LUPUS: A GP Guide to Diagnosis
This chapter considers the major morbidity associated with lupus from coronary artery disease, steroid induced osteoporosis and infection. It also considers some of the conditions which may overlap with or masquerade as lupus, such as Sjögren's syndrome and fibromyalgia.
In women with lupus in the years before the menopause the risk of myocardial infarction is up to 50 times higher than in healthy women. Recent studies suggest that lupus may be the strongest risk factor for heart disease and stroke yet described. This greatly increased risk is probably not just related to antiphospholipid antibodies or steroid therapy. The usual risk factors appear to be important, as well as the disease and its therapy.
'Traditional' risk factors should be treated with as much attention as would be given to a patient with diabetes: advice on smoking, treating hypertension and optimising the lipid profile. Folic acid supplements may be useful to optimise the homocysteine levels especially in those on methotrexate or with renal impairment. Aim to keep the cholesterol below 5 mmol/l.
Steroid therapy above daily doses of 5mg or thereabouts tends to accelerate osteoporosis in the long run. This is all the more so when patients require steroids in higher doses. The days are long gone when patients were blanketed with steroids to avoid any expression of inflammation but osteoporosis and it complications remain a major problem as the survival of lupus improves and patients grow older. The dose of prednisolone can be kept to a minimum by adding in other medications such as anti-malarials and immunosuppressives and by trying to reduce the dose whenever possible. Deflazacort may have some benefit over prednisolone if the 6:5 dose equivalence is genuine. Bisphosphonates probably inhibit steroid-induced bone loss and this has been demonstrated for cyclical etidronate with calcium (didronel PMO).
There has always been some concern about the use of hormone replacement therapy (HRT) in patients with lupus but, in practice, the dose of oestrogen appears to be too small to cause exacerbations of the disease. It is in patients with a tendency to thrombosis through the presence of antiphospholipid antibody (lupus anticoagulant, false positive WR or antibody to cardiolipin) where there should still be concern. HRT is associated with about a threefold increase in thrombotic events in the general population and the worry is that there may also be a threefold increase in lupus where thrombotic events are so much more common. For the time being, it seems best to avoid HRT and evista in patients with a history of thrombosis or with positive tests for antibody to phospholipid.
Infection is a major problem in lupus and still a killer. Both disease and treatment impair immune defences and steroid therapy can mask symptoms of infection. Hence, it is often difficult to tell whether illness and fever are due to active lupus or infection or both. The white cell count is often low in lupus so a "normal" count may suggest infection. The ESR is raised in either case but it is useful to know that elevation of the CRP very often indicates infection. It is important to send off appropriate samples for culture and if in doubt seek help. Avoid sulphonamides as these may exacerbate lupus.
Pseudo-Lupus: a sheep in wolf's clothing
An important role for the doctor interested in lupus is to give an opinion on patients who just might have lupus. There is the patient with multiple sclerosis and dry eyes, the patient with acne rosacea and fatigue, the patient with migraine and little white spots showing up in the MR scan of the brain, or the patient with fibromyalgia and irritating eyes. Often these are worried people who are seeking the haven of a diagnosis and have read about lupus along the way. A positive test for antinuclear antibody (ANA) may muddy the waters further and one must remember that ANA is a biological phenomenon occurring by chance or induced by medication more often than indicating lupus. It remains to be seen whether patients benefit more from the grey area being painted black or white - no diagnosis may be preferable to a misdiagnosis.
All too easy to forget, this is a chance to cure a patient. Please read 'Drug Induced Lupus - New Research'.
We now recognise several entities which could at least sometimes be called lupus. Quite often there are particular autoantibodies specifically associated with these conditions.
Primary Sjögren's Syndrome is the most common autoimmune rheumatic disease after rheumatoid arthritis. Most patients present with symptoms of dryness in the eyes and mouth and there can be systemic illness. In some cases the illness can be traced back to joint pains and rash in earlier years and a diagnosis of lupus may have been appropriate in the past. Indeed, we know that some patients with lupus will go on to develop Sjögren's syndrome whether or not they give up their lupus features. The blood tests linking these lupus patients with primary Sjögren's syndrome include antibodies to the soluble antigens Ro and La, rheumatoid factor, high immunoglobulin G level and elevated ESR but with normal CRP. This constellation is not present in all cases but there is usually enough to avoid a diagnosis of rheumatoid arthritis (where the IgG would be normal and the CRP elevated in active disease).
Primary Antiphospholipid Syndrome refers to the typical clinical picture described elsewhere in this guide but in the absence of other features of lupus. There may be venous or arterial thrombosis, recurrent miscarriage, thrombocytopenia, labile hypertension and blotchy markings on the skin called livedo reticularis.
Mixed Connective Tissue Disease is a term used to describe an overlap syndrome in which Raynaud's phenomenon is almost invariable and there may be swollen fingers, myositis, arthritis, inflammation of the lungs and a tendency later on to develop scleroderma. These patients are picked out because they have mainly antibody to a soluble cellular antigen called RNP. However, this antibody is often seen together with other antibodies in patients diagnosed as ordinary lupus, so some people doubt that there is a need for the term MCTD.
Myositis can occur alone as an organ specific disease. Rheumatologists tend to see the cases with features of systemic disease such as Raynaud's phenomenon, arthritis, fibrosing alveolitis, dry eyes or scleroderma. Several distinct syndromes or "subsets" have been delineated, each associated with a different autoantibody (Jo-I, PM-Scl and so on).
1. Cardiac deaths are now a major concern:
2. Osteoporosis in lupus:
Dr. Robert Bernstein
Consultant Rheumatologist
Manchester Royal Infirmary
Oxford Road
Manchester, M13 9WL