Clinicopathological characteristics of low‐dose methotrexate‐induced epidermal dysmaturation: A study of 22 patients

Summary Background and Objective Erosions of the skin and mucous membranes with epidermal dysmaturation are a known side effect of cytostatic chemotherapy regimens and can also be observed during low‐dose methotrexate (MTX) therapy. The study aimed to delineate the clinical and histopathological alterations. Patients and Methods A database search of the archive for dermatopathology was conducted, identifying 22 patients who developed epidermal dysmaturation on low‐dose MTX. Clinical and laboratory changes, along with an array of histologic parameters were analyzed and statistically evaluated using SPSS. Results Patients were predominantly female with a mean age of 69.1 years. The main indications were psoriasis vulgaris and rheumatoid arthritis. Clinically, patients mostly presented erosive plaques at the injection site, on mucosal surfaces, and disseminated lesions. Most patients showed normal laboratory values. Histopathologically, key findings included enlarged keratinocytes with pale cytoplasm and enlarged nuclei with prominent nucleoli, along with the degeneration of the basal layer. Consistent observations in the dermal compartment included infiltration of neutrophilic granulocytes, lymphocytes, and histiocytes. Conclusions This study proposes clinicopathological criteria for the diagnosis of MTX‐associated skin toxicity, aiming to increase awareness among clinicians and pathologists for early diagnosis. Early recognition can prevent potentially life‐threatening progression.