Yu Huan, Wang Wenhui, Liang Haiyan, Wang Kun, Ling Bin
Department of Obstetrics and Gynaecology, China-Japan Friendship Hospital, Beijing, China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Med (Lausanne). 2021 Nov 18;8:738315. doi: 10.3389/fmed.2021.738315. eCollection 2021.
Low-dose methylenetetrahydrofolate (LD-MTX) has been widely used for the treatment of the ectopic pregnancy (EP) for many decades, and related severe adverse toxic effects are rare. Current studies have shown that the polymorphisms of methylenetetrahydrofolate reductase () gene can decrease the MTX clearance, leading to the metabolite accumulation. However, there is a lack of literature report on an gene polymorphism associated with adverse toxic effects resulting from the use of LD-MTX in an EP. We report a rare case of a 38-year-old female who developed persistent fever, grade IV myelosuppression, skin lesions, mucositis, and liver injury after single dose of LDMTX to treat EP. The personalized genetic testing showed that TT (677C>T) and AA (1298A>C) were detected. Gradually, the symptoms improved after calcium leucovorin (CF) rescue, continuous renal replacement therapy (CRRT), promoting blood system regeneration, and multiple supportive treatments. This is the first report on the serious adverse toxic effects of LD-MTX on an EP patient with mutations. We aim to alert obstetricians and gynecologists to this rare condition. The unexpected life-threatening toxicity with LD-MTX should be highly considered and recognized early. In particular, some easily overlooked gastrointestinal, skin, and mucosal symptoms occur earlier than severe myelosuppression. When toxic effects are suspected, detecting the polymorphisms of an gene and monitoring MTX concentration in blood could assist us to formulate individualized and active treatments.
低剂量亚甲基四氢叶酸（LD-MTX）已被广泛用于治疗异位妊娠（EP）数十年，且相关严重不良毒性反应罕见。目前研究表明，亚甲基四氢叶酸还原酶（MTHFR）基因多态性可降低MTX清除率，导致代谢产物蓄积。然而，关于EP患者使用LD-MTX所致不良毒性反应相关的MTHFR基因多态性，尚无文献报道。我们报告一例罕见病例，一名38岁女性在单次使用LD-MTX治疗EP后出现持续发热、IV级骨髓抑制、皮肤损害、黏膜炎和肝损伤。个性化基因检测显示检测到MTHFR TT（677C>T）和MTHFR AA（1298A>C）。经亚叶酸钙（CF）解救、持续肾脏替代治疗（CRRT）、促进血液系统再生及多种支持治疗后，症状逐渐改善。这是首例关于LD-MTX对具有MTHFR突变的EP患者产生严重不良毒性反应的报告。我们旨在提醒妇产科医生注意这种罕见情况。应高度重视并早期识别LD-MTX意外的危及生命的毒性。特别是，一些容易被忽视的胃肠道、皮肤和黏膜症状比严重骨髓抑制出现得更早。当怀疑有毒性反应时，检测MTHFR基因多态性并监测血液中MTX浓度有助于我们制定个体化的积极治疗方案。
