LAUSR

DEAR EDITOR, Pemphigus vulgaris (PV) is a life-threatening autoimmune mucocutaneous disease with formidable treatment challenges. Since the first report of successful treatment of PV in 1969 with azathioprine (AZA), which was originally used to treat cancers and prevent rejection in organ transplantation recipients, AZA has been often used concomitantly with steroids in the treatment of PV. Although generally well tolerated by most patients, AZA can induce severe myelosuppression, especially leukopenia, in some susceptible individuals, thus resulting in serious microbial infections. It has been well documented that myelosuppression induced by AZA and other thiopurines is significantly associated with specific single-nucleotide polymorphisms of the thiopurine methyltransferase (TPMT) gene and the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene. Allele frequencies of TPMT and NUDT15 variants vary among ethnicities. For instance in the Asian population, TPMT variants are infrequent and can explain only a small proportion of thiopurine-induced toxicity events, while NUDT15 variants (e.g. rs116855232) are relatively common and strongly associated with thiopurine-induced leukopenia, particularly in patients with inflammatory bowel disease (IBD) and paediatric acute lymphoblastic leukaemia (ALL). However, there has been a lack of reports of thiopurine-induced myelosuppression associated with NUDT15 variants in dermatology. Here we report a case of thiopurine-induced severe leukopenia in a Chinese patient with PV with a NUDT15 variant. This patient, a 47-year-old man of Han ethnicity, was diagnosed with PV based on clinical manifestations and pathological examination of a skin biopsy with direct immunofluorescence. He was initially treated with prednisone (60 mg per day) for 3 weeks without positive responses. Subsequently AZA was added at 150 mg per day for 7 weeks, with no new lesions or adverse reactions. Prednisone was then reduced to 50 mg per day while AZA was maintained at 150 mg per day. After 65 days of AZA treatment, he presented high fever (39 5 C) and cough with white expectoration, and was admitted to the respiratory intensive care unit of our hospital. Routine blood tests showed decreased red blood cells and white blood cells. Blood gas analysis indicated respiratory