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Clinical History

A 55-year-old male a known case of diabetes and hypertension, presented with progressive dyspnea, swelling of bilateral lower limbs and fever for the past week. ECG was suggestive of non-ST segment elevation myocardial infarction (NSTEMI). Blood investigations revealed elevated total counts. His blood culture was positive for Acinetobacter Baumenii. He had a prior history of ischaemic heart disease (IHD) for which he had undergone a coronary artery bypass graft (CABG) and was on long-term amiodarone therapy.

Imaging Findings

Serial chest radiographs revealed inhomogeneous opacities in the right mid zone, bilateral basal zones, and left pleural effusion.

High-Resolution Computed Tomography (HRCT) of the chest was performed on a 128-slice CT scanner, which demonstrated high attenuation dense consolidation involving the right upper lobe, superior and posterior segments of the right lower lobe, left apicoposterior segment and left lower lobe. There was also the presence of diffuse hyperattenuation of the liver with a mean HU (Hounsfield unit) of 93-95.

These findings were most consistent with Amiodarone toxicity.

Subsegmental consolidation with surrounding ground glass opacities and septal thickening were also observed in bilateral lung fields. Multiple enlarged mediastinal lymph nodes and bilateral moderate pleural effusion were evidenced.  

These findings were consistent with infectious etiology.

Cardiomegaly with normal myocardial density was also noted.

Discussion

Background

Amiodarone lung is an interstitial lung disease that occurs in patients on amiodarone therapy. Amiodarone is an iodinated benzofuran derivative that is used to treat ventricular and supraventricular tachyarrhythmias. Pulmonary toxicity is one of the most serious adverse effects of amiodarone [1].

Several forms of the pulmonary disease occur among patients treated with amiodarone, including interstitial pneumonitis, eosinophilic pneumonia, organizing pneumonia, acute respiratory distress syndrome (ARDS), diffuse alveolar haemorrhage (DAH), pulmonary nodules, and (rarely) pleural effusion [2].

Interstitial pneumonitis usually occurs when the dose of amiodarone exceeds 400 mg per day for 2 months or more, or 200mg/day for more than 2 years [3].

Pathogenesis —. Two major hypotheses have been suggested, a direct toxic injury to lung cells and an indirect immunologic reaction. The mechanism for direct injury involves phospholipid accumulation. Although the mechanism of indirect injury is poorly understood, CD8 lymphocytosis, T cell injury and increased IgM, consistent with hypersensitivity reaction are postulated as a mechanism. [4]

Clinical Perspective

Exertional dyspnoea is usually the dominant symptom. Low-grade fever, anorexia and muscle weakness have also been reported [5].

Risk factors for pulmonary toxicity include a high cumulative dose, duration of therapy exceeding two months, pre-existing lung diseases, elderly age, surgery, and pulmonary angiography [6-10].

Lung function tests typically show a restrictive pattern. A reduction in diffusing capacity for carbon monoxide (DLCO) of more than 15% is a reliable indicator for amiodarone-induced pulmonary toxicity, with high sensitivity and specificity. Lung biopsy, alveolar cytogram and bronchoalveolar lavage are used to formulate the diagnosis [6].

Imaging Perspective

Chest radiography usually shows peripheral consolidation. High-resolution CT (HRCT) is the imaging modality of choice with typically bilateral and asymmetrical involvement of predominantly the lung bases. Findings include consolidation, patchy ground-glass opacities, and reticulonodular opacities. In addition, the liver (80% of cases) and sometimes the heart (20%) show high attenuation [11].

Outcome

The preliminary therapeutic management involves the replacement of Amiodarone with another anti-arrhythmic agent, followed by corticosteroid therapy. All patients taking amiodarone should perform a chest radiograph and liver function tests before starting therapy and should be followed up and monitored appropriately [12]. Our patient, unfortunately, succumbed to septic shock and congestive cardiac failure shortly after admission before the amiodarone toxicity could be addressed.

Take Home Message / Teaching Points

In conclusion, diagnosis of Amiodarone pulmonary toxicity is challenging owing to the multiform clinical aspects of this complication. We must consider it among the differential diagnoses in patients undergoing amiodarone therapy who present with progressive or acute respiratory symptoms or who present with radiological interstitial lesions in the absence of symptoms. With a prompt diagnosis, appropriate therapeutic management can be started to achieve a favourable outcome [12].