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Amiodarone Pulmonary Toxicity Presenting as a Solitary Lung Mass

1988; Elsevier BV; Volume: 93; Issue: 2 Linguagem: Inglês

10.1378/chest.93.2.425

1931-3543

Ron Arnon, Itamar Raz, T. CHAJEK‐SHAUL, Neville Berkman, Scott Fields, H. Bar‐On,

Pulmonary Hypertension Research and Treatments

Following treatment with amiodarone, a patient developed weight loss, fatigue and severe myopathy, without respiratory symptoms. A solitary lung infiltrate, impaired thyroid and liver function tests, and leukocytosis were evident Biopsies from the lung lesion, liver, and bone marrow revealed foam cells. All these signs and symptoms subsided following cessation of amiodarone therapy. It is demonstrated that amiodarone may induce a localized lung lesion rather than diffuse pulmonary disease. Following treatment with amiodarone, a patient developed weight loss, fatigue and severe myopathy, without respiratory symptoms. A solitary lung infiltrate, impaired thyroid and liver function tests, and leukocytosis were evident Biopsies from the lung lesion, liver, and bone marrow revealed foam cells. All these signs and symptoms subsided following cessation of amiodarone therapy. It is demonstrated that amiodarone may induce a localized lung lesion rather than diffuse pulmonary disease. Amiodarone has been widely used in the last 15 years for the treatment of cardiac arrhythmias.1Rosenbaum MB Chiale PA Halpern MS Nau GS Przybylski J Levi RJ et al.Clinical efficacy of amiodarone as an antiarrhythmic agent.Am J Cardiol. 1976; 38: 934-944Abstract Full Text PDF PubMed Scopus (455) Google Scholar One of its most serious side effects is pulmonary toxicity.2Rakita L Sobol SM Mostow ND Vrobel T Amiodarone pulmonary toxicity.Am Heart J. 1983; 106: 906-916Abstract Full Text PDF PubMed Scopus (121) Google Scholar Early symptoms in most patients include exertional dyspnea and non-productive cough. The characteristic x-ray film findings are diffuse bilateral alveolar and interstitial infiltrates.3Lok-wan Liu F Cohen RD Downar E Butarry JW Edelson JD Rebuck AS Amiodarone pulmonary toxicity: functional and ultrastructural evaluation.Thorax. 1986; 41: 100-105Crossref Scopus (60) Google Scholar We report a case of amiodarone pulmonary toxicity presenting as a solitary lung lesion. A 65-year-old man with ischemic heart disease, left ventricular aneurysm and congestive heart failure, underwent cardiac aneurysmectomy in 1968. In September 1983 he began to suffer from recurrent attacks of ventricular tachycardia and was treated with quinidine sulfate 1200 mg/day. In September 1984 recurrent bouts of ventricular tachycardia occurred and the quinidine was replaced by procainamide 1 g/day and amiodarone hydrochloride 400 mg/day. Two years later he was hospitalized due to severe fatigue, dysphagia and an 11 kg weight loss. On admission, he appeared cachectic. A grade 3/6 systolic murmur was heard over the apex. The lungs were clear. The liver was palpated 2 cm below the costal margin. Laboratory results revealed ESR of 110 mm in the first hour. The haemoglobin was 14.5 g/dl, white blood cell count 26 × 109/liter and platelet count 700 × 109/liter. The globulin was 4.5 g/dl and the albumin 3.4 g/dl. Protein electrophoresis revealed polyclonal elevation of gamma globulin. Thyroid function tests revealed T4 of 25 μg/dl, T3 of 146 ng/dl, T3 resin uptake of 60 percent and FTI of 20. TRH test results were compatible with thyrotoxicosis. The ANF was +2. Chest x-ray film (Fig 1) showed an infiltrative lesion in the right upper lobe. On chest CT scan (Fig 2) a round mass with irregular borders was seen. Bronchoscopy did not demonstrate any airway obstruction. Eight biopsies taken from the mass showed a mononuclear infiltration with scattered foam cells in the alveolar walls. Liver biopsy revealed chronic active hepatitis with fibrosis, and foam cells were found in the sinusoids. Bone marrow was hypercellular and contained some foam cells.Figure 2Chest CT scan on admission showing a round mass with irregular borders in the right upper lobe.View Large Image Figure ViewerDownload (PPT) During the following month the patient lost another 12 kg and became bedridden due to severe proximal myopathy. The treatment with procainamide was stopped without any improvement. Two weeks later, the treatment with amiodarone was replaced by mexiletene. Within several weeks, the patient improved tremendously. The dysphagia disappeared and he gained weight. The chest x-ray film showed clearing and the CT scan revealed nearly complete disappearance of the lung infiltrate (Fig 3). The white blood cell count decreased to 14 × 109/L. The platelet count decreased to 445 × 109/L. Liver function test results were all normal except for alkaline phosphatase of 155 IU and results of thyroid function tests were normal. Administration of amiodarone is associated with toxic effects in various organs, mainly lung, liver, thyroid, nerves, heart and skin. The side effects are mediated via inhibition of lysosomal enzymes resulting in the accumulation of phospholipids in foam cells.4KY Hostetler, MH Reasor, ER Walker, PJ Yazaki, BW Frazee. Role of phospholipase A inhibition in amiodarone pulmonary toxicity in rats. Biochim et Biophys Acta. 1986:400-05Google Scholar The main clinical manifestations of amiodarone-induced pulmonary disease include exertional dyspnea, non-productive cough and weight loss. The white blood count is often normal to moderately elevated, but may be markedly elevated.5Marchlinski FE Gansler TS Waxman HL Josephson ME Amiodarone pulmonary toxicity.Ann Intern Med. 1982; 97: 839-845Crossref PubMed Scopus (195) Google Scholar The erythrocyte sedimentation rate is elevated and there may be mild disturbance in liver function tests.5Marchlinski FE Gansler TS Waxman HL Josephson ME Amiodarone pulmonary toxicity.Ann Intern Med. 1982; 97: 839-845Crossref PubMed Scopus (195) Google Scholar Radiographic findings characteristically consist of diffuse or patchy bilateral alveolar infiltrates. Chest x-ray film findings suggest pulmonary edema, pneumonitis, or tuberculosis; rarely, pleural effusion or areas of pleural thickening may be found.2Rakita L Sobol SM Mostow ND Vrobel T Amiodarone pulmonary toxicity.Am Heart J. 1983; 106: 906-916Abstract Full Text PDF PubMed Scopus (121) Google Scholar, 6Lubbe WF Mercer CJ Amiodarone: its side effects, adverse reactions and dosage schedules.N Zealand Med J. 1982; 95: 502PubMed Google Scholar Amiodarone-induced pulmonary toxicity may be at least in part dose-related and most of the patients developed the infiltrates with a dose greater than 600 mg/day, usually after treatment with more than 130 g of the drug. The histologic finding is compatible with nonspecific pneumonitis with intra-alveolar accumulation of foamy macrophages and hyperplasia of type 2 pneumocytes. Our case represented a unique, outstanding clinical laboratory and roentgenographic finding. There was no symptom related to the lung disease. Instead, dysphagia, severe myopathy and severe weight loss were the prominent signs. Moreover, leukocytosis and thrombocytosis, together with normal bone marrow, protean clinical and laboratory manifestations compatible with the so-called paraneoplastic syndrome, were evident. The finding of a solitary lung lesion without any other lung involvement, to the best of our knowledge, has never been reported with amiodarone lung disease. Yet, the impaired thyroid function, liver disease, leukocytosis and lung infiltrate were suggestive of amiodarone toxicity, especially in view of the foam cells found in bone marrow, lung, and liver biopsy, and the relatively high dose of amiodarone used by the patient. Indeed, discontinuation of amiodarone resulted in clinical improvement with resolution of the lung mass. We have no explanation for the solitary, localized lung lesion. It is possible that a very early diagnosis of the lung involvement due to severe extrapulmonary symptoms resulted in a solitary finding in the lung. Alternatively, some prior localized vascular or inflammatory pulmonary process could have resulted in increased localized accumulation of the drug. The authors wish to thank Raphael Breuer, M.D., from the Pulmonary Unit at Hadassah University Hospital, for his assistance in the work-up of the case.