Amiodarone is an iodinated benzofuran derivative that is used to suppress ventricular and supraventricular tachyarrhythmias. (See "Clinical uses of amiodarone".)
Pulmonary toxicity is among the most serious adverse effects of amiodarone. Several forms of pulmonary disease occur among patients treated with amiodarone, including interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome (ARDS), diffuse alveolar hemorrhage (DAH), pulmonary nodules and solitary masses, and also (rarely) pleural effusion. Other adverse effects from amiodarone include photosensitivity, blue-gray discoloration of the skin, thyroid dysfunction, corneal deposits, abnormal liver function tests, and bone marrow suppression .
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".)
Interstitial pneumonitis is the most common presentation of amiodarone-induced pulmonary disease. Interstitial pneumonitis usually presents after two or more months of therapy, especially in patients in whom the dose of amiodarone exceeds 400 mg per day . The incidence of pulmonary toxicity from amiodarone is not precisely known; it is estimated to be 1 to 5 percent, depending on the dose of amiodarone [3-6]. The rate increases at higher doses of amiodarone, particularly long-term use of doses over 500 mg daily.
Pathology — The histopathologic findings of amiodarone-induced interstitial pneumonitis include a nonspecific interstitial pneumonitis (with a mononuclear cell infiltrate), type II cell hyperplasia, interstitial edema, fibrosis, and lipid-laden alveolar macrophages . The presence of numerous lipid-laden, "foamy" macrophages in the air spaces is a characteristic finding in all patients exposed to amiodarone (picture 1). The "foamy" appearance is due to amiodarone-phospholipid complexes (image 1) and is also seen in patients without lung toxicity who are taking amiodarone. Amiodarone can cause an accumulation of phospholipids within lysosomes in other lung cells, although this is less common [1,7]. Ultrastructural studies show myelinoid (lamellated) inclusion bodies in the affected tissue.