Amiodarone lung

Amiodarone lung is an interstitialrefers to the various manifestations of amiodarone toxicity in the lung disease including acute lung injuryseen in patients being administered the cardiac drug amiodarone, fibrosis, nodules, haemorrhage and can manifest in a number of histopathologic patternspleural disease.

Epidemiology

Amiodarone is a vasodilator which was found to be an effective anti-arrhythmic agent and is consequently in common usage. The reported prevalence of pulmonary toxicity in patients receiving amiodarone is ~10% (range 2-18%) ⁸.

Patients are usually elderlyToxicity is related to cumulative dose and have been exposed to amiodarone, usually fortypically occurs after at least sixtwo months, although there is a poor correlation with dosage on 400 mg/day or cumulativetwo years on 200 mg/day ¹¹. The minimum effective dose should be used and baseline pulmonary function assessed.

Risk factors include ⁶¹¹:

• dose and duration of treatment longer than two months

• increasing age over 60 years

• daily dose >400 mgmale

• antecedent lung disease or surgeryethnicity, e.g. Japanese

• prior angiographic investigationspre-existing lung disease

• cardiothoracic surgery, e.g. pneumonectomy

• high-dose supplemental oxygen

• pulmonary angiography.

Clinical presentation

Patients typically present with exertionalprogressive dyspnoea as the dominant symptom. Low grade fever, dry cough, malaise, anorexia, pleurisy and muscle weakness have also been reported ^{2, 11}. In approximately a third of patients, the 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 historyOpen lung biopsy should be avoided as toxicity may be exacerbated and radiographic features suffice to guide therapythese patients may already have compromised cardiopulmonary function ¹¹.

Pathology

Amiodarone hydrochloride is a tri-iodinated antiarrhythmic, comprised of 37% iodine by weight, which accumulates in type II pneumocytes ^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 and no evidence of toxicity.

Radiographic features

There are two main patterns of involvement, which may coexist.

1. multiple peripheral areas of dense air space opacity: most common ⁵

2. interstitial fibrosis

Plain radiograph

Appearances on chest radiography are non-specific, typically consisting of:

• peripheral areas of consolidation

• upper lobe predominance

• underlying interstitial disease

CT

As with other pulmonary diseases 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

  • peripheral

  • often hyperdense ^1,6 cf. muscle (on account of the iodine)

• patchy ground-glass opacities

• coexisting interstitial disease

  • reticulonodular opacities

In addition, the liver (80% of cases) and sometimes the heart (20%) are high density ⁶. However, high hepatic and splenic attenuation are also seen in patients exposed to amiodarone in the absence of drug toxicity. 

Nuclear medicine

• gallium-67 scan: sensitive but non-specific

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.

Differential diagnosis

Imaging differential considerations include:

• pulmonary eosinophilia

  • 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