Chapter 158: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Other Connective Tissue Diseases

CONNECTIVE TISSUE DISEASE

DEFINITION

Heterogeneous disorders that share certain common features, including inflammation of skin, joints, and other structures rich in connective tissue; as well as altered patterns of immunoregulation, including production of autoantibodies and abnormalities of cell-mediated immunity. While distinct clinical entities can be defined, manifestations may vary considerably from one pt to the next, and overlap of clinical features between and among specific diseases can occur.

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

DEFINITION AND PATHOGENESIS

Disease of unknown etiology in which tissues and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. Genetic, environmental, and sex hormonal factors are likely of pathogenic importance. T- and B-cell hyperactivity, production of autoantibodies with specificity for nuclear antigenic determinants, and abnormalities of T-cell function occur.

CLINICAL MANIFESTATIONS

Approximately 90% of pts are women, usually of child-bearing age; more common in blacks than whites. Course of disease is often characterized by periods of exacerbation and relative quiescence. May involve virtually any organ system and have a wide range of disease severity. Common features include:

• Constitutional: fatigue, fever, malaise, weight loss

• Cutaneous: rashes (especially malar “butterfly” rash), photosensitivity, vasculitis, alopecia, oral ulcers

• Arthritis: inflammatory, symmetric, nonerosive

• Hematologic: anemia (may be hemolytic), neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly, venous or arterial thrombosis

• Cardiopulmonary: pleuritis, pericarditis, myocarditis, endocarditis. Pts are also at increased risk of myocardial infarction usually due to accelerated atherosclerosis.

• Nephritis: classification is primarily histologic (Table 378-2, p. 2127, in HPIM-19)

• 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; in particular: procainamide, hydralazine, isoniazid, chlorpromazine, methyldopa, minocycline, anti-TNF agents. Features are predominantly constitutional, joint, and pleuropericardial; CNS and renal disease are rare. All pts have ANAs; antihistone antibodies may be present, but antibodies to dsDNA and hypocomplementemia are uncommon. Most pts improve following withdrawal of offending drug.

EVALUATION

• History and physical examination

• Presence of ANA is a cardinal feature, but a (+) ANA is not specific for SLE. Laboratory assessment should include: CBC, ESR, ANA and ANA subtypes (antibodies to dsDNA, ssDNA, Sm, anti-Ro/SS-A, anti-La/SS-B, histone), complement levels (C3, C4, CH50), serum immunoglobulins, VDRL, PT, PTT, anticardiolipin antibody, lupus anticoagulant, urinalysis.

• Appropriate radiographic studies

• ECG

• Consideration of renal biopsy if evidence of glomerulonephritis

DIAGNOSIS

Classification criteria used to confirm SLE in studies can provide a basis in individual patients for estimating the probability that a disease is SLE. Four or more published criteria carry a 93% specificity and 92% sensitivity for SLE (Table 378-3, p. 2127, in HPIM-19).