DR. SHULMAN:The subjects we will be discussing in this section may be divided into two categories: ( 1 ) the role of certain drugs in the pathogenesis of certain cases of systemic lupus erythematosus; and (2) the interrelationships between systemic lupus and various allied diseases, including consideration of clinical and serologic "overlaps" among these disorders.Many observers have related the onset of systemic lupus erythematosus, or exacerbations of this disease, to allergic reactions to one of a variety of drugs, such as penicillin, sulfonamides or gold. Moreover, in rare instances L.E. cells have been reported in patients with drug reactions, notably to penicillin> and without any clinical evidence of lupus. These events have been variously interpreted. To some observers these allergic reactions are an integral part of the disease process, systemic lupus being a disease of hypersensitivity. Others believe that the allergic drug reactions have no etiologic significance, but do induce flare-ups in already-established lupus. To still others, these allergic reactions occur only coincidentally; they do not influence the course of the disease, except for being an additional burden in an ill individual. In our own experience the frequency of drug reactions was appreciable after the disease had become established, but was not striking prior to diagnosis. In addition, the drug reactions were often followed by severe exacerbations which often persisted long after the offending drug had been discontinued.In some patients a history of multiple episodes of drug hypersensitivity has been particularly impressive. I would like to describe one such patient It has thus been assumed generally that hydralazine had produced reversible systemic lupus in patients with no evidence of antecedent connective tissue disease. The supposed rarity of hypertension in systemic lupus, in the absence of appreciable renal insufficiency had been used as ancillary evidence that they had not had lupus before treatment.Lacking, however, in many reports, is full information about the patients before hydralazine had been given, and even more absent are prolonged observations after it had been stopped. In some measure, such information has been obtained in the two patients developing a lupus-like syndrome out of the 105 hydralazine-treated hypertensives studied at our hospital. Prior to having been given hydralazine, both of these patients had had leukopenia and hypergammaglobulinemia; and one had had a series of illnesses which one could construe to be systemic lupus. Although the lupus-like syndromes INDUCING AGENTS AND OTHER DISEASES 561 disappeared once the hydralazine was discontinued, the protein abnormalities in both patients persisted: elevated sedimentation rates, hypergammaglobulinemia, and extracellular L.E. material ( similar to the inclusion body within L.E. cells). Both patients have now been followed for 8 years after the discontinuance of hydralazine.As a result of these observations we have previously offered the concept that som...
