1. Epidemiology and aetiology
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that can affect almost any organ, often resulting in diverse clinical features.
Most patients will require specialist input but the role of the GP includes recognition of common presentations and the ability to identify potentially serious complications.
GPs should also have a basic understanding of relevant investigations and of monitoring disease activity and therapy.
Support for patients with SLE through their chronic disease is often a fundamental role of the primary care physician.
The aetiology of SLE is multifactorial, although genetic factors are important. SLE is probably precipitated by triggers that produce an autoimmune reaction in genetically predisposed people. Drugs are also known to induce lupus, most notably hydralazine and procainamide, but many other agents have been implicated.
These generally cause relatively mild symptoms, usually without major organ involvement, which should resolve on cessation of the relevant agent.
Prevalence is higher in women (approximately 10 times higher than in men) and also varies between racial groups, being more common in Chinese and African-Caribbean populations.
It can be diagnosed at any age, but typically patients present between the ages of 14 and 50 years.
SLE mortality rates are three to five times greater than those expected in the normal population and show a bimodal pattern, with early mortality mainly due to active lupus and renal disease and late mortality due to infections and cardiovascular disease.
Poor prognostic markers include renal and CNS involvement, race (African-Americans have more severe disease) and an older age of onset ([s19]50 years).
The excess cardiovascular mortality in SLE is independent of classic cardiovascular risk factors, and studies have shown that young women with SLE have accelerated atherosclerosis and an increased risk of MI equal to that of triple-vessel disease.
A good history should detect features that patients may not have regarded as important but which may lead to the diagnosis, and so a systematic approach is required. A full general examination is essential.
Non-specific symptoms are common, including fever, myalgia and arthralgia. Arthritis is often asymmetrical and reversible rheumatoid-like deformity, known as Jaccoud's arthropathy, is well recognised. This should appear non-erosive radiologically. Fatigue is a common and sometimes severely disabling feature. Patients should also be questioned about oral ulceration and symptoms of serositis.
Classically, patients may develop a photosensitive 'butterfly' rash over the malar regions and bridge of the nose. Sparing of the nasolabial folds can be helpful in distinguishing it from rosacea. Other possible skin disorders include alopecia and vasculitis.
Headaches in SLE may be severe and migrainous in nature with poor response to analgesics. Additionally, seizures and psychosis might all indicate cerebral SLE. Features of associated autoimmune conditions may be evident, such as dry eyes and mouth.
A urine dipstick test is a simple but vital tool for detecting renal involvement and may indicate the presence of glomerulonephritis well before a rise in urea or creatinine is detected.
Suspicion should be high if blood and protein are present.
Full blood count may reveal leucopoenia, commonly due to lymphopaenia, although anaemia, neutropaenia and thrombocytopenia may all be seen.
Antinuclear antibody (ANA) is also found in 95 per cent of patients but can be detected in normal individuals, other autoimmune diseases and infection.
The low prevalence of SLE in the general population means that most people with positive ANA do not have SLE. Anti-dsDNA and anti-Sm, however, are highly specific for SLE and their presence usually indicates a much greater likelihood of disease.
Other autoantibodies including anti-Ro and anti-La (found in Sjogren's syndrome), anticardiolipin antibodies and lupus anticoagulant (found in antiphospholipid syndrome) might indicate a risk of additional clinical problems.
ANA is not a useful tool for monitoring SLE. Instead, activity is better predicted by a rise in titre of anti-dsDNA and by complement consumption (falling C3 or C4 levels). ESR tends to be elevated in active lupus but CRP is often normal.
Elevation of CRP can be related to arthritis or pleuro-pericarditis but is most useful in distinguishing severe infection from disease flare.
Assessing SLE patients in primary care
Have you had any of the following?
- Skin rash/photosensitivity.
- Oral ulceration.
- Joint pain/swelling.
- Pain on deep breathing/pleurisy.
- A history of psychiatric disorder/fits.
- Blood clots in the legs or lungs.
Do your hands change colour in the cold?
Is there a family history of immune disorders?'
- ANA (when pre-test suspicion for SLE is high).
- Anticardiolipin antibodies/lupus anticoagulant.
- Coombs' test (in anaemia).
- Urine dipstick/microscopy.
- 24-hour urine collection.
- Chest X-ray.
The most important step in management is an early diagnosis and referral to secondary care.
A positive urine dipstick for blood and protein will generally require an urgent referral to a renal/lupus unit.
General patient advice should include that UV light can lead to a disease flare, and recommend the use of hats, long sleeves and maximum sun block in the summer. Fatigue responds poorly to most interventions but regular physical exercise can be helpful.
Pharmacological treatment is not necessary in many cases, but in mild-to-moderate disease hydroxychloroquine can be effective for control of arthralgia, myalgia and rashes. Annual optician review is recommended because of the small risk of macular toxicity with prolonged use.
Acute flares and persistently active disease may need treatment with corticosteroids but long-term oral steroids alone are best avoided in favour of alternative immunosuppression.
Azathioprine and methotrexate are valuable as steroid-sparing agents and maintenance therapy.
With major organ involvement, cyclophosphamide in pulsed IV or oral regimens may be required to induce remission. The implications of this drug need to be carefully considered, particularly in younger patients who might wish to start a family.
Newer treatments such as mycophenolate mofetil and rituximab may also have a role in more severe cases. All these treatments require regular monitoring for toxicity.
Cardiovascular mortality and morbidity is high in lupus patients, therefore cardiovascular risk factors, including BP, fasting lipids and glucose, should be screened annually and treated aggressively to achieve a target BP of 130/80mmHg (lower in renal patients) and LDL cholesterol of less than 2.6mmol/l.
The effect of pregnancy is unclear but increased flares have been reported in some studies. Pregnancy is best planned for periods of relative disease inactivity, where possible.
Anti-Ro antibody may indicate neonatal lupus risk and congenital heart block. Anticardiolipin antibodies/lupus anticoagulant should be checked before conception and low-dose aspirin and/or heparin considered.
Prednisolone, azathioprine and hydroxychloroquine are considered safe when pharmacological treatment is necessary. Early referral to antenatal clinics is recommended.
October is Lupus Awareness Month. For more information visit www.lupusuk.org.uk.