1. Aetiology and epidemiology
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a broad spectrum of clinical presentations. There is a peak age of onset among young women between the late teens and early 40s and a female to male ratio of nine to one. Ethnic groups such as those with African or Asian ancestry are more at risk of developing the disorder and it may be more severe compared to Caucasian patients. SLE is a relatively common chronic illness that may be life-threatening when major organs are affected but more commonly results in chronic debilitating ill health.
No single cause for SLE has been identified though factors such as sunlight and drugs may precipitate the condition and there is a complex genetic basis. Although there a familial tendency, in most patients SLE occurs sporadically. It is therefore worth asking about a family history of autoimmune disease when considering a diagnosis of SLE.
Many other weak associations with silica, occupational exposure to mercury and pesticides have been described.
SLE is characterised by episodes of relapses or flares and remissions, and the outcome ranges from long-term remission to death. However, both morbidity and mortality have improved. Over the past 50 years, survival has improved dramatically in patients with SLE.
Many reports suggest that exogenous oestrogens exacerbate lupus or increase the risk of developing this disorder. Recent studies have shown that both HRT and the combined oral contraceptive pill may be used in women with SLE with only a small risk of major flares. Oestrogens remain contraindicated if antiphospholipid antibodies are present because of the thrombosis risk.
Antiphospholipid syndrome (APS)
The APS or Hughes syndrome is characterised by recurrent foetal losses and thrombosis, though the ramifications of the syndrome extend to all branches of medicine. There is a wide spectrum of clinical features arising from thrombosis in any organ system. Livedo reticularis is a useful clinical marker.
The clinical features of APS continue to broaden with descriptions of renal artery stenosis, metatarsal fractures, avascular necrosis and abnormalities of vascular function. Therapy is mainly long-term anticoagulation in patients who have suffered a thrombotic event.
2. Clinical features and diagnosis
Joint pains occur in about 90 per cent of SLE patients and are usually symmetrical, intermittent and flitting in nature. Tenosynovitis is more common than erosive synovitis and is the cause of the ‘swan-neck’ deformities and ulnar deviation seen in the Jaccoud’s arthritis of lupus.
Cutaneous lesions may occur in up to 85 per cent of SLE patients. The butterfly rash is the best recognised lesion of lupus but it is not the most common presenting feature.
In addition to maculopapular and discoid lesions, splinter haemorrhages, dilated capillaries at the nail base, bullous lesions, livedo reticularis and oral and nasal ulceration also occur. Vasculitic skin lesions are usually found at the finger tips, toes and feet or on the extensor surface of the forearm.
More than 70 per cent of patients with SLE have renal involvement at some stage of their disease. If detected early, lupus nephritis is very treatable and may prevent progression to end stage renal disease.
Chest infections are common and may be due to a variety of pathogens. Other features include interstitial fibrosis, pulmonary vasculitis and interstitial pneumonitis. Pleural effusions may be found in about half of SLE patients especially during generalised disease flares .
Cardiac manifestations include pericarditis and pericardial effusions. Systolic murmurs are heard in around 30 per cent of SLE patients. Libman-Sacks endocarditis is a classical complication of SLE.
Central nervous system lupus
The spectrum of recognised CNS lupus features has grown from seizures and psychosis to 19 different syndromes such as Guillan-Barre syndrome. An emerging concept is the distinction between CNS manifestations due to lupus and those due to APS.
Abdominal pain occurs in about 20 per cent of patients (especially children) and may be due to peritoneal inflammation analogous to the serositis that leads to pleuro-pericardial disease. Hepatosplenomegaly and/or liver function test abnormalities may occur in up to 30 per cent of patients.
A normochromic, normocytic anaemia of chronic disease is common. Thrombocytopenia (platelet count <100 x 109/l) may be acute or chronic. Persistent leucopenia (<4.0 x 109/l) is a classic feature of SLE. Immuno-suppressive drugs may also cause a marked leucopenia hence the need for regular blood monitoring tests.
Serological tests for SLE include antinuclear antibodies and anti-double stranded DNA antibodies and anti-phospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies).
A negative result for anti-dsDNA antibodies does not exclude a diagnosis of lupus. The characteristic acute phase response is a high ESR with a normal C-reactive protein (CRP). The CRP, however, rises normally in SLE patients who have bacterial infections making this a useful way of differentiating acute lupus flares from sepsis.
Some autoantibodies are useful in sub-setting lupus patients. For example, anti-Ro (SSA) antibodies, often accompanied by anti-La (SSB), are found in 20–30 per cent of SLE patients. Women with these autoantibodies contemplating pregnancy should be counselled about the risk (between 1 and 5 per cent) of having babies complicated by neonatal lupus syndrome: complete congenital heart block and transient neonatal rashes.
Clinical diagnosis of SLE
Diagnosis of SLE hinges on careful assessment of presenting clinical features, examination of all the organ systems and selected investigations.
3. Management of SLE
The majority of SLE patients can be managed jointly between primary and secondary care. Early identification of disease flares is important and secondary care facilities should be accessible rapidly for these patients.
Arthralgia and skin rashes
Discoid lupus lesions often respond to topical therapies and in combination with hydroxychloroquine are often useful. Topical preparations of tacrolimus and pimecrolimus have shown benefit in small open case series.
NSAIDs are widely prescribed for SLE patients with joint pains but their use is discouraged in favour of simple analgesics. In particular the COX-2 selective agents are contraindicated in SLE on account of the potential CV risks and even conventional NSAIDs are not without gastrointestinal, renal and cardiovascular risks.
Hydroxychloroquine remains the mainstay for patients with mild SLE especially with arthralgia, skin rashes, alopecia and oral/genital ulceration. It is well-tolerated and is disease-modifying, as well as having other properties such as a weak anti-thrombotic action. Other beneficial effects on serum lipids and blood glucose profiles and a lower risk of cataracts make it especially useful in patients who also need long-term corticosteroids.
Mepacrine is another safe anti-malarial widely used in mild lupus, often in combination with hydroxychloroquine where the latter has not produced a response on its own. Ocular toxicity is rare and providing there is no major renal impairment and annual visual field checks are performed, long-term anti-malarial therapy is relatively safe. No blood monitoring is needed but patients should be warned about the risk of skin rashes which may occur in 5–10 per cent of patients and resolve on withdrawal.
Short courses of low dose pulse cyclophosphamide followed by azathioprine achieve good results in lupus nephritis.
Mycophenolate mofetil, widely used in organ transplantation, is also showing potential as both induction and maintenance therapy for severe proliferative lupus nephritis and may eventually supercede the use of cyclophos- phamide for the majority of patients.
Biologic agents are beginning to make an impact on the treatment of patients with resistant lupus. Rituximab is widely used in the management of lymphoma and is relatively safe and well-tolerated. Several open studies have demonstrated dramatic and long-lasting remissions in lupus patients who were previously unresponsive to conventional and even novel immunosuppressive agents after only two to four infusions.