Chamorro-Petronacci C, García-García A, Lorenzo-Pouso A-I, Gómez-García F-J, Padín-Iruegas M-E, Gándara-Vila P, Blanco-Carrión A, Pérez-Sayáns M
Entrerríos s/n, Santiago de Compostela, C.P. 15782, Spain,
Med Oral Patol Oral Cir Bucal. 2019 Mar 1;24(2):e181-e189. doi: 10.4317/medoral.22851.
Oral ulcers caused by methotrexate (MTX) at low doses are a known side effect of this drug. Although increasingly more patients are medicated with MTX, these painful ulcers, without traumatic origin and resistant to any type of treatment, are not usually identified by health professionals as a side effect of the medication.
In the absence of a consensus protocol for the effective treatment of oral lesions produced by MTX, the objective of this article was to review and analyse the information from articles related to oral ulcers produced by low-dose MTX and to record the clinical management performed and the MTX dose given to the patient. Data sources - Medline, Web of Science, and Cochrane Library. Participants - Patients treated with low-dose MTX (less than 25 mg/week). Interventions - Management of oral lesions caused by MTX. Study eligibility criterion, study appraisal and synthesis method: An initial search was carried out in the aforementioned databases with the terms 'methotrexate AND oral OR ulcer'. The search was carried out using both medical subject heading (MeSH) terms and a free search between January 2003 and January 2018. Of the results obtained, two independent researchers analysed abstracts that met the search criteria, that is, those that mentioned oral ulcers produced by MTX at low doses. Next, both researchers read the complete article and determined whether it met the following inclusion criteria: written in English, specified the dose of MTX prescribed for the patient and specified the protocol of action for the ulcers. A third investigator acted as a mediator in cases of dispute. Agreement was calculated using Cohen's kappa coefficient, with a k value of 0.82. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide for systematic reviews was used.
The initial search resulted in a total of 66 articles, of which 30 were selected to assess their inclusion in this study. Finally, 16 met the inclusion criteria. Using the Pierson and Newcastle-Ottawa scales and Bradford Hill criteria modified for studies of case series and "in relation to a case", 2 were rated as high quality, 2 were rated as low quality and 12 were rated as medium quality. The limitations of this study are based on the fact that all of the articles available to carry out the systematic review were "in relation to a case or series of cases", with the heterogeneity of data that this implies.
Evidence on the management of oral ulcers in the oral cavity produced by MTX at low doses is scarce due to the heterogeneity of data and the measures adopted in the selected studies. Therefore, it seems that this management is relegated to the perception of the clinician rather than to a specific protocol of action. Studies with a longer follow-up duration and larger sample size are needed to guide different health professionals on the management of these lesions.
低剂量甲氨蝶呤（MTX）引起的口腔溃疡是该药物已知的副作用。尽管越来越多的患者使用MTX进行治疗，但这些无创伤性起源且对任何类型治疗均有抵抗性的疼痛性溃疡，通常未被卫生专业人员识别为药物副作用。
由于缺乏针对MTX所致口腔病变的有效治疗的共识方案，本文的目的是回顾和分析与低剂量MTX所致口腔溃疡相关的文章信息，并记录所实施的临床管理及给予患者的MTX剂量。数据来源——医学期刊数据库（Medline）、科学引文索引（Web of Science）和考克兰图书馆。参与者——接受低剂量MTX（每周少于25毫克）治疗的患者。干预措施——MTX所致口腔病变的管理。研究入选标准、研究评估和综合方法：最初在上述数据库中使用“甲氨蝶呤与口腔或溃疡”等术语进行检索。检索使用医学主题词（MeSH）术语及自由检索方式，检索时间为2003年1月至2018年1月。在获得的结果中，两名独立研究人员分析了符合检索标准的摘要，即那些提及低剂量MTX所致口腔溃疡的摘要。接下来，两名研究人员阅读全文并确定其是否符合以下纳入标准：用英文撰写、明确规定给患者开具的MTX剂量以及明确溃疡的治疗方案。在出现争议的情况下，由第三名研究人员担任调解人。使用科恩kappa系数计算一致性，k值为0.82。本系统评价采用系统评价和Meta分析的首选报告项目（PRISMA）指南。
最初的检索共得到66篇文章，其中30篇被选来评估其是否纳入本研究。最终，16篇符合纳入标准。使用皮尔逊量表和纽卡斯尔-渥太华量表以及针对病例系列研究和“与病例相关”研究修改后的布拉德福德·希尔标准，2篇被评为高质量，2篇被评为低质量，12篇被评为中等质量。本研究的局限性基于这样一个事实，即所有可用于进行系统评价的文章均“与一个病例或一系列病例相关”，这意味着数据存在异质性。
由于数据的异质性以及所选研究中采用的措施，关于低剂量MTX所致口腔内口腔溃疡管理的证据很少。因此，这种管理似乎更多地取决于临床医生的认知，而非特定的治疗方案。需要开展随访时间更长、样本量更大的研究，以指导不同卫生专业人员对这些病变的管理。
