RHEUMATOLOGY1

GOUT
Precipitation of amounts of monosodium urate (MSU)
in body fluids and tissues.
50 yo most common. Premenopausal rarely
experience gout estrogen promotes renal
excretion of urate.
Major manifestations
!. recurrent attac"s of inflammatory art#ritis single
$oint% esp. !
st
toe M&P $oint. 'an manifest for !
st

time in multiple $oints.
(. top#aceous deposits
). "idney stones
*. urate nep#ropat#y.
Hyperuricemia:
Primary Hyperuricemia +are ,-erproduction due
to genetic defects in "ey metabolism en.ymes.
'ommon Under secretion by "idney
econ!ary Hyperuricemia:
/t,0
Myeloproliferati-e d.
Myeloid dysplasia and polycyt#emia
0emoglobinopat#ies Sic"le cell d.
1rugs
1iuretics 2nitial transient urcosuria t#en tubular
reabsorption of filtered urate. &#is may not occur
34sufficient #ydration.
5nti6&b /t#ambutol and Pyra.inamide. Uric acid
#ad been used to follo3 compliance 3it# anti6&b
meds. +esponse is seen in ! to 70 days. See le-el of
8 9. Mec#anism not "no3n.
:o3 1ose 5S5 ; !.( gm4day.
'ancer Most often 34disseminated undifferentiated
cancers.
+enal in <=+ in filtered uric acid.
0yperuricemia does not de-elop until by 8 50>.
Uremia and periodic #emodialysis.
'#ronic lead poisoning
Sarcoid
,t#er Star-ation% exercise% psoriasis% obesity% 1M%
#yperlipidemia.
Asymptomatic Hyperuricemia:
Pts fre?uently #a-e urate concentration% but no
symptoms. Pre-alence of #yperuricemia is 5 to @>
in adult 5merican .
Symptomatic manifestations appear usually only after
(06)0 yrs of sustained #yperuricemia.
0yperuricemia #as no clinical importance in
determining course of renal function.
"ia#nosis
5nalysis of syno-ial fluid under t#e polari.ing
microscope.
$oint Aspiration
MSU crystals
needle6s#aped
brig#t under polari.ed lig#t (strongly birefringent).
ABegati-e birefringenceA axis of t#e MSU crystal
appears yello3 3#en it is parallel to t#e axis of t#e
microscopeCs first6order red compensator (Ayello36
parallel goutA).
5spiration of top#i easy to do t#ic"% 3#ite Amil" of
urate%A 3#ic# can be examined 34polari.ing
microscope.
Dray of affected $oints top#aceous erosion into
subc#ondral bone punc#ed6out lesion
34o-er#anging osteop#yte.
La% &a'ues Serum uric acid s#ould be ele-ated% by may
be in normal range.
"RUG THERAPY
<out is treated in t3o p#asesE
!
st
to control t#e acute attac"
(
nd
to pre-ent recurrence t#is ta"es t#e form of finding
and treating a secondary cause% lo3er uric acid (
production 345llopurinol% or excretion
34Probenecid).
Beed to continue anti6inflammatory &x t#roug#
induction p#ase of uric acid lo3ering &x.
(A)"s
Useful to treat acute inflammation4pain
!. 1o not use 5S5 doses uric acid.
(. Bot useful to alter uric acid le-els.
Pts not #oo! can!i!ates for (A)" t#erapeutic
anticoagulation% no P,% -olume depletion% '0=% or
renal insufficiency. ',D6( in#ibitors do not in#ibit
plt function. May pro-e useful in pts in 3#om
anticoagulation contraindicates use of t#e traditional
BS521s . FFsafety in pts 3it# renal insufficiency is
unclear.
+esponse to maximal doses of BS521s is usually
excellent in pt 3#o can ta"e t#ese medications.
2ndomet#acin may be considered t#e drug of c#oice
but may not be 3ell tolerated by elderly patients.
5fter se-eral days of #ig#6dose BS521 t#erapy% t#e
patient can gradually dose o-er a period of a
3ee".
*o'c+icine
&x of acute attac"s and for prop#ylaxis of acute attac"s
Mec+anism of action
2n#ibition of microtubular (M&) polymeri.ation
disappearance of M& from PMBs in#ibition of
PMB migration and p#agocytosis of urate crystals%
and release of lactic acid% proinflammatory
en.ymes% and glycoprotein
Gloc" cell di-ision
2n#ibits release of #istamine from mast cells
P+armaco,inetics Hell absorbed P,. Metaboli.ed by
li-erI primarily <2 :i-er excretion contributes to
toxicity. :ong & J in PMB.
To-icity
<2 Substantial Bausea% -omiting% diarr#ea% pain
limits oral use.
0emorr#agic gastroenteritis occasionally
,t#er toxicities :eu"openia% leu"ocytosis% myopat#yI
neuropat#yI a.ospermia
*'inica' use
5cute attac" Hit# nl renal function P, dosing 0.5 mg
or 0.K mg #ourly until relief or toxicity (diarr#ea)%
but max dose is 56K mg per day (!06!( tablets).
&#en c#ange to bid dosing. 2L not preferred
because of loss of early signs of toxicity <2 S/
(diarr#ea).
Prop#ylactic use P, G21 dosing (;( mg4day). /sp.
useful in peri6operati-e period
A''opurino'
2n#ibits xant#ine oxidase en.yme t#at forms uric acid
from oxidation of #ypoxant#ine% xant#ine. 5lso its
!M metabolite alloxant#ine
!) 5llopurinol 'ompetiti-e and noncompetiti-e
in#ibition
() 5lloxant#ine Boncompetiti-e in#ibition
)) '#ange urinary purines from solely uric acid to also
#ypoxant#ine% xant#ine can get xant#ine6stones
"ru# interactions
!) 5llopurinol probenecid #alf6life
() metab of mercaptopurine N a.at#ioprine must
dosage
)) metab of 3arfarin
To-icity
0ypersensiti-ity reactions s"in ras#% fe-er% malaise
5cute gouty attac" during initial treatment may
re?uire prop#ylactic colc#icine
&arget organ damage HG'% li-er% "idney
.RHEUMATOLOGY
*'inica' use
!) Primary #yperuricemia
() Secondary #yperuricemia myeloproliferati-e. Beed
to use 34 fluid inta"e
)) '#ronic goutI esp. 3it# top#i% renal stones%
nep#ropat#y
<oal is to reduce uric acid to ;K mg4dl
1o not use during acute gouty attac".
Use doses to a-oid precipitating acute attac" use
34colc#icine N ade?uate fluids
Pro%eneci!
Uricosuric "ru#
renal excretion of penicillin
excretion of uric acid bloc"ade of reabsorption
Usually 3ell tolerated except for <2 irritation%
#ypersensiti-ity reactions
=or #yperuricemia use 34 fluid inta"e to pre-ent uric
acid stones from forming.
May precipitate acute gouty attac" use 3it# colc#icine
or BS521
Salicylate blunts probenecid action