Methotrexate induced pneumonitis

Methotrexate induced pneumonitis is characterised 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.

Epidemiology

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.

The most recent studies suggest a reported prevalence from 0.3-11.6% and a pooled median prevalence of 5.1% ^1,2.

Pathology

Current 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

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

• hypoxaemia

• tachypnoea

• crackles on auscultation

Radiographic features

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

Plain radiograph

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

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 and prognosis

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.