Much has been learned over the past 32 years with regard to the mysterious toxicity first noted in hydralazine-treated hypertensive patients. A diversity of drugs capable of altering the normal state of immunologic unresponsiveness to self-antigens has emerged. The importance of genetic factors, particularly the acetylator phenotype, in the development of autoimmunity during the course of treatment with procainamide and hydralazine is now well established. Research in drug-related lupus has led to drug modifications such as the acetylation of procainamide which will soon permit the use of this potent antiarrythmic agent without the development of lupus. Since the discovery of the LE cell, considerable progress has been made in the further delineation of the diverse spectra of antinuclear antibodies that characterize idiopathic SLE and drug-induced lupus. Surprising cross-reactivities have been' discovered involving histone proteins, lymphocyte membranes, and the Fc portion of IgG. The precise mechanism by which given drugs alter the normal state of immunoregulation remains uncertain. Interactions between the drugs that induce lupus and self-macromolecules have been demonstrated, and could account for either enhanced autoantigenicity, or altered immunoregulatory mechanisms. Continued research in the area of DIL should provide a more definitive understanding of its pathogenesis and also enhance our knowledge of the contrasting and more prevalent syndrome of idiopathic SLE.
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