Lupus: Complications and Associated Conditions
IntroductionThis 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.
Coronary Artery DiseaseIn women with lupus, the risk of myocardial infarction is increased at least as much as in diabetes. 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 4 mmol/l.
OsteoporosisSteroid 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 reduce steroid-induced bone loss. There has always been some concern about the use of hormone replacement therapy (HRT) in patients with lupus, but the dose of estrogen turns out 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 raloxifene in patients with a history of thrombosis or with a positive test for antibodies to phospholipids.
InfectionInfection 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 recognise 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 clothingAn 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 MRI scan of the brain, the patient with fibromyalgia and sore eyes and the patient prone to somatisation. 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. If all the lupus antibody tests, including the lupus anticoagulant, are negative, a patient may be concerned about ‘seronegative lupus’, but this is a contentious area, best treated with a degree of sympathetic scepticism to avoid the slippery slope of unnecessary treatment. 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.
Drug Induced LupusAll too easy to forget, this is a chance to cure a patient. Minocycline is the chief culprit these days.
See page - Drug Induced Lupus
First Cousins of LupusWe now recognise several entities which could at least sometimes be called lupus. Quite often there are particular autoantibodies specifically associated with these conditions.
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).
Other cousins include overlap syndromes such as mixed connective tissue disease, anti-synthetase syndrome and anti-phospholipid syndrome.
FibromyalgiaFibromyalgia or fibrositis has become a popular notion in general practice and on the internet just as some rheumatologists sound a note of caution. Fibromyalgia is defined as widespread pain (which is a condition reported by 10% of women) together with pain on palpation at certain test points (this tenderness also being associated with distress). Fibromyalgia is also characterised by sleep disturbance, waking feeling unrefreshed and day-time fatigue. It is often associated with functional bladder and bowel disturbance such as irritable bowel syndrome and with restless legs and the like, and there is much overlap with Chronic Fatigue Syndrome. Fibromyalgia is commoner in women, where the prevalence is about 2% in the general population (a fifth of all the widespread pain). Management includes acceptance, commiseration and support, advice on pacing and regular exercise, low-dose tricyclic drug such as amitriptyline at night and cognitive behavioural therapy.
The important point here is that fibromyalgia may complicate other rheumatic diseases such as rheumatoid arthritis, lupus and primary Sjögren’s Syndrome in at least 20% of cases. This means that the assessment of pain, fatigue and increasing symptoms in a patient with lupus must take into account not just the question of depression but also of fibromyalgia.
So what are the concerns with fibromyalgia? Apart from the patient unlucky to have a bad back, two tennis elbows and a trochanteric bursa or the like, there is no physical problem in the musculoskeletal tissues to explain fibromyalgia, and the explanation lies in the brain. There are quite often psychosocial issues, somatisation behaviour and mood disturbance and it can be helpful for the family doctor to manage the symptoms in that light, rather than giving a pseudophysical label. The diagnosis of fibromyalgia may satisfy the patient and reduce consultation time and use of clinical resources, but this is at the expense of medicalising unhappiness, reinforcing a sense of chronic illness, risking missing other disease and transferring expenditure from the NHS to the Department of Work and Pensions. The good news is that fibromyalgia and widespread pain can have a better prognosis than used to be reported. They often improve or clear up within a few years.
Bullet points1. Cardiac deaths are now a major concern:
o Keep the cholesterol below 4 mmol/l
o No smoking
o Folic Acid?
2. Osteoporosis in lupus:
o Is the dose of steroids justified?
o Consider adding a bisphosphonate and vitamin D
o Consider HRT unless a risk of clotting
3. Drug-induced lupus:
o Minocycline is now the commonest cause
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