Severe thiopurine-induced leukocytopenia and hair loss in Japanese patients with defective NUDT15 variant: Retrospective case-control study
| Autor: | Mizue Fujii, Masaru Honma, Satomi Igawa, Kan Kishibe, Hiroyoshi Nozaki, Akemi Ishida-Yamamoto, Sawa Ohtsubo, Kensaku Okamoto, Kyoko Kanno, Mari Kishibe, Shin Iinuma |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Azathioprine Single-nucleotide polymorphism Dermatology Gastroenterology Polymorphism Single Nucleotide Severity of Illness Index Skin Diseases 03 medical and health sciences 0302 clinical medicine Leukocytopenia Asian People Internal medicine Medicine Humans Pyrophosphatases Retrospective Studies Thiopurine methyltransferase biology business.industry Case-control study Alopecia General Medicine Leukopenia Middle Aged medicine.disease 030104 developmental biology Hair loss 030220 oncology & carcinogenesis Case-Control Studies biology.protein Female ITPA Gene polymorphism business Immunosuppressive Agents medicine.drug |
| Zdroj: | The Journal of dermatology. 45(10) |
| ISSN: | 1346-8138 |
| Popis: | Azathioprine (AZA)-metabolizing enzyme gene polymorphism is strongly related to thiopurine-induced leukocytopenia, which has not been well recognized in dermatological practice. We tried to see whether NUDT15 gene polymorphism can be the most susceptible genetic factor for AZA toxicity and the gene screening is beneficial to avoid the adverse events of AZA for the treatment of skin diseases. A retrospective study was carried out on 15 adult Japanese patients who were treated with AZA. Gene polymorphism of thiopurine-metabolizing enzymes NUDT15 R139C, ITPA 94C>A, TPMT*2, TPMT*3B and TPMT*3C was analyzed. The single nucleotide polymorphisms were prospectively investigated in eight patients who were considered to have received AZA treatments. Two NUDT15 R139C homozygous patients developed agranulocytosis, severe thrombocytopenia and massive hair loss. The gene screening prior to AZA treatment identified one heterozygote of NUDT15 R139C and ITPA 94C>A, and three heterozygotes of ITPA 94C>A or TMPT*3C. Although this study was a retrospective single-center case-control observational study that enrolled a small number of patients, NUDT15 R139C homozygosity is a genetic risk of thiopurine-induced potentially fetal hematological abnormalities. To avoid serious adverse events, gene screening of thiopurine-metabolizing enzymes, at least NUDT15 R139C, should be considered prior to administration in genetically predisposed populations, such as Japanese. We highlight that massive hair loss in the early period of the initiation of AZA would be a sign of impending severe myelotoxicity. |
| Databáze: | OpenAIRE |
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