Methotrexate-Induced Pulmonary Fibrosis

Introduction to Pulmonary Toxicity

Methotrexate can cause pulmonary fibrosis, a severe manifestation of methotrexate toxicity that can be potentially fatal, characterized by new pulmonary symptoms such as cough in patients, according to the American Academy of Dermatology 1
Of 164 reported methotrexate-associated fatalities, 30 were caused by pulmonary fibrosis, making it the second most common cause of methotrexate-related death after myelosuppression, as reported by the American Academy of Dermatology 1, 2

Pulmonary fibrosis appears to be more common in patients with rheumatoid arthritis than in those with psoriasis, as noted by the American Academy of Dermatology 1, 2
Risk factors for increased pulmonary toxicity include renal impairment, as reported by the European League Against Rheumatism 3
Advanced age is also a risk factor for increased pulmonary toxicity, according to the American Academy of Dermatology 4
Pre-existing pulmonary disease is a risk factor for increased pulmonary toxicity, as reported by the American Academy of Dermatology 5

Patients may present with dry, nonproductive cough, according to the American Academy of Dermatology 1
Reduced diffusion capacity on pulmonary function tests is a diagnostic finding, as reported by the American Academy of Dermatology 5

Patients with pulmonary diseases may not be candidates for methotrexate therapy, as reported by the American Academy of Dermatology 5
Consider pulmonary function studies in consultation with a pulmonologist prior to initiating therapy in high-risk patients, according to the American Academy of Dermatology 5

Obtain a baseline chest x-ray for all patients starting methotrexate, as recommended by the European Crohn’s and Colitis Organisation 6
Monitor for pulmonary symptoms at each visit, according to the American Academy of Dermatology 1
Folate supplementation may reduce some methotrexate toxicities, though its specific effect on preventing pulmonary toxicity is not well established, as reported by the American Academy of Dermatology and the European Crohn’s and Colitis Organisation 1, 6