Drug-Induced Lung Disease
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Direct answer
Drug-induced lung disease is injury to the lung caused by medicines, presenting as pneumonitis, interstitial fibrosis, organising pneumonia, pulmonary oedema or eosinophilia. Amiodarone, bleomycin, methotrexate and nitrofurantoin are the classic causes tested in exams. Amiodarone and bleomycin toxicity is linked to dose or cumulative exposure, while methotrexate and nitrofurantoin often cause acute hypersensitivity-type pneumonitis. Stopping the drug is the first step, and corticosteroids are added for significant disease.
What you must remember
- Amiodarone: dose-related toxicity, most likely above about 400 mg a day, with interstitial pneumonitis, organising pneumonia or fibrosis and foamy alveolar macrophages on biopsy.
- Bleomycin: pneumonitis and fibrosis that rise with cumulative dose, and injury that is worsened by high inspired oxygen during anaesthesia.
- Methotrexate: an acute hypersensitivity-type pneumonitis that can occur at any dose, and chronic interstitial pneumonitis, NSIP or organising pneumonia pattern after longer use.
- Nitrofurantoin: acute pneumonitis with fever, dyspnoea and eosinophilia, or chronic interstitial fibrosis after prolonged use.
- Timing: acute reactions appear within days to weeks of starting a drug, while chronic toxicity follows months or years of exposure.
- Management: withdraw the drug promptly, give corticosteroids for significant or progressive pneumonitis, and avoid rechallenge after a serious reaction.
A patient on amiodarone with new breathlessness
A 64-year-old man on long-term amiodarone for atrial fibrillation has three months of dry cough and exertional breathlessness. His chest film shows bilateral reticulonodular shadowing, and his DLCO is reduced.
- Exclude the commoner causes: Infection, heart failure and pulmonary embolism are checked first, since they can produce the same symptoms.
- Match the drug to the pattern: Each drug produces a characteristic histology and imaging picture, and the table below helps link them.
- Use the dose and timing: The dose, duration and cumulative exposure guide how likely drug toxicity is.
- Withdraw the drug: The offending drug is stopped promptly, and the physician looks for improvement over the following weeks.
- Treat the lung injury: Corticosteroids are added for significant pneumonitis, and lung function and imaging are repeated to track recovery.
| Drug | Typical lung pattern | Dose or timing clue |
|---|---|---|
| Amiodarone | Pneumonitis, OP, fibrosis | Above about 400 mg a day |
| Bleomycin | Pneumonitis, fibrosis | Cumulative dose, high oxygen |
| Methotrexate | Acute pneumonitis, NSIP, OP | Acute at any dose, chronic on longer use |
| Nitrofurantoin | Acute pneumonitis, fibrosis | Acute within days, chronic after months |
Drug toxicity is a diagnosis of exclusion, so infection and cardiac causes are excluded before the drug is blamed. A careful timeline of drug start, dose change and symptom onset is often the decisive clue in the viva.
Where the exam tests drug causes
The exam tests whether the drug is recognised and whether the next step is correct.
- Trap: assuming amiodarone lung toxicity is rare at any dose Correct: risk rises with dose and duration, so baseline lung function and chest imaging are essential.
- Trap: giving high-flow oxygen freely in a patient who has received bleomycin Correct: high inspired oxygen worsens bleomycin lung injury, so the lowest effective concentration is used.
- Trap: rechallenging the drug to confirm the cause Correct: rechallenge after a serious pneumonitis is dangerous and is avoided.
- Trap: blaming the drug without excluding infection Correct: infection and cardiogenic oedema must be ruled out before drug toxicity is diagnosed.
Frequently asked questions
What is the main lung complication of amiodarone?
Pulmonary toxicity is the main lung complication of amiodarone, and it can present as interstitial pneumonitis, organising pneumonia or fibrosis. Risk is higher at doses above about 400 mg a day and with longer exposure, so baseline lung function and a chest film are recorded before treatment.
Why is oxygen restricted in patients who have received bleomycin?
Bleomycin causes pneumonitis and fibrosis that become more severe with high inspired oxygen concentrations. Patients who have received bleomycin are therefore given the lowest effective oxygen concentration during anaesthesia or critical care.
How does nitrofurantoin cause lung disease?
Nitrofurantoin can cause an acute hypersensitivity-type pneumonitis with fever, dyspnoea and eosinophilia, or chronic interstitial fibrosis after prolonged use. Stopping the drug is the first step, and the timing of symptoms helps distinguish the acute and chronic forms.
What is the first step in managing drug-induced lung disease?
Stopping the offending drug is the first step in managing drug-induced lung disease, because recovery depends on withdrawal. Corticosteroids are added for significant or progressive pneumonitis, and rechallenge with the same drug is avoided.