Adverse reactions to nitrofurantoin in relation to cellular and humoral immune responses

Eighteen patients showing hypersensitivity to nitrofurantoin with symptoms like sudden fever, malaise, cough, pleuritis, leucocytosis and sometimes eosinophilia were analysed for immune reactions, i.e. lymphocyte transformation and specific antibodies. In addition, thirty-three individuals treated with the drug but with no clinical signs of the described reactions were included as controls. The lymphocyte transformation test (LTT) was found positive in ten out of the eighteen sensitive patients while one to three out of fourteen tested control patients were positive, depending on test conditions. An incubation period of 4 days in culture medium supplemented with autologous serum gave stimulation to a greater extent than did isologous serum and/or incubation for 6 days. The antibody determinations, with the enzyme-linked immunosorbent assay (ELISA), showed no IgE antibodies to nitrofurantoin in any of the patients. In contrast, most of the hypersensitive and even the control patients had specific IgG antibodies. The mean value of the antibodies of the sensitive group was higher than of the control group, but considerable overlapping between the groups was noted. In adverse reactions to nitrofurantoin a positive LTT and/or a high antibody titre to the drug favours an allergic mechanism and contributes to a more reliable diagnosis.