Objective: Laryngotracheal stenosis (LTS) involves narrowing of the proximal upper airway that can cause obstructed airflow and respiratory distress. Individual retrospective studies and case reports have shown that methotrexate has been used to treat LTS. This narrative review consolidated the findings from these studies into one resource that clinicians can use while evaluating treatment for patients with LTS.

Methods: A literature search was conducted using PubMed, Embase, and Scopus using the terms: "laryngotracheal stenosis", “supraglottic stenosis”, “subglottic stenosis”, “glottic stenosis”, “tracheal stenosis” and “methotrexate”. Only English-language studies were considered. Titles and abstracts were screened first, followed by full-text review for inclusion based on relevance of the use of methotrexate in the management of LTS. A total 42 articles was identified. After screening and full-text review, 10 articles were included. Patient demographics, past medical history, etiology, treatment, outcomes, and complication data from each article were compiled to complete a narrative review of clinical evidence.

Results: Patients in this review had various etiologies including post-intubation subglottic stenosis, relapsing polychondritis, idiopathic subglottic stenosis, rapidly recurrent nonvasculitic laryngotracheal stenosis, granulomatosis with polyangiitis, Immunoglobulin G4-related disease, and microscopic polyangiitis. Across all studies, methotrexate was administered weekly at a dose between 2.5mg and 25mg, and the duration of treatment ranged from 2 months to 11.4 years. In most cases, methotrexate appeared to result in improvement of symptoms, including longer intervals between operative interventions, increased post-drug recurrence intervals, no recurrence of stenosis following drug-initiation, tracheotomy-dependent patients being decannulated, or patients reporting at least some clinical improvement after starting treatment. While methotrexate was tolerated well in most patients, not all patients experienced relief of their symptoms, and adverse events were reported in some cases.

Conclusion: Methotrexate is a widely used and well-understood drug that has been associated with documented cases of improvement of symptoms when used in the management of LTS. Benefits of methotrexate for the management of LTS for some patients include rapid airway improvement, stabilization, and long-term management; and with mild side effects that can be monitored, methotrexate should be considered when treating a patient with LTS.