h a gea l strictu res a re con tra in d ica tion s to
ora l bisp h osp h on a te th era py. W h ile m ost GI toxicity of bisp h osp h on a tes is a n on -
seriou s sid e effect, th ere h ave been ra re rep orts of severe esop h agitis. Som e stu d -
ies su ggest th a t GI sa fety m ay be better for p a rticu la r agen ts. Esop h agea l ca n cer
h a s been a ssocia ted w ith ch ron ic bisp h osp h on a te a d m in istra tion in on e rep ort.
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 211

In traven ou s bisp h osp h a tes, p a rticu la rly zoled ron ic a cid ,

Figure 21.5 Osteonecrosis of the pa la ta l torus in pa tients with oste-
oporosis ta king a lendrona te. (Woo SB, Hellstein JW, ka lma r JR. Systema tic
ca n lea d t o a n a cu t e-p h a s e rea ct ion , w it h a rt h ra lgia s
a n d u like s ym p t om s in u p t o 15% of p e rs on s . Th es e
s ym p t om s a re a t t e n u a t e d w it h coa d m in is t ra t ion of
a ceta m in op h en a n d less freq u en t w ith rep ea ted in trave-
n ou s a d m in is t ra t ion or a m on g p rior u s e rs of ora l
bis p h os p h on a t e s . In t rave n ou s bis p h os p h on a t e s m ay
a lso a t lea st tra n sien tly com p rom ise ren a l fu n ction . All
bisp h osp h on a tes, p a rticu la rly in traven ou s p rep a ra tion s,
req u ire a crea tin in e clea ra n ce in excess of 30 m L/m in u te
to m in im ize ren a l risk a n d a lso to h elp a ssu re th a t th e
bon e d isea se bein g trea ted is a ctu a lly osteop orosis a n d
n ot a form of m eta bolic bon e d is ea s e a ss ocia te d w ith
ch ron ic kid n ey d is ea se. An a d d it ion a l p ote n t ia l sa fe ty
sign a l w ith in traven ou s zoled ron ic a cid w a s th e rep ort of
clin ically relevan t a tria l brilla tion in on e of th e la rge clin -
ica l trials. Th is ou tcom e w a s n ot observed in oth er large

e
review: bisphosphona tes a nd osteonecrosis of the ja ws. Ann Intern Med

n
zoled ron ic acid stu d ies or w ith oth er bisp h osp h on a tes.

o
2006;144:753–761.)

B
W h ile b is p h o s p h o n a t e s a fe t y ove ra ll h a s b e e n

c
i
l
a ccep t a ble in clin ica l t ria ls , beyon d clin ica l t ria ls , t h e re h ave be e n n u m e rou s

o
b
ca s e rep ort s lin kin g a le n d ron a t e, a n d t o a le s s e r d egre e, ot h e r bis p h os p h on a t e s

a
t
e
w it h a va rie t y of a d ve rs e e ffe ct s t h a t cou ld p ot e n t ia lly re s u lt from p rolon ge d or

M
s ign i ca n t s u p p re s s ion of bon e re m od e lin g.

d
n
Os t e on e cros is of t h e jaw (ONJ) h a s be e n a s s ocia t e d w it h bis p h os p h on a t e

a
e xp os u re a n d is d e n e d a s a n a re a of ba re a lve ola r bon e occu rrin g a n yw h e re

s
i
t
i
in t h e m ou t h (s e e Fig. 21.5 ). It occu rs m os t com m on ly follow in g d e n t a l m a n ip -

r
h
t
u la t ion s u ch a s t oot h e xt ra ct ion . Os t e on e cros is of t h e ja w h a s be e n rep ort e d in

r
a
o
u p t o 10% of p e rs on s w h o re ce ive h igh -d os e bis p h os p h on a t e s (p re d om in a t e ly

e
t
in t ra ve n ou s ly) for t h e t re a t m e n t of m a lign a n t con d it ion s . Th e in cid e n ce in p e r-

s
O
s o n s w it h o s t e o p o ro s is t a k in g b is p h o s p h o n a t e s a p p e a rs t o b e m u ch low e r,

4
a lt h ou gh e xa ct ra t e s a re u n kn ow n .

N
O
A n ew e r con ce rn is t h e d eve lop m e n t of a t yp ica l fra ct u re s in t h e s u bt ro -

I
T
ch a n t e ric (s e e Fig. 21.6A) a n d m ore d is t a l region s of t h e h ip a n d fe m u r t h a t a re

C
E
S
A B

Figure 21.6 Ra diogra phs of a typica l femora l fra ctures. A: Fra cture demonstra ting cha ra cteristic tra nsverse
pa ttern in subtrocha nteric region with media l bone “bea king.” B: Contra la tera l femur showing a rea of stress
rea ction over la ter femora l cortex. This pa ttern is commonly a ssocia ted with hip pa in.
 212 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

e xp e rie n ce d w it h ou t t ra u m a a n d a re oft e n p re ce d e d by a h ip p a in s yn d rom e

a s s ocia t e d w it h a ra d iogra p h ic s t re s s re a ct ion ove r t h e ou t e r cor t e x of bon e
(s e e Fig. 21.6B). Obs e rva t ion a l s t u d ie s t o d a t e h ave n ot e s t a blis h e d a p os it ive
lin k w it h bis p h os p h on a t e, bu t con s e n s u s s t a t e m e n t s of e xp e rt grou p s s u gge s t
t h is is s u e m e rit s a t t e n t ion . Th is m a y be re leva n t p a rt icu la rly fo r lon g-t e rm
bis p h os p h on a t e u s e rs , t h os e on glu cocort icoid s , a n d t h os e re ce ivin g bis p h os -
p h on a t e s w it h a s t a t e of low e r bon e t u rn ove r.
An ove ra rch in g is s u e w it h a ll bis p h os p h on a t e t h e ra p ie s is h ow lon g t o t re a t
a n d w h e t h e r t h e re is a ra t ion a le for a n eve n t u a l “d ru g h olid ay.” On t h e ba s is of
t h e p rot ra ct e d s u p p re s s ion of bon e t u rn ove r by bis p h os p h on a t e s a lon g w it h
e m e rgin g p ot e n t ia l s a fe t y con ce rn s t h a t m ay re la t e t o p rolon ge d bis p h os p h o-
n a t e e xp os u re, it m ay be p ru d e n t t o s t op bis p h os p h on a t e t h e ra p y for a ye a r or
m ore in p e rs on s w h o h a ve h a d a s ign i ca n t BMD re s p on s e, a re a t re la t ive ly low
ris k for fe m ora l n e ck fra ct u re, a n d h a ve h a d 5 ye a rs or m ore of ora l t h e ra p y or
s eve ra l ye a rs or m ore of in t ra ve n ou s t h e ra p y. Mon it orin g bon e t u rn ove r for
“e s ca p e ” d u rin g t h is t im e m ay p rove a s or m ore u s e fu l t h a n BMD ch a n ge s in
d e t e rm in in g w h e n t o re in it ia t e bis p h os p h on a t e or a lt e rn a t e t h e ra p ie s .
S
E
C
T
Te riparatide (Re co mbinant Parathyro id Ho rmo ne 1–34)
I
O
Terip a ra tid e is a n osteop orosis a n a bolic th era py a p p roved for u s e in p ostm en o-
N
p a u sa l a n d m a le os t e op oros is in t h e Un it ed St a t e s . In con t ra s t t o bis p h os p h o-
4
O
n a t es , w h ich block bon e re s orp t ion , t e rip a ra t id e p re d om in a t e ly s t im u la t e s t h e
s
t
osteobla st to form n ew bon e. La rge clin ica l t ria ls su p p ort its ef ca cy on in crea sin g
e
o
BMD a n d red u cin g vertebra l (65% ris k red u ction ) a s w ell a s sign i ca n t ly red u cin g
a
r
t
n on vert ebra l fra ctu res. Th ere is n o sp eci c d a ta on h ip fra ct u re risk red u ction . In
h
r
con t ra s t t o a n t ire s orp t ive a ge n t s s u ch a s bis p h os p h on a t e s a n d d e n os u m a b,
i
t
i
s
m a rkers of bon e form a tion a n d , t o a les ser d egree, bon e resorp tion a re in crea sed .
a
n
In ea rly p h a se in ves tiga t ion s w ith terip a ra tid e, a Fish er ra t m od el d evelop ed os te-
d
osa rcom a . W h ile t h is t oxicity con cern w a s n ot rep lica t ed in oth er a n im a l m od els
M
e
a n d t h e rep ort s of os t e os a rcom a t h rou gh p a s s ive s u rve illa n ce a p p e a r rou gh ly
t
a
com m e n s u ra t e w it h t h e ba ckgrou n d ra t e in t h e ge n e ra l p op u la t ion , t h is is a n
b
o
is s u e t h a t s h ou ld be d is cu s s e d w it h p a t ie n t s a n d t h a t m a n d a t es on ly a 2-yea r
l
i
c
p eriod of u s e. Alon g w ith in jection site rea ct ion s, a rth ra lgia s, m ya lgia s, a n d u sh -
B
o
in g m ay follow th e d a ily in jection s of t h is com p ou n d . Hyp erca lcem ia is a lso seen
n
e
bu t ra rely exceed s 1 m g/d L in crea s e in overa ll ca lciu m level.

De no sumab
De n os u m a b is a m on oclon a l a n t ibod y t h a t is s olu ble re cep t or t h a t bin d s a n d
in h ibit s RANKL. RANKL is a s ign a lin g m ole cu le p rod u ce d by os t e obla s t s t h a t
a re re s p on s ible for d iffe re n t ia t ion a n d a ct iva t ion of os t e ocla s t s a n d t h e ir p re -
cu rs o rs . De n o s u m a b is p ot e n t in h ibit o r of bo n e re s o rp t ion w it h a ve ry ra p id
on s e t a n d a n e q u a lly q u ick offs e t of a ct ion , re s e m blin g t h e d egre e of ch a n ge s
in bo n e t u rn ove r s e e m w it h s e x s t e ro id a d m in is t ra t ion a n d d is con t in u a t io n .
Mu lt is it e clin ica l t ria ls d e m on s t ra t e d it s s ign i ca n t im p a ct on bon e d e n s it y
a n d it s 68% a n d 40% re d u ct ion in s p in e a n d h ip fra ct u re s , re s p e ct ive ly. A s m a ll
in cre a s e in in fe ct ion s h a s be e n s e e n w it h d e n os u m a b in s om e, bu t n ot in a ll,
clin ica l t ria ls . It is u n ce rt a in if it s p ow e rfu l a n t ire s orp t ive e ffe ct s w ill be a s s oci-
a t e d in t h e fu t u re w it h ja w os t e on e cros is or a t yp ica l fra ct u re s t h a t h ave be e n
p u t a t ive ly lin ke d w it h t h e bis p h os p h on a t e s .

SURGICAL AND OTHER INTERVENTIONAL APPROACHES

Pe rcu t a n e ou s ve rt e brop la s t y a n d kyp h op la s t y, p roce d u re s t h a t t yp ica lly in je ct
p oly(m e t h yl m e t h a cryla t e ) in t o t h e ve rt e bra l bod y, a re u s e d for t h e t re a t m e n t of
p a in fu l ve rt ebra l com p re s s ion d e form it ie s . Som e, bu t n ot a ll, s t u d ie s h ave d e m -
on s t ra t e d s h ort -t e rm p a in re lie f a n d a n im p rove m e n t in a cu t e fu n ct ion . Th e
m e ch a n is m of p a in re lie f of t h is p rop os e d t e ch n iq u e is n ot w e ll u n d e rs t ood a n d
it is a ls o u n cle a r w h a t a d va n t a ge on e p roce d u re (ve rt e brop la s t y vs . kyp h op la s t y)
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 213

m ay h ave ove r t h e ot h e r. Kyp h op la s t y t ra d it ion a lly re q u ire s ge n e ra l a n e s t h e s ia

bu t u s e s a n in a t a ble ba lloon t o e xp a n d t h e ve rt ebra l s p a ce p rior t o in je ct ion of
t h e bon e ce m e n t . On e con ce rn w it h in t rod u cin g a ve ry rigid xa t ion in t o a ve ry
os t e op orot ic s p in e is t h e p ot e n t ia l for a n a cce le ra t ion of fra ct u re s a bove a n d
be low t h e s p in a l leve l be in g t re a t e d .

Gluco co rtico id- induce d Oste o po ro sis

INTRODUCTION
Os t e op oros is is a w e ll-re cogn ize d com p lica t ion of s u p ra p h ys iologic leve ls of
glu cocort icoid s . Glu cocort icoid -in d u ce d os t e op oros is (GIOP) is s e con d in fre -
q u e n cy on ly t o t h e os t e op oros is a ft e r m e n op a u s e a n d is t h e m os t com m on
form of d ru g-in d u ce d os t e op oros is . Du rin g t h e rs t 6 t o 12 m on t h s of glu cocor-
t icoid t h e ra py, t h e re is a n in it ia l ra p id los s of 3% t o 27% of BMD. Tra be cu la r bon e
is p re fe re n t ia lly a ffe ct e d , follow e d u lt im a t e ly by los s e s in cort ica l bon e. Cu m u -
la t ive s t e roid d os e is t h e p rim a ry p re d ict or of bon e los s . Follow in g a p p roxi-

e
m a t e ly 2 ye a rs o f glu co co r t ico id t h e ra p y, ra t e o f b o n e lo s s s low s in m a n y

n
o
p a t ie n t s . How eve r, BMD con t in u e s t o be los t a t a ra t e h igh e r t h a n t h a t w it h n or-

B
c
m a l a gin g. St u d ie s of s t e roid -d os e e ffe ct s a re con fou n d e d by t h e va ria ble t im in g

i
l
o
of glu cocort icoid a d m in is t ra t ion , d iffe rin g d is e a s e p roce s s e s , va ria ble a lt e rn a -

b
a
t ive os t e op oros is ris k fa ct ors (in d ep e n d e n t of glu cocort icoid u s e ), a n d t h e fa ct

t
e
M
t h a t fra ct u re ris k is u lt im a t e ly d e t e rm in e d by fa ct ors ot h e r t h a n on ly BMD. Glu -

d
cocort icoid s in cre a s e t h e ris k of fra ct u re s rou gh ly by t w ofold , in d ep e n d e n t of

n
a ge, ge n d e r, a n d rh e u m a t oid a rt h rit is (RA). Wom e n w it h RA t a kin g low -d os e

a
s
p re d n is on e h ave a n e a rly 33% ch a n ce of s e lf-rep ort in g a clin ica l fra ct u re a ft e r

i
t
i
r
5 yea rs. Alt h ou gh s a fer for bon e th a n ora l or en tera l glu cocorticoid s , even n on s ys-

h
t
r
tem ica lly a d m in istered glu cocorticoid s m ay h ave biologica l effects on bon e.

a
o
Th e e t iology of GIOP is m u lt ifa ct oria l a n d occu rs , in m a n y ca s e s , con com i-

e
t
s
t a n t ly w it h n orm a l a ge - a n d m e n op a u s e -a s s ocia t e d bon e los s . Th e re a re t w o

O
m a jor p a t h w ays by w h ich p a t ie n t s on glu cocort icoid s d eve lop a bn orm a lit ie s in

4
N
bon e m e t a bolis m : re d u ce d bon e form a t ion a n d in cre a s e d bon e re s orp t ion . W h ile

O
I
a cce le ra t ion of bon e re s orp t ion is cle a rly a n im p ort a n t p a t h w ay, t h e p re d om i-

T
C
n a n t p roble m in glu cocort icoid -in d u ce d os t e op o ros is m a y be s u p p re s s io n of

E
S
bon e form a t ion via a d ire ct t oxic e ffe ct on os t e obla s t s a n d os t e ocyt e s in bon e.

HISTORY AND PHYSICAL EXAMINATION

Th e re s h ou ld be a h igh s u s p icio n fo r p ot e n t ia l bo n e lo s s a m o n g a ll p a t ie n t s
in it ia t in g or ch ron ica lly u s in g glu cocort icoid s . A p a rt ia lly e ffe ct ive w a y t o d e t e r-
m in e a glu cocort icoid u s e r’s ris k for fu t u re bon e los s is t o a s s e s s BMD by DXA.
Mos t gu id e lin e s s u gge s t a s s e s s in g BMD if t h e p a t ie n t re ce ive s 7.5 m g p re d -
n is on e or it s e q u iva le n t for a t le a s t 1 t o 6 m on t h s . Bon e m in e ra l d e n s it y u n d e r-
e s t im a t e s t h e e ffe ct s of glu cocort icoid s on bon e ; p e rs on s fra ct u re a t a be t t e r
BMD t h re s h old . Th is s h o u ld be con s id e re d w h e n m a k in g r is k s t ra t i ca t io n
d e cis ion s on t h e ba s is of bon e m a s s m e a s u re m e n t .

PREVENTION AND TREATMENT

Th e m os t e ffe ct ive in t e rve n t ion t o p reve n t bon e los s a n d fra ct u re s a m on g glu -
cocort icoid u s e rs is d is con t in u a t ion of t re a t m e n t or, a t a m in im u m , re d u cin g
t h e d os e. Pra ct ica lly, t h is is n ot a lw ays p os s ible be ca u s e of t h e s eve rit y of m a n y
ch ron ic in a m m a t ory d is e a s e s .

Calcium and Vitamin D

Su p p le m e n t s o f e le m e n t a l ca lciu m 1,200 t o 1,500 m g/ d a y a re n e ce s s a ry,
a lt h ou gh ge n e ra lly n ot s u f cie n t a s a s ole t h e ra py, for m os t p a t ie n t s on glu co-
co rt ico id s . Vit a m in D ca n b e a d m in is t e re d in a va rie t y o f fo rm u la t io n s t h a t
h a ve b e e n in ve s t iga t e d fo r GIOP p reve n t io n a n d t re a t m e n t . Su b je ct s w h o
 214 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

re ce ive d a com bin a t ion con t a in in g ca lcit riol, ca lciu m , a n d ca lcit on in e xp e ri-
e n ce d s ign i ca n t ly le s s bon e los s in t h e s p in e t h a n t h os e re ce ivin g ca lciu m
a lon e. In a ct iva t e d vit a m in D p re p a ra t ion s a ls o h ave m e rit . Be ca u s e of im p a ir-
m e n t in ca lciu m a b s o r p t io n m e d ia t e d by glu co co r t ico id s a n d t h e co m m o n
occu rre n ce of vit a m in D d e cie n cy a m on g h ou s e bou n d p a t ie n t s s u ffe rin g w it h
ch ron ic in a m m a t ory con d it ion s , vit a m in D s h ou ld be p re s cribe d for a ll glu co-
cort icoid u s e rs . Th is ca n be a ccom p lis h e d w it h 800 IU/d ay vit a m in D 3 , ava ila ble
in m a n y m u lt ivit a m in s a n d vit a m in D–s u p p le m e n t e d ca lciu m p re p a ra t io n s .
W it h ca re fu l u s e o f e x oge n o u s ca lciu m a n d m o n it o rin g o f u rin e a n d s e ru m
ca lciu m , vit a m in D ca n be a d m in is t e re d a lt e rn a t ive ly a s ca lcit riol.

Bispho spho nate s and Te riparatide

Sim ila r to p ostm en op a u sa l a n d m a le osteop orosis, bisp h osp h on a tes con stitu te th e
p red om in a n t th era py for th ose w ith or a t risk for steroid -a ssocia ted bon e loss a n d
fra ctu re. W h en a d m in istered over 1 or 2 yea rs to p a tien ts on glu cocorticoid s for a
va riety of ch ron ic in a m m a tory d isord ers, a len d ron a te, rised ron a te, a n d zoled ron ic
a cid p reve n t a n d /or reve rs e bon e los s a t t h e s p in e a n d of t h e h ip . Th e m a gn it u d e
S
E
of ve rt ebra l fra ct u re ris k re d u ct ion s e e n for bis p h os p h on a t e in p e rs on s on glu -
C
T
cocort icoid s is ve ry s im ila r t o t h a t obs e rve d for p os t m e n op a u s a l w om e n . Te ri-
I
O
N
p a ra t id e a ls o in cre a s e s BMD in p e rs on s a t h igh ris k for glu cocort icoid -a s s ocia t e d
4
os t e op oros is a n d low e re d ve rt e bra l fra ct u re ris k com p a re d t o a le n d ron a t e.
O
s
t
e
Tre atme nt Alg o rithm
o
a
A t re a t m e n t a lgorit h m is p rop os e d in Figu re 21.7 . Give n t h e a ccu m u la t in g d a t a
r
t
h
on t h e e f ca cy of bis p h os p h on a t e s a n d t e rip a ra t id e for p reve n t in g a n d t re a t in g
r
i
t
GIOP, in it ia l a d m in is t ra t ion of a bis p h os p h on a t e s h ou ld be s t ron gly con s id e re d
i
s
a
in m a n y p e rs on s on ch ron ic glu cocort icoid s a n d t e rip a ra t id e give n t o t h os e a t
n
d
h igh e s t ris k. W h ile t h is a lgorit h m rep re s e n t s a ra t ion a l a p p roa ch , GIOP m a n -
M
a ge m e n t is ra p id ly ch a n gin g a n d w ill b e fu rt h e r re n e d , b a s e d o n e m e rgin g
e
t
lit e ra t u re a s w e ll a s s ocie t a l cos t -e ffe ct ive n e s s con s id e ra t ion s .
a
b
o
l
i
Current or anticipated steroid therapy >3 months
c
B
o
Atraumatic fractures
n
e
or high risk ?

Yes No

Yes Measurement of BMD:

T-score below – 1.5 ?
No

Calcium: 1,200–1,500 mg/day

Vitamin D3: 800 IU/day
Risk factor modification
Calcium: 1,500 mg/day
Vitamin D3: 800 IU/day Significant
Risk factor modification bone loss
Repeat BMD in 6–12 months*
Add bisphosphonate or
consider teriparatide Insignificant
bone loss

Continue conservative therapy as

long as bone loss not significant

Figure 21.7 Trea tment a lgorithm for the ma na gement of glucocorticoid-a ssocia ted
bone disease. Asterisks indicate during the rst 2 years of therapy and then less regularly.
(Adapted from Rosen HN, Rosenblatt M. Prevention and treatment of glucocorticoid-induced
osteoporosis. In: Rose B, ed. UptoDate . Vol. 6, No. 3. Wellesley, MA: UpToDa te. Reprinted
in, Saag KG, Morgan SL, Cao X, et al. Bone in health and disease In: Koopman WJ, ed.
Arthritis and Allied Condition: A Textbook of Rheumatology. 15th ed. Phila delphia: Lippincott
Williams & Wilkins; 2005:2449–2541.)
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 215

Ma le Oste o po ro sis
INTRODUCTION
Os t e op oros is in m e n is com m on : a bou t 20% of a ll os t e op orot ic fra ct u re s occu r
in m e n . As t h e p o p u la t io n a ge s , o s t e o p o ro s is in m e n is b e co m in g a n eve n
gre a t e r p u blic h e a lt h p roble m .
In Nort h Am e rica , m e n a ge d 50 ye a rs h a ve a n a p p roxim a t e 13% life t im e
ris k for fra ct u re of t h e h ip , s p in e, or fore a rm . In t h e Un it e d St a t e s , t h e in cid e n ce
of h ip fra ct u re in m e n old e r t h a n 65 ye a rs is 4 t o 5 in 1,000; a bou t h a lf t h a t in
w om e n of s im ila r a ge. In cid e n ce of h ip fra ct u re in m e n d iffe rs be t w e e n d iffe r-
e n t e t h n ic grou p s . Africa n -Am e rica n m e n h ave a ra t e a bou t h a lf t h a t of Ca u ca -
s ia n s , a n d Ja p a n e s e m e n livin g in Ja p a n or Haw a ii m ay h a ve a low e r fre q u e n cy
t h a n Ca u ca s ia n Am e rica n m e n . Os t e op o rot ic ve r t e bra l fra ct u re s in m e n a re
m ore com m on in t h e low t h ora cic region , bu t m ay occu r a t a n y leve l. Eld e rly
m e n le s s oft e n fra ct u re m ore t h a n on e ve rt e bra l bod y. Mos t fra ct u re s a re t h e
a n t e r io r co m p re s s io n t yp e ; cr u s h fra ct u re s o ccu r le s s co m m o n ly t h a n in
w om e n , t h e re by a ccou n t in g for le s s kyp h os is in m e n .

e
n
o
Th e gre a t e r bon e m a s s in m e n t h a n in w om e n is m os t ly re la t e d t o bod y

B
s ize, w it h t h e e xcep t ion of a few s it e s s u ch a s t h e ra d iu s . Aft e r a t t a in in g p e a k

c
i
l
o
bon e m a s s , m e n m a in t a in a s t a ble BMD d u rin g m id d le a ge a n d t h e n los e bon e

b
a t a n a cce le ra t in g ra t e in t o old a ge. Th is ra t e m ay re a ch 5% t o 10% p e r d e ca d e,

a
t
e
a n d is gre a t e r in t ra be cu la r t h a n cort ica l bon e. As m a n y a s 20% t o 40% of m e n

M
w it h a n os t e op orot ic fra ct u re h ave n o id e n t i a ble m e d ica l con d it ion or ris k fa c-

d
n
t or a s s ocia t e d w it h os t e op oros is ; t h ey a re d e s ign a t e d a s h a vin g p rim a ry os t e -

a
s
op oros is t o d is t in gu is h t h e m from m e n w h o h a ve los t s u bs t a n t ia l bon e m a s s

i
t
i
r
s e con d a ry t o a n y of va riou s con d it ion s .

h
t
r
a
o
e
HISTORY AND PHYSICAL EXAMINATION

t
s
O
In m e n w it h clin ica l fe a t u re s or n d in gs s u gge s t ive of m e t a bolic bon e d is e a s e

4
(s u ch a s ra d iogra p h ic os t e op e n ia , low -t ra u m a fra ct u re s , or d is ord e rs a s s ocia t e d

N
O
w it h bon e los s ), m e a s u re m e n t of BMD s h ou ld be con s id e re d . Th e s e m e a s u re -

I
T
m e n t s m ay be u s e d t o con rm low bon e m a s s , ga u ge it s s eve rit y, a n d s e rve a s a

C
E
ba s e lin e t o a s s e s s t h e p rogre s s ion of d is e a s e or t h e ra p e u t ic re s p on s e. Crit e ria t o

S
d e n e os t e op oros is in m e n a re n ot a s cle a r a s for w om e n . Es t im a t e s of fra ct u re
ris k d e rive d from m e a s u re m e n t s of w om e n m ay n ot a p p ly t o m e n . Low e r bon e
d e n s it y is a s s ocia t e d w it h a n in cre a s e d ris k for fra ct u re a n d m e a s u re m e n t s ca n
be u s e d t o m on it or s e ria l ch a n ge s in bon e m a s s .
Th e in it ia l h is t ory a n d p h ys ica l e x a m in a t io n s h o u ld be u n d e rt a ke n w it h
kn ow le d ge of con d it ion s a s s ocia t e d w it h os t e op oros is . Sp e cia l a t t e n t ion s h ou ld
be give n t o s ign s of ge n e t ic, n u t rit ion a l, a n d life s t yle fa ct ors (a lcoh ol or t oba cco),
s ys t e m ic illn e s s , a n d m e d ica t ion u s a ge. If t h e ca u s e of os t e op oros is re m a in s
u n d e n e d , m e a s u re m e n t of s e ru m t h yroid -s t im u la t in g h orm on e, a n d 24-h ou r
u rin a ry ca lciu m a n d cort is ol s h ou ld be con s id e re d .

TREATMENT
To a ch ieve m a xim a l a d u lt bon e m a s s , a d ole s ce n t boys s h ou ld be e n cou ra ge d t o
in ge s t 1,300 m g ca lciu m d a ily in t h e ir d ie t s , p a rt icip a t e in regu la r w e igh t -be a rin g
exe rcis e, m a in t a in id e a l bod y w e igh t , a n d avoid u s e of t oba cco a n d exce s s ive
a lcoh ol. Ext e n d in g t h is a p p roa ch in t o a d u lt h ood , it is re com m e n d e d t h a t m e n
a ge d 19 t o 50 con s u m e 1,000 m g ca lciu m d a ily a n d t h a t m e n old e r t h a n 50 ye a rs
con s u m e 1,000 t o 1,200 m g d a ily (s e e Ta ble 21.6 ).
Te s t os t e ron e in cre a s e s BMD in h yp ogon a d a l m e n or t h os e on glu cocort i-
coid t h e ra py, a n d h a s be e n u s e d e m p irica lly in e u gon a d a l m e n , a lbe it in s h ort -
t e rm t ria ls . Th e goa l of t h e ra p y is a p h ys iologic t e s t os t e ron e p ro le. Sid e e ffe ct s
ge n e ra lly a re n ot s e riou s , a lt h ou gh lon g-t e rm s a fe t y is n ot w e ll e s t a blis h e d .
 216 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Exce s s ive libid o is u n com m on . We igh t m ay in cre a s e be ca u s e of a n a bolic e ffe ct s

on le a n m a s s or s a lt a n d w a t e r re t e n t ion , p a rt icu la rly in m e n w it h ca rd ia c d is -
e a s e, cirrh os is , or n ep h rot ic s yn d rom e. Urin a ry re t e n t ion is u n com m on in t h e
a b s e n ce o f p ro s t a t ic ca n ce r, a n d t h e re is ge n e ra lly n o s ign i ca n t e ffe ct o n
s e ru m p ros t a t ic-s p e ci c a n t ige n or p ros t a t ic volu m e. W h e t h e r t h e lik e lih ood
for p ros t a t ic ca n ce r in cre a s e s m u s t aw a it la rge clin ica l t ria ls . Som e m e n d eve lop
e ryt h rocyt os is be ca u s e of a u gm e n t e d e ryt h rop oie s is . Leve ls of t ot a l a n d HDL
ch o le s t e ro l fre q u e n t ly d e cre a s e . Gyn e co m a s t ia m a y d eve lo p . 17 α-a lkyla t e d
a n d ro ge n s s h o u ld b e a vo id e d b e ca u s e o f gre a t e r r is k s fo r in cre a s e d live r
e n zym e s , ch ole s t a s is , a n d live r t u m ors . Con t ra in d ica t ion s t o a n d roge n t h e ra py
in clu d e p ros t a t ic ca n ce r, p ros t a t ic h yp e rt rop h y, a n d s le ep a p n e a .
Am on g ot h e r t h e ra p ie s , bis p h os p h on a t e s cu rre n t ly offe r s u bs t a n t ia l p rom -
is e a lon g w it h t e rip a ra t id e a n d d e n os u m a b. Corre ct ion of h yp e rca lciu ria w it h
h yd roch lorot h ia zid e 25 m g t w ice d a ily ca n s ign i ca n t ly in cre a s e bon e m a s s .
Su p p le m e n t a t io n w it h vit a m in D a n d ca lciu m s h o u ld be e n co u ra ge d , s in ce
t h ey a re re la t ive ly in e xp e n s ive a n d s a fe, m ay h ave m od e s t in d e p e n d e n t be n e -
t s t o bon e, a n d m ay p ot e n t ia t e ot h e r t h e ra p e u t ic in t e rve n t ion s .
S
E
C
T
I
O
Oste o ma la cia
N
4
INTRODUCTION
O
s
t
No r m a l b on e grow t h a n d m in e ra liz a t io n re q u ire a d e q u a t e vit a m in D, ca lciu m ,
e
o
a n d p h os p h o ru s . A p ro lo n ge d d e cie n cy o f a n y o f t h e s e le a d s t o a ccu m u la -
a
r
t
t io n o f u n m in e ra liz e d b o n e m a t r ix , o r o s t e o id , a n d s low b o n e fo r m a t io n .
h
r
i
De cre a s e d m in e ra liz a t io n in yo u n g p a t ie n t s ca u s e s rick e t s b e ca u s e o f d a m a ge
t
i
s
o f grow t h p la t e s (e p ip h ys e s ) a n d n ew ly fo rm e d t ra be cu la r a n d co r t ica l b o n e .
a
n
St re n gt h of t h e bo n e m a t r ix is d e cre a s e d , le a d in g t o s t r u ct u ra l d e fo rm it ie s in
d
M
w e igh t -b e a rin g bo n e s , s u ch a s bow in g. In o ld e r in d ivid u a ls in w h om e p ip h y-
e
s e s h a ve clo s e d a n d o n ly b o n e is a ffe ct e d , t h is d e fe ct ive m in e ra liz a t io n is
t
a
b
ca lle d o s t e o m a la cia .
o
l
i
c
B
Cause s 0f Oste o malacia
o
n
e
Vit a m in D-re la t e d
Lo w d ie t a ry in t a ke
Lo w su n lig h t e xp o su re
Ma la b so rp t io n
Bilia ry d ise a se
Ce lia c d ise a se
Ba ria t ric su rg e ry
Bile a cid -b in d in g re sin s
In cre a se d re n a l cle a ra n ce
Ne p h ro t ic syn d ro m e
In cre a se d ca t a b o lism
Ph e n yt o in
Ba rb it u ra t e s
Rifa m p in
Pse u d o vit a m in D-d e cie n t ricke t s
He re d it a ry vit a m in D-re sist a n t ricke t s
Hyp o p h o sp h a t e m ia
Tu m o r in d u ce d o st e o m a la cia
Ge n e t ic Hyp o p h o sp h a t e m ic ricke t s syn d ro m e s
Fa n co n i’s syn d ro m e
Re n a l t u b u la r a cid o sis (t yp e 2)
Misce lla n e o u s
Hyp o p h o sp h a t a sia
Alu m in u m in t o xica t io n
Flu o ro sis
Bisp h o sp h o n a t e o ve rd o se
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 217

HISTORY AND PHYSICAL EXAMINATION

Clin ica l m a n ife s t a t ion s of os t e om a la cia m ay m im ic rh e u m a t ic d is ord e rs w it h
ge n e ra lize d a ch in g bon e p a in , e a s y fa t igu e, p roxim a l w e a kn e s s , a n d p e ria rt icu -
la r t e n d e rn e s s . Th e s e s ym p t om s p rom p t ly re s olve w it h t re a t m e n t t o corre ct t h e
m in e ra liza t ion d e fe ct . Ra d iogra p h s of p a t ie n t s w it h ricke t s m ay s h ow ge n e ra l
d e m in e ra liza t ion w it h t h in n in g of cort ica l s u rfa ce s of lon g bon e s , w id e n in g,
frayin g, a n d cu p p in g of d is t a l e n d s of t h e s h a ft , a n d los s of t h e zon e of p rovi-
s ion a l ca rt ila gin ou s ca lci ca t ion . Som e p a t ie n t s w it h os t e om a la cia e xh ibit t h in
cort ica l ra d iolu ce n t lin e s (s t re s s fra ct u re s ) p e rp e n d icu la r t o t h e bon e s h a ft t h a t
a re oft e n s ym m e t rica l a n d bila t e ra l (ca lle d Loos e r’s zon e s ); ot h e r p a t ie n t s m ay
h ave m u lt ip le old rib fra ct u re s w it h p oor ca llu s form a t ion .

STUDIES
La bora t ory fe a t u re s of vit a m in D–d e cie n cy os t e om a la cia a re low or n orm a l
s e ru m ca lciu m leve l, h yp op h os p h a t e m ia , in cre a s e d s e ru m a lka lin e p h os p h a t a s e

e
leve l, a n d a low s e ru m 25-h yd roxyvit a m in D. Se con d a ry h yp e ra p a ra t h yroid is m

n
o
e n s u e s t o ra is e s e ru m ca lciu m t o n e a r n orm a l. Hyp op h os p h a t e m ia is t h e re s u lt

B
of p h os p h a t e w a s t in g be ca u s e of e leva t e d PTH a s w e ll a s re d u ce d gu t a bs orp -

c
i
l
o
t io n fro m vit a m in D d e cie n cy. In d ivid u a lly, e leva t e d PTH a n d h yp o p h o s -

b
p h a t e m ia s t im u la t e re n a l s yn t h e s is of 1,25-d ih yd roxyvit a m in D t o m a in t a in

a
t
e
n orm a l s e ru m leve ls . Urin e ca lciu m is a ls o exp e ct e d ly low. Ca lciu m -d e cie n cy

M
os t e om a la cia is a s s ocia t e d w it h s im ila r la bora t ory n d in gs e xcep t t h a t vit a m in

d
n
D a n d s e ru m p h os p h oru s a re oft e n n orm a l.

a
s
In o s t e o m a la cia b e ca u s e o f h yp o p h o s p h a t e m ic s t a t e s a s s o cia t e d w it h

i
t
i
r
h yp e rp h os p h a t u ria , s e ru m ca lciu m , PTH, a n d 25-h yd roxyvit a m in D a re n orm a l,

h
t
r
s e ru m a lka lin e p h o s p h a t a s e leve ls a re u s u a lly in cre a s e d , s e ru m p h os p h o ru s

a
o
a n d 1,25-d ih yd roxyvit a m in D leve ls a re low, a n d u rin a ry p h os p h oru s e xcre t ion

e
t
is ve ry h igh . Pa t ie n t s w it h t yp e II re n a l t u bu la r a cid os is h a ve d e fe ct ive re a b-

s
O
s o rp t io n o f b ica rb o n a t e a n d m a n ife s t h yp e rch lo re m ic h yp o k a le m ic a cid o s is

4
w it h h yp o p h o s p h a t e m ia b e ca u s e o f a u gm e n t e d p h o s p h a t u r ia . Low s e r u m

N
O
1,25-d ih yd roxyvit a m in D leve ls in s om e p a t ie n t s m ay be t h e con s e q u e n ce of

I
T
C
a bn orm a l p roxim a l t u bu la r m e t a bolis m . Hyp op h os p h a t a s ia is a ra re a u t os om a l-

E
S
d o m in a n t d is ord e r w it h d e cre a s e d s e r u m bon e a lk a lin e p h o s p h a t a s e leve l;
s e ru m ca lciu m , p h os p h oru s , 25-h yd roxyvit a m in D, a n d 1,25-d ih yd roxyvit a m in D
leve ls a re n ot re d u ce d .

TREATMENT
Tre a t m e n t is ba s e d on t h e u n d e rlyin g d is ord e r. Vit a m in D–d e cie n t os t e om a la -
cia re q u ire s h igh d o s e s o f vit a m in D t o re s t o re p ro p e r b o n e m in e ra liza t io n .
Ergoca lcife rol, or vit a m in D 2 , s h ou ld be a d m in is t e re d a t a d o s e of 50,000 IU
t w ice a w e e k for a t le a s t 8 w e e ks be fore re a s s e s s m e n t of s e ru m ca lciu m a n d
vit a m in D. Vit a m in D leve ls gre a t e r t h a n 30 n g/m L h ave be e n p rop os e d t o be
a s s ocia t e d w it h op t im a l bon e h e a lt h . On ce t h a t leve l h a s be e n a ch ieve d , s ev-
e ra l vit a m in D m a in t e n a n ce regim e n s a re a va ila ble, in clu d in g ch ole ca lcife rol
(vit a m in D 3 ) 1,000 t o 2,000 IU d a ily or e rgoca lcife rol 50,000 IU eve ry 2 t o 4 w e e ks .
In p a t ie n t s w it h gu t m a la bs orp t ion , eve n h igh e r d os e s m a y be re q u ire d . Ge n e r-
a lly, t h e a ct ive form of vit a m in D (1,25-d ih yd roxyvit a m in D) s h ou ld be avoid e d
a s it h a s a s h ort h a lf-life a n d is a s s ocia t e d w it h a h igh e r ris k of h yp e rca lce m ia .
Su n ligh t is a n ot h e r m e t h od t o m a in t a in vit a m in D s t ore s in p a t ie n t s w h o a re
n ot p ron e t o s u n bu rn or s kin ca n ce r. Su p p le m e n t a l ca lciu m , 1,000 t o 2,000 m g/
d ay, is n e ce s s a ry for bot h vit a m in D– a n d ca lciu m -d e cie n t os t e om a la cia .
In p a t ie n t s w it h re n a l t u b u la r a cid o s is , re s t o ra t io n o f t h e s e r u m b ica r b o -
n a t e leve l t o n o r m a l u s in g s o d iu m o r p o t a s s iu m cit ra t e s u p p le m e n t s reve r s e s
b o n e re s o r p t io n a n d h yp e rca lciu r ia . Pa t ie n t s w it h o s t e o m a la cia b e ca u s e o f
h y p e r p h o s p h a t u r ia r e q u ir e o r a l p h o s p h a t e s u p p le m e n t s , ge n e r a lly 1 t o
 218 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

4 g/ d a y d ivid e d in fo u r t o s ix d o s e s a n d 1,25-d ih yd ro x yvit a m in D, 0.5 t o 1.5 µg/

d a y. Ca lciu m s u p p le m e n t s m a y b e n e ce s s a ry t o a vo id s ym p t o m a t ic h yp o ca l-
ce m ia , b u t s h o u ld n o t b e t a k e n co n co m it a n t ly w it h a p h o s p h o r u s s u p p le -
m e n t . On ce t h e b o n e d is e a s e h a s h e a le d , t h e 1,25-d ih yd rox yvit a m in D ca n b e
d is co n t in u e d .

Prima ry Hype rpa ra thyro idism

INTRODUCTION
Pr im a ry h yp e r p a ra t h yro id is m a n d m a lign a n cy a re t h e t w o m o s t co m m o n
ca u s e s of h yp e rca lce m ia , a ccou n t in g for m ore t h a n 90% of p a t ie n t s w it h h yp e r-
ca lce m ia . Th e p reva le n ce of p rim a ry h yp e rp a ra t h yroid is m ra n ge s from 1 in 400
t o 1 in 1,000, a n d h a s in cre a s e d s eve ra l-fold in t h e la s t 25 ye a rs be ca u s e of m ore
rou t in e s e ru m ca lciu m m e a s u re m e n t s . Mos t in d ivid u a ls a re be t w e e n 40 a n d
60 ye a rs a n d t h e fe m a le /m a le ra t io is a bou t 3:1. A p a ra t h yroid a d e n om a is t h e
ca u s e in a bou t 80% of p a t ie n t s , w h e re a s h yp e rp la s ia of a ll gla n d s is fou n d in
a bou t 15% t o 20% of p a t ie n t s a n d p a ra t h yroid ca rcin om a in le s s t h a n 0.5%. If
S
E
C
t h e d is ord e r a p p e a rs in ch ild h ood , a fa m ilia l h yp e rp a ra t h yroid s yn d rom e s u ch
T
I
a s a m u lt ip le e n d ocrin e n e op la s ia s h ou ld be con s id e re d .
O
N
4
HISTORY AND PHYSICAL EXAMINATION
O
s
t
Ove rs e cre t ion of PTH p rim a rily a ffe ct s t h e s ke le t on a n d kid n eys . Pron ou n ce d
e
o
o s s e o u s m a n ife s t a t io n s , s u ch a s s u b p e r io s t e a l re s o r p t io n o f t h e m id d le
a
r
t
p h a la n ge s a n d d is t a l cla vicle, “s a lt -a n d -p ep p e r” s ku ll, a n d bon e cys t s a re n ow
h
r
i
re la t ive ly u n co m m o n . Mo re fre q u e n t is lo s s o f b o n e m a s s , p re fe re n t ia lly in
t
i
s
s it e s rich in cort ica l bon e, s u ch a s t h e d is t a l t h ird of t h e fore a rm or fe m o ra l
a
n
n e ck . Ne p h rolit h ia s is d eve lop s in a b ou t 5% o f p a t ie n t s . Diffu s e d e p os it ion of
d
M
ca lciu m –p h o s p h a t e co m p le x e s m a y ca u s e n e p h ro ca lcin o s is t h a t ca n le a d t o
e
in t e rs t it ia l bros is a n d re d u ce re n a l cle a ra n ce. Abou t 25% t o 30% of p a t ie n t s
t
a
b
h ave h yp e rca lciu ria . Com p lica t ion s be ca u s e of s eve re h yp e rca lce m ia , s u ch a s
o
l
p roxim a l w e a kn e s s in t h e legs , w e igh t los s , n a u s e a , con s t ip a t ion , p a n cre a t it is ,
i
c
B
a n d ba n d ke ra t op a t h y, a re n ow ra re.
o
n
e
STUDIES
Th e d ia gn os is is ge n e ra lly e s t a blis h e d by a n in cre a s e d s e ru m in t a ct PTH con ce n -
t ra t ion in a p a t ie n t w it h h yp e rca lce m ia . Th e s e ru m p h os p h oru s con ce n t ra t ion is
low n orm a l or low, a n d s om e p a t ie n t s e xh ibit a m ild n on ga p h yp e rch lore m ic
m e t a bolic a cid os is . Pa t ie n t s w it h s ign i ca n t bon e d is e a s e m ay h ave in cre a s e d
leve ls of m a rke rs of bon e form a t ion . Prim a ry h yp e rp a ra t h yroid is m s h ou ld be
d is t in gu is h e d from t h e le s s com m on fa m ilia l h yp oca lciu ric h yp e rca lce m ia
(FHH). Th is a u t os om a l-d om in a n t ge n e t ic con d it ion is ca u s e d by m u t a t ion s in
t h e ca lciu m -s e n s in g re cep t or. A low u rin e ca lciu m /cre a t in in e cle a ra n ce ra t io of
le s s t h a n 0.01 is ch a ra ct e ris t ic of FHH. Th is con d it ion d oe s n ot re q u ire s p e ci c
t re a t m e n t , a n d p a t ie n t s a n d ot h e r a ffe ct e d fa m ily m e m be rs s h ou ld be cou n -
s e le d t h a t s u rgica l p a ra t h yroid e ct om y is n ot re q u ire d .

TREATMENT
Th e cu re for p rim a ry h yp e rp a ra t h yroid is m is s u rgica l re m ova l of t h e p a ra t h y-
ro id a d e n om a o r ca rcin o m a , o r m o s t of t h e h yp e rp la s t ic t is s u e, a ft e r w h ich
bon e m a s s oft e n in cre a s e s for s eve ra l ye a rs . Th e ge n e ra l gu id e lin e s for re com -
m e n d in g s u rge ry in p a t ie n t s w it h ou t ca rcin om a a re a s e ru m ca lciu m con ce n -
t ra t ion gre a t e r t h a n 1 m g/d L a bove t h e u p p e r lim it of n orm a l, a cre a t in in e cle a r-
a n ce le s s t h a n 60 m L/m in u t e, a DXA T-s core e q u a l t o or le s s t h a n −2.5 in t h e h ip ,
s p in e, or d is t a l ra d iu s a n d a ge le s s t h a n 50. Ra re ly, p os t op e ra t ive h yp oca lce m ia ,
h yp o p h o s p h a t e m ia , a n d h yp o m a gn e s e m ia , o r “h u n gry bo n e ” s yn d ro m e, ca n
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 219

occu r e s p e cia lly in p a t ie n t s w it h e xt re m e ly low vit a m in D s t ore s . Ot h e r ris k

fa ct ors in clu d e re s e ct ion of la rge a d e n om a s a n d old e r a ge.
For p re op e ra t ive m a n a ge m e n t or p a t ie n t s d e e m e d u n a ble t o u n d e rgo p a r-
a t h yroid s u rge ry, m e d ica l m a n a ge m e n t in clu d e s a d e q u a t e h yd ra t ion a n d m od -
e ra t e in t a k e o f ca lciu m , a vo id a n ce o f t h ia z id e d iu re t ics t h a t m a y in cre a s e
s e ru m ca lciu m con ce n t ra t ion s , a n d regu la r a m bu la t ory e xe rcis e. Me d ica t ion s
p re s crib e d fo r os t e op oro s is t h a t re d u ce s bo n e re s o rp t ion s u ch a s e s t roge n –
p roge s t in , ra loxife n e, a n d bis p h os p h on a t e s re d u ce bon e los s , bu t t h ey a re m in -
im a lly e ffe ct ive a t low e rin g s e ru m ca lciu m . Re ce n t evid e n ce s u gge s t s be n e t in
re d u cin g s e r u m ca lciu m in p r im a ry h yp e r p a ra t h yro id is m , b u t is n o t FDA
a p p rove d for t h is in d ica t ion .

Se co nda ry Hype rpa ra thyro idism

Se con d a ry h yp e rp a ra t h yroid is m is re la t ive ly com m on a n d m ay ca u s e e n ou gh
bon e los s t o con t ribu t e t o t h e ge n e s is of os t e op oros is . Vit a m in D d e cie n cy, low

e
d ie t a ry ca lciu m , glu cocort icoid t h e ra py, fa t m a la bs orp t ion , loop d iu re t ic t h e ra py,

n
o
a n d re n a l in s u f cie n cy m ay ca u s e s e con d a ry h yp e rp a ra t h yroid is m . Tre a t m e n t

B
c
in clu d e s ca lciu m s u p p le m e n t s a n d vit a m in D rep la ce m e n t . In ch ron ic kid n ey

i
l
o
d is e a s e, con ve r s ion o f vit a m in D t o t h e a ct ive 1,25-d ih yd roxyvit a m in D is

b
a
im p a ire d , s o rep la ce m e n t w it h t h e a ct ive vit a m in D is in d ica t e d . Th e ca lcim i-

t
e
M
m e t ic a ge n t cin a ca lce t is e ffe ct ive in m a n a gin g s e con d a ry h yp e rp a ra t h yroid is m

d
be ca u s e of ch ron ic kid n ey d is e a s e.

n
a
s
i
Oste o g e ne sis Impe rfe cta

t
i
r
h
t
r
a
Occa s ion a lly a n a d u lt w it h m u lt ip le fra ct u re s , e s p e cia lly in t h e lon g bon e s of

o
e
t h e legs , a n d ra d iogra p h ic os t e op e n ia h a s os t e oge n e s is im p e rfe ct a . A ge n e t i-

t
s
O
ca lly d e t e rm in e d in a bilit y t o form q u a n t it a t ive ly or q u a lit a t ive ly n orm a l colla -

4
ge n ch a ra ct e rize s t h is grou p of d is ord e rs . Seve ra l m u t a t ion s in t h e ge n e for t yp e

N
1 p rocolla ge n h ave be e n id e n t i e d ; a ll re s u lt in form a t ion of u n s t a ble colla ge n

O
I
T
h e lice s . Mos t p a t ie n t s d eve lop fra ct u re s in ch ild h ood . Som e in d ivid u a ls a re d e a f

C
E
or h ave blu e s cle ra , bu t ot h e rs h ave on ly os s e ou s m a n ife s t a t ion s .

S
If n o p h en otyp ic ch a ra ct e ris t ic of os t e oge n e s is im p erfe ct a is p res e n t excep t
for fra gile bon e s , d ia gn osis ca n be d if cu lt . A p os it ive fa m ily h is tory a n d a h is t ory
of m u lt ip le fra ct u re s in ch ild h ood a re su gges t ive. Ra d iogra p h s s h ow t h in n in g of
cortica l a n d t ra becu la r a re a s of bon e s , es p ecia lly m et a ca rp a ls a n d m e t a ta rs a ls .
Pla t yba s ia of t h e s ku ll a n d bon e is la n d s in t h e cra n iu m s u gge s t os t e oge n e s is
im p erfe ct a . Bon e biop s y s h ow s d im in is h e d q u a n t ities of os t eoid a n d exce s s ive
os t e ocyt e n u m be rs . Th e ra py w it h gon a d a l h orm on e s , bis p h os p h on a t e s , a n d
a n e cd ota l u s e of t erip a ra t id e h a s be en a dvoca t ed . Bis p h os p h on a t e s m ay re d u ce
th e su bs e q u e n t fra ct u re ra t es .

Hype rthyro idism

Bon e d is e a s e of h yp e rt h yroid is m (e it h e r orga n ic or ia t roge n ic from ove rze a lou s
u s e o f t h yroid s u p p le m e n t s ) is a t yp e o f h igh -t u rn ove r o s t e op o ros is . Se ru m
t riiod ot h yron in e leve ls in ve rs e ly corre la t e w it h bon e m a s s . Pa t ie n t s m ay h a ve
bon e p a in a n d fra ct u re, in a d d it ion t o ot h e r fe a t u re s of h yp e rt h yroid is m . Ra d i-
ogra p h s m a y s h ow d iffu s e os t e op e n ia ; a bn orm a l s t ria t ion s of cort ica l bon e a re
o b s e r ve d o cca s io n a lly. Bio ch e m ica l p a ra m e t e r s u s u a lly in clu d e n o r m a l o r
m ild ly in cre a s e d s e r u m ca lciu m leve ls a n d in cre a s e d s e r u m a lk a lin e p h o s -
p h a t a s e leve ls . Urin a ry e xcre t ion of ca lciu m a n d colla ge n bre a kd ow n fra gm e n t s
is oft e n in cre a s e d . Corre ct io n o f t h e h yp e rt h yroid s t a t e o ft e n re s t ore s bo n e
m a s s . Es t roge n for w om e n or bis p h os p h on a t e s m a y be con s id e re d if a n a cce l-
e ra t e d ra t e of bon e los s or d e cre a s e d bon e m a s s is p re s e n t .
 220 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Me ta bo lic Bo ne Ma nife sta tio ns o f GI Dise a se s

Pa t ie n t s a f ict e d w it h GI d is ord e rs m a y d eve lop a s p e ct ru m of bon e d is e a s e,
ra n gin g fro m o s t e o p o ro s is t o o s t e o m a la cia . Seve ra l p a t h oge n ic m e ch a n is m s
con t ribu t e (a ) ca lciu m m a la bs orp t ion , a lon e or com bin e d w it h m a la bs orp t ion
of vit a m in D, le a d in g t o s e con d a ry h yp e rp a ra t h yroid is m ; (b) im p a ire d a bs orp -
t ion of vit a m in D, a lt e re d m e t a bolis m of vit a m in D, or re d u ce d e n t e roh e p a t ic
circu la t io n o f vit a m in D m e t a b o lit e s ; a n d (c) glu co co r t ico id t re a t m e n t o f
in a m m a t ory bow e l d is e a s e. Alt h ou gh e a rly re p ort s s u gge s t e d t h a t t h e bon e
d is ord e r in p a t ie n t s w it h p rim a ry bilia ry cirrh os is w a s p re d om in a n t ly os t e o-
m a la cia , s u b s e q u e n t h is t o m o r p h o m e t r ic s t u d ie s s h ow e d t h a t o s t e o p o ro s is
w a s m o re co m m o n . Bo n e d is e a s e a ft e r ga s t re ct o m y is a ls o m o re co m m o n ly
os t e op oros is t h a n os t e om a la cia . Ca lciu m m a la bs orp t ion is m ore like ly d u e t o
los s of d u od e n a l a bs orp t ive s u rfa ce t h a n a ch lorh yd ria . Ce lia c s p ru e h a s lon g
b e e n kn ow n t o ca u s e r ick e t s in ch ild re n a n d o s t e o m a la cia in a d u lt s . Th e s e
s k e le t a l co m p lica t io n s d eve lo p eve n w it h o u t s t e a t o r rh e a o r fre q u e n t b ow e l
m ove m e n t s . Pa t ie n t s w it h in a m m a t o ry b ow e l d is e a s e m a y h a ve d e cre a s e d
S
E
BMD b e ca u s e o f o s t e o m a la cia o r o s t e o p o ro s is , a n d t h e r is k is gre a t e r fo r
C
T
Cro h n ’s d is e a s e t h a n u lce ra t ive colit is .
I
O
N
4
Oste o ne cro sis
O
s
t
e
INTRODUCTION
o
a
r
Os t e on e cros is , a ls o com m on ly re fe rre d t o a s a va s cu la r n e cros is , is a n in s id iou s
t
h
r
d is ord e r le a d in g t o d e s t ru ct ion of via ble p e ria rt icu la r ep ip h ys e a l a n d s u bch on -
i
t
i
s
d ra l bon e. Os t e on e cros is le a d s t o a ch a n ge in join t con t ou r a n d a s e con d a ry
a
n
p a in fu l d e s t ru ct ive a rt h rop a t h y. It p re d om in a t e ly a ffe ct s w e igh t -be a rin g join t s ,
d
m os t com m on ly t h e fe m ora l h e a d , le a d in g t o join t m ot ion -in d u ce d p a in . It is
M
e
e s t im a t e d t o e ffe ct u p t o 20,000 p e rs on s a ye a r a n d le a d s t o a n e s t im a t e of 10%
t
a
of a ll t ot a l kn e e a rt h rop la s t ie s . Th e re is a s t ron g m a le p re d om in a n ce. A re la t e d
b
o
con d it ion , p re d om in a t e ly a ffe ct in g ch ild re n , is os t e och on d ros is . Th is con d it ion
l
i
c
is a d ege n e ra t ion follow e d by re os s i ca t ion of n on fu s e d e p ip h ys e s . Os good –
B
o
Sch la t t e r d is e a s e of t h e t ibia l t u be ros it y is t h e be s t -kn ow n va ria n t of os t e o-
n
e
ch on d ros is , bu t ot h e r t yp e s a re w e ll d e s cribe d a n d m ay occu r in a d u lt s .
Th e re a re a va rie t y of ris k fa ct ors for os t e on e cros is , w it h t ra u m a be in g t h e
m o s t co m m o n . A cla s s ic p re s e n t a t io n is t h e d eve lo p m e n t o f fe m o ra l h e a d
os t e on e cros is m on t h s t o ye a rs a ft e r op e n re d u ct ion a n d in t e rn a l xa t ion of a
fe m ora l n e ck fra ct u re. Th is is t h o u gh t t o occu r s e con d a ry t o a com p ro m is e of
t h e t e n u ou s blood s u p p ly t o t h e fe m ora l h e a d . Th e le s s com m on n on t ra u m a t ic
ca u s e s a re p re d om in a n t ly by glu cocort icoid s a n d a lcoh ol a bu s e. Os t e on e cros is
o f t h e h ip s , k n e e s , o r h u m e ra l h e a d s is d e t e ct a ble by m a gn e t ic re s o n a n ce

Table 21.8 Pot ent ial Et iologic Fact ors for Ost eonecrosis

TRAUMATIC
NONTRAUMATIC (LESS RARE) NONTRAUMATIC (RARE)
St e ro id s Co a g u lo p a t h y
Alco h o l Pa n cre a t it is
Syst e m ic lu p u s e ryt h e m a t o sis Ga u ch e r’s d ise a se
Org a n t ra n sp la n t Ch ro n ic kid n e y d ise a se
Sickle ce ll d ise a se Pre g n a n cy
Hyp e rlip id e m ia
Ca isso n ’s d ise a se
 Ch a p te r 21 Os t e op e n ic Bon e Dis e a s e s a n d Os t e on e cros is 221

e
n
o
B
Figure 21.9 Osteonecrosis on ma gnetic resona nce ima ging. “Double-line

c
i
l
sign” on T2 ima ges with periphera l ma rgin da rk surrounding bright inner

o
b
line. (Mitchell DG, Ra o VM, Da linka MK, et a l: Femora l hea d a va scula r

a
t
Figure 21.8 Hip radiogra ph demonstra ting crescent sign. Area of colla pse necrosis: correla tion of MR ima ging, ra diogra phic sta ging, ra dionuclide

e
M
of subchondra l bone with a ccompa nying ra diolucency. ima ging, and clinica l ndings. Ra diology 1987;162:709–715.)

d
n
a
im a gin g (MRI) in 5% t o 10% of re n a l t ra n s p la n t re cip ie n t s w it h in 3 t o 6 m o n t h s

s
i
t
i
r
o f e n gra ft m e n t . Os t e o n e cro s is m a y a cco m p a n y HIV d is e a s e , p a r t icu la r ly in

h
t
r
t h e s e s e t t in g o f lip o d ys t rop h y. Ot h e r s om ew h a t com m o n a n d le s s co m m o n

a
o
fa ct ors e t iologica lly a s s ocia t e d w it h os t e on e cros is a re p rovid e d in Ta ble 21.8 .

e
t
Th e r e a r e m u lt ip le p a t h o ge n ic m e ch a n is m s t h a t m a y co n t r ib u t e t o

s
O
os t e on e cros is , in clu d in g com p rom is e of t h e bon ey va s cu la t u re (m os t com m on

4
w it h t ra u m a ) a n d a s p rogra m m e d ce ll d e a t h (a p op t os is ) of t h e os t e obla s t s a n d

N
O
os t e ocyt e s . Th e la t t e r m e ch a n is m m ay p re d om in a t e in glu cocort icoid -m e d ia t e d

I
T
C
os t e on e cros is .

E
S
STUDIES/ IMAGING
Pla in ra d iogra p h s ca n yie ld clu e s , bu t s u ffe r from p o or s e n s it ivit y fo r e a rly
le s ion s . Ch a ra ct e ris t ic ra d iogra p h ic a p p e a ra n ce s of bon e colla p s e a n d s u bch on -
d ra l fra ct u re a re s e e n in la t e r s t a ge d is e a s e (s e e Fig. 21.8 ). Bon e s cin t igra p h y
(b o n e s ca n s ) is u s e fu l in t h e e a rly d ia gn os is a n d d e m o n s t ra t e s d e cre a s e d o r
NOT TO BE MISSED a b s e n t ra d io t ra ce r a ct ivit y s u rro u n d e d by in cre a s e d a ct ivit y (“d o n u t le s io n ”)
be ca u s e of reva s cu la riza t ion . W h ile bon e s ca n h a s con s id e ra ble s e n s it ivit y, it
On w he n to pre scribe anti-
h a s low s p e ci cit y for d iffe re n t ia t in g os t e on e cros is from in fe ct ion , m ye lom a ,
o ste o po ro sis the rapy
a n d m e t a s t a t ic d is e a s e . Ma gn e t ic re s o n a n ce im a gin g is t h e m o s t s e n s it ive
• A h ist o ry o f a h ip o r m od a lit y for e a rly d ia gn os is a n d s t a gin g. A “d ou ble -lin e ” s ign is evid e n t , a n d
ve rt e b ra l fra ct u re .
in ve rs ion re cove ry p rot on d e n s it y im a gin g m ay p rovid e a s e n s it ive m e a n s t o
• T-sco re 2.5 in t h e d e t e ct e a rly le s ion s (s e e Fig. 21.9 ).
fe m o ra l n e ck o r sp in e . A s im ila r a p p e a r in g, b u t s e lf-lim it in g, e n t it y is t ra n s ie n t re gio n a l o s t e -
• T-sco re 1.0 a n d a FRAX op oros is (TRO) of t h e h ip . Ma gn e t ic re s on a n ce im a ge s for TRO a re ve ry s im ila r
10-ye a r p ro b a b ilit y o f a t o os t e on e cros is , bu t t h is con d it ion com m on ly re s olve s in 6 t o 12 m on t h s . It
h ip fra ct u re 3% in US m os t com m on ly follow s p regn a n cy, bu t is a ls o obs e rve d in m id d le -a ge d m e n .
p o p u la t io n s.
• T-sco re 1.0 a n d a FRAX
10-ye a r p ro b a b ilit y o f a TREATMENT
m a jo r o st e o p o ro sis-re la t e d Th e re is n o p rove n s t a n d a rd t h e ra p y for e ffe ct ive ly m a n a gin g o s t e o n e cro s is
fra ct u re 20% in US
p o p u la t io n s. on ce it d eve lop s . Ma n y p a t ie n t s go on t o bon ey colla p s e a n d re q u ire t ot a l join t
re p la ce m e n t , in join t s w h e re t h is is p os s ible. Wit h d raw a l of a n y in cit in g a ge n t s
 222 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

cou p le d w it h a p e riod on lim it e d or n on –w e igh t be a rin g m ay circu m ve n t s u r-

WHEN TO REFER ge ry a n d le a d t o gra d u a l s e lf-lim it e d h e a lin g. Su rgica l a p p roa ch e s t o t h is p rob-
le m , s h ort of eve n t u a l t ot a l join t s , in clu d e core d e com p re s s ion w it h or w it h ou t
• Ost e o p o ro sis t h a t is
a ce n t ra l bon e gra ft . Th e evid e n ce s u rrou n d in g t h e op t im a l t im in g a n d e ffe c-
p ro g re ssin g in sp it e o f
a p p ro p ria t e ca lciu m a n d t ive n e s s of t h e s e a p p roa ch e s is e q u ivoca l. Join t re a lign m e n t a n d p a rt ia l or t ot a l
vit a m in D su p p le m e n t a - jo in t a rt h ro p la s t y a re ge n e ra lly b e s t t o le ra t e d a n d a s s o cia t e d w it h t h e b e s t
t io n a s w e ll a s u se o f p a in a n d fu n ct ion ou t com e s . Op t ion s for m e d ica l m a n a ge m e n t of os t e on e cro-
b isp h o sp h o n a t e s. s is a re a ls o ra t h e r lim it e d . Mos t s m a ll s t u d ie s a re m os t ly a n e cd ot a l, bu t a t le a s t
• Pa t ie n t s w it h o st e o p o ro sis on e op e n -la be l ra n d om ize d , bu t n on blin d e d , s t u d y s u gge s t s a p ot e n t ia l role for
in t o le ra n t t o b isp h o sp h o - bis p h os p h on a t e s .
n a t e s.
• Evalua t ion o f o st e o mala cia.
• Eva lu a t io n o f yo u n g
p a t ie n t s w it h m u lt ip le ICD9
fra ct u re s. 756.51 Oste o g e ne sis impe rfe cta
268.2 Oste o malacia, unspe ci e d
S
733.00 Oste o po ro sis (g e n e raliz e d )
E
C
737.30 Sco lio sis (acq u ire d ) (p o st u ral)
T
I
O
733.00 [737.43] d u e t o o r asso ciat e d w it h o st e o p o ro sis
N
4
O
s
t
e
o
Sug g e ste d Re a ding s
a
r
t
h
Bile zikia n JP, Kh a n AA, Pot t s JT, Jr . Gu id e lin e s for t h e m a n a ge m e n t of a s ym p t om a t ic p rim a ry h yp e rp a ra t h y-
r
roid is m : Su m m a ry s t a t e m e n t from t h e t h ird in t e rn a t ion a l w orks h op . J Clin Endocrinol Metab 2009 ;94 (2 ):
i
t
i
s
335 –339 .
a
Bla ck DM , De lm a s PD, Ea s t e ll R, e t a l. On ce -ye a rly zole d ron ic a cid for t re a t m e n t of p os t m e n o p a u s a l os t e -
n
op oros is . N Engl J Med 2007 ;356 (18 ):1809 –1822 .
d
Bon n ick SL. Bone Densitom etry in Clinical Practice. Tot ow o a , NJ: Hu m a n a ; 1998 .
M
Ca u ley JA, Robbin s J, Ch e n Z , e t a l. Effe ct s of e s t roge n p lu s p roge s t in on ris k of fra ct u re a n d bon e m in e ra l
e
t
d e n s it y: t h e Wom e n ’s He a lt h In it ia t ive ra n d om ize d t ria l. JA MA 2003 ;290 (13 ):1729 –1738 .
a
b
Ch e s n u t CH, III, Silve rm a n S, An d ria n o K, e t a l. A ra n d om ize d t ria l of n a s a l s p ray s a lm on ca lcit on in in p os t -
o
m e n o p a u s a l w o m e n w it h e s t a blis h e d o s t e o p o ro s is : Th e p reve n t re cu rre n ce o f o s t e o p o ro t ic fra ct u re s
l
i
c
s t u d y. PROOF St u d y Grou p . A m J Med 2000 ;109 (4 ):267 –276 .
B
Ch e s n u t CH , III, Ska g A, Ch ris t ia n s e n C, e t a l. Effe ct s of o ra l iba n d ron a t e a d m in is t e re d d a ily or in t e rm it -
o
n
t e n t ly on fra ct u re ris k in p os t m e n op a u s a l os t e op oros is . J Bone Miner Res 2004 ;19 (8 ):1241 –1249 . Ep u b Ma rch
e
29, 2004.
Cu m m in gs SR, Bla ck DM , Th om p s on DE, e t a l. Effe ct of a le n d ro n a t e on ris k of fra ct u re in w om e n w it h low
b o n e d e n s it y b u t w it h o u t ve r t e b ra l fra ct u re s : Re s u lt s fro m t h e Fra ct u re In t e r ve n t io n Tr ia l . JA MA
1998 ;280 (24 ):2077 –2082 .
Et t in ge r B, Bla ck DM , Mit la k BH , e t a l. Re d u ct ion of ve rt e bra l fra ct u re ris k in p os t m e n op a u s a l w om e n w it h
os t e op oros is t re a t e d w it h ra loxife n e : Re s u lt s from a 3-ye a r ra n d om ize d clin ica l t ria l. Mu lt ip le Ou t com e s
of Ra loxife n e Eva lu a t ion (MORE) In ve s t iga t ors . JA MA 1999 ;282 (7 ):637 –645 .
Ha rris ST, Wa t t s NB, Ge n a n t HK, e t a l. Effe ct s of ris e d ron a t e t re a t m e n t on ve rt e bra l a n d n on ve rt e bra l fra c-
t u re s in w o m e n w it h p os t m e n o p a u s a l os t e op oros is : a ra n d om ize d con t ro lle d t r ia l. Ve rt e bra l Ef ca cy
W it h Ris e d ron a t e Th e ra py (VERT) St u d y Grou p . JA MA 1999 ;282 (14 ):1344 –1352 .
In s t it u t e of Me d icin e of t h e Na t ion a l Aca d e m ie s . Dietary Reference Intakes for Calcium and Vitam in D. Nove m be r
30, 2010, Con s e n s u s Rep ort .
Orw oll ES. Os t e op o ros is in m e n . Endocrinol Metab Clin North A m 1998 ;27 (2 ):349 –367 .
Na t ion a l Os t e op oro s is Fou n d a t ion . Clinician’s Guide to Prev ention and Treatm ent of Osteoporosis. Wa s h in gt on ,
DC: Na t ion a l Os t e op o ros is Fou n d a t io n ; 2010 .
Prim er on the Metabolic Bone Diseases and Disorders of Mineral Metabolism . Ros e n , CJ (Ed .) 7t h e d . Wa s h in gt on ,
DC: Th e Am e rica n Socie t y for Bon e a n d Min e ra l Re s e a rch . ; 2008 .
Riggs BL, Kh os la S, Me lt on LJ, III. A u n it a ry m od e l for in volu t ion a l os t e op oros is : Es t roge n d e cie n cy ca u s e s
bot h t yp e I a n d t yp e II os t e op oros is in p os t m e n op a u s a l w om e n a n d con t ribu t e s t o bon e los s in a gin g
m e n . J Bone Miner Res 1998 ;13 (5 ):763 –773 .
W rit in g Grou p for t h e Wom e n ’s He a lt h In it ia t ive In ve s t iga t ors . JA MA 2002 ;288 :321.
CHAPTER
22 Arthropa thies
Associa ted with
Systemic Disea ses
Leann Maska and A m y C. Cannella

e
n
o
B
c
Endo crine Dise a se s

i
l
o
A 60-ye ar-o ld Cau casian

b
w ith Asso cia te d

a
t
g e n t le m an w it h lo n g -

e
Arthro pa thie s

M
st an d in g p o o rly co n t ro lle d

d
n
t yp e 2 d iab e t e s m e llit u s DIABETES MELLITUS

a
s
Dia b e t e s is a n in cre a s in gly co m -

i
p re se n t s t o yo u r o f ce

t
i
r
m o n m e d ic a l c o n d it io n in t h e

h
w it h sym pt om s of sw e lling

t
r
Un it e d St a t e s , w it h a p reva le n ce of

a
o
an d m o d e rat e p ain in h is m o r e t h a n 23 m illio n p e o p le ,

e
t
s
rig h t m id f o o t o ve r t h e in c lu d in g b o t h d ia gn o s e d a n d

O
u n d ia gn os e d ca s e s , or o n e in t e n

4
p ast 3 w e e k s. He is u n ab le

N
a d u lt s (2 ). He a lt h ca re p rovid e r s

O
t o re call an y sp e ci c t rau -
m u s t be fa m ilia r w it h t h e m yr ia d

I
T
C
m at ic e ve n t . On e xam in at io n , t h e f o o t is w arm , sw o lle n , t e n d e r, of e xt ra gla n d u la r com p lica t ion s of

E
S
an d e ryt h e m at o u s (Fig . 22.1 ). Yo u r d iff e re n t ial in clu d e s ce llu lit is, t h e d is e a s e . It is t h ou gh t t h a t t h e
acu t e g o u t y art h rit is, o st e o m ye lit is, an d f ract u re . A n im p o rt an t a s s ocia t e d a rt h rop a t h ie s a re d u e t o
co m p lica t io n s o f d ia b e t e s , in clu d -
ad d it io n t o t h is d iff e re n t ial is co n sid e rat io n o f acu t e Ch arco t
in g n e u rop a t h y a n d m icrova s cu la r
n e u ro art h ro p at h y (CN). To ru le o u t u n d e rlyin g in f e ct io n , t h e b e st d is e a s e . Fu r t h e r m o r e , a h igh -
im ag in g st u d y is co m b in at io n o f a t h re e -p h ase b o n e scan w it h a glu co s e a n d in s u lin e n viro n m e n t
lab e le d w h it e b lo o d ce ll (W BC) scan . h a s be e n s h ow n t o h ave p a t h ologic
e ffe c t s o n m a n y k e y ce lls a n d
Jo in t p ain is o n e o f t h e m o st co m m o n re aso n s f o r a p at ie n t
m a t r ix co m p o n e n t s o f co n n e ct ive
t o se e h is o r h e r p rim ary care p ro vid e r. Of ce visit s in t h e Un it e d t is s u e s (3 ). Alt h o u gh r e la t ive ly
St at e s f o r m u scu lo sk e le t al p ain in 2000 acco u n t e d f o r 280 visit s u n com m on , ch a rcot n e u roa rt h rop -
p e r 1,000 p e o p le , an d w e re e ve n ly d ivid e d b e t w e e n acu t e an d a t h y is a n im p o r t a n t p ro ble m t o
re cogn ize a s it le a d s t o s ign i ca n t
ch ro n ic sym p t o m s (1 ). A lt h o u g h n o t in clu sive , t h is ch ap t e r aim s
d e fo r m it y a n d jo in t d e s t r u ct io n .
t o co ve r asso ciat io n s b e t w e e n a varie t y o f syst e m ic d ise ase s an d Co n ve rs e ly, a d h e s ive ca p s u lit is o f
t h e ir re lat e d m u scu lo sk e le t al m an if e st at io n s. t h e s h ou ld e r is q u it e com m on , bu t
o ft e n im p rove s w it h co n s e rva t ive
m a n a ge m e n t . Bo t h a re d is cu s s e d
in m o re d e t a il b e low. Ot h e r n o t a ble a rt h rop a t h ie s a s s o cia t e d w it h d ia b e t e s
m e llit u s in clu d e d iffu s e id iop a t h ic s ke le t a l h yp e ros t os is (DISH), ca rp a l t u n n e l
s yn d rom e, a n d os t e oa rt h rit is .

223
 224 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

CHARCOT NEUROARTHROPATHY
Clinical Pre se ntatio n
Th e in cid e n ce of CN is rep ort e d a t a p p roxim a t e ly 1 in
333 p a t ie n t s w it h d ia be t e s (4 ). Th e e xa ct p a t h oge n ic
m e ch a n is m of CN is in com p le t e ly u n d e rs t oo d ; h ow -
eve r, a com bin a t ion of bot h n e u rova s cu la r a n d n e u ro-
t ra u m a t ic t h e orie s is ge n e ra lly a cce p t e d (4 ). Cu rre n t
h yp ot h e s is s u gge s t s t h a t s om a t ic a n d a u t on om ic n e u -
ro p a t h y le a d s t o in cre a s e d blo o d ow t o t h e jo in t ,
re s u lt in g in bon e re s orp t ion a n d s u s cep t ibilit y t o m in or
t ra u m a . Con t in u e d m e ch a n ica l s t re s s occu rs be ca u s e
of los s of p rot e ct ive p a in s e n s a t ion , a n d m a jor d e s t ru c-
t ive ch a n ge s re s u lt in fra ct u re s a n d d e form it ie s .
Pa tien ts w ith CN ca n p resen t w ith a n a cu te or ch ron ic
p rocess. In a cu te CN, th e ea rliest sym p tom s a re p ersist-
en t sw ellin g a n d p a in , a lth ou gh sen sory d e cits m ay p re-
Figure 22.1 Subluxa tion of the na vicula r a nd soft tissue swelling a s
S
clu d e a ssocia ted d iscom fort. A h istory of tra u m a m ay be
E
a n ea rly ma nifesta tion of a neuropa thic joint (Courtesy of Gera ld F.
C
p resen t, a lth ou gh on e stu dy sh ow ed th a t n ea rly 75% of
T
Moore, MD.)
I
O
p a tien ts d id n ot reca ll a n y p recip ita tin g even t. Progres-
N
sion from a cu te to ch ron ic n eu roa rth rop a th y ca n be ra p id , w ith irreversible d a m -
4
age seen in less th a n 6 m on th s. Pa tien ts w ith ch ron ic CN ca n p resen t w ith estab-
O
s
lish ed d eform ity a n d m ay com p la in of a ssocia ted d if cu lties w ith a m bu la tion .
t
e
o
a
Examinatio n
r
t
h
On p h ys ica l exa m in a t ion , a foot w it h a cu t e CN is t yp ica lly w a rm , sw olle n , a n d
r
i
t
i
t e n d e r. Mod e ra t e -t o-m a rke d e ryt h e m a m ay a ls o be p re s e n t (4 ). Th e m id foot is
s
a
m os t com m on ly in volve d a n d h a s a be t t e r p rogn os is t h a n h in d foot in volve m e n t
n
d
be ca u s e of w e igh t d is t ribu t ion e ffe ct s . Typ ica l d e form it ie s in clu d e a colla p s e d
M
a rch a n d rocke r-bot t om foot w it h ca llu s form a t ion a n d p os s ible u lce ra t ion s .
e
t
a
b
Studie s
o
l
i
Dia gn os is is p rim a rily m a d e by clin ica l h is t ory a n d e xa m in a t ion . Pla in
c
B
ra d iogra p h s a re in exp e n s ive a n d ca n s h ow a n a t om ic bon y d e form it ie s ,
o
n
d e m in e ra liza t ion , a n d p e rios t e a l re a ct ion . W h e n s eve re, CN ca n re s u lt in
e
fra gm en ta tion of t h e m eta ta rs a l h ea d s, or even “p en cil a n d cu p ” d eform ities
of th e MTP join t s . Ra d iogra p h ic p rogre ss ion ca n occu r ra p id ly, oft en tim e s
w ith in severa l w eeks of a n orm a l x-ray (Fig. 22.2 ) (4 ).
It is crit ica l t o ru le ou t in fe ct ion in t h e d ia gn os t ic w ork-u p of CN. Ra d i-
ogra p h s a re n eit h e r s e n s it ive n or s p eci c for d iffe ren t ia t in g in fe ct ion from
CN. Th e com bin a t ion of a t h re e -p h a s e bon e s ca n w it h a t a gge d W BC s ca n
h a s a s en s it ivit y a n d s p e ci cit y of 80% t o 90%. In a cu t e CN, a t h re e -p h a s e
bon e s ca n s h ou ld be p os it ive in a ll t h ree p h a s e s , re e ct in g in crea s ed bon e
t u rn ove r, a n d a t a gge d W BC s ca n s h ou ld be n ega t ive in t h e a bs e n ce of
in fe ct ion . How eve r, fa ls e p os it ive W BC s ca n s ca n occu r in t h e s e t t in g of ve ry
ra p id ly a d va n cin g CN. Fu rt h e r im a gin g ca n be d on e w it h com p le m en t a ry
m a rrow s ca n n in g, w h ich if p os it ive in t h e s a m e a re a , in d ica t e s a cu t e n eu -
roa rt h rop a t h ic ch a n ge s a n d n ot in fe ct ion (4 ). Alt h ou gh m a gn e t ic re s on a n ce
im a gin g (MRI) d oe s n ot d iffe re n t ia t e CN from in fe ct ion , it give s exce lle n t
a n a t o m ic d e n it io n , d o e s n o t re q u ire ga d o lin iu m t o s e e e d e m a t o u s
ch a n ge s , a n d m ay be u s e fu l for m on it orin g p rogre s s ion of d is e a s e (4 ).

Figure 22.2 Destruction of midfoot joints in
Cha rcot neuroa rthropa thy. (Courtesy of Gera ld
F. Moore, MD.)
Tre atme nt
Th e m a n a ge m e n t of CN is lim it e d a n d m a in ly con s is t s o f re d u ct io n in
w e igh t -b e a r in g a ct ivit y. Pla s t e r ca s t in g fo r s eve ra l w e e k s t o a llow t h e
a cu t e p h a s e t o re s olve, follow e d by t ot a l-con t a ct ca s t a p p lica t ion s t h a t
a llow for be t t e r a m bu la t ion , is com m on ly u t ilize d . Ot h e r s p e cia lize d foot -
w e a r for a cu t e CN a p p lica t ion s in clu d e Ch a rcot re s t ra in t ort h ot ic w a lke rs ,
 Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 225

p a t e lla r t e n d o n -b e a r in g b ra ce s , t o t a l-co n t a ct b iva lve a n k le -fo o t o r t h o s e s ,

a n d p n e u m a t ic w a lk in g b ra ce s t h a t a llow e a r lie r m o b iliz a t io n w it h re la t ive
jo in t im m o b ilit y (4 ). Tr e a t m e n t o f ch ro n ic CN ce n t e r s o n re d u cin g p la n t a r
p re s s u re s a n d p re s e r vin g s k in in t e gr it y t o p reve n t u lce ra t io n s . Or t h o t ic co n -
s u lt a t io n ca n b e ve ry h e lp fu l in m a n a gin g a n d t re a t in g ch ro n ic d e fo r m it ie s .
Rou t in e s u rge ry is n ot a d voca t e d , a s p ot e n t ia l ris ks in clu d e lon g-t e rm w ors e n -
in g of t h e con d it ion , p os s ible n on u n ion , in fe ct ion , a n d ge n e ra l ris k of s u rge ry
a n d a n e s t h e s ia .

Clinical Co urse
Ea rly d ia gn os is of CN ca n p ot e n t ia lly p reve n t com p lica t ion s in clu d in g s eve re
d e form it y, u lce ra t ion s , a n d eve n lim b a m p u t a t ion . Be ca u s e CN is a re la t ive ly
u n com m on co n d it ion , re fe rra l t o a s p e cia lis t w it h a m u lt id is cip lin a ry t e a m
a p p roa ch is p re fe rre d .

ADHESIVE CAPSULITIS

e
n
Clinical Pre se ntatio n

o
B
Com p a re d t o 2% t o 5% of t h e ge n e ra l p op u la t ion , a p p roxim a t e ly 20% of p e op le

c
i
l
w it h d ia be t e s a re a ffe ct e d a t s om e t im e by a d h e s ive ca p s u lit is of t h e s h ou ld e r.

o
b
Th is re la t ive ly com m on con d it ion is d e n e d a s t h e in s id iou s on s e t of s h ou ld e r

a
t
p a in w it h a gra d u a l los s of bot h a ct ive a n d p a s s ive ra n ge of m ot ion (ROM) (5 ).

e
M
Th e n a t u ra l h is t o ry o f a d h e s ive ca p s u lit is is a p rogre s s ion t h rou gh fou r

d
n
s e q u e n t ia l a n d d e s crip t ive s t a ge s : (a ) p re a d h e s ive s t a ge (d iffu s e gle n oh u m e ra l

a
s yn ovit is s e e n on a rt h ros copy); (b) fre e zin g s t a ge (h yp e rt rop h ic a n d h yp e rva s -

s
i
t
i
cu la r s yn ovit is w it h ca p s u la r brop la s ia a n d s ca r form a t ion ); (c) froze n s t a ge

r
h
t
(s ign i ca n t h yp e r t ro p h y a n d h yp e r va s cu la r it y w it h d e n s e ca p s u la r s ca r );

r
a
(d ) t h a w in g p h a s e (a p p a re n t re m od e lin g w it h ou t s yn ovit is ) (5 ). Pa in is in it ia lly

o
e
t
s eve re a n d im p rove s w it h d e cre a s in g s yn ovit is in la t e r s t a ge s . A p rogre s s ive

s
O
d e clin e in ROM is n ot a ble u n t il s t a ge 4, or t h aw in g occu rs .

4
Sle e p -d is t u rbin g p a in is oft e n a m ot iva t in g fa ct or for p a t ie n t s t o s e e k m e d -

N
O
ica l a t t e n t ion . Ce rt a in e le m e n t s of t h e h is t ory ca n h e lp d e t e rm in e w h e re e a ch

I
T
p a t ie n t re s id e s on t h e co n t in u u m (Ta ble 22.1 ). For e xa m p le, a p a t ie n t w h o is

C
E
u n a ble t o s le ep t h rou gh t h e n igh t , h a s s ign i ca n t lim it a t ion s in ROM, a n d s u f-

S
fe rs from on goin g p a in is like ly in s t a ge 2, or a ct ive fre e zin g.

Examinatio n
Sign i ca n t lim it a t io n o f bo t h a ct ive a n d p a s s ive a bd u ct io n o f t h e s h o u ld e r
e xis t ; h ow eve r, t h e e xt e n t of re s t rict ion is s t a ge d ep e n d e n t . Act ive ROM t h a t is
a ccom p a n ie d by s ca p u la r m ove m e n t is a clu e t o d ia gn os is . Pa t ie n t s oft e n d is -
p lay t ra n s ie n t s eve re p a in w it h a bru p t or e n d -ra n ge m ove m e n t s . Alt h ou gh n or-
m a l s t re n gt h h a s be e n con s id e re d a cla s s ic n d in g, re ce n t s t u d ie s u s in g h a n d -
h e ld d yn a m om e t ry h ave d e m on s t ra t e d w e a kn e s s in t h e in t e rn a l a n d e xt e rn a l
rot a t ors , a bd u ct ors , a n d e leva t ors (5 ).

Table 22.1 St ages of Adhesive Capsulit is

DURATION SLEEP
STAGE (MONTHS) PAIN DISRUPTION STIFFNESS
Pre a d h e sive 0–3
Fre e zin g 3–9
Fro ze n 9–15
Th a w in g 15–24
 226 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Studie s
His t ory a n d p h ys ica l e xa m in a t ion a lon e a re oft e n a d e q u a t e t o d ia gn os e a d h e -
s ive ca p s u lit is . How eve r, im a gin g s t u d ie s ca n h e lp ru le o u t o t h e r p a t h o logy.
Pla in ra d iogra p h s a re lim it e d t o n d in g bon y p a t h ology. Ma gn e t ic re s on a n ce
im a gin g ca n d iffe re n t ia t e s o ft -t is s u e a b n o r m a lit ie s o f t h e ro t a t o r cu ff a n d
la bru m . Ult ra s on ogra p h y h a s a ls o p rove d t o be u s e fu l in d e cip h e rin g a d h e s ive
ca p s u lit is from rot a t or cu ff t e n d in op a t h y (5 ).

Tre atme nt
Dis cu s s ion s w it h t h e p a t ie n t s h ou ld in clu d e e d u ca t ion rega rd in g t h e n a t u ra l
h is t ory of a d h e s ive ca p s u lit is , p re p a ra t ion for a n e xt e n d e d re cove ry, a n d a lle -
via t ion of fe a r of a m ore s e riou s d is e a s e. A h om e e xe rcis e p rogra m ou t lin e d by
a p h ys ica l t h e ra p is t ca n be e ffe ct ive in re lievin g s ym p t om s , a n d a ls o p la ce s t h e
p a t ie n t in a n a ct ive role. Gle n oh u m e ra l cort icos t e roid in je ct ion , e xe rcis e, a n d
join t m obiliza t ion a ll le a d t o im p rove d s h ort - a n d lon g-t e rm ou t com e s . Cort i-
cos t e roid in je ct ion s h a ve be e n s h ow n t o re s u lt in m ore ra p id im p rove m e n t s a t
4- t o 6-w e e k in t e rva ls a n d a re t h e re fore a re a s on a ble op t ion for p a t ie n t s w it h
S
E
m o re s eve re s ym p t o m s , w h o h a ve n o t re s p o n d e d w e ll t o re h a b ilit a t io n (5 ).
C
T
How eve r, t h e re is co n ce r n fo r p o t e n t ia lly e leva t e d s e r u m glu co s e leve ls in
I
O
p a t ie n t s w it h d ia be t e s w h o re ce ive in t ra -a rt icu la r cort icos t e roid s . If con s e rva -
N
4
t ive m a n a ge m e n t is u n s u cce s s fu l, obs t in a t e froze n s h ou ld e r m a y be fu rt h e r
O
m a n a ge d w it h m a n ip u la t ion u n d e r a n e s t h e s ia or s u rgica l ca p s u la r re le a s e.
s
t
e
o
Clinical Co urse
a
r
t
Ad h e s ive ca p s u lit is is u s u a lly s e lf-lim it e d , la s t in g 12 t o 24 m on t h s . How eve r,
h
r
i
m ild s ym p t om s ca n p e rs is t for ye a rs , d e p e n d in g on t h e e xt e n t of brop la s ia s .
t
i
s
Som e s t u d ie s re p ort t h a t u p t o h a lf of p a t ie n t s h a ve lim it e d ROM m ore t h a n
a
n
3 ye a rs a ft e r s ym p t om on s e t .
d
M
e
t
HYPOTHYROIDISM
a
b
o
Sym m e t rica l a rt h rop a t h y w it h s t iffn e s s of t h e h a n d s a n d kn e e s is a com m on
l
i
c
in it ia l p re s e n t a t ion of p a t ie n t s w it h h yp ot h yroid is m . Exa m in a t ion in clu d in g
B
o
p a lp a t ion of in volve d join t s m a y reve a l s yn ovit is . Syn ovia l u id is t yp ica lly
n
e
n on in a m m a t ory w it h h igh leve ls of h ya lu ron ic a cid .
Hyp ot h yroid is m is a ls o a s s ocia t e d w it h ca lciu m pyrop h os p h a t e d ep os it ion
(CPPD), w h ich w ou ld re s u lt in a n in a m m a t ory s yn ovia l u id w it h w e a kly p os -
it ive ly bire frin ge n t rh om boid a l crys t a ls s e e n u n d e r p ola rize d ligh t m icros cop y
(Fig. 22.3 ). In d e e d , m u lt ip le s ys t e m ic d is e a s e s a re a s s ocia t e d w it h CPPD a rt h rop -
a t h y (Ta ble 22.2 ). Ca rp a l t u n n e l s yn d rom e ca n a ls o be
a n in it ia l p re s e n t a t io n in u p t o 7% o f p a t ie n t s w it h
h yp ot h yroid is m .
Ch ro n ic a u t oim m u n e t h yro id it is , or Ha s h im o t o ’s
t h yro id it is , h a s a va r ie t y o f a s s o cia t e d r h e u m a t ic
m a n ife s t a t ion s , s u ch a s m ild n on e ros ive a rt h rit is , p ol-
ya rt h ra lgia , m ya lgia , a n d s icca s yn d rom e. Mos t m a n i-
fe s t a t ion s a re s e co n d a ry t o h yp ot h yroid is m a n d d o
n o t re s olve u n t il a e u t h yroid s t a t e is a ch ieve d . How -
eve r, in t re a t e d or e u t h yroid Ha s h im ot o’s t h yroid it is ,
a r t h rop a t h ie s m a y be d u e t o a n a s s ocia t e d a u t o im -
m u n e e t iology, s u ch a s Sjogre n ’s s yn d rom e, rh e u m a -
t oid a rt h rit is , or s ys t e m ic lu p u s e ryt h e m a t os u s .

HYPERTHYROIDISM
Hyp erth yroid ism , in clu d in g Grave’s d isea se, ca n p resen t
Figure 22.3 Ca lcium pyrophospha te deposition crysta l. (Courtesy of a s p retibia l m yxed em a a n d op h th a lm op a th y. Digita l soft-
Gera ld F. Moore, MD.) tissu e sw ellin g w ith p eriostitis of m eta ca rp op h a la n gea l

Figure 22.4 Brown tumors hyperpa r-
a thyroid. (Courtesy of Gera ld F. Moore,
MD.)
Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 227
Table 22.2 Syst emic Diseases Associat ed wit h Calcium
Pyrophosphat e Deposit ion Art hropat hy
Hyp e rp a ra t h yro id ism
Hyp o t h yro id ism
He m o ch ro m a t o sis
Hyp o p h o sp h a t e m ia
Hyp o m a g n e se m ia
(MCP) join t s a ls o occu rs . Na il ch a n ge s in clu d e on ych olys is a n d clu bbin g (t h y-
roid a crop a ch y).
Os t e op oros is is a re la t ive ly com m on a n d s e riou s m a n ife s t a t ion of h yp e r-
t h yroid is m t h a t s h ou ld n ot be m is s e d . Ia t roge n ic ove rrep la ce m e n t of t h yroxin e
e
ca n a ls o le a d t o os t e o p oros is . Tre a t m e n t go a ls in clu d e n o rm a liza t ion of t h y-
n
o
roid -s t im u la t in g h orm on e a n d im p rove m e n t in bon e m in e ra l d e n s it y a s m e a s -
B
u re d by d e n s it om e t ry.
c
i
l
o
b
a
t
HYPERPARATHYROIDISM AND HYPOVITAMINOSIS D
e
M
Ca lciu m h o m e o s t a s is w it h b o n e m e t a b o lis m a n d re m o d e lin g a re in t r ica t e ly
d
n
con t rolle d by p a ra t h yroid h orm on e (PTH), vit a m in D, a n d ca lcit on in leve ls . Pri-
a
m a ry h yp e r p a ra t h yro id is m is o ft e n s e co n d a ry t o a p a ra t h yro id a d e n o m a ,
s
i
t
i
r
w h e re a s s e con d a ry d is e a s e is m os t com m on ly re la t e d t o re n a l fa ilu re, vit a m in
h
t
r
D d e cie n cy, a n d os t e om a la cia . Art h ra lgia s a re com m on in bot h p rim a ry a n d
a
o
s e con d a ry d is e a s e, a n d ca n in volve s m a ll join t s of t h e h a n d s , oft e n s p a rin g t h e
e
t
p roxim a l in t e rp h a la n ge a l (PIP) join t s . Ra d iogra p h ic ch a n ge s in clu d e os t e it is b-
s
O
ro s a cys t ica , e ro s io n s , p h a la n ge a l s u b p e r io s t e a l re s o r p t io n a lo n g t h e ra d ia l
4
e d ge s , a n d eve n d is t a l t u ft re s orp t ion . Rh e u m a t oid fa ct or is t yp ica lly n ega t ive
N
O
a n d e ryt h rocyt e s e d im e n t a t ion ra t e n orm a l. Ca lciu m p yrop h os p h a t e d e p os i-
I
T
C
t ion is a s s ocia t e d w it h h yp e rp a ra t h yroid is m , a n d a cu t e gou t a t t a cks ca n a ls o
E
occu r (Ta ble 22.2 ). Eit h e r ca lciu m p yrop h os p h a t e or u ric a cid crys t a ls ca n be
S
fou n d in a s p ira t e d join t u id from a n a cu t e ly in a m e d join t of a p a t ie n t w it h
h yp e r p a ra t h yro id is m . Brow n t u m o rs (Fig. 22.4 ), w h ich a re lyt ic b o n e le s io n s ,
ca n be s e e n on ra d iogra p h s a n d rep re s e n t loca lize d a re a s of brou s t is s u e w it h
in cre a s e d os t e ocla s t ic a ct ivit y.
ACROMEGALY
Acrom ega ly is a ra re con d it ion w it h a n es t im a t e d a n n u a l in cid e n ce of 4 ca s e s p er
m illion p e rs on s a n d is typ ica lly d u e t o h yp e rse cre tion of grow t h h orm on e s e c-
on d a ry to a ben ign p itu it a ry a d en om a (6 ). W h ile ca rd iova s cu la r d is ea s e a ccou n ts
for t h e m a jorit y of m ort a lit y in t h e s e p a t ien t s , a rt icu la r m a n ifes t a t ion s a re t h e
le a d in g ca u s e of m orbid ity. Acrom ega lic a rth rop a t h y a ffect s bot h th e a xia l a n d
a p p e n d icu la r s ke le t on , w it h t h e kn e e s be in g t h e m os t com m on ly in volve d
p e rip h e ra l join t . Non in a m m a t ory a rt h rit is w it h join t s t iffn e s s a n d sw e llin g is
com m on . Art icu la r w id e n in g w it h s oft -t is s u e h yp e rtrop h y a n d join t h yp erm obil-
it y p red om in a t es in ea rly s t a ges w h en con trol of grow t h h orm on e a n d in s u lin -
like grow t h fa ct or 1 (IGF-1) m ay revers e t h e a rt h rop a t h y (6 ). La t er s t a ge s m a n ife s t
in ca rtila ge u lce rs , s u bch on d ra l cys t form a t ion , a rt icu la r t h icke n in g, lim it e d ROM,
a n d u ltim a t ely s eve re d ege n e ra t ive a rth ritis . Ra d iogra p h ic a bn orm a lit ie s in clu d e
d is ta l t u ft in g of t h e p h a la n ge s , os t eop h yt e form a t ion , es p ecia lly a t th e ba s e of
d is ta l p h a la n ge s , a n d su bch on d ra l cys t form a t ion . Up to on e h a lf of p a t ien t s h ave
sym p t om a t ic ca rp a l t u n n el s yn d rom e ; h ow eve r, t h is is like ly rela t ed t o m e d ia n
n e rve ed e m a ra t h e r t h a n ext rin s ic com p re s s ion in t h e s e p a t ie n ts .
 228 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Ma lig na ncie s w ith Asso cia te d

Arthro pa thie s
HYPERTROPHIC OSTEOARTHROPATHY
Clinical Pre se ntatio n
Hyp e r t rop h ic os t e oa rt h rop a t h y (HOA) is a s yn d rom e
cla s s ica lly com p ris in g d igit a l clu bbin g a n d p e rios t it is
o f t u b u la r b o n e s . It is d ia gn o s e d in t h e s e t t in g o f
com orbid m a lign a n cy ove r 80% of t h e t im e. Lu n g ca n -
ce r, bot h p rim a ry a n d m e t a s t a t ic, is m os t com m on ly
a s s ocia t e d w it h t h e con d it ion . Th e m a jorit y of ca s e s
in volve n on –s m a ll-ce ll m a lign a n cie s , in clu d in g s q u a -
m ou s ce ll a n d a d e n oca rcin om a (7 ). In t ra t h ora cic lym -
p h om a s a lon g w it h s eve ra l ot h e r e xt ra t h ora cic m a lig-
n a n cie s a re a ls o a s s ocia t e d . Ot h e r p u lm on a ry p roce s s e s
in clu d in g in fe ct io n s , in t e r s t it ia l d is e a s e , a n d cys t ic
Figure 22.5 Digita l Clubbing. (Courtesy of Gera ld F. Moore, MD.)
S
bros is , a s w e ll a s ch ron ic live r d is e a s e, h ave a ls o be e n
E
C
a s s o cia t e d w it h HOA. Sym p t o m s o f HOA in clu d e a
T
I
O
d e ep s e n s a t ion of p a in w it h in t h e lon g bon e s . Sw e llin g
N
of t h e e xt re m it ie s , p a rt icu la rly t h e low e r lim bs , a n d a n a s s ocia t e d s ym m e t rica l
4
n o n in a m m a t o ry a rt h rit is o f la rge join t s ca n be p a in fu l (7 ). How eve r, s o m e
O
s
p a t ie n t s m ay be com p le t e ly a s ym p t om a t ic.
t
e
o
a
Examinatio n
r
t
h
Digit a l clu bb in g is t h e m o s t n o t a ble p h ys ica l n d in g in p a t ie n t s w it h HOA
r
i
t
i
s
(Fig. 22.5 ). Pe riu n gu a l s kin m ay be t h in a n d s h in y. De rm a l in volve m e n t of t h e
a
fa ce a n d e xt re m it ie s ca n a ls o o ccu r be ca u s e of s kin a n d bo n e p rolife ra t ion .
n
d
Re la t ive ly la rge join t e ffu s ion s a re p os s ible.
M
e
t
a
Studie s
b
o
Alth ou gh n o sp eci c labora tory tests a re u sed for d iagn osis, ra d iogra p h s ca n be
l
i
c
h elp fu l. Periostitis, or cortica l th icken in g of lon g bon es, rem a in s th e cla ssic n d in g
B
o
on ra d iogra p h s (Fig. 22.6 ). Bon e sca n s m ay revea l u p ta ke in th e cortex of lon g bon es,
n
e
re ectin g p rolifera tion beca u se of p eriostitis. Acro-osteolysis of th e
n ge rs a n d t oe s ca n a ls o be s e e n . Not a bly, join t s p a ce s re m a in
n orm a l a n d e ros ion s a re n ot t yp ica l (7 ). Art h roce n t e s is reve a ls a
vis co u s s yn ovia l u id w it h m in im a l W BCs o n u id a n a lys is .
Im p ort a n t ly, t h e d ia gn os is of HOA w a rra n t s eva lu a t ion for a n d
t re a t m e n t of p ot e n t ia l u n d e rlyin g ca u s e s .

Tre atme nt
As ym p t o m a t ic p a t ie n t s d o n o t re q u ire s p e ci c t re a t m e n t fo r
HOA. No n s t e ro id a l a n t i-in a m m a t o ry d r u gs (NSAIDs ) m a y b e
u s e fu l fo r s ym p t o m s o f p a in . Ca s e s t u d ie s h a ve re p o r t e d
im p rove d p a in con t rol in re fra ct ory ca s e s w it h a d m in is t ra t ion
of in t rave n ou s bis p h os p h on a t e t h e ra p y (7 ).

Clinical Co urse
In ge n e ra l, t h e clin ica l con d it ion is m o s t d e p e n d e n t on t re a t -
m e n t of t h e u n d e rlyin g s ys t e m ic d is e a s e. For e xa m p le, clu bbin g
ca n im p rove or eve n re s olve w it h ch e m ot h e ra py or re s e ct ion of
t h e a s s ocia t e d m a lign a n cy.

CARCINOMATOUS POLYARTHRITIS
Figure 22.6 Periostitis in hypertrophic osteoa rthropa thy. Ge n e ra lly a s e ron ega t ive p olya rt h ro p a t h y, ca rcin om a t o u s p ol-
(Courtesy of Gera ld F. Moore, MD.) ya r t h rit is re p re s e n t s a co n d it io n t h a t ca n m im ic rh e u m a t o id
 Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 229

a rt h rit is w it h a vola t ile p re s e n t a t ion . Typ ica lly fou n d in old e r a d u lt s , s ym p t om s

oft e n d eve lop in clos e t e m p ora l re la t ion s h ip t o t h e d ia gn os is of a m a lign a n cy.
As ym m e t rica l in vo lve m e n t o f low e r e x t re m it y jo in t s is m o s t fre q u e n t w it h
re la t ive s p a rin g of t h e h a n d s . Th e m os t com m on ly rep ort e d co-occu rrin g m a lig-
n a n cie s a re colon , bre a s t , ova ria n , a n d lu n g. Ar t h rop a t h y ca n im p rove w it h
t re a t m e n t of t h e m a lign a n cy.

COMPLEX REGIONAL PAIN SYNDROME

Co m p le x re gio n a l p a in s yn d ro m e (CRPS) is d e n e d a s p a in , a u t o n o m ic d ys -
fu n ct io n , t ro p h ic ch a n ge s , a n d fu n ct io n a l im p a ir m e n t w it h o u t id e n t i a ble
n e rve d a m a ge (8 ). His t ory m a y reve a l re ce n t s u rge ry or t ra u m a . How eve r, in t h e
a bs e n ce of s u ch e t iology, u n d e rlyin g m a lign a n cy m u s t be con s id e re d . Pa in is
d e s cribe d a s bu rn in g, t h robbin g, s e a rin g, or a ch in g, a n d m a y be a ggrava t e d by
h e a t , cold , or co n t a ct . Pa t ie n t s w it h CRPS e xp e rie n ce s ign i ca n t s k in t e n d e r-
n e s s , ch ron ic m ild sw e llin g, lim it e d re lie f w it h n a rcot ics , a n d d if cu lt y s le ep -
in g. Ph ys ica l e xa m in a t ion ca n reve a l cla s s ic n ge r p os t u rin g w it h MCP e xt e n -

e
n
s ion a n d PIP e xion or e xt e n s ion . Con ve rs e ly, e xion of bot h MCP a n d PIP join t s ,

o
B
or cle n ch e d s t , m ay s u gge s t m a lin ge rin g (8 ). Ot h e r s ign s a n d s ym p t om s m ay

c
i
l
in clu d e s t iffn e s s , loca l os t e op e n ia , a t rop h y of n a ils a n d h a ir, s kin h yp e rt rop h y,

o
b
a n d n e m ot or d if cu lt ie s . Ma gn e t ic re s on a n ce im a gin g a n d t h re e -p h a s e bon e

a
t
s ca n ca n be p os it ive in la t e d is e a s e, s h ow in g in cre a s e d p e ria rt icu la r u p t a ke in

e
M
in vo lve d jo in t s . A m u lt id is cip lin a ry a p p ro a ch t o m a n a ge m e n t is im p o rt a n t ,

d
n
w it h in p u t from a n in t e rn is t , s u rge on , p a in s p e cia lis t , p h ys ica l t h e ra p is t , p s y-

a
ch ologis t or p s ych ia t ris t , a n d rh e u m a t ologis t . Ph a rm a cologic t h e ra py in clu d e s

s
i
t
i
a n t id e p re s s a n t s , a n t icon vu ls a n t s , ca lciu m ch a n n e l blocke rs , a d re n e rgic com -

r
h
t
p ou n d s , a n d cort icos t e roid s , a s w e ll a s a n t i-in a m m a t ory a n d a n a lge s ic a ge n t s .

r
a
A com bin a t ion of a ge n t s w it h con cu rre n t h a n d t h e ra py is m os t be n e cia l (8 ).

o
e
t
s
O
MULTICENTRIC RETICULOHISTIOCYTOSIS

4
N
A ra re d is ord e r w it h u n kn ow n p a t h oge n e s is , m u lt ice n t ric re t icu loh is t iocyt os is

O
I
T
(MR) is ch a ra ct e rize d by p rogre s s ive e ros ive p olya rt h rit is a n d n od u la r s kin a n d

C
E
m u cos a l le s ion s (Fig. 22.7 ). Mu lt ice n t ric re t icu loh is t iocyt os is h a s be e n rep ort e d

S
in a s s ocia t ion w it h s eve ra l m a lign a n cie s , m os t oft e n bre a s t a n d s t om a ch ca r-
cin om a . Mid d le -a ge d w om e n a re m os t com m on ly a ffe ct e d , w it h a rt h ra lgia s fol-
low e d by s kin m a n ife s t a t ion s m on t h s t o ye a rs la t e r. Th e lon g clin ica l cou rs e
m a ke s d ia gn os is d if cu lt . Con rm a t ion is by h is t ologic p re s e n ce of m on on u -
cle a r h is t iocyt e s a n d m u lt in u cle a t e d gia n t ce lls . Sym m e t rica l a rt h rop a t h y p ri-
m a rily a ffe ct s t h e in t e rp h a la n ge a l jo in t s o f t h e h a n d s a n d ca u s e s m o d e ra t e
p a in , s t iffn e s s , a n d s w e llin g. Dis t a l in t e r p h a la n ge a l
(DIP) join t in volve m e n t ca n h e lp d is t in gu is h t h e p roc-
e s s fro m o t h e r d is e a s e s , a lt h o u gh a n y jo in t ca n b e
a ffe ct e d . Na t u ra l p rogre s s ion le a d s t o s eve re d e s t ru c-
t io n a n d d is gu ra t io n . Aggre s s ive t r e a t m e n t w it h
im m u n os u p p re s s ive m e d ica t ion s is im p ort a n t in s u ch
ca s e s (9 ).

REMITTING SERONEGATIVE SYMMETRICAL

Figure 22.7 Multicentric reticulohistiocytosis. (Courtesy of Gera ld F.
Moore, MD.)
SYNOVITIS WITH PITTING EDEMA
De s cribe d a s a lim it e d s yn d rom e of s yn ovit is t o t h e
b ila t e ra l h a n d s a n d w r is t s , re m it t in g s e ro n e ga t ive
s ym m e t rica l s yn ovit is w it h p it t in g e d e m a (RS3PE) h a s
be e n re p ort e d a lm os t e xclu s ive ly in t h e e ld e rly m a le
p op u la t ion . Pa in fu l p it t in g e d e m a of t h e d ors a l s u rfa ce
of t h e h a n d s is u s u a lly p re s e n t . Ve ry ra p id o n s e t is
 230 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

t yp ica l, w it h p a t ie n t s com m on ly a ble t o p in p oin t on s e t of s ym p t om s t o n e a rly

NOT TO BE MISSED t h e h ou r. In a m m a t ory m a rke rs in clu d in g e ryt h rocyt e s e d im e n t a t ion ra t e a n d
C-rea ct ive p rot ein leve ls a re u s u a lly m a rked ly eleva t ed . Non s te roid a l a n t i-in a m -
Sym p t o m s t h a t m a y in d ica t e
m a lig n a n cy a sso cia t e d w it h m a t ory d ru gs a re oft e n of lit t le be n e t . How eve r, ora l cort icos t e roid s p rovid e
a rt h ro p a t h y: ra p id clin ica l res p on se, a n d s u bs eq u e n t re m is sion p e rs ist s a fte r d is con tin u a t ion
of s t eroid s (10 ). Ma lign a n cie s in clu d in g lym p h om a , m yelodysp la s tic d is ord er, a n d
• We ig h t lo ss, co n st it u t io n a l
sym p t o m s solid tu m ors a re rep ort ed , a n d s h ou ld be su s p e ct ed in ca s es p oorly res p on s ive to
glu cocorticoid s .
• Clu b b in g o f d ig it s
• De e p b o n e p a in
• No d u la r skin le sio n s
He ma to lo g ic Diso rde rs w ith
• At yp ica l clin ica l co u rse o f
Asso cia te d Arthro pa thie s
a rt h ra lg ia SICKLE CELL DISEASE
Clinical Pre se ntatio n
Beca u s e of a n a bn orm a l -globu lin ch a in w it h in h e m oglobin , sickle cell d is ea s e
is m a n ife s t e d a s a n e m ia . Ad d it ion a l im p ort a n t con s e q u e n ce s in clu d e va s o-
S
E
occlu s ion a n d in fa rct ion of bon e w it h re s u lt a n t os t e on e cros is . Ap p roxim a t e ly
C
T
50% of p a t ie n t s w it h s ickle cell d is ea s e d evelop ava s cu la r n e cros is by 35 yea rs of
I
O
N
a ge (11 ). Hyp os p le n is m a ls o p ort e n d s h e igh t e n e d ris k of in fe ct ion , in clu d in g
4
os t eom ye lit is a n d s ep t ic a rt h rit is . In fa rct ion ca n occu r a n yw h e re w ith in t h e s kel-
O
et on a n d is a d irect res u lt of s ickled ce lls , ca u sin g st a sis of blood a n d isch em ia .
s
t
e
Cold -in d u ce d va s ocon s triction ca n a lso con t ribu t e. In fa rct s t yp ica lly occu r in t h e
o
a
m e d u lla ry cavit ies a n d ep ip h ys e s, ca u s in g p a in fu l bon e cris es . How ever, a sym p -
r
t
h
tom a t ic silen t in fa rcts d o occu r a n d a re fou n d in cid e n t a lly on ra d iogra p h s .
r
i
t
i
s
a
Examinatio n
n
d
Sign s a n d s ym p t om s in clu d e join t or bon e t e n d e rn e s s a n d sw e llin g w it h lim -
M
it e d ROM. Feve r ca n a ls o be s e e n . How eve r, p a t ie n t s ca n be a s ym p t om a t ic. Ch il-
e
t
d re n m ay p re s e n t w it h s ickle ce ll d a ct ylit is .
a
b
o
l
i
Studie s
c
B
Acu t e in fa rct s ca u s e o s t e o lys is , w it h la t e r d eve lo p m e n t o f in t ra m e d u lla ry
o
n
lu ce n cy a n d s cle ros is in a p a t ch y d is t ribu t ion . Ep ip h ys e a l is ch e m ic n e cros is in
e
p a t ie n t s w it h s ickle ce ll a n e m ia is com m on ly s e e n in t h e h u m e ra l a n d fe m ora l
h e a d s , w it h bila t e ra l in volve m e n t m ore fre q u e n t ly s e e n t h a n in ot h e r d is e a s e s
w it h a s s ocia t e d ava s cu la r n e cros is . In it ia l ra d iogra p h s ca n be n orm a l, w it h t h e
e a rlie s t s ign s o f n e cro s is s e e n o n MRI. (11 ). W it h p ro gre s s io n , ra d io gra p h ic
ch a n ge s in clu d e lu ce n cy, s cle ros is , a n d eve n t u a lly d e p re s s ion of t h e a rt icu la r
s u rfa ce w it h colla p s e a n d fra gm e n t a t ion (Fig. 22.8 ).

Tre atme nt
Acu t e t h e ra py for s ickle ce ll cris is in clu d e s h yd ra t ion
a n d p a in co n t ro l. Co n s e rva t ive m a n a ge m e n t ve r s u s
s u rgica l in t e rve n t ion for os t e on e cros is is ba s e d on t h e
p a t ie n t a n d s t a gin g of s eve rit y. Core d e com p re s s ion ,
s t ru ct u ra l bon e gra ft in g, os t e ot om y, a n d a rt h rop la s t y
a re a va ila ble op t ion s . Con s e rva t ive m e a s u re s in clu d e
lim it a t io n s in w e igh t b e a rin g a n d p a in co n t ro l w it h
a n a lge s ic a ge n t s (11 ).

Clinical Co urse
Progre s s ion a n d p rogn os is of os t e on e cros is is d ep e n d -
e n t o n t h e s ize a n d lo ca t io n o f t h e in fa rct e d le s io n .
Ra n ge of m ot ion t yp ica lly d e clin e s s low ly ove r t im e .
Figure 22.8 Osteonecrosis of left femora l hea d. (Courtesy of Gera ld F. Eve n t u a lly, colla p s e ca n occu r. Th e re fore m on it orin g is
Moore, MD.) w a rra n t e d .
 Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 231

HEMOPHILIA
Join t d is e a s e is on e of t h e m os t im p ort a n t ca u s e s of m orbid it y in p a t ie n t s w it h
s eve re h e m op h ilia . Re cu rre n t ble e d in g in t o t h e join t le a d s t o ca rt ila ge d a m a ge,
s yn ovia l h yp e rt rop h y, n a rrow e d join t s p a ce, a n d eve n a lt e ra t ion s in bon e s t ru c-
t u re (12 ). Pa t ie n t s m ay p re s e n t w it h p a in , sw e llin g, s t iffn e s s , or “lockin g” w it h
in s t a bilit y of t h e kn e e s or e lbow s . Ma gn e t ic re s on a n ce im a gin g is a s e n s it ive
t ool s h ow in g low s ign a l in t e n s it y on T 1 - or T 2 -w e igh t e d im a ge s w h e re p e rs is t -
e n t h e m os id e rin d ep os it ion occu rs from rep e a t e d in t ra -a rt icu la r h e m orrh a ge.
Ph ys ica l t h e ra p y a n d re h a b ilit a t io n —in clu d in g p h ys io t h e ra p y, h yd ro t h e ra p y,
s p lin t in g, a n d ort h ot ics —a re im p ort a n t in bot h t h e t re a t m e n t a n d t h e p reve n -
t ion of h e m op h ilic a rt h rop a t h y (12 ). Syn ove ct om y a n d join t rep la ce m e n t a re
a d d it ion a l op t ion s .

He re dita ry Diso rde rs w ith

Asso cia te d Arthro pa thie s

e
n
HEMOCHROMATOSIS

o
B
Clinical Pre se ntatio n

c
i
l
o
He re d it a ry h e m och rom a t os is is a re la t ive ly com m on a u t os om a l-re ce s s ive d is -

b
a
ord e r w it h a p p roxim a t e ly 1 in 200 p e rs on s a ffe ct e d . A s u bs t it u t ion of t yros in e

t
e
M
for cys t e in e a t a s p e ci c loca t ion on e a ch a lle le re s u lt s in in cre a s e d in t e s t in a l
iron a bs orp t ion a n d eve n t u a l iron ove rloa d . Th e a rt h rop a t h y a s s ocia t e d w it h

d
n
h e m och rom a t os is is w e ll re cogn ize d a n d rep ort e d in u p t o 81% of p a t ie n t s (13 ).

a
s
Fa t igu e a n d a rt h ra lgia s a re com m on n on s p e ci c e a rly s ym p t om s , w h ile cla s s ic

i
t
i
r
bron ze d ia be t e s , CHF, a n d cirrh os is a re a m u ch le s s com m on p re s e n t a t ion , a n d

h
t
r
s u gge s t e n d -s t a ge d is e a s e (14 ).

a
o
Pa in fu l a rt h ra lgia s a re a m a jor ca u s e of m orbid it y, d is a bilit y, a n d re d u ce d

e
t
s
q u a lit y o f life fo r p a t ie n t s w it h h e re d it a ry h e m o ch ro m a t o s is . It ca n a ffe ct

O
n e a rly a n y join t , bu t m os t com m on ly in volve s t h e MCP a n d ra d ioca rp a l join t s ,

4
N
a n kle s , h ip s , e lbow s , kn e e s , a n d s h ou ld e r s (13 ). Lo n g-s t a n d in g u n e xp la in e d

O
jo in t p a in o r o s t e o a r t h r it is in a p a t ie n t yo u n ge r t h a n 55

I
T
C
ye a rs o f a ge s h o u ld w a rra n t s u s p icio n o f p o s s ible h e m o -

E
S
ch rom a t os is (14 ).

Examinatio n
Bon y sw e llin g ca n be s ign i ca n t a n d re s e m ble os t e oa rt h ri-
t is . In volve m e n t of t h e s e con d a n d t h ird MCP join t s in a
s ym m e t rica l p a t t e rn is a h a llm a rk (15 ).

Studie s
Se ru m leve ls of iron , t ot a l iron -bin d in g ca p a cit y (TIBC), a n d
fe rrit in s h ou ld be obt a in e d . If iron s a t u ra t ion is gre a t e r t h a n
50%, o r a n e leva t e d fe rr it in leve l p re s e n t , ge n e t ic t e s t in g
s h ou ld fo llow (14 ). Re fe rra l t o a ga s t ro e n t e ro logis t is w a r-
ra n t e d . Ra d iogra p h ic ch a n ge s in clu d e broa d e n in g of m e t a -
ca rp a l h e a d s w it h cla s s ic “h ook-like ” os t e op h yt e s a n d join t
s p a ce n a rrow in g (Fig. 22.9 ). Se co n d a ry CPPD d is e a s e fro m
h e m och rom a t os is ca n a ls o reve a l crys t a ls on a rt h roce n t e -
s is of in volve d join t s .

Figure 22.9 Joint spa ce na rrowing with “hook” osteophytes a nd
hypertrophic cha nges seen in Hemochroma tosis. (Courtesy of
Gera ld F. Moore, MD.)
Tre atme nt
Tre a t m e n t op t ion s a re lim it e d , w it h on ly s ym p t om a t ic t h e r-
a p ie s a va ila ble for m a n a ge m e n t of a r t h rop a t h y. Un fo rt u -
n a t e ly, regu la r p h le bot om y w it h s ys t e m ic iron d ep le t ion is
s e ld om h e lp fu l for join t s ym p t om re lie f, a n d h a s n o e ffe ct
on t h e p rogre s s ive d e t e riora t ion of join t s t ru ct u re (13 ).
 232 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

Clinical Co urse
Alth ou gh ea rly d ia gn osis a n d trea tm en t h ave little effect on th e a rth rop a th y, m ore
seriou s com p lica tion s secon d a ry to system ic iron overloa d , n otably cirrh osis, CHF,
a n d d ia betes m ellitu s, m ay be avoid ed .

WILSON’S DISEASE
Wils on ’s d is e a s e is a ra re, bu t t re a t a ble, a u t os om a l-re ce s s ive d is ord e r ca u s e d
by a m u t a t ion in cop p e r-t ra n s p ort in g ATPa s e. Th is re s u lt s in a n a ccu m u la t ion
of fre e cop p e r in orga n s in clu d in g t h e live r, bra in , a n d join t s . Ne u rologic m a n i-
fe s t a t ion s in clu d e d ys a rt h ria , d ys t on ia , a n d t re m or. Pa t ie n t s m ay com p la in of
p a in a n d s t iffn e s s , e s p e cia lly in volvin g t h e kn e e s , w ris t s , or ot h e r la rge join t s .
Mu s cu los ke le t a l p a in m ay be t h e on ly p re s e n t in g s ym p t om a n d is like ly s e c-
on d a ry t o s yn ovia l in a m m a t ion a n d bon e d e m in e ra liza t ion (16 ).

ALKAPTONURIA (OCHRONOSIS)
S
E
Alka p t on u ria is a ra re m e t a bolic a u t os om a l-re ce s s ive d is e a s e w it h e s t im a t e d
C
T
in cid e n ce of 1 in 250,000 t o 1 m illion live birt h s . A d e cie n cy of h om oge n t is a t e
I
O
N
1,2-d ioxyge n a s e e n zym e re s u lt s in e xce s s h om oge n t is ic a cid . Och ron ot ic p ig-
4
m e n t d ep os it s in t is s u e, p a rt icu la rly join t s , ca u s in g in a m m a t ion a n d a rt icu la r
O
d ege n e ra t ion (17 ). A ch ild ’s rs t s ym p t om s ca n in clu d e d a rke n e d or bla ck u rin e.
s
t
e
How eve r, p a t ie n t s ca n b e u n d ia gn o s e d a n d p re s e n t a s a n a d u lt w it h lo n g-
o
a
s t a n d in g ba ck p a in a s t h e ir on ly com p la in t . Seve re s p on d yloa rt h rop a t h y is t h e
r
t
h
m os t com m on p re s e n t a t ion of och ron ot ic a rt h rop a t h y. Clin ica l re s e m bla n ce t o
r
i
t
a n kylos in g s p on d ylit is e xis t s ; h ow eve r, s a croilia c join t s a re t yp ica lly s p a re d .
i
s
Arth rop a th y begin s in th e th ird or fou rth d eca d e of life a n d resu lts in ROM
a
n
lim ita tion s, effu sion s, a n d even tu a lly ch ron ic p a in . Kn ee, h ip, or sh ou ld er rep la ce-
d
M
m e n t s a re com m on . Sp in a l in volve m e n t le a d s t o kyp h os is , h e igh t los s , a n d
e
d ecrea sed lu m ba r exion . Den sely ca lci ed in tervertebra l d iscs a re ch a ra cteristic
t
a
b
on im agin g stu d ies. Th era p ies in clu d e vita m in C beca u se of a n tioxid a n t p rop erties
o
l
i
a n d p rote in rest riction in a n a t tem p t t o d ecrea s e h om ogen tis ic a cid excretion .
c
B
How ever, ef ca cy h a s n ot bee n p roved . In gen era l, su rveilla n ce for ca rd ia c a n d
o
n
ren a l com p lica tion s a n d a tten tion to p a in con trol a re m ost p ra ctica l (17 ).
e
HEREDITARY DISORDERS OF CONNECTIVE TISSUES
Polya rt icu la r h yp e rm obilit y is p re s e n t in u p t o 30% t o 40% of you n g m e n a n d
w om e n , re s p e ct ive ly. For m os t , h ow eve r, h yp e rm obilit y is of n o m e d ica l con s e -
q u e n ce a n d t e rm e d benign hyperm obility syndrom e. Con d it ion s in clu d in g Eh le rs –
Da n lo s s yn d ro m e , o s t e o ge n e s is im p e r fe ct a , a n d Ma r fa n s yn d ro m e in vo lve
a bn orm a lit ie s of colla ge n , brillin , a n d m a t rix p rot e in s w it h s ign i ca n t m u s cu -
los ke le t a l m a n ife s t a t ion s . Pa t ie n t s w it h t h e s e d is e a s e s ca n p re s e n t w it h loca l-
ize d or d iffu s e a rt h ra lgia , m ya lgia s , t e n d in op a t h ie s , re cu rre n t join t d is loca t ion ,
s u blu x a t io n s , fra gilit y fra ct u re s , liga m e n t o r ca p s u la r p a t h o logy, e a r ly o n s e t
os t e oa rt h rit is , a n d fa t igu e (18 ). Pa in is t h e m os t com m on re a s on t h e s e p a t ie n t s
s e e k m e d ica l a t t e n t ion . In m os t ca s e s t h e re is n o evid e n ce of s ign i ca n t d a m -
a ge t o join t s , m u s cle s , or s u rrou n d in g s t ru ct u re s t o a ccou n t for t h e w id e s p re a d
p a in . Ph ys ica l a n d o ccu p a t io n a l t h e ra p y m e t h o d s n e e d t o b e m o d i e d t o
a ccou n t for la xit y of t is s u e s , in clu d in g s p lin t s t o p rot e ct u n s t a ble join t s , d eve l-
op m e n t of m u s cle s re s p on s ible for core s t a bilit y, re s t ora t ion of p rop riocep t ion ,
a n d ort h ot ics t o corre ct m e ch a n ica l d is crep a n cie s (18 ).
For m os t h e rit a ble d is ord e rs , re fe rra l t o a ge n e t icis t is w a rra n t e d for a p p ro-
p ria t e re p rod u ct ive ris k s t ra t i ca t ion a n d cou n s e lin g. Alt h ou gh m u s cu los ke le -
t a l m a n ife s t a t ion s a re d is cu s s e d h e re , in h e rit e d d is e a s e s oft e n h a ve a w id e
a rray of s ys t e m ic a n d m u lt iorga n in volve m e n t n e ce s s it a t in g in t e rd is cip lin a ry
a p p roa ch t o m a n a ge m e n t .
 Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 233

Misce lla ne o us Dise a se s w ith

Asso cia te d Arthro pa thie s
AMYLOIDOSIS
Am yloid os is is a h e t e roge n e ou s grou p of d is e a s e s ch a ra ct e rize d by d e p os it ion
of p la s m a p rot e in s in a n a bn orm a l, in s olu ble, brilla r form (19 ). Con go re d s t a in
m a k e s t h e d e p o s it s a p p e a r a p p le gre e n w it h b ire frin ge n ce u n d e r p o la rize d
m icros copy. Am yloid d e p os it ion in t o t h e join t a n d p e ria rt icu la r t is s u e s occu rs
in m os t form s of t h e d is e a s e. Dia gn os is re lie s on h is t ology a n d m a y be e a s ily
obt a in e d by n e -n e e d le a s p ira t ion of a bd om in a l fa t , con rm in g a m yloid d e p os -
it s in 80% t o 88% of p a t ie n t s (19 ).
• A L am yloidosis: It is t h e m os t com m on form of s ys t e m ic a m yloid a n d is d u e
t o d ep os it ion of im m u n oglobu lin ligh t ch a in s . Ap p roxim a t e ly 9% of p a t ie n t s ,
e s p e cia lly m a le s , h a ve m u s cu lo s k e le t a l s ym p t o m s a s a d o m in a n t clin ica l
fe a t u re (19 ). Join t s t iffn e s s a n d sw e llin g occu r, occa s ion a lly w it h p a in fu l con -
t ra ct u re s be ca u s e of a m yloid in lt ra t ion of p e ria rt icu la r a n d s yn ovia l t is s u e s .

e
n
Th e “s h o u ld e r p a d ” s ign is t h e m o s t cla s s ic a r t icu la r m a n ife s t a t io n o f AL

o
B
a m yloid os is a n d is d u e t o in lt ra t ion of t e n d on s a n d ca p s u la r s t ru ct u re s of

c
i
l
t h e s h ou ld e r, le a d in g t o sw e llin g a n d m ot ion lim it a t ion . W h e n cou p le d w it h

o
b
m a croglo s s ia a n d p e r io r b it a l cu t a n e o u s e cch ym o s is (“ra cco o n eye s ”), t h e

a
t
e
s h o u ld e r p a d s ign is co n s id e re d n e a r ly p a t h ogn o m o n ic. Pa t ie n t s w it h AL

M
a m yloid os is h ave t h e w ors t p rogn os is s e con d a ry t o a s s ocia t ion s w it h h e a rt

d
n
fa ilu re. Tre a t m e n t focu s e s on re d u ct ion of a m yloid oge n ic p rot e in con ce n t ra -

a
t ion by ch e m ot h e ra py.

s
i
t
i
• A A am yloidosis: An y ch ron ic in a m m a tory p rocess th a t ca u ses p ersisten t eleva -

r
h
t
tion of a cu te-p h a se rea ct a n ts ca n lea d to d ep osition of seru m a m yloid A (SAA)

r
a
o
p rotein a n d res u lt in AA a m yloid osis. Rh eu m a tic d is ea ses in clu d in g rh eu m a -

e
t
t oid a rt h rit is , a n kylos in g s p on d ylit is , p s oria t ic a rt h rit is , ju ve n ile id iop a t h ic

s
O
a rth ritis, a n d fa m ilia l Med iterra n ea n fever (FMF) a ccou n t for 70% of AA a m yloi-

4
d osis (19 ). Pa tien ts h ave a m u ch better p rogn osis th a n th ose w ith AL a m yloid osis,

N
O
w it h a m e d ia n s u rviva l of 4 t o 10 ye a rs , d ep e n d in g on ca rd ia c in volve m e n t .

I
T
Th era py focu ses on trea tin g th e u n d erlyin g d isord er to su p p ress ch ron ic in a m -

C
E
m a t io n a n d t h u s re d u ce circu la t in g leve ls o f SAA

• 2 -m icroglobulin ( 2M) am yloidosis: Pa t ie n t s on lon g-
Figure 22.10 Ma gnetic resona nce ima ging of a myloid in ltra ting right
femora l hea d. (Courtesy of Gera ld F. Moore, MD.)
S
p rot e in . Colch icin e is h igh ly e ffe ct ive in p reve n t in g
th e AA a m yloid osis of fa m ilia l Med iterra n ea n fever.
term h em od ia lysis a re a t risk of d evelop in g a m yloid o-
sis ca u sed by d ep osition of brilla r 2M p rotein . Pa th o-
gen es is is u n kn ow n bu t felt to be m u ltifa ctoria l a n d
a s s ocia t e d w it h a ge a n d d u ra t ion of h e m od ia lys is .
Ea rly m a n ifesta tion s in clu d e ca rp a l tu n n el syn d rom e
a n d ch ron ic a rth ra lgia , com m on ly in volvin g th e sh ou l-
d ers. Un fortu n a tely, a n erosive a n d d isablin g a rth rop a -
th y of la rge join ts ca n d evelop. Ra d iogra p h ic sign s of
a xia l in volve m e n t in clu d e e ros ion s of ve rt ebra l cor-
n ers a n d severe in tervertebra l sp a ce n a rrow in g. Mag-
n etic reson a n ce im a gin g ca n sh ow a m yloid d ep osits
a s w e ll (Fig. 22.10 ). Ap p ro xim a t e ly 50% t o 60% o f
p a tien ts receivin g h em od ia lysis for m ore th a n 10 yea rs
w ill h ave s u bch on d ra l ra d iolu cen t bon e cys t s in t h e
sh ou ld er, h ip s, w rists, or vertebra e on im agin g. Bon y
cys t s ca n a ccou n t for fra ct u re s of t h e fe m ora l n e ck
a n d vertebra e. Th era py a im s a t p rom otin g clea ra n ce of
2M p rotein a n d p reven tin g a m yloid d ep osition ; h ow -
ever, th e u se of h igh - u x d ia lysis m em bra n es h a s n ot
been p roved to be effective (19 ).
 234 Se ctio n 4 Os t e oa rt h rit is a n d Me t a bolic Bon e a n d Join t Dis e a s e

SARCOIDOSIS
WHEN TO REFER
Sa rcoid os is is a p oorly u n d e rs t ood d is e a s e of n on ca s e a t in g gra n u lom a d eve lop -
• Fo r a ssist a n ce in d if cu lt m e n t , t yp ica lly in t h e lu n gs a n d lym p h n od e s . It a ffe ct s virt u a lly a n y orga n ,
d ia g n o se s a lt h ou gh p a t ie n t s m ay be com p le t e ly a s ym p t om a t ic. Mu s cu los ke le t a l m a n ife s -
• Wh e n co n se rva t ive m e a s-
t a t ion s in clu d e in a m m a t ory a rt h rit is , t e n os yn ovit is , d a ct ylit is , p e ria rt icu la r
u re s a re n o t h e lp fu l s o ft -t is s u e s w e llin g, m yo p a t h y, a n d gra n u lo m a t o u s b o n e in lt ra t io n (20 ).
Löfgre n ’s s yn d rom e is bila t e ra l h ila r a d e n op a t h y w it h a cu t e e ryt h e m a n od os u m ,
• Whe n t h e clin ica l p ict u re
n o lo ng e r t s t he dia g no sis
a n d m ay in clu d e feve r, a n t e rior u ve it is , a n d a rt h rit is , e s p e cia lly of t h e a n kle s .
Tw o t yp e s of a rt h rit is a re re cogn ize d . Acu t e s a rcoid a rt h rit is is s e lf-lim it e d a n d
• Fo r m a n a g e m e n t o f im m u - re s olve s w it h ou t p e rm a n e n t s e q u e la e . Ch ron ic a rt h rit is is le s s com m on a n d
n o su p p re ssa n t m e d ica t io n s
ca n p ro gre s s t o jo in t d e fo r m it y b e ca u s e o f p ro life ra t ive a n d in a m m a t o ry
• For therapeutic measures ch a n ge s in t h e s yn oviu m . Non s t e roid a l a n t i-in a m m a t ory d ru gs , cort icos t e r-
including special procedures oid s , colch icin e, a n t im a la ria ls , a n d /or im m u n os u p p re s s ive m e d ica t ion s h a ve
a ll be e n u s e d a s d ru g t h e ra py of s a rcoid a rt h rit is (20 ).
S
E
ICD9
C
T
726.90 Capsulitis (jo in t )
I
O
726.0 ad h e sive (sh o u ld e r)
N
4
250.0 Diabe te s, diabe tic (b rit t le ) (co n g e n it al) (f am ilial) (m e llit u s)
O
(se ve re ) (slig h t ) (w it h o u t co m p licat io n )
s
t
e
244.9 Hypo thyro idism (acq u ire d )
o
a
715.9 Oste o arthro pathy
r
t
h
757.39 ch ro n ic id io p at h ic h yp e rt ro p h ic
r
i
t
757.39 f am ilial id io p at h ic
i
s
731.2 h yp e rt ro p h ic p u lm o n ary
a
n
731.2 se co n d ary
d
M
757.39 id io p at h ic h yp e rt ro p h ic
e
731.2 p rim ary h yp e rt ro p h ic
t
a
b
731.2 p u lm o n ary h yp e rt ro p h ic
o
l
i
731.2 se co n d ary h yp e rt ro p h ic
c
B
716.59 Po lyarthritis, po lyarthro pathy NEC
o
n
714.9 in am m at o ry
e
Re fe re nce s
1. Ca u d ill-Slo s b e rg MA, Sch w a r t z LM , Wolo s h in S. Of ce vis it s a n d a n a lge s ic p re s cr ip t ion s for m u s cu -
lo s ke le t a l p a in in US: 1980 vs . 2000 . Pain 2004 ;109 (3 ):514 –519 .
2. Preve n t ion , C.f.D. C. a ., National Diabetes Fact Sheet: General Inform ation and National Estim ates on Diabetes
in the United States, 2007. US Dep a rt m e n t of He a lt h a n d Hu m a n Se rvice s ; 2008 .
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2002 ;45 (8 ):1085 –1096 .
5. Kelley MJ, McClu re PW, Leggin BG. Frozen sh ou ld er: Evid e n ce a n d a p rop os ed m od el gu id in g reh a bilit a t ion .
J Orthop Sports Phys Ther 2009 ;39 (2 ):135 –148 .
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a n d m a n a ge m e n t . Endocr Rev 2004 ;25 (1 ):102 –152 .
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a n d review of t h e lit e ra t u re . Sem in A rthritis Rheum 2009 ;38 (6 ):458 –466 .
8. Li Z , Pa t e rs on Sm it h B, Sm it h TL, e t a l. Dia gn os is a n d m a n a ge m e n t of com p lex region a l p a in s yn d rom e
com p lica t in g u p p e r e xt re m it y re cove ry. J Hand Ther 2005 ;18 (2 ):270 –276 .
9. Trot t a F, Ca s t e llin o G, Lo Mo n a co A. Mu lt ice n t ric re t icu loh is t io cyt os is . Best Pract Res Clin Rheu m atol
2004 ;18 (5 ):759 –772 .
10. Ke e n a n RT, Ha m a lia n GM , Pillin ge r MH . RS3PE p re s e n t in g in a u n ila t e ra l p a t t e rn : Ca s e rep ort a n d review
of t h e lit e ra t u re . Sem in A rthritis Rheum 2009 ;38 (6 ):428 –433 .
11. Ejin d u VC, Hin e AL, Ma s h aye kh i M, e t a l. Mu s cu lo s ke le t a l m a n ife s t a t ion s of s ickle ce ll d is e a s e . Radio-
graphics 2007 ;27 (4 ):1005 –1021 .
12. Bo s s a rd D, Ca r r illo n Y, St ie lt je s N, e t a l. Ma n a ge m e n t o f h a e m o p h ilic a r t h r o p a t h y. Haem ophilia
2008 ;14 (Su p p l 4 ):11 –19 .
13. Ca rro ll G, Bre id a h l W H, Bu ls a ra MK, e t a l. He re d it a ry h a e m o ch rom a t o s is (HH) is ch a ra ct e riz e d by a
clin ica lly d e n a ble a rt h rop a t h y t h a t corre la t e s w it h iron loa d . A rthritis Rheum 2011;63(1):286–94 .
 Ch a p te r 22 Art h rop a t h ie s As s ocia t e d w it h Sys t e m ic Dis e a s e s 235

14. Ca rls s on A. He re d it a ry h e m och rom a t os is : A n egle ct e d d ia gn os is in ort h op e d ics : A s e rie s of 7 p a t ie n t s

w it h a n kle a rt h rit is , a n d a review of t h e lit e ra t u re . A cta Orthop 2009 ;80 (3 ):371 –374 .
15. von Ke m p is J. Art h rop a t h y in h e re d it a ry h e m och rom a t os is . Curr Opin Rheu m atol 2001 ;13 (1 ):80 –83 .
16. So lt a n z a d e h A , So lt a n za d e h P, Na s s i S, e t a l. W ils o n ’s d is e a s e : A gre a t m a s q u e ra d e r . Eu r N eu rol
2007 ;57 (2 ):80 –85 .
17. Al-Ma h fou d h R, Cla rk S, Bu xt on N . Alka p t on u ria p re s e n t in g w it h och ron ot ic s p on d yloa rt h rop a t h y. Br J
Neurosurg 2008 ;22 (6 ):805 –807 .
18. Ha kim AJ, Sa h ot a A. Join t h yp e rm obilit y a n d s kin e la s t icit y: Th e h e re d it a ry d is ord e rs of con n e ct ive t is s u e .
Clin Derm atol 2006 ;24 (6 ):521 –533 .
19. Pe rfe t t o F, Moggi-Pign on e A, Livi R, e t a l. Sys t e m ic a m yloid os is : A ch a lle n ge for t h e rh e u m a t ologis t . Nat
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20. Torra lb a KD, Qu is m or io FP, Jr . Sa rcoid a rt h rit is : A review of clin ica l fe a t u re s , p a t h ology a n d t h e ra p y.
Sarcoidosis Vasc Diffuse Lung Dis 2003 ;20 (2 ):95 –103 .

e
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a
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M
d
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a
s
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SECTION
5

Infectious Arthritis

Chapter 23 Bacte rial Arth ritis

A rthur Kavanaugh and Maika Onishi

Chapter 24 Lym e Dis e as e

W illiam F. Iobst and Kristin M. Ingraham

Chapter 25 Viral Arth ritis

Katherine Holm an and Martin Rodriguez

237
CHAPTER
23 Ba cteria l Arthritis
A rthur Kavanaugh and Maika Onishi

A 30-ye ar-o ld
Intro ductio n
Ba ct e r ia l a r t h r it is is a t ru e r h e u m a t o -
m ale p re se n t in g
logic e m e rge n cy t h a t ca n le a d t o irre -
w it h acu t e -o n se t

s
ve r s ib le jo in t d e s t r u ct io n , in cr e a s e d

i
t
i
le f t k n e e p ain ,

r
m o r b id it y, a n d a cce le ra t e d m o r t a lit y,

h
t
r
w arm t h , an d w it h o u t p ro m p t d ia gn o s is a n d t re a t -

A
m e n t . Alt h ou gh m a n y in fe ct iou s a ge n t s

s
sw e llin g (Fig . 23.1 ).

u
m ay ca u s e a rt h rit is , ba ct e ria l a rt h rit is is

o
i
t
c
t h e m os t s ign i ca n t be ca u s e of it s ra p -

e
f
id ly p rogre s s ive a n d h igh ly d e s t ru ct ive

n
I
n a t u re. De s p it e re ce n t a d va n ce s in a n t i-

5
N
m icro b ia l t h e ra p y, d ia gn o s t ic t e s t in g,

O
I
a n d ge n e ra l m e d ica l ca re, t h e p rogn os is

T
C
for p a t ie n t s w it h ba ct e ria l a rt h rit is con t in u e s t o be gu a rd e d w it h 25% t o 50% of

E
S
p a t ie n t s s u ffe rin g p e rm a n e n t join t d a m a ge a n d a n e s t im a t e d 5% t o 15% ca s e
fa t a lit y s e con d a ry t o com p lica t ion s in clu d in g s ep s is . Pe rh a p s t h e m os t im p or-
t a n t fa ct o r rega rd in g t h e o u t com e o f p a t ie n t s w it h ba ct e ria l a rt h rit is is t h e
s p e e d w it h w h ich a p p rop ria t e t h e ra py is in s t it u t e d . Th e re fore, it re m a in s t ru e

Figure 23.1 Pla in ra diogra ph of septic a rthritis. Media l a nd la tera l x-ra ys of the left knee showing mild joint
effusion, but is otherwise norma l.
239
 240 Se ctio n 5 In fe ct iou s Art h rit is

a t t h e s t a rt o f t h e n ew m ille n n iu m a s it h a s fo r m o re t h a n h a lf a ce n t u ry;
clin ica l s u s p icion of t h e d ia gn os is of ba ct e ria l a rt h rit is is t h e m os t crit ica l con -
s id e ra t ion for t h e clin icia n .
Ba ct e ria l a rt h rit is e n s u e s w h e n fore ign orga n is m s in va d e t h e s yn oviu m or
join t s p a ce. In t h e m a jority of ca ses , in fect ion is in trod u ced via h e m a togen ou s
sp re a d from a d is ta n t s ite. Less com m on ly, ba cte ria l p a t h ogen s rea ch t h e join t
s p a ce via d ire ct in ocu la t ion t h rou gh a p e n e t ra t in g t ra u m a or p roce d u re (e.g.,
a rt h roce n t e s is , s u rge ry) or via con t igu ou s s p re a d from a d ja ce n t s oft -t is s u e or
bon e in fection s , in clu d in g cellu lit is, osteom yelitis , a n d bu rsitis . Up on en t ry in t o
th e join t sp a ce, ba cteria in d u ce a n a cu te in a m m a tory resp on s e, w h ich ra p id ly
p rogresses to s yn ovia l h yp erp la sia a n d in ltra t ion by in a m m a tory cells. With ou t
p rom p t trea tm en t in itia t ion , th is ca n lea d to en zym a tic a n d cytokin e-m ed ia ted
ca rtila ge a n d bon e d egra d a tion w it h in d ays . Ad d it ion a lly, in ba cteria l a rth ritis, th e
u rgen cy of t rea tm en t is fu rth er h eigh ten ed beca u s e of p oten tia l in fection w ith
ba cteria l stra in s w ith viru len ce fa ct ors (e.g., toxin s, a d h esin s ), w h ich a re a s soci-
a ted w it h in crea s ed p a th ogen icit y a n d d isea s e severity (1 ).
Th e t w o m a jor cla s s e s of ba ct e ria l a rt h rit is a re n on gon ococca l a n d gon o-
cocca l a rt h rit is (d is cu s s e d be low ), w it h n on gon ococca l a rt h rit is a ccou n t in g for
t h e m a jorit y of ca s e s a cros s a ll a ge a n d ris k grou p s . Staphylococcus aureus is t h e
m os t com m on orga n is m in fe ct in g n a ïve join t s in 60% t o 70% of ca s e s . Be ca u s e
S
E
it is s u ch a fre q u e n t ca u s e of ba ct e ria l a rt h rit is , t h e in cre a s in g p reva le n ce of
C
T
com m u n it y- a n d h os p it a l-a cq u ire d m e t h icillin -re s is t a n t Staph. aureus (MRSA)
I
O
is a n im p ort a n t con s id e ra t ion w h e n in it ia lly t re a t in g ba ct e ria l a rt h rit is . Ad d i-
N
5
t ion a lly, s t a p h ylococci in fe ct ion s a re a s s ocia t e d w it h h igh e r ra t e s of fu lm in a n t
I
n
d is e a s e a n d re s id u a l join t d a m a ge, t h u s n e ce s s it a t in g p rom p t d ia gn os is a n d
f
e
a ggre s s ive t re a t m e n t .
c
t
i
Th e m a in re m a in in g ca u s e s of ba ct e ria l a rt h rit is in clu d e s t rep t occci, gra m -
o
u
s
n ega t ive ba cilli, a n d a n a e robe s . Hos t –p a t h oge n a s s ocia t ion s m ay be h e lp fu l in
A
gu id in g in it ia l a n t im icrobia l t re a t m e n t . St rep t ococci (e.g., Streptococcus v iridans ,
r
t
h
Strep. pneum oniae, grou p A a n d B s t rep t ococci) a ccou n t for 15% t o 20% of n on -
r
i
t
i
gon ococca l a rt h rit is a n d m ay be p re ce d e d by p rim a ry s kin or s oft -t is s u e in fe c-
s
t ion s . Grou p A s t re p t ococci a re t h e m os t com m on s t re p t ococca l s p e cie s a n d a re
oft e n is ola t e d a ft e r d e n t a l p roce d u re s . Gra m -n ega t ive ba cilli in fe ct ion s (e.g.,
Pseudom onas aeruginosa , Escherichia coli, Proteus m irabilis ) a re re s p on s ible for 5%
t o 25% of ca s e s , a n d a re a s s ocia t e d w it h ch ron ic s ys t e m ic illn e s s , im m u n os u p -
p re s s ion , in t ra ve n ou s d ru g u s e , a n d a d va n cin g a ge (e.g., in e ld e rly p a t ie n t s ).
Th e s e in fe ct ion s m ay begin a s u rin a ry t ra ct or s kin in fe ct ion s w it h s u bs e q u e n t
h e m a t oge n ou s s p re a d t o a join t . La s t ly, a n a e ro bic ba ct e ria (e .g., Bacteroides ,
Clostridium , Fusobacterium ) a ccou n t for 1% t o 5% of ba ct e ria l a rt h rit is , a lt h ou gh
t h is m ay be a n u n d e re s t im a t e a s a n a e robe s h ave h is t orica lly be e n m ore d if -
cu lt t o is o la t e. W h ile m o s t b a ct e ria l a rt h rit is in fe ct io n s a re m o n o m icro b ia l,
a n a e ro b ic in fe ct io n s m a y b e p o lym icro b ia l in n a t u re . Pre d is p o s in g fa ct o r s
in clu d e d ia b e t e s m e llit u s , im m u n o co m p ro m is e d s t a t e s , a n d p o s t o p e ra t ive
w ou n d in fe ct ion s . Su s p icion for a n a n a e robic a ge n t s h ou ld be ra is e d in t h e ca s e
of fou l-s m e llin g s yn ovia l u id or p la in ra d iogra p h s d ep ict in g ga s in t h e join t
s p a ce. Ad e q u a t e d ra in a ge of t h e join t is a key a d ju n ct t o a n t im icrobia l t h e ra py
in t h e ca s e of a n a e robic in fe ct ion .
Le s s co m m o n ly, ot h e r o rga n is m s m a y a ls o b e a s s ocia t e d w it h ba ct e r ia l
a rt h rit is . On e w ort h m e n t ion in g is t h e Brucella s p e cie s (e.g., B. m elitensis ), w h ich
is be com in g m ore p reva le n t w orld w id e (2 ). Ris k fa ct ors in clu d e con s u m p t ion of
u n p a s t e u rize d m ilk or ch e e s e or d ire ct con t a ct w it h in fe ct e d a n im a ls . Pre s e n -
t a t ion is u s u a lly ch a ra ct e rize d by m on oa rt h rit is of t h e h ip or kn e e, a lt h ou gh
o ligo a rt h r it is , s a cro iliit is , o r s p on d ylit is m a y a ls o b e s e e n . Fu r t h e r w o rk -u p
s h ou ld be gu id e d by t h e clin ica l s e t t in g if on e of t h e com m on e t iologic a ge n t s
is n ot id e n t i e d .
Go n o co cca l a rt h rit is is t h e m os t co m m on ca u s e o f ba ct e r ia l a r t h rit is in
you n g, s e xu a lly a ct ive in d ivid u a ls w it h ou t a h is t ory of join t d is e a s e. Wom e n

CLINICAL POINTS
• Clin ica l su sp icio n o f t h e
d ia g n o sis o f b a ct e ria l
a rt h rit is is t h e m o st
im p o rt a n t co n sid e ra t io n
fo r t h e clin icia n .
• Ext e n sive , ra p id jo in t
d e st ru ct io n m a y o ccu r
w it h o u t p ro m p t in it ia t io n
o f a p p ro p ria t e a n t ib io t ics.
• Acu t e m o n o a rt icu la r a rt h ri-
t is sh o u ld b e co n sid e re d
b a ct e ria l a rt h rit is u n t il
p ro ve n o t h e rw ise .
• Jo in t d ra in a g e a n d
a n t ib io t ic t h e ra p y a re
t h e ke y co m p o n e n t s o f
t re a t m e n t .
• St ap h ylo co ccu s au re u s
is t h e m o st co m m o n
o rg a n ism a cro ss a ll a g e s
a n d risk g ro u p s, w h ile
Ne isse ria g o n o rrh o e ae
a cco u n t s fo r m o st ca se s
a m o n g yo u n g , se xu a lly
a ct ive in d ivid u a ls.
Ch a p te r 23 Ba ct e ria l Art h rit is 241
a re a t gre a t e s t ris k for d is s e m in a t e d gon ococca l in fe ct ion , e s p e cia lly d u rin g
p regn a n cy a n d m e n s e s , a n d a re a ffe ct e d t w o t o t h re e t im e s m ore oft e n t h a n
m e n . W h ile, ove ra ll, t h e p rogn os is for gon occoca l a rt h rit is is be t t e r t h a n t h a t
for n on gon ococca l a rt h rit is , ra p id d ia gn os is is e q u a lly im p ort a n t in t h is s e t t in g
give n t h e p ot e n t ia l for join t d e s t ru ct ion w it h d e lays in t re a t m e n t .
Dia gn os is of gon ococca l a rt h rit is ca n be d if cu lt , a s on ly 25% of p a t ie n t s
m ay re ca ll s ign s of m u cos a l in volve m e n t of t h e u re t h ra , ge n it a lia , or re ct u m .
Clin ica l s u s p icio n s h o u ld b e ra is e d in t h e s e t t in g o f p u ru le n t m o n o a rt icu la r
a rt h rit is , a s w e ll a s in t h e s e t t in g of a rt h rit is –d e rm a t it is s yn d rom e, t h e t yp ica l
p re s e n t a t ion of gon ococca l a rt h rit is in 60% of ca s e s . It is ch a ra ct e riz e d by a
t ria d of m igra t ory p olya rt h rit is , t e n os yn ovit is , a n d d e rm a t it is . At d is e a s e on s e t ,
p a t ie n t s com m on ly e xp e rie n ce m igra t ory a rt h ra lgia s in t h e u p p e r e xt re m it ie s
(e.g., w ris t , e lbow s ) a n d , le s s fre q u e n t ly, in t h e low e r e xt re m it ie s . La t e r, p a t ie n t s
m ay d eve lop t e n os yn ovit is , a n d in g n ot com m on ly s e e n in in fe ct iou s a rt h rit is
re la t e d t o ot h e r orga n is m s . Gon ococca l t e n os yn ovit is m os t oft e n occu rs in t h e
d ors u m of t h e w ris t , h a n d , or a n kle. Th e s kin le s ion s of d is s e m in a t e d gon ococca l
in fe ct ion a re t yp ica lly p a in le s s , n on p ru rit ic, m a cu lop a p u la r le s ion s d is t ribu t e d
ove r t h e d is t a l e xt re m it ie s , e s p e cia lly t h e p a lm s a n d s ole s .
Dia gn os is of gon ococca l a rt h rit is is fu rt h e r com p lica t e d by t h e d if cu lt y in
is ola t in g gon ococci in s yn ovia l u id a n d blood . Eve n w it h a t t e n t ion t o p rop e r
s
i
t
cu lt u re t e ch n iq u e (e.g., ch ocola t e a ga r, ra p id p la t in g), gra m s t a in s a n d cu lt u re s
i
r
h
of s yn ovia l u id a re p os it ive in few e r t h a n 40% of ca s e s , a n d blood cu lt u re s a re
t
r
A
a lm os t a lw ays n ega t ive (3 ). Mu cos a l cu lt u re s of t h e u re t h ra , p h a ryn x, ce rvix, a n d
s
u
re ct u m s h ou ld be p e rform e d in a ll p a t ie n t s , s in ce t h ey h ave a h igh e r yie ld a n d
o
i
t
m ay be p os it ive eve n in t h e a bs e n ce of s ym p t om s . More s e n s it ive t e ch n iq u e s for
c
e
id e n t i ca t ion of gon ococci, s u ch a s p olym e ra s e ch a in re a ct ion , a re cu rre n t ly n ot
f
n
I
rou t in e ly u s e d , bu t m ay p rovid e a d d it ion a l d ia gn os t ic va lu e in t h e fu t u re.
5
Alt h o u gh m os t p a t ie n t s re s p o n d d ra m a t ica lly t o a n t ibio t ics w it h in 24 t o
N
O
48 h ou rs a n d n e a rly a ll m a ke a com p le t e re cove ry, w h e n gon occoca l a rt h rit is is
I
T
C
s u s p e ct e d , p a t ie n t s s h o u ld b e co n s id e re d fo r h o s p it a l a d m is s io n t o co n rm
E
d ia gn os is , e xclu d e co m p lica t ion s s u ch a s m e n in git is a n d e n d o ca rd it is , a n d
S
re ce ive p a re n t e ra l t h e ra p y.
Clinica l Pre se nta tio n
Clin ica l s u s p icion for ba ct e ria l a rt h rit is s h ou ld be ra is e d in p a t ie n t s w it h u n d e r-
lyin g jo in t d is e a s e, co m p ro m is e d im m u n e fu n ct io n , a n d in cre a s e d in fe ct io n
ris k, a ll of w h ich a re key ris k fa ct ors for join t in fe ct ion . Join t s t h a t h ave be e n
d a m a ge d by a r t h r it is (e .g., r h e u m a t o id a r t h r it is , o s t e o a r t h r it is , crys t a llin e
a rt h rit is ) or t ra u m a a re m ore s u s cep t ible t o in fe ct ion t h a n n orm a l join t s . Th is
m ay be s e con d a ry t o s t ru ct u ra l d a m a ge, n e ova s cu la riza t ion , or loca l fa ct ors . As
t h e s yn oviu m s e rve s a n im p or t a n t p rot e ct ive role in join t d e fe n s e, p a t ie n t s
w it h rh e u m a t oid a rt h rit is a re p a rt icu la rly s u s ce p t ible. Pa t ie n t s w it h im p a ire d
h os t d e fe n s e s be ca u s e of e xt re m e s of a ge, s ys t e m ic illn e s s (e.g., d ia be t e s m e l-
lit u s , m a lign a n cy, live r or kid n ey d is e a s e ), im m u n os u p p re s s ive m e d ica t ion s , or
im m u n o co m p ro m is e d co n d it io n s (e .g., HIV/ AIDs ) a re a ls o a t in cre a s e d ris k .
Likew is e, it follow s t h a t ris k fa ct ors for in fe ct ion s u ch a s p ros t h e t ic join t s in
w h ich fore ign bod ie s s e rve a s a n id u s for in fe ct ion , in t ra -a rt icu la r join t in je c-
t ion s , s kin in fe ct ion s , a n d in t rave n ou s d ru g a bu s e m ay p re d is p os e p a t ie n t s t o
ba ct e ria l a rt h rit is . As a clin icia n , obt a in in g a t h orou gh h is t ory rega rd in g t h e s e
ris k fa ct ors p lays a n im p ort a n t role in d ia gn os is a n d t re a t m e n t .
Exa mina tio n
Th e cla s s ic p re s e n t a t ion for ba ct e ria l a rt h rit is is a cu t e m on oa rt icu la r join t p a in
w it h sw e llin g, w a rm t h , a n d e ryt h e m a . On exa m in a t ion , p a t ie n t s t yp ica lly e xh ibit
242 Se ctio n 5 In fe ct iou s Art h rit is
PATIENT ASSESSMENT
• Th e cla ssic p re se n t a t io n
is a cu t e m o n o a rt icu la r
jo in t p a in w it h sw e llin g ,
w a rm t h , a n d e ryt h e m a .
• Pa t ie n t s w it h g o n o co cca l
a rt h rit is m a y e xh ib it
m ig ra t o ry p o lya rt h ra lg ia s,
t e n o syn o vit is, a n d
ch a ra ct e rist ic skin le sio n s.
• Jo in t a sp ira t io n sh o u ld b e
p e rfo rm e d in a ll p a t ie n t s
w it h su sp e ct e d b a ct e ria l
a rt h rit is p rio r t o st a rt in g
e m p iric a n t ib io t ic t h e ra p y.
• Syn o via l u id w ill b e
in a m m a t o ry w it h w h it e
b lo o d ce ll (WBC) co u n t
2,500/m m 3 a n d 75%
n e u t ro p h ils; in fe ct io u s
a rt h rit is m a y b e a sso cia t e d
w it h ve ry h ig h WBC
co u n t s in t h e syn o via l
u id , fo r e xa m p le , WBC
co u n t 50,000/m m 3 .
• A n e g a t ive g ra m st a in
a n d cu lt u re d o e s n o t
e xclu d e a d ia g n o sis o f
b a ct e ria l a rt h rit is.
Table 23.1 Different ial Diagnosis of Bact erial Art hrit is
Ot h e r in fe ct io u s a rt h rit id e s
Vira l a rt h rit is
Myco b a ct e riu m a rt h rit is
Fu n g a l a rt h rit is
Lym e d ise a se
Cryst a llin e a rt h rit is
Go u t
Pse u d o g o u t
Sp o n d ylo a rt h ro p a t h ie s
Re it e r’s syn d ro m e
An kylo sin g sp o n d ylit is
Re a ct ive a rt h rit is (e .g ., p o st st re p t o co cca l)
No n a rt h rit ic co n d it io n s
Ce llu lit is
Bu rsit is
Tra u m a /fra ct u re
Fo re ig n b o d y re a ct io n
obviou s join t e ffu s ion , t e n d e rn e s s t o p a lp a t ion , a n d re s t rict e d ra n ge of m ot ion .
La rge join t s a re m ore com m on ly a ffe ct e d t h a n s m a ll join t s , a n d in u p t o 70% of
ca s e s , t h e kn e e or h ip is in volve d . In t ra ve n ou s d ru g u s e rs m a y p re s e n t w it h
s t e rn ocla vicu la r or s a croilia c join t in volve m e n t . Feve r is t h e m os t com m on ly
a s s ocia t e d s ym p t om on p re s e n t a t ion a n d is fou n d in 50% of p a t ie n t s , w h ile
sw e a t s a n d ch ills a re le s s com m on (4 ).
Clin ica l a cu it y for t h e d ia gn os is of ba ct e ria l a rt h rit is is p a rt icu la rly im p or-
t a n t in a t yp ica l p re s e n t a t ion s , give n t h e ra p id p a ce of join t d e s t ru ct ion ove r a
m a t t er of d ays . Clin ica l s u s p icion s h ou ld re m a in h igh w it h p olya rt icu la r p re s e n -
t a t ion s , w h ich m ay a ccou n t for a q u a rt e r of s ep t ic a rt h rit is ca s es (5 ). Polya rt icu la r
in fe ct ion is m ore like ly in t h e s e t t in g of Staph. aureus in fe ct ion , gon ococca l d is -
ea s e, a n d in p a t ie n t s w it h rh e u m a t oid a rt h rit is a n d ot h e r s ys t e m ic con n e ct ive
t is s u e d is e a s e s . On t h e ot h e r h a n d , p re exis t in g p olya rt icu la r join t d is e a s e m ay
con fou n d t h e d ia gn os is of a m on oa rt icu la r in fe ct ion . In t h e s e p a t ie n t s , ba ct e ria l
a rt h rit is s h ou ld be s u s p e ct e d in t h os e w h o p re s e n t w it h n ew s ym p t om s in on e
join t t h a t a re ou t of p rop ort ion t o t h e ot h e r join t s . Ad d it ion a lly, it is im p ort a n t
n ot t o exclu d e a d ia gn os is of ba ct e ria l a rt h rit is in p a t ie n t s w it h a gra d u a l on s e t
of s ym p t om s , w h ich m ay be fou n d in p a t ie n t s w it h p ros t h e t ic join t s , rh e u m a t ic
d is e a s e, or im m u n ocom p rom is e d s t a t e s .
Give n t h e ris ks a s s ocia t e d w it h a d e la y in d ia gn os is , it is n ot u n re a s on a ble
t o s u gge s t t h a t a bs e n t a cle a rly e s t a blis h e d ot h e r ca u s e, a cu t e m on oa rt icu la r
a rt h rit is is in fe ct iou s u n t il p rove n ot h e rw is e. Likew is e, a h igh d egre e of clin ica l
s u s p icion for ba ct e ria l a rt h rit is s h ou ld be h e ld in p a t ie n t s w it h p re d is p os in g
ris k fa ct ors for s ep t ic a rt h rit is . Th e d iffe re n t ia l d ia gn os is for ba ct e ria l a rt h rit is
is review e d in Ta ble 23.1 . A t h orou gh h is t ory a n d p h ys ica l e xa m in a t ion m a y
h e lp d is t in gu is h be t w e e n a n in fe ct iou s a n d in a m m a t o ry p roce s s . To d is t in -
gu is h p e ria rt icu la r con d it ion s , d ia gn os is w ill be fa cilit a t e d if t h e clin icia n is
con d e n t in h is or h e r p h ys ica l e xa m in a t ion s kills rega rd in g d iffe re n t ia t ion of
a r t h r it is fro m in vo lve m e n t o f s t r u ct u re s s u r ro u n d in g t h e jo in t (e .g., s k in ,
bu rs a s , t e n d on s ).
Studie s
Th e corn e rs t on e of t h e d ia gn os is of ba ct e ria l a rt h rit is is p rom p t a rt h roce n t e s is
a n d s yn ovia l u id a n a lys is (Ta ble 23.2 ). Sa m p le s s h ou ld be s e n t for W BC cou n t

NOT TO BE MISSED
• A t h o ro u g h h ist o ry a n d
p h ysica l e xa m in a t io n
a re crit ica l, a lt h o u g h it
m a y st ill b e d if cu lt t o
d ist in g u ish b e t w e e n a n
in fe ct io u s ca u se a n d a n
in a m m a t o ry a rt h rit is
o f o t h e r e t io lo g y (e .g .,
cryst a llin e , a u t o im m u n e ).
• Se p t ic a rt h rit is m a y b e
su p e rim p o se d o n o t h e r
jo in t d ise a se s a n d m a y b e
m ist a ke n fo r e xa ce rb a t io n
o f t h e p re e xist in g
co n d it io n .
• Ke e p a h ig h in d e x o f
su sp icio n in p a t ie n t s
w h o a re e ld e rly, yo u n g ,
im m u n o co m p ro m ise d , o r
h a ve p re e xist in g jo in t
d ise a se .
• Pe d ia t ric p a t ie n t s m a y
p re se n t w it h su b t le a n d
n o n sp e ci c n d in g s;
h e ig h t e n e d clin ica l
su sp icio n is e sp e cia lly
crit ica l g ive n t h e p o t e n t ia l
fo r ca t a st ro p h ic o u t co m e s.
Ch a p te r 23 Ba ct e ria l Art h rit is 243
Table 23.2 Suspect ed Bact erial Art hrit is: Key Point s in
Joint Aspirat ion
Ne ve r a sp ira t e a jo in t t h ro u g h in fe ct e d skin o r so ft t issu e s
Ob t a in WBC co u n t w it h d iffe re n t ia l, g ra m st a in a n d cu lt u re , a n d p o ssib ly cryst a l
a n a lysis fro m t h e a sp ira t e d syn o via l u id
Wh e n t h e re is clin ica l su sp icio n o f in fe ct io n , in it ia t e a n t im icro b ia l t h e ra p y
im m e d ia t e ly a ft e r a sp ira t io n
Jo in t a sp ira t io n m a y b e p e rfo rm e d se ria lly t o re m o ve in fe ct e d u id a n d a sse ss
WBC co u n t s o ve r t im e t o m o n it o r re sp o n se t o t h e ra p y
Co n sid e r o rt h o p e d ic co n su lt a t io n fo r p ro st h e t ic jo in t s, h ip jo in t s (p a rt icu la rly in
ch ild re n ), o r o p e n d ra in a g e if clin ica l re sp o n se is su b o p t im a l
Use e xt re m e ca re in a sp ira t in g a p ro st h e t ic jo in t
WBC, w h it e b lo o d ce ll.
s
i
t
i
a n d d iffe re n t ia l, gra m s t a in , cu lt u re, a n d crys t a l a n a lys is ; t h e s e a re t h e on ly
r
h
t
t e s t s of p rove n d ia gn os t ic va lu e in t h is clin ica l s e t t in g (6 ). In fe ct e d u id is ch a r-
r
A
a ct e ris t ica lly in a m m a t ory (i.e., w it h W BC cou n t 2,500/m m 3 a n d 75% n e u -
s
u
t rop h ils ) in t h e d iffe re n t ia l ( 75%); n ot u n com m on ly, it is p u ru le n t w it h s yn o-
o
i
via l W BC co u n t s o f 30 t o 50,000/m m 3 or h igh e r. Th e like lih o od o f in fe ct io n
t
c
e
f
in cre a s e s w it h ris in g W BC cou n t (4 ). Th e p re d om in a n t d iffe re n t ia l d ia gn os is for
n
I
h igh ly in a m m a t ory s yn ovia l u id is crys t a llin e a rt h rit is (e.g., gou t ). Syn ovia l
5
u id gra m s t a in s give a p os it ive re s u lt in 50% t o 70% of ca s e s of n on gon occoca l
N
O
a rt h rit is a n d s h ou ld be u s e d t o gu id e in it ia l t h e ra py. Pos it ive cu lt u re s in cre a s e
I
T
C
t h e yie ld t o 70% t o 90% of ca s e s of n on gon ococca l a rt h rit is , bu t a n ega t ive gra m
E
S
s t a in or cu lt u re d oe s n ot ru le ou t a n in fe ct e d join t (7 ). For e xa m p le, fa ls e n ega -
t ive s m a y o ccu r in p a t ie n t s p reviou s ly t re a t e d w it h a n t ibio t ic t h e ra p y o r in
p a t ie n t s w it h gon ococca l in fe ct ion s .
Ad d it ion a l t e s t s t h a t s h o u ld be p e rform e d in clu d e blood cu lt u re s , w h ich
a re p os it ive in u p t o 50% of ca s e s , a n d s h ou ld be obt a in e d t o e xclu d e a ba ct e r-
e m ic origin of t h e in fe ct e d join t . W h e n clin ica lly a p p rop ria t e, u re t h ra l, n a s a l,
t h roa t , re ct a l, or ce rvica l sw a bs m a y be p e rform e d t o eva lu a t e for gon ococca l
in fe ct ion . Ot h e r la bora t ory s t u d ie s s u ch a s p e rip h e ra l W BC cou n t , e ryt h rocyt e
s e d im e n t a t ion ra t e, a n d C-re a ct ive p rot e in a re u s u a lly e leva t e d a n d m a y h e lp
in m on it orin g t re a t m e n t .
Im a gin g s t u d ie s a re of lim it e d d ia gn os t ic va lu e e a rly in t h e d is e a s e cou rs e
of ba ct e ria l a rt h rit is . Pla in ra d iogra p h s m a y on ly reve a l s oft -t is s u e sw e llin g or
join t e ffu s ion (Fig. 23.1 ). De s p it e t h is , t h ey s h ou ld be obt a in e d a s a ba s e lin e a n d
t o e xclu d e os t e om ye lit is . In la t e r s t a ge s of ba ct e ria l a rt h rit is ( 10 d a ys a ft e r
in fe ct io n o n s e t ), ca rt ila ge a n d b o n e d e s t ru ct io n m a y b e vis u a lize d o n p la in
ra d iogra p h s , h igh ligh t in g it s ra p id cou rs e . Of n ot e, u n t re a t e d s e p t ic a rt h rit is
t e n d s t o b e ch a ra ct e riz e d by e ro s io n s w it h re la t ive ly in d is t in ct m a rgin s a s
op p os e d t o ot h e r join t p a t h ology (e.g., gou t , rh e u m a t oid a rt h rit is [RA]), w h ich
is ch a ra ct e rize d by e ros ion s w it h cle a rly d e n e d e d ge s . Ot h e r m e t h od s of im a g-
in g s u ch a s com p u t e d t om ogra p h y (CT) a n d m a gn e t ic re s on a n ce im a gin g (MRI)
a re m ore s e n s it ive for d is t in gu is h in g os t e om ye lit is , join t e ffu s ion s , a n d p e ri-
a r t icu la r a b s ce s s e s , b u t a re n o t co m m o n ly u s e d fo r t h e eva lu a t io n o f jo in t
in fe ct ion s . Us u a lly t h ey a re re s e rve d for eva lu a t in g t h e s t e rn ocla vicu la r or s a c-
ro ilia c jo in t s , w h ich a re d if cu lt t o vis u a liz e u s in g p la in ra d iogra p h y. La s t ly,
ra d ion u clid e s ca n s m ay h e lp loca lize a re a s of in a m m a t ion , bu t a re u n a ble t o
d e n it ive ly e s t a blis h in fe ct ion . Give n t h e ir low s p e ci cit y, t h ey a re ra re ly u s e d
in t h e d ia gn os is of ba ct e ria l a rt h rit is .
 244 Se ctio n 5 In fe ct iou s Art h rit is

Tre a tme nt
All p a t ie n t s w it h s u s p e ct e d ba ct e ria l a rt h rit is s h ou ld be con s id e re d for h os p it a l
a d m is s ion . Ba ct e ria l a rt h rit is is n ot fre q u e n t ly t re a t e d a s a n ou t p a t ie n t a s it
t yp ica lly re q u ire s in t rave n ou s a n t ibiot ics a n d p os s ibly re p e a t e d d ra in a ge of t h e
a ffe ct e d join t d ep e n d in g on t h e clin ica l cou rs e. Con s id e ra t ion s h ou ld be give n
t o rh e u m a t ology or ort h op e d ic s u rge ry con s u lt a t ion , a n d in m ore com p lica t e d
ca s e s , a n in fe ct io u s d is e a s e co n s u lt m a y b e h e lp fu l in gu id in g w o rk -u p a n d
t re a t m e n t .
Ea rly in it ia t ion of a n t ibiot ic t re a t m e n t is crit ica l for im p rovin g p rogn o s is
a n d ou t com e s . If t h e re is a h igh s u s p icion for ba ct e ria l a rt h rit is , e m p iric t h e r-
a py s h ou ld be s t a rt e d im m e d ia t e ly a ft e r cu lt u re s h a ve be e n d ra w n . Cu rre n t ly,
t h e re a re n o ra n d om ize d con t rolle d t r ia ls eva lu a t in g a n t ibiot ic re gim e n s for
ba ct e ria l a rt h rit is (8 ). Th u s , ch oice of in it ia l t h e ra p y s h ou ld be gu id e d by gra m
s t a in , r is k fa ct o r s , a n d clin ica l s e t t in g. Fu r t h e r m o re , re s is t a n ce p a t t e r n s o f
p ot e n t ia l orga n is m s s h ou ld a ls o be t a ke n in t o a ccou n t d u rin g s e le ct ion of in i-
t ia l t h e ra p y. In ge n e ra l, t re a t m e n t d u ra t ion is 3 t o 6 w e e ks , in t ra ve n ou s , a n d
ora l com bin e d .
Join t d ra in a ge a n d lava ge is t h e ot h e r m a in s t ay of t re a t m e n t a n d is im p or-
t a n t in re m ovin g t h e in a m m a t ory ce lls a n d m e d ia t ors t h a t ca u s e p e rm a n e n t
S
E
join t d e s t ru ct ion . W h ile t h e re is con t rove rs y rega rd in g w h e t h e r clos e d n e e d le
C
T
a s p ira t ion s , a rt h ros copy, or op e n a rt h rot om y is be t t e r, in m os t circu m s t a n ce s ,
I
O
re p e a t e d n e e d le a s p ira t ion is u s u a lly s u f cie n t . Se ria l s yn ovia l u id a n a lys e s
N
s h ou ld d e m on s t ra t e a d ow n w a rd t re n d in W BC n u m be rs a n d d e cre a s e in e ffu -
5
I
s ion volu m e w it h re s p on s e t o t re a t m e n t .
n
f
e
c
t
i
o
Clinica l Co urse
u
s
A
r
Lo n g-t e r m p ro gn o s is fo r jo in t p re s e r va t io n co r re la t e s w it h t h e o rga n is m
t
h
r
in volve d , p rom p t n e s s of d ia gn os is , a n d in s t it u t ion of a p p rop ria t e a n t im icrobia l
i
t
i
s
t h e ra p y, a s w e ll a s h os t -re la t e d ch a ra ct e ris t ics . In ge n e ra l, p a t ie n t s w it h gon o-
cocca l a rt h rit is h a ve t h e be s t p rogn os is w it h p rom p t re s olu t ion of s ym p t om s
a n d ra re lon g-t e rm join t m orbid it y from t h is in fe ct ion . Pa t ie n t s w it h s ign i ca n t
com orbid it ie s , e s p e cia lly t h os e w h o a re im m u n os u p p re s s e d , a re m os t vu ln e r-
a ble t o join t d a m a ge be ca u s e of t h e ir in a bilit y t o e ffe ct ive ly cle a r in fe ct ion s in
s p it e of a p p rop ria t e a n t im icrobia l t h e ra py. In fe ct ion s w it h p a rt icu la rly viru le n t
orga n is m s s u ch a s Staph. aureus ca n p rod u ce lo n g-t e rm a rt icu la r d a m a ge in
s p it e of a p p rop ria t e t im in g a n d s e le ct ion of a n t ibiot ic t h e ra py.
Pa t ie n t s w it h p ros t h e t ic d evis e p os e a d if cu lt ch a lle n ge a s s u cce s s fu l join t
re cove ry re q u ire s s u rgica l d e brid e m e n t in con ju n ct ion w it h a n t ibiot ic t h e ra p y;
on occa s ion s , t h is com bin e d fa ils t o cle a r t h e in fe ct ion n e ce s s it a t in g re m ova l
of t h e p ros t h e t ic d evice follow e d by p rolon ge d a n t ibiot ic t h e ra py a n d eve n t u a l
join t re p la ce m e n t .

Spe cia l Circumsta nce s

BACTERIAL ARTHRITIS IN CHILDREN
Th e re a re s eve ra l ch a ra ct e ris t ics of ba ct e ria l a rt h rit is in ch ild re n w h o a re d is -
t in ct from t h os e in a d u lt s . Be ca u s e of t h e im m a t u re va s cu la r a n a t om y of t h e ir
join t s , n e on a t e s a n d you n g ch ild re n oft e n h ave coe xis t in g s ep t ic a rt h rit is a n d
os t e om ye lit is . Th e s p e ct ru m of com m on p a t h oge n s a ls o va rie s be ca u s e of t h e ir
le s s d eve lop e d im m u n e s ys t e m . W h ile Staph. aureus re m a in s t h e m os t com m on
o rga n is m , gro u p B s t re p t o co cci a n d gra m -n e ga t ive b a cilli (Kingella k ingae ,
N. gonorrhoeae) m a y a ls o be fou n d . Haem ophilus in uenz ae w a s a d om in a n t p a t h -
oge n in t h e p a s t a lt h ou gh le s s s o n ow a d a ys , give n w id e s p re a d u s e of va ccin e s .
Ad d it ion a lly, on e of t h e m a in con ce rn s in ch ild re n is h ip in volve m e n t , w h ich

WHEN TO REFER
• All p a t ie n t s sh o u ld b e
co n sid e re d fo r h o sp it a l
a d m issio n .
• Co n sid e r co n su lt in g rh e u -
m a t o lo g y o r o rt h o p e d ics if
a se p t ic jo in t is su sp e ct e d
o r co n rm e d .
• Co n sid e r co n su lt a t io n
w ith a n in fe ct io u s d ise a se
sp e cia list in t h e im m u n o -
com p rom ise d h o st o r w h e n
u n usu a l o rga n ism s a re
im p lica t e d in t h e p ro ce ss.
• All p a t ie nt s w it h p ro sth e t ic
joint infe ct ions shou ld be
co n sid e re d fo r re fe rra l t o
a n o rth o p e d ic su rg e o n fo r
furthe r e va lua t ion a nd p os-
sible re mova l o f pro sthe sis.
Ch a p te r 23 Ba ct e ria l Art h rit is 245
ca n le a d t o p o t e n t ia lly ca t a s t ro p h ic co n s e q u e n ce s . Ph ys ica l e x a m in a t io n
s h ou ld in clu d e ca re fu l a s s e s s m e n t of t h e h ip , bu t t ocks , a n d groin , a n d w ork-u p
s h ou ld in clu d e u lt ra s ou n d , w h ich h a s a h igh n ega t ive p re d ict ive va lu e for ba c-
t e ria l a rt h rit is in t h e h ip .
BACTERIAL ARTHRITIS IN IMMUNOCOMPROMISED PATIENTS
Im p a irm e n t s in im m u n e d e fe n s e a re im p ort a n t fa ct ors in t h e d eve lop m e n t of
ba ct e ria l a rt h rit is in m os t a ffe ct e d p a t ie n t s . In a d d it ion , p a t ie n t s w it h d e fe ct s in
s p e ci c com p on e n t s of t h e im m u n e re s p on s e t e n d t o d eve lop p a rt icu la r in fe c-
t ion s re e ct ive of t h e ir im m u n od e cie n cy. For e xa m p le, p a t ie n t s w it h d e fe ct s in
a n t ib o d y-m e d ia t e d re s p o n s e s (e .g., co m m o n va r ia ble im m u n o d e ficie n cy,
X-lin ke d a ga m m a globu lin e m ia ) a re m ore s u s cep t ible t o in fe ct ion by e n ca p s u -
la t e d coa t e d orga n is m s (e.g., Streptococcus pneum ococci, H. in uenz ae). Pa t ie n t s
w it h d e fe ct s in ce llu la r im m u n it y (e.g., AIDS) a re p a rt icu la rly s u s ce p t ible t o
in fe ct ion w it h in t ra ce llu la r orga n is m s , in clu d in g viru s e s , m ycoba ct e ria , a n d Lis-
teria a m on g ot h e rs . Pa t ie n t s w it h im p a ire d n e u t rop h il fu n ct ion (e.g., ch ron ic
gra n u lom a t ou s d is e a s e ) a re m ore s u s cep t ible t o in fe ct ion w it h ca t a la s e -p os it ive
orga n is m s , s u ch a s Staph. aureus . Th u s , p a t ie n t s w it h kn ow n im m u n od e cie n -
cie s s h ou ld be con s id e re d t o be a t p a rt icu la r ris k for ce rt a in orga n is m s .
s
i
t
i
r
h
t
r
PROSTHETIC JOINT INFECTIONS
A
s
As join t rep la ce m e n t p roce d u re s be com e in cre a s in gly com m on , it is im p ort a n t
u
o
i
t o ke e p in m in d t h e u n iq u e ch a ra ct e r is t ics a s s o cia t e d w it h p ros t h e t ic join t
t
c
e
in fe ct ion s . Th e e t iology, m icrobiology, a n d t re a t m e n t of a n in fe ct ion ca n va ry
f
n
I
d e p e n d in g on t h e t im in g of in fe ct ion . Ea rly p os t op e ra t ive in fe ct ion s (w it h in t h e
5
rs t 3 m on t h s ) a re u s u a lly s e con d a ry t o con t a m in a t ion a cq u ire d d u rin g im p la n -
N
O
t a t ion a n d a re a s s ocia t e d w it h viru le n t orga n is m s s u ch a s Staph. aureus a n d
I
T
gra m -n ega t ive ba cilli. As t im e p a s s e s , t h e like lih ood of h e m a t oge n ou s s e e d in g
C
E
a n d in fe ct ion w it h low -viru le n ce orga n is m s (e.g., Staph. epiderm idis , Diptheroides )
S
in t rod u ce d d u rin g s u rge ry in cre a s e s . It is t h e s e orga n is m s t h a t p rod u ce bio lm s
a n d a ccou n t for t h e m ore in d ole n t p re s e n t a t ion in p ros t h e t ic join t in fe ct ion s .
W h ile m a n a ge m e n t for p ros t h e t ic join t in fe ct ion s d ep e n d s on t h e clin ica l s e t -
t in g, in ge n e ra l, t re a t m e n t for e a rly on s e t in fe ct ion s in volve s s u rgica l d e brid e -
m e n t , a n e xt e n d e d cou rs e of a n t ibiot ics , a n d im p la n t re t e n t ion , w h e re a s fo r
la t e -on s e t in fe ct ion s , it re q u ire s p ros t h e s is re m ova l w it h e it h e r im m e d ia t e or
d e la ye d re im p la n t a t ion (9 ). In ca s e s of s u s p e ct e d in fe ct ion of join t p ros t h e s e s ,
con s u lt a t ion w it h a n ort h op e d is t s h ou ld be s t ron gly con s id e re d .
Co nclusio ns
Ba ct e ria l a rt h rit is con t in u e s t o be a n im p ort a n t h e a lt h p roble m . Clin ica l s u s p i-
cion , ra p id d ia gn os is , a n d p rom p t t h e ra py a re key t o im p rovin g ou t com e s .
ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
040.89 [711.4] d u e t o o r asso ciat e d w it h b act e rial d ise ase NEC
098.50 g o n o co ccal
727.3 Bursitis NEC
726.79 an k le
726.33 e lb o w
726.8 n g e r
(Co n t in u e d )
 246 Se ctio n 5 In fe ct iou s Art h rit is

ICD9 (Co n t in u e d )
726.79 f o o t
726.4 h an d
726.5 h ip
726.60 k n e e
726.33 o le cran o n
726.61 p e s an se rin u s
726.65 p re p at e llar
726.10 sh o u ld e r
726.5 t ro ch an t e ric are a
726.4 w rist
730.2 Oste o mye litis (g e n e ral) (in f e ct ive ) (lo caliz e d ) (n e o n at al)
(p u ru le n t ) (p yo g e n ic) (se p t ic) (st ap h ylo co ccal) (st re p t o co ccal)
(su p p u rat ive ) (w it h p e rio st it is)
730.1 sicca

Re fe re nce s
S
E
1. Sh irt liff ME, Ma d e r JT. Acu t e s ep t ic a rt h rit is . Clin Microbiol Rev 2002 ;15 (2 ):527 –544 .
C
2. Fra n co MP, Mu ld e r M , Gilm a n RH , e t a l. Hu m a n bru ce llos is . Lancet Infect Dis 2007 ;7 (12 ):775 –786.
T
I
O
3. Ros s JJ. Sep t ic a rt h rit is . Infect Dis Clin North A m 2005 ;19 (4 ):853 –861 .
N
4. Ma rga re t t e n ME, Koh lw e s J, Moore D, e t a l. Doe s t h is a d u lt p a t ie n t h a ve s e p t ic a rt h r it is ? JA MA 2007 ;
5
297 (13 ):1478 –1488 .
5. Du bos t JJ, Fis I, De n is P, e t a l. Polya rt icu la r s e p t ic a rt h rit is . Medicine (Baltim ore) 1993 ;72 (5 ):296 –310 .
I
n
f
6. Sch m e rlin g RH , De lba n co ML, Tos t e s o n AN , e t a l. Syn ovia l u id t e s t s : W h a t s h ou ld be ord e re d ? JA MA
e
c
1990 ;264 :1009 –1014 .
t
i
7. Rya n MJ, Ka va n a gh R, Wa ll PG, e t a l. Ba ct e ria l join t in fe ct ion s in En gla n d a n d Wa le s : An a lys is of ba ct e ria l
o
u
is o la t e s ove r a fou r-ye a r p e riod . Br J Rheum atol 1997 ;36 (3 ):370 –373 .
s
8. St e n ga l D, Ba u w e n s K, Se h ou li J, e t a l. Sys t e m a t ic review a n d m e t a -a n ayls is of a n t ibiot ic t h e ra py for bon e
A
r
a n d join t in fe ct io n s . Lancet Infect Dis 2001 ;1 (3 ):175 –188 .
t
h
9. Zim m e rli W, Tra m p u z A, Och s n e r PE. Pros t h e t ic-join t in fe ct ion s . N Engl J Med 2004 ;351 (16 ):1645 –1654 .
r
i
t
i
s
CHAPTER
24 Lyme Disea se
W illiam F. Iobst and Kristin M. Ingraham

A 39-ye ar-old w hit e m ale pre se nt s t o

Intro ductio n
Th e clin ica l p re se n ta t ion d e s cribe d
yo ur of ce w it h a 3-m ont h hist ory
a bove is t h a t of la t e -s t a ge Lym e
o f a p ain f u l, sw o lle n le f t k n e e . He

s
d is ea s e. W h ile Lym e d ise a s e is t h e

i
t
i
cu rre n t ly d e n ie s o t h e r sig n i can t

r
m os t com m on t ick-born e illn e s s

h
t
r
jo in t p ain , b u t d e scrib e s w h at in t h e Un ite d St a te s , a ccu ra t e d ia g-

A
n os is re q u ire s a n a p p re cia t ion of

s
h e t h o u g h t w as a u -t yp e illn e ss,

u
region a l va ria t ion in d is e a s e p rev-

o
i
ch aract e riz e d b y f at ig u e , h e ad ach e ,

t
c
a le n ce (Fig. 24.1 ). Lym e d is e a s e

e
f
m alaise, and arthralgias 3 to 4 m onths is e n d e m ic in t h e n ort h e a s t e rn ,

n
I
m idw e s t e rn , a n d w e s t e rn region s

5
p rio r t o t h e o n se t o f h is k n e e p ain .

N
o f t h e Un it e d St a t e s . In 2009,

O
He also n o t e s alt e re d se n sat io n in

I
a p p roxim a t ely 30,000 ca s e s of con -

T
C
h is h an d s an d f e e t . He h as n o h ist o ry o f k n e e in ju ry, an d b e lie ve s rm ed a n d s u sp e ct e d d is ea s e w ere

E
S
t h at u se o f o ve r-t h e -co u n t e r ib u p ro f e n h as h e lp e d t ak e t h e e d g e re p ort e d by t h e Ce n t e rs for Dis -
o ff t h e p ain . Th is m e d icat io n h as n o t re d u ce d t h e sw e llin g o r ea s e Con trol a n d Preve n t ion (CDC).
Th e s t a t e s w it h t h e h igh e s t t ot a l
se n sat io n o f w arm t h w h e n h e t o u ch e s t h e k n e e .
n u m b e r o f r e p o r t e d ca s e s a r e
The p at ie n t live s in rural so ut h e ast e rn Pe nn sylvania, an d is an New York, Pe n n s ylva n ia , a n d Ma s -
active hunter. He denies fam ily history of arthritis or arthritis-re lat e d s a ch u s e t t s . Th e h igh e s t in cid e n ce
d ise ase s. He is aw are t h at Lym e d ise ase is a co m m o n illn e ss in t h is of d is e a s e occu rre d in De la w a re
a n d w a s re p o r t e d a t 111.2 p e r
are a an d w o n d e rs if h e in f act h as t h is illn e ss.
100,000 in d ivid u a ls (Fig. 24.2 ).

Reported Cases of Lyme Disease – United States, 2009

Figure 24 .1 2009 representa tion of distribution of Lyme disea se ca ses.

Courtesy of Yehia Mishriki, MD. Centers for Disea se Control a nd Prevention,
a va ila ble a t http:/ / www.cdc.gov/ ncidod/ dvbid/ lyme/ ld_Incidence.htm.
Accessed Ja nua ry 21, 2011. 1 dot placed randomly within county of residence for each confirmed case
247
 248 Se ctio n 5 In fe ct iou s Art h rit is

Reported Lyme disease cases by state, 1995-2009

TABLE. Reported cases of Lyme disease by state or locality, 1995-2009

2009
State 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008†
Confirmed Probable Incidence*

Alabama 12 9 11 24 20 6 10 11 8 6 3 11 13 6 3 0 0.1

Alaska 0 0 2 1 0 2 2 3 3 3 4 3 10 6 7 0 1.0

Arizona 1 0 4 1 3 2 3 4 4 13 10 10 2 2 3 4 0.0

Arkansas 11 27 27 8 7 7 4 3 0 0 0 0 1 0 0 0 0.0

California 84 64 154 135 139 96 95 97 86 48 95 85 75 74 117 0 0.3

Colorado 0 0 0 0 3 0 0 1 0 0 0 0 0 2 0 1 0.0

Connecticut 1548 3104 2297 3434 3215 3773 3597 4631 1403 1348 1810 1788 3058 2738 2751 1405 78.2

Delaware 56 173 109 77 167 167 152 194 212 339 646 482 715 772 984 0 111.2

DC 3 3 10 8 6 11 17 25 14 16 10 62 116 71 53 8 8.8

Florida 17 55 56 71 59 54 43 79 43 46 47 34 30 72 77 33 0.4

Georgia 14 1 9 5 0 0 0 2 10 12 6 8 11 35 40 0 0.4

Hawaii 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.0

Idaho 0 2 4 7 3 4 5 4 3 6 2 7 9 5 4 12 0.3

Illinois 18 10 13 14 17 35 32 47 71 87 127 110 149 108 136 0 1.1

Indiana 19 32 33 39 21 23 26 21 25 32 33 26 55 42 61 22 0.9

Iowa 16 19 8 27 24 34 36 42 58 49 89 97 123 85 77 31 2.6

Kansas 23 36 4 13 16 17 2 7 4 3 3 4 8 16 18 0 0.6
S
E
Kentucky 16 26 20 27 19 13 23 25 17 15 5 7 6 5 1 0 0.0
C
T
Louisiana 9 9 13 15 9 8 8 5 7 2 3 1 2 3 0 0 0.0
I
O
Maine 45 63 34 78 41 71 108 219 175 225 247 338 529 780 791 179 60.0
N
Maryland 454 447 494 659 899 688 608 738 691 891 1235 1248 2576 1746 1466 558 25.7
5
Massachusetts 189 321 291 699 787 1158 1164 1807 1532 1532 2336 1432 2988 3960 4019 1237 61.0
I
n
f
Michigan 5 28 27 17 11 23 21 26 12 27 62 55 51 76 81 22 0.8
e
c
Minnesota 208 251 256 261 283 465 461 867 474 1023 917 914 1238 1046 1063 480 20.2
t
i
o
Mississippi 17 24 27 17 4 3 8 12 21 0 0 3 1 1 0 0 0.0
u
s
Missouri 53 52 28 12 72 47 37 41 70 25 15 5 10 6 3 0 0.1
A
Montana 0 0 0 0 0 0 0 0 0 0 0 1 4 6 3 0 0.3
r
t
h
Nebraska 6 5 2 4 11 5 4 6 2 2 2 11 7 8 4 1 0.2
r
i
t
i
Nevada 6 2 2 6 2 4 4 2 3 1 3 4 15 9 10 3 0.4
s
New
28 47 39 45 27 84 129 261 190 226 265 617 896 1211 996 419 75.2
Hampshire
New Jersey 1703 2190 2041 1911 1719 2459 2020 2349 2887 2698 3363 2432 3134 3214 4598 375 52.8

New Mexico 1 1 1 4 1 0 1 1 1 1 3 3 5 4 1 4 0.0

New York 4438 5301 3327 4640 4402 4329 4083 5535 5399 5100 5565 4460 4165 5741 4134 1517 21.2

North Carolina 84 66 34 63 74 47 41 137 156 122 49 31 53 16 21 75 0.2

North Dakota 0 2 0 0 1 2 0 1 0 0 3 7 12 8 10 5 1.5

Ohio 30 32 40 47 47 61 44 82 66 50 58 43 33 40 51 7 0.4

Oklahoma 63 42 45 13 8 1 0 0 0 3 0 0 1 1 2 0 0.1

Oregon 20 19 20 21 15 13 15 12 16 11 3 7 6 18 12 26 0.3

Pennsylvania 1562 2814 2188 2760 2781 2343 2806 3989 5730 3985 4287 3242 3994 3818 4950 772 39.3

Rhode Island 345 534 442 789 546 675 510 852 736 249 39 308 177 186 150 85 14.2

South Carolina 17 9 3 8 6 25 6 26 18 22 15 20 31 14 25 17 0.5

South Dakota 0 0 1 0 0 0 0 2 1 1 2 1 0 3 1 0 0.1

Tennessee 28 24 45 47 59 28 31 28 20 20 8 15 31 7 10 27 0.2

Texas 77 97 60 32 72 77 75 139 85 98 69 29 87 105 88 188 0.4

Utah 1 1 1 0 2 3 1 5 2 1 2 5 7 3 6 3 0.2

Vermont 9 26 8 11 26 40 18 37 43 50 54 105 138 330 323 85 51.9

Virginia 55 57 67 73 122 149 156 259 195 216 274 357 959 886 698 210 8.9

Washington 10 18 11 7 14 9 9 11 7 14 13 8 12 22 15 1 0.2

West Virginia 26 12 10 13 20 35 16 26 31 38 61 28 84 120 143 58 7.9

Wisconsin 369 396 480 657 490 631 597 1090 740 1144 1459 1466 1814 1493 1952 637 34.5

Wyoming 4 3 3 1 3 3 1 2 2 4 3 1 3 1 1 2 0.2

U.S. TOTAL 11,700 16,455 12,801 16,801 16,273 17,730 17,029 23,763 21,273 19,804 23,305 19,931 27,444 28,921 29,959 8,509 13.4

†
confirmed cases presented for all years except most recent
*
confirmed cases per 100,000 population

Figure 24 .2 2009 reported Lyme disea se ca ses by sta te, 1995 to 2009. Courtesy of Yehia Mishriki, MD. Centers for Disea se Control
a nd Prevention, a va ila ble a t http:/ / www.cdc.gov/ ncidod/ dvbid/ lyme/ ld_rptdLymeCa sesbySta te.htm. Accessed Ja nua ry 21, 2011.
 Ch a p te r 24 Lym e Dis e a s e 249

Effe ct ive p reve n t ion , d ia gn os is , a n d t re a t m e n t of t h is

d isea se a lso req u ire a n u n d ersta n d in g of th e p reva len ce,
t ra n s m is s ion ve ct or, a n d n a t u ra l h is t ory of Lym e d is -
e a s e. Th e d is e a s e is ca u s e d by t h e s p iroch e t e Borrelia
burgdorferi a n d is t ra n s m it t e d t h rou gh t h e bit e of t h e
bla ck-legged tick or d eer tick Ixodes scapularis (Fig. 24.3 ).
Th e s p iroch e t e is m os t fre q u e n t ly t ra n s m it t e d by t h e
bite of th e n ym p h a l stage of th e tick in th e sp rin g of th e
ye a r. Th e n ym p h a l-s t a ge t ick is ve ry s m a ll, n ot be in g
la rger th a n a p op py seed (Fig. 24.4 ). Less freq u en tly, a d u lt
ticks tra n sm it th e d isea se in th e fa ll of th e yea r. Ca ses
typ ica lly clu ster in ch ild ren you n ger th a n 15 yea rs a n d
in m id d le-a ged a d u lts, a n d a re a ssocia ted w ith h istories
of ou td oor a ctivities th a t exp ose in d ivid u a ls to th e tick.
Figure 24 .3 Bla ck-legged tick or deer tick. Courtesy of Ja mes Ga tha ny. Lym e d isea se is a rep orta ble illn ess a n d both con rm ed
Centers for Disea se Control a nd Prevention, a va ila ble a t http:/ / www.cdc. a n d p roba ble ca ses h ave been tra cked by th e CDC sin ce
gov/ ncidod/ dvbid/ lyme/ ld_tra nsmission.htm. Accessed Ja nua ry 21, 2011. 1995. From 1995 to 2009, m ore th a n 400,000 ca ses of con -
rm ed a n d p roba ble Lym e d isea se h ave been rep orted
w ith th e n u m ber of ca ses in crea sin g on a yea rly ba sis (Fig. 24.5 ). W h ile in fection
w ith B. burgdorferi is a w orldw id e occu rren ce, th is ch a p ter d iscu sses on ly th e m a n -

s
i
t
ifesta tion s, d iagn osis, a n d trea tm en t of th is illn ess in North Am erica .

i
r
h
t
r
A
s
u
o
i
t
c
e
f
1 inch

n
I
5
Blacklegged Tick (Ixodes scapularis)

N
O
I
T
C
E
S
adult adult
female male nymph larva

Lone Star Tick (Amblyomma americanum)

Dog Tick (Dermacentor variabilis)

Figure 24 .4 Dime ticks tra nsmission a nd size. Ima ge a ccessed Ja nua ry 11, 2011, a t Centers for Disea se
Control a nd Prevention Web site http:/ / www.cdc.gov/ ncidod/ dvbid/ lyme/ ld_tra nsmission.htm.
 250 Se ctio n 5 In fe ct iou s Art h rit is

Reported Cases of Lyme Disease by Year, United States, 1995–2009

45,000

40,000
Confirmed cases
35,000 Probable cases*

30,000

25,000
s
se
a
20,000
C
15,000

10,000

5,000

0
S
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
E
C
T
*National Surveillance case definition revised in 2008 to include probable cases;
I
O
details at http://www.cdc.gov/ncphi/disss/nndss/casedef/lyme_disease_2008.htm
N
5
Figure 24 .5 Lyme disea se incidence by yea r. Courtesy of Ja mes Ga tha ny. Centers for Disea se Control a nd Prevention, a va ila ble
I
a t http:/ / www.cdc.gov/ ncidod/ dvbid/ lyme/ ld_UpClimbLymeDis.htm. Accessed Ja nua ry 21, 2011.
n
f
e
c
t
i
o
Clinica l Pre se nta tio n
u
s
A
Th e clin ica l p re s e n t a t ion of Lym e d is e a s e is ge n e ra lly d ivid e d in t o t h re e s t a ge s :
r
t
h
e a r ly lo ca liz e d , e a r ly d is s e m in a t e d , a n d la t e -s t a ge d is e a s e . Tw o a d d it io n a l
r
i
t
i
s
s t a ge s h ave a ls o be e n d e s cribe d , bu t a re n ot u n ive rs a lly a ccep t e d a s p a rt of t h e
n a t u ra l h is t ory of t h e d is e a s e. An u n d e rs t a n d in g of t h e s e s t a ge s is crit -
ica l for e ffe ct ive d ia gn os is a n d t re a t m e n t of Lym e d is e a s e.

EARLY LOCALIZED DISEASE

Ea rly lo ca lize d Lym e d is e a s e occu rs w it h in d a ys t o u p t o 1 m on t h o f
in it ia l t ick bit e a n d is ch a ra ct e rize d by a s kin ra s h a n d con s t it u t ion a l
s ym p t om s in clu d in g m a la is e, fa t igu e, h e a d a ch e, m ild s t iff n e ck, m ya l-
gia s , a n d a rt h ra lgia s . Exa m in a t ion ca n reve a l region a l lym p h a d e n op a -
t h y. Eryt h e m a m igra n s (EM) occu rs in on ly 80% of p a t ie n t s d ia gn os e d ,
a n d on ly 25% of p a t ie n t s w it h t h is ra s h eve r re ca ll a t ick bit e. Fu rt h e r-
m ore, n ot a ll p a t ie n t s p re s e n t w it h t h e cla s s ica lly d e s cribe d s kin ra s h .
Th e cla s s ica l ra s h h a s a n e xp a n d in g a n d s ligh t ly ra is e d e ryt h e m a t ou s
bord e r w it h a n a re a of ce n t ra l cle a rin g a n d is fre q u e n t ly re fe rre d t o a s
a “t a rge t le s ion ” (Fig. 24.6 ).

EARLY DISSEMINATED DISEASE

Figure 24.6 Target lesion. Courtesy of Ja mes
Gathany. Centers for Disease Control and Prevention,
available at http:/ / www. cdc.gov/ ncidod/ dvbid/
lyme/ ld_LymeDiseaseRashPhotos.htm. Accessed
January 21, 2011.
Ea r ly d is s e m in a t e d d is e a s e t yp ica lly o ccu r s w it h in a few w e e k s t o
m on t h s a ft e r t ick bit e, a n d ca n p re s e n t in t h e a bs e n ce of a cle a r h is t ory
of e a rly loca lize d d is e a s e. In a d d it ion t o con s t it u t ion a l s ym p t om s s im i-
la r t o t h os e d e s cribe d in e a rly Lym e d is e a s e, p a t ie n t s ca n p re s e n t w it h
m u s cu lo s k e le t a l, n e u ro logic, a n d ca rd ia c s ym p t o m s . Ap p rox im a t e ly
60% of p a t ie n t s rep ort m igra t ory a rt h ra lgia s ; 15% e xp e rie n ce n e u rologic
s ym p t om s , w h ich ca n ra n ge from m e n in git is (lym p h ocyt ic), e n cep h a li-
t is , cra n ia l n e u rop a t h y (fa cia l n e rve ), p e rip h e ra l n e u rop a t h y, m ye lit is ,

CLINICAL POINTS
• Lym e d ise a se is t h e m o st
co m m o n t ick-b o rn e illn e ss
in t h e Un it e d St a t e s.
• Ca se s a re m o st co m m o n ly
se e n in ch ild re n yo u n g e r
t h a n 15 ye a rs a n d in
m id d le -a g e d a d u lt s.
• Effe ct ive t re a t m e n t re q u ire s
a n u n d e rst a n d in g o f t h e
th re e st a g e s o f Lym e d is-
e a se a n d a n u n d e rst a n d in g
th a t n o t a ll p a t ie n t s re p o rt
p ro g re ssin g t h ro u g h e a ch
o f t h e se st a g e s.
• Pe rsist e n t sym p t o m s
fo llo w in g a p p ro p ria t e
t re a t m e n t o f Lym e d ise a se
sh o u ld p ro m p t re in ve st ig a -
t io n fo r o t h e r p o t e n t ia l
co m o rb id d ise a se st a t e s.
Ch a p te r 24 Lym e Dis e a s e 251
a n d ce re be lla r a t a xia . Up t o 8% of p a t ie n t s d eve lop ca rd ia c a bn orm a lit ie s . Ca r-
d ia c a bn or m a lit ie s fre q u e n t ly p re s e n t w it h s ym p t om s of ligh t -h e a d e d n e s s ,
p a lp it a t ion s , a n d s yn cop e. He a rt block is t h e m os t fre q u e n t a bn orm a lit y a n d
ca n occu r in u p t o 8% of p a t ie n t s . He a rt block ca n ra n ge from rs t d egre e t o
com p le t e h e a rt block. Myoca rd it is h a s a ls o be e n re p ort e d bu t is ra re.
LATE- STAGE DISEASE
La t e -s t a ge d is e a s e occu rs m on t h s t o ye a rs follow in g t ick bit e. Mu s cu los ke le t a l
s ym p t om s a re t h e m os t com m on n d in g in la t e -s t a ge d is e a s e, w it h s ligh t ly
m o re t h a n h a lf o f p a t ie n t s d eve lo p in g in t e rm it t e n t m o n o - o r o ligo a rt icu la r
a rt h rit is . Ap p roxim a t e ly 10% of p a t ie n t s d eve lop p e rs is t e n t m on oa rt h rit is of t h e
kn e e. Eve n w it h a p p rop ria t e t re a t m e n t , a s m a ll n u m be r of la t e -s t a ge p a t ie n t s
p e rs is t w it h obje ct ive n d in g s u ch a s m on o- or oligoa rt h rit is . Pe rs is t e n ce of
t h e s e n d in gs is n ot a n in d ica t ion t o e xt e n d a n t ibiot ic t h e ra p y. Cu rre n t ly t h e re
is n o con clu s ive evid e n ce t o s u gge s t t h a t s u ch n d in gs a re d u e t o on goin g
a ct ive in fe ct ion u n le s s t h e re is re a s on t o s u s p e ct t re a t m e n t n on com p lia n ce.
On e p ot e n t ia l e xp la n a t ion for on goin g join t m a n ife s t a t ion s follow in g a p p rop ri-
a t e a n t ibiot ic t h e ra py is t h e d eve lop m e n t of a s e con d a ry a u t oim m u n e re s p on s e
in t h e join t . Pos t t re a t m e n t join t s ym p t om s t yp ica lly s u bs id e w it h in m on t h s t o
s
a few ye a rs a n d d o n ot n e ce s s a rily re q u ire a d d it ion a l t re a t m e n t . On goin g s ym p -
i
t
i
r
t om a t ic join t p a in ca n be t re a t e d w it h a n t i-in a m m a t ory m e d ica t ion s .
h
t
r
A
La t e -s t a ge p a t ie n t s ca n a ls o p re s e n t w it h ch ron ic low -gra d e e n cep h a lop a -
s
t h y, e n ce p h a lom ye lit is , a n d /or p e rip h e ra l n e u rop a t h y. Pe rip h e ra l n e u rop a t h y
u
o
t yp ica lly p re s e n t s w it h p a re s t h e s ia s in t h e s e t t in g of u n re m a rka ble s e n s ory
i
t
c
a n d m ot or e xa m in a t ion s . Th e s e s ym p t om s a re s im ila r t o t h os e of e a rly d is -
e
f
n
s e m in a t e d d is e a s e, a n d d iffe re n t ia t in g be t w e e n e a rly d is s e m in a t e d a n d la t e -
I
5
s t a ge d is e a s e ca n be d if cu lt u n le s s t h e re is a cle a r h is t ory of t ick bit e or e a rly
N
s t a ge s ym p t o m s . En ce p h a lo p a t h y a n d e n ce p h a lo m ye lit is ca n p re s e n t ye a r s
O
I
T
a ft e r in fe ct ion a n d ca n be s u bt le a n d d if cu lt t o d ia gn os e.
C
E
In a d d it ion t o t h e t h re e cla s s ica l p h a s e s of Lym e d is e a s e, clin icia n s s h ou ld
S
be aw a re of t w o a d d it ion a l, bu t con t rove rs ia l, s t a ge s ca lle d “p os t –Lym e d is e a s e
s yn d rom e ” a n d “ch ron ic Lym e d is e a s e ” (1 ).
Ch ron ic Lym e d is e a s e d e s cribe s a con d it ion s om e p h ys icia n s a n d p a t ie n t s
be lieve t o be p e rs is t e n t B. bu rgd orfe ri in fe ct ion . Fre q u e n t ly, t h e s e p a t ie n t s h ave
n o re p rod u cible or con vin cin g s cie n t i c evid e n ce lin kin g s ym p t om s t o B. bu rg-
d orfe ri in fe ct ion .
Ch ron ic Lym e d is e a s e ca n be a p p roa ch e d a s h avin g fou r ca t egorie s . In ca t -
egory on e, p a t ie n t s p re s e n t w it h n on s p e ci c s ym p t om s w it h n o obje ct ive clin -
ica l or la bora t ory evid e n ce of in fe ct ion .
In ca t egory t w o, p a t ie n t s p re s e n t w it h a h is t ory of p ot e n t ia l Lym e d is e a s e,
by h a ve evid e n ce of illn e s s ot h e r t h a n Lym e d is e a s e.
Ca t egory t h re e p a t ie n t s h a ve a n t ibod ie s a ga in s t B. bu rgd orfe ri, bu t h ave n o
obje ct ive clin ica l n d in gs .
Fin a lly, ca t e gory fou r p a t ie n t s h a ve s ym p t om s of w h a t h a s b e e n t e rm e d
“p os t -Lym e d is e a s e s yn d rom e ”.
Po s t –Lym e d is e a s e s yn d ro m e is ch a ra ct e r iz e d by s u b je ct ive s ym p t o m s ,
in clu d in g fa t igu e, m a la is e, h e a d a ch e, a n d cogn it ive d ys fu n ct ion . Th e In fe ct iou s
Dis e a s e Socie t y of Am e rica (IDSA) h a s p rop os e d t h e follow in g crit e ria for t h is
s yn d rom e (2 ):
• Sym p t om s m u s t occu r w it h in 6 m on t h s of t h e d ia gn os is of Lym e d is e a s e a n d
m u s t p e rs is t for 6 m on t h s a ft e r re com m e n d e d t re a t m e n t .
• Prior d ia gn os is of Lym e d is e a s e w it h re s olu t ion of obje ct ive s ym p t om s fol-
low in g a p p rop ria t e a n t ibiot ic t h e ra py.
• Exclu s ion of ot h e r com orbid d is e a s e s t a t e s in clu d in g brom ya lgia , a bn orm a l
t h yroid fu n ct ion , lon g-s t a n d in g h is t ory of u n e xp la in e d n e u rologic or m u s cu -
los ke le t a l s ym p t om s cle a rly p re ce d in g t h e d ia gn os is of Lym e d is e a s e, s le ep
252 Se ctio n 5 In fe ct iou s Art h rit is
PATIENT ASSESSMENT
• Erythema migrans skin rash
is a classical nding in early
a n d e a rly d isse m in a t e d
Lym e d ise a se , b u t is
id e n t i e d o n ly in 80%
o f p a t ie n t s re p o rt in g a
h ist o ry o f t ick b it e .
• Bila t e ra l fa cia l n e rve
p a lsy is h ig h ly su g g e st ive
o f Lym e d ise a se . Ot h e r
ca u se s o f b ila t e ra l fa cia l
n e rve p a lsy ca n in clu d e
tuberculosis and sarcoidosis.
• Mo n o - o r o lig o a rt h rit is
ca n b e se e n in a s m a n y
a s 60% o f p a t ie n t s in
la t e -st a g e Lym e d ise a se
a n d m o st co m m o n ly
o ccu rs in t h e kn e e .
a p n e a , e s t a blis h e d a u t oim m u n e d is e a s e, live r d is e a s e, p s ych ia t ric illn e s s , or
d ocu m e n t e d h is t ory of d ru g or a lcoh ol a bu s e.
Th e ca re of p a t ie n t s p re s e n t in g w it h p os s ible ch ron ic Lym e d is e a s e or p os t -
Lym e d is e a s e s yn d rom e is ch a lle n gin g. Th e p rim a ry ca re clin icia n s h ou ld con -
s id e r re fe r r in g s u ch p a t ie n t s t o a re cogn iz e d s p e cia lis t fo r s e co n d o p in io n
be fore in it ia t in g t re a t m e n t .
UNIQUE SITUATIONS
Re infe ctio n
Re in fe ct ion w it h B. burgdorferi h a s be e n rep ort e d in p a t ie n t s follow in g e ffe ct ive
t re a t m e n t . Pa t ie n t s w h o re ce ive a n t ibiot ics for e a rly loca lize d or e a rly d is s e m i-
n a t e d Lym e d is e a s e a re a t gre a t e r ris k fo r re in fe ct io n t h a n p a t ie n t s w h o a re
t re a t e d for la t e -s t a ge Lym e d is e a s e. In la t e -s t a ge d is e a s e, h os t a n t ibod y re s p on s e
t o B. burgdorferi is robu s t a n d u s u a lly p rovid e s p rot e ct ion a ga in s t re in fe ct ion .
An t ibod y p rod u ct ion in e a rly a n d e a rly d is s e m in a t e d s t a ge s of d is e a s e is le s s
robu s t a n d u n like ly t o p rovid e t h e s a m e leve l of im m u n it y t o re e xp os u re (3 ).
Pre g nancy
Cu rre n t evid e n ce d oe s n ot s u p p ort t h e occu rre n ce of con ge n it a l Lym e d is e a s e.
Wit h a d e q u a t e t re a t m e n t , fu t u re p a re n t s s h ou ld be re a s s u re d t h a t t h e re is n ot
s ign i ca n t ris k of t ra n s m is s ion t o t h e fe t u s a n d n o in cre a s e d ris k of a d ve rs e
ou t com e s or fe t a l d e m is e. Th e re is a ls o n o evid e n ce t h a t Lym e d is e a s e ca n be
t ra n s m it t e d t h rou gh bre a s t -fe e d in g. In p regn a n cy, u s e of t e t ra cyclin e a n d d ox-
ycyclin e a re con t ra in d ica t e d (4 ).
Co infe ctio n
In a d d it ion t o B. burgdorferi, t h e bla ck-legge d t ick or d e e r t ick ca n a ls o t ra n s m it
t h e p a ra s it e s Theileria m icroti a n d A naplasm a phagocytophilum . Th e s e p a ra s it e s
ca u s e b a b e s io s is a n d h u m a n gra n u lo cyt ic a n a p la s m o s is (HGA), re s p e ct ive ly,
a n d s h ou ld be s u s p e ct e d in t h e s e t t in g of in com p le t e or a t yp ica l re s p on s e t o
a p p rop ria t e a n t ibiot ic t re a t m e n t fo r Lym e d is e a s e . Up t o 40% of e a rly Lym e
d is e a s e ca s e s ca n be coin fe ct e d w it h T. m icroti (ba be s io s is ) a n d 12% w it h A .
phagocytophilum (HGA).
Th e n d in g of a h e m o lyt ic a n e m ia s u gge s t s t h e p os s ibilit y of ba be s io s is
coin fe ct ion .
Th e n d in gs o f t h r o m b o cy t o p e n ia , le u co p e n ia , a n d e le va t e d s e r u m
t ra n s a m in a s e leve ls s h o u ld p ro m p t a n eva lu a t io n fo r HGA. Co in fe ct ion h a s
a ls o be e n rep ort e d w it h Bartonella , Ehrlichia , a n d Rickettsia (5 ).
Physica l Exa mina tio n
Ph ys ica l exa m in a t ion of p ot e n t ia l p a t ie n t s w it h Lym e d is e a s e is re q u ire d t o con -
rm t h e d ia gn os is , id e n t ify t h e s t a ge of t h e d is e a s e, a n d p re s cribe a p p rop ria t e
t re a t m e n t . Give n t h e ove rla p of p h ys ica l n d in gs a cros s m u lt ip le d is e a s e s t a ge s ,
t h e follow in g d is cu s s ion of p h ys ica l n d in gs is p re s e n t e d by orga n s ys t e m .
SKIN
Occa sion a lly, p a tien ts p resen t for exa m in a tion w ith a tick rm ly a tta ch ed to th e
skin . If en gorged , th e tick is feed in g a n d th e likelih ood of d isea se tra n sm ission
in crea ses. Un en gorged ( a t) a n d u n a tta ch ed ticks a re u n likely to tra n sm it d isea se.
Th e likelih ood of d isea se tra n sm ission ca n be estim a ted on th e ba sis of th e d u ra -
tion of feed in g. Given th e m ech a n ism of sp iroch ete tra n sm ission , feed in g p eriod s
of less th a n 48 to 72 h ou rs red u ce th e likelih ood of d isea se tra n sm ission .
In e a rly loca lize d a n d e a rly d is s e m in a t e d d is e a s e, t h e n d in g of a n EM ra s h
ca n p rovid e a n im p ort a n t clu e t o t h e d ia gn os is of t h is d is e a s e. Eryt h e m a m igra n s
d eve lop s d ays t o w e e ks a ft e r t h e in it ia l t ick bit e, a n d is t yp ica lly loca t e d in t h e
a xilla , in gu in a l region , p op lit e a l fos s a , or be lt lin e. At t h e t im e of t h e t ick bit e,
 Ch a p te r 24 Lym e Dis e a s e 253

s
i
t
i
Figure 24.7 Solid erythema migrans skin rash. Courtesy of Alison Young, MD.

r
h
Centers for Disea se Control a nd Prevention, a va ila ble a t http:/ / derma tla s. Figure 24 .8 Multiple erythema migra ns skin lesions

t
r
A
med.jhmi.edu/ derm/ indexdispla y.cfm?Ima geID=-323138275. Accessed indica ting ea rly dissemina ted disea se. Courtesy of

s
Ja nua ry 21, 2011. Yehia Mishriki.

u
o
i
t
c
e
f
t h e s p iroch e t e is in ocu la t e d in t o t h e s kin . Aft e r a p e riod of t im e ra n gin g from 3

n
I
t o 30 d ays , t h e s p iroch e t e begin s t o m igra t e ou t w a rd s from t h e in ocu la t ion s it e

5
N
ca u s in g t h e ra s h . Th e ra s h is m in im a lly p a in fu l, bu t is fre q u e n t ly h ot t o t ou ch .

O
I
It e xp a n d s s low ly ove r d ays t o w e e ks a n d is u lt im a t e ly ch a ra ct e rize d by a region

T
C
of ce n t ra l cle a rin g. A fu lly m a t u re ra s h h a s a ch a ra ct e ris t ic a p p e a ra n ce d e s cribe d

E
S
a s a “t a rge t le s ion ” (Fig. 24.6 ). Ea rly le s ion s ca n be a t yp ica l a n d a p p e a r u n iform ly
re d (Fig. 24.7 ). Th e ave ra ge t im e from d is cove ry of a ra s h t o m e d ica l eva lu a t ion
h a s be e n d e m on s t ra t e d t o be a bou t 3 d ays (6 ). Pre s e n t in g ra s h e s in t h e s e p a t ie n t s
w e re u n iform ly re d in a lm os t 60% of ca s e s , w it h on ly 9% of ra s h e s d e m on s t ra t -
in g ce n t ra l cle a rin g. Clin icia n s s h ou ld t h e re fore be w illin g t o d ia gn os e EM eve n
w h e n t h e cla s s ic t a rge t le s ion is a bs e n t . Clin icia n s s h ou ld a ls o re m e m be r t h a t
on ly 80% of p a t ie n t s d eve lop ECM follow in g a t ick bit e.
W h e n m u lt ip le ECM (EM?) les ion s a re id e n t i e d (Fig. 24.8 ), t h e d is e a s e h a s
p rogres se d from e a rly loca lized t o ea rly d is s em in a t ed d is ea s e. Th is n d in g d oe s
n ot rep re s en t m u lt ip le t ick-bite exp os u res .
Pa t ie n t s p re s e n t in g for eva lu a t ion im m e d ia t e ly follow in g t ick re m ova l ca n
a ls o d e m on s t ra t e a n on s p e ci c loca l irrit a t ion a t t h e bit e s it e. Th e s e p a t ie n t s
s h ou ld be re a s s u re d t h a t t h is loca l irrit a t ion is n ot EM a n d d oe s n ot re q u ire s p e -
ci c t re a t m e n t for Lym e d is e a s e.

CARDIAC
Ca rd ia c s ym p t om s a re t yp ica lly s e e n in e a rly d is s e m in a t e d (s t a ge 2) d is e a s e.
On p h ys ica l e x a m in a t io n , ca rd ia c a rrh yt h m ia s ca n in d ica t e t h e p re s e n ce o f
h e a rt blo ck , w h ich ca n ra n ge fro m rs t -d egre e a t riove n t ricu la r (AV) blo ck t o
com p le t e h e a rt block. In a d d it ion , ca rd it is ca n occu r a n d p re s e n t w it h n d in gs
of ve n t ricu la r e ct op y or con ge s t ive h e a rt fa ilu re.

NEUROLOGIC
Neu rologic a bn orm a lities d evelop in both ea rly d issem in a ted (s ta ge 2) a n d la t e -
s t a ge (s t a ge 3) Lym e d is e a s e. Abn orm a l n e u rologic n d in gs in clu d e p e rip h e ra l
n e u rop a t h y, cra n ia l n e u rop a t h y, m e n in git is , a n d ra d icu lon e u rit is .
 254 Se ctio n 5 In fe ct iou s Art h rit is

Pe r ip h e ra l n e u ro p a t h ie s w it h o u t o b je ct ive s e n s o ry o r m o t o r a b n o r m a li-
t ie s occu r in bo t h e a r ly d is s e m in a t e d a n d la t e -s t a ge d is e a s e . Cra n ia l n e u ro p a -
t h ie s d eve lo p in u p t o 10% t o 20% o f e a r ly d is s e m in a t e d p re s e n t a t io n s a n d
fre q u e n t ly in clu d e e it h e r u n ila t e ra l o r b ila t e ra l fa cia l n e r ve p a ls ie s . W h e n
fa cia l n e rve p a ls y p re s e n t s w it h h e a d a ch e a n d / o r s ign s o f m é n a ge irr it a b ilit y
(n u ch a l r igid it y), eva lu a t io n fo r p o s s ible m e n in git is is w a r ra n t e d . Lym p h o cyt ic
m e n in git is p re s e n t in g w it h t yp ica l s ign s o f m e n in ge a l ir r it a t io n ca n a ls o
o ccu r w it h o u t cra n ia l n e r ve p a ls y d u rin g e a r ly d is s e m in a t e d d is e a s e . Ra d icu -
lo n e u r it is t yp ica lly p re s e n t s w it h a cu t e o n s e t o f s eve re p a in o r m o t o r w e a k -
n e s s . Eve n w it h o u t t r e a t m e n t , t h e s e s ym p t o m s t yp ica lly r e s o lve w it h in
m on th s of on set.
Ch ro n ic e n ce p h a lo p a t h y a n d e n ce p h a lo m ye lit is ca n a ls o p re s e n t w it h
m e m ory ch a n ge a n d fa t igu e, a n d m ay p re s e n t ye a rs a ft e r t h e on s e t of d is e a s e.
Th e s e n d in gs d o n o t t yp ica lly re m it s p on t a n e ou s ly a n d re q u ire a n t ib io t ic
t re a t m e n t for t re a t m e n t .

MUSCULOSKELETAL
In t e rm it t e n t , m igra t ory a rt h ra lgia s yn d rom e s a re fre q u e n t ly s e e n in t h e rs t
t w o s t a ge s of Lym e d is e a s e. On e xa m in a t ion , p a in fu l join t s ca n be id e n t i e d in
S
t h e a bs e n ce of e ryt h e m a , sw e llin g, or w a rm t h .
E
C
Weeks to yea rs a fter in it ia l in fect ion (sta ge 3), p a tien ts ca n p res en t w it h oligo-
T
I
or m on a rticu la r a rth ritis. Up to 60% of p a tien ts w it h la te-sta ge d isea se rep ort a n
O
N
a sym m et ric rela tively p a in less a rth ritis. W h ile m u ltip le la rge join t ca n be in volved ,
5
th e m ost typ ica l s ite of in volvem en t is th e kn ee. W h ile rela t ively p a in less , kn ee
I
n
a rth ritis ca n be a ssocia ted w ith join t effu sion s a n d Ba ker’s cysts (6 ).
f
e
c
t
i
o
u
Studie s
s
A
r
t
Th e d ia gn osis of Lym e d isea se req u ires kn ow led ge of th e in cid en ce of th e d isea se,
h
r
i
th e p a tien t’s clin ica l p resen ta tion , a n d w h en a p p rop ria te, serologic con rm a tion
t
i
s
of im m u n e resp on se to th e sp iroch ete. Serologic testin g is n ot recom m en d ed a s
a s cre en in g t e s t for d is e a s e in t h e s e t t in g of p os s ible t ick-bit e exp os u re in t h e
absen ce of su p p ortin g clin ica l p resen ta tion a n d is u sefu l for con rm a tion of d ia g-
n osis in on ly certa in in sta n ces. Gu id elin es for th e a ssessm en t a n d trea tm en t of
su sp ected Lym e d isea se h ave been issu ed by th e IDSA (7 ).

NOT TO BE MISSED
• Coinfection with other tick-
borne illne ss. Inco mp le te
or a t yp ica l re spo nse to
sta nda rd a ntibiotic the ra py
or a bn o rma lit ie s o n
perip h e ra l b lo o d a n a lysis
should ra ise the possibility
of e it h e r b a b e sio sis o r
HGA co in fe ct io n .
• Pa t ie n t s p re se n t in g w it h
m u lt ip le ECM le sio n s d o
n o t h a ve m u lt ip le in it ia l
e xp o su re s. Mu lt ip le ECM
le sio n s in d ica t e e a rly
d isse m in a t e d d ise a se .
• The d ia g no sis o f Lyme
disea se d oe s no t re quire a
positive Lym e se ro lo g y in
e a rly d ise a se p re se n ta tio ns.
NONSPECIFIC EVALUATION
Eva lu a t io n o f p a t ie n t s p re s e n t in g w it h s ign s o f m e n in git is o r a r t h r it is fre -
q u e n t ly re q u ire fu r t h e r eva lu a t io n . W h ile jo in t a n d s p in a l u id a n a lys is m a y
n o t co n r m t h e d ia gn o s is o f Lym e d is e a s e , e va lu a t io n o f t h e s e u id s ca n
s e r ve t h e im p o r t a n t p u r p o s e o f e x clu d in g o t h e r ca u s e s o f jo in t or m e n in ge a l
ir r it a t io n .
Th e m e n in git is of Lym e d is e a s e is t yp ica lly a lym p h ocyt ic m e n in git is ch a r-
a ct e rize d by s p in a l u id ce ll cou n t s ra n gin g from occa s ion a l t o a few h u n d re d
lym p h ocyt e s . Mild s p in a l u id p rot e in e leva t ion s ca n a ls o occu r, bu t glu cos e
leve ls a re u s u a lly n orm a l. Sp in a l u id a n a lys is for Lym e a n t ibod ie s ca n be p e r-
form e d , bu t in t e rp re t a t ion of t e s t re s u lt s ca n be ch a lle n gin g give n t h e la ck of
a s s ay s t a n d a rd iza t ion . Be ca u s e n e u rologic s ym p t om s d eve lop in t h e e a rly d is -
s e m in a t e d s t a ge of d is e a s e, t h e a bs e n ce of s e ru m a n t ibod ie s m a ke s t h e d ia g-
n os is of Lym e d is e a s e h igh ly u n like ly a n d s h ou ld ca ll in t o q u e s t ion a t t ribu t in g
n e u rologic n d in gs t o B. burgdorferi in fe ct ion .
Join t u id ca n a ls o be a n a lyze d w h e n join t e ffu s ion s a re id e n t i e d on p h ys -
ica l e xa m in a t ion . Kn e e e ffu s ion s ca n ra n ge from m in im a lly t o h igh ly in a m -
m a t ory e ffu s ion s w it h s yn ovia l u id w h it e blood ce ll cou n t s of p re d om in a n t ly
n e u t rop h ils ra n gin g from 500 t o 100,000 ce lls . Syn ovia l u id ca n a ls o be a n a -
lyze d of B. burgdorferi DNA u s in g p olym e ra s e ch a in re a ct ion (PCR) t e s t in g. Th is

WHEN TO REFER
• Pa t ie n t s w h o re q u e st
o n g o in g IV a n t ib io t ic
t h e ra p y fo r n o n sp e ci c
sym p t o m s in clu d in g
ch ro n ic fa t ig u e o r
b ro m ya lg ia .
• Pa t ie n t s w h o b e lie ve t h e y
h a ve p o st –Lym e d ise a se
syn d ro m e o r ch ro n ic Lym e
d ise a se .
• Pe rsiste n t m on o - or o li-
go a rt icu la r a rt hritis a fte r
a p p ro p ria te a n tib io tic th e r-
a p y th a t h a s n o t re sp o n d e d
to re com me nde d a nti-
in a m ma tory tre a tme nt.
Ch a p te r 24 Lym e Dis e a s e 255
t e s t is p os it ive in m os t u n t re a t e d p a t ie n t s a n d be com e s n ega t ive w it h t re a t -
m e n t . How eve r, w h ile s yn ovia l u id PCR t e s t in g m ay be com m e rcia lly ava ila ble,
it h a s n ot be e n s t a n d a rd ize d or va lid a t e d for rou t in e clin ica l u s e (8 ).
Skin biop s y of EM le s ion s ca n d e m on s t ra t e t h e p re s e n ce of B. burgdorferi,
bu t is ge n e ra lly n ot re q u ire d for d ia gn os is in p a t ie n t s p re s e n t in g w it h le s ion s
con s is t e n t w it h e a rly or m ore cla s s ica l EM p re s e n t a t ion s .
SEROLOGIC EVALUATION
Se ro logic s t u d ie s s h ou ld b e ord e re d w h e n t h e h is t ory a n d p h ys ica l e xa m in a -
t io n s t ro n gly s u gge s t Lym e d is e a s e . Mo s t la b o ra t o rie s be gin w it h t h e s e n s it ive
e n zym e -lin ke d im m u n os orbe n t a s s ay (ELISA). If t h is is p os it ive, a re e x We s t e rn
blo t s h o u ld b e p e r fo r m e d a s o t h e r in fe ct io n s a n d co n d it io n s m a y ca u s e a
p o s it ive ELISA. Th e cr it e r ia for a p o s it ive We s t e r n blo t t e s t in clu d e t w o o f t h e
follow in g IgM ba n d s e a r ly in t h e d is e a s e : 24, 39, 41, o r ve o f t h e fo llow in g IgG
b a n d s la t e r in t h e d is e a s e : 18, 23, 28, 30, 39, 41, 45, 58, 66, 93 (9 ). Pa t ie n t s w it h
e a r ly lo ca liz e d d is e a s e p re s e n t in g w it h EM a re o ft e n s e ro n e ga t ive a n d s h o u ld
b e t r e a t e d im m e d ia t e ly o n t h e b a s is o f c lin ic a l gr o u n d s . Th is t w o -s t e p
a p p ro a ch h a s be e n e n d o r s e d by t h e CDC a n d s h o u ld gu id e t h e s e ro logic eva l-
u a t io n of p o t e n t ia l ca s e s o f Lym e d is e a s e . W h ile a d d it io n a l t e s t in g is o ffe re d
s
for t h e d ia gn o s is o f Lym e d is e a s e , t h e a ccu ra cy o f t h e s e t e s t s h a s n o t b e e n
i
t
i
r
e s t a blis h e d . Su ch t e s t in g in clu d e s u r in e a n t ige n t e s t in g, im m u n o u o re s ce n t
h
t
r
s t a in in g fo r ce ll-w a ll–d e cie n t fo r m s o f B. bu rgdorferi, a n d lym p h o cyt e t ra n s -
A
fo rm a t ion t e s t in g.
s
u
An t ibod ie s t o Lym e d is e a s e m a y p e rs is t eve n a ft e r a p p rop ria t e t re a t m e n t ;
o
i
t
c
t h e re fore, re p e a t e d cou rs e s of a n t ibiot ics a re n ot n e ce s s a ry if t h e clin ica l s ym p -
e
f
t o m s h a ve re s olve d . Pa t ie n t s w h o h a ve re ce ive d t h e va ccin e (LYMErix) m a y
n
I
e xh ibit p os it ive ELISA a n d We s t e rn blot ba n d s . Th e Lym e va ccin e is n o lon ge r
5
N
ava ila ble.
O
I
T
C
E
Tre a tme nt
S
Th e t re a t m e n t of Lym e d is e a s e d ep e n d s on a ge of t h e p a t ie n t a s w e ll a s clin ica l
s t a ge of t h e d is e a s e a t t h e t im e of p re s e n t a t ion . Doxycyclin e is n ot re co m -
m e n d e d in ch ild re n you n ge r t h a n 8 ye a rs or p a t ie n t s w h o a re p regn a n t or la c-
t a t in g. Re la p s e a ft e r t re a t m e n t is p os s ible ; h ow eve r, on ly p a t ie n t s w it h obje ct ive
clin ica l s ign s of d is e a s e s h ou ld be con s id e re d for a s e con d cou rs e of a n t ibiot ics .
Th e follow in g re e ct t h e clin ica l p ra ct ice gu id e lin e s from t h e IDSA (7 ).
Prop h yla xis w it h d oxycyclin e 200 m g on e -t im e d os e is in d ica t e d if t h e t ick
is id e n t i e d a s a d e e r t ick , t h e le n gt h o f e x p o s u re (fe e d in g) w a s a t le a s t
36 h ou rs , p rop h yla xis is begu n w it h in 72 h ou rs of t ick re m ova l, loca l ra t e of
in fe ct ion of t icks w it h B. burgdorferi is a t le a s t 20%, a n d t h e p a t ie n t is a ble t o
t a ke d oxycyclin e. W h ile p rop h yla xis ca n be give n t o ch ild re n 8 ye a rs a n d old e r
(d oxycyclin e 4 m g/kg u p t o a m a xim u m d os e of 200 m g), t h is re com m e n d a t ion
h a s n ot be e n form a lly eva lu a t e d for e f ca cy or s a fe t y. W h e n d oxycyclin e ca n -
n ot be p re s cribe d , t h e IDSA d oe s n ot re com m e n d p rop h yla xis .
EARLY LOCALIZED DISEASE (ERYTHEMA MIGRANS)
Doxycyclin e 100 m g PO BID for 10 t o 21 d a ys
Am oxicillin 500 m g PO TID for 14 t o 21 d a ys
Ea rly Disse mina te d Dise a se
Is ola t e d fa cia l n e rve p a ls y is t re a t e d t h e s a m e a s e a rly loca lize d ; h ow eve r, it
m a y re q u ire 14 t o 28 d ays of t h e ra p y.
Me n in git is or e n ce p h a lit is is t re a t e d w it h ce ft r ia xon e 2 g in t ra ve n ou s ly (IV)
d a ily for 28 d ays .
 256 Se ctio n 5 In fe ct iou s Art h rit is

Ca rd it is w it h rs t -, s e con d -, or t h ird -d egre e AV block is t re a t e d w it h ce ft ria xon e

2 g IV d a ily for 21 d ays . Ora l regim e n s m ay be con s id e re d for rs t -d egre e AV
block w it h PR in t e rva l 300 m s .

La te - sta g e Dise a se
Lym e a rt h rit is is t re a t e d w it h t h e s a m e ora l regim e n s a s e a rlie r d is e a s e ; h ow -
eve r, t h e ra p y s h o u ld be con t in u e d for 28 d a ys . If s yn ovia l in a m m a t io n p e r-
s is t s , t re a t m e n t w it h n o n s t e r o id a l a n t i-in a m m a t o ry d r u gs (NSAIDs ) o r
h yd roxych loroq u in e 200 m g BID s h ou ld be con s id e re d (10 ).
A Ja ris ch –He rxh e im e r re a ct ion h a s be e n obs e rve d in u p t o 10% of p a t ie n t s
d u rin g t h e rs t 24 h ou rs of t re a t m e n t (11 ). Th e re a ct ion ca n in clu d e feve r, ra s h
w it h o r w it h ou t p ru rit u s , n on s p e ci c ga s t ro in t e s t in a l com p la in t s , m ya lgia s ,
a n d a rt h ra lgia s .

Clinica l Co urse
Tre a t e d Lym e d is e a s e s h ou ld n ot re s u lt in ch ron ic s ym p t om s . Pa t ie n t s co m -
p la in in g of d iffu s e bod y p a in w it h ou t obje ct ive n d in gs of in a m m a t ion or
S
E
in fe ct ion s h ou ld be eva lu a t e d for brom ya lgia . Coe xis t in g m igra in e h e a d a ch e s ,
C
T
e n d om e t rios is , irrit a ble bow e l s yn d rom e , in t e rs t it ia l cys t it is , a n d u n d e rlyin g
I
O
p s ych ia t ric d is e a s e s h ou ld a ls o p rom p t t h e p h ys icia n t o con s id e r brom ya lgia
N
or ot h e r p os s ible d ia gn os is .
5
I
Lym e d is e a s e ca n p re s e n t a d ia gn os t ic a n d t h e ra p e u t ic ch a lle n ge u n le s s
n
f
e
ca re fu l a t t e n t io n is give n t o co m p le t in g a n a ccu ra t e h is t o ry a n d t h o ro u gh
c
t
i
p h ys ica l e xa m in a t ion . W it h a p p rop ria t e d a t a co lle ct ion , clin icia n s ca n u t ilize
o
u
evid e n ce -ba s e d a p p roa ch e s t o t re a t m e n t a n d p reve n t ion t h a t w ill e n s u re s a fe
s
A
a n d e ffe ct ive ca re for a ll p a t ie n t s d ia gn os e d w it h t h is illn e s s .
r
t
h
r
i
t
i
s
ICD9
088.81 Lyme

Re fe re nce s
1. Fe d e r H , Joh n s on BJ, O’Con n e ll S, e t a l. Cu rre n t con ce p t s : A crit ica l a p p ra is a l of “ch ron ic Lym e d is e a s e.”
N Engl J Med 2007 ;357 :1422 .
2. Ce n t e rs fo r Dis e a s e Co n t rol a n d Preve n t ion . Ca s e d e n it io n s for in fe ct iou s con d it ion s u n d e r p u blic
h e a lt h s u rve illa n ce . MMW R Morb Mortal Recom m Rep 1997 ;46 (RR-10 ):1 .
3. Na d e lm a n RB, Worm s e r GP. Re in fe ct ion in p a t ie n t s w it h Lym e d is e a s e . Clin Infect Dis 2007 ;45 :1032 .
4. Silve r HM . Lym e d is e a s e d u rin g p regn a n cy. Infect Dis Clin North A m 1997 ;11 :93 .
5. Worm s e r GP. Clin ica l p ra ct ice. Ea rly Lym e d is e a s e . N Eng J Med 2006;354 (26 ):2794 –801 .
6. Sm it h RP, Sch oen RT, Ra h n DW, e t a l. Clin ica l ch a ra ct erist ics a n d t re a t m en t ou t com e of e a rly Lym e d ise a se
in p a t ie n t s w it h m icrobiologica lly co n rm e d e ryt h e m a m igra n s . A nn Intern Med 2002 ;136 :421 .
7. Worm s e r GP, Da t t w yle r RJ, Sh a p iro ED, e t a l. Th e clin ica l a s s e s s m e n t , t re a t m e n t , a n d p reve n t ion of Lym e
d is e a s e, h u m a n gra n u locyt ic a n a p la s m os is , a n d ba be s ios is : Clin ica l Pra ct ice Gu id e lin e s by t h e In fe ct iou s
Dis e a s e Socie t y of Am e rica . Clin Infect Dis 2006 ;43 :1089 .
8. Noct on JJ, Dre s s le r F, Ru t le d ge BJ, e t a l. De t e ct ion of Borrelia burgdorferi DNA by p olym e ra s e ch a in re a ct ion
in s yn ovia l u id from p a t ie n t s w it h Lym e a rt h rit is . N Engl J Med 1994 ;330 (4 ):229 –234 .
9. Dre s s le r F, W h a le n JA, Re in h a rd t BN , e t a l . We s t e rn blot t in g in t h e s e rod ia gn os is of Lym e d is e a s e . J Infect
Dis 1993 ;167 (2 ):392 –400 .
10. St e e re AC, An ge lis SM . Th e ra py for Lym e a rt h rit is : St ra t egie s for t h e t re a t m e n t of a n t ibiot ic-re fra ct ory
a rt h rit is . A rthritis Rheum 2006 ;54 (10 ):3079 –3086 .
11. St e e re AC, Hu t ch in s on GJ, Ra h n DW, e t a l. Tre a t m e n t of t h e e a rly m a n ife s t a t ion s of Lym e d is e a s e . A nn
Intern Med 1983 ;99 :22 –26.
CHAPTER
25 Vira l Arthritis
Katherine Holm an and Martin Rodriguez

A 21-ye ar-o ld Cau casian

Intro ductio n
Vir u s e s a ffe ct in g h u m a n s a re u b iq u i-
w o m an w it h n o sig n i can t
t o u s , a n d t h e ir clin ica l s yn d ro m e s a re
p ast m e d ical h ist o ry p re se n t s

s
d ive rs e . Th e ir a b ilit y t o e it h e r ca u s e a n

i
t
i
w it h a 3-d ay h ist o ry o f jo in t

r
a cu t e illn e s s w it h fu ll re cove ry o r e s t a b-

h
t
r
p ain an d sw e llin g . Sh e st at e s lis h a la t e n t co u r s e —p ro gre s s in g t o a

A
re la p s in g s yn d ro m e o r ch ro n ic p rogre s -

s
t h at t h e sym p t o m s st art e d

u
s ive illn e s s —ca n m a k e t h e ir d ia gn o s e s

o
i
w it h f e ve r u p t o 102 °F an d

t
c
d if cu lt (1 ). Am o n g t h e w id e m a n ife s -

e
f
d iff u se m yalg ias. Th e jo in t t a t ion s o f vira l illn e s s e s , a r t h r it is is a n

n
I
u n co m m o n s ym p t o m ; h ow eve r, in t h e

5
p ain b e g an ab ru p t ly in h e r

N
ca s e o f s p e ci c vir u s e s , a rt h r it is ca n b e

O
k n e e s an d sp re ad t o in vo lve

I
o n e o f t h e m o s t co m m o n s ym p t o m s

T
C
m u lt ip le jo in t s o ve r t h e n e xt f e w d ays. Sh e n o t e s t h at h e r (i.e ., a lp h a vir u s e s ). Th e r e fo r e , va r io u s

E
S
p ain an d st iff n e ss are w o rse in t h e m o rn in g s. He r so cial vira l illn e s s e s s h o u ld be co n s id e re d in
h ist o ry is sig n i can t f o r w o rk in g at an e st ab lish m e n t t h at t h e d iffe re n t ia l d ia gn o s is o f a p a t ie n t
p r e s e n t in g w i t h u n d i ffe r e n t ia t e d
h e ld p art ie s f o r ch ild re n . Ph ysical e xam in at io n is n o t ab le
a r t h r it is .
f o r a t e m p e rat u re o f 102.7 °F, an d t e n d e rn e ss t o p alp at io n
w it h lim it e d ran g e o f m o t io n o ve r k n e e s, w rist s, e lb o w s,
an d p ro xim al in t e rp h alan g e al (PIP) jo in t s sym m e t rically. Pa rvo virus B19
Rash is n o t e d as sh o w n in Fig u re 25.1 . Lab o rat o ry d at a w e re CLINICAL PRESENTATION
sig n i can t f o r w h it e b lo o d ce ll (W BC) 11.3 w it h a n o rm al Pa rvoviru s B19 w a s id e n t i e d in h u m a n
diff e re n t ial, e ryt hro cyt e se dim e nt at io n rat e (ESR) 25 m m /hou r, s e ru m in t h e m id -1970s (2 ). How eve r, it s
d is e a s e m a n ife s t a t ion s h ave be e n re cog-
an d C-re act ive p ro t e in (CRP) 12.2 m g /L; h u m an im m u n o d e -
n ize d s in ce t h e 1800s , w it h t h e in it ia l
cie n cy viru s (HIV) an d h e p at it is B an d C se ro lo g ie s w e re d e s crip t ion of “ ft h d is e a s e ” or e ryt h e m a
n e g at ive . A n t in ucle ar ant ib o die s (A NA ), ant icyclic cit ru llin at e d in fe ct ios u m in ch ild re n (3 ). Th e cla s s ic
p e p t id e an t ib od ie s (an t i-CCP), and rh e u m at o id f act o r (RF) form s of p a rvoviru s B19 in fe ct ion occu r
a t e it h e r t h e vire m ic s t a ge (t ra n s ie n t
w e re n e gat ive . Parvo viru s Ig M an d IgG w e re p o sit ive at 3.4
a p la s t ic cris is a n d p u re re d ce ll a p la s ia )
an d 5.3 re spe ct ive ly. o r t h e p o s t vir e m ic s t a ge (e r yt h e m a
in fe ct ios u m a n d a rt h rop a t h y; 2 ). W h ile
ch ild re n co m m o n ly p re s e n t w it h t h e
cla s s ic “s la p p e d ch e e k” a n d re t icu la r ra s h of e ryt h e m a in fe ct ios u m , ra s h is u s u -
a lly a bs e n t or s u bt le in a d u lt s (1 ). Con ve rs e ly, a rt h ra lgia s or a rt h rit is is fa r m ore
com m on in a d u lt s w it h a cu t e in fe ct ion s (4 ). Th e cla s s ic a rt h rit is begin s p re cip i-
t ou s ly in a few join t s , s p re a d s ra p id ly in 24 t o 48 h ou rs , a n d is ch a ra ct e rize d by
s eve re, p rolon ge d m orn in g s t iffn e s s .
257
258 Se ctio n 5 In fe ct iou s Art h rit is
Figure 25.1 Pa rvovirus infection. Photogra ph demonstra tes the la celike
reticula ted ra sh on the a rm of a youngster with fth disea se. From Sweet
RL, Gibbs RS. Atla s of Infectious Disea ses of the Fema le Genita l Tra ct.
Phila delphia : Lippincott Willia ms & Wilkins; 2005.
CLINICAL POINTS
• Th e re is n o “ cla ssic” p re s-
e n t a t io n t h a t is t yp ica l o f
vira lly a sso cia t e d a rt h rit is.
• Ma n y vira lly a sso cia t e d
a rt h rit id e s ca n b e m ist a ke n
fo r e a rly rh e u m a t o id
a rt h rit is (RA).
• Art h rit is m a y o ccu r b e fo re
t h e o n se t o f a t yp ica l
clin ica l vira l syn d ro m e
(i.e ., HBV, HIV).
PATIENT ASSESSMENT
• Th o ro u g h h ist o ry,
in clu d in g im m u n iza t io n s,
e xp o su re s, o ccu p a t io n ,
t ra ve l, se xu a l, a n d so cia l.
• Clo se e xa m in a t io n
fo r sig n s o f o t h e r
rh e u m a t o lo g ic co n d it io n s.
• Sp eci c la b ora to rie s o n
the basis of risk assessment
a b ove .
EXAMINATION
Pa tien ts ten d to p resen t w ith a low tem p era tu re. A la cy
ra sh , m ost com m on ly p resen t in th e extrem ities, ca n be
fou n d . Ten d er, sw ollen join ts a re com m on ly seen , bu t n o
d eform ities a re p resen t. Both sm a ll- a n d m ed iu m -s ize
join ts a re p red om in a n tly a ffected u su a lly in a sym m etri-
ca l fa sh ion (1 ). Axia l join ts a re sp a red .
DIAGNOSIS
Virem ia is evid en t by 5 t o 6 d ays p ostexp osu re, w it h a
p ea k a t 8 to 9 d ays. Th e viru s clea rs q u ickly, a n d IgM is
p resen t by d ays 10 to 12 a n d m ay p ersist for 2 to 3 m on th s
(2 ). Se ru m of in fe ct e d p a t ie n t s ca n s h ow t ra n s ie n t
a u t oa n t ibod ies , in clu d in g, bu t n ot lim it e d t o, ANA, RF,
a n d a n ti-DNAs (4 ). Diagn osis th erefore relies on seru m
IgM a n t ibod ies t o p a rvoviru s B19, w ith or w ith ou t IgG
a n d d em on strable p a rvoviru s DNA.
TREATMENT
Tre a t m e n t is s u p p ort ive, w it h n on s t e roid a l a n t i-in a m m a t ory d ru gs (NSAIDs )
a s n e e d e d for p a in a n d in a m m a t ion . In t ra ve n ou s im m u n oglobu lin h a s be e n
u s e d in ca s e s of p u re re d ce ll a p la s ia in im m u n ocom p rom is e d p a t ie n t s , bu t it
is n ot re com m e n d e d in a rt h rit is (4 ).
CLINICAL COURSE
Acu t e a rt h rit is re s olve s w it h in w e e ks a lt h ou gh , u n com m on ly, ca s e s h ave p e r-
s is t e d for m on t h s . W h e t h e r p a rvoviru s B19 in fe ct ion ca u s e s a ch ron ic a rt h rit is
re m a in s con t rove rs ia l (4 ), a s d oe s it s p os s ible a s s ocia t ion w it h RA a n d ot h e r
in a m m a t o ry a r t h ro p a t h ie s . So m e s t u d ie s h a ve fo u n d o n go in g B19 DNA in
s e ru m , bon e m a rrow, a n d s yn oviu m of p a t ie n t s w it h ch ron ic a rt h rit is a n d /or
RA, bu t t h ey h ave be e n fou n d in h e a lt h y con t rols a s w e ll, m a kin g a d e t e rm in a -
t ion of t h e ca u s e d if cu lt (1 , 2, 4 – 6 ).
He pa titis C
CLINICAL PRESENTATION
He p a t it is C (HCV) is a s in gle -s t ra n d e d RNA Flav iv irus . It is e s t im a t e d t h a t gre a t e r
t h a n 170 m illion p e op le w orld w id e a re in fe ct e d w it h t h e viru s (7 ). Pa re n t e ra l
in fe ct ion occu rs m os t com m on ly, oft e n in t h e s e t t in g of in t ra ve n ou s d ru g u s e.
Tra n s m is s ion in h e a lt h ca re s e t t in gs h a s be com e ra re in d eve lop e d cou n t rie s
s in ce rou t in e t e s t in g of blood p rod u ct s bega n in t h e e a rly 1990s ; h ow eve r, occa -
s ion a l ca s e s con t in u e t o b e re p ort e d (7 ). Follow in g a cu t e in fe ct ion w it h HCV,
74% t o 86% of p a t ie n t s d eve lop p e rs is t e n t vire m ia a n d 15% t o 20% of t h e s e
p a t ie n t s w it h ch ron ic in fe ct io n d eve lo p cirr h os is (7 ), w h ich ca n p rogre s s t o
h e p a t oce llu la r ca rcin om a a n d e n d -s t a ge live r d is e a s e.
Ex t ra h e p a t ic m a n ife s t a t ion s of HCV in fe ct ion a re va r ie d , w it h join t p a in
be in g a com m on on e. St u d ie s e s t im a t e t h a t 9% t o 29% of a ll p a t ie n t s w it h HCV
com p la in o f a rt h ra lgia s , w h ile 2% t o 4% o f p a t ie n t s h a ve a rt h rit is (1 , 8 ). Tru e
in a m m a t ory a rt h rit is a p p e a rs t o m a n ife s t in fou r d is t in ct w a ys : (1 ) re la t in g
d ire ct ly t o HCV in fe ct ion (2 ) a s a s ign of m ixe d cryoglobu lin e m ia (3 ) coe xis t in g,
bu t s e p a ra t e rh e u m a t ic d is e a s e (4 ) occu rrin g ra re ly s e con d a ry t o t h e ra p y for
HCV (4 ). As t h e ra py-re la t e d a rt h rit is is e xce e d in gly ra re, fu rt h e r d is cu s s ion of
1 t o 3 follow s .
 Ch a p te r 25 Vira l Art h rit is 259

HCV- RELATED ARTHRITIS

Pa t ie n t s ca n d eve lop a n in a m m a t ory a rt h rit is d ire ct ly re la t e d t o HCV, w h ich
occu rs in few e r t h a n 5% of p a t ie n t s (4 ). Ph ys ica l e xa m in a t ion reve a ls evid e n ce
of s yn ovit is of s m a ll join t s in a s ym m e t rica l p a t t e rn .

Diag no sis
De m on s t ra t ion of HCV a n t ibod y or RNA in s e ru m a n d ru lin g ou t ot h e r ca u s e s
of bot h HCV-re la t e d , s u ch a s m ixe d cryoglobu lin e m ia , a n d n on re la t e d in a m -
m a t ory a rt h rit is .

Tre atme nt/ Clinical Co urse

Mos t com m on ly u s e d t re a t m e n t s a re a n a lge s ics a n d low -d os e cort icos t e roid s .
Dis e a s e -m od ifyin g a n t irh e u m a t ic d ru gs (DMARDs ) a n d biologic a ge n t s , s u ch a s
a n t it u m or n e cros is fa ct or (a n t i-TNF), h ave a ls o be e n u s e d , a lbe it u n com m on ly
(4 ). St u d ie s of a n t ivira l t h e ra p y s h ow m ixe d re s u lt s , w it h evid e n ce of be n e t
a n d occa s ion a lly e xa ce rba t ion of s ym p t om s ; h ow eve r, m os t of t h e s e s t u d ie s
d id n ot cle a rly d e n e if t h e s e p a t ie n t s h a d cryoglo bu lin e m ia -re la t e d ve r s u s
HCV-re la t e d a rt h rit is (9 ).

s
i
t
i
MIXED CRYOGLOBULINEMIA

r
h
t
r
Es s e n t ia l m ixe d cryoglobu lin e m ia is a s s ocia t e d w it h HCV in fe ct ion , a n d s ym p -

A
s
t om s in clu d e p u rp u ra , glom e ru lon e p h rit is , lym p h a d e n op a t h y, s kin u lce rs , a n d

u
o
p e rip h e ra l n e u rop a t h y. Ma n y p a t ie n t s com p la in of a rt h ra lgia s ; h ow eve r, le s s

i
t
c
t h a n 10% d eve lop fra n k a rt h rit is (4 ). Th e cla s s ic t ria d is d e s cribe d a s t h a t of

e
f
n
p u rp u ra , glo m e r u lon e p h rit is , a n d a r t h ra lgia s . Ph ys ica l e x a m in a t ion s e ld o m

I
5
reve a ls evid e n ce of s yn ovit is or d e form it y; s kin e xa m in a t ion s h ow s p a lp a ble

N
p u rp u ra m os t fre q u e n t ly in t h e low e r e xt re m it ie s .

O
I
T
C
E
Diag no sis

S
Dia gn os is re q u ire s d e m on s t ra t ion of t h e clin ica l s yn d rom e in a d d it ion t o s e ro-
logic, in clu d in g s e ru m cryoglobu lin s , low C4 leve l, a n d p os it ive RF (s e rologic),
w it h h is t o logic n d in gs s u ch a s evid e n ce o f le u ko cyt o cla s t ic va s cu lit is (4 ).
No t a bly, t e s t s for HCV a n t ibo d ie s ca n be fa ls e ly n e ga t ive in t h is con d it io n ,
re q u irin g t e s t s d ire ct e d t ow a rd HCV RNA for d ia gn os is (7 ).

Tre atme nt/ Clinical Co urse

Tre a t m e n t ge n e ra lly in volve s a n t ivira l t h e ra py d ire ct e d t ow a rd HCV, bu t cort i-
cos t e roid s , rit u xim a b, cyclop h os p h a m id e, a n d p la s m a p h e re s is a re s om e t im e s
re q u ire d for t h e m ore s eve re ca s e s (4 ).

COEXISTING INFLAMMATORY ARTHRITIS

Give n t h e p reva le n ce of ch ron ic HCV, a n u m be r of t h e s e p a t ie n t s a ls o h ave a
coe xis t in g rh e u m a t ic d is e a s e, in clu d in g, bu t n ot lim it e d t o, rh e u m a t oid a rt h rit is
(RA), s ys t e m ic lu p u s e ryt h e m a t os u s (SLE), a n d Sjogre n s yn d rom e (4 ).

Diag no sis
Clin ica l n d in gs com bin e d w it h ove rla p p in g la bora t ory n d in gs —p os it ive RF,
cyt op e n ia s , ANA, low C4 leve l—m a ke a rm d ia gn os is d if cu lt . To a d d re s s t h is ,
a n t i-CCP a n t ibod y, a fa irly s p e ci c t e s t for RA, h a s be e n eva lu a t e d in p a t ie n t s
w it h HCV. In p a t ie n t s w it h RA, 76.6% h a d p os it ive a n t i-CCP a n t ibod ie s , bu t n o
HCV p a t ie n t s w it h o r w it h o u t jo in t in vo lve m e n t w e re p o s it ive . No t a bly, in
10 p a t ie n t s in it ia lly t h ou gh t t o h a ve HCV-a s s ocia t e d a rt h rit is bu t w h o w e re
u lt im a t e ly fou n d t o h ave RA, 60% of t h e ir in it ia l blood s a m p le s s h ow e d a n t i-CCP
a n t ibod ie s (10 ).
 260 Se ctio n 5 In fe ct iou s Art h rit is

Tre atme nt / Clinical Co urse

In a m m a t ory a rt h ritis, su ch a s RA, req u ires ea rly im m u n e-m od ifyin g a p p roa ch es
th a t ca n w ors en th e u n d erlyin g liver dysfu n ction , m a kin g a ccu ra t e d ia gn osis cru -
cia l. More d a ta a re n eed ed rega rd in g th e u s e of im m u n om od u la t ory th era p ies in
th e s ettin g of HCV-a ssocia ted liver d isea se. Meth otrexa te is kn ow n to h ave h ep a tic
com p lica t ion s a ssocia ted w ith its u s e; a n ti-TNF a gen t s a re ju st begin n in g to be
eva lu a ted in t h ese p a tien t s (6 ). Th era py req u ires a m u ltid is cip lin a ry a p p roa ch .

He pa titis B
CLINICAL PRESENTATION
He p a t it is B viru s (HBV) is a s m a ll DNA viru s o f t h e fa m ily He p a d n a vir id a e .
Tra n s m is s ion occu rs m os t com m on ly in t h re e w a ys : p e rin a t a lly, s e xu a lly, or
p a re n t e ra lly (11 ). Pe rs is t e n ce of vira l in fe ct ion is la rge ly d e t e rm in e d by a ge a t
in fe ct ion . Pe rin a t a l in fe ct ion oft e n re s u lt s in ch ron ic HBV in fe ct ion , w h e re a s
cle a ra n ce of HBV is m ore com m on w h e n con t ra ct e d in a d u lt h ood , w it h on ly 5%
t o 10% of p e op le in fe ct e d d eve lop in g ch ron ic HBV (1 ). Art h rit is occu rs in t w o
form s . Th e rs t form a p p e a rs d u rin g t h e p re s ym p t om a t ic p h a s e of a cu t e in fe c-
t ion , m os t ly a few d ays a n d u n u s u a lly w e e ks p rior t o t h e on s e t of ja u n d ice or
S
evid e n ce of h e p a t it is . Ch ron ic a rt h rit is , t h e s e con d form , occu rs in t h e s e t t in g
E
C
of HBV-a s s ocia t e d p olya rt e rit is n od os a (PAN; 1 ).
T
I
O
N
5
EXAMINATION
I
n
f
Acu t e HBV-a s s ocia t e d a rt h rit is p re s e n t s a s a s ym m e t ric p olya rt h rit is in volvin g
e
c
t h e PIP join t s , kn e e s , a n d a n kle s (1 , 4 ), w h ich is s im ila r t o RA; h ow eve r, d is t in -
t
i
o
u
gu is h in g fe a t u re s a re a n a bru p t on s e t , a ccom p a n ie d by a con com it a n t ra s h . In
s
HBV-a s s ocia t e d PAN, a rt h ra lgia s a re com m on ly rep ort e d . Fra n k a rt h rit is a ffe ct s
A
r
t
t h e m id -s ize join t s (w ris t , a n kle s , a n d kn e e s ) a n d is m u ch le s s com m on .
h
r
i
t
i
s
DIAGNOSIS
In t h e a cu t e form , t h e d ia gn os is of a rt h rit is is m a d e re t ros p e ct ive ly a ft e r t h e
a p p e a ra n ce of ja u n d ice a n d /or t ra n s a m in it is . Hep a t it is B s u rfa ce a n t ige n (HBs Ag)
is d e t e ct a ble in s e ru m a p p roxim a t e ly 4 t o 10 w e e ks a ft e r in fe ct ion , a ccom p a n ie d
by a s ign i ca n t vire m ia , a n d h e n ce is h e lp fu l t o d ia gn os e on ly t h e ch ron ic form
of t h is d is e a s e. An t ibod ie s t o core a n t ige n (a n t i-Hbc) d eve lop s h ort ly a ft e r (12 ;
Fig. 25.2 ). Sim ila r t o HCV, e ros ive a rt h rit is a n d a n t i-CCP a n t ibod ie s a re n ot u s u -
a lly s e e n a n d s h ou ld p rom p t w ork-u p for a d d it ion a l ca u s e s (4 , 6 ).

TREATMENT/ CLINICAL COURSE

Pre s ym p t om a t ic a rt h rit is is s e lf-lim it e d , re q u ire s n o s p e ci c t h e ra py, a n d u s u -
a lly re s olve s a rou n d t h e t im e t h a t ja u n d ice d eve lop s . Tre a t m e n t for a rt h rit is
re la t e d t o HBV-a s s o cia t e d PAN in vo lve s im m u n o m o d u la t o ry p lu s a n t ivira l
a ge n t s , w it h in it ia l re m is s ion in d ica t ive of good ove ra ll p rogn os is (4 ).

Alpha viruse s
EPIDEMIOLOGY AND CLINICAL PRESENTATION
Th e a lp h aviru s e s , a ge n u s of t h e fa m ily Toga virid a e, a re a rt h rop od born e a n d
d ivid e d in t o “Old World ” a n d “New Wor ld ” s p e cie s . Th e form e r ca u s e a s yn -
d rom e of feve r, ra s h , a n d a rt h ra lgia s , w h e re a s t h e ir “New World ” cou n t e rp a rt s
com m on ly ca u s e e n cep h a lit is (13 ). Th e a rt h rit is -in d u cin g a lp h aviru s e s h ave a
w id e ge ogra p h ic d is t ribu t ion a n d ca n ca u s e va s t o u t bre a ks . O’Nyo n g-n yon g
a n d Igbo-Ora occu r m a in ly in Africa , Ba rm a h Fore s t a n d Ros s Rive r m a in ly in
 Ch a p te r 25 Vira l Art h rit is 261

Incubation period Acute disease Recovery

• Clinical symptoms Antibodies in blood

• Increased liver enzymes
in blood Anti-HBc Anti-HBs

l
e
• Increased bilirubin in blood

v
e
l
HBsAg

e
v
i
t
Virus in

a
l
e
blood

R
1 2 3 4 5 6
Exposure Months Years
A Acute hepatitis B with recovery

• Clinical symptoms
• Increased liver enzymes
in blood
• Increased bilirubin in blood Anti-HBs does
l
not appear
e
Antibody in blood
v
HBsAg
e
l
Virus in Anti-HBc
e
v
s
blood
i
i
t
a
t
i
l
r
e
h
R
t
r
A
s
u
1 2 3 4 5 6

o
i
t
Exposure Months Years

c
e
f
B Chronic hepatitis B

n
I
5
N
• Clinical symptoms

O
• Increased liver enzymes Anti-HBs does

I
T
in blood Antibody in blood

C
not appear
• Increased bilirubin in blood

E
S
Anti-HBc
l
e
HBsAg
v
e
Virus in
l
e
blood
v
i
t
a
l
e
R
1 2 3 4 5 6
Exposure Months Years

C Hepatitis B carrier state

Figure 25.2 Hepa titis B clinica l pha ses a nd blood ma rkers of infection. A: Acute infection is cha ra cterized by
ra pid a ppea ra nce of the virus in blood before symptoms a ppea r, disa ppea ra nce of the virus from blood, a nd
a ppea ra nce in blood of a ntibodies to hepa titis B surfa ce a ntigen (HBsAg). B: Chronic hepa titis is signa led by
continuing ja undice or clinica l symptoms, or the continued presence of virus in blood (a s is indica ted by the
detection in blood of HBsAg). C: The ca rrier sta te is indica ted by disa ppea ra nce of clinica l symptoms a nd the
persistence of virus in blood (a s is indica ted by the detection in blood of HBsAg).

Au s t ra lia , a n d Ma ya ro in So u t h Am e r ica , w h e re a s ch ik u n gu n ya a n d Sin d b is

h a ve w id e r ge ogra p h ic ra n ge (14 ). Sym p t om s from t h e s e viru s e s occu r a bru p t ly,
w it h feve r, m a la is e, m ya lgia s , re t ro-orbit a l p a in , a n d h e a d a ch e occu rrin g e a rly.
Art h ra lgia s , oft e n in ca p a cit a t in g, a re n e a rly u biq u it ou s in t h os e w h o p re s e n t
w it h s ym p t om a t ic in fe ct ion .

EXAMINATION
Th e a rt h rop a t h y t yp ica lly a ffe ct s m u lt ip le s m a ll join t s , e s p e cia lly t h os e p revi-
ou s ly in ju re d ; p a t ie n t s oft e n t ry t o lim it m ove m e n t (13 ). Ra s h fre q u e n t ly occu rs ,
 262 Se ctio n 5 In fe ct iou s Art h rit is

a n d in ce rt a in in fe ct ion s , n ot a bly ch iku n gu n ya , o’n yon g-n yon g, a n d Ma ya ro,

p e t e ch ia e, p u rp u ra , a s w e ll a s ble e d in g from ga s t roin t e s t in a l t ra ct , gu m s , a n d
n a s op h a ryn x ca n occu r (14 ).

DIAGNOSIS
Dia gn os is of a s p e ci c a lp h a viru s re m a in s a ch a lle n ge, a s t h ey clin ica lly re s e m -
ble e a ch ot h e r a n d m a n y ot h e r vira l illn e s s e s . In e n d e m ic a re a s , d iffe re n t ia t in g
b e t w e e n t h e m a jo r a lt e r n a t e d ia gn o s e s is k ey: d e n gu e fo r ch ik u n gu n ya o r
Ma ya ro; m a la ria for o’n yon g-n yon g (15 ). Th e Ce n t e rs for Dis e a s e Con t rol a n d
Preve n t ion (CDC) h a s t e s t in g ca p a bilit y for ch iku n gu n ya , o’n yon g-n yon g, Ros s
Rive r, Ba rm a h Fore s t , a n d lim it e d t e s t in g for Sin d bis (16 ). De t a ile d t ra ve l h is t ory
a n d kn ow le d ge of re ce n t a n d on goin g ou t bre a ks a re e s s e n t ia l in t h e eva lu a t ion
of re t u rn in g t ra ve le rs .

TREATMENT
Tre a t m e n t for t h e a lp h a vir u s e s is la rge ly s u p p o rt ive, w it h NSAIDs fo r p a in .
As p irin s h o u ld b e a vo id e d in ca s e s w h e re d e n gu e o r o t h e r h e m o rrh a gic ill-
n e s s e s a re in t h e d iffe re n t ia l a s t h is ca n e xa ce rba t e ble e d in g m a n ife s t a t ion s
S
(15 ). Preve n t ion re m a in s t h e m a in s t a y of t h e ra p y. Th e CDC s p e ci ca lly re com -
E
C
m e n d s t h a t a p e rs on d ia gn os e d w it h ch iku n gu n ya feve r s h ou ld lim it e xp os u re
T
I
O
t o m os q u it oe s t o a void s p re a d of t h e in fe ct ion (17 ).
N
5
I
n
CLINICAL COURSE
f
e
c
As s t u dy of t h e a lp h aviru s e s is lim it e d in m os t ca s e s , clin ica l cou rs e ca n on ly be
t
i
o
u
e s t im a t e d . Ch iku n gu n ya a n d Ros s Rive r a re t h e m os t s t u d ie d of t h e s e a lp h avi-
s
ru s e s . Wit h rega rd t o Ros s Rive r, s ym p t om s ge n e ra lly re s olve w it h in 6 m on t h s
A
r
(15 ). How eve r, rep ort s of ot h e r a lp h aviru s e s h ave d e s cribe d ch ron ic a n d /or re cu r-
t
h
r
re n t a rt h rit is (14 ). Rep ort s from t h e re ce n t ch iku n gu n ya ou t bre a ks h ave d e s cribe d
i
t
i
s
join t s ym p t om s la s t in g fre q u e n t ly for lon ge r t h a n 6 m on t h s (18 ) a n d in s om e
ca s e s for 18 m on t h s follow in g s eve re clin ica l in fe ct ion (19 ). As m ore d a t a be com e
ava ila ble, it is like ly t h a t t h e n a t u ra l p rogre s s ion w ill be fu rt h e r e lu cid a t e d .

Rube lla a nd Rube lla Va ccine

RUBELLA
Epide mio lo g y and Clinical Pre se ntatio n
Ru be lla , a n ot h e r m e m be r of t h e fa m ily Togavirid a e, is a n RNA viru s s p re a d by
a irborn e d rop le t s . W h ile t h e clin ica l m a n ife s t a t ion s of t h e d is e a s e a re ge n e ra lly
m ild in ch ild re n —u s u a lly feve r, ra s h , a n d coryza (1 )—e xp os u re t o ru be lla d u rin g
p regn a n cy, p a rt icu la rly d u rin g t h e rs t t rim e s t e r, ca n h ave d eva s t a t in g con s e -
q u e n ce s for t h e fe t u s . Th u s , a m a jor focu s h a s be e n va ccin a t ion , re s u lt in g in a
m a rke d d e cre a s e in it s in cid e n ce.
In a d u lt s , s ym p t om s a re bot h m ore com m on a n d s eve re, in clu d in g feve r,
m a la is e , co ryz a , a n d p o s t e r io r ce r vica l lym p h a d e n o p a t h y, w h ich p re s e n t
a p p roxim a t e ly 1 w e e k p os t exp os u re (1 ). Ra s h , w h ich m ay be s u bt le, ge n e ra lly
occu rs 2 t o 3 w e e ks a ft e r exp os u re (1 ), w it h a rt h ra lgia s or fra n k a rt h rit is u s u a lly
d eve lop in g w it h in 1 w e e k of t h e ra s h (20 ). Ne a rly on e t h ird of p a t ie n t s m ay e xp e -
rie n ce join t s ym p t om s (21 ). Wit h in cre a s in g n u m be rs of in d ivid u a ls re fu s in g
va ccin e s w e m ay s e e a re s u rge n ce of t h is vira l illn e s s in t h e fu t u re.

Examinatio n
Ha n d s a n d kn e e s a re m os t fre q u e n t ly a ffe ct e d , u s u a lly s ym m e t rica lly; h ow eve r
a m igra t ory p a t t e rn ca n a ls o occu r (1 ). Fra n k a rt h rit is occu rs m ore com m on ly
in a d u lt w om e n com p a re d t o m e n a n d ch ild re n (21 ).

NOT TO BE MISSED
• Ra sh .
• Ma y in d ica t e p a rvo viru s,
a cu t e HIV, a cu t e HBV,
ru b e lla , a rb o viru s.
• Jo in t d e fo rm it y.
• Mo re like ly t o b e
n o n vira l.
Ch a p te r 25 Vira l Art h rit is 263
Diag no sis
Dia gn os is re s t s on is ola t ion of viru s from t h roa t cu lt u re or d e m on s t ra t ion of
s e ru m a n t ibod ie s t o ru be lla . Pre s e n ce of IgM t o ru be lla in d ica t e s in fe ct ion like ly
in t h e p a s t 1 t o 2 m on t h s ; IgG ca n be u s e d for d ia gn os is on ly if p a ire d a cu t e a n d
con va le s ce n t s e ra a re u s e d (1 ).
Tre a tme nt
SUPPORTIVE AND SYMPTOMATIC
Clinical Co urse
Sym p t o m s ge n e ra lly re s olve w it h in a few w e e ks ; h ow eve r, ca s e s h a ve be e n
re p ort e d in w h ich join t s ym p t om s w e re p e rs is t e n t for m on t h s t o ye a rs (1 , 20 ).
RUBELLA VACCINE
W h ile va ccin a t ion p reve n t s ru be lla in fe ct ion , it ca rrie s a ris k of a rt h rit is a s w e ll,
w it h h igh e s t in cid e n ce s in a d u lt w om e n . Ge n e ra lly, p os t va ccin a t ion a rt h rit is
occu rs 10 t o 28 d ays a ft e r ru be lla va ccin a t ion (22 ). Alt h ou gh it is p os t u la t e d t h a t
t h e in it ia l HPV77/DK12 s t ra in ca rrie d t h e gre a t e s t ris k of p os t im m u n iza t ion
a rt h rit is , rep ort s p os t va ccin a t ion w it h t h e p re s e n t ly u s e d RA 27/3 h ave e m e rge d
s
i
t
(1 , 23 ). Th e In s t it u t e of Me d icin e re le a s e d a rep ort review in g t h e evid e n ce a n d
i
r
h
con clu d e d , it “. . . is con s is t e n t w it h a ca u s a l re la t ion be t w e e n t h e RA 27/3 ru be lla
t
r
A
va ccin e s t ra in a n d ch ron ic a rt h rit is in a d u lt w om e n , a lt h ou gh t h e evid e n ce is
s
u
lim it e d in s cop e ” (23 ). Th u s , d e s p it e w id e s p re a d va ccin a t ion in t h e Un it e d St a t e s ,
o
i
bot h w ild ru be lla a n d it s va ccin e s h ou ld be con s id e re d in t h e d iffe re n t ia l ce r-
t
c
e
t a in ly for a cu t e, a n d p os s ibly ch ron ic, a rt h rit is , p a rt icu la rly in a d u lt w om e n .
f
n
I
5
Huma n Immuno de ficie ncy Virus
N
O
I
T
C
Join t com p la in t s a re d e scribe d a t a ll s t a ge s of HIV in fect ion , eve n d u rin g a cu t e
E
S
in fe ct ion , w h ere a rt h ra lgia s ca n be s e en in 28% t o 54% of ca s e s (24 ). A p a in fu l
a rt icu la r s yn d rom e w a s d es cribe d e a rly in t h e HIV ep id e m ic, m os t com m on ly a s
seve re p a in in volvin g t h e kn ee s (les s fre q u e n tly, s h ou ld ers a n d e lbow s). Typ ica lly,
it la st s 2 t o 24 h ou rs a n d resolves , bu t m ay req u ire NSAIDs or op ia tes (24, 25 ). It is
n ot com m on ly s e en n ow a d ays . Fra n k a rt h rit is a ls o occu rs , e it h er d ire ct ly re la t e d
to HIV or in t h e s e t tin g of a se con d a ry in a m m a tory a rt h rop a t h y. HIV-a ss ocia t e d
a rt h rit is , d e n e d a s a d is a blin g a rt h rit is com m on ly a ffe ct in g t h e kn e e s a n d
a n kle s , h a s a se lf-lim ite d cou rs e. De n it ion of th is d is ord e r in volve s a n on e ros ive
oligoa rth rit is , w it h n ega t ive s tu d ies for RF, ANA, a n d HLA-B27 (24 –26 ).
High ly a ct ive a n t ire t rovira l t h e ra py (HAART) h a s ch a n ge d t h e s p e ct ru m of
join t d is e a s e s in HIV. Hu m a n im m u n od e cie n cy viru s –a s s ocia t e d a rt h rit is a n d
p s oria t ic a rt h rit is occu r m ore com m on ly w it h a d va n ce d s t a ge s of d is e a s e ; t h e
s eve rit y of t h e s e a rt icu la r m a n ife s t a t ion s d e cre a s e s w it h e ffe ct ive a n t ire t rovi-
ra l t h e ra p y. Con ve rs e ly, coe xis t in g in a m m a t ory d is ord e rs s u ch a s RA a n d SLE
t e n d t o im p rove w it h a d va n cin g s t a ge s of HIV d is e a s e (24 , 27 ). Th is obs e rva t ion
p rovid e d bot h a n e loq u e n t p roof of t h e e ffe ct ive n e s s of a n t ire t rovira l t h e ra p y
a n d a clu e t ow a rd t h e p a t h oge n e s is of t h e s e rh e u m a t ic con d it ion s . W h ile t re a t -
m e n t of HIV-a s s ocia t e d a rt h rit id e s ge n e ra lly in volve s t re a t in g t h e HIV in fe c-
t ion , m o s t im p ort a n t ly, p a t ie n t s p re s e n t in g w it h a s im ila r a rt h rit is h a ve a n
in d ica t ion for HIV t e s t in g. It is im p ort a n t t o re m e m be r t h a t t h e CDC re com -
m e n d s u n ive rs a l HIV t e s t in g in a d u lt s a ge d 13 t o 64 in t h e Un it e d St a t e s a t le a s t
on ce a n d m ore fre q u e n t ly in t h os e a t ris k (28 ).
Othe rs
Ot h e r viru s e s h a ve be e n im p lica t e d in t h e s e t t in g o f a rt h rit is . Hu m a n T-ce ll
lym p h ot rop h ic viru s -1 (HTLV-1) ca n ca u s e in a m m a t ory a rt h rop a t h ie s , m os t ly
 264 Se ctio n 5 In fe ct iou s Art h rit is

in e n d e m ic a re a s (4 ). Ep s t e in –Ba rr viru s a n d coxs a ckieviru s h ave be e n im p li-

WHEN TO REFER
• Art h rit is n e e d s sp e ci c
t re a t m e n t o f ca u sa l viru s
fo r re co ve ry (i.e ., HIV,
HCV, HBV).
• In a m m a t o ry a rt h rit is (i.e .,
RA) d ia g n o se d in se t t in g
o f HCV.
ca t e d in a few ca s e s o f p o lya rt h rit is ; h ow eve r, a ca u s a l re la t ion s h ip re m a in s
d if cu lt t o p rove (4 , 21 ).
Co nclusio n
Alt h o u gh vira lly a s s o cia t e d a rt h rit is re m a in s a ra re e t io logy o f t h e co m m o n
com p la in t of a rt h rit is , it is im p ort a n t for clin icia n s t o be aw a re of t h e p os s ibil-
it y. Dia gn os in g a vira l e t iology of a rt h rit is ca n s p a re a p a t ie n t a n in va s ive w ork-
u p , a s w e ll a s p reve n t p ot e n t ia lly h a rm fu l t h e ra p y (4 ). Dia gn os in g HIV, h e p a t it is ,
o r a n a lp h a viru s h a s bo t h in d ivid u a l a n d p u blic h e a lt h be n e t s . Give n t h e ir
u biq u it y, viru s e s s h ou ld a lw ays be in clu d e d in t h e d iffe re n t ia l of a p a t ie n t p re -
s e n t in g w it h a rt h rit is .

ICD9
716.9 Arthritis, arthritic (acu t e ) (ch ro n ic) (su b acu t e )
079.99 [711.5] viral d ise ase NEC
S
E
Re fe re nce s
C
T
I
O
1. Ca la bre s e LH , Na id e s SJ. Vira l a rt h rit is . Infect Dis Clin N A m 2005 ;19 :963 –980 .
N
2. You n g NS, Brow n KE. Pa rvoviru s B19 . N Engl J Med 2004 ;350 :586 –597 .
5
3. Brow n KE. Hu m a n p a rvoviru s e s , in clu d in g p a rvoviru s B19 a n d h u m a n bocaviru s . In : Ma n d e ll GL, Be n n e t t
I
JE, Dolin R, e d s . Mandell, Douglas, and Bennett’s: Principles and Practice of Infectious Diseases. Vol. II. 7t h e d .
n
f
Ph ila d e lp h ia , PA: Els evie r ; 2010 :2087 –2095 .
e
c
4. Va s s ilo p o u lo s D, Ca la bre s e LH . Vira lly As s o cia t e d Ar t h r it is 2008: Clin ica l, e p id e m iologic, a n d p a t h o-
t
i
o
p h ys iologic con s id e ra t ion s . A rthritis Res Ther 2008 ;10 :215 .
u
5. Lu n d q vis t A, Is a A, Tolfve n s t a m T. High fre q u e n cy of p a rvoviru s B19 DNA in bon e m a rrow s a m p le s from
s
A
rh e u m a t ic p a t ie n t s . J Clin Virol 2005 ;33 :71 –74 .
r
6. Be cke r J, Win t h ro p KL. Up d a t e on rh e u m a t ic m a n ife s t a t ion s of in fe ct iou s d is e a s e s . Curr Opin Rheum atol
t
h
2010 ;22 :72 –77 .
r
i
t
7. La u e r GM , Wa lke r BD. He p a t it is C viru s in fe ct ion . N Engl J Med 2001 ;345 :41 –52 .
i
s
8. Va s s ilop ou los D, Ca la bre s e LH . Rh e u m a t ic m a n ife s t a t ion s of h ep a t it is C in fe ct ion . Curr Rheum atol Rep
2003 ;5 :200 –204 .
9. Zu ck e r m a n E, Ye s h u r u n D, Ro s n e r I. Ma n a ge m e n t o f h e p a t it is C vir u s -re la t e d a r t h r it is . BioDru gs
2001 ;15 :573 –584 .
10. Bom ba rd ie ri M , Ale s s a n d r i C, La b ba d ia G, e t a l. Role of a n t i-cyclic cit ru llin a t e d p e p t id e a n t ibod ie s in
d iscrim in a tin g p a tien ts w ith rh eu m a toid a rth ritis from p a tien ts w ith ch ron ic h ep a titis C in fection -a ssocia ted
p olya rt icu la r in volve m e n t . A rthritis Res Ther 2004 ;6 :R137-R141 .
11. Kozie l MJ, Th io CL. Hep a t it is B viru s a n d h ep a t it is d e lt a viru s . In : Ma n d e ll GL, Be n n e t t JE, Do lin R, e d s .
Mandell, Douglas, and Bennett’s: Principles and Practice of Infectious Diseases. Vol II. 7t h e d . Ph ila d e lp h ia , PA:
Els evie r ; 2010 :2059 –2086 .
12. Ga n e m D, Prin ce AM . Hep a t it is B viru s in fe ct ion —n a t u ra l h is t ory a n d clin ica l con s e q u e n ce s . N Engl J Med
2004 ;350 :1118 –1129 .
13. Ma rkoff L. Alp h aviru s e s . In : Ma n d e ll GL, Be n n e t t JE, Dolin R, e d s . Mandell, Douglas, and Bennett’s: Principles
and Practice of Infectious Diseases. Vol II. 7t h e d . Ph ila d e lp h ia , PA: Els evie r ; 2010 :2117 –2125 .
14. Toiva n e n A. Alp h aviru s e s : An e m e rgin g ca u s e of a rt h rit is ? Curr Opin Rheum atol 2008 ;20 :486 –490 .
15. Su h rb ie r A, Lin n ML. Clin ica l a n d p a t h o logic a s p e ct s of a r t h r it is d u e t o Ros s Rive r vir u s a n d o t h e r
a lp h aviru s e s . Curr Opin Rheum atol 2004 ;16 :374 –379 .
16. Dia gn os t ic Te s t in g/CDC Ch iku n gu n ya . Ce n t e rs for Dis e a s e Con t rol a n d Preve n t ion We b s it e . h t t p ://w w w.
cd c.gov/n cid od /d vbid /Ch iku n gu n ya /CH_Dia gn os t ic.h t m l. Acce s s e d Oct o be r 29, 2010.
17. Fa ct Sh e e t /CDC Ch iku n gu n ya . Ce n t e rs for Dis e a s e Con t rol a n d Preve n t ion We b s it e . h t t p ://w w w.cd c.gov/
n cid od /d vbid /Ch iku n gu n ya /CH_Fa ct Sh e e t .h t m l. Acce s s e d Oct obe r 5, 2010.
18. Ta u bit z W, Cra m e r JP, Ka p a u n A, e t a l. Ch iku n gu n ya feve r in t rave le rs : Clin ica l p re s e n t a t ion a n d cou rs e .
Clin Infect Dis 2007 ;45 :e 1 –4 .
19. Borgh e rin i G, Pou be a u P, Jos s a u m e A, e t a l. Pe rs is t a n t a rt h ra lgia a s s ocia t e d w it h ch iku n gu n ya viru s : A
s t u d y of 88 a d u lt p a t ie n t s on re u n ion is la n d . Clin Infect Dis 2008 ;47 :469 –475 .
20. Tin gle AJ, Alle n M , Pe t t y RE. Ru be lla -a s s ocia t e d a rt h rit is . I. Com p a ra t ive s t u dy of join t m a n ife s t a t io n s
a s s ocia t e d w it h n a t u ra l ru be lla in fe ct ion a n d RA 27/3 ru be lla im m u n is a t ion . A nn Rheum atic Dis 1986 ;
45 :110 –114 .
21. Yt t e rbe rg SR. Vira l a rt h rit is . Curr Opin Rheum atol 1999 ;11 :275 –280 .
22. Ge ie r DA, Ge ie r MR. Ru be lla va ccin e a n d a rt h rit ic a d ve rs e re a ct io n s : An a n a lys is of t h e va ccin e a d ve rs e
eve n t s rep ort in g s ys t e m (VAERS) d a t a ba s e from 1991 t h rou gh 1998 . Clin Exp Rheum atol 2001 ;19 :724 –726 .
23. How son CP, Ka tz M, Joh n ston RB, Jr. Ch ron ic a rth ritis a fter ru bella va ccin a tion . Clin Infect Dis 1992 ;15 :307 –312 .
24. Wa lk e r UA, Tyn d a ll A, Da ike le r T. Rh e u m a t ic con d it ion s in h u m a n im m u n od e cie n cy viru s in fe ct ion .
Rheum atology 2008 ;47 :952 –959 .
 Ch a p te r 25 Vira l Art h rit is 265

25. Te h ra n za d e h J, Te r-Oga n e s ya n RR, St e in ba ch LS. Mu s cu los ke le t a l d is ord e rs a s s ocia t e d w it h HIV in fe ct ion

a n d AIDS. Pa rt II: Non -in fe ct iou s m u s cu los ke le t a l con d it ion s . Skeletal Radiol 2004 ;33 :311 –320 .
26. Allrogge n A, Fre s e A, Ra h m a n n A. HIV a s s ocia t e d a rt h rit is : Ca s e rep ort a n d review of t h e lit e ra t u re . Eur
J Med Res 2005 ;10 :305 –308 .
27. Ngu ye n BY, Reve ille JD. Rh e u m a t ic m a n ife s t a t ion s a s s ocia t e d w it h HIV in t h e h igh ly a ct ive a n t ire t rovira l
t h e ra py e ra . Curr Opin Rheum atol 2009 ;21 :404 –410 .
28. Cen ters for Disea se Con trol a n d Preven tion . Revised recom m en d a tion s for HIV testin g of a d u lts, a d olescen ts
a n d p regn a n t w om en in h ea lth -ca re settin gs . MMW R 2006 ;55 (No. RR-14 ):1 –17 . h ttp ://w w w.cd c.gov/m m w r/
p review /m m w rh tm l/rr5514a 1.h tm . Accessed October 27, 2010.

s
i
t
i
r
h
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S
SECTION
6

Specia l Dia gnostic a nd

Thera peutic Conditions

Chapter 26 Us e of th e Laboratory in
Diagn os in g Rh e u m atic
Dis orde rs
Terry Shaneyfelt and Gustav o R. Heudebert

Chapter 27 Te ch n iqu e s of
Arth roce n te s is
Dennis W. Boulw are

Chapter 28 Mon itorin g of Patie n ts on

An tirh e u m atic Th e rapy
W. W inn Chatham

267
CHAPTER
26 Use of the La bora tory
in Dia gnosing
Rheuma tic Disorders
Terry Shaneyfelt and Gustav o R. Heudebert

y
p
As clin icia n s , w e co m b in e clin ica l

a
r
Patient 1: An 80-year-old retire d s kills w it h in form a t ion from d ia gn os -

e
h
T
carpenter presents for e valuation t ic t e s t s t o e s t a blis h a ccu ra t e d ia g-

d
n os e s s o t h a t w e m ay in it ia t e a p p ro-

n
of diffuse joint pain. He re ports

a
p ria t e t re a t m e n t for ou r p a t ie n t s . In

s
gradual onset and progression of

i
t h is ch a p t e r, w e focu s on p roba bilis t ic

s
o
d ia gn os t ic re a s on in g in w h ich p re t e s t

n
pain in the right rst m etacar-

g
p roba bilit y is in form e d by d ia gn os t ic

a
pophalangeal (MCP) joint and

i
D
t e s t in g re s u lt in g in p os t t e s t p roba bili-
bilateral proxim al inte rphalangeal

6
t ie s . We d o n ot focu s on t h e com m on ly

N
(PIP) and distal interphalangeal

O
u s e d d ia gn o s t ic m e t h od of p a t t e rn

I
T
(DIP) joints over the past 5 years. re cogn it ion . We re cogn ize t h a t bot h

C
E
d ia gn os t ic m e t h od s a re a p p rop ria t e

He also has pain in both kne es. He has som e stiffness in all the
affected joints, w hich lasts approxim ate ly 15 to 30 m inute s each
m orning. Pain is w orse w ith activity. He denies any sw elling, rash-
es, fe vers, or other joint involvem ent. Physical exam in ation of the
hands re veals hard enlarge m e nt of the second through fourth
DIP and PIP joints, and painful range of m otion of the right rst
MCP joint. No synovitis is detected. Knee e xam ination re veals
cre pitance w ith preserved range of m otion and no joint effusion.
Pat ie n t 2: A 25-ye ar-o ld f e m ale p re se n t s f o r e valu at io n
o f f at ig u e , m yalg ias, an d in t e rm it t e n t h an d p ain . Sh e re p o rt s
t h at t h e p ain t e n d s t o “m o ve aro u n d ” b o t h t h e h an d s an d is
m o d e rat e in se ve rit y an d can re so lve w it h in 24 h o u rs. On
f u rt h e r q u e st io n in g , sh e re p o rt s an e ryt h e m at o u s rash o n h e r
ch e e k s af t e r w o rk in g o u t in t h e su n a f e w w e e k s e arlie r, b u t it
re so lve d an d h as n o t re cu rre d . Sh e also re p o rt s a sh o rt -live d
e p iso d e o f p le u rit ic ch e st p ain a m o n t h e arlie r. Ph ysical e xam i-
n at io n re ve als m ild p ain w it h ran g e o f m o t io n in se ve ral PIP
jo in t s an d h e r le f t w rist . No e ff u sio n s o r d e f o rm it ie s are se e n .
No p le u ral o r card iac ru b s are h e ard o n au scu lt at io n an d n o
rash e s are n o t e d o n sk in e xam in at io n .
S
a n d com p lem en ta ry. Probabilistic d iag-
n os t ic re a s on in g is u s e fu l e s p e cia lly
for m ore ch a lle n gin g or le s s fa m ilia r
clin ica l s it u a t ion s w h e re p a t t e rn re c-
ogn ition fa ils.
Th e ge n e ra t ion of a d iffe re n t ia l
d iagn osis relies on u s, h avin g both gen -
e ra l m e d ica l kn ow le d ge a n d d is e a s e
p reva le n ce kn ow le d ge. Key fe a t u re s
d e rive d from t h e h is t ory, in con ju n c-
t ion w it h p h ys ica l exa m in a t ion n d -
in gs , s e r ve t o e it h e r in cre a s e o r
d ecrea se th e likelih ood of ea ch d iagn o-
sis u n d er con sid era tion in a p rocess of
h yp o t h e s is t e s t in g. In e s t a blis h in g
h yp o t h e s e s , it is im p o r t a n t t h a t w e
a ccu ra t e ly a s s e s s t h e pretest probabil-
ity of t h e d ia gn os e s w e a re con s id e r-
in g s o t h a t s u b s e q u e n t t e s t in g ca n
h e lp u s t o r u le in o r ru le o u t t h o s e
p os s ibilit ie s . Pre t e s t p roba bilit y is t h e
ch a n ce or p roba bilit y t h a t t h e p a t ie n t
u n d e r co n s id e ra t io n h a s t h e t a rge t
d is ord e r be fore a n y t e s t in g is ca rrie d

269
 270 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

ou t . It ca n be d e t e rm in e d in s eve ra l w a ys . Va li-
Test threshold Treatment threshold
d a t e d clin ica l p re d ict ion ru le s a re d e cis ion a id s
t h a t com bin e e le m e n t s of h is t ory, p h ys ica l e xa m -
Diagnosis Diagnosis Diagnosis
excluded uncertain established in a t ion , a n d ba s ic d ia gn os t ic or la bora t ory t e s t in g
t o a ccu ra t e ly e s t im a t e p re t e s t p roba bilit y. Dis e a s e
Test further p roba bilit y s t u d ie s , in w h ich rep re s e n t a t ive s a m -
p le s of p a t ie n t s w it h ce rt a in s ym p t om s (e.g., s yn -
0 A B 1.0 cop e ) u n d e rgo e xt e n s ive d ia gn os t ic w ork-u p s a n d
Probability of diagnosis re p ort t h e fre q u e n cy of t h e u n d e rlyin g d is ord e rs
t h a t ca u s e d t h e p a t ie n t s ’ illn e s s e s , ca n p rovid e
ve ry a ccu ra t e e s t im a t e s of p re t e s t p roba bilit y bu t
Disease Present Disease Absent
a re a va ila ble for few d is ord e rs . Mos t com m on ly,
a n d le a s t a ccu ra t e, clin icia n s u s e clin ica l in t u it ion
a n d e xp e rie n ce t o gu e s s a t t h e p re t e s t p roba bilit y.
True Positive False Positive How eve r, t h e re a re few w e ll-va lid a t e d clin ica l p re -
Test Positive d ict ion ru le s in ge n e ra l a s w e ll a s s p e ci ca lly in
(a) (b) t h e a re a of rh e u m a t ologic d is ord e rs ; a s s u ch it is
of cru cia l im p ort a n ce t o u n d e rs t a n d t h e in t e rp lay
be t w e e n re s u lt s of d ia gn os t ic t e s t s a n d t h e clin i-
S
E
False Negative True Negative
cia n in t u it io n o f t h e lik e lih o o d o f t h e d ia gn o s is
C
Test Negative
T
for w h ich t h e t e s t is be in g ord e re d . Sin ce p re t e s t
I
(c) (d)
O
p roba bilit y in form s p os t t e s t p roba bilit y, clin icia n s
N
6
m u s t begin w it h a n a ccu ra t e p re t e s t p roba bilit y.
D
Th e con s e q u e n ce s of in a ccu ra t e p re t e s t p roba bil-
i
a
g
Figure 26.1 Test a nd trea tment thresholds. it y a s s e s s m e n t in clu d e p o o r s e le ct io n o f t e s t s ,
n
p o o r in t e r p re t a t io n o f re s u lt s , a n d u lt im a t e ly
o
s
i
d ia gn os t ic e rror.
s
a
On ce p re t e s t p roba bilit y is d e t e rm in e d , clin icia n s m u s t d e cid e w h e t h e r t o
n
d
in it ia t e t re a t m e n t or t o p e rform fu rt h e r d ia gn os t ic t e s t in g. Th e t re a t m e n t t h re s h -
T
h
old is t h e t h re s h old a bove w h ich t h e p roba bilit y of d is e a s e is s o h igh t h a t fu rt h e r
e
r
t e s t in g is u n n e ce s s a ry a n d t rea t m e n t ca n be in it ia t e d . Th e t e s t in g t h re s h old is
a
p
t h e t h re s h old be low w h ich th e p roba bilit y of d is e a se is s o low t h a t fu rt h e r te s t in g
y
is u n n e ces s a ry a n d t h e d ia gn os is is con s id e re d exclu d e d (Fig. 26.1 ). Dia gn os t ic
t e s t in g is on ly u s e fu l t o in form in t e rm e d ia t e p roba bilit ie s be t w e e n t h e t e s t in g
a n d t re a t m e n t t h re s h old s . Th e s e t h re s h old s va ry on t h e ba s is of t h e d is e a s e
p rogn os is u n d e r con s id e ra t ion , t h e p rop e rt ie s of t h e d ia gn os t ic t e s t s , a n d t h e
n a t u re o f t h e t re a t m e n t . Th e s a fe r t h e t e s t in g s t ra t e gy, t h e m o re s e r iou s
t h e con d it ion if le ft u n d ia gn os e d , a n d t h e m ore e ffe ct ive a n d s a fe t h e ava ila ble
t re a t m e n t , t h e low e r t h e t e s t t h re s h old . For t h e t re a t m e n t t h re s h old , t h e m ore
be n ign t h e p rogn os is of t h e illn e s s a n d t h e h igh e r t h e m orbid it y a s s ocia t e d w it h
t h e ra p y, t h e h igh e r w e w ou ld p la ce t h e t h re s h old . For e xa m p le, ou r t e s t in g
t h re s h old w ou ld be low if a clin icia n s u s p e ct s d e ep ve n ou s t h rom bos is a s t h e
d u p lex u lt ra s on ogra p h y is a t e s t t h a t is bot h s a fe a n d e a s ily ava ila ble ; on t h e
ot h e r h a n d , ou r t re a t m e n t t h res h old w ou ld be re la t ive ly h igh a s a n t icoa gu la t ion ,
e s p e cia lly w h e n con s id e rin g s h ort - a n d lon g-t e rm cou rs e s of t h e ra py, is p ot e n -
t ia lly d a n ge rou s for a p a t ie n t .
Th e rs t p a t ie n t like ly h a s os t e oa rt h rit is . No va lid a t e d clin ica l p re d ict ion
ru le s for t h e d ia gn os is of os t e oa rt h rit is of t h e kn e e or h a n d e xis t , n or a n y d is -
e a s e p roba bilit y s t u d y h a s be e n con d u ct e d . Clin ica l in t u it ion w ou ld p la ce t h e
p re t e s t p roba bilit y of os t e oa rt h rit is a t a rou n d 85% t o 90%. For m os t clin icia n s ,
t h e t re a t m e n t t h re s h old t o in it ia t e a ce t a m in op h e n in t h is p a t ie n t is fa irly low
a n d cou ld be in it ia t e d w it h ou t fu rt h e r t e s t in g (a s w e a re fa irly con d e n t h e h a s
os t e oa rt h rit is a n d t h e con s e q u e n ce s of m od e ra t e d os e s of a ce t a m in op h e n a re
low ). Th e a lt e rn a t ive w ou ld be t o ord e r h a n d lm s , w h ich w e s u s p e ct w ou ld be
d on e t o ru le ou t ot h e r con d it ion s (i.e., rh e u m a t oid a rt h rit is ), a lt h ou gh t h e clin -
ica l s ce n a rio w o u ld m a k e t h is d ia gn os is h igh ly u n like ly ( 5%). Of in t e re s t , a
re la t ive ly n on d ia gn os t ic ra d iologic s t u d y like ly w ou ld n ot s t op m os t clin icia n s

Sensitivity = TP / TP + FN = a / a+c
Specificity = TN / TN + FP = d / d+b
PPV = TP / TP + FP = a / a+b
NPV= TN / TN + FN = d / d+c
Figure 26.2 2 × 2 ta ble.
KEY POINT 1
• Se n sit ive t e st s, w h e n
n e g a t ive , ru le o u t d ise a se
(Sn No u t ) w h e n t h e p re t e st
p ro b a b ilit y is lo w.
• Sp e ci c t e st s, w h e n p osit ive ,
ru le in d ise a se (Sp Pin ) w h e n
t h e p re t e st p ro b a b ilit y is
h ig h .
Ch a p te r 26 Us e o f t h e La bora t ory in Dia gn os in g Rh e u m a t ic Dis ord e rs 271
t o in it ia t e a ce t a m in op h e n t h e ra p y; in ot h e r w ord s , ord e rin g a h a n d lm h a d n o
be a rin g on ou r t re a t m e n t d e cis ion bu t p e rh a p s m a d e u s fe e l be t t e r rega rd in g
ot h e r d ia gn os t ic p os s ibilit ie s . Th e d if cu lt q u e s t ion t h e n be com e s if t h e cos t or
in con ve n ie n ce of t h e h a n d lm is w ort h e xclu d in g h igh ly u n like ly d ia gn os e s .
Pa t ie n t 2, on t h e ot h e r h a n d , like ly h a s s ys t e m ic lu p u s e ryt h e m a t os u s (SLE).
No va lid a t e d clin ica l p re d ict ion ru le s t o d e t e rm in e t h e p re t e s t p roba bilit y of
SLE h a ve b e e n p u blis h e d . On e p o p u la t ion -ba s e d s cre e n in g s t u d y (1 ) o f SLE
rep ort e d a p reva le n ce of 200 ca s e s p e r 100,000 w om e n (18 t o 65 ye a rs of a ge ) in
En gla n d , w h e re a s a n ot h e r review e s t im a t e d t h e ove ra ll U.S. p reva le n ce of d e -
n it e SLE p lu s in com p le t e SLE (d is e a s e m e e t in g on ly s om e d ia gn os t ic re q u ire -
m e n t s for SLE) t o be 40 t o 50 ca s e s p e r 100,000 p e rs on s (2 ). Pop u la t ion p reva -
le n ce s t u d ie s s u ch a s t h e s e t w o ca n give m is le a d in g e s t im a t e s o f p re t e s t
p roba bilit y be ca u s e t h ey h a ve t h e w ron g d e n om in a t or, n a m e ly bot h h e a lt h y
a n d d is e a s e d p e rs on s , bot h m e n a n d w om e n . W h a t w e w a n t t o kn ow is w h a t
is t h e p rop ort ion of a ll you n g w om e n p re s e n t in g w it h a rt h rit is , m a la r ra s h , a n d
p os s ible p le u rit is , s im ila r t o ou r s e con d p a t ie n t , w h o a re u lt im a t e ly d ia gn os e d
w it h SLE. Aga in w e h ave t o re ly on clin ica l in t u it ion a n d e s t im a t e t h is p a t ie n t ’s
p re t e s t p roba bilit y t o be 50%. Th e t re a t m e n t t h re s h old t o in it ia t e im m u n os u p -
p re s s ive t h e ra p y in t h is ca s e w ou ld be fa irly h igh (i.e., t h e clin icia n w ou ld w a n t
y
p
t o be ce rt a in of or ru le in t h e d ia gn os is of SLE). Th e con s e q u e n ce s of u n d ia g-
a
r
e
n os e d SLE a re gre a t , m a kin g t h e t e s t in g t h re s h old fa irly low. Th u s fu rt h e r t e s t in g
h
T
for SLE is in d ica t e d in p a t ie n t 2 p rior t o in it ia t in g d is e a s e -s p e ci c t h e ra py.
d
n
a
s
i
s
Cho o sing a Dia g no stic Te st
o
n
g
a
Th e m a in d e t e rm in a n t of d ia gn os t ic t e s t ch oice (a s s u m in g m ore t h a n on e t e s t
i
D
is a va ila ble ) is t h e in t e n d e d role of t h e t e s t —w h e t h e r t h e clin icia n w a n t s t o ru le
6
in or ru le ou t a p a rt icu la r d is e a s e. Pre t e s t p roba bilit y in fo rm s t h is d e cis io n .
N
O
W h e n p re t e s t p roba bilit y is low, t h e goa l of d ia gn os t ic t e s t in g s h ou ld be t o ru le
I
T
ou t d is e a s e. Wit h h igh p re t e s t p roba bilit ie s t h e goa l is t o ru le in d is e a s e. On ce
C
E
t h e d e cis ion t o ru le in or ru le ou t d is e a s e is m a d e, clin icia n s t h e n ch oos e a m on g
S
d ia gn os t ic t e s t s on t h e ba s is of t h e ir t e s t p rop e rt ie s (i.e., s e n s it ivit y, s p e ci cit y,
a n d like lih ood ra t ios ).
Sensitiv ity of a d ia gn os t ic t e s t is t h e p rop ort ion of p e op le w it h d is e a s e w h o
t e s t p os it ive. (“PID,” p os it ive in d is e a s e, is a m n e m on ic t o h e lp re m e m be r t h is
a s s ocia t ion .) It re e ct s t h e true positiv e rate of a t e s t (Fig. 26.2 ). Te s t s w it h 100%
s e n s it ivit y d e t e ct eve ry s in gle p e rs on w it h d is e a s e. Te s t s w it h 80% s e n s it ivit y
m is s 20% of p e rs on s w it h d is e a s e, re s u lt in g in a 20% fa ls e n ega t ive ra t e. Se n s i-
t ivit y is ca lcu la t e d by d ivid in g t h e t ru e p os it ive ra t e by t h e t ru e p os it ive p lu s
fa ls e n ega t ive ra t e s . Se n s it ive t e s t s a re m os t u s e fu l t o ru le ou t d is e a s e w h e n
p re t e s t p roba bilit y is low (i.e., u s in g fe ca l occu lt t e s t in g t o s cre e n for colore ct a l
ca n ce r in ave ra ge -ris k in d ivid u a ls ).
Speci city of a d ia gn os t ic t e s t is t h e p rop o rt ion of p e op le w it h ou t d is e a s e
w h o t e s t n ega t ive. (“NIH,” n ega t ive in h e a lt h , is a m n e m on ic t o h e lp re m e m be r
t h is a s s ocia t ion .) It re e ct s t h e true negativ e rate of a t e s t (Fig. 26.2 ). Te s t s w it h
100% s p e ci cit y h ave n o fa ls e p os it ive s a n d a re n ega t ive w h e n d is e a s e is a bs e n t .
Te s t s w it h 80% s p e ci cit y a re fa ls e ly p os it ive 20% of t h e t im e. Sp e ci cit y is
ca lcu la t e d by d ivid in g t h e t ru e n ega t ive ra t e by t h e t ru e n e ga t ive p lu s fa ls e
p os it ive ra t e s . Sp e ci c t e s t s a re u s e d t o ru le in d is e a s e. For e xa m p le, colon os -
co p y h a s a h igh e r s p e ci cit y t h a n fe ca l o ccu lt t e s t in g a n d w o u ld be u s e d t o
follow u p p os it ive fe ca l occu lt t e s t in g.
Pa t ie n t 1 h a s s u ch a low p re t e s t p roba bilit y of SLE t h a t fu rt h e r t e s t in g for
SLE is n ot u s e fu l (i.e., p re t e s t p roba bilit y is be low t h e t e s t t h re s h old ). Pa t ie n t 2,
on t h e ot h e r h a n d , h a s a fa irly h igh p re t e s t p roba bilit y of h a vin g SLE. In t h is
ca s e w e w a n t t o r u le in SLE a n d w o u ld ch o o s e t h e t e s t w it h t h e h igh e s t
s p e ci cit y. Ta ble 26.1 s h ow s t h e t e s t p ro p e rt ie s a n d a s s o cia t io n s o f d iffe re n t
272 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s
Table 26.1 Sensit ivit y and Speci cit y of Different Ant inuclear Ant ibodies in Syst emic
Lupus Eryt hemat osus
ds-DNA (%) ss-DNA (%) HISTONE (%) SMITH (%)
Se nsitivity 70
Spe ci city 95
ADVANCED TOPIC 1
Likelihood ratios summarize
both sensitivity and speci city
into a single number. Hence
they too are useful for choos-
ing a test. Readers wanting
more information on likeli-
hood ratios are referred to the
Duke University EBM Web site
(http://www.mclibrary.duke.
edu/subject/ebm/ratios.html)
and to McGee (3 ).
KEY POINT 2
• Further testing should not
be done in patients with low
p re t e st p ro b a b ilit y u n le ss
d o n e t o e xclu d e se rio u s
a n d t re a t a b le co n d it io n
(i.e ., ca n ce r scre e n in g )
w it h a h ig h se n sit ivit y t e st .
Ot h e rw ise a p o sit ive t e st
re su lt is like ly t o b e fa lse
positive and hence
misleading.
• Fu rt h e r t e st in g sh o u ld n o t
b e d o n e in p a t ie n t s w it h
h ig h p re t e st p ro b a b ilit y
u n le ss t h e t h e ra p y t o b e
in st it u t e d is risky t o t h e
patie n t (i.e ., ch e m ot he ra p y).
Ot h e rw ise a n e g a t ive t e st
re su lt w o u ld like ly b e a
fa lse n e g a t ive a n d h e n ce
m isle a d in g .
ANTIBODY
RIBONUCLEAR
PROTEIN (%) RO (%) LA (%)
80 30–80 30 27 25–35 15
50 96 82 87–94
a n t in u cle a r a n tibod ie s w it h SLE. Clin icia n s sh ou ld ch oos e e it h er a n t i-d s DNA or
a n t i-SM a n tibody t es t s a s t h ey h ave t h e h igh e s t s p eci city, a n d if p os it ive, w ill
in crea s e t h e p os t te s t p roba bilit y of SLE in t h is p a tie n t . Of in t e re s t, m os t clin icia n s
w ou ld a ls o a p p rop ria t ely ord e r a n a n t in u cle a r a n t ibody (ANA) t e s t for t h is p a t ie n t ,
w it h th e t h ou gh t of “ru lin g ou t ” th e p os s ibilit y of SLE. Un fort u n a t e ly, if t h e t e s t
re t u rn e d n ega t ive, t h is d oe s n ot d e cre a s e t h e p roba bilit y of d is ea s e e n ou gh t o
exclu d e t h e d ia gn os is in t h e s e t t in g of h igh clin ica l s u s p icion .
Ma n y t e s t s h a ve m u lt ip le cu t off p oin t s t h a t ca n be u s e d t o d e t e rm in e p os -
it ivit y (i.e., t h ey a re n ot ju s t p os it ive or n ega t ive ). For e xa m p le, ANA t e s t s a re
p os it ive a t a va rie t y of t it e rs ( 1:40, 1:320, e t c.). Diffe re n t p os it ive cu t off p oin t s
a ffe ct s e n s it ivit y a n d s p e ci cit y o f d ia gn o s t ic t e s t s . In ge n e ra l, low e rin g t h e
p os it ivit y crit e rion in cre a s e s s e n s it ivit y (t e s t s n d s m ore d is e a s e ) w h ile low e r-
in g s p e ci cit y (m ore fa ls e p os it ive s ). Con ve rs e ly, ra is in g t h e p os it ivit y crit e rion
low e rs s e n s it ivit y (t e s t d e t e ct s le s s d is e a s e ) b u t ra is e s s p e ci cit y (le s s fa ls e
p os it ive s ). For e xa m p le, re q u irin g a t re a d m ill s t re s s t e s t t o be p os it ive w it h on ly
0.5-m m ST e leva t ion w ou ld d e t e ct m os t eve ry bod y w it h coron a ry a rt e ry d is -
e a s e (CAD) a t a s ign i ca n t ris k if e rron e ou s ly la be lin g m a n y p a t ie n t s w it h ou t
CAD w it h t h is d ia gn os is ; t h e op p o s it e e ffe ct w o u ld be a ch ieve d by re q u irin g
4-m m ST e leva t ion a s t h e d ia gn os t ic crit e rion for p os it ivit y a s in t h is s ce n a rio
w e w ou ld m is s m a n y p a t ie n t s w it h CAD bu t n ot la be l a s d is e a s e d t h os e w it h -
ou t CAD. Th is in t e re s t in g p a ra d ox is kn ow n a s t h e t ra d e -off p h e n om e n on w h e n
ch a n gin g t h e crit e rion t o in t e rp re t a t e s t a s p os it ive or n ega t ive.
Inte rpre ting Dia g no stic Te st Re sults
Th e role of d ia gn os t ic t e s t in g is t o low e r or in cre a s e in t e rm e d ia t e p re t e s t p rob-
a bilit ie s . It is im p ort a n t t o re m e m be r t h a t n ot eve ry p os it ive t e s t in d ica t e s t h e
p re s e n ce of d is e a s e , n or d oe s eve ry n ega t ive t e s t in d ica t e d is e a s e is a bs e n t .
Mos t t e s t s yie ld a t le a s t s om e fa ls e p os it ive a n d fa ls e n ega t ive re s u lt s (u n le s s
t h e t e s t is bot h 100% s e n s it ive a n d s p e ci c). A p os it ive t e s t re s u lt is m ore like ly
t o be fa ls e ly p os it ive w h e n t h e p re t e s t p roba bilit y w a s low. Likew is e, a n ega t ive
t e s t re s u lt is m ore like ly t o be fa ls e n ega t ive w h e n t h e p re t e s t p roba bilit y w a s
h igh (s e e e xa m p le s be low ).
Th e re a re t w o m e t h od s t o d e t e rm in e p os t t e s t p roba bilit y p re d ict ive va lu e
m e t h o d a n d lik e lih o o d ra t io m e t h od ; in t h e in t e re s t of b revit y a n d cla r it y,
w e d is cu s s on ly t h e form e r h e re. Mos t d ia gn os t ic t e s t s t u d y m a n u s crip t s re p ort
t h e p re d ict ive va lu e of t h e d ia gn os t ic t e s t u n d e r s t u d y. Positiv e predictiv e value is
t h e p roba bilit y t h a t a p e rs on w it h a p os it ive t e s t re s u lt h a s d is e a s e. Negativ e
predictive value is t h e p roba bilit y t h a t a p e rs on w it h a n ega t ive t e s t re s u lt d oe s
n ot h ave d is e a s e. Th e s e ca n be ca lcu la t e d from a 2 × 2 t a ble (s e e Fig. 26.2 ) or
u s in g on lin e EBM ca lcu la t ors (h t t p ://kt cle a rin gh ou s e.ca /cebm /t oolbox/s t a t s ca lc).
Clin icia n s m u s t be ca u t iou s in u s in g p re d ict ive va lu e s rep ort e d in d ia gn os t ic t e s t
s t u dy m a n u s crip t s be ca u s e p re d ict ive va lu e s a re a ffe ct e d by p reva le n ce or p re -
t e s t p roba bilit y of d is e a s e. Un le s s you r p a t ie n t h a s t h e s a m e p re t e s t p roba bilit y
of d is e a s e a s t h os e in t h e s t u d y, you ca n n ot u s e t h e p re d ict ive va lu e rep ort e d
 Ch a p te r 26 Us e o f t h e La bora t ory in Dia gn os in g Rh e u m a t ic Dis ord e rs 273

in t h e m a n u s crip t . It m u s t be re ca lcu la t e d a d ju s t in g for you r p a t ie n t ’s p re t e s t

ADVANCED TOPIC 2
• Re a d e rs w a n t in g m o re
in fo rm a t io n o n a d ju st in g
p re d ict ive va lu e s re p o rt e d
in d ia g n o st ic t e st st u d ie s
a re re fe rre d t o Alt m a n a n d
Bla n d (6 ).
• Alt e rn a t ive ly, like lih o o d
ra t io s ca n b e u se d t o ca lcu -
la t e p o st t e st p ro b a b ilit y
(3,4 ,5 ).
• Se ve ra l d ia g n o st ic t e st
ca lcu la t o rs a re a va ila b le
o n t h e In t e rn e t t o a id clin i-
cia n s in t h e se ca lcu la t io n s.
Ep o cra t e s (w w w.e p o cra t e s.
co m ) is a p o p u la r o n lin e
d rug re fe ren ce tha t contains
se ve ra l clin ica l a n d EBM
p roba bilit y (w h ich is beyon d t h e s cop e of t h is ch a p t e r; 4 ,5 )
Summa ry
Th e rs t s t ep in m a kin g a n a ccu ra t e d ia gn os is is t o in t egra t e evid e n ce from ou r
kn ow le d ge of d is e a s e a n d d is e a s e p reva le n ce w it h a p a t ie n t ’s h is t ory a n d p h ys -
ica l e x a m in a t io n t o fo r m u la t e a d iffe re n t ia l d ia gn o s is a n d e s t im a t e p re t e s t
p roba bilit y. Seve ra l re s ou rce s ca n be u s e d t o h e lp gu id e ou r e s t im a t ion of p re -
t e s t p roba bilit y, s u ch a s clin ica l p re d ict ion ru le s . Clin icia n s s h ou ld be w a ry of
ord e rin g t e s t s w h e n t h e p re t e s t p roba bilit y of d is e a s e is h igh or low. Te s t s a re
u n like ly t o a lt e r d is e a s e p ro ba bilit y a n d o n ly co n fu s e t h e s it u a t io n a s u n e x-
p e ct e d re s u lt s a re u s u a lly fa ls e p os it ive s or fa ls e n ega t ive s .
ICD9
796.4 Finding s, (ab n o rm al), w it h o u t d iag n o sis (e xam in at io n )

y
ca lcu la t o rs. Th e Ce n t re fo r (lab o rat o ry t e st s)

p
Evidence-Based Medicine also 795.79 an t ib o d y t it e rs, e le vat e d

a
r
h a s se ve ra l EBM ca lcu la t o rs

e
795.79 an t ig e n -an t ib o d y re act io n

h
T
(h t t p ://kt cle a rin g h o u se .ca /
cebm/practise/ca/calculators). 790.95 C-re act ive p ro t e in (CRP)

d
n
791.9 cryst als, u rin e

a
790.1 se d im e n t at io n rat e , e le vat e d

s
i
s
795.79 sk in t e st , p o sit ive

o
n
g
a
i
D
Re fe re nce s

6
N
O
1. Joh n s on AE, Gord o n C, Hobbs FD , e t a l. Un d ia gn os e d s ys t e m ic lu p u s e ryt h e m a t os u s in t h e com m u n it y.

I
T
Lancet 1996 ;347 :367 –369 .

C
2. Law re n ce RC, He lm ick CG, Arn e t t FC, e t a l. Es t im a t e s of t h e p reva le n ce of a rt h rit is a n d s e le ct e d m u s cu -

E
S
los ke le t a l d is ord e rs in t h e Un it e d St a t e s . A rthritis Rheum 1998 ;41 :778 –799 .
3. McGe e S. Sim p lifyin g like lih ood ra t ios . J Gen Intern Med 2002 ;17 :646 –649 .
4. Fa ga n TJ. Le t t e r: Nom ogra m for Baye s t h e o re m . N Engl J Med 1975 ;293 :257
5. Grim e s DA, Sch u lz KF. Re n in g clin ica l d ia gn os is w it h like lih ood ra t ios . Lancet 2005 ;365 :1500 –1505 .
6. Alt m a n DG, Bla n d JM . St a t is t ics n ot e s : Dia gn os t ic t e s t s 2: Pre d ict ive va lu e s . BMJ 1994 ;309 :102 .
 CHAPTER
27 Techniques of
Arthrocentesis
Dennis W. Boulw are

Con t ra in d ica t ion s t o a rt h roce n t e s is a re

A 52-ye ar-o ld m an w it h rh e u - r e la t ive a n d t yp ica lly r e la t e d t o t h e
m at o id art h rit is p re se n t s w it h p ot e n t ia l for ble e d in g a n d /or in fe ct ion .
S
Ca u t io n in p e r fo r m in g a r t h ro ce n t e s is
E
a 36-h o u r h ist o ry o f acu t e
C
s h o u ld b e e x e rcis e d in t h e fo llow in g
T
I
k n e e p ain w it h f e ve r af t e r a
O
clin ica l s e t t in gs :
N
w e e k o f m o d e rat e f e ve r an d 1. Infection of the ov erlying skin: Pa s s in g a
6
a p ro d u ct ive co u g h . His o ral
D
s t e rile n e e d le t h rou gh a n a re a of s kin
i
a
t e m p e rat u re is 39.6 °C, an d h is t h a t is in fe ct e d or ca n n ot be p rep p e d
g
n
t o re t a in t h e n e e d le ’s re a s on a ble s t e -
o
k n e e h as a larg e , w arm , t e n se
s
i
rilit y cre a t e s ris k of in t rod u cin g a n in -
s
e ff u sio n w it h lim it e d ran g e
a
fe ct ion in t o a join t . Are a s of obviou s
n
o f m o t io n se co n d ary t o p ain . His w h it e b lo o d ce ll co u n t is
d
or p ot e n t ia l in fe ct ion m u s t be avoid -
T
e d t o p re s e rve t h e s t e rilit y of t h e join t .
h
24,100 w it h m an y im m at u re p o lym o rp h o n u cle ar w h it e b lo o d
e
r
2. Bacterem ia: Perform in g a rt h rocen tesis
a
ce lls. Th e re is co n ce rn o f se p t ic art h rit is, an d h e re q u ire s
p
in th e clin ica l s ettin g of kn ow n ba c-
y
art h ro ce n t e sis f o r cu lt u re an d re lie f . terem ia s im ila rly in crea ses th e risk
A rt h ro ce n t e sis is a f re q u e n t p art o f t h e e valu at io n an d /o r of in trod u cin g a n in fection in to t h e
t re at m e n t o f a p at ie n t w it h a m u scu lo sk e le t al co n d it io n . Th is join t. Clin ica l ju d gm en t m u st be exer-
ch ap t e r f o cu se s o n t h e t e ch n iq u e f o r acce ssin g ce rt ain jo in t s cised on th e rela tive ben e t a n d ris k
of p erform in g th e a rt h rocen tes is for
w ith a sterile ne e dle w it h speci c indications for art hroce nt esis d ia gn ost ic p u rp oses in d ocu m en tin g a
an d t re at m e n t re co m m e n d at io n s lo cat e d in t h e sp e ci c p olym icrobia l in fection or t h era p eu t ic
ch ap t e rs re g ard in g t h at m u scu lo sk e le t al co n d it io n . ben e t of t h e rem ova l of syn ovia l u id .
3. Bleeding diathesis: Pa t ie n t s o n a n t i-
co a gu la t ion , w it h t h rom bocyt op e n ia ,
h e m op h ilia , or ot h e r ca u s e s le a d in g t o a ble e d in g d ia t h e s is , a re a t ris k of
h e m a rt h ros is from t h e a rt h roce n t e s is . Com p lica t ion s ca n be avoid e d by u s -
in g t h e s m a lle s t n e e d le ga u ge fe a s ible a n d p rovid in g a d e q u a t e h e m os t a s is
CLINICAL POINTS
a ft e r t h e p roce d u re. In re a lit y, w e a re n ot h e s it a n t t o p e rform ve n ip u n ct u re
• Kn o w le d g e o f lo ca l in t h e s e s e t t in gs w it h a d e q u a t e a t t e n t ion t o h e m os t a s is p os t p roce d u re, s o
a n a t o m y is e sse n t ia l.
w e s h ou ld h ave a s im ila r a t t it u d e t ow a rd a rt h roce n t e s is in t h e s e s e t t in gs .
• We ig h b e n e t s a n d 4. Prosthetic joints: Art h roce n t e s is of a p ros t h e t ic join t ca n be m ore ch a lle n gin g
risks o f a rt h ro ce n t e sis in be ca u s e of s ca rrin g from t h e s u rgica l p roce d u re a n d t h e ris k of in fe ct ion
b a ct e re m ia a n d b le e d in g
s in ce t h e p ros t h e s is ca n a ct a s a fore ign bod y. As p ira t ion of t h e p ros t h e t ic
d ia t h e sis.
join t is p os s ible, bu t be t t e r d e fe rre d t o t h e ort h op e d ic s u rge on or in t e rve n -
• Ha ve a ll n e e d e d e q u ip m e n t t ion a l ra d iologis t u n d e r im a gin g.
(syrin g e , n e e d le , g a u g e ,
5. Uncooperativ e patient: Art h roce n t e s is re q u ire s s ign i ca n t coop e ra t ion from
Ba n d -Aid , e t c.) re a d ily
a cce ssib le t o t h e o p e ra t o r. t h e p a t ie n t in p os it ion in g a n d s h ou ld be p e rform e d on ly on p a t ie n t s w h o
ca n be fu lly coop e ra t ive.

274
 Ch a p te r 27 Te ch n iq u e s o f Art h roce n t e s is 275

PATIENT ASSESSMENT Table 27.1 Necessary Equipment

• Pre se n ce o f syst e m ic o r
lo ca l in fe ct io n .
• Evid e n ce o f lo ca l ra sh
o ve rlyin g in je ct io n sit e .
• Co n sid e r b le e d in g
d ia t h e sis.
• Disp o sa b le g lo ve s
• Po vid o n e –io d in e a n t ise p t ic so lu t io n
• Alco h o l w ip e s
• Syrin g e o r m u lt ip le syrin g e s if d ra in in g la rg e e ffu sio n s
• Ap p ro p ria t e n e e d le
• Et h yl ch lo rid e sp ra y (o p t io n a l)
• He m o st a t t o a ssist in ch a n g in g syrin g e s d u rin g t h e p ro ce d u re
• Ga u ze fo r p o st p ro ce d u re h e m o st a sis
• Ba n d a g e

Equipme nt
Ap p ro p ria t e e q u ip m e n t (s e e Ta ble 27.1 ) s h o u ld b e a s s e m ble d a t t h e b e d s id e

y
p rior t o t h e p roce d u re a n d e a s ily a cce s s ible t o t h e op e ra t or d u rin g t h e p roce -

p
a
r
d u re , w it h o u t t h e op e ra t or ch a n gin g p os it io n . An a s s is t a n t is op t ion a l a n d

e
h
d e p e n d e n t on t h e op e ra t or, bu t h e or s h e w ill be h e lp fu l if t h e re is con ce rn of

T
d
p a t ie n t coop e ra t io n or a la rge r e ffu s ion is t o be d ra in e d re q u irin g ch a n gin g

n
s yrin ge s .

a
s
i
s
o
n
Te chnique

g
a
i
D
Aft e r s e le ct in g a n a p p rop ria t e e n t ry s it e, t h e e n t ry s it e ca n be m a rke d u s in g a

6
ba ll-p oin t p e n w it h t h e p e n t ip re t ra ct e d . Th e p e n ’s a p e rt u re ca n be p re s s u re d

N
O
t o t h e s it e t o le ave a n im p re s s ion of t h e s e le ct e d e n t ry s it e be fore cle a n s in g t h e

I
T
C
a re a . Th e s e le ct e d e n t ry p o in t is cle a n s e d a p p ro p r ia t e ly w it h a n a n t is e p t ic

E
s olu t ion follow e d by re m ova l of t h e a n t is e p t ic s olu t ion u s in g t h e a lcoh ol w ip e s .

S
Aft e r cle a n s in g t h e a re a , ca u t ion s h ou ld be e xe rcis e d t o a void con t a m in a t in g
t h e s it e by fu rt h e r p a lp a t ion w it h a n u n s t e rile glove d n ge r. If fu rt h e r p a lp a t ion
is d e s ire d , t h e n a s t e rile glove ca n be u s e d or a s t e rile 4 × 4 ga u ze ca n be p la ce d
ove r t h e a re a a n d p a lp a t ion d on e ove r t h e s t e rile ga u ze t o p re s e rve t h e s it e ’s
a n t is ep t ic con d it ion . Som e t op ica l a n e s t h e s ia is obt a in e d by s p ra yin g t h e s it e
w it h e t h yl ch lorid e u n t il t h e a re a “fros t s .” Alt e rn a t ive ly, a s m a ll a m ou n t of lid o-
ca in e ca n be in je ct e d s u bcu t a n e ou s ly in t o t h e p rop os e d in je ct ion a re a .
W h e n a d va n cin g t h e n e e d le in t o t h e join t cavit y, t h e p a t ie n t e xp e rie n ce s
d is com fort w h e n t h e n e e d le p a s s e s t h rou gh t h e s kin a n d a ga in w h e n it cros s e s
t h e s yn oviu m . Le s s d is com fort is e xp e rie n ce d w h e n t h e s kin a n d s yn oviu m is
cros s e d q u icke r a s op p os e d t o s low ly a n d d e libe ra t e ly. On ce t h e n e e d le is in t ro-
d u ce d in t o t h e join t ca vit y, u id s h ou ld ow e a s ily in t o t h e s yrin ge if u s in g a
n e e d le ga u ge of 20 or la rge r. If n o u id ca n be a s p ira t e d , or u id s t op s ow in g,
t h e m os t com m on ca u s e is t h a t s yn ovia l t is s u e or s olid m a t e ria l (clot , brin ,
ca rt ila ge fra gm e n t s , e t c.) w it h in t h e u id is obs t ru ct in g t h e n e e d le. Rot a t in g t h e
n e e d le o r in je ct in g ba ck a s m a ll a m ou n t o f t h e a s p ira t e d u id in t o t h e join t
ca vit y m ay re m ove t h e obs t ru ct ion . At t h a t p oin t . ge n t le n ega t ive p re s s u re ca n
be p la ce d a n d t h e u id m ay a s p ira t e. As t h e t ot a l e ffu s ion a p p roa ch e s com p le t e
d ra in a ge, t h e s yn ovia l lin in g be com e s clos e r t o t h e n e e d le t ip a n d fu rt h e r d if-
cu lt y is t yp ica lly e x p e rie n ce d o r fre s h blo o d n ow a p p e a r s in t h e a s p ira t e d
u id . Dis com fort by t h e p a t ie n t is com m on a t t h is p oin t , a n d a d e cis ion t o con -
t in u e a s p ira t in g a t t h e p a t ie n t ’s d is com fort s h ou ld be w e igh e d by t h e be n e t of
re m ovin g m ore u id a t t h is t im e. On ce s u f cie n t u id is re m ove d , t h e n e e d le
ca n b e w it h d ra w n a n d a p p ro p ria t e h e m o s t a s is a p p lie d t o t h e in je ct io n s it e .
Alt e rn a t ively, if s t e roid s or m ed ica t ion a re p la n n e d t o be in je cte d a fte r a s p ira t ion ,
 276 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

t h e s yrin ge ca n be s e p a ra t e d from t h e n e e d le t h a t re m a in s in t h e join t a n d a

s yrin ge w it h t h e m e d ica t ion a t t a ch e d t o t h e n e e d le a n d t h e m e d ica t ion in je ct e d .
Th is s it u a t ion w h e re a n in je ct ion follow s a n a s p ira t ion is w h e re a h e m os t a t
ca n be h e lp fu l t o gra s p t h e h u b of t h e n e e d le w h ile ch a n gin g s yrin ge s . In je ct in g
m e d ica t ion in t o a join t cavit y s h ou ld n ot re q u ire m u ch p re s s u re on t h e p lu n ge r,
a lt h ou gh t h e la rge r t h e d is crep a n cy be t w e e n a la rge s yrin ge bore a n d a s m a ll-
ga u ge n e e d le , t h e gre a t e r t h e p re s s u re re q u ire d . If s ign i ca n t p re s s u re is
re q u ire d , t h e n e e d le h a s le ft t h e join t s p a ce a n d s h ou ld be p os it ion e d a ga in
p rop e rly.
W h e n a s p ira t ion is n ot p la n n e d a n d on ly in je ct ion of m e d ica t ion is p la n n e d ,
a s p ira t ion of u id is n ot a lw ays p os s ible w h e n u s in g s m a ll-ga u ge n e e d le s of
le s s t h a n 20 a n d t h e op e ra t or m u s t be con d e n t of t h e n e e d le p os it ion . Aga in ,
in je ct in g m e d ica t ion in t o a join t ca vit y s h ou ld n ot re q u ire m u ch p re s s u re on
t h e p lu n ge r e xcep t w h e n t h e re is a gre a t e r d is cre p a n cy be t w e e n a la rge -bore
s yrin ge a n d a s m a ll-ga u ge n e e d le, w h e n gre a t e r p re s s u re re q u ire d . If s ign i -
ca n t p re s s u re is re q u ire d , t h e n e e d le is n ot p os it ion e d in t h e join t s p a ce a n d
s h ou ld be p os it ion e d p rop e rly.
W h e n in je ct in g m e d ica t ion on ly w it h ou t a s p ira t ion , u s in g a 27-ga u ge n e e -
d le is m ore com fort a ble t o t h e p a t ie n t , a lt h ou gh it re q u ire s gre a t e r p lu n ge r
S
E
p re s s u re from t h e op e ra t or. If lim it in g t h e s yrin ge t o a 3-cc volu m e, t h e p re s s u re
C
T
s h ou ld n ot be t oo d if cu lt . If in je ct in g vis cou s s olu t ion s s u ch a s in vis cos u p -
I
O
p le m e n t a t ion or ce rt a in d ep ot s t e roid p rod u ct s , t h e op e ra t or re q u ire s a la rge r
N
6
bore n e e d le t h a n a 27-ga u ge n e e d le a n d s h ou ld con s id e r a 25-ga u ge n e e d le for
D
d ep ot s t e roid s a n d a 22-ga u ge n e e d le for vis cos u p p le m e n t a t ion .
i
a
g
n
o
Co mplica tio ns
s
i
s
a
n
Proce d u re -re la t e d com p lica t ion s s u ch a s in fe ct ion or ble e d in g a re ra re if a n t i-
d
s ep t ic t e ch n iq u e s a re p ra ct ice d , s e le ct ion of in je ct ion s it e is p ru d e n t , a n d a p p ro-
T
h
e
p ria t e h e m os t a s is is im p le m e n t e d . Com p lica t ion s from t h e s t e roid in je ct e d a re
r
a
m o re co m m o n a n d t h e p a t ie n t s h o u ld be in fo rm e d p rio r t o t h e p ro ce d u re .
p
y
W h e n in je ct e d in t o s oft t is s u e s , cort icos t e roid s ca n ca u s e fa t a t rop h y, cu t a n e -
ou s h yp op igm e n t a t ion a lon g t h e n e e d le t ra ck, a n d a t rop h y of liga m e n t a n d
t e n d on s t ru ct u re s , m a kin g ru p t u re a ris k. Fa t a t rop h y a n d h yp op igm e n t a t ion
u s u a lly re s o lve , a lt h o u gh t h ey m a y t a ke ye a r s . A crys t a l-in d u ce d a r t h r it is
(p os t in je ct ion a re ) is n ot com m on , bu t it ca n occu r w it h in h ou rs of in je ct ion
a n d la s t for s eve ra l. Th e a re occu rs like ly be ca u s e of t h e in a m m a t ory e ffe ct
of t h e s t e roid crys t a ls , ca u s in g a t ra n s ie n t crys t a l-in d u ce d s yn ovit is . If in je ct in g
a com bin a t ion of s t e roid s a n d a loca l a n e s t h e t ic s u ch a s lid oca in e, t h e p a t ie n t
s h ou ld be w a rn e d of t h e t h e ra p e u t ic w in d ow of e ffe ct w h e n u s in g t h is com bi-
n a t ion , a s t h e a n e s t h e t ic m ay w e a r off be fore t h e s t e roid s t a rt s t o w ork. Fin a lly,
p a t ie n t s w it h d ia be t e s s h ou ld be ca u t ion e d t o obs e rve t h e e ffe ct of t h e s t e roid s
on t h e ir glu cos e con t rol ove r t h e n e xt s eve ra l d ays follow in g in je ct ion .

Te chnique fo r Spe cific Jo ints

NOT TO BE MISSED
• Syst e m ic o r lo ca l in fe ct io n .
• Ra sh o ve rlyin g in je ct io n
sit e .
• Ble e d in g d ia t h e sis, a s it
re q u ire s m o re a t t e n t io n t o
h e m o st a sis p o st p ro ce d u re .
KNEE
• Patient position: Su p in e w it h t h e kn e e t o be a s p ira t e d fu lly e xt e n d e d or e x-
t e n d e d a s m u ch a s is t ole ra ble t o t h e p a t ie n t . Su p p ort p la ce d u n d e r a kn e e
u n a ble t o fu lly e xt e n d p rovid e s gre a t e r com fort t o t h e p a t ie n t a n d a llow s for
gre a t e r re la xa t ion .
• Entry site: Me d ia l or la t e ra l.
• Technique: Wit h t h e p a t ie n t re la xe d , t h e p a t e lla s h ou ld be m ova ble a n d t h e
la n d m a rks of t h e p a t e lla id e n t i e d , p a rt icu la rly t h e s u p e rior m e d ia l or la t e ra l
corn e r, a s t h e e n t ry p oin t w ill be in fe rior t o t h a t la n d m a rk (Fig. 27.1 ). Pos it ion
t h e n e e d le p e rp e n d icu la r t o t h e leg a n d a n gle d t o be p a ra lle l t o t h e in fe rior
 Ch a p te r 27 Te ch n iq u e s o f Art h roce n t e s is 277

Figure 27.1 Medial entry point of knee beneath the superior medial Figure 27.2 Entry point of the a nkle joint, a t the sa me pla ne of the media l
pole of the patella. Needle is positioned parallel to the inferior surface ma lleolus a nd media l to the a nterior tibia lis tendon.

y
p
of the patella.

a
r
e
h
T
s u rfa ce of t h e p a t e lla , t yp ica lly a bou t 30 t o 45 d egre e s from h orizon t a l. Ad -

d
va n ce t h e n e e d le q u ickly t h rou gh t h e s kin a n d t h e n a d va n ce fu rt h e r u n t il t h e

n
a
s yn oviu m is cros s e d .

s
i
s
o
n
g
ANKLE (TIBIOTALAR) JOINT

a
i
D
• Patient position: Pa t ie n t s u p in e a n d a n kle re la xe d .

6
• Entry site: An t e rom e d ia l.

N
O
• Technique: Id en tify t h e p a tien t’s m e d ia l m a lleolu s a n d a n t erior t ibia lis t en d on .

I
T
Th e en t ry p oin t w ill be in th e s a gitt a l, or h orizon ta l, p la n e of t h e m ed ia l m a lleo-

C
E
lu s a n d im m ed ia t ely m ed ia l to t h e a n te rior tibia lis t en d on (Fig. 27.2 ). Th e n ee d le

S
sh ou ld be d irect ed t ow a rd th e cen t er of th e con cave d is ta l en d of t h e t ibia . Th is
tra ject ory w ill p os it ion th e n ee d le betw een th e ta lu s a n d t h e d ist a l tibia .

METATARSOPHALANGEAL,
METACARPOPHALANGEAL, AND
INTERPHALANGEAL JOINTS
• Patient position: Pa t ie n t s u p in e a n d join t re la xe d .
• Entry site: Dors a l, m e d ia l, or la t e ra l t o t h e e xt e n s or
t e n d on .
• Technique: Id e n t ify t h e ba s e of t h e d is t a l p h a la n x a n d
t h e e xt e n s or t e n d on a s it cros s e s t h e join t s p a ce. Se -
le ct t h e a re a m e d ia l or la t e ra l t o t h e e xt e n s or t e n d on
t h a t a void s a n y vis ible s u bcu t a n e ou s ve in s . Us e t h is
a s you r e n t ry p oin t a n d d ire ct t h e n e e d le t ow a rd t h e
ce n t e r of t h e con ca ve p roxim a l e n d of t h e d is t a l p h a -
la n x (Figs . 27.3 a n d 27.4 ). Th is t ra je ct ory w ill p os it ion
t h e n e e d le be t w e e n t h e con ve x h e a d of t h e p roxim a l
bon e a n d t h e d is t a l p h a la n x.

SHOULDER
• Patient position: Pa t ie n t s e a t e d , e lbow e xe d t o 90 d e -
gre e s , fore a rm re s t in g on t h e la p , a n d join t re la xe d .
Figure 27.3 Entry point of the ha nd—meta ca rpopha la ngea l joint. • Entry site: Pos t e rior.
 278 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

Figure 27.4 Entry point of the foot—meta ta rsopha la ngea l joint. Figure 27.5 Posterior entry point into the shoulder benea th the sca pula r
spine’s a cromia n with the needle directed towa rd the cora coid process.
S
E
C
• Technique: St a n d in g be h in d t h e p a t ie n t , id e n t ify t h e s ca p u la r s p in e a n d d is t a l
T
I
O
a crom ia n on t h e ba ck of t h e p a t ie n t , a n d t h e cora coid p roce s s on t h e a n t e rior
N
ch e s t of t h e p a t ie n t . Pla ce t h e h a n d n ot h old in g t h e n e e d le on t h e s h ou ld e r
6
a n d id e n t ify or p a lp a t e t h e cora coid p roce s s . Th e e n t ry p oin t w ill be im m e -
D
i
d ia t e ly in fe rior t o t h e d is t a l a crom ia n a n d t h e n e e d le t ip d ire ct e d t ow a rd t h e
a
g
p a lp a ble cora coid s p roce s s (Fig. 27.5 ).
n
o
s
i
s
a
SUBACROMIAL BURSA
n
d
• Patient position: Pa t ie n t s e a t e d , e lbow e xe d t o 90 d egre e s , fore a rm re s t in g on
T
h
t h e la p , a n d join t re la xe d .
e
r
a
• Entry site: La t e ra l.
p
y
• Technique: St a n d in g on t h e s id e of t h e p a t ie n t , id e n t ify t h e a crom ia n p roce s s .
Th e e n t ry p oin t w ill be in fe rior t o t h e la t e ra l m os t p oin t of t h e a crom ia n
p roce s s a n d t h e n e e d le d ire ct e d s u p e riorly rou gh ly 30 d egre e s be low t h e h ori-
zon t a l leve l. Th is w ill p la ce t h e n e e d le a bove t h e h u m e ra l h e a d a n d be low t h e
a crom ia n p roce s s (Fig. 27.6 ).

ELBOW
• Patient position: Pa t ie n t lyin g, e lbow e xe d t o 90 d e -
gre e s , fore a rm re s t in g on t h e a bd om e n , a n d join t
re la xe d .
• Entry site: La t e ra l.
• Technique: Id e n t ify t h e la t e ra l e p icon d yle, ra d ia l
h e a d , a n d ole cra n on p roce s s , a n d e s t a blis h t h e ce n -
t e r of t h is t ria n gle (Fig. 27.7 ). Th e n e e d le w ill e n t e r
in t h e ce n t e r of t h e t ria n gle, d ire ct e d p e rp e n d icu la r
t o t h e s kin ’s e n t ry p oin t , a n d e n d u p in t h e e lbow ’s
la t e ra l p a ra ole cra n on groove.

Figure 27.6 Entry point of the suba cromia l bursa .
WRIST
• Patient position: Pa t ie n t s e a t e d or lyin g, w ris t in m ild
p a s s ive e xion of 10 d egre e s w it h a s u p p ort be n e a t h
t h e w ris t for com fort , a n d re la xe d .
• Entry site: Dors a l.
 Ch a p te r 27 Te ch n iq u e s o f Art h roce n t e s is 279

Figure 27.7 Entry point of the elbow between la tera l epicondyle, ra dia l Figure 27.8 Entry point between the dista l ra dius a nd sca phoid bone in
hea d, a nd olecra non process. the wrist dista l to the ra dia l tubercle.

y
p
a
• Technique: Id en tify t h e ra d ia l tu bercle on t h e d ist a l ra d iu s a n d a n in d en t a tion

r
e
WHEN TO REFER

h
bet w een th e d ist a l ra d iu s a n d th e sca p h oid bon e in th e w rist. En try p oin t w ill

T
be d is ta l t o th e ra d ia l tu bercle in th e in d en t a tion a n d d irectin g th e n eed le p er-

d
• Wh e n in d o u b t a b o u t

n
p en d icu la r to t h e skin (Fig. 27.8 ).

a
p e rfo rm in g t h e p ro ce d u re .

s
i
s
• Jo in t s in a cce ssib le w it h o u t

o
n
im a g in g g u id a n ce .

g
ICD9

a
i
D
81.91 Arthro ce nte sis

6
Jo in t asp irat io n

N
O
I
T
C
E
Additio na l Re a ding

S
1. Moo re GF. Te ch n iq u e s of a rt h roce n t e s is a n d in je ct ion t h e ra p y. In : Koop m a n W J, Bou lw a re DW, He u d e be rt
GR, e d s . Clinical Prim er of Rheum atology . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d W ilkin s ; 2003:354 –367 .
2. Lo t k e PA. In je ct ion t e ch n iq u e s for jo in t s a n d bu rs a . In : Lot ke PA, Ab bou d JA, En d e J, e d s . Lippincott’s
Prim ary Care Orthopaedics . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s ; 2008:389 –394 .
3. Moo re GF. Art h ro ce n t e s is t e ch n iq u e a n d in t ra -a rt icu la r t h e ra p y. In : Ko o p m a n W J, More la n d LW, e d s .
A rthritis and A llied Conditions . 15t h e d . Ph ila d e lp h ia : Lip p in cot t Willia m s a n d Wilkin s ; 2005:755 –774.
 CHAPTER
28 Monitoring of Pa tients
on Antirheuma tic
Thera py
W. W inn Chatham
S
Th e ch ron icit y of t h e m a jorit y of rh e u m a t ic d is e a s e s oft e n in volve s t h e lon g-
E
C
t e r m u s e of a n t ir h e u m a t ic t h e ra p ie s . Mu lt ip le in a m m a t ory m e d ia t o r s a n d
T
I
O
m e ch a n is m s of t is s u e in ju ry op e ra t ive in bot h a cu t e a n d ch ron ic in a m m a t ion
N
fre q u e n t ly re q u ire t h e con cu rre n t u s e of s eve ra l re a ge n t s t o a d e q u a t e ly s u p -
6
p re s s d is e a s e a ct ivit y. More ove r, t h e in cre a s e d p reva le n ce of rh e u m a t ic d is e a s e
D
i
a
w it h a ge d ict a t e s t h a t u s e of a n t irh e u m a t ic a n d im m u n om od u la t in g t h e ra p ie s
g
n
m u s t oft e n be p re s cribe d in t h e con t e xt of com orbid it ie s . As s u ch , it is im p or-
o
s
t a n t for clin icia n s in volve d in t h e ca re of p a t ie n t s w it h rh e u m a t ic d is e a s e t o be
i
s
m in d fu l of t h e s h ort -t e rm a s w e ll a s lon g-t e rm con s e q u e n ce s of a n t irh e u m a t ic
a
n
t h e ra p ie s , n ot on ly on orga n s ys t e m s a ffe ct e d by t h e ra py, bu t a ls o on t h e cou rs e
d
T
or t re a t m e n t of coe xis t in g d is e a s e.
h
e
r
a
p
Co rtico ste ro ids
y
Glu cocort icoid s h ave broa d in h ibit ory e ffe ct s on s p e ci c im m u n e re s p on s e s
m ed ia t ed by T- a n d B-cell lym p h ocyt es a s w ell a s p oten t su p p re ss ive effe cts on
t h e effe ctor fu n ct ion s of m on ocyt es a n d n eu trop h ils. Alt h ou gh th ese a t tribu tes
cou p le d w it h t h e ir ra p id on s e t of a ct ion re n d e r s t e roid s ext re m e ly va lu a ble in
s u p p re s s in g u n d e s ire d in a m m a t ory p roce s s e s , cort icos t e roid s h a ve s im ila r
COMMON PITFALLS TO broa d e ffects on th e fu n ction of cells com p risin g ot h er orga n syst em s. Th e im m u -
AVOID WHEN USING
GLUCOCORTICOSTEROIDS n ocom p rom ised st a t u s a n d ca t a bolic con s eq u en ces a ss ocia t ed w it h u se of corti-
cos teroid s lim it t h eir lon g-term u se in h igh d os es a n d d ict a t e t h e n eed for ca refu l
1. Infection with mycobacteria, s u rve illa n ce a n d p reven t ive in t erven t ion s to avoid u n d es ired com p lica tion s.
list e ria , cryp t o co cci, a n d
n o ca rd ia Us e of h igh d os e s of cort icos t e roid s rs t a n d fore m os t re q u ire s vigila n ce
for t h e d eve lop m e n t of in t e rcu rre n t in fe ct ion s . Pa t ie n t s w it h e it h e r rh e u m a t oid
2. Sa lt a n d w a t e r re t e n t io n a rt h rit is or s ys t e m ic lu p u s e ryt h e m a t os u s (SLE) h a ve a n in t rin s ic s u s cep t ibilit y
3. Glu co se in t o le ra n ce t o in fe ct ion , a n d t h e a d m in is t ra t ion o f glu coco rt icoid s e n h a n ce s t h e ris k of
4. Mu scle a n d skin w a st in g in fe ct ion . In a d d it ion t o t yp ica l ba ct e ria l orga n is m s , in fe ct ion s w it h m ycoba c-
t e ria , cryp t ococci, lis t e ria , a n d n oca rd ia h ave be e n a s s ocia t e d w it h cort icos t e r-
5. Ost e o p o ro sis oid t h e ra p y. Th e co m b in a t io n of s t e ro id u s e w it h cyt ot oxic a ge n t s , s u ch a s
6. Ost e o n e cro sis cyclop h os p h a m id e, h a s be e n a s s ocia t e d w it h h igh e r ris k of in fe ct ion w it h Pneu-
m ocystis jirov ecii p n e u m on ia , m os t n ot a bly a m on g p a t ie n t s w it h lym p h op e n ia .
Un le s s life - or orga n -t h re a t e n in g d is e a s e com p lica t ion s d ict a t e ot h e rw is e, in
t h e s e t t in g of s e riou s in t e rcu rre n t in fe ct ion , d os e s of cort icos t e roid s s h ou ld be
a t t e n u a t e d t o t h a t re q u ire d t o avoid a d re n a l cris is .
Give n t h e s ign i ca n t ca t a bolic e ffe ct s of glu cocort icoid s on m u s cle, s kin ,
a n d bon e , p a t ie n t s t a kin g m od e ra t e o r h igh d o s e s of s t e roid s for p rolon ge d
in t e rva ls re q u ire p e riod ic a s s e s s m e n t for t h e evolu t ion of s t e roid m yop a t h y or
280

COMMON PITFALLS TO
AVOID WHEN USING NSAIDs
1. De clin e in g lo m e ru la r
lt ra t io n ra t e
2. Ga st ro p a t h y in clu d in g
u lce ra t io n a n d b le e d in g
3. Pla t e le t d ysfu n ct io n a n d
b le e d in g
4. Sa lt a n d w a t e r re t e n t io n
NSAIDs, n o n st e ro id a l a n t i-
in a m m a t o ry d ru g s.
Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 281
d eve lop m e n t of s t e roid -in d u ce d os t e o p oro s is . Sin ce s t e roid m yo p a t h y m os t
com m on ly a ffe ct s t h e p roxim a l h ip -gird le m u s cu la t u re, a s s e s s m e n t of h ip -gird le
s t re n gt h by h avin g t h e p a t ie n t s q u a t or a ris e from a ch a ir u n a s s is t e d a re s im p le
m a n e u ve rs t h a t ca n be e m p loye d d u rin g clin ic vis it s . Cort icos t e roid -in d u ce d
m u s cle w a s t in g a n d w e a kn e s s m ay be d if cu lt t o d is t in gu is h from in a m m a -
t ory m u s cle d is e a s e s for w h ich t h ey a re p re s cribe d . Mu s cle t e n d e rn e s s a n d
e leva t ion in cre a t in e kin a s e favor t h e p re s e n ce of a ct ive m yos it is . On m u s cle
b iop s y, lo s s of t yp e I a n d t yp e II be rs a s w e ll a s va cu ola r ch a n ge s m a y be
obs e rve d in s t e roid -in d u ce d m yop a t h y or m yos it is .
Pe riod ic a s s e s s m e n t for os t e op oros is is n ow a s t a n d a rd of ca re for p a t ie n t s
on ch ron ic cort icos t e roid s . Th e e m p loym e n t of a lt e rn a t e -d ay d os in g regim e n s
d oe s n ot a p p e a r t o con fe r p rot e ct ion from s t e roid -in d u ce d os t e op e n ia . Exoge -
n ou s a d m in is t ra t ion of ca lciu m a n d vit a m in D m ay s u f ce t o p rot e ct p a t ie n t s
from s t e roid -in d u ce d os t e op e n ia . Glu cocort icoid -in d u ce d s u p p re s s ion of a d re -
n a l d e h yrd oep ia n d ros t e ron e (DHEA) p rod u ct ion m ay re n d e r w om e n a t in cre a s e d
ris k for t h e ca t a bolic e ffe ct of s t e roid s on bon e, bu t a role for DHEA a d m in is t ra -
t ion in t h e p reve n t ion o f bon e com p lica t io n s h a s n ot ye t be e n con r m e d .
Bis p h os p h on a t e s (a le n d ron a t e, ris e d ron a t e, iba n d ron a t e, a n d zole d ron ic a cid )
a n d h ave e m e rge d a s p rove n t h e ra p ie s for t h e p reve n t ion a n d t re a t m e n t of glu -
y
p
cocort icoid -in d u ce d os t e op oros is (1 ). Pe riod ic a s s e s s m e n t of bon e d e n s it y a t 1-
a
r
e
t o 2-ye a r in t e rva ls is re com m e n d e d t o a s s e s s t h e e f ca cy of t h e s e in t e rve n t ion s
h
T
in p a t ie n t s on ch ron ic s t e roid t h e ra py.
d
Th e p re d ict a ble m e t a bolic con s e q u e n ce s of s t e roid s in clu d e s a lt a n d w a t e r
n
a
re t e n t ion a s w e ll a s va ria ble d egre e s of in s u lin re s is t a n ce w it h h yp e rglyce m ia .
s
i
s
Th e m in e ra locort icoid e ffe ct s of s t e roid s w a rra n t e xp e ct a n t obs e rva t ion for t h e
o
n
d eve lop m e n t of h yp e rt e n s ion or h e a rt fa ilu re e xa ce rba t ion s in p a t ie n t s w h o
g
a
h a ve or a re a t ris k for t h e s e ca rd iova s cu la r d is ord e rs . Lon g-t e rm m e t a bolic con -
i
D
s e q u e n ce s of cort icos t e roid u s e in p a t ie n t s w it h rh e u m a t ic d is e a s e m ay in clu d e
6
a cce le ra t e d a t h e roge n e s is . At t e n t ion t o ot h e r ca rd iova s cu la r ris k fa ct ors in clu d -
N
O
in g a s s e s s m e n t for a n d t re a t m e n t of h yp e rch ole s t e role m ia m ay s low t h e p ro-
I
T
gre s s ion of a t h e roge n e s is a n d low e r t h e ris k for va s cu la r eve n t s in p a t ie n t s
C
E
w h o re q u ire lon g-t e rm s t e roid u s e for m a n a ge m e n t of rh e u m a t ic d is e a s e m a n -
S
ife s t a t ion s .
Ot h e r co m p lica t io n s o f co r t ico s t e ro id t h e ra p y a re le s s p re d ict a ble b u t
n on e t h e le s s re q u ire vigila n ce for t h e ir occu rre n ce s o a s t o a void u n fa vora ble
ou t com e s . Cort icos t e roid s m ay h a ve u n t ow a rd e ffe ct s on t h e ce n t ra l n e rvou s
s ys t e m , in clu d in g e m ot ion a l irrit a bilit y, d if cu lt y in con ce n t ra t ion , d e p re s s ion ,
con fu s ion , or p s ych os is . High -d os e cort icos t e roid s t h e ra py h a s be e n im p lica t e d
a s a p os s ible in d u ce r of p a n cre a t it is . Sin ce p a n cre a t it is m a y be a m a n ife s t a t ion
of lu p u s , t h e occu rre n ce of p a n cre a t it is in p a t ie n t s w it h lu p u s re ce ivin g glu co-
cort icoid t h e ra py m ay re s u lt in a t h e ra p e u t ic d ile m m a . Os t e on e cros is is a re c-
ogn ize d co m p lica t io n o f h igh -d os e s t e ro id u s e. In p a t ie n t s w it h lu p u s , o t h e r
d is e a s e -re la t e d fa ct ors m ay a ccou n t for t h e d eve lop m e n t of os t e on e cros is , bu t
t h e in cid e n ce a p p e a rs t o corre la t e w it h t h e cu m u la t ive s t e roid d os e. Sin ce rou -
t in e ra d iogra p h s t yp ica lly fa il t o reve a l t h e p re s e n ce of os t e on e cros is d u rin g it s
e a rly s t a ge s , p a t ie n t s on h igh d os e s of s t e roid s w h o d eve lop ot h e rw is e u n e x-
p la in e d p a in in t h e s h ou ld e rs , h ip s , kn e e s , or a n kle s s h ou ld be eva lu a t e d w it h
m a gn e t ic re s on a n ce im a gin g t o ru le ou t t h e p re s e n ce of os t e on e cros is .
No nste ro ida l Anti- infla mma to ry Drug s
Non s t e roid a l a n t i-in a m m a t ory d ru gs con s t it u t e t h e m os t fre q u e n t ly p re s cribe d
cla s s of m e d ica t ion u s e d in t h e t re a t m e n t of p a t ie n t s w it h rh e u m a t ic d is ord e rs .
A ra p id o n s e t of a ct ion a n d t h e ir co m bin e d a n a lge s ic or a n t i-in a m m a t o ry
a t t ribu t e s re n d e r NSAIDs ve ry u s e fu l in t h e m a n a ge m e n t of rh e u m a t ic d is e a s e.
Alt h ou gh a n u m ber of cellu la r effe ct s d is tin ct from th os e re la t ed t o p rosta gla n d in
 282 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

p rod u ct ion h a ve be e n d e s cribe d for va riou s NSAIDs , t h e m a jor t h e ra p e u t ic

e ffe ct of NSAIDs re la t e s t o t h e ir a bilit y t o in h ibit cyclooxyge n a s e -m e d ia t e d
s yn t h e s is of p ros t a gla n d in s , a ffe ct in g va s cu la r p e rm e a bilit y a n d h yp e ra lge s ia .
How eve r, p ros t a gla n d in s ge n e ra t e d by cyclooxyge n a s e a ls o p lay a n im p ort a n t
role in h e m os t a s is , in m a in t a in in g t h e in t egrit y of t h e in t e s t in a l m u cos a , a n d in
regu la t in g re n a l blood ow. Th e s e p h ys iologic e ffe ct s of p ros t a gla n d in s a ccou n t
for t h e m a jorit y of NSAID s id e e ffe ct s a n d t oxicit y, m os t n ot a bly ble e d in g, in t e s -
t in a l u lce ra t ion , a zot e m ia , a n d re t e n t ion of s a lt a n d w a t e r.
Ce rt a in t oxic e ffe ct s of a give n NSAID m ay be gove rn e d by it s s p e ci cit y for
t h e r e s p e ct ive is o fo r m s o f cyclo o x yge n a s e , COX-1 a n d COX-2. COX-1 is
e xp re s s e d con s t it u t ive ly in m os t orga n s ys t e m s a n d is t h e is oform p rim a rily
re s p on s ible fo r s yn t h e s is of p ro s t a gla n d in s m a in t a in in g t h e in t e grit y of t h e
ga s t roin t e s t in a l (GI) m u cos a a n d t h e h e m os t a t ic fu n ct ion of p la t e le t s . COX-2 is
p rim a rily in d u ce d a n d e xp re s s e d in re s p on s e t o cyt okin e s a t s it e s of t is s u e
in ju ry a n d in a m m a t ion a n d is n ot e xp re s s e d in p la t e le t s . Tra d it ion a l n on s e -
le ct ive NSAIDs in h ibit bot h COX-1 a n d COX-2, w h e re a s ce le coxib s e le ct ive ly
in h ibit s COX-2, s u bs t a n t ia lly s p a rin g a ct ivit y of COX-1.
Mon it orin g of p a t ie n t s t a kin g NSAIDs , p a rt icu la rly t h os e n ot s e le ct ive for
COX-2, e n t a ils ca re fu l a t t e n t ion t o s ym p t om s re fe ra ble t o t h e GI t ra ct a n d t h e
S
E
p os s ibility of ble ed in g com p lica tion s . As th e m a jorit y of NSAID-in d u ce d u lcera -
C
T
tion s a re s ilen t , p e riod ic a s s e s s m en t of t h e h e m a t ocrit a n d red ce ll in d ice s a re
I
O
p ru d en t in p a t ie n ts t a kin g NSAIDs for ext e n d ed d u ra t ion s . Alt h ou gh th e re a re n o
N
6
p u blis h e d s t u d ie s t o p rovid e gu id e lin e s for h ow fre q u e n t ly s u ch m on it orin g
D
sh ou ld occu r, ris k fa ct ors for NSAID-in d u ced GI blee d in g a n d p erfora t ion a re n ow
i
a
g
w e ll re cogn ize d (Ta ble 28.1 ) (2,3 ), a n d t h e p res e n ce of t h es e ris k fa ct ors in a given
n
p a t ie n t sh ou ld gu id e t h e fre q u en cy of blood cou n t or h em occu lt m on itorin g.
o
s
i
Bot h COX-1 a n d COX-2 a re con s t it u t ive ly exp res s ed in t h e kid n ey a n d ge n e r-
s
a
a t e p ros t a gla n d in s (PGE2 a n d PGI2) t h a t regu la t e re n a l blood ow u n d e r con d i-
n
d
t ion s of volu m e con t ra ct ion a n d /or d e cre a s e d e ffe ct ive a rt e ria l blood volu m e.
T
h
PGE2 a n d PGI2 fu rt h erm ore s t im u la t e s e cre t ion of ren in w it h a t t e n d a n t re lea s e of
e
r
a ld os t e ron e a n d p ot a s s iu m s ecre t ion . Accord in gly, d im in u t ion in GFR w it h s a lt
a
p
y
Table 28.1 Risk Fact ors for NSAID-Induced Gast roint est inal
Bleeding and Perforat ion

Pre vio u s p e p t ic u lce r d ise a se

Pre vio u s g a st ro in t e st in a l b le e d
Pre vio u s h o sp it a liza t io n fo r g a st ro in t e st in a l d ise a se
Hist o ry o f NSAID-in d u ce d g a st rit is o r d ysp e p sia
Use o f H2 -b lo cke r o r a n t a cid fo r d ysp e p sia
Co n cu rre n t co rt ico st e ro id u se
Old e r a g e
Hig h e r d o se o f NSAID
Hist o ry o f ca rd io va scu la r d ise a se
Hig h e r a rt h rit is-re la t e d d isa b ilit y sco re
Co n cu rre n t a n t ico a g u la n t u se
Sm o kin g
Alco h o lism

NSAID, n o n st e ro id a l a n t i-in a m m a t o ry d ru g s.
Risk fa ct o rs co m p ile d fro m t h e ARAMIS d a t a b a se a n d o u t co m e s in t h e MUCOSA t ria l (2,3).
 Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 283

a n d w a t er re t e n t ion a n d /or h yp e rka lem ia m ay occu r a s a con s e q u e n ce of t re a t -

m en t w it h e it h e r n on s e le ct ive or COX-2 s e lect ive NSAIDs . Pa t ie n t s w it h p reexis t -
in g ren a l d is e a s e or d im in is h e d effe ct ive a rt e ria l blood volu m e (con ge s t ive h e a rt
fa ilu re, cirrh os is , a n d re n a l va s cu la r d is ea s e) a re a t p a rt icu la r ris k for effe ct s of
NSAIDs on glom e ru la r p e rfu s ion . Effe ct s of NSAIDs on GFR m ay ca u s e s ign i ca n t
com p lica t ion s in p a t ie n t s w it h d ia be t e s w it h t yp e IV re n a l t u bu la r a cid os is
(h yp ore n in e m ic h yp oa ld os t e ron is m ), a s t h e a t t en d a n t in h ibit ion of ren in rele a s e
a ccom p a n ied by d im in u t ion of s a lt loa d t o d is t a l n ep h ron s m ay p recip it a t e s ig-
n i ca n t h yp erka le m ia . Ca refu l m on it orin g for u id ret e n t ion a n d e leva t ion s of
cre a t in in e or p ot a s s iu m s h ou ld be u n d ert a ke n in t h e s e a t -ris k p a t ie n t p op u la -
t ion s w it h in s eve ra l d ays of in s t it u t in g t re a t m e n t w it h a n NSAID.
In a d d it ion t o t h e ir p ot e n t ia l e ffe ct s on glom e r u la r p e rfu s ion a n d re n in
s e cre t io n , NSAIDs m a y in d u ce id io s yn cra t ic, d r u g-s p e ci c co m p lica t io n s o f
in t e rs t it ia l n e p h rit is . W h ile t h is com p lica t ion m ay occu r w it h a n y NSAID, in t e r-
COMMON PITFALLS TO s t it ia l n ep h rit is h a s be e n re p ort e d m os t com m on ly in p a t ie n t s re ce ivin g fe n o-
AVOID WHEN USING p rofe n . Alt h o u gh a n a p p rop r ia t e fre q u e n cy o f m on it or in g re n a l fu n ct ion in
COLCHICINE
p a t ie n t s t a kin g NSAIDs h a s n ot be e n e s t a blis h e d by re leva n t ou t com e s t u d ie s ,
1. Do se -re la t e d d ia rrh e a a t le a s t s e m ia n n u a l a s s e s s m e n t of cre a t in in e a n d u r in a lys is is p r u d e n t for
p a t ie n t s on lon g-t e rm NSAID t h e ra py t o m in im ize t h e ris k of p e rm a n e n t kid n ey

y
2. Myo p a t h y w it h ch ro n ic u se

p
d a m a ge from d ru g-in d u ce d in t e rs t it ia l n e p h rit is .

a
r
e
h
T
COLCHICINE

d
n
a
Colch icin e is m os t com m on ly u s e d in t h e t re a t m e n t of a cu t e gou t or p s eu d ogou t ;

s
i
t h e d ru g m ay be u s e d for ext e n d e d p e riod s of t im e t o p reve n t rep e a t e d a res of

s
o
a cu t e crys t a llin e -in d u ce d a rt h rit is . Th e a n t i-in a m m a t ory e ffe ct s of colch icin e

n
g
a re a t t ribu t e d t o t h e d ru g’s in t e rfe ren ce w it h t h e fu n ct ion of t u bu la r m icro la -

a
i
D
m en t s re q u ired for ch e m ot a xis , m igra t ion , a n d re lea s e of gra n u le con s t it u e n t s by

6
n e u t rop h ils . Th e t oxicit y of colch icin e w h e n u s e d a cu t e ly is p rim a rily re la t e d t o

N
O
effe ct s on t h e in t e s t in a l m u cos a w h e n a d m in is t e re d exces s ive ly. W h e n u s e d in

I
T
t h e a p p rop ria t e s e t t in g of a n a cu t e a t t a ck of crys t a llin e -in d u ce d a rt h rit is of

C
E
s h ort e r t h a n 24 h ou rs ’ d u ra t ion , it is s e ld om n ece s s a ry t o a d m in is t e r ora l d os in g

S
of colch icin e t h a t in d u ce s d ia rrh e a . Tw o ora l d os e s of 0.6 m g a d m in is t e red 1 h ou r
a p a rt follow ed by a t h ird d os e 6 h ou rs la t er is u s u a lly s u f cien t t o m a n a ge a n
a cu t e a t t a ck of gou t or p s e u d ogou t . At t a cks of crys t a llin e -in d u ce d a rt h rit is of
lon ge r t h a n 24 h ou rs ’ d u ra t ion a re le s s likely t o re s olve w it h a d m in is t ra t ion of
colch icin e a n d a lt e rn a t ive t h era p ies , s u ch a s NSAIDs , or cort icos t e roid s s h ou ld
be con s id e re d in t h is s et t in g.
A va cu ola r m yop a t h y m a y evolve in t h e s e t t in g of ch ron ic colch icin e u s e,
p a rt icu la r ly a m on g p a t ie n t s w it h re n a l s u f cie n cy. For p a t ie n t s t re a t e d w it h
colch icin e ove r e xt e n d e d p e riod s , m on it orin g for t h e d eve lop m e n t of m yop a t h y
w it h p e riod ic a s s e s s m e n t for s e ru m e leva t ion s in cre a t in e kin a s e is p ru d e n t .
Pa t ie n t s w it h re n a l in s u f cie n cy m ay a ls o be a t gre a t e r ris k for m a rrow t oxicit y
a n d s h o u ld a ls o be m o n it ore d p e riod ica lly for evid e n ce of cyt op e n ia s w h e n
t a kin g colch icin e ove r e xt e n d e d p e riod s .

Dise a se - mo difying Antirhe uma tic Drug s

Us e of on e or m ore d is e a s e -m od ifyin g a n t irh e u m a t ic d ru gs (DMARDs ) is n ow
t h e s t a n d a rd of ca re for p a t ie n t s w it h a ct ive rh e u m a t oid a rt h rit is . Ma n y DMARDs ,
in clu d in g m e t h ot re xa t e, h yd roxych lo roq u in e, a za t h iop rin e, cyclos p orin e, a n d
m yco p h e n o la t e a re u s e d t o m a n a ge m a n ife s t a t io n s o f d is e a s e s o t h e r t h a n
rh e u m a t oid a rt h rit is , in clu d in g lu p u s a n d p olym yos it is . Us e of DMARDs e n t a ils
t it ra t ion of t h e d os e t o a ch ieve t h e d e s ire d clin ica l be n e t w it h ou t in d u cin g
t oxicit y. Se le ct ion a n d s u cce s s fu l u s e of a DMARD or DMARD com bin a t ion for
a give n p a t ie n t re s t s u p o n m u lt ip le clin ica l co n s id e ra t io n s , in clu d in g s t a ge
a n d a ct ivit y of t h e d is e a s e, p a t ie n t com orbid it ie s , con cu rre n t m e d ica t ion u s e,
 284 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

a n d t h e kn ow n s id e -e ffe ct p ro le s of t h e re s p e ct ive DMARDs . Mon it orin g for

DMARD t oxicit y a n d s id e e ffe ct s is t h e re fore crit ica l t o t h e a p p rop ria t e u s e of
t h e s e d ru gs .

METHOTREXATE
An a n a logu e of folic a cid , m eth otrexa te in h ibits folic a cid –d ep en d en t p a th w ays
t h rou gh n u m e rou s m e ch a n is m s . At h igh d os e s , m e t h ot rexa t e is a n e ffe ct ive
ch em oth era p eu tic a gen t for th e trea tm en t of lym p h oid n eop la sm s a n d som e solid
tu m ors . At low e r d os es , m et h otrexa t e h a s im m u n osu p p re ss ive a n d s ign i ca n t
a n ti-in a m m a tory effects, m ost likely m ed ia ted by effects of its p olyglu ta m a ted
m e t a bolit e s on AICAR t ra n s form yla s e. In h ibit ion of AICAR t ra n s form yla s e by
p olyglu t a m a t e d m e t h o t re x a t e re s u lt s in im p a ire d s yn t h e s is of p u r in e s a n d
p yrim id in e s , a s w e ll a s a ccu m u la t ion of AICAR, a p ot e n t in d u ce r of a d e n os in e
re le a s e. Th e la t t e r m ay a ccou n t for m e t h ot re xa t e ’s a n t i-in a m m a t ory e ffe ct s ,
a s e n ga ge m e n t of a d e n os in e re cep t ors on le u kocyt e s a t t e n u a t e s t h e ir a d h e r-
e n ce t o e n d ot h e lia l ce lls .
Alt h ou gh u n com m on in t h e d os e s u s u a lly e m p loye d for m a n a ge m e n t of
rh e u m a t oid a rt h rit is , m u cos it is , bon e m a rrow s u p p re s s ion , a n d h ep a t oce llu la r
S
E
in ju ry con s t it u t e t h e p rim a ry t oxicit ie s a s s ocia t e d w it h t h e u s e of m e t h ot re xa t e.
C
T
Le s s com m on com p lica t ion s in clu d e a cu t e in t e rs t it ia l p n e u m on it is , in t e rs t it ia l
I
O
N
n e p h rit is , a n d t ra n s ie n t p os t d os e s yn d rom e s t h a t m ay in clu d e feve r, n e u rocog-
6
n it ive im p a irm e n t , a rt h ra lgia , a n d /or m ya lgia . Th e occu rre n ce of m u cos it is or
D
cyt op e n ia s m ay d ep e n d in p a rt on fola t e s t ore s , a s t h e s e com p lica t ion s ca n be
i
a
g
p reve n t e d or s ign i ca n t ly re d u ce d w it h folic a cid s u p p le m e n t a t ion (4 ). Folic
n
o
a cid d oes n ot im p a ir th e form a t ion of p olyglu ta m a ted m et h ot rexa te m eta bolites ,
s
i
a n d u s e of folic a cid su p p lem e n ts h a s been sh ow n n ot to a lter th e a n tirh eu m a t ic
s
a
ef ca cy of m e th otrexa te.
n
d
Effe ct s o f m e t h o t re xa t e o n h e m a t op o ie s is a re t yp ica lly d os e d e p e n d e n t ,
T
h
bu t t h e re is con s id e ra ble in d ivid u a l va ria bilit y in t h e d os e t h re s h old for d eve l-
e
r
op m e n t of m e t h ot re xa t e -in d u ce d cyt op e n ia s . Ra re, s eve re id ios yn cra t ic cyt op e -
a
p
n ia s m ay d eve lop eve n in t h e s e t t in g of low w e e kly d os e s a n d a d e q u a t e fola t e
y
s t ore s . Re n a l in s u f cie n cy gre a t ly e n h a n ce s t h e like lih ood of m a rrow t oxicit y,
d u e in la rge p a rt t o t h e p rom in e n t role of re n a l e xcre t ion in e lim in a t ion of t h e
d ru g. Us e of m e t h ot re xa t e in p a t ie n t s w it h e n d -s t a ge re n a l d is e a s e, eve n w h ile
on regu la r h e m od ia lys is , m ay h a ve d e le t e riou s a n d irreve rs ible con s e q u e n ce s .
Alt h ou gh s e ru m leve ls of m e t h ot re xa t e ca n be e f cie n t ly low e re d by h e m od i-
a lys is u s in g h igh - u x d ia lyze rs , p e rit on e a l d ia lys is is in e ffe ct ive a t low e rin g
s e ru m leve ls of m e t h ot re xa t e, a n d d ia lys is of a n y t yp e like ly h a s lit t le e ffe ct on
re m ova l of t h e a ct ive p olyglu t a m a t e d m e t a bolit e s w it h in ce lls .
Gu id e lin e s for m on it orin g of p a t ie n t s w it h rh e u m a t oid a rt h rit is re ce ivin g
m e t h ot re xa t e h ave be e n e s t a blis h e d (Ta ble 28.2 ) (5,6 ). Prior t o s t a rt in g m e t h -
ot re xa t e, a com p le t e blood cou n t (CBC) w it h s e ru m leve ls of live r t ra n s a m in a s e s
(ALT, AST), a lbu m in , a n d cre a t in in e s h ou ld be ch e cke d . Scre e n in g for h ep a t it is
B a n d C in fe ct ion is a ls o a d vo ca t e d . Tra n s a m in a s e leve ls a n d CBC s h ou ld be
ch e cke d w it h in 4 w e e ks of in s t it u t in g t h e ra py a n d w it h in 4 w e e ks of a n y d os e
in cre m e n t . More fre q u e n t a s s e s s m e n t of blood cou n t s m a y be in d ica t e d for
p a t ie n t s w it h re n a l in s u f cie n cy. Alt e rn a t ive ly, t h e in t e rva l be t w e e n a s s e s s -
m en t of blood cou n t s a n d liver fu n ct ion t es t s m ay be exte n d e d to 3 m on th s for
p a t ie n t s w h o h ave be e n on a s t a ble d os e of m e t h ot re xa t e in e xce s s of 6 m on t h s .
Cre a t in in e leve ls s h ou ld be ch e cke d a t le a s t eve ry 6 m on t h s .
Fo r p a t ie n t s w h o d e ve lo p cyt o p e n ia s (W BC 3,000; h e m a t o cr it 30;
p la t e le t s 130,000), m e t h ot re xa t e s h ou ld be w it h h e ld u n t il t h e ca u s e o f t h e
cyt op e n ia is e lu cid a t e d or t h e leve l of t h e d ep re s s e d blood e le m e n t re cove rs .
A s im ila r s t ra t egy s h ou ld be e m p loye d for p a t ie n t s w h o d eve lop e leva t ion in
live r t ra n s a m in a s e s in e xce s s of t w ice t h e u p p e r lim it of n orm a l. In e it h e r ca s e,
if it is d e e m e d t h e a b n o r m a lit y w a s d u e t o m e t h o t re x a t e , t re a t m e n t w it h
 Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 285

Table 28.2 Guidelines for Monit oring Pat ient s Receiving

Met hot rexat e

Ba se lin e e va lu a t io n :
Co m p le t e b lo o d co u n t
Live r fu n ct io n t e st s—AST, ALT, b iliru b in , a lka lin e p h o sp h a t a se , a lb u m in
He p a t it is B su rfa ce a n t ig e n , h e p a t it is C a n t ib o d y
Pre t re a t m e n t live r b io p sy fo r p a t ie n t s w it h :
Prio r h ist o ry o f e xce ssive a lco h o l co n su m p t io n
Pe rsist e n t a b n o rm a l e le va t io n s in t ra n sa m in a se s (AST, ALT) le ve ls
Evid e n ce o f p e rsist e n t in fe ct io n w it h h e p a t it is B o r C
Mo n it o r CBC, AST, ALT, a n d a lb u m in a t 4- t o 12-w e e k in t e rva ls
Mo n it o r cre a t in in e a t 3- t o 6-m o n t h in t e rva ls
In se t t in g o f cyt o p e n ia o r e le va t io n in AST, ALT t w ice u p p e r ra n g e o f n o rm a l:
Ho ld m e t h o t re xa t e a n d re su m e a t lo w e r d o se o n ce la b o ra t o ry
a b n o rm a lit y re so lve s
Pe rfo rm live r b io p sy b e fo re co n t in u in g t re a t m e n t if:
Five o f n in e o r six o f t w e lve AST d e t e rm in a t io n s in a 1-ye a r t im e fra m e a re

y
a b n o rm a l, o r

p
a
Alb u m in d e cre a se s b e lo w n o rm a l ra n g e d e sp it e a d e q u a t e co n t ro l o f syn o vit is

r
e
h
T
d
n
a
m e t h ot re xa t e a t a low e r d os e ca n oft e n be e m p loye d w it h s u cce s s . Eleva t ion s

s
i
s
of cre a t in in e w h ile on m e t h ot re xa t e w a rra n t e xclu s ion of in t e rs t it ia l n ep h rit is

o
n
a n d a t t e n t ion t o t h e n e e d for d os e a d ju s t m e n t t o avoid m a rrow t oxicit y. Th e

g
a
occu rre n ce of cou gh , d ys p n e a , a n d feve r s h ou ld p rom p t w it h h old in g of m e t h -

i
D
ot re xa t e u n t il it ca n be e s t a blis h e d t h a t t h e s yn d rom e is n ot like ly a t t ribu t a ble

6
t o m e t h ot re xa t e p n e u m on it is .

N
O
Th e rep ort ed occu rren ce of cirrh os is a m on g p a t ien ts w ith p s oria s is t re a t ed

I
T
C
w it h lon g-t e rm w e e kly m e t h ot rexa t e in it ia lly p rom p t e d re com m e n d a t ion s for

E
rou t in e live r biop s y in p a t ie n t s w it h rh e u m a t oid a rt h rit is t re a t e d w it h m e t h -

S
ot rexa t e on ce t h e cu m u la t ive d ose a p p roa ch e d 2 g. How eve r, given t h e in freq u en t
occu rre n ce of s e riou s live r d is e a s e obs e rve d a m on g p a t ie n t s w it h rh e u m a t oid
a rt h rit is t rea t ed w it h m et h ot rexa t e (es t im a t ed ris k a t 5 yea rs 1 in 1,000), cu rren t
gu id e lin e s d o n ot a d voca t e rou t in e live r biop s y for p a t ie n t s t re a t e d w it h lon g-
t e rm m e t h ot re xa t e w h o h ave n orm a l live r fu n ct ion . Live r biop s y is a d voca t e d
p re t re a t m e n t for p a t ie n t s w it h kn ow n h is t ory of p reviou s h e avy a lcoh ol u s e,
a ctive h ep a t it is B, or h ep a t it is C in fection , a n d for p a t ie n t s on m e th ot rexa te w h o
d eve lop p ers is t e n t e leva t ion in liver t ra n s a m in a s e s or a fa ll in s e ru m a lbu m in
d es p ite w e ll-con trolled rh eu m a toid a rt h rit is .

ANTIMALARIALS—HYDROXYCHLOROQUINE,
CHLOROQUINE, AND QUINACRINE
Mos t com m on ly e m p loye d in t h e m a n a ge m e n t of lu p u s or rh e u m a t oid a rt h rit is ,
a n t im a la ria ls h ave m u lt ip le e ffe ct s on im m u n ologic fu n ct ion a n d h ave a ve ry
favora ble t oxicit y/be n e t p ro le. Hyd roxych loroq u in e a n d ch loroq u in e d o n ot
s u p p re s s bon e m a rrow fu n ct ion a n d live r t oxicit y is u n com m on . Sid e e ffe ct s
con s is t p rim a rily of cu t a n e ou s re a ct ion s , GI in t ole ra n ce, a n d m ild CNS s ym p -
t om s . Wit h t h e e xcep t ion of s eve re s kin e ru p t ion s , m a n y of t h e GI a n d n e u ro-
logic s id e e ffe ct s m ay a ba t e w it h re d u ct ion in t h e d os e of a n t im a la ria ls . Alt h ou gh
ra re, ca rd ia c con d u ct ion a bn orm a lit ie s , ca rd iom yop a t h y, a n d n e u rom yop a t h y
h ave be e n rep ort e d a s m ore s e riou s com p lica t ion s . As is re com m e n d e d follow -
in g in it ia t ion of t h e ra py w it h m os t a n t irh e u m a t ic d ru gs , a s s e s s m e n t of live r
t ra n s a m in a s e s s h ou ld be p e rform e d w it h in t h e rs t 2 or 3 m on t h s of t re a t m e n t
t o e n s u re t h e a bs e n ce of id ios yn cra t ic live r t oxicit y.
 286 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

Alt h ou gh u n com m on in t h e d os e s e m p loye d (200 t o 400 m g d a ily), ocu la r

t oxicit y m ay occu r w it h u s e of a n t im a la ria ls . Corn ea l d ep os it s a s s ocia t e d w it h
p ercep tion of h a los a rou n d ligh ts m ay occu r, bu t often rem it sp on t a n eou sly even
w ith con tin u ed a n tim a la ria l u se. Cen t ra l n ervou s system (CNS) effects of h yd rox-
ych loroq u in e or ch loroq u in e follow in g in itia tion of eith er d ru g m ay res u lt in tra n -
s ien t d efects in a ccom m od a tion or con vergen ce. Retin op a th y is a m ore seriou s
com p lica tion th a t m ay resu lt in p erm a n en t vis u a l im p a irm en t. Alth ou gh op in ion
rem a in s va ried w ith rega rd to th e a p p rop ria te freq u en cy of m on itorin g, p a tien ts
on h yd roxych loroq u in e sh ou ld u n d ergo a t lea st yea rly ocu la r eva lu a tion for evi-
d en ce of h yd roxych loroq u in e retin op a th y (7,8 ). An tim a la ria l-in d u ced retin a toxic-
ity is often , a lth ou gh n ot u n iform ly, id en t i a ble before a n y p erceived a ltera t ion s
in visu a l a cu ity. With regu la r ocu la r a ssessm en t for p igm en t a ry a bn orm a lities in
t h e retin a , a ltera tion s in vis u a l eld , a n d ch a n ges in a cu it y or color p ercep tion ,
p erm a n en t vis u a l im p a irm en t from a n tim a la ria l u se ca n u s u a lly be avoid ed .

SULFASALAZINE
Su lfa s a la zin e con s ist s of a sa licyla te (5-a m in os a licylic a cid ) a n d a su lfa pyrid in e
m ole cu le a d join ed by a n a zo bon d t h a t is cle ave d by ba cte ria l orga n is m s in t h e
S
E
gu t. In a d d it ion t o th e a n ti-in a m m a t ory effe ct s a fford e d by t h e libera t ed s a li-
C
T
cyla t e, su lfa pyrid in e a n d /or its m e ta bolite s a p p e a r to h ave im m u n om od u la t ory
I
O
N
effects t h a t a re of ben e t in th e m a n a ge m e n t of p a t ie n t s w it h rh eu m a t oid a rt h ri-
6
tis, a n kylos in g s p on dylit is , or on e of t h e ot h e r s p on dyloa rt h rop a t h ies . Ga s t roin -
D
tes t in a l s ym p t om s a re u s u a lly t h e m os t com m on s id e e ffect s rep ort ed w ith u s e
i
a
g
of s u lfa sa la zin e, bu t t h e se oft en res olve w it h d os e a tt en u a t ion . Th e le ss com m on ,
n
o
bu t p ot e n t ia lly m ore s e riou s , h e m a t ologic con s e q u e n ce s of s u lfa s a la zin e u s e
s
i
in clu d e a p la s t ic a n e m ia , a gra n u locyt os is , or h e m olyt ic a n e m ia , w it h t h e la t t e r
s
a
occu rrin g p re d om in a n t ly in p a t ie n t s w it h glu cos e -6-p h os p h a t e d e h yd roge n a s e
n
d
d e cie n cy. Le u kop en ia m os t oft en occu rs d u rin g t h e rs t s eve ra l m on th s of t re a t -
T
h
m e n t , bu t m ay occu r a t a n y tim e. In d e cre a sin g ord er of fre q u en cy, cu ta n eou s ,
e
r
h ep a t ic, p u lm on a ry, a n d ren a l h yp ers en s it ivit y rea ct ion s m ay a lso occu r.
a
p
W h e n in it ia t in g t h e ra py w it h s u lfa s a la zin e, it is a d vis a ble t o ch e ck ba s e lin e
y
blo o d co u n t s a n d live r fu n ct io n t e s t s , a n d s cre e n fo r glu co s e -6-p h o s p h a t e
d e h yd roge n a s e d e cie n cy. Th e d ru g is be s t in t rod u ce d in cre m e n t a lly, s t a rt in g
w it h a 500 m g d a ily d os e a n d t h en in cre a s in g by 500 m g w e e kly u n t il t h e t h e ra -
p e u t ic t a rge t d os e of 1 t o 2 g t w ice d a ily is re a ch e d . Blood cou n t s a n d live r fu n c-
t ion t e s t s h ou ld be a s s e s s e d a t 2-w ee k in t e rva ls u n t il t h e p a t ie n t h a s be e n on t h e
t a rge t m a in t e n a n ce d os e for a t le a s t 1 m on t h . Blood cou n t s a n d liver t ra n s a m i-
n a s e leve ls ca n t h e n be m on it ore d le s s fre q u e n t ly, bu t s h ou ld be a s s e s s e d a t
le a s t eve ry 3 m on t h s . As le u kop e n ia m ay occu r p recip it ou s ly, p a t ie n t s s h ou ld be
in s t ru ct e d t o p rom p t ly rep ort t h e occu rre n ce of feve r, m a la is e, m ou t h u lce rs , or
s ore t h roa t .

LEFLUNOMIDE
Le u n om id e is a n in h ibit or of d ih yd ro-orot a t e d e h yd roge n a s e, a n e n zym e m e d i-
a t in g s yn t h e s is of pyrim id in e s . Le u n om id e h a s s ign i ca n t in h ibit ory e ffe ct s on
p rolife ra t ion of lym p h ocyt e s a n d h a s d e m on s t ra t e d e f ca cy in t h e m a n a ge m e n t
of rh e u m a t oid a rt h rit is . Ad ve rs e e ffe ct s of le u n om id e a re re la t ive ly m ild a n d
in fre q u e n t , a n d in clu d e reve rs ible a lop e cia , s kin ra s h , d ia rrh e a , a n d e leva t ion in
live r e n zym e s . Le u n om id e is t e ra t oge n ic in a n im a ls a n d con t ra in d ica t e d in
w om e n w h o a re or w is h t o be com e p regn a n t .
Live r fu n ct ion t e s t s s h ou ld be a s s e s s e d a t ba s e lin e a n d a t m on t h ly in t e r-
va ls fo llow in g in it ia t io n o f t h e ra p y. Fre q u e n cy o f t e s t in g ca n b e e xt e n d e d t o
eve ry 3 m on t h s for p a t ie n t s w h o h ave be e n on t h e ra p y in e xce s s of 6 m on t h s
w it h ou t s ign s of live r t oxicit y. Le u n om id e s h ou ld be p rom p t ly d is con t in u e d if
s ign i ca n t e leva t ion s in live r t ra n s a m in a s e s occu r. Th e s e ru m h a lf-life of t h e
 Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 287

m a jor a ct ive m e t a bolit e of le u n om id e (re fe rre d t o a s M1) e xce e d s 2 w e e ks , bu t

be ca u s e of s ign i ca n t e n t e roh e p a t ic circu la t ion , t h e s e ru m leve ls of M1 ca n be
ra p id ly d e cre a s e d w it h a d m in is t ra t ion of ch ole s t yra m in e. In t h e s e t t in g of s ig-
n i ca n t live r or t h e occu r re n ce of p re gn a n cy, a 10- t o 14-d a y co u r s e of 8 g
ch o le s t yra m in e t a k e n t h re e t im e s d a ily s h o u ld b e a d m in is t e re d t o e n h a n ce
ra p id e lim in a t ion of d ru g a n d brin g t h e s e ru m leve ls of M1 be low 0.02 µg/m L. It
is re com m e n d e d t h a t s e q u e n t ia l d e t e rm in a t ion s of M1 be p e rform e d a t 2-w e e k
in t e rva ls u n t il it is e s t a blis h e d t h a t e lim in a t ion is com p le t e.

GOLD SALTS—AUROTHIOGLUCOSE AND AURANOFIN

Gold s a lt s h a ve a va rie t y of e ffe ct s on ce lls a n d e n zym e s t h a t regu la t e im m u n e
re s p on s e s a n d in a m m a t ory re a ct ion s re leva n t t o t h e p a t h oge n e s is a n d e xp re s -
s ion of rh e u m a t oid a rt h rit is . Alt h ou gh p a re n t e ra l gold s a lt s , s u ch a s a u rot h i-
oglu cos e, a re ve ry e ffe ct ive d is e a s e -m od ifyin g d ru gs , be ca u s e of t h e fre q u e n cy
o f s id e e ffe ct s p a t ie n t s e xp e r ie n ce ove r t im e a n d n ew e r t h e ra p ie s t h a t a re
m u ch be t t e r t ole ra t e d , t h e u s e of gold s a lt s h a s d im in is h e d con s id e ra bly. Th e
p re p a ra t ion s s t ill cu r re n t ly in u s e in s e le ct e d p a t ie n t s a re a u ro t h ioglu cos e ,
a d m in is t e re d p a re n t e ra lly, a n d a u ra n o n , a d m in is t e re d ora lly.

y
p
Th e m o s t co m m o n a d ve r s e eve n t s lim it in g u s e of gold co m p o u n d s a re

a
r
e
m u cocu t a n e o u s re a ct io n s in clu d in g s t om a t it is , p r u r it is , a n d a n y n u m b e r of

h
T
va rio u s fo rm s o f d e rm a t it is . Alt h ou gh ra re ly re p o rt e d w it h u s e of a u ra n o n ,

d
p rot e in u ria m a y be a com p lica t ion of p a re n t e ra l gold s a lt t h e ra p y t h a t m a y

n
a
re q u ire e it h e r d os e a t t e n u a t ion or ce s s a t ion of t h e ra p y. Le u kop e n ia , t h rom bo-

s
i
s
cyt op e n ia , a n d a p la s t ic a n e m ia a re ra re , bu t p ot e n t ia lly, fa t a l co n s e q u e n ce s

o
n
t h a t m a y occu r a t a n y t im e d u rin g t h e cou rs e of gold t h e ra py.

g
a
For p a tien ts on p a ren tera l gold th era py, blood cou n ts a n d a u rin a lysis sh ou ld

i
D
be ch ecked p rior to ea ch in jection d u rin g th e rst yea r of trea tm en t. On ce a p a tien t

6
is on a stable regim en beyon d th e in itia l yea r, th e m on itorin g in terva l for p rotein u -

N
O
ria a n d cytop en ia s ca n be exten d ed to every oth er in jection . Th e d evelop m en t of

I
T
sign i ca n t leu kop en ia ( 3,500/m m 3), th rom bocytop en ia ( 100,000/m m 3), or a p er-

C
E
sisten t d ow n w a rd tren d in th e p la telet cou n t or h em a tocrit sh ou ld p rom p t cessa -

S
t ion of ch rysoth e ra py. In th e a bs en ce of oth er id en ti a ble ca u ses for observed
cytop en ia (s), trea tm en t w ith gold com p ou n d s sh ou ld n ot be rein stitu ted . Protein u -
ria d u rin g trea tm en t w ith gold com p ou n d s is often tra n sien t, resp on d in g to tem -
p ora ry w ith h old in g of gold ; m ost p a tien ts ca n resu m e trea tm en t a t low er d oses
w ith ou t recu rren ce of th e p rotein u ria . Gold sh ou ld n ot be rein stitu ted in p a tien ts
w h o d evelop n ep h rotic-ra n ge p rotein u ria ( 1 g p rotein excreted /24 h ou rs).
Mon it orin g of p a t ie n t s on gold t h e ra py a ls o re q u ire s a t t e n t ion t o t h e occu r-
re n ce of s kin ra s h , p ru rit is , or m ou t h u lce rs . Prior t o e a ch in je ct ion of p a re n t e ra l
go ld , p a t ie n t s s h o u ld b e q u e s t io n e d a s t o t h e o ccu rre n ce of m u co cu t a n e o u s
s ym p t om s ; p a t ie n t s on ora l gold s h ou ld be a d vis e d t o rep ort t h e occu rre n ce of
s kin ra s h o r s ym p t o m s o f s t o m a t it is t h a t m a y a ris e b e t w e e n m o n t h ly bloo d
ch e cks . Th e m a jorit y of m u cocu t a n e ou s s id e e ffe ct s a re be s t m a n a ge d by in t e r-
ru p t ion of t h e ra p y a n d t h e n re s u m in g t re a t m e n t a t a low e r d os e on ce t h e d e r-
m a t it is or s t om a t it is h a s re s olve d .
Nit rit oid re a ct ion s a re va s om ot or re s p on s e s t o in je ct ion of gold m a n ife s t by
s ym p t om s of u s h in g, n a u s e a , vom it in g, sw e a t in g, or d izzin e s s . Su ch re a ct ion s
a re ra re ly s e e n follow in g a d m in is t ra t ion of a u rot h ioglu cos e, bu t h a ve be e n
rep ort e d w it h u s e of a u ra n o n . Th e p e rip h e ra l va s od ila t a t ion a s s ocia t e d w it h
n it rit oid re a ct ion s is u s u a lly w e ll t ole ra t e d , bu t in e ld e rly p a t ie n t s w it h a rt e rio-
s cle rot ic va s cu la r d is e a s e m ay, it re s u lt in s t roke or m yoca rd ia l in fa rct ion .

TETRACYCLINES—MINOCYCLINE AND DOXYCYCLINE

In a d d it ion t o t h e ir w e ll-e s t a blis h e d a n t im icrobia l e ffe ct s , t e t ra cyclin e s h ave a
va rie t y of e ffe ct s on le u kocyt e s a n d e n zym e s in volve d in im m u n e re s p on s e s
 288 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

t h a t like ly a ccou n t for t h e ir m od e ra t e e f ca cy in t h e m a n a ge m e n t of rh e u m a -

t oid a rt h rit is . Te t ra cyclin e s in h ibit t h e a ct ivit y of m a t rix m e t a llop rot e a s e s a n d
h a ve d e m on s t ra t e d e f ca cy in p reve n t in g bon e re s orp t ion in p a t ie n t s w it h p e r-
iod on t a l d is e a s e.
In con t rolle d t ria ls exa m in in g t h e e f ca cy of m in ocyclin e in t h e t re a t m e n t
of rh e u m a t oid a rt h rit is , ve ry few s id e e ffe ct s w e re e xp e rie n ce d t h a t re q u ire d
d is con t in u a t ion of t h e d ru g. Sid e e ffe ct s m os t com m on ly exp e rie n ce d a m on g
p a t ie n t s u s in g t e t ra cyclin e s ove r e xt e n d e d t im e p e riod s in clu d e n a u s e a a n d
a n ore xia . Ph ot os e n s it ivit y is n ot u n com m on , p a rt icu la rly a s s ocia t e d w it h u s e of
d oxycyclin e. Ve rt igo a n d t h e d eve lop m e n t of s la t e -gray s kin p igm e n t a t ion a re
m os t oft e n a s s ocia t e d w it h u s e of m in ocyclin e. Ra re com p lica t ion s ot h e r t h a n
h yp e rs e n s it ivit y re a ct ion s in clu d e h ep a t it is , in t e rs t it ia l n ep h rit is , p ron ou n ce d
e os in op h ilia , le u ke m oid re a ct ion s , a n d d ru g-in d u ce d lu p u s s yn d rom e s .
Given th e a dverse effects of tetra cyclin es on skeleta l d evelop m en t in th e fetu s
a s w ell a s p igm en ta tion of u n eru p ted teeth , tetra cyclin es sh ou ld n ot be given to
p regn a n t w om en or you n g ch ild ren . Alth ou gh th ere a re n o p u blish ed gu id elin es
for a d u lt p a tien ts ta kin g tetra cyclin es over exten d ed tim e p eriod s, su rveilla n ce a t
3-m on th in terva ls for p ossible h em a tologic, liver, or ren a l a bn orm a lities w ith rou -
tin e blood cou n ts, seru m crea tin in e, a n d liver tra n sa m in a ses is a dvisa ble. Fla re of
S
E
join t sym p tom s w h ile on m in ocyclin e req u ires con sid era tion of th e p ossibility of
C
T
a n evolvin g d ru g-in d u ced lu p u s syn d rom e; th e syn d rom e is often a ssocia ted w ith
I
O
h ep a titis, u su a lly a ssocia ted w ith a p ositive a n tin u clea r a n tibody test a n d p rom p t
N
6
resolu tion of join t sym p tom s u p on w ith d raw a l of th e d ru g.
D
i
a
g
n
Cyto to xic a nd Antipro life ra tive Drug s
o
s
i
s
CYCLOPHOSPHAMIDE
a
n
d
Th e e ffe ct s of cyclop h os p h a m id e a re m e d ia t e d t h rou gh it s a ct ive m e t a bolit e s ,
T
h
h yd roxycyclop h os p h a m id e a n d p h os p h ora m id e m u s t a rd , w h ich a lkyla t e DNA,
e
r
re s u lt in g in b re a k s in DNA, d e cre a s e d DNA s yn t h e s is , a n d ce ll a p o p t o s is .
a
p
Alt h ou gh t h e re la t ion s h ip be t w e e n t h e d ru g’s cyt ot oxic e ffe ct s a n d it s im m u -
y
n oregu la t ory e ffe ct s re m a in u n cle a r, T-ce ll p rolife ra t ion a n d t h e p rolife ra t ion
a n d fu n ct ion of B-ce ll lym p h ocyt e s a re s ign i ca n t ly a ffe ct e d by cyclop h os p h a -
m id e . Da ily o ra l cyclo p h o s p h a m id e is fre q u e n t ly t h e d r u g o f ch o ice fo r t h e
m a n a ge m e n t of p a t ie n t s w it h s ys t e m ic n e crot izin g va s cu lit is a n d for p a t ie n t s
w it h a ct ive lu n g in a m m a t ion a s s ocia t e d w it h a u t oim m u n e d is e a s e. In t e rm it -
t e n t in t ra ve n ou s “p u ls e ” cyclop h os p h a m id e is com m on ly e m p loye d in p a t ie n t s
w it h ce r t a in m a n ife s t a t io n s o f lu p u s . Th e t ox icit ie s o f cyclo p h o s p h a m id e
in clu d e reve rs ible m ye los u p p re s s ion , bla d d e r t oxicit y, ova ria n fa ilu re, a n d irre -
ve rs ible oligos p e rm ia .
Th e a d ve rs e e ffe ct s of cyclop h os p h a m id e a re d e p e n d e n t in p a rt o n t h e
a d m in is t e re d d os e a n d w h e t h e r t h e d ru g is give n a s a d a ily ora l d os e or a s a
p e riod ic in t rave n ou s p u ls e. Effe ct s of in t rave n ou s p u ls e d os in g on p e rip h e ra l
le u kocyt e cou n t s a re fa irly p re d ict a ble, w it h a n a d ir in t h e le u kocyt e cou n t occu r-
rin g w it h in 8 t o 14 d ays follow in g a s in gle in t rave n ou s d os e a n d fu ll re cove ry
21 d ays p os t d os e. To a ch ieve t h e d e s ire d clin ica l e ffe ct s in lu p u s p a t ien t s w it h ou t
in d u cin g s eve re le u kop e n ia a n d t h e a t t e n d a n t ris k of in fe ct ion , s u bs e q u e n t
d os e s of in t rave n ou s cyclop h os p h a m id e a re u s u a lly a d ju s t e d on t h e ba s is of t h e
W BC n a d ir 10 t o 14 d ays p os t d os e, a t t e n u a t in g t h e d os e if t h e W BC n a d ir is
1,500/m m 3 . It is a ls o p ru d e n t t o a s s e s s t h e W BC im m e d ia t e ly p rior t o e a ch
in t rave n ou s d os e. In t h e d os e s e m p loye d for m a n a ge m e n t of rh eu m a t ologic d is -
ord e rs , p u ls e in t rave n ou s d os e s of cyclop h os p h a m id e ge n e ra lly h ave m in im a l, if
a n y, im p a ct on p la t e let cou n t s .
Th e h e m a t ologic e ffe ct s of d a ily ora l cyclop h os p h a m id e a re m u ch le s s p re -
d ict a ble. Dru g-in d u ce d le u kop e n ia a s w e ll a s t h rom bocyt op e n ia m a y occu r a t
a n y t im e d u rin g t h e cou rs e of t re a t m e n t . Blood cou n t s s h ou ld be m on it ore d a
 Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 289

m in im u m of eve ry 2 w e e ks follow in g in it ia t ion of t h e ra py. For m a n a ge m e n t of

va s cu lit id e s s u ch a s m icros cop ic p olya n giit is or gra n u lom a t os is w it h a n giit is
(Wege n e r’s gra n u lom a t os is ), clin ica l e f ca cy d oe s n ot re q u ire in d u ct ion of cyt o-
p e n ia . On ce a s t a ble t a rge t d os e (u s u a lly 2 m g/kg/d a y) h a s be e n e s t a blis h e d a n d
blo o d co u n t s h a ve b e e n s t a ble fo r a m in im u m o f 6 t o 8 w e e k s , t h e in t e rva l
be t w e e n blood cou n t d e t e rm in a t ion s ca n be e xt e n d e d t o eve ry 4 w e e ks ; lon ge r
in t e rva ls be t w e e n blood cou n t d e t e rm in a t ion s a re n ot re com m e n d e d .
Toxic e ffe ct s of cyclop h os p h a m id e on t h e bla d d e r a re a ls o re la t e d t o t h e
rou t e of a d m in is t ra t ion a s w e ll a s t h e d u ra t ion of t h e ra p y. W it h a t t e n t ion t o
h yd ra t ion a t t h e t im e of a d m in is t ra t ion , p u ls e in t rave n ou s cyclop h os p h a m id e
in d os e s e m p loye d for m a n a ge m e n t of lu p u s ge n e ra lly d oe s n ot re s u lt in bla d -
d e r t oxicit y. Bla d d e r t oxicit y p rim a rily occu rs in t h e s e t t in g of lon g-t e rm d a ily
ora l cyclop h os p h a m id e a n d is d u e t o exp os u re of ve s icu la r ep it h e liu m t o a cro-
le in , a cyclop h os p h a m id e m e t a bolit e. Micros cop ic or gros s h e m a t u ria is t h e
com m on p re s e n t in g fe a t u re of a crole in t oxicit y. In t h e s e t t in g of e it h e r ora l or
in t rave n ou s cyclop h os p h a m id e t h e ra py, u rin a lys is s h ou ld be p e rform e d m on t h ly
w it h p rom p t u rologic eva lu a t ion of n on glom e ru la r h e m a t u ria . Th e ris k of bla d -
d e r ca n ce r is s ign i ca n t ly in cre a s e d in p a t ie n t s w h o re ce ive cyclop h os p h a m id e ;
m a jor ris k fa ct ors a re d a ily ora l d os in g, a h is t ory of cyclop h os p h a m id e -in d u ce d

y
p
cys t it is , s m okin g, d u ra t ion of t h e ra py of m ore t h a n 2 ye a rs , a n d a cu m u la t ive

a
r
e
d os e in e xce s s of 100 g (9 ). For p a t ie n t s w h o h ave e xp e rie n ce d a n ep is od e of

h
T
cyclop h os p h a m id e -in d u ce d cys t it is , life -lon g s u rve illa n ce for bla d d e r ca n ce r is

d
re com m e n d e d w it h ye a rly u rin a lys is a n d u rin e cyt ologic eva lu a t ion .

n
a
Rega rd le s s of t h e rou t e of a d m in is t ra t ion , t h e re is a 45% t o 71% p e rce n t ris k

s
i
s
of ova ria n fa ilu re follow in g t re a t m e n t w it h cyclop h os p h a m id e, w it h h igh e s t

o
n
ra t e s o bs e rve d a m o n g w om e n w h o a re o ld e r a n d w h o h a ve re ce ive d h igh e r

g
a
cu m u la t ive d os e s . Sim ila r ra t e s of a zoos p e rm ia a re rep ort e d for m a le s re ce ivin g

i
D
a lkyla t in g a ge n t s , s u ch a s cyclop h os p h a m id e. To p re s e rve fu t u re fe rt ilit y, s p e rm

6
or ova ca n be ba n ke d be fore t re a t m e n t w it h cyclop h os p h a m id e is in it ia t e d .

N
O
Th e re is n o evid e n ce t h a t p rior t re a t m e n t of e it h e r p a re n t w it h cyclop h os p h a -

I
T
m id e is a s s ocia t e d w it h ge n e t ic a bn orm a lit ie s in s u bs e q u e n t offs p rin g.

C
E
Tre a t m e n t w it h ora l cyclop h os p h a m id e is a s s ocia t e d w it h a t w o- t o fou rfold

S
in cre a s e d ris k of m a lign a n cy. Bla d d e r, s kin , m ye lop rolife ra t ive, a n d orop h a ryn -
ge a l ca n ce r s h a ve be e n re p ort e d m ore com m o n ly a m on g p a t ie n t s w it h RA
t re a t e d w it h d a ily cyclop h os p h a m id e t h a n p a t ie n t s w it h RA n ot t re a t e d w it h
cyclop h os p h a m id e. Alt h ou gh t h e re a re in s u f cie n t d a t a t o re n d e r a q u a n t i a ble
ris k for m a lign a n cy follow in g t re a t m e n t w it h p u ls e in t rave n ou s cyclop h os p h a -
m id e, few m a lign a n cie s h ave be e n rep ort e d in t h is s e t t in g.

CHLORAMBUCIL
Ch lora m bu cil a n d it s p rim a ry m e t a bolit e, p h e n yla ce t ic a cid m u s t a rd , a re p ot e n t
a lkyla t in g a ge n t s . Th e clin ica l e ffe ct s a re com p a ra ble t o cyclo p h os p h a m id e ,
a lt h ou gh s low e r in on s e t . Ch lora m bu cil d oe s n ot in d u ce bla d d e r t oxicit y a n d is
m os t oft e n u s e d a s a n a lt e rn a t ive t o cyclop h os p h a m id e w h e n cyt ot oxic t h e r-
a p y is in d ica t e d . It is o ft e n t h e d ru g of ch oice t o s u p p re s s clon e s of im m u -
n oglobu lin ligh t ch a in s e cre t in g ce lls in p a t ie n t s w it h p rim a ry (AL) a m yloid os is .
Th e p rim a ry t oxicit y of ch lora m bu cil is t h a t of m ye los u p p re s s ion , w h ich m a y
occu r a bru p t ly a t a n yt im e d u rin g t h e cou rs e of t re a t m e n t . Alt h ou gh reve rs ible,
ch lora m bu cil-in d u ce d le u kop e n ia m ay p e rs is t for m on t h s follow in g d is con t in -
u a t ion of t h e d ru g.
Be ca u s e of t h e o ccu r re n ce of p re cip it o u s le u ko p e n ia in p a t ie n t s t a k in g
ch lora m bu cil, fre q u e n t s u rve illa n ce for cyt op e n ia is im p e ra t ive. Follow in g t h e
in it ia t ion of t re a t m e n t , CBCs s h ou ld be a s s e s s e d a m in im u m of eve ry 2 w e e ks .
On ce t h e d os e a n d le u kocyt e cou n t a re s t a ble, t h e m on it orin g in t e rva l ca n be
e xt e n d e d t o eve ry 4 w e e ks . Th e ris k of m ye loid le u ke m ia s a s w e ll a s lym p h o-
m a s is in cre a s e d a m on g p a t ie n t s w h o h a ve be e n t re a t e d w it h ch lora m b u cil;
 290 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

t h is a s s ocia t ion s h ou ld be con s id e re d w h e n p a t ie n t s t re a t e d w it h ch lora m bu cil

d eve lop p e rs is t e n t cyt op e n ia , a d e n op a t h y, or ot h e rw is e u n e xp la in e d con s t it u -
t ion a l s ym p t om s .

AZATHIOPRINE AND 6- MERCAPTOPURINE

Aza t h iop rin e is a p u rin e a n a logu e a n t im e t a bolit e t h a t is con ve rt e d follow in g
in gestion by glu ta th ion e S -tra n sfera se a n d su lfh yd ryl grou p s to 6-m erca p top u rin e
(6-MP). Th iop u rin e m etabolites of 6-MP d ecrea se th e syn th esis of p u rin e n u cle-
ot id e s re s u lt in g in a n t ip rolife ra t ive e ffe ct s , w h ile in corp ora t ion of t h iop u rin e
n u cleotid es in to DNA a n d RNA resu lts in cytotoxicity. Th e n et im m u n osu p p res-
sive effects of a za th iop rin e a n d 6-MP a re com p a rable, bu t a za th iop rin e is better
tolera ted , favorin g its u se. Alth ou gh ef ca ciou s a s a d isea se-m od ifyin g d ru g in th e
t re a t m e n t of rh e u m a t oid a rt h rit is , a za t h iop rin e is u s e d m os t com m on ly a s a
steroid -sp a rin g a gen t in th e m a n agem en t of lu p u s a n d in a m m a tory m yositis.
Th e m ye los u p p re s s ive e ffe ct s of a za t h iop r in e a re d os e re la t e d a n d va ry
con s id e ra bly a m on g in d ivid u a ls . Seve re m ye los u p p re s s ion is m os t oft e n a s s o-
cia t e d w it h a ge n e t ic p olym orp h is m in t h e a ct ivit y of t h iop u rin e m e t h ylt ra n s -
fe ra s e (TPMT), on e of t h e t w o e n zym e s (xa n t h in e oxid a s e be in g t h e ot h e r) t h a t
S
E
co n ve r t 6-MP t o in a ct ive m e t a b o lit e s . Th io p u rin e m e t h ylt ra n s fe ra s e a ct ivit y
C
T
h a s a t rim od a l d is t ribu t ion , w it h 90% of t h e p op u la t ion h avin g n orm a l a ct ivit y,
I
O
N
ju s t few e r t h a n 10% h avin g in t e rm e d ia t e a ct ivit y, a n d a bou t 1 in 300 in d ivid u a ls
6
h om ozygou s for p oorly fu n ct ion in g TPMT; m e d ia n TPMT a ct ivit y is rep ort e d t o
D
be low e r a m on g Africa n Am e rica n s re la t ive t o Ca u ca s ia n s (10 ). Mye los u p p re s -
i
a
g
s io n a s s o cia t e d w it h im p a ire d TPMT a p p e a rs a n yw h e re fro m 1 t o 3 m o n t h s
n
o
fo llow in g in it ia t ion o f t re a t m e n t w it h a za t h io p rin e. As s a ys for TPMT a ct ivit y
s
i
a re co m m e rcia lly a va ila ble ; p ru d e n t a p p roa ch e s a t p re s e n t t o a void s eve re
s
a
m ye los u p p re s s ion a re e it h e r t o a s s e s s TPMT a ct ivit y u p on in it ia t ion of t h e ra py
n
d
o r t o ca re fu lly follow bloo d cou n t s in p a t ie n t s a t 2-w e e k in t e rva ls follow in g
T
h
in it ia t ion of t re a t m e n t w it h a za t h iop rin e a s t h e d os e is s e q u e n t ia lly in cre a s e d
e
r
by 25 t o 50 m g t o t h e t a rge t a m ou n t (u s u a lly 2 t o 3 m g/kg/d ay). On ce t h e t a rge t
a
p
d os e h a s be e n a ch ieve d w it h s t a ble blood cou n t s , t h e in t e rva l for blood cou n t
y
s u rve illa n ce ca n be e xt e n d e d t o eve ry 1 t o 3 m on t h s .
Aza th iop rin e a n d 6-MP a re m etabolized by xa n th in e oxid a se, a n d u se of eith er
d ru g is best avoid ed in p a tien ts ta kin g a xa n th in e oxid a se in h ibitor, su ch a s a llop -
u rin ol or febu xosta t. For p a tien ts req u irin g a xa n th in e oxid a se in h ibitor to m a n -
age gou t, em p loyin g a n a ltern a tive im m u n osu p p ressa n t su ch a s m ycop h en ola te
is recom m en d ed . If n o effective a ltern a tive op tion s exist, th e d ose of a za th iop rin e
sh ou ld be a tten u a ted 75% to 80% a n d blood cou n ts m on itored w eekly.
Ga s t roin t e s t in a l s ym p t om s a re t h e m os t com m on s id e e ffe ct s a s s ocia t e d
w it h u s e of a za t h iop rin e. Na u s e a , vom it in g, or d ia rrh e a oft e n re s p on d s t o d os e
a t t e n u a t ion follow e d by m ore gra d u a l d os e in cre a s e s (25 m g/w e e k) a s clin ica lly
in d ica t e d . It is im p ort a n t t o re cogn ize t h a t re la t ive le u kop e n ia is n ot re q u ire d
t o a ch ieve t h e ra p e u t ic im m u n os u p p re s s ion w it h a za t h iop rin e. Alt h ou gh s eve re
h e p a t it is a n d ch o le s t a s is a re ra re co m p lica t io n s o f a z a t h io p r in e u s e , m ild
in cre a s e s in live r e n zym e s occu r in u p t o 10% of p a t ie n t s . Live r fu n ct ion t e s t s
s h ou ld be ch e cke d w it h in t h e rs t m on t h of in it ia t in g t re a t m e n t a n d eve ry 3 t o
4 m on t h s t h e re a ft e r. A re a s on a ble a p p roa ch t o p a t ie n t s w h o d eve lop s e ru m
leve ls of live r t ra n s a m in a s e s in e xce s s of t w ice t h e u p p e r lim it of n orm a l is t o
w it h h old t h e ra p y a n d re in it ia t e t re a t m e n t a t a low e r d os e.
Ot h e r ra re com p lica t ion s of a za t h iop rin e u s e in clu d e a cu t e h yp e rs e n s it iv-
it y s yn d rom e s , e os in op h ilia , d ru g feve r, a n d d ru g-in d u ce d p a n cre a t it is . Th e re is
co n ict in g d a t a w it h re ga rd t o a n y in cre a s e d ris k o f m a lign a n cy a s s o cia t e d
w it h a za t h iop rin e u s e. Alt h ou gh n ot a p p rove d for u s e d u rin g p regn a n cy, favora -
ble ou t com e s h ave be e n rep ort e d w h e n a za t h iop rin e h a s be e n u s e d t o m a n a ge
a n d s u p p re s s t h e e m e rge n ce of s eve re lu p u s com p lica t ion s t h rou gh t h e cou rs e
of p regn a n cy.
 Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 291

MYCOPHENOLATE MOFETIL
Mycop h e n ola t e m ofe t il is a n e s t a blis h e d t h e ra p y for t h e s u p p re s s ion of gra ft
re je ct ion in orga n t ra n s p la n t re cip ie n t s t h a t is a cq u irin g a n exp a n d e d role a s a n
im m u n os u p p re s s a n t in t h e m a n a gem e n t of p a t ie n t s w it h a u t oim m u n e d is ea s e.
Follow in g in ge s t ion t h e d ru g is h yd rolyzed t o it s a ct ive m e t a bolit e, m ycop h e n olic
a cid , a n in h ibit or of in os in e m on op h os p h a t e d e h yd roge n a s e. As lym p h ocyt e s a re
p a rt icu la rly d ep e n d e n t on t h is e n zym e for d e n ovo s yn t h e s is of p u rin e s , m yco-
p h e n ola t e s e lect ive ly t a rge t s p rolife ra t ion of T- a n d B-ce ll lym p h ocyt es w it h ou t
a s ign i ca n t im p a ct on gra n u lop oie s is , e ryt h rop oies is , or t h rom bop oies is .
Mycop h e n ola t e h a s be e n s t u d ie d a s a n a lt e rn a t ive t o cyclop h os p h a m id e in
t h e m a n a ge m e n t o f lu p u s n e p h r it is a n d is ge n e ra lly w e ll t o le ra t e d . Mo s t
a d ve rs e eve n t s re la t e t o GI in t ole ra n ce in clu d in g n a u s e a , vom it in g, d ia rrh e a ,
a n d a bd om in a l p a in . For p a t ie n t s e xp e rie n cin g s ign i ca n t GI in t ole ra n ce, u s e of
m ycop h e n olic a cid p rep a ra t ion s m ay be be t t e r t ole ra t e d . Live r e n zym e a bn or-
m a lit ie s m ay occu r, a n d p a t ie n t s t a kin g m ycop h e n ola t e s h ou ld h ave live r fu n c-
t ion t e s t p e rfor m e d a t ba s e lin e, 1 m on t h follow in g in it ia t ion of t h e ra p y a n d
eve ry 3 t o 4 m on t h s t h e re a ft e r.

y
p
Othe r Immuno mo dula ting Drug s

a
r
e
h
CYCLOSPORINE A AND TACROLIMUS

T
d
Origin a lly d eve lop e d a n d e m p loye d t o s u p p re s s gra ft re je ct ion in re cip ie n t s of

n
a
orga n t ra n s p la n t s , cyclos p orin e a n d t a crolim u s a re u s e d a s a d is e a s e -m od ifyin g

s
i
s
d r u gs in t h e m a n a ge m e n t o f r h e u m a t o id a r t h r it is a n d o t h e r a u t o im m u n e

o
n
d is ord e rs , in clu d in g ch ron ic re cu rre n t a n t e rior u ve it is , p s oria t ic a rt h rit is , a n d

g
a
Be h ce t ’s s yn d rom e. Th e s e d ru gs in h ibit t h e a ct iva t ion of T ce lls a n d s e cre t ion

i
D
of IL-2 (a m a jor T-ce ll grow t h fa ct or) by form in g a cyt op la s m ic com p le x w it h

6
cyclo p h ilin . Th e re s u lt in g co m p le x in a ct iva t e s a p h o s p h a t a s e (ca lcin e u r in )

N
O
re q u ire d for t h e t ra n s loca t ion of a fa ct or t o t h e n u cle u s t h a t a ct iva t e s t ra n -

I
T
C
s crip t ion of IL-2 a n d ot h e r ge n e s a s s ocia t e d w it h a ct iva t ion of T ce lls .

E
Alt h ou gh cyclos p orin e a n d t a crolim u s a re ge n e ra lly w e ll t ole ra t e d , m e a s u r-

S
a ble bu t reve rs ible d e cre a s e s in re n a l fu n ct ion occu r in t h e m a jorit y of p a t ie n t s
t re a t e d . A s m a ll ris e in s e ru m cre a t in in e w it h in t h e rs t 3 m on t h s of t re a t m e n t
is fa irly p re d ict a ble, bu t oft e n re m a in s s t a ble t h e re a ft e r. How eve r, a n in cre a s e
in s e ru m cre a t in in e t h a t e xce e d s 30% of t h e ba s e lin e va lu e p ort e n d s p os s ible
irreve rs ible n e p h rot oxicit y. In s u ch in s t a n ce s t h e a d m in is t e re d d os e s h ou ld be
a t t e n u a t e d by 1 m g/kg/d ay a n d t e m p ora rily d is con t in u e d if t h e s e ru m cre a t i-
n in e re m a in s e leva t e d . Provid e d t h e s e ru m cre a t in in e leve l re t u rn s t o w it h in
15% of t h e e s t a blis h e d ba s e lin e leve l, cyclos p orin e ca n be s a fe ly re s t a rt e d a t t h e
a t t e n u a t e d d os e (11 ). Hyp e rt e n s ion is re p ort e d t o occu r in a p p roxim a t e ly 20%
p e rce n t of p a t ie n t s bu t ca n be m a n a ge d w it h e it h e r a t t e n u a t ion in t h e d os e of
cyclos p orin e or a d d it ion of a n t ih yp e rt e n s ive d ru g t h e ra py.
Ot h e r com m o n s id e e ffe ct s of cyclo s p o rin e in clu d e t re m or, p a re s t h e s ia ,
h yp e r t r ich o s is , h yp e r k a le m ia , h yp o m a gn e s e m ia , a n d h yp e r u r ice m ia . Live r
e n zym e a bn orm a lit ie s , p a rt icu la rly a ris e in s e ru m a lka lin e p h os p h a t a s e, occu r
n o t u n com m on ly, bu t a re s e ld om of clin ica l s ign i ca n ce. W h ile cyclo s p o rin e
u s e in re cip ie n t s of orga n t ra n s p la n t s h a s be e n a s s ocia t e d w it h a n in cre a s e d
ris k of s kin ca n ce r a n d lym p h om a , t h is a s s ocia t ion h a s n ot be e n con rm e d
a m on g s m a lle r coh ort s of p a t ie n t s w it h RA t re a t e d w it h cyclos p orin e.

DAPSONE
Origin a lly e m p loye d in t h e t re a t m e n t of lep ros y, d a p s on e is a s u lfon e w it h s ig-
n i ca n t in h ibit ory e ffe ct s on t h e fu n ct ion of n e u t rop h ils . Alt h ou gh t h e re a re few
con t rolle d t ria ls e xa m in in g it s e f ca cy, it is m os t com m on ly u s e d in t h e m a n -
a ge m e n t of cu t a n e ou s le u kocyt ocla s t ic va s cu lit is , u rt ica ria l va s cu lit is , bu llou s
 292 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

or u lce ra t ive cu t a n e ou s lu p u s , a n d oroge n it a l u lce rs a s s ocia t e d w it h Be h ce t ’s

s yn d rom e.
Us e of d a p s on e re q u ire s a t t e n t ion t o d os e -d ep e n d e n t e ffe ct s of t h e d ru g on
e ryt h ro cyt e s a n d t h e p o t e n t ia l fo r d ru g-in d u ce d a gra n u lo cyt o s is . Reve rs ible
a gra n u locyt os is a ffe ct in g a s m a n y a s on e of eve ry 250 in d ivid u a ls m ay occu r
d u rin g t h e rs t 2 m on t h s of t re a t m e n t . Som e d egre e of m e t h e m oglobin e m ia
a n d h e m olys is is s e e n in a lm os t a ll p a t ie n t s re ce ivin g d os e s of 100 m g d a ily or
h igh e r. Alt h ou gh in d ivid u a l va ria t ion e xis t s , t h e a d ve rs e e ffe ct s of d a p s on e on
re d ce ll m e m bra n e s a re u s u a lly w e ll t ole ra t e d a n d oft e n s t a bilize or re s olve
a ft e r 6 w e e ks . How eve r, p a t ie n t s d e cie n t in glu cos e -6-p h os p h a t e d e h yd roge -
n a s e a re p a r t icu la r ly s u s ce p t ible t o h e m o lys is t h a t m a y b e s eve re a n d life
t h re a t e n in g, a n d it is a d vis a ble t o p re s cre e n p a t ie n t s for evid e n ce of t h is d e -
cie n cy p rior t o in s t it u t in g t re a t m e n t w it h d a p s on e.
Th e d ru g is be s t t ole ra t e d s t a rt in g w it h a 25 m g d a ily d os e, a d va n cin g t o t h e
t a rge t t h e ra p e u t ic d os e of 100 m g d a ily ove r t h e cou rs e of s eve ra l w e e ks . Blood
cou n t s s h ou ld be m on it ore d w e e kly u n t il t h e t a rge t d os e h a s be e n a ch ieve d for
a m on t h a n d t h e n m on t h ly t h e re a ft e r. Sh ou ld a s ign i ca n t fa ll in h e m a t ocrit
a n d h e m oglobin leve ls occu r, t h e d ru g s h ou ld be w it h h e ld a n d re in t rod u ce d a t
a low e r d os e. Live r fu n ct ion t e s t s s h ou ld be a s s e s s e d w it h in t h e rs t s eve ra l
S
E
w e e ks o f t re a t m e n t , fo llow in g a n y d os e in cre m e n t s , a n d p e r io d ica lly eve ry
C
T
3 m on t h s t h e re a ft e r. A ra re h yp e rs e n s it ivit y s yn d rom e ch a ra ct e rize d by feve r,
I
O
e xfolia t ive ra s h , ja u n d ice, a n d h e m olys is m ay occu r w it h d a p s on e u s e ; p a t ie n t s
N
6
w it h t h is com p lica t ion s h ou ld n ot be re t re a t e d .
D
i
a
g
THALIDOMIDE
n
o
s
Follow in g its w ith d raw a l in 1961 beca u se of its w ell-p u blicized a n d d ra m a tic tera -
i
s
togen ic effects, th a lid om id e w a s rein t rod u ced sp eci ca lly for th e m a n a gem en t of
a
n
eryt h e m a n od os u m lep ros u m , p re s e n t ly it s on ly a p p rove d in d ica t ion . Th a lid o-
d
T
m id e h a s in h ibitory effects on th e p rod u ction of tu m or n ecrosis fa ctor (TNF- )
h
e
a n d h a s been rep orted to be of ef ca cy in th e trea tm en t of s evere m u cocu ta n eou s
r
a
u lce rs a s s ocia t e d w it h Be h cet ’s s yn d rom e, a s w ell a s s eve re cu t a n e ou s le s ion s
p
y
a ssocia ted w ith lu p u s, sa rcoid osis, a n d pyod erm a ga n gren osu m . It h a s a lso been
rep orted to be of ben e t in th e m a n a gem en t of gra ft-vers u s-h os t d isea se.
In a d d it io n t o t h e kn ow n t e ra t oge n ic e ffe ct s , p e rip h e ra l n e u rop a t h y is a
fre q u e n t co m p lica t io n o f t h a lid o m id e u s e , a n d a s id e from t h e t e ra t oge n ic
COMMON PITFALLS TO e ffe ct s , it is t h e m a jor lim it in g fa ct or in it s lon g-t e rm u s e. Ne rve d a m a ge from
AVOID WHEN USING
TNF INHIBITORS t h a lid om id e is u s u a lly m a n ife s t by s ym m e t ric, p a in fu l p a re s t h e s ia s t h a t oft e n
p e rs is t d e s p it e d is con t in u a t ion of t h e d ru g. Sin ce n e rve con d u ct ion a bn orm a l-
1. In fe ct io n s e sp e cia lly w it h it ie s m ay be n ot e d p rior t o t h e on s e t of n e u rop a t h y s ym p t om s , p e riod ic e le c-
re a ct iva t e d m yco b a ct e ria
o r h e p a t it is B t rop h ys iologic t e s t in g o f p e rip h e ra l n e rve s h a s b e e n a d vo ca t e d for p a t ie n t s
re ce ivin g t h a lid om id e ove r e xt e n d e d t im e in t e rva ls , w it h d is con t in u a t ion of
2. In fu sio n re a ct io n s w it h t h e d ru g if n e u rop a t h y occu rs .
in ixim a b

Tumo r Ne cro sis Fa cto r Anta g o nists

ETANERCEPT
Et a n e rce p t is a ge n e t ica lly e n gin e e re d ch im e ric m ole cu le com p ris in g t w o of
t h e h u m a n p 75 s olu ble re ce p t o rs for TNF- a d join e d t o t h e Fc p o rt io n o f a
h u m a n IgG. By bin d in g TNF, e t a n e rcep t p re clu d e s liga t ion of TNF re cep t ors on
e ffe ct or ce lls p a rt icip a t in g in im m u n e a n d in a m m a t ory re s p on s e s p rom ot e d
by t h is cyt o k in e . Ad m in is t e re d a s a s u b cu t a n e o u s in je ct io n t w ice w e e k ly,
e t a n e rcep t is p re d om in a n t ly u s e d for t h e m a n a ge m e n t of rh e u m a t oid a rt h rit is
a n d ju ve n ile id iop a t h ic a rt h rit is . Et a n e rce p t is a ls o a p p rove d for a n d u s e d in
t h e m a n a ge m e n t of ot h e r rh e u m a t ic d is e a s e s in clu d in g p s oria t ic a rt h rit is a n d
a n kylos in g s p on d ylit is ; it h a s a ls o be e n u s e d w it h s u cce s s in m a n a gin g m a n i-
fe s t a t ion s of Be h ce t ’s s yn d rom e.
 Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 293

Sin ce e t a n e rcep t is a fu lly h u m a n ize d m ole cu le, it is u s u a lly w e ll t ole ra t e d

a n d it s u s e d oe s n ot re q u ire rou t in e la bora t ory m on it orin g. In je ct ion s it e re a c-
t ion s co n s is t in g o f m ild e ryt h e m a a n d sw e llin g la s t in g 1 t o 3 d a ys o ccu r in
m ore t h a n a t h ird of p a t ie n t s , bu t t h ey a re w e ll t ole ra t e d a n d d o n ot p re clu d e
con t in u a t ion of t h e ra p y.

ANTI- TNF- MONOCLONAL ANTIBODIES (INFLIXIMAB,

ADALIMUMAB, GOLIMUMAB)
Origin a lly a p p rove d for u s e in p a t ie n t s w it h s eve re com p lica t ion s of Croh n ’s
d is e a s e, a n t i-TNF- a n t ibod ie s a re a p p rove d for a n d m os t com m on ly u s e d in
t h e m a n a ge m e n t of rh e u m a t oid a rt h rit is , p s oria t ic a rt h rit is , a n d a n kylos in g
s p on d ylit is . Th ey m a y a ls o be u s e fu l in t h e m a n a ge m e n t of s eve re m a n ife s t a -
t ion s of Be h ce t ’s s yn d rom e.
In ix im ab is a ch im e ric m on oclon a l a n t ibody con s is t in g of a m u rin e d om a in
in t h e va ria ble region w it h bin d in g s p e ci cit y for h u m a n TNF- ; t h e re m a in d e r
of t h e a n t ibod y is of h u m a n origin . Ad m in is t e re d by in t rave n ou s in fu s ion , in f-
lixim a b bin d s a n d n e u t ra lize s s e cre t e d TNF- . Bin d in g of in ix im a b t o ce lls
e xp re s s in g s u rfa ce TNF- m a y a ls o re s u lt in a n t ibod y-m e d ia t e d cyt ot oxicit y.

y
p
In ixim a b is u s u a lly w e ll t ole ra t e d a n d rou t in e la bora t ory m on it orin g for t oxic-

a
r
e
it y is n ot re q u ire d . Hu m a n a n t ich im e ric a n t ibod y re s p on s e s t o m u rin e com p o-

h
T
n e n t s of t h e a n t ibody d eve lop in u p t o 40% of p a t ie n t s give n in ixim a b. In fu s ion

d
re a ct ion s w it h p ru rit is , u rt ica ria , a n d / or ch ills occu r in a s m a ll m in orit y of

n
a
p a t ie n t s a n d re s p on d favora bly t o h a lt in g of t h e in fu s ion a n d a d m in is t ra t ion of

s
i
s
a n t ih is t a m in e s . Re t re a t m e n t of p a t ie n t s w h o h a ve e xp e rie n ce d a n in fu s ion

o
n
re a ct ion is n ot re com m e n d e d . Alt h ou gh n ot re q u ire d for in it ia l e f ca cy, cot re a t -

g
a
m e n t w it h low -d os e w e e kly m e t h ot re xa t e h a s be e n s h ow n t o d e cre a s e (bu t n ot

i
D
a broga t e ) h u m a n a n t ich im e ric a n t ibody re s p on s e s a n d m ay ext e n d t h e d u ra t ion

6
of in ixim a b e f ca cy.

N
O
Fu lly h u m a n ized a n tibod ies to TNF- a re a d m in istered a s su bcu ta n eou s in jec-

I
T
tion s a t 1- to 2-w eek (adalim um ab ) or 4-w eek (golim um ab ) in terva ls. Th e d evelop -

C
E
m en t of n eu tra lizin g a n tibod ies is ra re, a n d a lth ou gh in jection site rea ction s m ay

S
occu r, th ey a re often tra n sien t a n d u su a lly d o n ot req u ire cessa tion of th era py.

CERTOLIZUMAB
Ce rt olizu m a b is a p egyla t e d con s t ru ct of F(a b’) com p on e n t s of m on oclon a l re a -
ge n t s h avin g s p e ci cit y for TNF- cova le n t ly bou n d t o p olye t h yle n e glycol. It s
e f ca cy in n e u t ra lizin g TNF- is com p a ra ble t o t h a t of a n t i-TNF- a n t ibod ie s ,
bu t t h e a bs e n ce of t h e Fc-a s s ocia t e d com p le m e n t xin g d om a in s m a y re n d e r
it le s s like ly t o e n ge n d e r in je ct ion s it e re a ct ion s occa s ion a lly s e e n w it h e t a n e r-
ce p t , a d a lim u m a b, or golim u m a b.

SURVEILLANCE FOR INFECTION, MALIGNANCY, AND

AUTOIMMUNE DISEASE
Sin ce TNF- like ly p lays a role in h os t d e fe n s e, p a t ie n t s w h o a re t a kin g a n y of
t h e TNF- in h ibit ors s h ou ld be ca u t ion e d a bou t t h e occu rre n ce of in fe ct ion a n d
a ll of t h e s e re a ge n t s s h ou ld be u s e d w it h ca u t ion in p a t ie n t s p re d is p os e d t o
s e riou s ba ct e ria l in fe ct ion s . It is ge n e ra lly a d vis a ble t o w it h h old a n t i-TNF- in
t h e s e t t in g of a cu t e ba ct e ria l in fe ct ion , re s u m in g t re a t m e n t on ce t h e in fe ct ion
h a s re s olve d w it h a p p rop ria t e a n t im icrobia l t h e ra p y. Rep ort e d re a ct iva t ion of
t u be rcu los is in p a t ie n t s give n a n t i-TNF- re a ge n t s e m p h a s ize s t h e n e e d fo r
ca u t ion a n d ca re fu l p re s cre e n in g a n d s u rve illa n ce w h e n a d m in is t e rin g TNF-
n e u t ra lizin g a n t ibod ie s t o p a t ie n t s w it h ris k fa ct ors for or kn ow n p rior h is t ory
of t u be rcu los is (12 ). Dis s e m in a t e d fu n ga l in fe ct ion s h a ve a ls o be e n re p ort e d ,
a n d ca re fu l m on it orin g for t h is com p lica t ion is p ru d e n t .
 294 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

In p a t ie n t s w it h a ct ive h ep a t it is C, t re a t m e n t w it h a n t i-TNF- re a ge n t s h a s
n ot in cre a s e d vira l loa d s , u n favora bly a lt e re d t h e cou rs e of d is e a s e, or im p a ire d
re s p on s e s t o a n t ivira l t h e ra py. How eve r, exa ce rba t ion of h ep a t it is B vira l (HBV)
in fe ct ion h a s be e n rep ort e d in t h e con t ext of t h e ra py w it h a n t i-TNF- re a ge n t s ,
a n d t h is cla s s of biologic t h e ra py is be s t avoid e d in t h e con t e xt of a ct ive HBV
d is ea s e ; a s s u ch , s cre e n in g for HBV is re com m e n d e d be fore s t a rt in g a n t i-TNF-
re a ge n t s . Pa t ie n t s w it h h u m a n im m u n od e cie n cy viru s (HIV) d is e a s e w h o
d eve lop s eve re p s oria s is m ay be t re a t e d w it h a n t i-TNF- re a ge n t s ; a lt h ou gh
d oin g s o d oe s n ot a p p e a r t o a d ve rs e ly a ffe ct re s p on s e s t o a n t ire t rovira l t h e ra py,
ext ra vigila n ce for ba ct e ria l, fu n ga l, a n d m ycoba ct e ria l in fe ct ion is re q u ire d in
p a t ien t s re ce ivin g a n t i-TNF- t h e ra py w h o a re im m u n ocom p rom is e d from HIV.
Em e rge n ce of lym p h om a s h a s be e n rep ort e d in p a t ie n t s re ce ivin g a n t i-TNF-
t h e ra p y; h ow eve r, t h e p reva le n ce of lym p h oid m a lign a n cie s h a s n ot be e n
s h ow n t o be h igh e r in coh ort s of p a t ie n t s w it h RA w h o h ave re ce ive d a n t i-TNF-
re a ge n t s re la t ive t o t h os e w h o h ave n ot . Give n t h e role of TNF- in h os t d e fe n s e
a ga in s t m a lign a n cy, d is con t in u a t ion of t re a t m e n t is n on e t h e le s s a d vis e d in t h e
con t e xt of t h e d eve lop m e n t of lym p h om a a n d ot h e r m a lign a n t n e op la s m s .
Ad m in is t ra t ion of a n t i-TNF- m on oclon a l re a ge n t s is a s s ocia t e d w it h t h e
d eve lop m e n t of a n t in u cle a r a n t ibod ie s in a m in orit y of p a t ie n t s . Clin ica l m a n -
S
E
ife s t a t ion s of lu p u s h a ve be e n re p ort e d t o occu r follow in g a d m in is t ra t ion of
C
T
in ixim a b, a n d a n t i-TNF- a n t ibod ie s a re n ot re com m e n d e d for u s e in p a t ie n t s
I
O
N
w it h s ys t e m ic lu p u s e ryt h e m a t os u s . Up t o 15% of p a t ie n t s t a kin g e t a n e rce p t
6
a re rep ort e d t o d eve lop n ew p os it ive a n t in u cle a r a n t ibod ie s , a n t ibod ie s t o d ou -
D
ble -s t ra n d e d DNA, or bot h . Alt h ou gh n o p a t ie n t s in p re m a rke t con t rolle d clin i-
i
a
g
ca l t ria ls w h o d eve lop e d s u ch a n t ibod ie s d eve lop e d clin ica l m a n ife s t a t ion s of
n
o
s ys t e m ic lu p u s e ryt h e m a t os u s , a n u m be r of p os t m a rke t ca s e re p ort s h a ve d oc-
s
i
u m e n t e d t h e occu rre n ce of d e m ye lin a t in g s yn d rom e s follow in g in it ia t ion of
s
a
t re a t m e n t w it h e t a n e rcep t . Alt h ou gh la bora t ory m on it orin g for e m e rge n ce of
n
d
a u t oa n t ibod ie s is n ot n e ce s s a ry, a n t i-TNF- t h e ra p y s h o u ld be d is con t in u e d
T
h
s h o u ld a u t o im m u n e d is e a s e m a n ife s t a t io n s n o t n o r m a lly a s s o cia t e d w it h
e
r
rh e u m a t oid a rt h rit is or s p on d yloa rt h rop a t h ie s e m e rge.
a
p
y
IL- 1 Anta g o nists
Biologics t a rge t in g IL-1 in clu d e an akin ra (re com bin a n t h u m a n IL-1 re cep t or
a n t a gon is t ), can akin u m ab (a n a n t i-IL-1 m on oclon a l a n t ibod y), a n d rilon oce pt
(a n IL-1 re ce p t o r/ a cce s s o ry p rot e in con s t ru ct fu s e d t o im m u n oglobu lin Fc).
An a k in ra is a p p rove d fo r t h e t re a t m e n t o f rh e u m a t o id a rt h rit is a n d is co m -
m on ly u s e d in t h e m a n a ge m e n t of s ys t e m ic-on s e t ju ve n ile id iop a t h ic a rt h rit is
a n d a d u lt St ill’s d is e a s e. Ca n a kin u m a b a n d rilon ocep t a re a p p rove d for u s e in
m a n a gin g p a t ie n t s w it h cryop yrin -a s s o cia t e d a u t oin a m m a t ory s yn d ro m e s ;
IL-1 a n t a gon is t s a re a ls o be in g s t u d ie d for p ot e n t ia l u s e in m a n a gin g a n d s u p -
p re s s in g a re s of gou t .
IL-1 a n t a gon is t s a re ge n e ra lly ve ry w e ll t ole ra t e d , a n d t h e ir u s e d oe s n ot
re q u ire la bora t ory m on it orin g ot h e r t h a n p e riod ic m on it orin g of blood cou n t s
t o m on it or for le u cop e n ia t h a t m ay d eve lop in a ve ry s m a ll m in orit y of p a t ie n t s .
In je ct ion s it e re a ct ion s w it h a n a kin ra a re com m on , p a rt icu la rly d u rin g t h e in i-
t ia l w e e ks o f t h e ra p y, bu t d o n o t re q u ire ce s s a t io n o f t re a t m e n t a n d oft e n
d im in is h in t h e ir fre q u e n cy a n d s eve rit y w it h con t in u e d t re a t m e n t .

IL- 6 Anta g o nists

Tocilizu m ab , a h u m a n ize d m on oclo n a l re a ge n t w it h s p e ci cit y for t h e IL-6
re cep t or, is a p p rove d for u s e in p a t ie n t s w it h rh e u m a t oid a rt h rit is w h o h ave
fa ile d t o re s p on d t o t re a t m e n t w it h a n t i-TNF- re a ge n t s . IL-6 h a s m u lt ip le e ffe ct s
on m u lt ip le ce lls of t h e im m u n e s ys t e m a s w e ll a s h ep a t ocyt e s . Eleva t ion s in
 Ch a p te r 28 Mon it orin g of Pa t ie n t s on An t irh e u m a t ic Th e ra py 295

s e r u m ch o le s t e ro l co m m o n ly o ccu r fo llow in g in it ia t io n o f t re a t m e n t w it h
t ocilizu m a b, a n d m on it orin g of s e ru m ch ole s t e rol is re com m e n d e d d u rin g t h e
in it ia l m on t h s of t re a t m e n t . Dos e -lim it in g e leva t ion s in live r t ra n s a m in a s e s
m ay a ls o occu r in t h e con t e xt of t re a t m e n t w it h t ocilizu m a b, a n d m on it orin g
of AST a n d ALT leve ls a t 3- t o 4-m on t h in t e rva ls is re com m e n d e d . Sin ce IL-6
p ro m ot e s t h ro m b op oie s is a s w e ll a s gra n u lo p o ie s is , p e r io d ic m on it or in g a t
3-m on t h in t e rva ls for le u cop e n ia a n d t h rom bocyt op e n ia is a ls o re com m e n d e d
for p a t ie n t s re ce ivin g t ocilizu m a b.

Bio lo g ics Ta rg e ting T- Ce ll Activa tio n

Abatace pt is a h u m a n re com bin a n t con s t ru ct of CTLA4 a n d im m u n oglobu lin
Fc t h a t bin d s t o liga n d s on a n t ige n -p re s e n t in g ce lls re q u ire d for s e n d in g cos -
t im u la t ory s ign a ls t o T ce lls t h rou gh CD28. Th e n e t e ffe ct of a ba t a ce p t t re a t -
m e n t is a d e cre a s e in a ct iva t ion of T ce lls by a n t ige n -p re s e n t in g ce lls . Aba t a -
cep t is a p p rove d for u s e in p a t ie n t s w it h rh e u m a t oid a rt h rit is w h o h ave fa ile d
t o re s p o n d t o con ve n t io n a l n on b io logic DMARD t h e ra p y. Pa t ie n t s re ce ivin g
a ba t a cep t d o n ot re q u ire s p e ci c la bora t ory m on it orin g, a n d ove ra ll in fe ct ion

y
ra t e s a re n ot re p ort e d t o be h igh e r in p a t ie n t s w it h rh e u m a t oid a rt h rit is re ce iv-

p
a
in g a ba t a ce p t . How eve r, vigila n ce for in fe ct ion s w it h p a t h oge n s in w h ich in t a ct

r
e
h
T-ce ll fu n ct ion m ay be re q u ire d for re s olu t ion is a p p rop ria t e. Tit e rs of a n t ibod -

T
ie s in re s p on s e t o p rim a ry im m u n iza t ion a re a t t e n u a t e d in p a t ie n t s re ce ivin g

d
n
a ba t a cep t re la t ive t o t h os e n ot re ce ivin g a ba t a ce p t . Alt h ou gh t h e clin ica l s ig-

a
s
n i ca n ce of t h is a t t e n u a t ion is u n cle a r, it is re co m m e n d e d t h a t p a t ie n t s in

i
s
o
n e e d of p rim a ry im m u n iza t ion re ce ive s u ch im m u n iza t ion s p rior t o in it ia t in g

n
g
t re a t m e n t w it h a ba t a cep t .

a
i
D
Us te kin u m ab is a h u m a n ge n om e –d e rive d m on oclon a l re a ge n t w it h s p e -

6
ci cit y for t h e p 40 s u bu n it s h a re d by IL-12 a n d IL-23. Blockin g IL-12 a t t e n u a t e s

N
t h e m a t u ra t ion a n d a ct iva t ion of t h e Th 1 lin e a ge of T ce lls , w h ile blockin g IL-23

O
I
T
a t t e n u a t e s t h e m a t u ra t ion a n d s u rviva l of T17 ce lls , a s u bs e t of T ce lls im p li-

C
E
ca t e d in t h e p a t h oge n e s is o f a n u m b e r o f a u t o im m u n e d is o rd e rs , in clu d in g

S
in a m m a t ory bow e l d is e a s e, p s oria s is or p s oria t ic a rt h rit is , a n d RA. High e r-
t h a n -e xp e ct e d ra t e s of in fe ct ion or m a lign a n cy h a ve n ot be e n obs e rve d in con -
t rolle d s t u d ie s of u s t e kin u m a b; h ow eve r, give n t h e in h ibit ory e ffe ct s on T-ce ll
m a t u ra t ion a n d a ct iva t ion , vigila n ce for t u be rcu los is a n d fu n ga l in fe ct ion s is
n on e t h e le s s re com m e n d e d .

Bio lo g ics Ta rg e ting B Lympho cyte s

Ritu x im ab is a ch im e ric a n t ibody, w it h t h e m u rin e com p on e n t of t h e a n t ige n -
bin d in g d om a in h avin g s p e ci cit y for CD20 e xp re s s e d on B lym p h ocyt e s , w it h
t h e n e t e ffe ct of t re a t m e n t d ep le t in g CD20 + B ce lls . Rit u xim a b is a p p rove d for
t re a t m e n t of rh e u m a t oid a rt h rit is n ot re s p on d in g t o con ve n t ion a l DMARD t h e r-
a py. Rit u xim a b h a s a ls o be e n u s e d in t h e m a n a ge m e n t of ot h e r a u t oa n t ibod y-
m e d ia t e d d is ord e rs in clu d in g SLE, a lt h ou gh clin ica l t ria ls in SLE w it h rit u xim a b
h ave fa ile d t o a ch ieve p rim a ry e f ca cy e n d p oin t s a n d it is n ot ye t a p p rove d for
t h is in d ica t ion . B-lym p h ocyt e d ep le t ion w it h rit u xim a b is w e ll t ole ra t e d by t h e
va s t m a jorit y of p a t ie n t s w it h ou t s ign i ca n t in cre a s e s in obs e rve d in fe ct ion ris k.
How eve r, ca s e s of p rogre s s ive m u lt ifoca l le u koe n cep h a lop a t h y (PML) be ca u s e of
p olyom a (JC) viru s rep lica t ion in t h e CNS h ave be e n rep ort e d in p a t ie n t s re ce iv-
in g rit u xim a b in com bin a t ion w it h ot h e r con com it a n t im m u n os u p p re s s ive t h e r-
a py. As s u ch , m on it orin g a n d vigila n ce for n eu rologic d ys fu n ct ion is p ru d e n t in
p a t ie n t s t re a t e d w it h rit u xim a b. Alt h ou gh p la s m a ce lls d o n ot e xp re s s CD20,
leve ls of IgG a s w e ll a s IgA a n d IgM m ay d e crea s e ove r t im e w it h rep e a t e d u s e of
rit u xim a b, a n d p e riod ic a s s e s s m e n t of im m u n oglobu lin leve ls is re com m e n d e d
for p a t ie n t s re ce ivin g m u lt ip le cou rs e s of t rea t m e n t .
 296 Se ctio n 6 Sp e cia l Dia gn os t ic a n d Th e ra p e u t ic Con d it ion s

Be lim u m ab is a h u m a n ge n o m e –d e rive d m on oclo n a l a n t ibo d y w it h s p e -

ci cit y for B-lym p h ocyt e s t im u la t or (BlyS), a ls o re fe rre d t o a s B-ce ll–a ct iva t in g
fa ct or (BAFF), a p p rove d for t h e t re a t m e n t of s ys t e m ic lu p u s e ryt h e m a t os u s .
B-lym p h ocyt e s t im u la t or (BAFF) is re q u ire d for t h e s u rviva l a n d p rolife ra t ion of
B lym p h o cyt e s in t o a n t ib od y-s e cre t in g p la s m a bla s t s . Be lim u m a b t re a t m e n t
re s u lt s in d e cre a s e s in t it e rs of a u t oa n t ibod ie s bu t d oe s n ot im p a ir t h e s u rviva l
of m a t u re p la s m a ce lls a n d is n ot a s s ocia t e d w it h s ign i ca n t h yp oglobu lin e m ia
or d e cre a s e s in a n t ibod y t it e rs ge n e ra t e d in re s p on s e t o p reviou s im m u n iza -
t ion . How eve r, h yp oglobu lin e m ia m a y p ot e n t ia lly occu r if be lim u m a b is u s e d in
com bin a t ion w it h o t h e r im m u n os u p p re s s ive t h e ra p ie s (s u ch a s a za t h io p rin e
o r m yco p h e n o la t e ), a n d leve ls o f im m u n o glo b u lin s s h o u ld b e p e r io d ica lly
a s s e s s e d in s u ch p a t ie n t s .

Re fe re nce s
1. Sa a g KG, Em key R, Sch n it ze r TJ, e t a l . Ale n d ron a t e for t h e p reve n t ion a n d t re a t m e n t of glu cocort icoid -
in d u ce d os t e o p oros is . N Engl J Med 1998 ;339 (5 ):292 –299 .
2. Fr ie s JF. Th e e p id e m io logy o f NSAID ga s t ro p a t h y: Th e ARAMIS e x p e r ie n ce . J Clin Rheu m atol 1998 ;
4 (Su p p l ):S11 .
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3. Silve rs t e in FE, Gra h a m DY, Se n ior JR, e t a l. Mis op ros t ol re d u ce s s e riou s ga s t ro in t e s t in a l com p lica t io n s
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in p a t ie n t s w it h rh e u m a t oid a rt h rit is re ce ivin g n on s t e roid a l a n t i-in a m m a t ory d ru gs . A nn Int Med 1995 ;
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123 :241 .
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4. Morga n SL, Ba ggot t JE, Va u gh n W H , e t a l. Th e e ffe ct of folic a cid s u p p le m e n t a t ion on t h e t oxicit y of low -
d os e m e t h ot re xa t e in p a t ie n t s w it h rh e u m a t oid a rt h rit is . A rthritis Rheum 1990 ;33 :9 .
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5. Kre m e r JM , Ala rcon GS, Ligh t foot RW, Jr , e t a l. Me t h ot re xa t e for rh e u m a t oid a rt h rit is : Su gge s t e d gu id e -
D
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lin e s fo r m on it orin g live r t oxicit y. A rthritis Rheum 1994 ;37 :316 .
a
g
6. Pa vy S , Con s t a n t in A, Ph a m T, e t a l. Me t h o t re xa t e t h e ra p y fo r rh e u m a t o id a rt h r it is : Clin ica l p ra ct ice
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gu id e lin e s ba s e d on p u blis h e d evid e n ce a n d e xp e rt op in ion . Joint Bone Spine 2006 ;73 (4 ):388 –395 .
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7. Ea s t e r b ro o k M . De t e ct io n a n d p reve n t ion o f m a cu lop a t h y a s s ocia t e d w it h a n t im a la r ia l a ge n t s . Int
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Ophthalm ol Clin 1999 ;39 (2 ):49 –57 .
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8. Blyt h C, La n e C. Hyd roxych loroq u in e re t in op a t h y: Is s cre e n in g n e ce s s a ry ? BMJ 1998 ;316 (7133 ):716 –717 .
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9. Ta la r-Willia m s C, Hija zi YM , Wa lt h e r MM e t a l. Cyclo p h os p h a m id e -in d u ce d cys t it is a n d bla d d e r ca n ce r
T
in p a t ie n t s w it h Wege n e r’s gra n u lom a t os is . A nn Intern Med 1996 ;124 :477 .
h
10. McLe od HL, Lin JS, Scot t EP, e t a l. Th iop u rin e m e t h ylt ra n s fe ra s e a ct ivit y in Am e rica n w h it e s u bje ct s a n d
e
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bla ck s u bje ct s . Clin Pharm acol Ther 1994 ;55 :15 .
a
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11. Pa n ayi GS, Tu gw e ll P. Th e u s e of cyclos p orin A m icroe m u ls ion in rh e u m a t oid a rt h rit is . Con clu s ion s of
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a n in t e rn a t ion a l review . Br J Rheum atol 1997 ;36 :808 .
12. Tu be rcu los is a s s ocia t e d w it h blockin g a ge n t s a ga in s t t u m or n e cros is fa ct or-a lp h a —Ca liforn ia , 2002–2003 .
MMW R Morb Mortal W kly Rep 2004 ;53 (30 ):683 .
Index

Pa ge n u m be rs follow e d by f in d ica t e gu re s ; t h os e follow e d by t in d ica t e t a ble s .

Aba t a cep t , 295 An kle s p ra in , 43, 71–73, 71f, 72f

Abd om e n , 105 An kylos in g s p on d ylit is , 3, 7, 96, 101
Ace t a bu la r d ys p la s ia , 57 An t e rior cru cia t e liga m e n t , 51
Ace t a m in op h e n , 26 An t e rior righ t h ip liga m e n t s , 57f
Ace t yls a licylic a cid (a s p irin ), 148 An t e rior t a lo bu la r liga m e n t s (ATFL), 71, 71f
Ach ille s t e n d in it is , 39–40 An t e rior t a rs a l t u n n e l s yn d rom e, 42
Ach ille s t e n d in op a t h y, 70–71 An t im a la ria ls , 285–286
Acrom ega lic a rt h rop a t h y, 227 An t in e u t rop h il cyt op la s m a n t ibod y
Acrom ega ly, 227 (ANCA), 134
Acro-os t e olys is , 115 An t in u cle a r a n t ibod ie s (ANA), 126, 160
Acu t e cu t a n e ou s lu p u s , 103, 105 An t ip h os p h olip id a n t ibod y, 108
Acu t e m on oa rt h rit is , 5 An t irh e u m a t ic t h e ra py
Acu t e t ra n s ie n t s yn ovit is , 55 a n t im a la ria ls , 285–286
Ad a lim u m a b, 293 B lym p h ocyt e s , biologics t a rge t in g, 295–296
Ad h e s ive ca p s u lit is , 225–226, 225t colch icin e, 283
Ad ve n t it iou s bu rs a , 38 cort icos t e roid s , 280–281
Ale n d ron a t e, 209 cyt ot oxic a n d a n t ip rolife ra t ive d ru gs
Alka p t on u ria (och ron os is ), 232 a za t h iop rin e, 290
Allop u rin ol, 192 ch lora m bu cil, 289–290
Alp h aviru s e s , 260–262 cyclop h os p h a m id e, 288–289
Am a u ros is fu ga x, 143 cyclos p orin e, 291
Am e rica n College of Rh e u m a t ology (ACR), 85, d a p s on e, 291–292
86t , 89, 90t , 106t , 145, 145t 6-m e rca p t op u rin e, 290
Am e rica n –Eu rop e a n Con s e n s u s Grou p , m ycop h e n ola t e m ofe t il, 291
80, 81t t a crolim u s , 291
5-a m in os a licylic a cid , 286 t h a lid om id e, 292
Am yloid os is , 233, 233f d is e a s e -m od ifyin g a n t irh e u m a t ic d ru gs
An a kin ra , 193, 294 (DMARDs ), 283–284
An a lge s ia , 34 gold s a lt s , 287
p h a rm a cologic, 53 IL-6 a n t a gon is t s , 294–295
An a lge s ics , 179 IL-1β a n t a gon is t s , 294
A naplasm a phagocytophilum , 252 le u n om id e, 286–287
An e m ia of ch ron ic in a m m a t ion , 104 m e t h ot re xa t e, 284–285, 285t
An kle join t , 277 n on s t e roid a l a n t i-in a m m a t ory d ru gs
s t a bilit y, 72f (NSAIDs ), 281–283, 282t

297
298 In d e x

An t irh e u m a t ic t h e ra py (Continued) h e m op h ilia , 231

s u lfa s a la zin e, 286 s ickle ce ll d is e a s e, 230, 230f
T-ce ll a ct iva t ion , biologics t a rge t in g, 295 w it h h e re d it a ry d is ord e rs
t e t ra cyclin e s , 287–288 a lka p t on u ria (och ron os is ), 232
t u m or n e cros is fa ct or (TNF)-α a n t a gon is t s of con n e ct ive t is s u e s , 232
a n t i-TNF-α m on oclon a l a n t ibod ie s , 293 h e m och rom a t os is , 231–232, 231f
ce rt olizu m a b, 293 Wils on ’s d is e a s e, 232
e t a n e rce p t , 292–293 w it h m a lign a n cie s
s u rve illa n ce for in fe ct ion , 293–294 ca rcin om a t ou s p olya rt h rit is , 228–229
An t i-Scl70, 115 com p le x region a l p a in s yn d rom e (CRPS), 229
An t is p a s m od ics , 180 h ypertroph ic osteoa rth ropath y (HOA), 228, 228f
An t i-TNF-α m on oclon a l a n t ibod ie s , 293 m u lt ice n t ric re t icu loh is t iocyt os is (MR), 229,
An xiolyt ics , 165 229f
Ap ley grin d t e s t , 50, 50f RS3PE, 229–230
Arc s ign , p a in fu l, 68f s a rcoid os is , 234
Art h ra lgia s , 6, 151, 231 Art h rop a t h ie s , crys t a llin e, 87–88
Art h rit is , HCV-re la t e d , 259 Art icu la r com p la in t s , p a t ie n t s w it h
Art h rit is –d e rm a t it is s yn d rom e, 3 com orbid it ie s , 6
Art h rit is m u t ila n s , 82, 82f p a t ie n t ’s ba ckgrou n d
Art h roce n t e s is , 53, 274 a ge, 3–4
com p lica t ion s , 276 e t h n ic p re d ile ct ion , 4
e q u ip m e n t , 275, 275t ge n d e r, 4
t e ch n iq u e s for, 275–276 s ym p t om a t ology
a n kle join t , 277 in a m m a t ory ch a n ge s , p re s e n ce of, 5–6
e lbow, 278, 279f p a t t e rn s of join t in volve m e n t , 4–5
kn e e, 276–277, 277f s ign s a n d s ym p t om s , 6
m e t a ca rp op h a la n ge a l join t , 277, 277f As p irin , low -d os e, 113
m e t a t a rs op h a la n ge a l join t , 277, 278f As ym m e t ric oligoa rt h rit is , 88
s h ou ld e r, 277–278 At h e ros cle ros is , 147
s u ba crom ia l bu rs a , 278, 278f At la s , a n a t om y of, 12, 13f
w ris t , 278–279, 279f Atypical con n ective tissu e disease (ACTD),
Art h rop a t h ie s , 224f. See also Gou t a n d 150, 151t
crys t a l–in d u ce d a rt h rop a t h ie s Au ra n o n , 287
a m yloid os is , 233, 233f Au rot h ioglu cos e, 287
crys t a l-in d u ce d , 3 Au t oim m u n e h e m olyt ic a n e m ia , 104
w it h e n d ocrin e d is e a s e s Au t oim m u n e t h yroid it is , ch ron ic, 226
a crom ega ly, 227 Ava s cu la r n e cros is , 62f, 63f
a d h e s ive ca p s u lit is , 225–226, 225t Axis , a n a t om y of, 12, 13f
ch a rcot n e u roa rt h rop a t h y, 224–225, 224f Aza t h iop rin e, 107, 290
d ia be t e s m e llit u s , 223
h yp e rp a ra t h yroid is m a n d h yp ovit a m in os is Ba ct e re m ia , 274
D, 227, 227f Ba ct e ria l a rt h rit is , 239–241, 239f
h yp e rt h yroid is m , 226–227 in ch ild re n , 244–245
h yp ot h yroid is m , 226, 227t clin ica l cou rs e, 244
w it h h e m a t ologic d is ord e rs clin ica l p re s e n t a t ion , 241

e xa m in a t ion , 241–242, 242t
in im m u n ocom p rom is e d p a t ie n t s , 245
p ros t h e t ic join t in fe ct ion s , 245
s t u d ie s , 242–243, 243t
t re a t m e n t , 244
B-ce ll–a ct iva t in g fa ct or (BAFF), 296
Be h çe t ’s d is e a s e, 4, 134
Be lim u m a b, 108, 296
Be n ign h yp e rm obilit y s yn d rom e, 232
Bicip it a l t e n d in it is , 33
Bis p h os p h on a t e s , 209–212, 210t , 211f
a n d t e rip a ra t id e, 214
Bla ck-legge d t ick, 249f, 252
Bla d d e r t oxicit y, 289
Ble e d in g d ia t h e s is , 274
B lym p h ocyt e (s ), 295–296
B-lym p h ocyt e s t im u la t or (BAFF), 296
β2 -m icroglobu lin a m yloid os is , 233
Boh a n a n d Pe t e r crit e ria , 121t
Bon e m in e ra l d e n s it y (BMD), 200, 201, 201f,
205, 205f
Bon e s ca n , 19, 39
Bon e s cin t igra p h y, 221
Bon e s p u rs , 175
Bon e tu rn over, bioch em ica l m a rkers of,
204, 204t
Bon y join t e n la rge m e n t , 175f
Bon y sw e llin g, 231
Borrelia burgdorferi (Lym e d is e a s e ), 159
Bos e n t a n , 113
Bou ch a rd ’s n od e s , 175
Bou t on n ie re d e form it y, 82, 82f
Bra ce s , 45–46
Brow n t u m ors h yp e rp a ra t h yroid , 227f
Bu cklin g of kn e e, 49
Bu n ion e t t e, 39
Bu rs e ct om y, 64
Ca ch e xia , 143
Ca lca n e o bu la r liga m e n t (CFL), 71, 71f
Ca lci c t e n d in it is , 35
Ca lcit on in , 209
Ca lciu m , 207
a n d vit a m in D, 207–208, 208t , 213–214
Ca lciu m ch a n n e l blocke rs , 113
In d e x 299
Ca lciu m pyrop h os p h a t e crys t a l d e p os it ion
(CPPD), 88
Ca lciu m pyrop h os p h a t e d ih yd ra t e d e p os it ion
d is e a s e, 194, 195t
Ca llu s e s , 38, 43
Ca n ce r-a s s ocia t e d m yos it is , 122k
Ca p s a icin , 179
Ca rcin om a t ou s p olya rt h rit is , 228–229
Ca rp a l t u n n e l s yn d rom e, 115
Ca u d a e q u in a s yn d rom e, 26
Ce ft ria xon e, 255
Ce lia c s p ru e, 220
Ce n t e rs for Dis e a s e Con t rol a n d Preve n t ion
(CDC), 247, 250f
Ce rt olizu m a b, 293
Ce rvica l colla rs , 19
Ce rvica l ra d icu lop a t h y, 19, 20
Ce rvica l s p in e, 84–85
Ce rvica l s p on d ylos is , 18
Ch a p e l Hill Con s e n s u s Con fe re n ce (CHCC), 133
Ch a rcot n e u roa rt h rop a t h y, 224–225, 224f
Ch e s t , 105
Ch lora m bu cil, 289–290
Ch loroq u in e, 285
Ch on d roit in s u lfa t e, 180
Ch on d rom a la cia p a t e lla e, 68–69
Ch ron ic fa t igu e s yn d rom e (CFS), 159
Ch ron ic gou t , 187
Ch u rg–St ra u s s s yn d rom e, 136
Clin ica l Dis e a s e Act ivit y In d e x (CDAI), 89
Cocke d -u p t oe s , 39
Cod m a n p e n d u lu m e xe rcis e s , 34, 34f
Colch icin e, 190, 283
Colla t e ra l liga m e n t s , 51
Com orbid it ie s , 55
Com p le t e blood cou n t (CBC), 284
Com p le x region a l p a in s yn d rom e (CRPS), 229
Com p u t e d t om ogra p h y, 19, 44, 52, 61
Con n e ct ive t is s u e d is e a s e (CTD). See under
Ove rla p s yn d rom e s
Coolin g of t is s u e s , 46
Cort icos t e roid s , 107, 129, 280–281
Cort icot rop in , 191
Cra n ia l a rt e rit is , 142–143
Crep it u s , 40
300 In d e x

Cre s ce n t s ign , 221f DMARD. See Dis e a s e -m od ifyin g a n t irh e u m a t ic

CREST s yn d rom e, 113 d ru gs (DMARD)
Cricoa ryt e n oid join t , 85 Don u t le s ion , 221
Croh n ’s d is e a s e, 97 Doxycyclin e, 255, 287
Cryoglobu lin e m ia , m ixe d , 259 Dra w e r t e s t , a n t e rior, 72
Crys t a l d e p os it ion d is e a s e, 5 Du a l-en ergy x-ray absorp tiom etry (DXA),
Crys t a l-in d u ce d a rt h rop a t h ie s , 3. See also Gou t 204, 205f
a n d crys t a l-in d u ce d a rt h rop a t h ie s Dyn a m ic s on ogra p h y, 62
Crys t a llin e a rt h rop a t h ie s , 87–88
Cu t a n e ou s bros is , 115 Elbow, 81, 278, 279f
Cu t a n e ou s lu p u s , 103–104 Ele ct rod ia gn os t ic s t u d ie s , 42, 43
Cu t a n e ou s s m a ll-ve s s e l va s cu lit is , 135 Ele ct rom yogra p h y, 18, 126
Cyclop h os p h a m id e, 288–289 Ely’s t e s t , 60
h igh d os e, 108 En cep h a lop a t h y, ch ron ic, 254
Cyclos p orin e, 186, 291 En d ocrin e d is e a s e s . See under Art h rop a t h ie s
Cyt ot oxic a n d a n t ip rolife ra t ive d ru gs En t e rop a t h ic a rt h rit is , 97–98, 101
En t h e s it is , 40
Da p s on e, 291–292 En t h e s op a t h ie s , 96
De com p re s s ive la m in e ct om y, 27 En zym e-lin ked im m u n osorben t a ssay (ELISA), 255
De ep p e ron e a l n e rve e n t ra p m e n t , 42 Ep ip h ys e a l is ch e m ic n e cros is , 230
De e r t ick, 249f, 252 Ep ip h ys is , 56f
De n it ive d ia gn os is , 87 Eryt h e m a m igra n s (EM), 250, 252, 253f
Dege n e ra t ive d is c d is e a s e, 21 Eryt h rocyt e s e d im e n t a t ion ra t e (ESR), 140, 144
Degen era tive join t d isea se. See Osteoa rth ritis Es t roge n , 208
(OA) Et a n e rce p t , 292–293
De n os u m a b, 212 Eu rop e a n Le a gu e Aga in s t Rh e u m a t is m (EULAR),
De p ocort icos t e roid s , 180 85, 86t
De p re s s ion , 27 Exe rcis e bikin g, 27
De rm a t om e s of ce rvica l s p in e, 16f Exe rcis e s , 177, 207
De rm a t om yos it is (DM), 118, 119, 120f, 121t , 153. q u a d rice p s -s t re n gt h e n in g, 53
See also In a m m a t ory m yop a t h ie s Extra -a rticu la r m a n ifesta tion s of RA (ExRA), 79,
Dia be t e s m e llit u s , 223 79t
Dia be t e s m yon e cros is , 8 Ext ra corp ore a l s h ockw ave t h e ra py (ESW T), 71
Dia gn os t ic t e s t , 271–273, 272t Ext re m it ie s , 105
Dia gn os t ic u lt ra s on ogra p h y, 44
Die t a n d a lcoh ol, 185 FABER m a n e u ve r, 59, 60f
Diffu s e s cle rod e rm a , 113 Fa cia l n e rve p a ls y t re a t m e n t , 255
Dim e t icks t ra n s m is s ion , 249f Fa m ilia l h yp oca lciu ric h yp e rca lce m ia (FHH),
Dis e a s e Act ivit y Score (DAS), 89 218
Dis e a s e -m od ifyin g a n t irh e u m a t ic d ru gs Fa m ilia l Me d it e rra n e a n feve r, 4
(DMARD), 283–284 Fe bu xos t a t , 192
biologic, 90, 92 Fe e t a n d a n kle s , 83–84, 84f
s yn t h e t ic, 90, 91t Fibrom ya lgia (FM), 146, 158–159
Dis t a l in t e rp h a la n ge a l join t (DIP), 80, 82 clin ica l cou rs e, 165
Dis t ra ct ion t e s t , 17 clin ica l p re s e n t a t ion , 159–160, 161t
 In d e x 301

e xa m in a t ion , 162 clin ica l p re s e n t a t ion , 183–184, 185t , 194, 195

s t u d ie s , 162, 163t d ie t a n d a lcoh ol, 185
t re a t m e n t , 162, 163–165 ge n e t ics , 184–185
Fibrom ya lgia im p a ct q u e s t ion n a ire, 164 m e d ica t ion s a n d t oxin s , 185–186
Fin ge rs , 82, 82f e xa m in a t ion , 186–187, 186f
Fla t fe e t , 38 s t u d ie s , 187–188, 188t , 196, 196t , 197
Flaviviru s , 258 d iffe re n t ia l d ia gn os is , 188–189, 189t
Foot ort h os e s , 44 t re a t m e n t , 197
Foot w e a r, 177 gou t a re s , m a n a ge m e n t of, 189–191, 190t
Fore foot va ru s a n d va lgu s d e form it ie s , 37 t h e ra p e u t ic a p p roa ch e s , 193–194
Fra n k a rt h rit is , 262 u ra t e -low e rin g t h e ra py for h yp e ru rice m ia ,
FRAX W HO fra ct u re ris k a s s e s s m e n t t ool, 191–193, 192f
206f Gou t a re s , m a n a ge m e n t of, 189–191,
Fre ibe rg d is e a s e, 39 190t
Fru ct os e, 185
Fu n ga l in fe ct ion s , 293 Ha e m op h ilu s in u e n za e, 3, 244
Ha llu x lim it u s , 39
Ga ba p e n t in , 26, 27 Ha llu x rigid u s , 38–39
Ga it a bn orm a lit ie s , 59 Ha llu x va lgu s , 38
Ge n e e xp re s s ion a n a lys is , 124 Ha m m e r t oe s , 39, 84
Gia n t ce ll a rt e rit is (GCA), 132, 133–134, 140, 141f Ha rd corn s , 43
a ort it is a n d p e rip h e ra l a rt e ria l occlu s ion , 143 Ha s h im ot o’s t h yroid it is , 226
clin ica l cou rs e, 148 HCV. See He p a t it is C
clin ica l p re s e n t a t ion , 141–142, 142t He a d , 105
cra n ia l a rt e rit is , 142–143 He a d a ch e, 142
p olym ya lgia rh e u m a t ica , 143 He a rt , 105
s t u d ie s , 144–145, 145t He a rt block, 251
d iffe re n t ia l d ia gn os e s , 145–147, 145t , 146t He a t in g p a d s , 26
t re a t m e n t , 147–148, 148t He liot rop e ra s h , 119, 120f
w a s t in g a n d ca ch e xia , 143 He m a t ologic d is ord e rs . See under
Gle n oh u m e ra l a rt h rit is , 30 Art h rop a t h ie s
Glu cocort icoid , 280 He m och rom a t os is , 231–232, 231f
Glu cocort icoid -in d u ce d os t e op oros is (GIOP), He m op h ilia , 231
213–215, 214f He n och -Sch on le in p u rp u ra , 135
Glu cocort icoid t a p e rin g, 148t He n och -Sch ön le in p u rp u ra , 4
Glu cos a m in e s u lfa t e, 180 He p a t it is B (HBV), 260, 261f
Gold s a lt s , 287 He p a t it is C, 258–260. See also under
Gon ococca l a rt h rit is , 240, 241 Vira l a rt h rit is
Got t ron ’s p a p u le s , 119, 120f He p a t os p le n om ega ly, 105
Gou t , 5 He re d it a ry d is ord e rs a s s ocia t e d w it h
a n d p s e u d ogou t , 3 a rt h rop a t h ie s . See under Art h rop a t h ie s
Gou t a n d crys t a l-in d u ce d a rt h rop a t h ie s He rn ia t e d lu m ba r d is cs , 25
ca lciu m pyrop h os p h a t e d ih yd ra t e d ep os it ion High ly a ct ive a n t ire t rovira l t h e ra py (HAART),
d is e a s e, 194, 195t 263
clin ica l cou rs e, 197 Hin d foot (ca lca n e a l) va ru s , 43, 44
302 In d e x
Hip , 84
fra ct u re s , 201
p a in
in a d u lt s , 56, 57–59, 58f
clin ica l p re s e n t a t ion , 55–56, 56f, 57f
e xa m in a t ion , 59–60, 59f, 60f
s t u d ie s , 60–63, 61f, 62f, 63f
t re a t m e n t a n d clin ica l cou rs e, 64
p rot e ct ors , 207
Hip bu rs a e, 58f
HLA-B27, 100
Hoa rs e n e s s , 85
Hu m a n im m u n od e cie n cy viru s (HIV), 263
Hu m a n le u kocyt e a n t ige n s (HLA), 78
Hya lga n (h ya lu ron a t e s od iu m ), 180
Hyd roxych loroq u in e, 285
Hyp e rp a ra t h yroid is m a n d h yp ovit a m in os is D,
227, 227f
Hyp e rt h yroid is m , 219, 226–227
Hyp e rt rop h ic os t e oa rt h rop a t h y (HOA),
228, 228f
Hyp e ru rice m ia , 184, 185t , 186f
Hyp e s t h e s ia , 42
Hyp ocom p le m e n t e m ia , 169
Hyp oglobu lin e m ia , 296
Hyp op h os p h a t a s ia , 217
Hyp op h os p h a t e m ia , 217
Hyp os p le n is m , 230
Hyp ot h yroid is m , 87, 226, 227t
Hyp ovit a m in os is D, 227, 227f
Id iop a t h ic in a m m a t ory m yop a t h y (IIM).
See In a m m a t ory m yop a t h ie s
IL-6 a n t a gon is t s , 294–295
IL-1β a n t a gon is t s , 294
Iliot ibia l ba n d s yn d rom e s , 69–70
Im m u n os u p p re s s ive d ru gs , 107–108, 121, 122t
Im p in ge m e n t s ign , 67f
In clu s ion bod y m yos it is (IBM), 118, 121
In fa rct s , a cu t e, 230
In fe ct iou s Dis e a s e Socie t y of Am e rica (IDSA),
251
In a m m a t ion , 5–6
In a m m a t ory a rt h rit is , 259–260
In a m m a t ory bow e l d is e a s e (IBD), 95, 97–98
In a m m a t ory m yop a t h ie s
biop s y n d in gs in , 127f
clin ica l ch e m is t ry, 125
clin ica l cou rs e, 130–131
clin ica l p re s e n t a t ion , 118–119, 120f
d ia gn os t ic crit e ria , 121, 121t , 122t
d iffe re n t ia l d ia gn os is , 119
e le ct rom yogra p h y, 126
im a gin g s t u d ie s , 128
im m u n ology, 126
m u s cle biop s y, 126–128, 127f
p a t h oge n e s is , 123, 124–125
p h ys ica l e xa m in a t ion , 122–123, 124t
t re a t m e n t , 128–129
re h a bilit a t ion , 129
t h e ra p e u t ic a p p roa ch e s , 129–130
In ixim a b, 293
In gu in a l m a s s , 63f
In s e rt ion a l t e n d in it is , 70
In t e rle u kin 1β, 193
In t e rn a t ion a l Cla s s i ca t ion of Fu n ct ion in g,
Dis a bilit y, a n d He a lt h (ICF), 11
In t e rn a t ion a l Myos it is As s e s s m e n t a n d Clin ica l
St u d ie s Grou p (IMACS), 129
In t e rn a t ion a l Socie t y of Nep h rology (ISN),
104
In t ra a rt icu la r cort icos t e roid s , 180
In t ra -a rt icu la r t h e ra py for OA, 180
Ja ccou d ’s a rt h rop a t h y, 82, 152
Ja ris ch –He rxh e im e r re a ct ion , 256
Join t d is e a s e, 231
Join t e ffu s ion s , 51
Join t in volve m e n t a n d d ia gn os is ,
4–5, 5t
Join t p a in , 223
Kn e e, 84, 84f, 276–277, 277f
bra ce s , 177
e ffu s ion s , 254
m e ch a n ica l d is ord e rs of
a n a t om ica l com p on e n t s of kn e e, 49f
clin ica l cou rs e, 53
clin ica l p re s e n t a t ion , 48–49
p h ys ica l e xa m in a t ion , 49–52
 In d e x 303

s t u d ie s , 52 Ma le os t e op oros is , 215–216
t re a t m e n t , 52–53 Ma lign a n cie s w it h a rt h rop a t h ie s . See under
Kyp h op la s t y, 212 Art h rop a t h ie s
Ma rfa n s yn d rom e, 57
La ch m a n t e s t , 51 McMu rra y t e s t , 50, 50f
La rge -ve s s e l va s cu lit is . See under Va s cu lit is Me ch a n ic’s h a n d s , 120f, 123, 153
Le u n om id e, 107, 286–287 Me d ia l re t in a cu la r la xit y, 52
Legg-Ca lve -Pe rt h e s ’ d is e a s e, Me d iu m -ve s s e l va s cu lit is , 134
55, 56f Me n in git is t re a t m e n t , 255
Liga m e n t la xit y, 45 Me n is ca l t e a rs , 52
Lim it e d s cle rod e rm a , 113 ch ron ic, 49
Lin e a r e xt e n s or e ryt h e m a , 120f 6-m e rca p t op u rin e, 290
Lin e a r s cle rod e rm a , 113 Me t a ca rp a l p h a la n ge a l join t (MCP), 80, 277,
Live r fu n ct ion t e s t s , 286 277f
Lofgre n s yn d rom e, 6 Me t a ca rp op h a la n ge a l join t , 82, 82f
Low ba ck p a in Me t a t a rs a lgia , 39
clin ica l cou rs e, 27 Me t a t a rs a l s t re s s fra ct u re, 39, 40f
clin ica l p re s e n t a t ion , 23–25, 24f Me t a t a rs op h a la n ge a l join t , 277, 278f
e xa m in a t ion , 25 Me t h ot re xa t e, 90, 107, 284–285, 285t
s t u d ie s , 25–26 ora l, 130
t re a t m e n t , 26–27 Me t h yls u lfon ylm e t h a n e (MSM), 180
Lu m be r s t e n os is . See Low ba ck p a in Mid foot d is e a s e, 84
Lu p u s n e p h rit is , 104 Migra t ory a rt h rit is , 3
Lym e d is e a s e, 247–250, 247f, 248f, Milw a u ke e s h ou ld e r, 197f
249f, 250f Min ocyclin e, 287
clin ica l cou rs e, 256 Mixe d con n e ct ive t is s u e d is e a s e (MCTD),
coin fe ct ion , 252 154–155, 154t
e a rly d is s e m in a t e d d is e a s e, 250–251, 255–256 Mon oa rt icu la r in volve m e n t , 5
e a rly loca lize d d is e a s e, 250, 250f Mon os od iu m u ra t e (MSU), 183
la t e -s t a ge d is e a s e, 251, 256 Morn in g s t iffn e s s , 15, 95, 158
p h ys ica l e xa m in a t ion Mort on n e u rom a , 42
ca rd ia c s ym p t om s , 253 MRI. See Ma gn e t ic re s on a n ce im a gin g (MRI)
m u s cu los ke le t a l, 254 Mu cos a l u lce rs , 96
n e u rologic a bn orm a lit ie s , 253–254 Mu lt ice n t e r Art h ros copy of t h e Hip Ou t com e s
s kin , 252–253, 253f Re s e a rch Ne t w ork, 59
in p regn a n cy, 252 Mu lt ice n t ric re t icu loh is t iocyt os is (MR), 229, 229f
re in fe ct ion w it h B. burgdorferi, 252 Mu s cle d is ord e rs , 7–8, 8t
s t u d ie s , 254 Mu s cle in a m m a t ion , 153
t re a t m e n t , 255 Mu s cu los ke le t a l lu p u s , 104
Lym p h om a s , 294 Mycop h e n ola t e m ofe t il, 108, 291
Myop a t h y, 7
Ma gn e t ic re s on a n ce im a gin g (MRI), 12, 40, 52,
61, 62f, 67, 221f, 231, 233f Na il-fold m icros copy, 111, 111f
Ma gn e t ic re s on a n ce im a gin g a n giogra p h y Na rcot ic a n a lge s ics , 34
(MRA), 144 Na s a l u lce rs , 105
304 In d e x

Na t ion a l Art h rit is Da t a Workgrou p , 183 p s ych os ocia l m e a s u re s , 178

Na t ion a l Os t e op oros is Fou n d a t ion (NOF), s u rgica l in t e rve n t ion , 181
206 s ys t e m ic ora l a ge n t s , 179–180
Ne ck p a in t op ica l a ge n t s , 179
clin ica l cou rs e, 20–22 Os t e oa rt h rit is v ersus rh e u m a t oid a rt h rit is , 80f
clin ica l p re s e n t a t ion , 11–15, 14f Os t e och on d ros is , 39
p h ys ica l e xa m in a t ion , 15–17, 16f, 17t Os t e oge n e s is im p e rfe ct a , 219
s t u d ie s , 17–19 Os t e om a la cia , 216–217
t re a t m e n t , 19–20 Os t e on e cros is , 220–222, 220t , 221f. See
Ne u rologic lu p u s , 104 Os t e op e n ic bon e d is e a s e s
Ne u rologic s ym p t om s a n d s ign s , 17t Os t e on e cros is of ja w (ONJ), 211, 211f
Ne u rop a t h y, ca u s e of, 43 Os t e op e n ic bon e d is e a s e s , 200–201, 200f, 200t ,
Nigh t t im e p a in , 143 201f
Noct u rn a l p a in , 31 clin ica l p re s e n t a t ion , 201–203, 202t
Non s t e roid a l a n t i-in a m m a t ory d ru gs (NSAID), e xa m in a t ion , 203
26, 101, 281–283, 282t . See also under glu cocort icoid -in d u ce d os t e op oros is
Sys t e m ic lu p u s e ryt h e m a t os u s (SLE) h is t ory a n d p h ys ica l e xa m in a t ion , 213
NSAID. See Non s t e roid a l a n t i-in a m m a t ory p reve n t ion a n d t re a t m e n t , 213–215, 214f
d ru gs h yp e rt h yroid is m , 219
Nu m bn e s s of foot , 41 im a gin g, 204–206, 205f, 206f
la bora t ory eva lu a t ion
OA. See Os t e oa rt h rit is (OA) bon e t u rn ove r m a rke rs , 204, 204t
Obe r’s m a n e u ve r, 59, 60f rou t in e la bora t ory t e s t in g, 203, 203t
Oligoa rt icu la r in volve m e n t , 5 m a le os t e op oros is , 215–216
Op h t h a lm os cop e, 112 m e t a bolic bon e m a n ife s t a t ion s , 219–220
Ora l a n a lge s ics , 27 n on p h a rm a cologic p reve n t ion , 207
Ora l bis p h os p h on a t e s , 210 os t e oge n e s is im p e rfe ct a , 219
Ora l h ygie n e, 92 os t e om a la cia , 216–217
Ora l u lce rs , 105 os t e on e cros is , 220–222, 220t , 221f
Ort h ot ics , 44 p h a rm a cologic p reve n t ion
Ort h ovis c (h ya lu ron a n ), 180 bis p h os p h on a t e s , 209–212, 210t , 211f
Os good –Sch la t t e r d is e a s e, 220 ca lcit on in , 209
Os t e oa rt h rit is (OA), 3, 174t ca lciu m a n d vit a m in D, 207–208, 208t
clin ica l cou rs e, 181 d e n os u m a b, 212
clin ica l p re s e n t a t ion , 174 e s t roge n , 208
d ia gn os t ic s t u d ie s , 175 s e le ct ive e s t roge n re ce p t or m od u la t ors
e p id e m iology, 173 (SERMs ), 208–209
e xa m in a t ion , 175, 175f t e rip a ra t id e, 212
p a t h oge n e s is of, 174 p reve n t ion a n d t h e ra py, 206–213
p reve n t ive t h e ra py, 176 p rim a ry h yp e rp a ra t h yroid is m , 218–219
s ym p t om a t ic t h e ra py of s e con d a ry h yp e rp a ra t h yroid is m , 219
a d ju va n t a ge n t s , 180 s u rgica l a p p roa ch e s , 212–213
in t ra -a rt icu la r t h e ra py, 180 Os t e op h yt e s , 32, 35, 38, 175
m e d ica t ion -ba s e d , 178–179, 178t Os t e ot om ie s , 181
p h ys ica l m e a s u re s , 176–178, 176t Ot t a w a An kle Ru le s , 72
 In d e x 305

Ove rla p s yn d rom e s , 150–151, 151t , 152t ort h os e s , 44–45

con n e ct ive t is s u e d is e a s e (CTD) s h oe m od i ca t ion , 45
m ixe d , 154–155, 154t s t e roid in je ct ion s , 46
u n cla s s i e d /u n d iffe re n t ia t e d , 155–157, 155t , t h e ra p e u t ic e xe rcis e, 46
156f Pa lin d rom ic rh e u m a t is m , 88–89
rh u p u s , 151–153, 152f Pa lp a t ion , 41, 43
s cle rod e rm a t om yos it is or s cle rom yos it is , Pa re s t h e s ia s , 42
153 Pa rvoviru s B19, 257–258, 258f
Oxa la t e crys t a l, 197 Pa t e lla r la xit y, 52
Pa t e llofe m ora l d is e a s e, 51
Pa in fu l fe e t Pa t e llofe m ora l p a in s yn d rom e (PFPS), 68–69
clin ica l cou rs e, 46 Pa t rick’s m a n e u ve r, 60, 99, 99f
e xa m in a t ion , 43 Pe d a l e d e m a , 105
m e ch a n ica l p roble m s Pe rcu t a n e ou s ve rt e brop la s t y, 212
a ch ille s t e n d in it is , 39–40 Pe rip h e ra l a rt e ria l occlu s ion , 143
a ch ille s t e n d on ru p t u re, 40 Pe rip h e ra l n e u rop a t h y, 41
bu n ion e t t e, 39 Pe ron e a l t e n d on d is loca t ion , 41
fore foot va ru s a n d va lgu s d e form it ie s , Pe s ca vu s , 38, 38f
37 Pe s p la n u s , 38, 38f
Fre ibe rg d is e a s e, 39 Ph ot os e n s it ive d iffu s e e ryt h rod e rm a , 120f
h a llu x rigid u s , 38–39 Pis t ol grip d e form it y, 57
h a llu x va lgu s , 38 Pla n t a r fa s ciit is , 41
h a m m e r t oe s , 39 Pla s t e r ca s t in g, 224
m e t a t a rs a lgia , 39 Polya rt h rit is , 5, 89
m e t a t a rs a l s t re s s fra ct u re, 39, 40f Polye t h yle n e glycol (PEG)–lin ke d u rica s e
p e ron e a l t e n d on d is loca t ion a n d p e ron e a l (p eglot ica s e ), 193
t e n d in it is , 41 Polym ya lgia rh e u m a t ica (PMR), 4, 89–92, 140,
p e s ca vu s , 38, 38f 143, 146t , 148t . See also Gia n t ce ll a rt e rit is
p e s p la n u s , 38, 38f (GCA)
p la n t a r fa s ciit is , 41 Polym yos it is , 118, 121t . See also In a m m a t ory
p os t e rior t ibia l t e n d in it is a n d ru p t u re, 41 m yop a t h ie s
re t roca lca n e a l bu rs a , 40–41 Pop lit e a l cys t s , 49, 84
s e s a m oid in ju rie s , 39 Pos t e rior lon git u d in a l liga m e n t , 12
s u bcu t a n e ou s a ch ille s bu rs it is , 41 Pos t e rior t a lo bu la r liga m e n t s (PTFL), 71, 71f
n e u rologica l p roble m s , 41 Pos t e rior t ibia l t e n d in it is a n d ru p t u re, 41
a n t e rior t a rs a l t u n n e l s yn d rom e, 42 Pra zos in , 113
m ort on n e u rom a , 42 Pre d n is on e, 107
s u p e r cia l p e ron e a l n e rve e n t ra p m e n t , Pregn a n cy a n d rh e u m a t ic d is e a s e s
42–43 clin ica l cou rs e, 168–169
s u ra l n e rve e n t ra p m e n t , 43 e xa m in a t ion , 167
t a rs a l t u n n e l s yn d rom e, 42 s t u d ie s a n d t re a t m e n t , 167–168
s t u d ie s , 43–44 Pre t e s t p roba bilit y, 269, 270
t re a t m e n t Prim a ry h yp e rp a ra t h yroid is m , 218–219
bra ce s , 45–46 Prop h yla ct ic t h e ra py, 108
m od a lit ie s , 46 Pros t h e t ic join t in fe ct ion s , 245
306 In d e x

Pros t h e t ic join t s , 274 m u s cle d is ord e rs , p a t ie n t s w it h

Proxim a l in t e rp h a la n ge a l join t s (PIP), clin ica l p re s e n t a t ion , 7
39, 80 p h ys ica l n d in gs , 7–8, 8t
Proxim a l m u s cle w e a kn e s s , 8 Rh e u m a t ic d is ord e rs , d ia gn os t ic t e s t s for,
Ps e u d ogou t , 5, 88, 194 269–273, 270f, 271f, 272t
Ps e u d orh e u m a t oid a rt h rit is , 195 Rh e u m a t oid a rt h rit is (RA), 4
Ps oria t ic a rt h rit is , 3, 97, 101 cla s s i ca t ion crit e ria of, 85, 86t , 87t
Pu lm on a ry d is e a s e, 115 clin ica l cou rs e, 92
Pu lm on a ry bros is , 130 clin ica l p re s e n t a t ion , 78–79, 79t
Pu lm on a ry fu n ct ion t e s t s , 117 crys t a llin e a rt h rop a t h ie s , 87–88
Pu lm on a ry h yp e rt e n s ion , 105 d ia gn os is of, 85
Pu ls e t h e ra py, 107 e p id e m iology, 77–78
Pu m p -bu m p s , 41 ge n d e r a n d h orm on a l in u e n ce s , 78
Pyom yos it is , 8 ge n e t ic a n d e n viron m e n t a l ris k fa ct ors , 78
Pyrim id in e s , 286 e xa m in a t ion
ce rvica l s p in e, 84
Qu a d ricep s -s t re n gt h e n in g e xe rcis e s , 53 cricoa ryt e n oid join t , 85
e lbow, 83
RA. See Rh e u m a t oid a rt h rit is fe e t a n d a n kle s , 83–84, 84f
Ra d iogra p h s , 52, 60, 61f, 77f, 83f n ge rs , 82, 82f
Ra d ion u clid e s ca n s , 243 h ip s , 84
Ra d ion u clid e s cin t igra p h y, 61 kn e e s , 84, 84f
Ra loxife n e, 209 m e t a ca rp op h a la n ge a l (MCP) join t s , 82, 82f
Ra n ge -of-m ot ion e xe rcis e s , 34, 46 s h ou ld e rs , 83
Ra yn a u d ’s p h e n om e n on (RP) w ris t s , 82–83, 83f
clin ica l cou rs e, 113 e xt ra -a rt icu la r m a n ife s t a t ion s of RA, 79, 79t
clin ica l p re s e n t a t ion , 111–112 m e d ica t ion s , 89–90
s t u d ie s , 112 biologic DMARDs , 90, 92
t re a t m e n t , 112–113 cort icos t e roid s , 90
Re a ct ive a rt h rit is , 3, 97, 101 NSAIDs , 90
Re com bin a n t p a ra t h yroid h orm on e, s yn t h e t ic DMARDs , 90, 91t
212 p a lin d rom ic rh e u m a t is m , 88–89
Re fe rre d p a in , 55 p olym ya lgia rh e u m a t ica (PMR), 89–90
Re u x e s op h a git is , 130 re m it t in g, s e ron ega t ive, s ym m e t ric s yn ovit is
Re it e r’s s yn d rom e, 3 w it h p it t in g e d e m a (RS3PE), 88
Re m it t in g, s e ron ega t ive, s ym m e t rica l Sjögre n ’s s yn d rom e, 79
s yn ovit is w it h p it t in g e d e m a (RS3PE), d ia gn os is of, 80, 81t
88–89, 229–230 t re a t m e n t of, 92
Re n a l in s u f cie n cy, 284 SLE, 88
Re n a l u ra t e e xcre t ion , 184 s p on d yloa rt h rop a t h ie s , 88
Re t roca lca n e a l bu rs a , 40–41 t re a t m e n t , 89, 90t
Rh e u m a t ic d is e a s e s vira l a rt h rit is , 89
a rt icu la r com p la in t s , p a t ie n t s w it h Rh e u m a t ologis t s , 160
clin ica l p re s e n t a t ion , 3–6, 4t , 5t Rh u p u s , 151–153, 152f
p h ys ica l n d in gs , 6–7 Rit u xim a b, 108, 295
 In d e x 307

Ros e Be n ga l t e s t s , 80 Sh ou ld e r, 83, 277–278

Rot a t or cu ff, 31 p a in
Rot a t or cu ff t e n d in it is , 66–68, 67f. See also under clin ica l cou rs e, 35
Sp ort s –re la t e d in ju rie s clin ica l p re s e n t a t ion , 30–31, 31f
Rou t in e As s e s s m e n t of Pa t ie n t In d e x Da t a 3 p h ys ica l e xa m in a t ion , 31–33, 32f
(RAPID-3), 89 s t u d ie s , 33
RS3PE. See Re m it t in g, s e ron ega t ive, s ym m e t rica l t re a t m e n t , 34–35, 34f
s yn ovit is w it h p it t in g e d e m a (RS3PE) Sickle ce ll d is e a s e, 230, 230f
Ru be lla a n d ru be lla va ccin e, Sin gle -p h ot on -e m is s ion com p u t e rize d
262–263 t om ogra p h y, 165
Ru p t u re of a ch ille s t e n d on , 40 Sjögre n ’s s yn d rom e, 108–109. See under
Rh e u m a t oid a rt h rit is (RA)
Sa croilia c join t s , 98 Skin , 105
Sa croiliit is , 99 le s ion s , 96
t e s t in g, 98f, 99f ra s h , 252, 253f
S-a d e n os ylm e t h ion in e (SAM-e ), 180 SLE. See Sys t e m ic lu p u s e ryt h e m a t os u s (SLE)
Sa rcoid os is , 4, 234 Sle e p d is t u rba n ce s , 160
Sa t u rn in e gou t , 3 w it h p a in , 225
Sch öbe r’s t e s t , 100f Slip p e d ca p it a l fe m ora l e p ip h ys is (SCFE), 55, 56
Scle rod a ct yly, 114 Sm a ll-ve s s e l va s cu lit is . See under Va s cu lit is
Scle rod e rm a s in e s cle rod e rm a , 14 Sm okin g, ris k of, 78
Scle rod e rm a t om yos it is , 153 Sn a p p in g h ip s yn d rom e, 58
Scle rom yos it is , 153 Soft corn s , 43
Se con d a ry h yp e rp a ra t h yroid is m , 219 Sp in a l fra ct u re, 205
Se le ct ive e s t roge n re ce p t or m od u la t ors (SERMs ), Sp in e a n a t om y, 25, 26f
208–209 Sp on d yloa rt h rop a t h ie s , 88
Se p t ic a rt h rit is , 189, 239f Sp on d ylos is , 21
Se rologic t e s t in g, 254 Sp ort s -re la t e d in ju rie s
Se ron ega t ive s p on d yloa rt h rop a t h ie s , 3, 4 a ch ille s t e n d in op a t h y, 70–71
a n kylos in g s p on d ylit is , 96 a n kle s p ra in , 71–73, 71f, 72f
clin ica l cou rs e, 101 iliot ibia l ba n d s yn d rom e s , 69–70
clin ica l p re s e n t a t ion , 95–96 p a t e llofe m ora l p a in s yn d rom e (PFPS), 68–69
e n t e rop a t h ic a rt h rit is , 97–98 of rot a t or cu ff
e xa m in a t ion , 98–99, 98f, 99f, 100f clin ica l cou rs e, 68
p s oria t ic a rt h rit is , 97 clin ica l p re s e n t a t ion , 66, 67f
re a ct ive a rt h rit is , 97 e xa m in a t ion , 66–67, 67f, 68f
s t u d ie s , 99–100 s t u d ie s , 67–68
t re a t m e n t , 100–101 t re a t m e n t , 68
Se ros it is , 105 Sp u rlin g’s t e s t , 17
Se ru m u ra t e, 187 St a n d a rd ize d in cid e n ce ra t io (SIR), 123
Se s a m oid in ju rie s , 39 St a p h ylococcu s a u re u s , 240
Se s a m oid it is , 39 Staphylococcus aureus, 134
Sh aw l s ign , 123 St e rn ocle id om a s t oid s , 15
Sh oe m od i ca t ion s , 45 St e roid in je ct ion s , 46
Sh ort t a u in ve rs ion rep e a t (STIR), 128 St e roid m yop a t h y, 281
308 In d e x

St iffn e s s , 95 clin ica l p re s e n t a t ion ,

St in ch e ld t e s t , 60 114–115
St ra igh t leg ra is e a ga in s t re s is t a n ce t e s t , 60 s t u d ie s , 115–116
St ra igh t leg-ra is in g t e s t , 25, 25f t re a t m e n t , 116
Su ba crom ia l bu rs a , 278, 278f Sys t e m ic va s cu lit is , 4, 86
Su ba cu t e cu t a n e ou s lu p u s e ryt h e m a t os u s
(SCLE), 104 Ta crolim u s , 291
Su bcu t a n e ou s a ch ille s bu rs it is , 41 Ta ilor’s bu n ion , 39
Su lfa s a la zin e, 286 Ta ka ya s u ’s a rt e rit is , 4, 134
Su p e r cia l p e ron e a l n e rve e n t ra p m e n t , 42–43 Ta rs a l t u n n e l s yn d rom e, 42
Su p e rvis e d re h a bilit a t ion , 53 T-ce ll a ct iva t ion , 295
Su p p ort ive d evice s , 177 Te la n gie ct a s ia s , 114
Su ra l n e rve e n t ra p m e n t , 43 Te n d e rn e s s
Sw a n n e ck, 82f t o p a lp a t ion , 58
Sw e llin g, 83 on p a s s ive a bd u ct ion , 33
Sym p t om a t ic t h e ra py of OA. See under Te n os yn ovit is , 3
Os t e oa rt h rit is (OA) Te rip a ra t id e, 212
Sym p t om s eve rit y (SS), 162 Te s t os t e ron e, 216
Syn ovia l u id , 226 Te t ra cyclin e s , 287–288
Syn vis c (HYLAN GF 20), 180 Th a lid om id e, 292
Sys t e m ic lu p u s e ryt h e m a t os u s (SLE), 4, 88, 271 Theileria m icroti, 252
clin ica l cou rs e, 106 Th e n a r a t rop h y, 83f, 84
con s t it u t ion a l, 105 Th e rm a l m od a lit ie s , 177
cu t a n e ou s lu p u s , 103–104 Th e rm op la s t ic m a t e ria ls , 44
e p id e m iology Th ia zid e d iu re t ics , 192
e xa m in a t ion , 105–106 Th iop u rin e m e t h ylt ra n s fe ra s e (TPMT), 290
h e m a t ologic lu p u s , 104 t e s t in g, 107
la bora t ory a s s e s s m e n t of, 106 Th om a s h e e l, 45
lu p u s n e p h rit is , 104 Th om a s t e s t , 60
m u s cu los ke le t a l lu p u s , 104 Th om p s on t e s t , 40, 70, 70f
n e u rologic lu p u s , 104 Th rom bocyt op e n ia , 104
NSAIDs Tibiot a la r join t , 277
a n t ip h os p h olip id a n t ibod y, 108 Tin e l s ign , 42, 43
biologics , 108 Tocilizu m a b, 294
ca rd iova s cu la r ris k fa ct ors , 109 Toga virid a e, 260, 262
im m u n os u p p re s s ive d ru gs , 107–108 Top h i, 187
p re d n is on e /cort icos t e roid s , 107 Tou rn iq u e t t e s t , 42
Sjögre n ’s s yn d rom e, 108–109 Tra be cu la r bon e, 213
orga n m a n ife s t a t ion s , 103 Tra m a d ol, 179
p a t h oge n e s is , 103 Tra p e ziu s m u s cle, 30, 31f
s e ros it is , 104 Tre a t m e n t a lgorit h m for glu cocort icoid -
t re a t m e n t , 106–107 a s s ocia t e d bon e d is e a s e, 214–215, 214f
Sys t e m ic s cle ros is (SSc), 4, 113–114. See also Tre n d e le n bu rg s ign , 59f
Rayn a u d ’s p h e n om e n on (RP) Tricyclic a n t id e p re s s a n t s (TCA), 26, 164
clin ica l cou rs e, 116–117 Troch a n t e ric bu rs it is , 64
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Troch a n t e ric p a in s yn d rom e, 58 s t u d ie s , 136–137

T-s core, 204, 205f t re a t m e n t , 137
Tu m or n e cros is fa ct or-α, 292–294. See also under Va s cu lop a t h y, 114
An t irh e u m a t ic t h e ra py Ve rt e bra , a n a t om y of, 13f
Ve rt e bra l fra ct u re a n a lys is (VFA), 205
Ulce ra t ive colit is , 97 Vira l a rt h rit is , 89
Ulce rs , 105 a lp h aviru s e s , 260–262
Uln a r d evia t ion , 82, 82f h e p a t it is B (HBV), 260, 261f
Un cla s s i e d /u n d iffe re n t ia t e d con n e ct ive t is s u e h e p a t it is C (HCV), 258
d is e a s e, 155–157, 155t , 156f coe xis t in g in a m m a t ory a rt h rit is ,
Ura t e -low e rin g t h e ra py for h yp e ru rice m ia , 259–260
191–193, 192f HCV-re la t e d a rt h rit is , 259
Ura t e oxid a s e (u rica s e ), 193 m ixe d cryoglobu lin e m ia , 259
Uric a cid , 3, 184 h u m a n im m u n od e cie n cy viru s (HIV), 263
Uricos u ric d ru gs , 193 p a rvoviru s B19, 257–258, 258f
Us t e kin u m a b, 295 ru be lla a n d ru be lla va ccin e, 262–263
Vira l in fe ct ion s , 6
Va ccin a t ion s for in u e n za , 106 Vire m ia , 258
Va cu ola r m yop a t h y, 283 Vis cos u p p le m e n t s , 180
Va lgu s d e form it ie s , fore foot va ru s a n d , 37 Vit a m in D, 207–208, 208t
Va s cu lit is
clin ica l cou rs e, 137–138, 138t Wa s t in g a n d ca ch e xia , 143
clin ica l h is t ory, 135 We a k h ip a bd u ct ors , 58f
clin ica l p re s e n t a t ion , 132–133, 132f, Wege n e r’s gra n u lom a t os is (W G), 134
133t We igh t los s , 176
e p id e m iology, 133 W h ip la s h in ju rie s , 21
e xa m in a t ion , 135–136 Wid e s p re a d Pa in In d e x (W PI), 163
la rge -ve s s e l Wils on ’s d is e a s e, 232
gia n t ce ll a rt e rit is , 133–134 W ris t , 82–83, 83f, 278–279, 279f
Ta ka ya s u ’s a rt e rit is , 134
m e d iu m - t o s m a ll-ve s s e l, 134 X-ra ys , 18, 56, 62f, 224f
m e d iu m -ve s s e l, 134
s m a ll-ve s s e l Zig-za g d e form it y, 81
cu t a n e ou s , 135 Zole d ron ic a cid , 210
He n och –Sch on le in p u rp u ra , 135 Z-s core s , 204, 205f