ReviewSystemic lupus erythematosus: Clinical presentations
Introduction
Systemic lupus erythemetosus (SLE) is a multisystemic disease that is caused by autoantibodies to a variety of autoantigens. It is characterised by a wide variety of clinical and serological manifestations and relapsing and remitting course. The clinical picture of SLE can be complicated by the simultaneous presence of acute lupus activity, chronic damage, drug side effects, infection and other co-morbid disease.
Section snippets
Epidemiology
In 1992 the point prevalence of SLE in Birmingham (UK) was 27.7/100,000 (95% CI 24.2–31.2/100,00), which equates to around 1:3500 [1]. This is similar to other European cities. The point prevalence in women was 49.6/100,000 (95% CI 43.2–56.1/100,000), which is around 1:2000 [1]. This was compared to a point prevalence in men of 3.6/100,000 (95% CI 2.0–6.0/100,000), giving a female to male sex ratio in Birmingham of 14:1 [1]. The female to male sex ratio is usually quoted between 4.3 and 13.6 [2]
Clinical presentations
The American College of Rheumatology developed criteria for the classification of SLE [3], [4]. A patient has to have four or more of these criteria to be classified as having SLE. These criteria were designed to allow comparison of clinical research from different centres. As the criteria have a bias towards severe and longer duration disease, a diagnosis of SLE should be considered if a patient has characteristic features of SLE associated with autoantibody formation, even if they do not
General features
The most common symptom at presentation is fatigue. Other constitutional features are fever, lymphadenopathy and weight loss. Unfortunately, these symptoms are associated with a large differential diagnosis including infection and malignancy.
Musculoskeletal manifestations
It is very common for patients to suffer a generalised arthralgia with early morning stiffness and some will develop mild joint swelling. Most patients do not have joint deformity, but some will develop Jaccoud's arthropathy, which is a reducible arthropathy due to capsular laxity. In a patient with a single painful joint, infection and avascular necrosis should be suspected. Diffuse myalgia is common, but inflammatory myositis is much rarer. Myopathy secondary to therapeutic agents such as
Skin presentations
One of the most widely recognised features of lupus is the malar or butterfly rash. Patients may develop photosensitive rashes that can last for several weeks after brief sun exposure. Most worryingly for the patients are the discoid rashes as they are associated with scarring. Clinicians also need to be vigilant for vasculitis in both hands and feet as early changes can proceed rapidly to gangrene.
Other skin manifestations include Raynaud's phenomenon, which is a reflex vasoconstriction in the
Pulmonary features
Patients may get chest pain on inspiration, most commonly in the form of pleurisy. This can be due to lupus activity, pulmonary embolism or secondary infection, so needs careful investigation to delineate the cause. Much rarer pulmonary manifestations include active lupus pneumonitis, pulmonary haemorrhage and pulmonary hypertension. Pulmonary hypertension is associated with a poor prognosis, especially in pregnancy.
Cardiac manifestations
Increasingly it is being recognised that premature coronary artery disease is associated with inflammatory conditions like SLE. It is important to give lifestyle advice and to consider preventative medication that reflects this increased risk, particularly as it is usually associated with hypercholesterolaemia [5].
The most common symptomatic cardiac manifestation of active disease is pericarditis. Less commonly a patient may get myocarditis, which may present with arrhythmias and heart failure.
Gastrointestinal disease
The most common and well known gastrointestinal manifestation of SLE is oral ulceration. However, gastrointestinal symptoms are an under recognised group of clinical manifestations in SLE. This is despite up to 50% of patients suffering abdominal pain, nausea, vomiting or diarrhoea at some stage of their disease, although side effects of therapeutic interventions will contribute some of those symptoms [6]. The most serious gastrointestinal complication of SLE is enteric vasculitis, because of
Renal disease
Renal disease is a well recognised clinical manifestation of SLE. Afrocaribbeans are more likely to get renal disease than Asian or Caucasian patients. As early renal disease is often asymptomatic, it is important that a measure of renal function should be done regularly and urine is monitored for proteinuria, red cells and cellular casts. Renal biopsy is useful to guide treatment and to gauge prognosis. If patients are not treated early and effectively with steroids and cytotoxic therapy they
Neuropsychiatric syndromes
Many different neurological conditions are associated with SLE. The most common manifestations are headaches, seizures, cerebrovascular accidents and asceptic meningitis. The cerebrovascular accidents can be due arteriovascular disease or thrombus formation, particularly in those with anti-phospholipid antibodies. Other neurological conditions include central nervous system manifestations such as chorea, cognitive dysfunction and psychosis, while peripheral conditions include both mono- and
Reproductive features
Many lupus patients are women of reproductive age. Patients can present with recurrent miscarriages particularly in those with APS or active disease during pregnancy. There is an increased risk of still-birth, premature delivery and babies being born with intrauterine growth restriction. There is also a risk of neonatal lupus syndrome and congenital heart block in babies born to mothers who are anti-Ro or anti-La positive. Fortunately this is rare and only affects 1% of mothers who are positive
Laboratory features
One of the first clues that a patient has lupus in the full blood count is leucopenia. Anaemia and thrombocytopenia may also be present. Another important feature is the discrepancy between a disproportionately raised ESR with a low or normal CRP. The activated prothrombin time (APTT) may be prolonged in patients with anti-phospholipid antibodies and is not corrected by mixing with normal plasma, as would be expected in deficiencies of the coagulation cascade. C3 and C4 levels can be low due to
Measuring disease activity
There have been many indices developed and validated to objectively measure SLE disease activity particularly for research. The most widely used indices are the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the British Isles Lupus Assessment Group (BILAG) index, the European Consensus Lupus Activity Measurement (ECLAM), the Systemic Lupus Activity Measure (SLAM) and the SLE activity Index Score (SIS). Most of these give a global score, which does not distinguish multiple mild
Mortality
In the Birmingham (UK) cohort the majority of the deaths over the last 20 years were in the Caucasian population not the Afro-Caribbeans, which is different to the North American experience [10] and other international data [11]. The SLE patients died about 25 yrs earlier in comparison to age and sex standardised data for England and Wales. The biggest cause of death was infection followed by heart disease, and deaths due to active lupus were uncommon. This is consistent with other recent studies
Take-home messages
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Lupus is more common than many people realise.
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Patients need close monitoring to reduce complications from the disease and its treatment.
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Mortality and morbidity are still significant.
References (11)
Epidemiology of systemic lupus erythematosus
Best Pract Res Clin Rheumatol
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Assessment of patients with systemic lupus erythematosus and the use of lupus disease activity indices
Best Pract Res Clin Rheumatol
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The prevalence and incidence of systemic lupus erythematosus in Birmingham, UK, related to ethnicity and country of birth
Arthritis Rheum
(1995) - et al.
The 1982 revised criteria for the classification of systemic lupus erythematosus
Arthritis Rheum
(1982) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus
Arthritis Rheum
(1997 Sep)
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