No history of arthritis Significant cardiomegaly on chest x-ray ** 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? The positive ANA confirms the diagnosis so no further evaluation is necessary Pancytopenia A history of a transient episode of confusion followed by numbness and tingling in the right arm No history of arthritis Significant cardiomegaly on chest x-ray

Immune Mediated Disease Etiology - unknown Multiple organ system involvement Immune complexes ANA Complement Other antibodies Treatment - usually corticosteroids

Facial rash

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 twins 5-12% cumulative incidence among first-degree relatives HLA 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

Vasculitis of fingers

Chest xray

Atherosclerotic plaque (controls vs. SLE patients) (controlled for corticosteroid use) NEJM 349:2003, 2399-2406

Immunofluorescence of glomerulus

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

or APL antibody MS Core - 2008

Systemic Lupus - Laboratory Findings Serology ANA - 95% (nDNA 50%, Sm 50%) Rheumatoid factor - 15-25% Complement - 50-75% CBC Leukopenia - 50% Anemia - 50-75% Thrombocytopenia - 10-20%

Autoantibodies in Rheumatic Diseases SLE DS DNA, Sm Drug induced SLE Histone SCLE 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

Outdated ANA – four types

Lupus Erythematosus - Subtypes SLE - systemic Discoid – relatively benign (skin and joints) SCLE - subacute cutaneous anti-Ro antibody positive neonatal lupus / congenital heart block Drug induced – anti-histone antibody Anti-phospholipid antibody syndrome

Discoid lupus rash

Drug-Induced Lupus Major drug associations Less common associations Hydralazine Procainamide Less common associations Alpha methyldopa, Diphenylhydantoin, PTU, PCN, Sulfa, INH, BCP, Minocycline, anti-TNF Antibody association Anti-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 criteria One clinical and one lab criteria must be found Clinical (either of following) Vascular thrombosis – one or more episodes of arterial, venous, or small vessel thrombosis Pregnancy 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%ile Lupus anticoagulant (prolonged PTT with failure to correct) x2 twelve weeks apart

Infarcts of pinna

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 95% 10 year survival

No history of arthritis Significant cardiomegaly on chest x-ray 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? The positive ANA confirms the diagnosis so no further evaluation is necessary Pancytopenia A history of a transient episode of confusion followed by numbness and tingling in the right arm No history of arthritis Significant cardiomegaly on chest x-ray

Positive VDRL test for syphilis History of previous miscarriage 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? Positive VDRL test for syphilis History of previous miscarriage Recurrent oral ulcerations 3+ proteinuria on UA History of allergy to multiple medications