Complete remission of refractory pemphigus vulgaris in a Chinese patient with mutated NUDT15 by combination of minimal doses of azathioprine and prednisone.
NUDT15
azathioprine
leukopenia
pemphigus vulgaris
Journal
Dermatologic therapy
ISSN: 1529-8019
Titre abrégé: Dermatol Ther
Pays: United States
ID NLM: 9700070
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
15
05
2020
revised:
22
07
2020
accepted:
24
07
2020
pubmed:
28
7
2020
medline:
15
5
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
Although azathioprine (AZA) combined with corticosteroids remains the first-line therapy to treat patients with pemphigus vulgaris (PV), there are increasing reports of AZA-induced leukopenia, which provides the rationale for monitoring the blood cell count and testing the genotypes at the thiopurine methyltransferase (TPMT) and the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes. Here, we reported a case of persistent refractory PV in a Chinese patient with three runs of AZA-corticosteroids treatment. In the first two runs he received AZA-corticosteroids at standard or slightly reduced doses and developed leukopenia. In the third run of treatment, he was found to have NUDT15 mutation (rs116855232) and wild-type homozygous TPMT*3C (rs1142345), treatment with minimal doses of AZA and prednisone resulted in a complete remission of PV without any side effects including leukopenia. Our observations not only highlight the benefits of testing the TPMT and NUDT15 genotypes and monitoring the dynamic changes of the white blood cell count in guiding the AZA therapy, but also suggest the potential of using the AZA-corticosteroids combination at very low doses in the treatment of refractory PV.
Substances chimiques
Azathioprine
MRK240IY2L
Prednisone
VB0R961HZT
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14079Subventions
Organisme : This work was supported by Chengdu Science & Technology Administration
ID : 2018-CY02-00058-GX
Organisme : Science & Technology Department of Sichuan Province
ID : 2019YJ0273
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Harman KE, Brown D, Exton LS, et al. British Association of Dermatologists' Guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017;177(5):1170-1201.
Lee KM, Kim YS, Seo GS, Kim TO, Yang SK, IBD Study Group of the Korean Association for the Study of Intestinal Diseases. Use of thiopurines in inflammatory bowel disease: a consensus statement by the Korean Association for the Study of Intestinal Diseases (KASID). Intest Res. 2015;13(3):193-207.
Cao Q, Zhu Q, Shang Y, Gao M, Si J. Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease. Digestion. 2009;79(1):58-63.
Firooz A, Ghandi N, Hallaji Z, Chams-Davatchi C, Valikhani M, Karbakhsh Davari M. Role of thiopurine methyltransferase activity in the safety and efficacy of azathioprine in the treatment of pemphigus vulgaris. Arch Dermatol. 2008;144(9):1143-1147.
Stocco G, Martelossi S, Decorti G, Bartoli F, Ventura A. Thiopurine-S-methyltransferase genotype and the response to azathioprine in inflammatory bowel disease. Aliment Pharmacol Ther. 2007;26(7):1083-1084.
Yang SK, Hong M, Baek J, et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014;46(9):1017-1020.
Kakuta Y, Naito T, Onodera M, et al. NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD. Pharmacogenomics J. 2016;16(3):280-285.
Zhu X, Wang XD, Chao K, et al. NUDT15 polymorphisms are better than thiopurine S-methyltransferase as predictor of risk for thiopurine-induced leukopenia in Chinese patients with Crohn's disease. Aliment Pharmacol Ther. 2016;44(9):967-975.
Chiengthong K, Ittiwut C, Muensri S, et al. NUDT15 c.415C>T increases risk of 6-mercaptopurine induced myelosuppression during maintenance therapy in children with acute lymphoblastic leukemia. Haematologica. 2016;101(1):e24-e26.
Shah SA, Paradkar M, Desai D, Ashavaid TF. Nucleoside diphosphate-linked moiety X-type motif 15 C415T variant as a predictor for thiopurine-induced toxicity in Indian patients. J Gastroenterol Hepatol. 2017;32(3):620-624.
Clinical Annotation for rs116855232 (NUDT15), azathioprine, mercaptopurine, Inflammatory Bowel Diseases and Precursor Cell Lymphoblastic Leukemia-Lymphoma (level 1B Dosage, Toxicity/ADR). https://www.pharmgkb.org/literature/15087808
Murrell DF, Pena S, Joly P, et al. Diagnosis and management of pemphigus: recommendations of an international panel of experts. J Am Acad Dermatol. 2020;82(3):575-585.
Shih YC, Zou YR, Wang B, Zheng J, Pan M. Azathioprine-induced myelosuppression in two pemphigus vulgaris patients with homozygous polymorphism of NUDT15. J Dermatol. 2019;46(2):e59-e61.
Yan W, Zhou YH, Wang L, Xiao J, Li W. NUDT15 polymorphism and severe azathioprine-induced myelosuppression in a Chinese man with pemphigus vulgaris. Br J Dermatol. 2018;178(1):e40-e41.
Huang PW, Tseng YH, Tsai TF. Predictive value of NUDT15 variants on neutropenia among Han Chinese patients with dermatologic diseases: a single-center observational study. Dermatol Ther (Heidelb). 2020;10(2):263-271.