Sustained cough in methotrexate therapy for rheumatoid arthritis

Sustained cough is a frequent complaint in methotrexate (MTX) treatment for rheumatoid arthritis and can be a symptom of incipient MTX-induced pneumonitis. This study was performed to characterize MTX-associated cough clinically and to clarify by which means this condition can be distinguished from incipient MTX pneumonitis. Three patients with MTX-induced pneumonitis and 10 patients with sustained cough unassociated with pneumonitis were examined clinically, by pulmonary function testing, and bronchoalveolar lavage (BAL). In MTX pneumonitis, cough was associated with progressive dyspnoea, constitutional symptoms, impaired pulmonary function, and interstitial infiltration of variable degree by chest X-ray. BAL cytology invariably showed lymphocytic alveolitis while transbronchial biopsy revealed active interstitial inflammation in only one patient. Ten patients had sustained, nonprogressive cough in the absence of constitutional symptoms, progressive dyspnoea and impaired pulmonary function. Neither X-ray nor BAL nor transbronchial biopsy revealed any evidence of interstitial lung disease. In the majority of these patients, cough abated with symptomatic treatment with or without temporary discontinuation of MTX. It is concluded that MTX-associated cough can be a reflection of isolated airway disease. Clinically, absence of constitutional symptoms, impaired pulmonary function, and interstitial infiltration on X-ray distinguished this condition from incipient MTX pneumonitis. Cough without pulmonary parenchymal involvement appears to result from an irritant effect of MTX on the airways.