Systemic Lupus Erythematosus (SLE)

• Definition
• Incidence
• Etiology
• Symptoms
• Diagnosis
• Treatment
• Recent Advances
• Conclusion

RECENT ADVANCES

TABLE 1 -- APPROACHES IN THE MANAGEMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS

*Mycophenolate mofetil has been tried as a treatment for several autoimmune diseases, on the basis of the positive experience with this drug in recipients of solid-organ transplants. The parent compound is hydrolyzed to mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, which blocks several steps in the effector arm of the immune system. In mice with lupus, mycophenolate mofetil prolonged overall survival and delayed the onset and severity of nephritis.7 In small studies of patients with lupus nephritis that was resistant to cyclophosphamide, mycophenolate mofetil appeared to be effective in controlling renal disease.

Treatment of Lupus Nephritis

The standard of care for the treatment of aggressive forms of the disorder is the administration of intravenous cyclophosphamide.3 In addition to oral glucocorticoids, cyclophosphamide is given in monthly intravenous pulses for at least six consecutive months. In one study, exacerbations of lupus nephritis were reduced when intravenous cyclophosphamide was given every three months for an additional two years.

Chan et al. present the results of a study in Hong Kong in which patients with diffuse proliferative lupus nephritis were treated with prednisolone and mycophenolate mofetil or with prednisolone and cyclophosphamide followed by prednisolone and azathioprine.The study provides evidence that treatment with mycophenolate mofetil is as effective as and has fewer side effects than sequential treatment with cyclophosphamide and azathioprine. There are several reasons for caution in generalizing these findings to other patients with diffuse proliferative lupus glomerulonephritis.

*Prophylactic anticoagulation therapy is not justified in patients with high titer anticardiolipin antibodies with no history of thrombosis.

*However, if a history of recurrent deep vein thrombosis or pulmonary embolism is established, long-term anticoagulant therapy with international normalized ratio (INR) of approximately 3 is needed.

Antiphospholipid syndrome
The syndrome occurs most commonly in young to middle-aged adults; however, it also can occur in children and the elderly. Among patients with SLE, the prevalence of antiphospholipid antibodies is high, ranging from 12% to 30% for anticardiolipin antibodies, and 15% to 34% for lupus anticoagulant antibodies. In general, anticardiolipin antibodies occur approximately five times more often then lupus anticoagulant in patients with antiphospholipid syndrome. This syndrome is the most common cause of acquired thrombophilia, associated with either venous or arterial thrombosis or both.

It is characterized by the presence of antiphospholipid antibodies, recurrent arterial and venous thrombosis, and spontaneous abortion. Rarely, patients with antiphospholipid syndrome may have fulminate multiple organ failure, or catastrophic antiphospholipid syndrome. This is caused by widespread microthrombi in multiple vascular beds, and can be devastating. Patients with catastrophic antiphospholipid syndrome may have massive venous thromboembolism, along with respiratory failure, stroke, abnormal liver enzyme concentrations, renal impairment, adrenal insufficiency, and areas of cutaneous infarction.

According to the international consensus statement, at least one clinical criterion (vascular thrombosis, pregnancy complications) and one laboratory criterion (lupus anticoagulant, antipcardiolipin antibodies) should be present for a diagnosis of antiphospholipid syndrome.

The hallmark result from laboratory tests that defines antiphospholipid syndrome is the presence of antibodies or abnormalities in phospholipid-dependent tests of coagulation, such as dilute Russell viper venom time. There is no consensus for treatment among physicians. Overall, there is general agreement that patients with recurrent thrombotic episodes require life-long anticoagulation therapy and that those with recurrent spontaneous abortion require anticoagulation therapy and low- dose aspirin therapy during most of gestation.

An appreciation of the many facets of SLE is essential, including a recognition of the current limit of our knowledge about the disease and its management. A better understanding of the pathogenesis of SLE promises to provide much information about the nature and the role of the immune response in this and other diseases.