Sulfadiazine sensitivity with demonstrable skin-sensitizing antibody in the serum

S INCE Prausnitz and Kiistner in 1921l described the phenomenon of passive transfer and established the skin-sensitizing antibody as the basis of a large group of allergic reactions, the possibility of demonstrating such antibodies in cases of idiosyncrasy to drugs of simple chemical structure has interested both clinicians as a diagnostic method and immunologists as evidence of the chemical nature of antigens. In 1926, Biberstein2 reported passive transfer of sensitivities to mercury salts, salvarsan, bismuth and pyramidon, and a few other similar reports have appeared in foreign literature. 3 However, numerous attempts by researchers in this country to reproduce these same results have failed and for years the existence of transferable antibodies for drugs of simple structure was doubted by most authorities in this country, 4* 5 although Kern6 in 1938 did describe a case of rhinitis and bronchial asthma due to Phthalic anhydride (a simple, nitrogen-free compound), with an immediate urticarial reaction to scratch test and a typical passive transfer reaction to this substance. More recently, Feinberg and Watrous’ reported similar cases of asthma and rhinitis in workers exposed to halazone and chloramine T, both simple synthetic drugs, also showing typical urticarial reactions by direct scratch tests and on passive transfers. Soon after the introduction of the sulfonamide drugs, numerous cases of acquired sensitivity to these compounds were reported. The usual story was that the patient tolerated the first course of the drug without symptoms, or, if the first course was prolonged, developed fever or a skin rash or both, only after receiving the drug for seven to ten days. However, when the drug was administered a second time weeks or months later, the skin rash or fever appeared within a few hours after the first dose.8 In many instances, the existence and specificity of the sensitivity were proven clinically by intentionally repeating small doses of the causative and related drugs,g-14 but attempts to confirm the diagnosis by skin tests were usually unsuccessful. In a few patients with drug rashes positive patch tests were obtained15~16~17 but scratch and intracutaneous tests with the drugs were uniformly negative. 13~18--23 Leftwich23 reported positive reactions when the sensitive patients were tested intracutaneously with serums of persons who were taking the causative drugs, but other authors had negative results with similar drugs22 as well as with normal human serum to which the drugs had been added.24 In a few instances, skin tests were made with diazotized sulfonamides coupled to normal human serum, but the results were again negative.gs25 Likewise, attempts to demonstrate antibodies in the serums of sulfonamide-sensitive patients by precipitin testsgsls and by passive sensitization of guinea pigs gave negative results. g,18 Passive transfer of sul-