** You are asked to see a 24 y/o female with fatigue, myalgias, and a positive ANA. Which of the following would NOT be consistent with SLE?
a) The positive ANA confirms the diagnosis so no further evaluation is necessary
b) Pancytopeniac) A history of a transient episode of confusion followed
by numbness and tingling in the right armd) No history of arthritise) Significant cardiomegaly on chest x-ray
Immune Mediated Disease
Etiology - unknown Multiple organ system involvement Immune complexes
ANAComplementOther antibodies
Treatment - usually corticosteroids
Systemic Lupus Erythematosus Multisystem disease - young female Antigen-antibody complexes
positive ANA, dsDNA, complement Common problems
Arthritis, dermatitis, hematologic, renal, polyserositis, CNS, splenomegaly
Treatment - corticosteroids
Lupus Demographics young women 5:1 over men ages - 15 - 40 Relatively uncommon – 50/100,000 individuals - 0.05%
population Males, Afro-Americans (increased Sm/RNP), Hispanics have
worse prognosis Genetic factors – variable
High prevalence among twins5-12% cumulative incidence among first-degree relativesHLA Class II (multiple associations) and C4a null alleles
Typical findings Skin - butterfly rash, alopecia, photosensitivity, mucosal
ulcerations Arthritis - 90%, symmetrical CNS - 25-50%
focal vs. general, headache most common Serositis - pericardial, pleural, peritoneal CV – Increased incidence of atherosclerotic plaques Splenomegaly
Atherosclerotic plaque (controls vs. SLE patients)(controlled for corticosteroid use)
NEJM 349:2003, 2399-2406
SLE - Renal Disease – 50% (acute vs chronic)
Normal - I Minimal change - IIA Mesangial - IIB Focal Proliferative - III Diffuse Proliferative - IV Membranous - V Sclerosis - VI
WHO Classification
Diffuse Proliferative Focal Proliferative
Membranous Mesangial
SLE - Classification criteria(4 of 11 criteria should be present) Malar rash Discoid rash Photosensitivity Oral Ulcers Arthritis Serositis
Renal disorder Neurologic disorder Hematologic disorder Immunologic disorder ANA positive
1997 update of the 1982 revision of the ACR classification criteria for SLE
MS Core - 2008
orAPL antibody
Systemic Lupus - Laboratory Findings Serology
ANA - 95% (nDNA 50%, Sm 50%)Rheumatoid factor - 15-25% Complement - 50-75%
CBCLeukopenia - 50%Anemia - 50-75%Thrombocytopenia - 10-20%
Autoantibodies in Rheumatic Diseases
SLE DS DNA, Sm
Drug induced SLE HistoneSCLE Anti Ro (SS-A)
MCTD RNP
Scleroderma Scl-70
CRST Centromere
Polymyositis/Dermatomyositis Jo-1 (histadyl tRNA synthetase)
Sjogren’s Syndrome SS-A, SS-B
Wegener’s Granulomatosis cANCA (Proteinase 3)
See appendix for more information
Lupus Erythematosus - Subtypes SLE - systemic Discoid – relatively benign (skin and joints) SCLE - subacute cutaneous
anti-Ro antibody positiveneonatal lupus / congenital heart block
Drug induced – anti-histone antibody Anti-phospholipid antibody syndrome
Drug-Induced Lupus Major drug associations
HydralazineProcainamide
Less common associationsAlpha methyldopa, Diphenylhydantoin, PTU, PCN, Sulfa, INH, BCP, Minocycline, anti-TNF
Antibody associationAnti-histone antibody
Anti-phospholipid Syndrome - lupus anticoagulant / anticardiolipin antibody
Increased clotting Screening - PTT, False + VDRL Associated with SLE - 30% of cases Anti-cardiolipin antibody may be present Treatment - anticoagulation
Anti-phospholipid Syndrome Classification criteriaOne clinical and one lab criteria must be found Clinical (either of following)
Vascular thrombosis – one or more episodes of arterial, venous, or small vessel thrombosisPregnancy morbidity
– Late term (>10 wk) abortion (normal fetus)– Premature birth (<34 week) with preeclampsia, eclampsia, or placental insufficiency– Three or more spontaneous abortions (<10 weeks) without other explanation
Abnormal lab (either test)Anticardiolipin antibody (IgG or IgM) X2 twelve weeks apart and not more than 5 years previously (must be moderate or high titer)Anti-β2 glycoprotein (IgM or IgG) - >99%ileLupus anticoagulant (prolonged PTT with failure to correct) x2 twelve weeks apart
SLE - treatment Nonsteroidals Corticosteroids - major organ dysfunction Antimalarials - Hydroxychloroquine skin and joint
manifestations (minor organ systems) Cytotoxics (CTX) - major renal involvement
high dose monthly IV (750-1000 mg/m2)OR
Daily oral (100-150 mg/d)
Mycophenolate mofetil
Mycophenolate Mofetil (MMF) Inhibits lymphocyte proliferation (both B and T cells) Inhibits glycosylation of adhesion molecules Relatively non toxic
Prognosis SLE
0102030405060708090
100
Initial 1 year 5 years 10 years
Perc
ent s
urvi
val
Pre-steroids Steroids Immunosup. Currently
95% 10 year survival
You are asked to see a 24 y/o female with fatigue, myalgias, and a positive ANA. Which of the following would NOT be consistent with SLE?
a) The positive ANA confirms the diagnosis so no further evaluation is necessary
b) Pancytopeniac) A history of a transient episode of confusion followed
by numbness and tingling in the right armd) No history of arthritise) Significant cardiomegaly on chest x-ray
A 18 y/o female presents with a five month history of joint complaints, easy bruisibility, pain with breathing on the left side, and occasional weakness in the left hand and right foot. Which of the following would you NOT expect to find on further evaluation?
a) Positive VDRL test for syphilisb) History of previous miscarriagec) Recurrent oral ulcerationsd) 3+ proteinuria on UAe) History of allergy to multiple medications
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