Systemic lupus erythematosus and related disorders

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disorder that can present with symptoms in almost any organ or system of the body. It is 10 to 20 times commoner in women than men, and commoner in Afro-Caribbeans than Asians than whites.

Aetiology is multifactorial, incorporating genetic, hormonal, and environmental elements. No single abnormality of the immune system can be considered responsible, pathogenesis depending on the interplay of a number of different factors, including autoantibodies, T lymphocytes, cytokines, the complement system, and apoptosis.

Clinical features

Common symptoms are constitutional (fatigue, anorexia), musculoskeletal (arthralgia/arthritis, myalgia), dermatological (alopecia, butterfly rash, vasculitic skin lesions, purpura), cardiopulmonary (breathlessness, pleurisy), and neurological (migraine, seizures, depression, psychosis).

Examination may show evidence of weight loss, low-grade fever, lymphadenopathy, arthritis (but rarely synovitis or deformity), skin rash, oral ulcers, dry eyes/mouth, pleural rub, and peripheral neuropathy (usually sensory).

Investigation and diagnosis

Investigation commonly reveals abnormalities in the following systems: (1) renal—proteinuria, microscopic haematuria, impaired glomerular filtration rate; (2) haematological—anaemia, leucopenia, lymphopenia, thrombocytopenia; and (3) cardiopulmonary—pulmonary function abnormalities.

The American College of Rheumatology classification criteria require four or more of the following to be present at some time: (1) malar rash; (2) discoid rash; (3) photosensitivity; (4) oral ulcers; (5) arthritis; (6) serositis; particular types of (7) renal, (8) neurological, and (9) haematological disorders; (10) immunological disorders (particular autoantibodies); and (11) raised titres of antinuclear antibody. In everyday practice, however, these requirements may be too stringent, and systemic lupus erythematosus should be suspected on the basis of typical clinical findings in one organ or tissue combined with the presence of appropriate autoantibodies. The antinuclear antibody assay is a sensitive (>95%) but not specific test for SLE, hence the absence of antinuclear antibody in a patient with suspected lupus raises serious doubt about the diagnosis. The presence of anti-dsDNA (and anti-Sm) antibodies is virtually specific for lupus. The most reliable measures of highly active disease are depletion of complement, and high anti-dsDNA levels.

Prognosis and management

SLE can kill (mortality c.10% at 10 years from diagnosis), but it may run a fairly indolent course in which an initial flare is followed by many years of low-grade activity. General treatment measures include (1) rest—as appropriate; (2) avoidance of overexposure to sunlight; (3) attention to modifiable cardiovascular risk factors—women with lupus between 35 and 45 years have a 50× increased risk of coronary disease; and (4) prophylaxis / treatment of osteoporosis—usually induced by steroid therapy.

Mild disease—patients whose disease activity is confined to arthralgia, tiredness, and/or mild rash can often be treated symptomatically, e.g. with simple analgesics and/or nonsteroidal anti-inflammatory agents (NSAIDs), with hydroxychloroquine added if these are not sufficient.

Treatment of flares of disease—corticosteroids and cytotoxic agents are used. A mild flare of arthralgia, myalgia, and general fatigue may be alleviated by a single intramuscular dose of corticosteroid. More severe flares of arthritis, pleuritis or pericarditis require oral prednisolone (20–40 mg daily). Renal flares require the most aggressive treatment, generally involving both corticosteroids (high-dose oral and/or intravenous pulse) and cyclophosphamide/mycophenolate mofetil. Biological therapies will be increasingly used in the future: B-cell depletion with the anti-CD20 chimeric reagent rituximab looks very promising, and trials are under way with many other agents.

Antiphospholipid antibody syndrome—immunosuppression is rarely useful and aspirin (150–300 mg daily) is recommended, with lifelong anticoagulation advised for those who have suffered recurrent thromboses or cerebral infarcts.

Pregnancy—SLE may be exacerbated during the pregnancy. Babies born to mothers with lupus are prone to the transient condition of neonatal lupus, also to heart block (particularly if the mother has anti-Ro and anti-La antibodies).