Methotrexate lung disease

Dr Bruno Di Muzio ◈ and Dr Yuranga Weerakkody ◉ et al.

Methotrexate lung disease is the specific etiological type of drug-induced lung disease. It can occur due to the administration of methotrexate which is an antimetabolite, which is given for various reasons but commonly to treat rheumatoid arthritis. It is also given alone or in combination with other chemotherapeutic agents to treat a wide variety of malignancies including lung, breast, and head and neck epidermoid cancers, non-metastatic osteosarcoma, and advanced-stage non-Hodgkin lymphoma.

The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever ⁶. Hypoxemia and tachypnea are always present and crackles are frequently audible. Symptoms typically manifest within months of starting therapy). There appear to be is no correlation between the development of drug toxicity and the duration of therapy or total cumulative dose)¹.

Pathology

There can be several manifestations of methotrexate-related lung changes:

inflammatory: fibrotic disease
- organizing pneumonia (formerly called bronchiolitis obliterans with organizing pneumonia or BOOP)
- acute interstitial pneumonia with non-cardiogenic pulmonary edema
- pulmonary fibrosis
- pleural effusion and symptomatic pleuritis occur infrequently
superimposed pulmonary infection: from immunosuppression
pulmonary lymphoproliferative disease: from immunosuppression

Radiographic features

CT

CT features can be variable and included diffuse parenchymal opacification, reticular opacities, and centrilobular nodules ². An NSIP pattern is considered the most common manifestation of methotrexate-induced lung disease ¹.

Treatment and prognosis

Overall prognosis would depend on the exact form of the disease. In general, the prognosis is considered good, with most patients improving despite the continuation of therapy. Patients with lung fibrosis at presentation may have worse prognosis ².