Systemic lupus erythematosus (SLE) is a complex, multisystem, autoimmune condition characterised by autoantibodies directed against nuclear components. It affects approximately 1 in 4000 and is more common in women (ratio 10 female:1 male) and Africans and Afro-Caribbeans. The variety of autoantigens (e.g. histone, ribonucleoprotein (RNP)) is responsible for an array of patterns and severity of disease, which can range from mild to life-threatening in the same patient over time. The variable and multisystem nature of SLE makes it a great mimic of other conditions, and it can be a difficult diagnosis to make. As a result, clinicians have adopted the diagnostic criteria of the American Rheumatological Association (ARA), which were originally created for research and epidemiological purposes.

Four or more of the following must be fulfilled, either simultaneously or sequentially.

Skin disease and arthropathy

In addition to the skin symptoms in the diagnostic criteria, patients with cutaneous manifestations of lupus may present with non-scarring alopecia, purpura, urticaria and hyperpigmentation. The musculoskeletal picture is dominated by polyarticular arthralgia, but the disease is more benign than rheumatoid arthritis and overt joint damage occurs in fewer than 10% of patients. Jaccoud’s arthropathy refers to reversible joint instability and subluxation due to tendonitis rather than irreversible destruction due to synovitis. Muscle disease is rare and may be a consequence of drug therapy.

Renal lupus

Renal disease is a serious complication and every patient should have their blood pressure checked, electrolytes measured and urine assessed for casts and protein at each clinic visit. SLE causes a range of glomerulonephritidies, which have been classified by the World Health Organisation according to biopsy findings. Although this system may offer some clues to prognosis, renal lupus is generally treated very aggressively.

Respiratory disease

Up to two-thirds of patients will complain of pain or pleuritis at some point during their disease, and a third develop pleural effusions. The more unusual complications of interstitial fibrosis, vasculitis and pneumonitis may present with an insidious development of shortness of breath and/or decrease in exercise tolerance. First-line investigations include a chest X-ray and lung function tests, which may indicate a greater extent of disease than is evident clinically. Pulmonary hypertension may occur as a result of fibrosis, vasculopathy or chronic thromboembolic disease, particularly in those with antiphospholipid syndrome (see below).

Haematological system

Autoantibodies against red cells, lymphocytes and platelets may reduce all of these cell counts, and an acute thrombocytopaenia can be dramatic and life-threatening. The commonest haematological finding, however, is anaemia of chronic disease, which is present in up to three-quarters of lupus patients. While the ESR is commonly raised in SLE, an elevated CRP (C-reactive protein) is unusual and should prompt a search for concurrent infection.

Raynaud’s phenomenon

Although not a diagnostic criterion, Raynaud’s is common in lupus patients and may predate the disease by some years. Treatment is identical to idiopathic Raynaud’s disease with vasodilators.

Hydralazine, procainamide, isoniazid, minocycline and sulfasalazine have all been implicated in causing SLE, but drug-induced disease is generally mild, with few renal or neurological features and the disease disappears with cessation of the drug.

These medications are not contraindicated in idiopathic SLE.

Autoantibodies

Autoantibodies directed against the nucleus are not specific for lupus but they are very sensitive and therefore a raised ANA titre is a useful first step in the diagnosis of SLE. A negative ANA in a patient with suspected SLE is very reassuring, but a raised ANA titre does not always lead to a diagnosis of lupus as elevated levels can be found in a number of other autoimmune conditions such as rheumatoid arthritis or Sjögren’s syndrome.

Antibodies directed against native DNA (dsDNA) are more specific for a diagnosis of SLE and the remaining autoantibodies are associated with particular complications as listed below.

Complement

SLE causes reduced levels of C3 and C4 due to immune complex deposition. In an exacerbation of lupus, the complement levels would be expected to fall, in association with an elevation in dsDNA titre. However, since patients often have persistently abnormal serology in the absence of active disease, results must be assessed in combination with the clinical picture.

All lupus patients should avoid sun exposure and use high-factor sun creams. Other treatment varies depending on the severity of the disease.