2050 NUDT 15 C415T Variant as a Cause of Azathioprine-Induced Pancytopenia With Severe Sepsis

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INTRODUCTION: Thiopurines (i.e. azathioprine [AZA] and mercaptopurine exert a glucocorticoid-sparing effect for patients with inflammatory bowel disease (IBD) who cannot maintain remission when glucocorticoids are tapered and withdrawn. However, side-effects like leucopenia, pancytopenia limit its use in several conditions where immune suppression is required. CASE DESCRIPTION/METHODS: 17-year-old female presented with abdominal pain for 10 months with acute deterioration for 1 month with intermittent episodes of low-grade fever, loose stools on and off non-bloody, with nausea and multiple episodes of vomiting for last 5 days. She was diagnosed to have Crohn’s disease and was started on Azathioprine 50 mg OD which was increased to 100 mg within next 7 days, along with with with Prednisolone 30 mg and Mesalamine 1500 mg for last 3 weeks. Her baseline investigations showed normocytic normochromic anemia (Hb 9 g/dl) with thrombocytosis. When she presented to us she had pancytopenia Hb-6.6, TLC 900/µL (DLC- N20% L77% M3%), Platelet count of 1,64,000/µL, ESR 31, CRP 140 with normal liver chemistries, Normal Vitamin B12 & Folate level. Patient also started developing alopecia. Azathioprine and steroids were stopped. Initial blood and urine cultures were sterile. She was started on broad-spectrum antibiotics along with G-CSF. Despite antibiotics, patient went on having high fever with falling leucocytes (TLC 300) with Absolute Neutrophil Count of 120/µL. Bone marrow biopsy revealed hypoplastic marrow. Repeat blood culture grew ESBL Escherichia coli sensitive to Tigecycline. After change in antibiotics, there was resolution in her symptoms. Genetic analysis for TPMT mutation and NUDT 15 was considered, which revealed wild type TPMT genotype and homozygous NUDT 15 C415T variant. In the meantime, the patient developed symptoms of intestinal obstruction. CT enterography revealed stricturing Crohn’s disease and was posted for surgery. DISCUSSION: In this report, we present a case of Azathioprine toxicity with pancytopenia with severe sepsis in a young patient with homozygous NUDT 15 variant and wild type TPMT genotype. This case, along with recent researches, enlightens us to consider NUDT 15 variant analysis before starting thiopurines in any patient, particularly in Asian population.