Severe Malnutrition and Methotrexate Toxicity as an Unusual Cause of Bone Marrow Aplasia and Multi-System Organ Failure

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INTRODUCTION: Pancytopenia is a common finding in the medical intensive care unit, and is often associated with drug toxicity. Methotrexate is a known cause of pancytopenia, and in one case review of 46 patients, the mortality rate was observed at 28% (1). Here we present a case of neutropenic sepsis attributed to a combination of chronic severe malnutrition and a single dose of methotrexate. CASE PRESENTATION: 41 year old gentleman with prior gastric sleeve, bulimia, psoriasis, and prior failed jejunostomy tube with diffuse intra-abdominal adhesions who presented with throat pain eight days after receiving one dose of 20mg of methotrexate. Exam notable for diffuse desquamating macular cutaneous lesions, severe muscle wasting, and BMI of 16. He displayed friable gingival mucosa with easy bleeding. Labs displayed pancytopenia with marked leukopenia of 0.1 x10^3/uL, an undetectable neutrophil count (<0.1bil/L), and platelets of 7 x10^3/uL. Numerous markers of malnutrition included an INR of 3.5, copper level of 387ug/L, vitamin D-25 OH of 15ng/mL, and undetectable vitamin C and zinc levels. He underwent bone marrow biopsy which showed complete bone marrow aplasia with "virtual absence of trilineage hematopoiesis and serous atrophy/stromal damage." Skin biopsy was consistent with methotrexate toxicity. He developed renal failure requiring hemodialysis. He was unable to tolerate oral intake, so a nasogastric small bowel feeding tube was placed under endoscopic guidance. This also displayed esophageal candidiasis with 75% involvement. His case was further complicated by Klebsiella bacteremia and tricuspid valve endocarditis. Within 4 days of initiating feeds, the patient's WBC improved from 0.1 x10^3/uL to 18.2 x10^3/uL and his neutrophil count improved from undetectable to a peak of 16.2 bil/L. DISCUSSION: This patient presented with multifactorial etiology to pancytopenia and neutropenia. While it has been documented that a single dose of methotrexate can induce severe pancytopenia, it is notably rare, and methotrexate is generally considered one of the safest DMARDs(2). Patients with renal dysfunction, low albumin, folate deficiency, and other immunosuppressants are at highest risk(3). Notably, our patient's albumin was low at ><2.0 g/dL. Given the rapid improvement in our patient's condition after initiating feeds and vitamin supplementation, it was felt that malnutrition played a major role in his hematologic derangements. CONCLUSIONS: Chronic, severe malnutrition is an underrecognized risk factor for methotrexate toxicity, especially as it relates to bone marrow aplasia and life-threatening pancytopenia. This case highlights the complicated interplay between physiologic and psychologic drivers for severe malnutrition, as well as the challenges in obtaining enteral access in a septic patient with severe pancytopenia and a history of hostile abdomen. Physicians working with critically ill patients with severe malnutrition should be vigilant of the potential for this to lead to acute critical illness and treat nutritional status aggressively.




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Chest Annual Meeting 2023, October 8-11, 2023, Honolulu, HI