SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

DEFINITION

Disease of unknown etiology in which tissues and cells are damaged by deposition of pathogenic autoantibodies and immune complexes Pathogenic importance : Genetic, environmental, and sex hormonal factors Characteristics :
a) b) c)

T and B cell hyperactivity Production of autoantibodies with specificity for nuclear antigenic determinants Abnormalities of T cell function

CLINICAL MANIFESTATIONS
90% of pts are women, child bearing age, more common in blacks than whites Course in disease is often on one of periods of exacerbation and relative passive Involve virtually any organ system Wide range of disease severity

COMMON FEATURES

Constitutional fatigue, fever, malaise, weight loss Cutaneous rashes, photosensitivity, vasculitis, alopecia, oral ulcers Arthritis inflammatory, symmetric, nonerosive Hematologic anemia, neutropenia, lymphadenopathy, thrombocytopenia, splenomegaly, venous or arterial thrombosis Cardiopulmonary pleuritis, pericarditis, myocarditis, endocarditis Nephritis GI peritonitis, vasculitis Neurologic organic brain syndromes, seizures, psychosis, cerebritis

DRUG INDUCED LUPUS

A clinical and immunologic picture similar to spontaneous SLE May be induced by drugs : procainamide, hydralazine, isoniazid, chlorpromazine, methyldopa Features are predominantly constitutional, joint, and pleuropericardial; CNS and renal disease are rare All pts have antinuclear antibodies (ANA), antihistone antibodies may be present but antibodies to dsDNA and hypocomplementemia are uncommon Most pts improve following withdrawal of offending drug

EVALUATION

Hx and physical exam Presence of ANA is a cardinal factor, but a (+) ANA is not specific for SLE Laboratory assessment should include : CBC, ESR, ANA and subtypes (antibodies to dsDNA, ssDNA, Sm, Ro, La, Histone), complement levels (C3, C4, CH50), serum immunoglobulins, VDRL, PT, PTT, anticardiolipin antibody, lupus anticoagulant, UA Appropriate radiographic studies ECG Consideration of renal biopsy if evidence of glomerulonephritis

TREATMENT

Choice of therapy is based on type and severity disease manifestations Goals are to control acute, severe flares, develop maintenance strategies where symptoms are suppressed to acceptable level Treatment choices depend on :
Whether disease is life threatening or likely to cause organ damage b) Whether manifestations are reversible c) The best approach to prevent complications of disease and treatment
a)

Conservative Therapies for Non Life Threatening Disease

NSAIDs (e.g. ibuprofen 400 800 mg tid qid) Antimalarials (hydroxychloroquine 400 mg/d) may improve constitutional, cutaneous, articular manifestations. Ophthalmologic evaluation required before and during Rx to rule out ocular toxicity

Treatments for Life Threatening SLE

Systemic glucocorticoids Anticoagulation - may be indicated in pts with thrombotic complications Cytotoxic agents beneficial in active glomerulonephritis; may be required for severe disease not successfully controlled by acceptable doses of steroids
1) 2) 3)

Cyclophosphamide considered the standard drug for controlling life threatening active lupus nephritis Mycophenolate motefil short term studies suggest efficacy in some pts with SLE Azathioprine indicated in pts who cannot take cyclophosphamide