Drug- and radiation-induced lung injury
- Lesion
Some drugs and thoracic radiation injure the lung, causing acute damage that may heal or scar. Always consider them in a treated patient with new infiltrates.
What it is
Drugs and radiation are frequent and avoidable causes of lung disease. They produce a range of patterns: diffuse alveolar damage, NSIP or fibrosis, organizing pneumonia, eosinophilic pneumonia, hypersensitivity-like reactions and bronchiolitis obliterans. Radiation pneumonitis appears weeks to months after treatment of thoracic cancers and may end in fibrosis.
Structure
- Acute drug or radiation injury: diffuse alveolar damage with markedly atypical, enlarged type II pneumocytes and fibroblasts.
- Radiation: foam cells in vessel walls, vascular sclerosis, then interstitial fibrosis confined to the radiation field.
- Amiodarone: clusters of foamy macrophages in alveoli; lamellar inclusions on electron microscopy.
- Talc granulomatosis: birefringent crystals inside foreign-body giant cells around small vessels.
Step by step
- Some drugs generate free radicals or are directly toxic to pneumocytes and endothelium (bleomycin, radiation).
- Others act as haptens and trigger hypersensitivity (methotrexate, nitrofurantoin).
- Cationic amphiphilic drugs such as amiodarone accumulate in lysosomes and block phospholipid breakdown.
- The injury evokes inflammation and, if it persists, fibroblast activation and fibrosis.
- Radiation damages DNA in dividing epithelial and endothelial cells, with acute exudation then chronic vascular sclerosis and scar.
Drugs and the lung lesions they cause
| Agent | Main pattern | Clue |
|---|---|---|
| Bleomycin | Diffuse alveolar damage, fibrosis | Chemotherapy for germ cell tumours and lymphoma |
| Amiodarone | Pneumonitis with foamy macrophages | Antiarrhythmic, cumulative exposure |
| Methotrexate | Hypersensitivity pneumonitis | Fever, eosinophilia, poorly formed granulomas |
| Nitrofurantoin | Acute eosinophilic reaction or chronic fibrosis | Long-term urinary prophylaxis |
| Radiation | Pneumonitis then fibrosis | Limited to the radiation field |
Clinical notes
- New cough, fever, dyspnoea and infiltrates in a patient on these drugs or after radiotherapy; exclude infection.
- Radiation pneumonitis causes dyspnoea out of proportion to the irradiated volume; many cases resolve with steroids.
- Stopping the drug is the key step; fibrosis that has formed does not reverse.
Test yourself
Think of the answer, then tap the question to see it.
What histologic finding is typical of amiodarone lung toxicity?
Foamy, lipid-laden alveolar macrophages from drug-induced phospholipidosis, with interstitial pneumonitis.
What is typical about the location of radiation fibrosis?
It is largely confined to the area of lung that was in the radiation field.
What lesion forms in the lungs of people who inject crushed tablets?
Foreign-body granulomas around small vessels containing birefringent filler particles such as talc.
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Interstitial Lung Disease (StatPearls (NCBI Bookshelf), 2025); Interstitial Lung Diseases (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.