Severe Myelosuppresion Secondary to Accidental Daily Methotrexate. Abstracts from the 38th annual meeting of the society of general internal medicine

Abstract

LEARNING OBJECTIVE #1: Early recognition and treatment of methotrexate toxicity and associated myelosuppresion. LEARNING OBJECTIVE #2: Importance of medication reconcillation in patient care. CASE: A 67-year-old Hispanic female presented with a 5-day history of bleeding sores from her mouth, pain on swallowing, watery diarrhea, and fatigue. She has a history of breast cancer diagnosed and treated 10 years ago with lumpectomy, chemotherapy, and radiation. She also has a significant history of psoriasis and diabetes mellitus type 2. She has no personal or family history of autoimmune diseases, leukemia, or lymphoma. She reported taking an unknown medication for psoriasis. On exam, she was febrile and tachycardic. She had erosions of lips with associated bleeding and oral ulcerations. Her abdominal exam revealed mild diffuse tenderness but no hepatosplenomegaly. Lab work revealed pancytopenia that decreased progressively to WBC 0.4 billion cells/L (ANC 0), hemoglobin 6.6 g/dL, and platelet count 17 billion/L. Other remarkable initial labs included elevated transaminases (AST 183 U/L, ALT 157 U/L). The initial differential diagnosis included acute leukemia, drug induced pancytopenia, and infectious processes. Broad-spectrum antibiotics were initiated during admission for neutropenic fever. Initial infectious work-up was negative. Further hematologic labs revealed normal iron studies and vitamin B12 level, low reticulocyte count and low folate (4.7 ng/ml). She underwent a bone marrow biopsy, which revealed marked trilineage hypolastic bone marrow without definitive evidence of lymphoproliferative disease. She did receive blood transfusions given low hemoglobin. On day five the patient’s family brought her medications along with her pillbox. It was discovered she was prescribed methotrexate 10 mg weekly. However, on inspection of her weekly pillbox, she was noted to have a methotrexate tablet for each day. A presumptive diagnosis of methotrexate toxicity was given. She was immediately initiated on intravenous folinic acid treatment. Methotrexate level was ordered on day five of admission, and returned<0.10 umol/L; however this was several days after her last exposure. Given she still had diarrhea and persistent fevers, a CT abdomen was ordered to rule out enterocolitis; it revealed cholelithiasis, with mild fat stranding surrounding the gallbladder. This was followed by a HIDA scan with findings consistent with acute cholecystitis. She also had urinalysis that was positive for ampicillinresistant and vancomycin-resistant enterococcus. Clostridium dificile testing was negative during admission. Although she was clinically asymptomatic from gallstones at the time of imaging, it was decided to pursue cholecystostomy placement in light of her neutropenia and persistent fevers. Her antibiotic coverage was changed to cefepime and metronidazole for cholecystitis, and daptomycin for the enterococcus. In addition, the decision was made to administer her granulocyte-colony stimulating factor. During her clinical course, she showed gradual symptomatic improvement and her blood counts increased. Upon follow-up with hematology as an outpatient, her blood counts had normalized and she was reportedly doing well. DISCUSSION: Methotrexate has been used as a treatment of psoriasis formany years and is generally prescribed as a low dose taken weekly. Generally, severe side effects are rare when taken as prescribed and with folic acid supplementation. This case highlights several clinical clues to identifying methotrexate toxicity including stomatitis, GI symptoms, fatigue, fever and transaminitis. However, it is important to recognize that fever should not be soley attributed to drug induced toxicity, and that infectious etiologies should be ruled out. Her labs showed low folate secondary to methotrexate’s antagonist effect on dihydrofolate reductase and replacement is one of the mainstays of overdose treatment. Myelosuppresion, as in this case, can be fatal and treatment should focus on rapid identification and treatment of an underlying etiology, empiric antibiotic coverage for neutropenic fever, supportive transfusions as needed, and consideration of granulocyte stimulating factors.Moreover, one of the most important learning points in this case is that a thorough medication review including efforts to identify unknown medications or nontraditional medications might lead to an earlier diagnosis. It is also important to ensure patient understanding of medication doses and frequency upon prescribing in order to prevent severe adverse events like in this case.