Severe cutaneous adverse reactions due to isoniazid in a HIV positive patient.

Severe Cutaneous Adverse Reaction (SCAR) represents the spectrum of adverse drug reactions from erythema multiforme, Stevens - Johnson syndrome (SJS) to Toxic Epidermal Necrolysis (TEN). A 55 year old lady presented in a toxic state with peeling of skin, blisters on the body of seven days duration following medications taken for fever and pulmonary tuberculosis. When referred to our institution, she was diagnosed as TEN. Immediately the suspected medications were stopped. The essential investigations were done including the screening for immunosuppression, which was found to be negative. The patient was treated symptomatically with emphasis on skilled nursing care. The patient's skin condition improved gradually but tuberculosis progressively worsened over three months. Thus patient was reinvestigated for seropositivity and was found to be positive. Considering the benefit - risk ratio along with the advice of the pulmonologist, a decision was made to give her a rechallenge test, first for antitubercular drugs and later for antipyretics. The patient developed SJS within two days of starting isoniazid (INH). On withdrawal of INH the patient recovered.

Does isoniazid increase the hepatotoxicity of the combination prothionamide-dapsone? Isoprodian Study Group.

In order to assess the potential additive liver toxicity of isoniazid to that of a thioamide-containing treatment, a prospective, randomized, double-blind trial of 24 weeks' duration involving 772 adult patients was conducted in four leprosy centers--two in India, one in Madagascar, and one in the Ivory Coast. Patients with multibacillary leprosy were given daily 100 mg dapsone (DDS) and 350 mg prothionamide (PTH) plus monthly 600 mg rifampin (RMP) in combination either with 350 mg isoniazid (INH) or with a placebo. After clinical and laboratory (including HBs-Ag testing) examinations on admission, the side effects (especially gastrointestinal disturbances and liver toxicity) were assessed at regular intervals during treatment by laboratory testing (aminotransferases, bilirubin, alkaline phosphatase) and by recording spontaneous complaints. Analysis of the frequency and seriousness of the side effects was made before breaking the code (with or without INH). Although 10% of the patients had liver toxicity leading to stopping treatment, no significant difference in the occurrence of side effects was observed between patients treated with or without INH. Most (75%) of the observed side effects occurred during the first 4 weeks of treatment, and the time of their onset was not related to INH. Body weight and age were factors related to the frequency of side effects [the higher the body weight, the lesser the rate of side effects (p = 0.03)] and the rate of serious side effects increased with age (p = 0.02). But, again, the frequency of the side effects was not related to INH administration. Therefore, from the present study it can be concluded that INH does not increase the toxicity of the thioamide-containing treatment.

[New drugs in the treatment of leprosy]. / Nuevas medicaciones en el tratamiento de la lepra

Two groups of patients were chosen for this treatment; the first group of 14 patients was treated with a daily dose of 600 mg. of Rifampicine and the second group with Rifampicine associated with Isoprodian (1-2 tablets). In the first group clinical and bacteriological improvement was apparent. This was parallel in bacteriological and morphological index. Two patients became negative in nasal mucous. Tolerance was good and number of leprosy reactions 65%. In the second group clinical improvement was good in general but one case that presented a continuous polyneuritis and hepatic intolerance. Bacteriological results were lightly lower than the first group and the number of leprosy reactions 85%. This treatment is considered inferior to the sulfons, which is very expensive. A longer period of time will be needed to appriase results.