Case 20

Systemic Lupus Erythematosus

February 12, 2008
Group C10
History of Present
Illness
 Patient Data
• H.H., 19 y.o., Filipino female,
single, Roman Catholic, a student
from San Pedro, Laguna

• Source: patient and her mother

• Reliability: 80%
• Date of Admission: Jan 17, 2008
• Date of Interview: Jan 25, 2008
Chief Complaint: Dyspnea
HPI:
Two years prior to • Headache- more prominent
admission on the right
– Self-medicated: mefenamic
acid  offered relief

• Joint and muscle pains

• Generalized weakness
– Persisted and progressed that
patient needed help in order
to ambulate
HPI:
51 weeks prior • Anorexia
to • Skin sores in the anterior
admission thorax
• Wounds on her breast around
the areolar region
• Recurrence of headache
• Persistence of joint and
muscle pains and
generalized weakness
• Prompted consultation at
Medical City
– Tested for visual problems = (-)
– Asked to consult psychiatrist
=did not comply
HPI:
50 weeks prior • Continuous fever = 400C
to – Persisted for a week
admission
• Bluish discoloration of fingers

• Prompted another
consultation at Medical City

• During consultation, suddenly

experienced difficulty of
breathing

• Rushed to the ER then moved

to the ICU because of
HPI:
48 weeks prior • Diagnosed with systemic
to lupus erythematosus (SLE)
admission with class V lupus nephritis
• Treated with hydrocortisone
(unrecalled dosage)

46 weeks prior to • Discharged with medications:

prednisone
admission
• She was not compliant due to
side-effects of treatment:
weight gain and acne
development
HPI:
10 months prior • Started to develop oral
sores and ulcers over most
to admission
of her buccal cavity
• Prompted consultation and
confined for five days at
Medical City
• Was given unrecalled
medications and was
discharged when sores were
healed
HPI:
7 months prior • Bilateral knee pain
• Could not stand alone
to admission
• Confined at Medical City for
fifteen days
• Treated with hydrocortisone
and methyprednisolone
(Solu-medrol) – unrecalled
dosage
• Soon experienced weakness
and hair fall (alopecia)
• Reduced dosage of the drugs
improved her condition
• Prescribed with prednisone,
vitamins (for anemia), and
calcium
• Not compliant with
HPI:
1 month prior • Abnormally enlarging
abdomen
to admission
• Self-medicated with
previously prescribed
steroids but to no avail
8 days prior
to admission • Consulted at USTH OPD
• Prescribed with prednisone
and hydroxychloroquine
7 days prior (Plaquenil)
– Abdominal flattened
to admission
• Returned to OPD for lab
results
• Diagnosed with UTI
HPI:
3 days prior • Abdomen started to
enlarge again
to admission
• Accompanied by swelling
of hands and feet
• Progressed rapidly
• Also experienced vomiting

2 hours prior • Difficulty of breathing

even at rest
to admission
• Rushed to USTH emergency
room and was admitted
Medical History
 Obstetric and
Gynecological History
• G0P0
• Menarche at 12 y.o.
• Irregular menstrual flow (1-2 months
with no period)
• Menstrual periods last 5 days
• Consumes 2-3 pads a day
• LMP: December 2007 (unrecalled
date)
Past Medical History
1988 • Bronchopneumonia: 3
months old

• Dislocated left knee

2001
while dancing
 Past Medical History

2006 • SLE with lupus nephritis

class V

Feb 2006 • Blood transfusion (1 bag

packed RBC)
 Past Medical History
• Has skin allergies with no identified
trigger/agent – takes Celestamine

• No history of surgery

• Current medications: prednisone as

treatment of SLE

• Immunizations: given DPT, BCG, OPV; no

hepatitis vaccines, MMR or influenza
 Family History
• No family history of gout or arthritis,
allergy, cancer or stroke

• Mother: (+) anemia

• Father: (+) hypertension, (+) heart

disease

• Grandmother, mother’s side: (+) DM

 Personal and Social
History
• Non-smoker, non-alcoholic, no illicit
drug use

• Fond of eating fried food, usually pork

or chicken and rarely eats vegetables
 Personal and Social
History
• Household chores are the only form
of exercise

• Lives in Laguna with her parents and

2 younger sisters which are all
healthy
 Personal and Social
History
• Piggeries around the house and a
nearby river, but is not polluted

• SLE has greatly affected her teenage

lifestyle

• Common concerns such as weight

gain and acne development has
made her non-compliant to steroid
therapy
 Review of Systems
• General: Has anorexia and weakness of the
whole body. No significant weight changes. No
fever, sweats, insomnia.

• Skin: Has erythematous, flat rash over the

malar eminences. No color change in the other
parts of the body

• HEENT:
– Head: No history of head injury.
– Eyes: No visual dysfunction or lacrimation. No
itchiness, pain or recent changes in vision.
– Ears: Hearing good. No tinnitus, vertigo,
infections.
– Nose, sinuses: No hay fever, sinus trouble.
– Throat: No soreness or tonsilitis.
 Review of Systems
• Neck: Has stiff neck. No lumps, goiter, pain. No
swollen glands

• Breasts: No lumps, pain, discharge

• Respiratory: Has dyspnea. Cough productive

of sputum that is difficult to expectorate.
Has back pains. No orthopnea

• Cardiovascular: Hypertensive with highest

recorded BP 150/110. Has edema in the
upper and lower extremities. No chest pain
and palpitations. No PND, syncope
 Review of Systems
• Gastrointestinal: Distended abdomen. No
nausea, vomiting, indigestion. Has regular bowel
movements. No abdominal pain.

• Urinary: Has oliguria and flank pains. No other

urinary problems

• Genital: No straining, genital lesions or urethral

discharge

• Musculoskeletal: Has generalized edema

and some limitations in movement of hands
and feet. Has generalized weakness.
 Review of Systems
• Endocrine: No neck surgery, irradiation,
polydypsia or polyphagia.

• Hematologic: Anemic. No bleeding

problems.

• Neurologic: No fainting, seizures, motor

or sensory loss. Memory good.

• Nails: No clubbing
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION
General Survey General Survey
• Conscious, coherent, • Conscious, coherent,
ambulatory and in oriented as to time,
cardiorespiratory place and person, not
in cardio-respiratory
distress distress

• BP -140/80 mmHg • BP – 140/90 mmHg

PR 140, regular PR 96, regular,
RR 40 RR 24, regular pattern
of breathing
Temp 38.2°C Temp 36.2 °C

• Height- 5’6’’
Weight- 65 kg
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION
General Survey General Survey

• Warm, moist skin, no • Skin is shiny, stretched

due to edema
active dermatoses
• erythematous flat rash
over malar eminences

• non-erythematous
macular lesions less
than 1cm in the anterior
thorax near the neck
 Malar Rash

Source: http://www.emedicine.com/med/images/329097-
332244-5270.jpg
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION

HEENT HEENT
• Pale palpebral • Pale palpebral
conjuctiva, anicteric conjuctiva, anicteric
sclera sclera

• No ear and nasal • No ear and nasal

discharge dischage

• Moist buccal mucosa, • Moist buccal mucosa,

(+) oral ulcers (+) oral ulcers

• No palpable cervical • No palpable cervical

lymphadenopathies, lymphadenopathies,
no neck masses no neck masses
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION

Respiratory Respiratory

• Symmetrical chest
expansion • Symmetrical chest
• no retractions expansion
• no retractions
• Resonant
• decreased tactile and • decreased tactile and
vocal fremiti
• decreased breath vocal fremiti in the
sounds on the left T6- left posterior lower
T7 down lung region
• (+) crackles on left • fine rales heard
lung field
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION

Cardiovascular Cardiovascular
• Adynamic precordium, • JVP 3.0cm above the
apex beat 5th LICS sternal angle at 300
MCL (apex: S1>S2; • CAP has rapid
base: S2>S1), no upstroke gradual
murmurs downstroke
• Adynamic precordium,
apex beat at the 5th
LICS, MCL.
• Apex: Loud S1
followed by soft S2;
base: Soft S1 followed
by loud S2, splits at
inspiration , no
murmurs, no heaves,
thrills, or lifts.
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION
Abdominal Abdominal
• Flabby abdomen • Abdomen is distended
and shiny with silvery
white striae
• normoactive bowel • normoactive bowel
sounds sounds, no bruits

• (+) dullness over

abdominal region

• could not assess liver

dullness
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION
Abdominal Abdominal
• no abnormal masses
• soft, direct tenderness • no tenderness upon
on LUQ palpation
• no costovertebral angle
tenderness
• (+) bulging flanks, (+) •
fluid wave (+) shifting dullness, (+)
fluid wave

Extremities Extremities
• Pulses full and equal, • (+) edema
(+) edema, (-)
cyanosis
 PHYSICAL
EXAMINATION
Central and Peripheral Pulses
(0)=absent
(+)=decreased
(++)=normal
(+++)=hyperactive
(Br)=bruit

PULSE CAROTID BRACHIAL RADIAL FEMORAL POPLITEAL DOR PEDIS POST TIBIAL

RIGHT ++ ++ ++ ++ ++ ++ ++

LEFT ++ ++ ++ ++ ++ ++ ++
 PHYSICAL
EXAMINATION
ON ACTUAL EXAMINATION
Musculoskeletal
• Temporomandibular joint: no skin changes,
abnormal contours or deformities; no swelling or
tenderness, good movement

Upper extremities
• Shoulder joint: no skin changes and deformities,
symmetrical, no swelling and tenderness, no
limitation in motion
• Elbow joint: no skin changes and deformities, no
tenderness and thickening, slight limitation in
motion due to edema, right elbow has an IV so
could not be moved
 PHYSICAL
EXAMINATION
ON ACTUAL EXAMINATION
Upper extremities
• Forearm, wrist and hand: edematous, bulky
hands; no redness, nodules, no
metacarpophalangeal tenderness; no
interphalangeal tenderness; right hand unable to
make a fist and has limited extension and flexion;
left hand has limited extension and slightly limited
flexion.

• Neck: Sternomastoid muscles are symmetrical,

has no deformities nor abnormal postures;
Trapezius muscles are tender; Cervical spinous
processes and muscles between the scapulae are
 PHYSICAL
EXAMINATION
ON ACTUAL EXAMINATION
Musculoskeletal
• Back: no skin changes, abnormal contours and
deformity; no swelling and tenderness of cervical,
thoracic and lumbar spinous processes; no
abnormal postures or lateral curvatures; no
limitation in movement

Lower Extremities
• Hip joint: no skin changes, abnormal contours
and deformity; no swelling and tenderness; no
limitation in movement
 PHYSICAL
EXAMINATION
ON ACTUAL EXAMINATION
Lower Extremities
• Knee joint: no skin changes, abnormal contours
and deformity; no muscle atrophies and
thickening; slight swelling due to edema and no
tenderness in the patellar region; no limitation in
movement, no instabilities; (-) bulge sign, (-)
balloon sign

• Ankle and foot joints: edematous feet, (+)

pitting edema = 3-4+, no abnormal contours and
deformity; no muscle atrophies and thickening; no
metatarsophalangeal tenderness; no
interphalangeal joint swelling and tenderness;
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION
Neurologic Neurologic
• Alert , awake. Can follow • Conscious ,GCS 15
simple commands.
• Coherent, oriented to time,
• Pupils 2-3mm ERTL, EOMs place and person; good
full and equal. registration, good
attention, calculation and
• V1V2V3 intact, can smile, recall, good sense of
clench teeth, raise language and
constructional ability, good
eyebrows, tongue midline, memory
can shrug shoulders
• DTR: normoreflexive on • CN I – XII are all intact
knee and ankle jerk • No muscle atrophy, good
• MMT: All major muscle muscle bulk and tone, MMT
groups of bilateral UE/LE 3/5 in the upper
extremities while 4/5 in the
are 4/5 lower extremities
 PHYSICAL
EXAMINATION
ON ADMISSION ON ACTUAL EXAMINATION
Neurologic Neurologic
• Can do FTNT and
• ROM: No alternating
limitations on pronation and
supination
range of motion • Balance and
• (-) nuchal rigidity, equilibrium was not
assessed
(-) Kernig’s sign, (-) • No sensory deficits
Brudzinski’s sign, • Reflexes was not
(-) Babinski assessed due to
edema
• (-) Babinski
• Good neck mobility,
(-) Brudzinski’s sign,
(-) Kernig’s sign
 SALIENT FEATURES
Objective Findings
PERTINENT POSITIVES PERTINENT NEGATIVES
• Female, 19 years old
(reproductive age) • No chest pain and
• Oral sores and ulcers palpitations
• Skin sores on anterior • Normal JVP, CAP and
thorax and breast adynamic precordium
• No musculoskeletal
• Erythematous flat rash
deformities
over malar eminences
• Anasarca
 SALIENT FEATURES
Subjective Findings
PERTINENT POSITIVES PERTINENT NEGATIVES
• Headache
• Fever • No family history of
• Joint and muscle gout or arthritis,
pains allergy, cancer or
• Generalized weakness stroke
– Assisted ambulation • No seizures
• Anorexia • No memory loss
• Bluish discoloration of
fingers
• Difficulty of breathing
• Bilateral knee pain
• Skin allergies
• Anemia
 CLINICAL MANIFESTATION PREVALENCE IN
PATIENTS, %
Hematologic 100
Arthritis 90
Skin 85
Fever 83
Fatigue 81
Weight loss 63
Renal 50
CNS 50
Pleuritis 46
Myalgia 33
Pericarditis 25
Gastrointestinal 21
Reynauds phenomenon 20
Ocular 15
Peripheral neuropathy 14

From Robbins and Cotran Pathologic Basis of Disease 7th ed.

 1997 REVISED CRITERIA FOR CLASSIFICATION OF
SYSTEMIC LUPUS ERYTHEMATOUS
CRITERION DEFINITION
1. Malar rash Fixed erythema over the malar
eminence
2. Discoid rash Erythematous raised patches
3. Photosensitivity Skin rash as a result of exposure to UV
light
4. Oral ulcers Oral or nasopharyngeal ulceration
5. Arthritis Nonerosive arthritis
6. Serositis Pleuritis, Pericarditis
7. Renal disorder Persistent proteinuria
8. Neurologic disorder Seizures, Psychosis
9. Hematologic disorder Hemolytic anemia, Leukopenia,
Lymphopenia, Thrombocytopenia
10. Immunologic disorder Anti-ds DNA, anti- Sm, and/or
antiphospholipid
11. Antinuclear antibody An abnormal titer of antinuclear
antibody

Data from Tan EM, et al. The Revised Criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271, 1982; and Hochberg, MC: Updating
the American College of Rheumatology revised criteria for he classification of systemic lupus eryhtematosus. Arthritis Rheum 40: 1735, 1997
 1997 REVISED CRITERIA FOR CLASSIFICATION
OF
SYSTEMIC LUPUS ERYTHEMATOUS

• 11 criteria

• SLE
– 4 or more are present
– serially or simultaneuosly, during any interval of
observation

• Patient
– arthritis
– oral ulcers
– malar rash
– renal disorder
– hematologic disorder
 Definition of Terms
• Rheumatology
– rheuma – that which flows as a river or
stream
– encompasses the autoimmune diseases,
arthritis, and musculoskeletal
conditions. While rheumatologists are
generally thought to be specialists
dedicated to rheumatoid arthritis, lupus
and scleroderma, we also care for
patients with a wide array of systemic,
inflammatory, autoimmune diseases as
well as very common musculoskeletal
disorders
Source: (e.g., osteoarthritis and
http://en.wikipedia.org/wiki/Rheumatology
osteoporosis) and sports-related
http://www.rheumatology.org/students/faq.asp injuries.
(American
College of Rheumatology)
 Definition of Terms
• Rheumatism
– non-specific term used to describe any
painful disorder affecting the loco-motor
system including joints, muscles,
connective tissues, soft tissues around
the joints and bones
– A term used for acute and chronic
conditions marked by inflammation,
muscle soreness and stiffness, and pain
in http://en.wikipedia.org/wiki/Rheumatology
Source: joints and associated structures
Pathophysiology of SLE
 Autoimmune Diseases
• autoantibodies react against self-antigens

• autoantibodies are not always pathological

• requirements to establish pathologic immunity

– presence of an autoimmune reaction

– evidence that the reaction is not secondary to

tissue damage

– absence of another well-defined cause of the

disease
 TABLE 6-7 Autoimmune Diseases
Organ-Specific Systemic
Hashimoto’s thyroiditis Systemic lupus erythematosus
Autoimmune hemolytic anemia Rheumat oid art hritis
Autoimmune atrophic gastritis of pernicious anemia Sjögren syndrome
Multiple sclerosis Reiter syndrome
Autoimmuse orchitis Inflammatory myopathies
Goodpasture syndrome Systemic sclerosis (scleroderma)
Autoimmune thrombocytopenia Polyarteritis nodosa
Insulin-depedndent diabetes mellitus
Myasthenia gravis
Graves disease
Primary biliary cirrhosis
Autoimmune (chronic active) hepatitis
Ulcerative colitis

From Robbins and Cotran Pathologic Basis of Disease 7th ed. p 223
 Self-tolerance
• lack of responsiveness to an individual’s own
antigens

• normal individuals: intact

• 2 postulated mechanisms

– Central Tolerance
• clonal deletions of self-reactive T and B cell clones occur during
their maturation
• some may still reach the periphery

– Peripheral Tolerance
• anergy - permanent inactivation of lymphocytes
• deletion by apoptosis
• suppression by regulatory T cells
• antigen sequestration

From Robbins and Cotran Pathologic Basis of Disease 7th ed.

 Mechanism of Autoimmune
Disease
• susceptibility genes
– influence the preservation of self-tolerance

• environmental factors
– infection
• co-stimulators on APCs are indcued loss of anergy
• molecular mimicry .

• progression and chronicity is sustained by

the continued recruitment of
autoreactive T cells that recognize
previously cryptic self-antigens
From Robbins and Cotran Pathologic Basis of Disease 7th ed.
 Systemic Lupus
Erythematosus
• characterized by the presence ANA, anti-dsDNA,
and anti-phospholipid Ab

• acute or insidious onset

• chronic, remitting, relapsing, and often febrile

illness

• injury to the skin, joints, kidney, serosal

membranes

• any other organ in the body may also be

affected

• tissue-binding autoantibodies and immune

From Robbins and Cotran Pathologic Basis of Disease 7th ed.
 Systemic Lupus
Erythematosus
• affects 1 in 700 women of child-bearing
age

• 90% of patients are of child-bearing age

• 9:1 female to male ratio

• 2:1 female to male ratio for SLE

occurring during childhood or after the
age of 65
From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of
Internal Medicine 16th ed.
 Systemic Lupus
Erythematosus
• fundamental defect
breakdown of mechanisms that
maintain self-tolerance

• Implicated factors
– Genetic
– Environmental
– Hormonal
– Primary abnormality in the immune system

From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of
Internal Medicine 16th ed.
 Genetic Factors
• HLA-DQ genes in chromosome 6

– encode MHC class II molecules

– dysfunction  production of anti-dsDNA,

anti-Sm, and anti-phospholpid antibody

– 1 susceptibility haplotype: 2x risk

– 2 or more susceptibility haplotypes 4x-6x

risk
From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles
of Internal Medicine 16th ed.
 Genetic Factors
• Complement deficiency (C2, C4, C1q)
– impaired removal of circulating immune
complexes

– C4 deficiency
• loss of B-cell tolerance

– C1q deficiency
• failure of phagocytosis of apoptotic cells
• nuclear components of such cells may
induce an immune response
• highest genetic risk
From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of
Internal Medicine 16th ed.
 Environmental Factors
• hydralazine, procainamide, and
D-penicillamine  lupus-like
response

• UV exposure
– exacerbations
– stimulates keratinocytes to
produce IL-1  apoptosis
– apoptotic cells may become
antigenic
From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles
of Internal Medicine 16th ed.
 Hormonal Factors
• OC pills, HRT
– 2x risk of developing SLE

• Estradiol
– bind to receptors on T cells and B cells
– increased activation and survival 
extended immune response

From Harrison’s Principles of Internal Medicine 16th ed.

 Immunologic Factors
• hyperreactive and hypersensitive T cells and B
cells

• antigen-specific helper T cell-dependent B cell

response  autoantibody production

• impaired elimination of apoptotic cells and

immune complexes

• antigens, autoantibodies, immune complexes

persist  tissue injury

From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of
Internal Medicine 16th ed.
 Autoantibodies
• ANAs can be grouped into:

– Antibodies to DNA

– Antibodies to histones

– Antibodies to nonhistone proteins bound to

RNA

– Antibodies to nucleolar antigens

From Harrison’s Principles of Internal Medicine 16th ed.

 Autoantibodies
• Other autoantibodies are directed
against:

– Red cells

– Platelets

– Lymphocytes

– Proteins complexed to phospholipids

From Harrison’s Principles of Internal Medicine 16th ed.
*Figure 6-30. Taken from Robbins and Cotran Pathologic Basis of Disease 7th ed. p 229
 Immune complex-mediated
(Type III) Hypersensitivity

• causes majority of the

visceral lesions in SLE

• 3 phases

• First phase: Immune

complex formation

Taken from Robbins and Cotran Pathologic

Basis of Disease 7th ed.
 Immune complex-mediated
(Type III) Hypersensitivity
• Second phase: Immune
complex deposition

– Determinants if deposition
will lead to a disease state
• size of complex: intermediate
or small
• Intact mononuclear
phagocyte system

– Favored sites:
• renal glomeruli
• joints
• skin
• heart
• serosal surfaces
• small blood vessels

Taken from Robbins and Cotran Pathologic Basis of

Disease 7th ed.
 Immune complex-mediated
(Type III) Hypersensitivity
• Third phase:
Inflammation
– from the activation of the
complement cascade

– neutrophil and macrophage

activation

– platelet aggregation and

Hageman factor activation

– microthrombi formation
• Vasculitis
• Glomerulonephritis
• Arthritis

Taken from Robbins and Cotran Pathologic Basis of

Disease 7th ed.
 Joints
• involvement is frequent
• typical lesion: nonerosive synovitis
with little deformity
– distinguishes this arthritis from that seen in
rheumatoid disease

• acute phases of arthritis in SLE

– exudation of neutrophils and fibrin into the
synovium
– perivascular mononuclear cell infiltrate in
the subsynovial tissue
From Robbins and Cotran Pathologic Basis of Disease 7th ed.
 Disorders of Joints
• Localize the complaint
• ARTICULAR vs NONARTICULAR
• Determine pathologic process
• INFLAMMATORY vs NONINFLAMMATORY
• Determine extent of involvement
• MONOARTICULAR, POLYARTICULAR, FOCAL,
WIDESPREAD
• Determine chronology
• ACUTE vs CHRONIC

From Harrison’s Principles of Internal Medicine 16th ed.

 Articular vs Nonarticular
Synovium, synovial fluid, Tendons, bursae, muscle,
articular cartilage, intraarticular fascia, bone, nerve, skin
ligaments, joint capsule,
juxtaarticular bone
Deep or diffuse pain Focal tenderness on areas
distinct from articular
structures
Limited ROM on active and Limited ROM only upon
passive movement active movement
swelling

Crepitus, instability, deformity Seldom demonstrate

crepitus, instability or
deformity
From Harrison’s Principles of Internal Medicine 16th ed.
 Inflammatory vs
noninflammatory
• Infectious; crystal • Related to trauma,
induced (gout); ineffective repair
Immune related (RA (osteoarthritis),
or SLE); Reactive neoplasm, pain
(rheumatic fever), or amplification
idiopathic • Pain without
• One or all four swelling/warmth
cardinal signs of • Absence of systemic
inflammation features
(erythema, warmth, • Minimal/absent
swelling, pain) morning stiffness
From Harrison’s Principles of Internal Medicine 16th ed.
 • Onset – abrupt or indolent
• Evolution
– Chronic, migratory, intermittent,
additive
• Duration
– Acute, chronic (>6 weeks)
*Chronic arthrides often include
noninflammatory and immunologic
disorders
• Involved articulations
– Mono-, oligo- or polyarticular
From Harrison’s Principles of Internal Medicine 16th ed.
 • In SLE musculoskeletal complaints
may be associated with systemic
features such as fever, rash, or
weakness

From Harrison’s Principles of Internal Medicine 16th ed.

From Harrison’s Principles of Internal Medicine 16th ed.
 Dyspnea
• “abnormally uncomfortable
awareness of breathing”

• stimulation of receptors in the lungs,

airways, respiratory muscles, or
chest wall

• excessive or abnormal activation of

the respiratory centers in the
brainstem
From Harrison’s Principles of Internal Medicine 16 ed.
th
 Pulmonary Manifestations
in SLE
• most common pulmonary
manifestations: pleuritis and
pleural effusion – 50% of
patients

• alveolar injury – edema or

hemorrhage

• chronic interstitial lung disease

From Robbins and Cotran Pathologic Basis of Disease 7th ed. and Harrison’s Principles of Internal
Medicine 16th ed.
 Pleural Effusion
• excess quantity of fluid in the pleural
space

• pleural fluid formation exceeds

pleural fluid absorption

From Harrison’s Principles of Internal Medicine 16th ed.

 Alveolar Hemorrhage
• abrupt onset with cough, fever, and
dyspnea

• hemoptysis – may be absent at the

time of presentation in 1/3 of the
cases

• patient: no fever and no hemoptysis

From Harrison’s Principles of Internal Medicine 16th ed.

 Interstitial Lung Disease
• involves lung parenchyma – alveoli,
alveolar epithelium, capillary
endothelium, perivascular and
lymphatic tissue

• inflammation and fibrosis (in SLE) or

granuomatous reaction in intersititial
or vascular areas

From Harrison’s Principles of Internal Medicine 16th ed.

Diagnostic Procedures
 Laboratory Diagnosis
• Laboratory tests serve to:
– To establish or rule out the diagnosis
– To follow the course of disease,
particularly to suggest that a flare is
occurring or organ damage is
developing
– To identify adverse effects of therapies

Harrison’s Principles of Internal Medicine 16th edition

 Laboratory Diagnosis
• Tests for autoantibodies
– SLE is characterized by a
heterogeneous and polyclonal
antibody response, and the usual
case of SLE has an average of three
different circulating antibodies
present simultaneously
– Diagnostically, the most important
autoantibodies to detect are ANA (anti-
nuclear antibodies) since the test is
positive
Harrison’s Principles in16>95%
of Internal Medicine
th
edition of patients, usually
Clinical Diagnosis and Management by Laboratory Methods 20th edition by John Bernard Henry
 Laboratory Diagnosis
• ANA
– Diffuse staining
pattern on
indirect
immunofluoresce
nce
• The whole nucleus is
evenly stained
• Most strongly
associated with SLE
 Laboratory Diagnosis
• Tests for autoantibodies
– High-titer IgG antibodies to double-
stranded DNA (dsDNA) (but not to
single-stranded DNA) are specific for
SLE
• Titer of anti-dsDNA correlates with
disease activity, particularly of nephritis or
vasculitis
• ELISA, IF and Farr assay

Harrison’s Principles of Internal Medicine 16th edition

Laboratory Diagnosis
• Anti-dsDNA
– Immunofluorescent
reaction of sera
with the dsDNA in
the flagellate
Crithidia lucilliae
 Laboratory Diagnosis
• Tests for autoantibodies
– Antibodies to Sm are also specific for
SLE and assist in diagnosis
• Present only in about 30% of patients with
SLE
• Thus (+) test – SLE; (-) test does not rule out
SLE
• Do not usually correlate with disease activity
and clinical manifestations

Harrison’s Principles of Internal Medicine 16th edition

 Laboratory Diagnosis
• Tests for autoantibodies
– aPL (anti-phospholipid) antibodies
are not specific for SLE but their
presence fulfils one of the classification
criterion and they identify patients at
increased risk for venous or arterial
clotting, thrombocytopenia and
fetal loss
• ELISA, phospholipid-based prothrombin time
(dilute Russell venom viper test)
Harrison’s Principles of Internal Medicine 16th edition
 Laboratory Diagnosis

Harrison’s Principles of Internal Medicine 16th edition

 Laboratory Diagnosis

Harrison’s Principles of Internal Medicine 16th edition

 Laboratory Diagnosis
• Standard tests for diagnosis
– CBC
• Hemolytic anemia
• Leukopenia (<4,000/μL)
• Lymphopenia (<1500/μL)
– Platelet count
• Thrombocytopenia (<100,000/μL)
– Urinalysis
• Proteinuria (>0.5 g/d or ≥+3), or cellular
casts
Harrison’s Principles of Internal Medicine 16th edition
 Laboratory Diagnosis

Harrison’s Principles of Internal Medicine 16th edition

 Laboratory Diagnosis
• Tests for following disease
course - indicate the status of organ
involvement known to be present
during SLE flares
– Hemoglobin
– Platelet count
– Urinalysis
– BUN, creatinine or albumin

Harrison’s Principles of Internal Medicine 16th edition

 Radiology
• Pleural effusion
– Most common
thoracic
manifestation
– Frequently bilateral
– Blunting of costo-
phrenic and
cardio-phrenic
angles
– Lateral upward
sloping of a
meniscus-shaped
Fraser and Pare’s Diagnosis of Diseases of the Chest 4 edition
th

contour
 Radiology
• Acute lupus
pneumonitis
– Increased opacity
and poorly defined
markings in the mid
and lower portions of
the chest - (R) x-ray
film

Fraser and Pare’s Diagnosis of Diseases of the Chest 4th edition

 Radiology
• Pulmonary fibrosis
– Irregular linear
opacities in the
lower lung zones

Fraser and Pare’s Diagnosis of Diseases of the Chest 4th edition

 Radiology
• Joint manifestations
– Metacarpophalangeal
subluxations
without erosions

Radiology of Bone Diseases 4th edition by Greenfield

Therapeutic Goals
• To control acute and severe flares
• To suppress/ alleviate the symptoms
• To prevent and treat complications
Treatment
Therapeutic Goals
• To control acute and severe flares
• To suppress/ alleviate the symptoms
• To prevent and treat complications
Treatment

Pharmacologic
 GLUCOCORTICOIDS
• Indications:
• life-threatening manifestations of SLE, such
as glomerulonephritis, CNS involvement,
thrombocytopenia, and hemolytic anemia
• debilitating manifestations of SLE (fatigue,
rash) that are unresponsive to conservative
therapy

Washington Manual of Therapeutics 31st Edition

 GLUCOCORTICOIDS
• Prednisolone
• Methylprednisolone

MOA: inhibits COX-2 and

phospholipase A2 which is
responsible for the breakdown of cell
membrane phospholipids into
arachidonic acid

Goodman and Gillman Pharmacological Basis of Therapeutics 11th Edition

 • Nonsteroidal Anti-inflammatory
Drugs (NSAIDS)
– Used for its’ analgesic and
antiinflammatory effects
– compete in a reversible manner with
arachidonic acid substrate at the active
site of COX-1 and COX-2 decreasing
prostaglandin synthesis
– Indomethacin, Ibuprofen , Ketorolac ,
Mefenamic acid, Naproxen, Diclofenac

Goodman and Gillman Pharmacological Basis of Therapeutics 11th Edition

• Disease Modifying Antirheumatic
Drugs (DMARDs)
– Drugs that modify the progression of
common rheumatic diseases
 DMARDS
• Antineoplastic agents
– Methotrexate
• For managing arthritis, serositis, cutaneous, and
constitutional symptoms.
• Blocks purine synthesis and AICAR, thus increasing
anti-inflammatory adenosine concentration at sites of
inflammation. Ameliorates symptoms of
inflammation.
– Cyclophosphamide
• cross-links DNA, thereby preventing cell replication.
• Standard for controlling life threatening active lupus
nephritis
– Chlorambucil
• Alkylating agent, cross-links DNA, thereby preventing
cell replication.
Basic and Clinical Pharmacology by Katzung 10th Edition
 DMARDS
• Immunosuppressants
– Indications:
• such life-threatening manifestations of SLE
as glomerulonephritis, CNS involvement,
thrombocytopenia, and hemolytic anemia
• the inability to reduce corticosteroid dosage
or severe corticosteroid side effects

Washington Manual of Therapeutics 31st Edition

 DMARDS
– Cyclosporine
MOA: inhibits IL-2 production by activated T cells
- Azathioprine
MOA: suppresses T and B cell functions
– Mycophenil mofetil
MOA: inhibits T cell proliferation and interferes
leukocyte adhesion
– Corticosteroids
MOA: inhibits COX-2 and phospholipase A2

Basic and Clinical Pharmacology by Katzung 10th Edition

 DMARDS
• Antimalarials
– Proposed mechanisms: T cell
suppression, decreases WBC
chemotaxis, stabilizes lysosomal
enzymes, inhibits DNA and RNA
synthesis, and free radical trapping
– reduce dermatitis, arthritis, and fatigue
– Chloroquine, Hydroxyhloroquine

Basic and Clinical Pharmacology by Katzung 10th Edition

 Prevent Complications
• Sunscreen
– Photosensitivity
– SPF >30

• Calcium and Vitamin D preparations

Harrison’s Principles Internal Medicine 16th Edition

 Treat Complications
Complications Treatment
Hypertension Antihypertensive (B
blockers)
Generalized Edema Corticosteroids

UTI Ciprofloxacin
Pulmonary Infiltration Corticosteroids

www.uic.edu/classes/pmpr/pmpr652/final/stevens/sle.html#SLE
• Adequate sleep and avoidance of fatigue
• Regular exercise
• Education about lupus and self-care
• Avoid smoking
• Eating a healthy balanced diet
• Salt restriction
• Developing a support system of family, friends,
and health professionals
• For patients with photosensitive rashes use
protective clothing, such as a hat and long
sleeves, and avoidance of sun exposure are
recommended to prevent flareups
Thank you!
 Kidneys
• Nephritis
– Immune complex deposition in renal
structures:
• Glomeruli
• Tubular & peritubular capillary basement
membranes
• Thrombosis
– Glomeruli
– Extraglomerular vasculature

From Harrison’s Principles of Internal Medicine 16th ed.

 Thrombosis
• Antiphospholipid antibody
– “lupus anticoagulant”

• Hypercoagulable state

From Harrison’s Principles of Internal Medicine 16th ed.

 Laboratory Diagnosis
• Staging of lupus nephritis – light
microscopy, IF and EM
– Class I - minimal mesangial lupus
nephritis
– Class II - mesangial proliferative lupus
nephritis
– Class III - focal lupus nephritis
– Class IV - diffuse lupus nephritis
– Class V - membranous lupus
nephritis
eMedicine.com: Nephritis, Lupus by Lawrence Brent MD, updated February 21, 2007
 Laboratory Diagnosis
• Class V
(membranous
lupus nephritis)
– Light microscopy
• Diffuse
thickening of
glomerular
basement
membrane
without
inflammatory
infiltrate
Lecture on Pathology of the Kidney by Normando Gonzaga MD
• Spikes
Internet Pathology using
for Medical Education, Florida State University - http://library.med.utah.edu/WebPath/RENAHTML/RENALIDX.html
 Laboratory Diagnosis
• Class V
(membranous
lupus nephritis)
– IF
• Granular IgG and
C3; diffuse
• “Rosary beads”
pattern

Lecture on Pathology of the Kidney by Normando Gonzaga MD

Internet Pathology for Medical Education, Florida State University - http://library.med.utah.edu/WebPath/RENAHTML/RENALIDX.html
 Laboratory Diagnosis
• Class V
(membranous
lupus nephritis)
– EM
• Subepithelial
deposits forming
“humps and
spikes”

Lecture on Pathology of the Kidney by Normando Gonzaga MD

Internet Pathology for Medical Education, Florida State University - http://library.med.utah.edu/WebPath/RENAHTML/RENALIDX.html