Methotrexate induced pneumonitis

Last revised by Arlene Campos on 20 May 2024

Methotrexate induced pneumonitis is characterized by interstitial inflammation of the lung parenchyma which can be life-threatening. Methotrexate induced pneumonitis falls under a subtype under the broader category of methotrexate induced lung disease.

Diagnosis of methotrexate-induced pneumonitis is based on a combination of clinical and radiological findings. Pulmonary function tests and bronchoalveolar lavage also assist in the diagnosis.

There is uncertainty regarding the incidence and prevalence of methotrexate-induced pneumonitis with varying figures quoted in literature. This could be due to changing diagnostic criteria.

Studies suggest a reported prevalence of 0.3-11.6% and a pooled median prevalence of 5.1% 1,2.

Histopathological evidence suggests that methotrexate pneumonitis is a hypersensitivity reaction leading to interstitial inflammation and fibrosis of the lung parenchyma due to infiltration by lymphocytes, histiocytes, and eosinophils. Histology may demonstrate a granulomatous reaction, typically non-caseating 3,4. However, there are few studies with biopsies and subsequent histopathology.

Clinical features are non-specific, typically occurring within less than 12 months of onset. They may include 2:

  • progressive shortness of breath

  • dry cough

  • fever

  • hypoxemia

  • tachypnea

  • crackles on auscultation

The radiographic features typically follow a non-specific interstitial pneumonia pattern but can demonstrate a bronchiolitis obliterans organizing pneumonia pattern 5,6. Patients can have one or more radiological features, and no single finding is pathognomonic.

Chest radiograph features can include:

  • diffuse heterogeneous pattern

  • bilateral opacities (typically lower lobe predominant but there are case reports of it occurring in the upper lobes) 5

CT features may include 6:

  • scattered or diffuse ground glass opacities

  • basal fibrosis (thought to be a late finding)

  • poor defined centrilobular nodules or nodular air-space filling pattern

  • reticular opacity

  • traction bronchiectasis

Post treatment (average of 31 days in one study), there is often marked improvement or disappearance in the ground glass opacities, consolidation, and centrilobular nodules 6.

Treatment involves the immediate cessation of methotrexate. Additionally, there are recommendations of steroids and combination of immunosuppressive drugs 7.

Following treatment, methotrexate induced pneumonitis carries a good prognosis, with typically full recovery. Nevertheless, in the acute period it does carry a high mortality anywhere from 10-20% 8,9.

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