A case of severe erythema nodosum induced by methimazole

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3. Discussion

Anti-thyroid drugs (ATDs) that are the members of the thioamide group include methimazole, carbimazole and propylthiouracil have been used in the treatment of the hyperthyroidism for approximately 60 years. Methimazole is active metabolite of carbimazole (Taylor and Vaidya, 2012). The most common side effects of ATDs are skin rash, low grade liver dysfunction, granulocytopenia and arthralgia. Myeloperoxidase antineutrophil cytoplasmic antibody (ANCA) related vasculitis, agranulocytosis and severe hepatotoxicity are rare but serious complications of ATDs (Yang et al., 2015). EN is an immune associated non-specific cutaneous reaction that develops as a response to a specific stimuli. It has been presumed to be a hypersensitivity reaction. Hypersensitivity reactions due to medications have been recognized as a cause of 3–10% of erythema nodosum cases (Schwartz and Nervi, 2007). Case reports of EN associated with the anti-thyroid drugs are quite rarely reported in the literature even if there is a common use of anti-thyroid drugs.

Up to date there are only a few anecdotal cases about these anti-thyroid drugs and EN. Two case reports of EN induced by propylthiouracil have been reported (Keren et al., 1985, Wan et al., 2012). In the EN case induced by propylthiouracil that was reported by Wan et al., ANCA positivity was also accompanied (Wan et al., 2012). The third case of EN induced by ATDs was due to carbimazole. EN, acute pancreatitis and hepatic cholestasis were reported in a 33 year-old female patient using carbimazole. These side effects were observed one month later from the beginning of the carbimazole treatment in this patient (Marazuela et al., 2002). Different from the other cases, our patient was the first case of EN that was observed after the usage of methimazole. In our patient lesions continued to develop by increasing even if there is an adequate treatment for EN in a period of one month and lesions had disappeared by improving fast in one week after the cessation of the treatment. We could not find any other etiologic reasons for EN. Streptococcal infections are one of the most common causes of EN (Chowaniec et al., 2016, Starba et al., 2016). We had prescribed empirical antibiotic therapy against possible streptococcal infections, by the time the laboratory tests resulted. But streptococcal infection was not found on laboratory examinations and we stopped antibiotic therapy. Therefore we thought that these EN lesions were induced by methimazole. The EN lesions were localized on the lower legs typically. While the lesions are present, the methimazole treatment was stopped and propylthiouracil treatment was started. There was no recurrence in a period of 1 year follow-up during propylthiouracil treatment. Since these lesions appeared 2 weeks after the beginning of the methimazole, we think that these EN lesions are idiosyncratic hypersensitivity reaction. Sulfonamides are well-known causes of EN. Marazuela et al. (2002) suggested that the sulphydryl groups that are the components of thioamides can cause hypersensitivity reaction and EN. However, in our case propylthiouracil did not induce EN which was also a member of thioamide group. Probably, in our case methimazole caused immune–mediated reaction by another different way. Therefore we should keep methimazole induced EN in mind in the patients that have EN like lesions that the etiologic factors cannot be illuminated during methimazole treatment.

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About the Author: Tung Chi