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Life sciences · Journal article
Egyptian Journal of Bronchology · October 13, 2026
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Abstract Background Methotrexate is commonly used to treat dermatological and rheumatological diseases, but in rare cases it can cause severe and potentially fatal pulmonary toxicity. Methotrexate-induced pulmonary toxicity most commonly manifests as hypersensitivity pneumonitis, whereas rapidly progressive interstitial lung disease (RP-ILD) with complications such as pneumothorax or pneumomediastinum is extremely uncommon. Case presentation A 69-year-old man with chronic erythrodermic dermatitis receiving immunosuppressive therapy was started on oral methotrexate (15 mg weekly). Two months later, he developed progressive dyspnea and hypoxemia. High-resolution computed tomography demonstrated bilateral ground-glass opacities with interlobular septal thickening, suggestive of acute interstitial pneumonitis. Extensive infectious and autoimmune workup was negative, and a diagnosis of probable methotrexate-induced lung injury was made. Methotrexate was discontinued, and the patient was treated with oxygen therapy, broad-spectrum antimicrobials, and pulse corticosteroids, resulting in transient improvement. Subsequently, he developed subcutaneous emphysema, and repeat imaging revealed bilateral pneumothorax with pneumomediastinum requiring intercostal drainage. Despite aggressive management, the patient deteriorated and eventually succumbed to progressive respiratory failure. Conclusion Methotrexate-induced lung injury may rarely present as rapidly progressive ILD complicated by life-threatening pneumothorax and pneumomediastinum. This case highlights a rare and fulminant manifestation of MTX pulmonary toxicity and underscores the importance of early recognition and prompt intervention.