Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, South Tower, 7th floor, Philadelphia, PA, 19104, USA.
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Am J Clin Dermatol. 2022 Jul;23(4):449-457. doi: 10.1007/s40257-022-00692-1. Epub 2022 Apr 29.
Methotrexate cutaneous ulceration is a rare methotrexate complication, and has only been described in case reports and case series.
To document patient characteristics, morphologic features, and mortality risk factors for methotrexate cutaneous ulceration.
A systematic literature review of PubMed and Embase (last date 1 November 2021) was performed with data collected from case reports and case series. This study was limited to cases of cutaneous ulceration; presence of oral ulceration was collected from within these cases.
114 cases (men = 57.9%, mean age = 61 years) of methotrexate cutaneous ulceration met inclusion criteria. Psoriasis (69.3%), rheumatoid arthritis (18.4%), and mycosis fungoides (6.1%) were the most common indications for methotrexate use. Morphologies included erosions localized to psoriatic plaques (33.3%), epidermal necrosis/necrolysis (35.1%), localized ulceration (16.7%), and skin-fold erosions (5.3%). Methotrexate dose preceding toxicity varied greatly; median 20 mg/week, interquartile range 15-40 mg/week, range 5-150 mg/week. Most patients had risk factors for serum toxicity (baseline renal dysfunction = 37.8%, concurrent NSAID use = 28.1%, inadequate folic acid use = 89.1%). Thirty percent of cases involved mistakenly high methotrexate doses. Fourteen patients (12%) died. Absence of folic acid use (69% vs. 100%, p value < 0.001), pancytopenia (33% vs. 86%, p value < 0.001), and renal dysfunction at presentation (47% vs. 92%, p value < 0.001) were associated with increased mortality.
Selection bias present due to abstraction from case reports and case series.
Methotrexate cutaneous ulceration is commonly preceded by dosage mistakes, absence of folic acid supplementation, and concurrent use of nephrotoxic medications. Renal impairment, pancytopenia, and absence of folic acid supplementation are key risk factors for mortality from this adverse medication reaction. Providers should regularly monitor methotrexate dosing adherence, drug-drug interactions, and perform routine laboratory evaluation. Index of suspicion for this toxicity should remain high given the varied clinical presentation and high mortality.
甲氨蝶呤皮肤溃疡是一种罕见的甲氨蝶呤并发症，仅在病例报告和病例系列中有所描述。
记录甲氨蝶呤皮肤溃疡患者的特征、形态特征和死亡风险因素。
对 PubMed 和 Embase 进行了系统的文献回顾（最后日期为 2021 年 11 月 1 日），数据来自病例报告和病例系列。本研究仅限于皮肤溃疡的病例；口腔溃疡的存在情况是从这些病例中收集的。
114 例（男性占 57.9%，平均年龄 61 岁）符合甲氨蝶呤皮肤溃疡的纳入标准。最常见的甲氨蝶呤使用指征是银屑病（69.3%）、类风湿关节炎（18.4%）和蕈样肉芽肿（6.1%）。形态学表现包括局限于银屑病斑块的糜烂（33.3%）、表皮坏死/坏死（35.1%）、局部溃疡（16.7%）和皮肤褶皱糜烂（5.3%）。毒性发生前的甲氨蝶呤剂量差异很大；中位数 20mg/周，四分位距 15-40mg/周，范围 5-150mg/周。大多数患者有血清毒性的风险因素（基线肾功能不全=37.8%，同时使用 NSAID=28.1%，叶酸使用不足=89.1%）。30%的病例涉及错误的高甲氨蝶呤剂量。14 例患者（12%）死亡。叶酸使用不足（69% vs. 100%，p 值<0.001）、全血细胞减少（33% vs. 86%，p 值<0.001）和发病时肾功能不全（47% vs. 92%，p 值<0.001）与死亡率增加相关。
由于从病例报告和病例系列中提取，存在选择偏倚。
甲氨蝶呤皮肤溃疡常发生在剂量错误、缺乏叶酸补充和同时使用肾毒性药物之前。肾功能不全、全血细胞减少和叶酸补充不足是这种药物不良反应死亡的关键风险因素。鉴于这种毒性的临床表现多种多样且死亡率较高，提供者应定期监测甲氨蝶呤的剂量依从性、药物相互作用，并进行常规实验室评估。由于这种毒性的临床表现多种多样且死亡率较高，因此对这种毒性的怀疑指数应保持较高水平。
