Need to know: SLE
Internationally renowned lupus expert Professor Graham Hughes answers questions on this condition from GP Dr Tonia Myers...
1. When I think of systemic lupus erythematosus (SLE), I usually think of a woman with a butterfly rash and arthropathy. Is this actually how SLE usually presents?
No – this is wrong. Although the butterfly rash is the most characteristic feature of lupus, it is probably present in less than half of the patients. Joint pains, however, are common, although unlike rheumatoid arthritis, these are often more 'flu-like' pains rather than active arthritis with swelling. In many cases, in retrospect, the disease has been present for years, even decades, before the diagnosis is made. Common early features in the diagnosis are teenage 'growing pains', teenage migraine (especially common in those with the Hughes' syndrome – antiphospholipid syndrome) and prolonged 'glandular fever'.
The American College of Rheumatology has provided guidelines for classification of lupus. It is important that these are used for classification (that is, for research purposes) and not for diagnosis. This is crucial, as many doctors use the ACR classification criteria in diagnosis, but to do so would only pick up the more 'classical' cases.I have drawn up a series of alternative criteria that are common features in the early diagnosis of lupus. These include multiple allergies, phobias (including photophobia), irritable eyes and a dry mouth (possible Sjögren's), co-trimoxazole (Septrin) allergy, allergy to insect bites, alopecia and, of course, in pregnancy, recurrent miscarriages (see question 8).
2. Do men get SLE? Are there ethnic differences in prevalence?
Yes, men get SLE. Throughout the world the ratio of women to men with SLE is 9:1 but it is said that lupus is often missed in men in the early stages. There have been a number of studies comparing male and female lupus and in general the disease is similar in both sexes. As far as ethnic differences in prevalence are concerned, there are a number of reports suggesting that lupus is more common (and often more severe) in Afro-Caribbean and Asian patients. Certainly throughout the world lupus is seemingly more common in, for example, the Far East than it is in the UK.
3. If a woman presents with painful joints, in the first instance I would usually request an FBC, ESR, RhF and CRP. What other tests would you suggest in a primary care?
Age is important here. If the woman is less than 40 then an antinuclear factor or antinuclear antibody (ANA) is more important than a rheumatoid factor. A negative ANA is statistically quite strong evidence against lupus (though does not entirely exclude it). Other vital tests in primary care are anti-DNA antibody (especially if the ANA is known to be positive) and the anticardiolipin test (important for the subset of patients with the thrombotic disease Hughes' syndrome). The latter test is absolutely vital if a patient is contemplating a pregnancy. The other routine test that is vital, of course, is urinalysis.
4. I have been told off by a rheumatologist in the past for asking for an auto-antibody screen in this situation, because of the non-specificity of a mildly positive test. What is the implication of a mildly elevated ANA in a woman with mild symptoms?
The more I see of lupus the more I disagree with this attitude. Mild positive tests are seen in the normal population but, unfortunately, from the diagnostic point of view, are also seen in people with genuine lupus. For those who believe that lupus is a 'spectrum', the patient with mild joint pains, occasional photosensitive rashes, fatigue and a mild positive ANA probably has lupus or a variant (often underlying Sjögren's). Such patients are often wrongly labelled, for example, with fibromyalgia or ME. It is clearly important not to miss a potentially treatable cause of these symptoms.
5. How important is early diagnosis in terms of prognosis?
Early diagnosis is more important in lupus than in almost any other connective tissue disease. Because of the wide spectrum of the disease and its various presentations, seemingly mild cases can hide potentially life-threatening problems such as early nephritis. The treatment of nephritis in lupus is now so successful if caught early that the need for prompt diagnosis becomes even more critical. As with many diseases, fairly active treatment for more severe disease in its early stages reverses lupus and the ultimate prognosis can be excellent in such situations.
6. The last time I had to explain a possible diagnosis of SLE to a patient, I found it very difficult to explain this 'multi-system autoimmune connective tissue disorder' without causing unnecessary alarm. What words do you use to explain SLE to new patients?
Lupus is a condition in which the immune system goes wrong and becomes overactive. Although this may sound like a good thing, an overproduction of antibodies can do more harm than good, clogging up delicate organs such as the blood vessels, for example, or the filters of the kidney. It's similar in some ways to driving a car with too rich a mixture of petrol. What switches on this overactivity? There are a number of suspects, including stress, ultraviolet light, some drugs such as the antibiotic co-trimoxazole (Septrin), possibly certain virus infections (such as the glandular fever 'E-B' virus), and in some cases hormone changes, such as after pregnancy. In many cases – probably still the majority – we have no real idea of the trigger.
7. What is the current approach to treatment and what monitoring is needed?
Following the early assessment of the patient, the treatment is pitched according to organ involvement. If the patient clearly has active kidney disease, the initial approach is active with immunosuppressives (such as cyclophosphamide or mycophenolate mofetil), to bring the disease under control.This is always accompanied by steroids but in far lower doses than those used 30 or 40 years ago. It is normal practice to wean the steroid dosage down and to maintain the patient on a lower dose of steroids, possibly changing to the milder and very useful anti-malaria tablets such as hydroxychloroquine (Plaquenil). Patients are monitored with blood tests including full blood count, renal function tests, anti-DNA antibodies, complement levels and urinalysis. I make it a routine to teach my patients to test their own urine protein. In the clinic the ideal programme is to monitor the patients on a three-monthly basis but, sadly, in the current NHS this goal is not achieved. It is a pity, as disease flare-ups certainly can and do occur within less than a year. At present the best that can be achieved in this situation is for the patient to be monitored by their own GP with cover from the local hospital and, if need be, from an annual visit to a lupus reference centre.
8. I understand that there is an overlap between SLE and Hughes' (antiphospholipid) syndrome. What are the clinical implications for patients with known SLE who are planning a pregnancy? When (and by whom) should antiphospholipid antibodies be requested?
In 1983 we described a group of lupus patients (about one in five) who had a tendency to 'sticky blood'. Complications of this tendency were thrombosis (for example, DVT or even more serious thromboses such as strokes and heart attacks). In pregnancy this thrombotic tendency affects the placenta with a resultant miscarriage and some of the patients with the syndrome present with recurring pregnancy losses. It soon became clear that this syndrome, easily diagnosed with a simple blood test (antiphospholipid antibodies or anticardiolipin antibodies), existed even without lupus and, in fact, the majority of patients have little or no evidence whatsoever of associated lupus. We now know that the Hughes' syndrome is responsible for a large proportion of patients with DVT (one in five), epilepsy, young strokes (one out of five of under 40-year-olds with strokes have this potentially treatable condition) and recurrent miscarriage. The ramifications of this discovery have been huge – for example, in managing miscarriage, patients with positive antiphospholipid antibodies can successfully be treated with aspirin or heparin, improving the success rate from less than 20 per cent to over 90 per cent in 2006.Antiphospholipid antibodies should, therefore, be requested in the following: all lupus patients; all young patients with unexpected thrombosis or recurrent miscarriage; patients with recurrent headaches, especially with recurrent migraine; any individual with unexpected heart attack or stroke, particularly if under the age of 40.
9. What is the increase in cardiovascular risk for patients with SLE? Can they be safely prescribed long-term NSAIDs?
During the past 20 years it has become clear that there is an increased cardiovascular risk in some patients with SLE, with a definite increased risk in the 40s and 50s of atheroma and heart attacks. The reasons for this increase are not yet clear but the usual suspects include steroids, chronic inflammation, the stress of inflammation and so on. The relative contributions of all these still have to be worked out. But the discovery has meant that doctors in general are much more proactive as far as treating known risk factors such as raised cholesterol and there is an increasing tendency to put people with borderline cholesterol levels on statins. Another known risk factor is the antiphospholipid syndrome and certainly there is wisdom in putting patients who have had clotting problems associated with this syndrome on either anti-platelet agents (for instance, aspirin) or in more severe cases heparin or warfarin. Clearly, selective cox-2 agents would be unwise in lupus patients who have antiphospholipid syndrome. Whether they are ruled out in all types of lupus remains a point of dispute and there is no firm guidance at this stage. In general, therefore, it is probably wiser to avoid them until the risks, or otherwise, are defined more precisely.
10. Is it possible to predict or prevent serious complications such as lupus nephritis or CNS disease?
It is certainly possible to predict and even to cut short lupus nephritis. The vigilance over urine analysis and widespread self-testing of urine in patients will, I am sure, contribute to less aggressive renal disease. This is already showing benefit in the statistics – the number of patients coming to end-stage kidney failure and to dialysis is now falling. It is more difficult to predict serious CNS disease. Again, vigilance is necessary. Subtle CNS problems such as depression, mood swings and phobias are sometimes missed despite their seriousness. The good news in lupus is that the neuropsychiatric aspects of lupus, once they improve, leave no residual problems whatsoever. More potentially serious is the Hughes' syndrome with its danger of transient ischaemic attacks and strokes. Any patient with lupus who gets recurrent and severe headaches should be tested for antiphospholipids and treated with anticoagulants.
What I will do now?
Dr Myers responds to Professor Hughes' answers...
• I will now feel justified in requesting an ANA in young women with vague joint symptoms
• Professor Hughes' description of SLE as a condition of an overactive immune system that can damage delicate organs will be very helpful in explaining the disease to newly diagnosed patients
• I was not aware of the importance of urinalysis in the diagnosis and monitoring of patients with SLE, and I will now do this routinely
• I will be alert to the possibility of Hughes' syndrome in patients with recurrent migraines and consider testing for antiphospholipid antibodies
Professor Graham Hughes is a consultant rheumatologist and head of the London Lupus Centre, London Bridge hospital. He is emeritus professor of medicine at St Thomas' Hospital where he set up the lupus clinics and lupus research unit. In 1983 he described the antiphospholipid (Hughes') syndrome. He is life president of patients' association Lupus UK and has published nine books on lupus and connective tissue disease.
By GP Dr Tonia Myers