A 2025 review article meticulously examines the clinical presentation, diagnosis, and management of Melkersson-Rosenthal Syndrome (MRS), a rare neuro-mucocutaneous disorder. The review synthesizes information from case reports, clinical trials, and previous studies to present a comprehensive overview of this condition, highlighting the challenges in timely diagnosis and effective management due to its variable presentations and overlap with other diseases like Bell’s palsy and Crohn’s disease. The authors state that methotrexate is used as an immunosuppressive agent for refractory cases of MRS, specifically when patients do not respond adequately to corticosteroid therapy. Methotrexate is typically administered at 7.5 to 25 mg weekly, with the intended effect of inhibiting immune-mediated inflammation and reducing recurrence rates of MRS symptoms. It is listed among systemic immunosuppressants used to manage persistent or recurrent orofacial edema and facial palsy, alongside azathioprine, and is described as a long-term option. However, documented adverse effects such as immunosuppression and liver toxicity are reported. Notably, no additional efficacy data, comparative outcomes, or detailed clinical results regarding methotrexate use in MRS are provided in the article. In general, managing MRS requires careful ethical consideration, emphasizing patient autonomy and a holistic approach due to the condition's significant psychosocial impact and the potential side effects of long-term medications. Future prospects for care include research into genetic pathways and targeted biological therapies for more effective and less invasive treatment. [1]
A 2020 review article provides an extensive analysis of the management strategies for MRS. This review highlights the challenges in diagnosing MRS due to its varied clinical presentation and the rarity of all three cardinal symptoms appearing simultaneously. While there are no randomized controlled trials specifying the optimal corticosteroid regimen, corticosteroids are a central treatment, often leading to significant improvement and reduced relapse rates, despite a lack of standardized protocols. For localized orofacial edema, intralesional triamcinolone acetonide injections are highly effective, often providing long-term relief. However, the authors note that second-line immunosuppressants may be required in refractory or recurrent MRSm and methotrexate is listed among these options. Specifically, the review cites methotrexate in the context of systemic involvement or possible collagen vascular disease, referencing a report in which cutaneous Crohn’s disease mimicking MRS was treated with methotrexate; however, no controlled studies, dosing information, or direct evidence of methotrexate efficacy for classic MRS are described. Overall, treatment for MRS is typically chosen based on symptom presentation, with oral corticosteroids preferred for concurrent facial paralysis and edema, and intralesional injections for isolated or persistent swelling. [2]
A 2021 article reviewed the clinical and histopathological characteristics of MRS and orofacial granulomatosis across a cohort of 51 patients. Due to the absence of a universally successful treatment for MRS, a trial-and-error approach is necessary, with clinicians advised to continue a drug for at least three months before deeming it ineffective. In one study, the most common treatments were intralesional steroid injections, thalidomide, and dapsone, which showed the highest improvement rates. Many patients required combination therapy. Surgical intervention was reserved for specific situations: complete resistance to medication, residual lip enlargement after the disease was controlled, or severe gingival involvement that did not improve with drugs alone. Notably, systemic immunosuppressants, including methotrexate, were used in 8 of 51 eligible patients (15.68%) as part of the therapeutic interventions. However, the study does not provide disaggregated outcomes for methotrexate specifically, nor does it report detailed response rates, dosing regimens, duration, or adverse effects attributable to methotrexate alone. Instead, the authors note that overall treatment responses varied across modalities, and no single therapy demonstrated universal efficacy. [3]