Lupus - the severe undiagnosed disease
Dr Graham Davenport
Systemic lupus erthematosus (SLE) is rare (prevalence of about one in 2000 and incidence one in 20,000 per annum) and affects women more than men (10:1), but is a systemic auto-immune connective tissue disease (CTD) which can be severe and carries a considerable morbidity and mortality unless diagnosed early.
Diagnosis in primary care can take up to seven years and this delay in diagnosis has not improved over the last 20 years with 45% of patients initially given a diagnosis other than SLE.
This is due to a number of factors:
- Lupus is chameleon-like and lupus symptoms often mimic those of other diseases.
- Presenting symptoms can be vague and non-specific, such as fatigue, lethargy and aches and pains (for most lupus patients the extreme fatigue is the most difficult symptom to live with).
- Multi-system effects such as pyrexia, anorexia and weight loss can suggest infection or malignancy but are common in SLE and other CTDs.
- Symptoms can present over a long time-line, e.g. a patient may develop Raynaud's phenomenon in her teens, have a miscarriage in her 20s, develop acute pleurisy in her 30s and persistent proteinuria in her 40s before SLE is diagnosed.
Signs and symptoms:
Raynaud's phenomenon is common in primary care and is usually idiopathic but can occur in 20% of SLE patients. Doctors should be alert to the presence of other symptoms associated with SLE such as mouth ulcers, headaches / migraines, hair loss and photosensitive skin rashes. The classical malar (butterfly) rash spares the naso-labial folds unlike acne rosacea and seborrhoeic dermatitis.
Most patients with SLE have marked arthralgia with joint pain and early morning stiffness especially in hands, wrists and knees, but the synovitis may not be as prominent and visible as in rheumatoid arthritis. Arthritis in SLE is usually asymmetrical and non-erosive.
Renal disease is common in SLE and asymptomatic proteinuria may be the only indication of auto-immune glomerulonephritis.
There is no specific diagnostic test so GPs must rely on recognising a constellation of symptoms and tests should only be ordered if there is reasonable clinical evidence to suspect SLE.
Antinuclear antibody (ANA) is a useful screening tool as it occurs in over 90% of SLE patients but can occur in up to 15% of healthy middle-aged women.
Inflammatory markers such as ESR and CRP are fairly non-specific tests of inflammation and may be normal in SLE.
Many patients will have a mild neutropenia, lymphopenia and thrombocytopenia in their FBC.
The extractable nuclear antigens, antigen (ENA) and antibodies which occur commonly in SLE are RNP, Sm, Ro and La.
Cardiolipin antibodies should be done on suspicion of anti-phospholipid (Hughes) syndrome.
Additional tests such as complement levels and anti-dsDNA antibodies are highly specific for SLE, but they have poor sensitivity and are usually associated with more severe disease activity and are not useful for diagnosis in primary care.
Urinalysis is very helpful as persistent heavy proteinuria after excluding infection requires referral to the nephrologist.
The usual treatments for SLE are anti-malarial therapy, low-dose corticosteroids in mild cases, immuno-suppressants for moderate cases but use of biologic therapies e.g. belimumab and rituximab are offering better control in selected more severe cases.
GPs have a key role in the monitoring of the co-morbidities which include hypertension, cardiovascular disease, depression and osteoporosis.
Osteoporosis is common in SLE with an increased risk due to a number of factors including corticosteroid therapy. Patients should be advised on increasing exercise, stopping smoking, optimising calcium and vitamin D supplementation and possible use of bisphosphonates depending on their FRAX score.
Severe infection is a common cause of mortality and includes bacterial infection, e.g. pneumonia and viral infections, such as herpes zoster. An acute hot joint in SLE should not be considered a flare-up of disease activity until septic arthritis has been excluded.
Prompt treatment of infections is vital and vaccination again flu and pneumonia is important in these high-risk patients.
Cardiovascular risks are increased in SLE patients due to accelerated atherosclerosis and the increased risk of myocardial infarction is equivalent to triple vessel coronary disease. Therefore, it should be managed vigorously with an annual screening review of cardiovascular risk factors. Strict control of the blood pressure is especially important if renal disease is present.
All women with SLE require advice on contraception and close support during pregnancy. There is no evidence that taking the contraceptive pull is harmful unless the patient has a positive lupus anticoagulant or cardiolipin antibodies when it should be avoided. Anti-phospholipid (Hughes) syndrome should be considered in patients who have had recurrent miscarriages and / or venous and arterial thrombosis.
Depression is common in all CTD including SLE but often goes unrecognised and should be screened for annually by simple depression screening questionnaires. Only a small proportion of depression patients have symptoms due to cerebral lupus.
Although SLE occurs rarely, GPs have a key role in suspecting it and referring early for specialist assessment and treatment. There is a need for the provision of holistic care for those established (high risk) SLE patients to reduce the mortality from their co-morbidities.
One of the current RCGP Clinical Priorities focusses on rare diseases. For more information on the work of Dr Imran Rafi (Royal College General Practitioners [RCGP] Clinical Champion for Rare Diseases) please visit here. To find out more about the RCGP Clinical Priorities click here.
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