Jara-Palacios Miguel A, Chun William, Traub Nomi L
Department of Internal Medicine, WellStar Atlanta Medical Center, Atlanta, GA, USA.
BMC Rheumatol. 2021 Feb 12;5(1):5. doi: 10.1186/s41927-020-00175-y.
Low dose methotrexate toxicity rarely occurs, but may present with severe complications, such as pancytopenia, hepatotoxicity, mucositis, and pneumonitis. Known risk factors for methotrexate toxicity include dosing errors, metabolic syndrome, hypoalbuminemia, renal dysfunction, lack of folate supplementation, and the concomitant use of drugs that interfere with methotrexate metabolism. Vitamin B12 deficiency leads to megaloblastic anemia and may cause pancytopenia, but its role in methotrexate toxicity has not been described.
We present a case of a patient with rheumatoid arthritis who was admitted with febrile neutropenia, pancytopenia, and severe mucositis, likely secondary to low dose methotrexate toxicity. She had multiple factors that potentially contributed to the development of toxicity, including concurrent sulfasalazine use for rheumatoid arthritis. An evaluation of the patient's macrocytic anemia revealed pernicious anemia. The patient's illness resolved with cessation of methotrexate and sulfasalazine, leucovorin treatment and vitamin B12 repletion.
This case illustrates the multiple factors that may potentially contribute to low dose methotrexate toxicity and highlights the importance of testing for vitamin B12 deficiency in rheumatoid arthritis patients with macrocytic anemia. Addressing all the modifiable factors that potentially contribute to low dose methotrexate toxicity may improve outcomes.
低剂量甲氨蝶呤毒性很少发生,但可能出现严重并发症,如全血细胞减少、肝毒性、粘膜炎和肺炎。已知的甲氨蝶呤毒性危险因素包括给药错误、代谢综合征、低白蛋白血症、肾功能不全、缺乏叶酸补充以及同时使用干扰甲氨蝶呤代谢的药物。维生素B12缺乏会导致巨幼细胞贫血,并可能引起全血细胞减少,但其在甲氨蝶呤毒性中的作用尚未见报道。
我们报告一例类风湿关节炎患者,因发热性中性粒细胞减少、全血细胞减少和严重粘膜炎入院,可能继发于低剂量甲氨蝶呤毒性。她有多个可能导致毒性发生的因素,包括同时使用柳氮磺胺吡啶治疗类风湿关节炎。对患者大细胞贫血的评估显示为恶性贫血。患者停用甲氨蝶呤和柳氮磺胺吡啶、接受亚叶酸治疗及补充维生素B12后病情缓解。
本病例说明了可能导致低剂量甲氨蝶呤毒性的多种因素,并强调了对患有大细胞贫血的类风湿关节炎患者进行维生素B12缺乏检测的重要性。处理所有可能导致低剂量甲氨蝶呤毒性的可改变因素可能会改善预后。