** 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