Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients

Eur Respir J. 2000 Feb;15(2):373-81. doi: 10.1034/j.1399-3003.2000.15b25.x.


Pneumonitis is a serious and unpredictable side-effect of treatment with methotrexate (MTX) that may become life-threatening. The clinical and histological features of nine cases of MTX pneumonitis are reported and the literature reviewed. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxaemia and tachypnoea are always present and crackles are frequently audible. Chest radiography reveals a diffuse interstitial or mixed interstitial and alveolar infiltrate, with a predilection for the lower lung fields. Pulmonary function tests show a restrictive pattern with diminished diffusion capacity. Lung biopsy reveals cellular interstitial infiltrates, granulomas or a diffuse alveolar damage pattern accompanied by perivascular inflammation. These clinical and pathological findings are not specific to MTX pneumonitis and can be seen with other drug-induced lung toxicities. It is important that all patients receiving methotrexate be educated concerning this potential adverse reaction and instructed to contact their physicians should significant new pulmonary symptoms develop while undergoing therapy. If methotrexate pneumonitis is suspected, methotrexate should be discontinued, supportive measures instituted and careful examination for different causes of respiratory distress conducted.

Publication types

  • Review

MeSH terms

  • Aged
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Female
  • Folic Acid Antagonists / adverse effects
  • Humans
  • Lung / pathology
  • Lung Diseases, Interstitial / chemically induced*
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Pneumonia / chemically induced*


  • Antirheumatic Agents
  • Folic Acid Antagonists
  • Methotrexate