Azathioprine-induced pancytopenia with normal TPMT activity presenting with HSV oral ulcers

Abstract

A 65-year-old man with treatment-resistant psoriatic arthritis, hypertension, dyslipidaemia and benign prostatic hyperplasia (BPH) presented with herpes simplex virus (HSV) oral ulcers and a recent 15 lb weight loss due to reduced consumption. Five weeks previously, his methotrexate was tapered and he had begun taking azathioprine. The patient's thiopurine S-methyltransferase (TPMT) activity level was normal prior to starting azathioprine. He was found to have pancytopenia with normal folate levels and azathioprine was discontinued. His pancytopenia worsened, with a nadir 8 days after stopping azathioprine, before returning to normal levels. His oral ulcers improved and he was able to tolerate solid food. This case illustrates that decreased TPMT activity is not the only risk factor for pancytopenia as an adverse reaction to azathioprine. Furthermore, HSV stomatitis may be the presenting symptom of pancytopenia. The timeline of improvement in cell counts illustrated in this patient has implications for the management of suspected azathioprine-induced pancytopenia.

Azathioprine‐induced severe myelosuppression accompanied by massive hair loss and painful oral ulcer in an autoimmune hepatitis patient with NUDT15 minor variant: A case report

“… 17 In contrast, little has been reported regarding severe oral ulcers as an adverse reaction of AZA. However, a similar case of AZA‐induced severe pancytopenia with stomatitis 18 was reported; hence, the oral mucosal reaction can also be considered as AZA‐related. Both reactions are subjective; thus, massive hair loss and oral ulcers allow early diagnosis of critical adverse reaction of AZA.…”

Azathioprine‐induced pancytopenia: A case report

“…Her blood counts only returned to normal 5 weeks after AZA cessation. Cell counts often decrease for several days after AZA discontinuation before recovering to normal, with one case reported to show pancytopenia for up to 2 weeks 9 . The delayed recovery of cell numbers is believed to arise from the continued accumulation of TG nucleotides after AZA discontinuation 13 .…”

“…Although a link between pancytopenia and intermediate‐to‐low TPMT activity has been established, few examples of AZA‐induced pancytopenia in patients with normal TPMT activity have been described 1,6,8,9 . No significant differences were noted in the clinical evaluation of AZA‐treated patients with normal TPMT levels.…”

A Case of Pancytopenia with Many Possible Causes: How Do You Tell Which is the Right One?

“…SLE patients seem to be more susceptible to these adverse events [ 4 ] , which tend to manifest in the first 3 weeks of treatment, and last for 3 weeks after drug suspension. Some patients may require colony-stimulating factors [ 5 ] .…”