Nodular Amiodarone Lung Disease

Abstract

The antiarrhythmic drug amiodarone accumulates in many organs of the body. Amiodarone lung disease (ALD) most commonly manifests clinically as an interstitial pneumonitis. The few reports of nodular ALD generally have been in the clinical and radiographic literature. No detailed histopathologic analysis of nodular ALD is available. We report 4 patients with nodular ALD, all of whom had excision of a nodule and none had a preoperative diagnosis of ALD. The radiographic suspicion before excisional biopsy in all 4 cases was malignancy. The initial pathologic suspicion in all 4 cases was either an abscess or vasculitis. In 3 of the 4 cases, where the dosages were known, each patient received 800 mg/d for 7 or more months. All cases have strikingly similar histopathology, with vacuolated histiocytes massed within alveoli to form macroscopic nodules with tissue breakdown. Ultrastructural examination of lung and peripheral nerve in 1 case showed the characteristic inclusions of amiodarone in the cytoplasm of swollen histiocytes. Vacuolated histiocytes filled with these inclusions indicate the effect of the drug, but in these 4 cases there was tissue destruction, which indicated disease. The necrotizing nature of the massed histiocytes in the absence of infection or obstruction suggests the correct etiologic diagnosis even when the history of administration of the drug is not available at initial review.

Intracellular sequestration of amiodarone: role of vacuolar ATPase and macroautophagic transition of the resulting vacuolar cytopathology

“…The therapeutic plasma range for amiodarone and its metabolite is 0.7-3.7 mM (Vassallo and Trohman, 2007), but it is widely acknowledged that the tissues accumulate the drug during chronic dosing. Amiodarone produces a constellation of side effects, many of which may be related to drug-induced phospholipidosis and/or vacuolar sequestration: concentric inclusions in peripheral blood leukocytes (Adams et al, 1986;Somani et al, 1986); corneal microdeposits (>90% incidence); blue-gray skin discoloration with photosensitivity (4-9%); non-alcoholic steatohepatitis that can lead to cirrhosis (<3%); and a serious pulmonary toxicity that includes interstitial pneumonia, fibrosis and 'foamy macrophages' that are vacuolar cells containing the typical multilamellar bodies (Myers et al, 1987;Vassallo and Trohman, 2007;Zimetbaum, 2007;Ammoury et al, 2008;Diaz-Guzman et al, 2008;Ruangchira-Urai et al, 2008). Similarly, intracytoplasmic inclusions (termed primary lipidosis) have been observed in the optic nerve axons of patients with slow-onset amiodarone-induced optic neuropathy (Li et al, 2008).…”

Differential diagnosis of usual interstitial pneumonia: when is it truly idiopathic?

“…Type 2 reactive pneumocytes have a peculiar foamy cytoplasm. Since amiodarone toxicity is characterised by an alveolar pattern of disease, the abnormalities observed in a SLB may potentially also be seen in a transbronchial biopsy, although unusual histological manifestations have also been reported [70,71].…”

Amiodarone-related pneumonitis and peripheral neuropathy in an elderly patient

“…Amiodarone toxicity was considered at second observation, when the patient presented with a recurrence of the previous thoracic symptoms after steroid discontinuation and a new symptom: perioral anesthesia. Amiodarone toxicity may also be observed in the neuromuscular system and is characterized by polyradiculoneuropathy; anesthesia or paresthesia are possible aspecific symptoms (1,13). Our patient presented with probable peripheric nerve involvement due to amiodarone toxicity: the anesthetic sensation in the perioral area resolved after discontinuation of the drug, as did all the other symptoms.…”