LYMPHOCYTE STIMULATION TEST WITH TETRAZOLIUM-BASED COLORIMETRIC ASSAYFOR DIAGNOSIS OF DRUG-INDUCED ALLERGIC HEPATITIS

The lymphocyte stimulation test (LST) is,useful for diagnosing drug-in duced allergy and identifying the causative drug. In this study, we ex amined the usefulness of 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl te trazolium bromide (MTT) as a marker for LST in diagnosing drug allergy . In a basic study using normal peripheral blood mononuclear cells, th e normal range of stimulation index (SI) was 0.92-1.38, and the mean S l for all drugs tested was 1.134 +/- 0.111 (mean + S.D.). The cut-off value of SI for diagnosis of drug allergy was thus set at over mean 2S.D. for possibly positive, and at over mean + 3S.D. as a definitely positive reaction. Forty-six cases of suspected drug-induced allergic hepatitis involving 85 drugs were diagnosed by this assay, and the pos sibly positive and definitely positive rates were 54.3% (SI greater-th an-or-equal-to 1.4) and 41.3% (SI greater-than-or-equal-to 1.5), respe ctively. A clinical study was made of 113 patients with diagnosed drug -induced allergic hepatitis. Forty-nine (43%) of the patients were mal e and 64 (57%) were female. In 85% of cases the allergic reaction occu rred within one month of taking medication, but there were a number of cases in whom onset occurred after long-term incubation. The main cli nical symptoms were jaundice, itching, eruption, fever, and general ma laise. In about 75% of cases glutamic oxaloacetic transaminase (GOT) o r glutamic pyruvic transaminase (GPT) returned to normal range within one month after medication was halted. Among the causative drugs, anti microbial agents were the most numerous accounting for 33.9% of the to tal, followed by central nervous system agents 21.2%, and cardiovascul ar agents 16.9%. These results indicate that LST with the MTT assay wo uld be useful in diagnosing drug-induced allergic hepatitis, and that among the drugs examined, antimicrobial agents were responsible for th e largest number of allergic reactions.