Systemic Lupus Erythematous (SLE)

Pathophysiology

1) systemic disorder with tissue damage secondary to autoantibodies and immune complex deposition 2) cause is unknown but likely requires an environmental stimulus (example is ultraviolet light) in presence of many susceptibility genes

Signs and Symptoms

1) butterfly rash on face 2) short hairs in frontal scalp (“lupus hairs”) 3) “carpet tack” skin lesions 4) pericarditis 5) pericardial effusions 6) pleurisy 7) pleural effusions 8) focal or diffuse proliferative nephritis 9) abdominal pain 10) blindness 11) fatigue (often debilitating) 12) cognitive dysfunction (“lupus cerebritis”) 13) subcutaneous nodules 14) puffiness of hands and feet 15) swan-neck deformities of fingers

Characteristic Test Findings

Laboratory – 1) anti-ANA antibody (98%) 2) anti-DNA antibody (70%) 3) antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody) 4) anti-Smith (Sm) antibody (30%) 5) increased sed rate 6) low complement (especially CH50) 7) pancytopenia 8) warm antibody hemolytic anemia

Histology/Gross Pathology

1) Libman-Sacks lesions (wart-like endocardial lesions) 2) marrow hypoplasia 3) thrombotic microangiography in kidney 4) deposition in glomerulus and mesangium of immune complexes (“wire-loop” deposition) 5) proliferative nephritis

Associated Conditions

1) HLA-DR2 or DR3 2) defective c4AQO class III allele 3) drugs – procainamide, quinidine, sulfonamides, barbiturates, cephalosporins 4) Raynaud’s phenomenon 5) increased rate of abortion and stillbirth (especially if lupus anticoagulant and anticardiolipin antibodies are present)

Inheritance/Epidemiology

1) 90% are women (especially premenopausal women) 2) occurs most commonly in blacks 3) clear genetic predisposition exists

Treatment

1) photoprotection for skin lesions 2) NSAIDS (especially Cox-2 inhibitors) and salicylates 3) antimalarials (hydroxychloroquine) or aminoquinoline in skin lesions 4) dehydroepiandrosterone (best in mild cases) 5) glucocorticoids 6) cytotoxic drugs – azathioprine, cyclophosphamide (especially in kidney disease), methotrexate, mycophenolate mofetil 7) anticoagulation if thrombosis is present 8) plasmapheresis with cytotoxic drugs 9) intravenous immunoglobulin

Tips for USMLE

1) repeat negative tests for anti-ANA antibody makes lupus very unlikely (but anti-ANA is positive in many diseases other than lupus 2) anti-SM antibody is highly specific for lupus 3) anti-double-stranded DNA antibody is relatively specific 4) most patients with systemic disease have discoid lupus (chronic cutaneous lupus), but only 10% with discoid lupus progress to systemic disease 5) skin lesions predominate in sun-exposed areas 6) if Libman-Sacks endocarditis is mentioned, think lupus 7) if low complement is mentioned (especially CH50), think SLE 8) some clinicians feel that Lyme disease may sometimes be misdiagnosed as lupus