Systemic lupus erythematosus

The American Rheumatology Association’s 1982 classification criteria for systemic lupus erythematosus were revised in 1997 (Box 18.3). These criteria were designed not for diagnosis but for classifying patients into studies and clinical trials. The diagnosis of SLE should be considered if a patient has characteristic features of lupus, even if they do not fulfil four of the 11 criteria. For example, a 25‐year‐old woman with malar rash, positive antinuclear antibody and histologically proven glomerulonephritis obviously has systemic lupus erythematosus, despite fulfilling only three criteria (Table 18.2).

The Systemic Lupus Collaborating Clinics (SLICC) revised and validated the American College of Rheumatology (ACR) SLE classification criteria (Table 18.3). The SLICC criteria for SLE classification require: (1) fulfilment of at least four criteria, with at least one clinical criterion AND one immunological criterion OR (2) lupus nephritis as the sole clinical criterion in the presence of ANA or anti‐dsDNA antibodies (Petri et al., 2012). These criteria are meant to be clinically more relevant, allowing the inclusion of more patients with clinically defined lupus in studies and clinical trials than when using the current ACR criteria.

General features

Fatigue is common, troublesome and difficult to evaluate. It may be associated with depression or fibromyalgia secondary to SLE, hypothyroidism (often autoimmune in nature), anaemia, pulmonary or cardiovascular problems. Other constitutional symptoms of active disease include fever, malaise, anorexia, lymphadenopathy and weight loss.

The most common form of anaemia is a normochromic normocytic anaemia of chronic disease. Some patients develop an antibody‐mediated haemolytic anaemia and others an iron deficiency anaemia secondary to peptic ulceration or gastritis (usually due to non‐steroidal anti‐inflammatory drugs.

Mucocutaneous manifestations

The most common mucocutaneous features are painful or painless mouth ulcers, diffuse alopecia (Figure 18.1), butterfly or malar rash (Figure 18.2) and photosensitivity. Nasal or vaginal ulcers may also occur. Mucocutaneous features are more prominent in Asians and whites. Subacute cutaneous lupus erythematosus is a non‐scarring rash found in areas of the body exposed to the sun. Discoid lesions are chronic scarring lesions that heal with hypo‐ or hyperpigmentation. Non‐scarring alopecia may be patchy or diffuse. Rapid, spontaneous hair loss indicates active disease. Raynaud’s phenomenon is usually milder than in scleroderma.

Musculoskeletal manifestations

Generalized arthralgia with early morning stiffness and no swelling is very common. A non‐erosive arthritis with joint tenderness and swelling may develop. Deformities are unusual but may occur due to ligamentous laxity (Jacoud’s arthropathy) (Figure 18.3) compared with rheumatoid arthritis where the deformities are due to joint erosions. Myalgia is common but inflammatory myositis occurs in only 5% of patients. Indeed, secondary causes of myopathy are more common and can be caused by corticosteroids, antimalarials and lipid‐lowering agents. Avascular necrosis and infection should be suspected if the patient complains of sudden‐onset, severe pain in only one joint. In addition, the risk of osteoporosis and subsequent fracture due to minimal or no trauma can be increased in patients with SLE.

Haematological manifestations

Leucopenia may be an early clue to the diagnosis of SLE. Lymphopenia is the most common manifestation of SLE other than positive antinuclear antibodies and, in untreated patients, is caused by lymphocytotoxic antibodies. Mild neutropenia is relatively common in black people even without SLE, but values <1.5 × 10⁹/L are usually related to disease or drugs. Thrombocytopenia may occur as an immune‐mediated condition associated with a risk of bleeding, as in idiopathic thrombocytopenic purpura, or as a milder abnormality with platelet counts >70 × 10⁹/L associated with a risk of thrombosis in the antiphospholipid syndrome (see below).

Renal manifestations

Renal disease is an important determinant of the outcome of SLE. It can occur in up to 50% of white patients and 75% of black patients. Studies have shown that renal disease is also more severe in non‐white patients. Early nephritis is often asymptomatic, so regular urinalysis for protein, blood and casts is essential. Some patients present with nephrotic syndrome and a few with devastating accelerated hypertension and renal shutdown. Renal biopsy is helpful for assessing the severity, nature, extent and reversibility of the involvement and is an important guide to treatment and prognosis. For example, those with mesangial nephritis (class I) rarely progress to renal failure. In contrast, those with diffuse proliferative glomerulonephritis (class IV) are at risk for end‐stage renal disease.

Nervous system manifestations

Systemic lupus erythematosus may affect the central and peripheral nervous systems. Definitions for these manifestations have been proposed by a consensus group (Boxes 18.4 and 18.5). The most common manifestations are headache, seizures, aseptic meningitis and cerebrovascular accidents. Antiphospholipid antibodies (including anticardiolipin antibodies) have been implicated in cerebrovascular accidents and chorea. It is often hard to determine whether the depression and headaches are due to lupus itself; in many cases, they are related to psychosocial issues. Other possible causes such as sepsis, drugs, uraemia, severe hypertension and other metabolic causes must be sought and treated. Steroids are often blamed for inducing psychosis but if any doubt exists, patients should be given more, not less, steroid while under medical supervision, particularly if active lupus is evident in other systems.