An Unexpected Cause of Severe Neutropenia in a Kidney Transplant Recipient

Introduction: Neutropenia in kidney transplant (KT) recipients poses a diagnostic and therapeutic challenge, necessitating evaluation for infectious, hematologic, drug-induced and non-immunologic etiologies. Case Description: A 50-year-old male with HTN, HLD, hypothyroidism, and kidney failure due to ADPKD underwent a cadaveric KT in 2015 with immediate graft function. His induction was with anti-thymocyte globulin with maintenance immunosuppression (IS) tacrolimus (TAC) and mycophenolate mofetil (MMF) After stable indices for a decade, he came with a 6-week history of worsening oral ulcerations (Figure 1), diarrhea, leukopenia (WBC as low as 1.3 ×109/L), and severe neutropenia (ANC as low as 470/μL). His TAC level was elevated at 10.2 ng/mL (goal 4-6) on evaluation but improved with diarrhea resolution and TAC dose adjustment. A GI panel revealed Enteropathogenic E. coli (EPEC) by PCR, but other infectious workup, including HSV-1/2 PCR, varicella-zoster virus (VZV) PCR, CMV PCR, EBV PCR, cryptococcal blood antigen, Histoplasma urine antigen, and serological testing for Hepatitis, HIV, and Parvovirus B19 negative. A biopsy of the oral lesion revealed reactive squamous mucosa and a lymphoplasmacytic inflammatory infiltrate. Management with granulocyte-colony stimulating factor (filgrastim) gave only transient improvement. Further investigation found TSH increased above 8 mIU/L from 0.08 mIU/L, and the patient revealed he had self-discontinued his daily 125 mcg levothyroxine due to loss of access to primary care. Resuming levothyroxine provided sustained resolution of neutropenia without further modification of his IS avoiding unnecessarily increasing his risk for allograft rejection. Discussion: This case highlights the need for vigilance when evaluating cytopenias in KT recipients. Although IS medications and infectious etiologies are commonly implicated, non-immunologic causes such as endocrinopathies must be considered. Hypothyroidism is a recognized cause of bone marrow suppression and resultant cytopenias.Figure 1. Ulcers on tongue and buccal mucosa