Discussion :
Amiodarone is one of the most commonly prescribed medications for the treatment of life-threatening ventricular arrhythmia.
Treatment with amiodarone has various known neurologic, ophthalmic, bone marrow
cutaneous, thyroid, hepatic, and pulmonary side effects.
Pulmonary toxicity is among the most serious adverse effects of amiodarone.
Interstitial pneumonitis, eosinophilic pneumonia, organizing pneumonia, acute respiratory distress syndrome, diffuse alveolar hemorrhage, lung mass or consolidation, and rarely pleural effusion can occur in amiodarone toxicity. [5]
Among these various types of pulmonary adverse effects, interstitial pneumonitis is the most common presentation after two or more months of treatment, particularly in individuals over 60 years old with preexisting lung disease and whose daily amiodarone dosage exceeds 400 mg could occur.
Most of these effects occur due to the accumulation of amiodarone metabolite so it rarely manifests in the early stage of administration like in our case.
Interstitial pneumonitis due to amiodarone toxicity is characterized by the sudden onset of nonproductive cough, dyspnea, and less likely malaise and fever could be seen. Our case also presented with abrupt onset of mentioned symptoms which could not be explained by pneumonia or pulmonary edema.
Other rare microorganisms such as fungal infection in immune-competent individuals were also unexpected.
A negative autoimmune panel was also more compatible with amiodarone pneumonitis diagnosis.
When the clinical diagnosis of amiodarone-induced interstitial pneumonitis is questionable, flexible bronchoscopy with (BAL) is done. This procedure is more beneficial in excluding other differential diagnoses.
Despite chronic amiodarone pneumonitis which lipoid cells are more likely to be seen in pathology in acute amiodarone pneumonitis BAL investigation, alveolar hemorrhage is more probable to be detected. [6]
So we can conclude that the absence of lipoid macrophages in BAL is not supported by excluding the diagnosis of amiodarone pneumonitis and clinical and radiologic features such as abrupt worsening dyspnea and cough, administering a high dosage of amiodarone, Exclusion of lung infection and hypersensitivity pneumonitis, and New ground glass on chest radiography are key features for diagnosis of early amiodarone pneumonitis.
Even if our patient had the chance for the BAL it is not the gold standard for diagnosing amiodarone pneumonitis and as mentioned in previous studies only 50 % of patients with amiodarone lung injury manifest with lipoid macrophages in BAL, on the other hand these lipoid cells could be seen in non-toxic patients who are taking amiodarone. [7]
Previous studies also mentioned that the route of administration might be another factor contributing to acute amiodarone pneumonitis like our reported case, patients who received amiodarone 150mg IV in less than an hour, followed by exceeding dose of 1000mg IV in a day, Amiodarone metabolites can accumulate more rapidly in lungs. [8]
On the other hand, some studies believe that acute oxidant lung injury also plays a major role in amiodarone lung injury in the acute phase.[9]
Treatment of amiodarone pneumonitis consists primarily of cessation of amiodarone and, in severe cases, initiating systemic glucocorticoids (prednisone 40 to 60 mg per day or methylprednisolone 500 to 1000 mg/day intravenously in severe cases) is recommended. [10]
It is reasonable not to administer antiarrhythmic with similar structure in amiodarone lung injuries such as Dronedarone and a personalized approach for each patient is recommended especially in the elderly patient with underlying lung diseases such as previous severe COVID-19 which lead to permanent lung injury. [11-15]
Acute amiodarone-related interstitial pneumonitis is a rare and more aggressive form of the disease, most often occurring in critically ill and post-surgery patients. Acute respiratory distress syndrome (ARDS ) and alveolar hemorrhage are the most common pattern of amiodarone pneumonitis, our case also encountered ARDS despite corticosteroid treatment. [16 17]
Conclusion :
In brief, our challenging case illustrates the difficulties in the diagnosis of acute amiodarone pneumonitis which should be considered as a differential diagnosis of ARDS causes especially in patients whose other related diagnoses are excluded and who had a history of receiving a high dosage of intravenous amiodarone.