The therapeutic role of methotrexate in chronic urticaria: A systematic review

Background: Chronic urticaria, in many cases, has an unsatisfactory response to antihistamines. The current recommendations in urticaria do not mention the dose and duration for methotrexate. Aims: This study aims to systematically review the use/efficacy of methotrexate in chronic urticaria. Methods: A systematic search in four databases, that is, PubMed/Medline, Cochrane central, Google Scholar and Clinicaltrials.gov was done to identify studies on the use of methotrexate in chronic urticaria using key words "methotrexate [MeSH terms]" and "urticaria" or "urticaria, chronic" or "urticaria, chronic spontaneous." Results: Nine articles (study participants 127), including three randomized control trials, one prospective interventional trial without control, three retrospective reviews and two case reports, were identified and finally included in the systematic review. There was a paucity of literature and the three randomized control trials did not show any benefit of methotrexate over antihistamines alone. However, in studies where steroid dependent cases were given methotrexate, marked benefit was reported with steroid-sparing effect, particularly on methotrexate dose escalation. Limitations: Due to a paucity of published literature on methotrexate in urticaria, a meta-analysis could not be done. Conclusion: In chronic recalcitrant or steroid-dependent cases, methotrexate may be a therapeutic agent of interest; however, current evidence does not point to any added advantage in efficacy over antihistamines. More evidence based on larger, well-executed randomized control trials is needed in the future to get more definitive answers.