031. Amiodarone induced pulmonary toxicity (APT)

Abstract: Male patient aged 68 was transferred to ED due to aggravation of dyspnea that started 10 days before. According to the medical history, he is a coronary patient and an active smoker (40 p/y) who was subject to Coronary artery bypass surgery (CABG) 12 months ago. His medication has included since one year acetylsalicylic acid (100 mg), clopidogrel (75 mg) and amiodarone (200 mg) on a daily basis. The clinical examination detected crackles on both lungs, desaturation (sat 78%, FiO₂: 21%), pH: 7.42, pCO₂=34.6 mmHg, pO₂=45.6 mmHg, HCO₃⁻: 23 mmol/L, bilateral diffuse infiltrates on the chest X-ray and restrictive pattern on PFTs (FVC: 67%, FEV₁: 71%, FEV₁%: 86.8%, DLCO: 59%). The patient was afebrile with negative markers of infection and we decided immediate discontinuation of amiodarone. The chest HRCT showed patchy loci of organizing pneumonia, traction bronchiectases and extended interstitial fibrosis, imaging compatible with NSIP. Bronchoscopy with BAL revealed a high percentage of lymphocytes (52%), specifically T cytotoxic lymphocytes (CD3⁺,CD8⁺), a relatively large percentage of neutrophils (48%) and a very low (0.23) TH/TC ratio in BAL, almost seven times lower than the blood ratio (1.56). We prescribed Oxygen therapy (LTOT) until follow up 20 days later. At follow up there was clear improvement in SpO₂, infiltrates and clinical symptoms. The APT is severe and potentially life-threatening while the percentages of incidence ranging between 5% and 13%. Risk factors include a daily dose >400 mg, treatment longer than two months, age over 60 years, antecedent lung disease or surgery and prior angiographic investigations. The most common clinical presentation of chronic APT is a subacute illness characterized by progressive dyspnea on exertion, nonproductive cough and occasionally malaise, weight loss and low-grade fever. HRCT findings include ground glass opacities, interstitial, alveolar or mixed infiltrates, lung nodules or ‘masses’ and pleural thickening. Pulmonary function tests usually reveal low volumes and a restrictive pattern, with a reduction in DLCO of 15-20%. Classic findings on histopathological examination of lung tissues are: foamy macrophages, reactive type II pneumocytes, and endothelial cells with cytoplasmic lamellar inclusions containing phospholipids. Regarding the treatment, if disease extent is limited, discontinuation of amiodarone may be sufficient. Corticosteroids should be given to patients who show substantial involvement on imaging or hypoxemia. Mortality is approximately 10% for those who develop pneumonitis, 20-30% for those admitted to hospital, and 50% for those who develop ARDS.

Keywords:Lung disease; spirometry; amiodarone