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Information ⬇

[Section Outline]

Definition and Pathogenesis !!navigator!!

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 !!navigator!!

Approximately 90% of pts are women, usually of child-bearing age; highest prevalence is in African-American and Afro-Caribbean women. 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 349-2, in HPIM-20).
  • GI: peritonitis, vasculitis
  • Neurologic: organic brain syndromes, seizures, psychosis, cerebritis

Drug-Induced Lupus !!navigator!!

A clinical and immunologic picture similar to spontaneous SLE may be induced by drugs; in particular: procainamide, hydralazine, isoniazid, chlorpromazine, methyldopa, minocycline, TNF inhibitors. 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 !!navigator!!

  • History and physical examination
  • ANA present in >98% of pts, 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 !!navigator!!

Classification criteria used to confirm SLE in studies can provide a basis in individual pts for estimating the probability that a disease is SLE. Four or more published criteria carry a 93% specificity and 92% sensitivity for SLE (Table 349-3, in HPIM-20).

TREATMENT

Systemic Lupus Erythematosus

Choice of therapy is based on type and severity of disease manifestations. Goals are to control acute, severe flares and to develop maintenance strategies, whereby symptoms are suppressed to an acceptable level. Treatment choices depend on (1) whether disease is life threatening or likely to cause organ damage; (2) whether manifestations are reversible; and (3) the best approach to prevent complications of disease and treatment (Fig. 349-2, and Table 349-5, in HPIM-20). As SLE predominantly affects young women, teratogenic potential and need for effective contraception must be considered with each prescribed medication.

CONSERVATIVE THERAPIES FOR NON-LIFE-THREATENING DISEASE

  • Sun protection: as UV exposure may exacerbate cutaneous and/or systemic SLE, sunscreen use is strongly recommended.
  • NSAIDs: Must consider renal, GI, and cardiovascular complications.
  • Antimalarials (hydroxycholoroquine): may improve constitutional, cutaneous, articular manifestations. Ophthalmologic evaluation required before and during treatment to rule out ocular toxicity.
  • Methotrexate: can be considered for dermatitis, arthritis.
  • Belimumab: B-lymphocyte stimulator (BLyS)-specific inhibitor. Should not be used in severe SLE such as nephritis or CNS disease and limited to pts with mild to moderate active disease.
  • Baricitinib: oral inhibitor of JAK1 and JAK2 (small molecule inhibitor). In a randomized trial, found to be effective for arthritis and rash in SLE.

TREATMENTS FOR LIFE-THREATENING SLE

  • Systemic glucocorticoids.
  • Cytotoxic/immunosuppressive agents: added to glucocorticoids to treat serious SLE.
    1. Cyclophosphamide: can be given as intermittent IV or daily oral. Two IV regimens have been studied-high-dose cyclophosphamide 500-1000 mg/M2 IV × 6 months used for severe nephritis or other life-threatening SLE. European studies have found low-dose cyclophosphamide 500 mg every 2 weeks for 6 doses to be effective, but it remains unclear whether these data apply to U.S. populations. Both regimens are followed by maintenance with mycophenolate or azathioprine.
    2. Mycophenolate (mycophenolate mofetil, mycophenolate sodium): A higher proportion of African-American pts appears to respond to mycophenolate mofetil compared with cyclophosphamide. As there is teratogenic potential, effective contraception must be discussed in women with child-bearing potential and men whose female partner can become pregnant.
    3. Azathioprine: may be effective but is slower in inducing therapeutic response.
    4. Rituximab: anti-CD20 B cell depleting monoclonal antibody. The role of rituximab in SLE is controversial. Use generally limited to those with severe disease that has not responded to standard approaches.

Outline ⬆

Section 12. Allergy, Clinical Immunology, and Rheumatology