20th February 2025

Drug-induced interstitial lung disease

Overview of drug-induced ILD

Drug-induced interstitial lung disease can be caused by a wide variety of medications including antibiotics, antiarrhythmics, chemotherapy agents and immunosuppressive drugs. Radiation can also result in lung damage.

Specific drugs associated with drug-induced ILD include nitrofurantoin, sulfasalazine, bleomycin, busulfan, cyclophosphamide, methotrexate, amiodarone and gold (Table 1).

Symptoms may include breathlessness, cough, fever, rash, wheeze and reduced exercise tolerance. Signs may include crackles on respiratory examination and clubbing. In later stages, signs of pulmonary hypertension may develop.

Clinical, radiological and histological findings are non-specific, and therefore a history suggestive of exposure to a medication known to cause ILD is paramount for diagnosis.

Table 1 Drug and radiation-induced ILD patterns of disease, causative agents and typical HRCT findings

Diagnosis of drug-induced ILD

This is a diagnosis of exclusion. Investigation findings may include:

• Bloods: may show eosinophilia
• HRCT: as per Table 1
• Lung function tests: results vary, but most cause a restrictive pattern with reduced TLCO
• Bronchoscopy and bronchoalveolar lavage: may help differentiate between patterns. HP shows lymphocytosis and a low CD4:CD8 ratio; bronchiolitis obliterans organising pneumonia shows increased lymphocytes; cytotoxic pneumonitis due to chemotherapy agents shows a neutrophil predominance. Of note, amiodarone can cause foamy intracytoplasmic alterations with alveolar macrophages

Management of drug-induced ILD

Management is focused on withdrawal of the causative medication. If disease persists or continues to progress, steroids might be helpful in some patterns of disease.

See note on nintedanib – this has now been approved as a treatment option for chronic progressive fibrosing interstitial lung diseases.

References

• Chapman SJR, G. V.; Shrimanker, R. S.; Turnbull, C. D.; Wrightson, J. M. Oxford Handbook of Respiratory Medicine. Fourth Edition ed. Oxford, United Kingdom: Oxford University Press; 2021
• Schwaiblmair M, Behr W, Haeckel T, Markl B, Foerg W, Berghaus T. Drug induced interstitial lung disease. Open Respir Med J. 2012;6:63-74
• NICE. Nintedanib for treating progressive fibrosing interstitial lung diseases. National Institute for Health and Care Excellence, 2021 [accessed 18/03/2024]