Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Lymphocyte Stimulation Test with Tetrazolium-Based Colorimetric Assay for Diagnosis of Drug-Induced Allergic Hepatitis
Tomoaki YOSHIMURAChikako KURITAFutoshi YAMAZAKISatoshi NAKANOHiroichi NAGAI
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1994 Volume 17 Issue 7 Pages 921-926

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Abstract

The lymphocyte stimulation test (LST) is useful for diagnosing drug-induced allergy and identifying the causative drug. In this study, we examined the usefulness of 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) as a marker for LST in diagnosing drug allergy. In a basic study using normal peripheral blood mononuclear cells, the normal range of stimulation index (SI) was 0.92-1.38, and the mean SI 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 possibly positive and definitely positive rates were 54.3% (SI≥1.4) and 41.3% (SI≥1.5), respectively. A clinical study was made of 113 patients with diagnosed drug-induced allergic hepatitis. Forty-nine (43%) of the patients were male and 64 (57%) were female. In 85% of cases the allergic reaction occurred within one month of taking medication, but there were a number of cases in whom onset occurred after long-term incubation. The main clinical symptoms were jaundice, itching, eruption, fever, and general malaise. In about 75% of cases glutamic oxaloacetic transaminase (GOT) or glutamic pyruvic transaminase (GPT) returned to normal range within one month after medication was halted. Among the causative drugs, antimicrobial agents were the most numerous accounting for 33.9% of the total, followed by central nervous system agents 21.2%, and cardiovascular agents 16.9%. These results indicate that LST with the MTT assay would be useful in diagnosing drug-induced allergic hepatitis, and that among the drugs examined, antimicrobial agents were responsible for the largest number of allergic reactions.

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