19th May 2025

Clinical features

Signs and symptoms

Symptoms are typically non-specific e.g. dyspnoea, cough, and pleuritic chest pain. Rash, wheeze and haemoptysis may be seen. Signs may include hypoxaemia, crackles on auscultation, clubbing of the fingers, and signs of pulmonary hypertension causing right ventricular dysfunction such as peripheral oedema and jugular venous distention. 

Pulmonary function tests 

Changes are nonspecific. Most drugs causing DILD cause a restrictive lung disease pattern with decreased total lung capacity. Reduction in diffusing capacity for carbon monoxide (DLCO) is typically seen. Drugs causing bronchiolitis obliterans may cause an obstructive pattern. 

Histology

In general, if there is exposure to a drug resulting in damage to the pulmonary interstitium, particularly in the case of persistent exposure or dysregulated repair processes, interstitial tissue replaces the capillaries and alveoli. Often nonspecific histopathological changes are seen, and almost all patterns of interstitial lung disease caused by therapeutic agents have been demonstrated, including: diffuse alveolar damage (DAD), hypersensitivity pneumonia (HP), granulomatous pneumonitis (GP), bronchiolitis obliterans organising pneumonia (BOOP), non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), organising pneumonia (OP), eosinophilic pneumonia (EP), and granulomatous lung disease (GLD). Some drugs may be responsible for more than one pattern of DILD. Several drugs demonstrate characteristic histopathologic changes; amiodarone may cause NSIP, and methotrexate causes an acute granulomatous ILD which closely resembles opportunistic infective histological changes.

Radiographic findings

Plain film radiographs commonly show bilateral pulmonary infiltrates but may also be normal. 

Computed tomography (CT) may demonstrate numerous patterns of interstitial change; most commonly ground glass opacification, with or without consolidation which can follow a basal, peripheral and bilateral distribution. Changes in keeping with OP, NSIP and HP are most commonly seen. 

High-resolution CT (HRCT) has been reported to be the best modality to demonstrate changes in DILD, which can correspond to the histological subtype. It can also be useful in identifying findings suggestive of an alternate pathology. As a general rule, pneumonitis induced by anti-neoplastic agents shows a pattern of scattered or diffuse ground glass opacities with intralobular interstitial thickening. Those agents causing hypersensitivity pneumonia, including cyclophosphamide, sulfonamides or sulfasalazine may show bilateral patchy ground-glass opacities and/or centrilobular upper lobe nodules. Antibiotic-induced pneumonitis has been reported as showing scattered ground-glass and centrilobular opacification and interlobular septal lines.

Serological tests

A sensitive marker for interstitial lung disease in general is Krebs von den Lungen-6 (KL-6), however its specificity in DILD is not yet established. SP-A and SP-D are serum biomarkers specific for pulmonary fibrosis; again, at present the diagnostic value in DILD is unclear. 

Bronchoscopy + bronchoalveolar lavage 

When performing bronchoalveolar lavage in DILD the most common finding is a lymphocytic alveolitis. Raised lymphocyte, neutrophil and eosinophil counts are typically seen. The presence of reactive type II pneumocytes has been reported in severe DILD cases. Bronchoscopy is also useful for detecting key differentials such as vasculitis, alveolar haemorrhage, pneumonia, and lymphangitic carcinomatosis. 

Biopsy

Lung biopsy is not typically recommended as part of the diagnostic workup as it is unlikely to aid in providing a definitive diagnosis of DILD, however it can be useful for excluding key differential diagnoses.