Methotrexate-induced Hypersensitivity Pneumonitis appearing after 30 years of use: a case report

J Med Case Rep. 2017 Jun 28;11(1):174. doi: 10.1186/s13256-017-1333-0.


Background: Methotrexate has been implicated in a variety of lung complications, one of which is hypersensitivity pneumonitis. Hypersensitivity pneumonitis most often occurs within the first year of starting low-dose orally administered methotrexate. We present a case of methotrexate-induced hypersensitivity pneumonitis after 30 years of methotrexate use, which is the first case to be reported so far.

Case presentation: A 77-year-old African American woman with a history of rheumatoid arthritis presented with progressively worsening shortness of breath and nonproductive cough. She was on a daily dose of 2.5 mg of methotrexate that had been orally administered for the last 30 years. A physical examination was significant for fever of 38.2 °C (100.8 °F), tachycardia, bilateral basal crackles, and oxygen saturation of 88% on room air. A laboratory work up was significant for normal white blood cell count, increased eosinophil count of 18.3%, and erythrocyte sedimentation rate of 111 mm/hour. Sputum cultures were negative for any bacterial pathogens including acid-fast bacilli. Influenza and respiratory syncytial viral infection were ruled out. A (1-3)-B-D-glucan assay (Fungitell®) was within normal limits. Pulmonary embolism was ruled out and echocardiography was normal. A chest X-ray showed hazy opacity with prominent reticulation within the upper lung fields bilaterally, right greater than the left with no pleural effusion. Lung computed tomography revealed nonspecific bilateral upper lung opacification. A pulmonary function test was significant for no obstruction, normal maximum voluntary ventilation, and no restriction, with mildly decreased diffusion. Methotrexate was stopped, and our patient was started on prednisone 60 mg orally administered daily with dramatic clinical and radiologic improvement.

Conclusions: Methotrexate-induced hypersensitivity pneumonitis usually occurs in the initial few weeks to months of starting treatment with methotrexate; however, it can occur late during therapy too, and prompt diagnosis is crucial as it is a reversible condition when diagnosed early.

Keywords: Hypersensitivity pneumonitis; Methotrexate; Rheumatoid arthritis.

Publication types

  • Case Reports

MeSH terms

  • Administration, Oral
  • Aged
  • Alveolitis, Extrinsic Allergic / chemically induced*
  • Alveolitis, Extrinsic Allergic / drug therapy
  • Anti-Inflammatory Agents / administration & dosage
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Hypersensitivity / diagnosis*
  • Female
  • Humans
  • Lung / diagnostic imaging
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Prednisone / administration & dosage
  • Radiography
  • Tomography, X-Ray Computed


  • Anti-Inflammatory Agents
  • Antirheumatic Agents
  • Prednisone
  • Methotrexate