The positive ANA confirms the diagnosis so no further evaluation is necessary Pancytopenia

1. ** 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

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

6. 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

7. 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

8. 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

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

13. 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

14. Diffuse Proliferative Focal Proliferative Membranous Mesangial

15. Malar rash Discoid rash Photosensitivity Oral Ulcers Arthritis Serositis Renal disorder Neurologic disorder Hematologic disorder Immunologic disorder ANA positive SLE - Classification criteria(4 of 11 criteria should be present) 1997 update of the 1982 revision of the ACR classification criteria for SLE

16. or APL antibody MS Core - 2008

19. 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%

20. Autoantibodies in Rheumatic Diseases See appendix for more information

21. Outdated

22. 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

27. Drug-Induced Lupus • Major drug associations • Hydralazine • Procainamide • Less common associations • Alpha methyldopa, Diphenylhydantoin, PTU, PCN, Sulfa, INH, BCP, Minocycline, anti-TNF • Antibody association • Anti-histone antibody

28. 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

29. 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

33. 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

34. Mycophenolate Mofetil (MMF) • Inhibits lymphocyte proliferation (both B and T cells) • Inhibits glycosylation of adhesion molecules • Relatively non toxic

35. Prognosis SLE 95% 10 year survival

36. 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

37. 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