Amiodarone lung is an interstitial lung disease seen in patients being administered amiodarone, and can manifest in a number of histopathologic patterns.
The reported prevalence of pulmonary toxicity in the patients receiving amiodarone is ~10% (range 2-18%) 8.
Patients are usually elderly, and have been exposed to amiodarone, usually for at least six months, although there is a poor correlation with dosage or cumulative dose. Risk factors include 6:
- treatment longer the 2 months
- age over 60 years
- daily dose >400 mg
- antecedent lung disease or surgery
- prior angiographic investigations
Overall pulmonary toxicity occurs in 5-10% of treated patients 4-6.
They typically present with exertional dyspnoea as the dominant symptom. Low grade fever, anorexia, muscle weakness have been reported also 2. In approximately a third of patients, presentation may mimic pulmonary infection 6.
Respiratory function tests are usually abnormal with a restrictive pattern on spirometry and decreased gas transfer 2,6. Hypoxaemia is almost always present 6.
In some cases tissue diagnosis is required to establish the diagnosis, although usually the combination of appropriate clinical history and radiographic features suffice to guide therapy.
Amiodarone hydrochloride is a triiodinated antiarrhythmic, comprised of 37% iodine by weight, which accumulates in type II alceocytes 5,7. As is the case with other drug induced pulmonary toxicity, amiodarone can cause a variety of histopathologic patterns including 6-7:
- chronic interstitial pneumonia: most common
- organising pneumonia (OP)
- diffuse alveolar damage (DAD): AIP and even ARDS
A distinctive feature of amiodarone lung is the presence of foamy histiocytes which contain intracytoplasmic osmiophilic lamellar bodies. However, this feature is also seen in patients with amiodarone exposure with no evidence of toxicity.
There are two main patterns of involvement, which may co-exist.
- multiple peripheral areas of dense air-space opacity: most common 5
- interstitial fibrosis
Appearances on chest radiography are non-specific typically comprising of :
- peripheral areas of consolidation
- upper lobe predominance
- underlying interstitial disease
As with other pulmonary disease with an interstitial component, HRCT is the modality of choice. Changes are usually bilateral, asymmetrical and particularly prominent in the lung bases 6. Findings include:
- areas of consolidation
- often hyperdense 1,6 cf. muscle (on account of the iodine)
- patchy ground-glass opacities
- co-existing interstitial disease
- reticulo-nodular opacities
In addition, the liver (80% of cases) and sometimes the heart (20%) are high density 6. However, high hepatic and splenic attenuation is also seen in patients exposed to amiodarone in the absence of drug toxicity.
Gallium67 scan: sensitive but nonspecific.
Treatment and prognosis
Cessation of amiodarone and treatment with steroids arrests and often results in resolution of imaging findings over time 3. Overall mortality from amiodarone lung is <10% 6.
Imaging differential considerations include:
- patients with amiodarone lung have normal blood and tissue eosinophil counts 2
- also peripheral distribution
- pulmonary tuberculosis: cavitation common
- pulmonary fibrosis from other causes
- Churg-Strauss syndrome
- other hyperattenuating pulmonary abnormalities 3
Interstitial lung disease
interstitial lung disease
- drug-induced interstitial lung disease
- hypersensitivity pneumonitis
idiopathic interstitial pneumonia (mnemonic)
- acute interstitial pneumonia (AIP)
- cryptogenic organising pneumonia (COP)
- desquamative interstitial pneumonia (DIP)
- idiopathic nonspecific interstitial pneumonia (NSIP)
- idiopathic pleuroparenchymal fibroelastosis
- lymphoid interstitial pneumonia (LIP)
- respiratory bronchiolitis–associated interstitial lung disease (RB-ILD)
- usual interstitial pneumonia / idiopathic pulmonary fibrosis (UIP/IPF)
- 1. Kuhlman JE, Teigen C, Ren H et-al. Amiodarone pulmonary toxicity: CT findings in symptomatic patients. Radiology. 1990;177 (1): 121-5. Radiology (abstract) - Pubmed citation
- 2. Gefter WB, Epstein DM, Pietra GG et-al. Lung disease caused by amiodarone, a new antiarrythmic agent. Radiology. 1983;147 (2): 339-44. Radiology (abstract) - Pubmed citation
- 3. Marchiori E, Souza AS, Franquet T et-al. Diffuse high-attenuation pulmonary abnormalities: a pattern-oriented diagnostic approach on high-resolution CT. AJR Am J Roentgenol. 2005;184 (1): 273-82. AJR Am J Roentgenol (full text) - Pubmed citation
- 4. Rossi SE, Erasmus JJ, Mcadams HP et-al. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 20 (5): 1245-59. Radiographics (full text) - Pubmed citation
- 5. Collins J, Stern EJ. Chest radiology, the essentials. Lippincott Williams & Wilkins. (2007) ISBN:0781763142. Read it at Google Books - Find it at Amazon
- 6. Maffessanti M, Polverosi R, Dalpiaz G et-al. Diffuse lung diseases, clinical features, pathology, HRCT. Springer Verlag. (2006) ISBN:8847004292. Read it at Google Books - Find it at Amazon
- 7. Naidich DP, Srichai MB, Krinsky GA. Computed tomography and magnetic resonance of the thorax. Lippincott Williams & Wilkins. (2007) ISBN:0781757657. Read it at Google Books - Find it at Amazon
- 8. Chai JL, Patz EF. CT of the lung: patterns of calcification and other high-attenuation abnormalities. AJR Am J Roentgenol. 1994;162 (5): 1063-6. AJR Am J Roentgenol (abstract) - Pubmed citation
- 9. Poll LW, May P, Koch JA et-al. HRCT findings of amiodarone pulmonary toxicity: clinical and radiologic regression. J. Cardiovasc. Pharmacol. Ther. 2001;6 (3): 307-11. Pubmed citation