Amiodarone is an iodinated benzofuran derivative that is highly effective in suppressing ventricular and supraventricular tachyarrhythmias. Adverse side effects are common and include photosensitivity, blue-gray discoloration of the skin, thyroid dysfunction, corneal deposits, abnormal liver function tests, and bone marrow suppression . Pulmonary toxicity is the most serious adverse effect of amiodarone.
The types, pathogenesis, risk factors, diagnosis, and treatment of amiodarone pulmonary toxicity will be reviewed here. The other major side effects of amiodarone are discussed separately. (See "Major side effects of amiodarone".)
TYPES OF DISEASE
Several forms of pulmonary disease occur among patients treated with amiodarone, including chronic interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome, and a solitary pulmonary mass. The incidence of pulmonary toxicity from amiodarone is not precisely known but is likely to be approximately 5 percent .
A characteristic finding in all patients exposed to amiodarone is the presence of numerous foamy macrophages in the air spaces (picture 1), which are filled with amiodarone-phospholipid complexes (image 1). Like other amphiphilic compounds, amiodarone can cause an accumulation of phospholipids within lysosomes in the lungs and other tissues due to the inhibition of phospholipase A . Ultrastructural studies show myelinoid inclusion bodies in the affected tissue.
Chronic interstitial pneumonitis — Chronic interstitial pneumonitis is the most common presentation of amiodarone-induced pulmonary disease. It is characterized by the insidious onset of nonproductive cough, dyspnea, and weight loss. The chest radiograph reveals focal or diffuse interstitial opacities. Interstitial pneumonitis is usually recognized after two or more months of therapy, especially in patients in whom the dose of amiodarone exceeds 400 mg per day . These manifestations are due to a nonspecific interstitial pneumonitis predominantly composed of mononuclear cells, foamy alveolar macrophages, type II cell hyperplasia, and fibrosis. Various forms of lymphocytic infiltration of the lungs have been described, including diffuse lymphoid hyperplasia, follicular bronchiolitis, and lymphoid interstitial pneumonia .