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Amiodarone Pulmonary Toxicity: Clinical, Radiologic, and Pathologic Correlations

Amiodarone Pulmonary Toxicity: Clinical, Radiologic, and Pathologic Correlations Abstract • We have studied 15 patients with amiodarone pulmonary toxicity and compared them with five amiodarone patients without evidence of toxic effect. Six of 15 patients who had toxic reactions presented with an acute illness that resembled an infectious disease. While diffuse interstitial disease was frequent on chest roentgenogram, seven of 15 had airspace opacities, and five had well-localized infiltrates. Physiologic changes were not uniformly found. An interstitial pneumonia with foamy alveolar macrophages was the most common pathologic finding. Foamy macrophages were also present in three of five nontoxic patients. Three of three patients who had toxic reactions, and two of five patients without toxic reactions had lamellated inclusion bodies by electron microscopy. We conclude that all features of amiodarone toxicity are protean, and it may mimic infectious diseases. While pathologic changes are often characteristic, neither foamy alveolar macrophages nor lamellated cytoplasmic inclusions reliably distinguish toxic from nontoxic patients. (Arch Intern Med 1987;147:50-55) References 1. Marcus FI, Fontaine GH, Frank R, et al: Clinical pharmacology and therapeutic applications of the antiarrhythmic agent, amiodarone. Am Heart J 1981;101:480-493.Crossref 2. Rosenbaum MB, Chiale PA, Halpern MS, et al: Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol 1976;38:934-944.Crossref 3. Waxman HL, Groh WC, Marchlinski FE, et al: Amiodarone for control of sustained ventricular tachyarrhythmia: Clinical and electrophysiologic effects in 51 patients. Am J Cardiol 1982;50:1066-1074.Crossref 4. Vos AK, van Ramshorst AGS, Grosfeld JCM, et al: A peculiar cutaneous pigmentation from Cordarone. Dermatologica 1972;145:297-303.Crossref 5. Delage C, Lagacé R, Huard J: Pseudocyanotic pigmentation of the skin induced by amiodarone: A light and electron microscopic study. Can Med Assoc J 1975;112:1205-1208. 6. D'Amico DJ, Kenyon KR, Ruskin JN: Amiodarone keratopathy: Druginduced lipid storage disease. Arch Ophthalmol 1981;99:275-261.Crossref 7. Greene HL, Graham EL, Werner JA, et al: Toxic and therapeutic effects of amiodarone in the treatment of cardiac arrhythmias. J Am Coll Cardiol 1983;2:1114-1128.Crossref 8. Harris L, McKenna WJ, Rowland E, et al: Side effects of long-term amiodarone therapy. Circulation 1983;67:45-51.Crossref 9. Burger A, Dinichert D, Nicod P, et al: Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. J Clin Invest 1976;58:255-259.Crossref 10. Saal AK, Werner JA, Greene HL, et al: Effect of amiodarone on serum quinidine and procainamide levels. Am J Cardiol 1984;53:1264-1267.Crossref 11. Oetgen WJ, Sobol SM, Tri TB, et al: Amiodarone-digoxin interaction: Clinical and experimental observations. Chest 1984;86:75-79.Crossref 12. McKenna WJ, Rowland E, Krikler DM: Amiodarone: The experience of the past decade. Br Med J 1983;287:1654-1656.Crossref 13. McGovern B, Garan H, Ruskin JN: Serious adverse effects of amiodarone. Clin Cardiol 1984;7:131-137.Crossref 14. Kory RC, Callahan R, Boren HG, et al: The Veterans Administration-Army cooperative study of pulmonary function: I. Clinical spirometry in normal men. Am J Med 1961;30:243-258.Crossref 15. Colgan T, Simon GT, Kay JM, et al: Amiodarone pulmonary toxicity. Ultrastruct Pathol 1984;6:199-207.Crossref 16. Rotmensch HH, Liron M, Tupilski M, et al: Possible association of pneumonitis with amiodarone therapy. Am Heart J 1980;100:412-413.Crossref 17. Sobol SM, Rakita L: Pneumonitis and pulmonary fibrosis associated with amiodarone treatment: A possible complication of a new antiarrhythmic drug. Circulation 1982;65:819-824.Crossref 18. Marchlinski FE, Gansler TS, Waxman HL, et al: Amiodarone pulmonary toxicity. Ann Intern Med 1982;97:839-845.Crossref 19. Gefter WB, Epstein DM, Pietra GG, et al: Lung disease caused by amiodarone, a new antiarrhythmic agent. Radiology 1983;147:339-344.Crossref 20. Darmanata J, van Zandwijk N, Duren DR, et al: Amiodarone pneumonitis: Three further cases with a review of published reports. Thorax 1984;39:57-64.Crossref 21. Kudenchuk PJ, Pierson DJ, Greene HL, et al: Prospective evaluation of amiodarone pulmonary toxicity. Chest 1984;86:541-548.Crossref 22. Raeder EA, Podrid PJ, Lown B: Side effects and complications of amiodarone therapy. Am Heart J 1985;109:975-983.Crossref 23. Rotmensch HH, Belhassen B, Swanson BN, et al: Steady-state serum amiodarone concentrations: Relationships with antiarrhythmic efficacy and toxicity. Ann Intern Med 1984;101:462-469.Crossref 24. Olson LK, Forrest JV, Friedman PJ, et al: Pneumonitis after amiodarone therapy. Radiology 1984;150:327-330.Crossref 25. Hunt D, Kertes P, Venables S, et al: Exacerbation of bronchial asthma following treatment with amiodarone: Demonstration of an antiadrenergic effect in vitro. Chest 1984;86:492-494.Crossref 26. Van Zandwijk N, Darmanata JI, Duren DR, et al: Amiodarone pneumonitis. Eur J Respir Dis 1983;64:313-317. 27. Pollak PT, Sami M: Acute necrotizing pneumonitis and hyperglycemia after amiodarone therapy. Am J Med 1984;76:935-939.Crossref 28. Farmakis M, Litos G, Melissinos C, et al: Diffuse interstitial pulmonary disease during amiodarone treatment. Arzneimittelforsch 1984;34: 223-225. 29. Jirik FP, Henning H, Huckell VF, et al: Diffuse alveolar damage syndrome associated with amiodarone therapy. Can Med Assoc J 1983;128: 1192-1195. 30. Riley SA, Williams SE, Cooke NJ: Alveolitis after treatment with amiodarone. Br Med J 1982;284:161-162.Crossref 31. Zaher C, Hamer A, Peter T, et al: Low-dose steroid therapy for prophylaxis of amiodarone-induced pulmonary infiltrates. N Engl J Med 1983;308:779.Crossref 32. Dan M, Greif J: Amiodarone and pneumonitis. Ann Intern Med 1983;99:732.Crossref 33. Joelson J, Kluger J, Cole S, et al: Possible recurrence of amiodarone pulmonary toxicity following corticosteroid therapy. Chest 1984;85:284-286.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Amiodarone Pulmonary Toxicity: Clinical, Radiologic, and Pathologic Correlations

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Publisher
American Medical Association
Copyright
Copyright © 1987 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1987.00370010054014
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Abstract

Abstract • We have studied 15 patients with amiodarone pulmonary toxicity and compared them with five amiodarone patients without evidence of toxic effect. Six of 15 patients who had toxic reactions presented with an acute illness that resembled an infectious disease. While diffuse interstitial disease was frequent on chest roentgenogram, seven of 15 had airspace opacities, and five had well-localized infiltrates. Physiologic changes were not uniformly found. An interstitial pneumonia with foamy alveolar macrophages was the most common pathologic finding. Foamy macrophages were also present in three of five nontoxic patients. Three of three patients who had toxic reactions, and two of five patients without toxic reactions had lamellated inclusion bodies by electron microscopy. We conclude that all features of amiodarone toxicity are protean, and it may mimic infectious diseases. While pathologic changes are often characteristic, neither foamy alveolar macrophages nor lamellated cytoplasmic inclusions reliably distinguish toxic from nontoxic patients. (Arch Intern Med 1987;147:50-55) References 1. Marcus FI, Fontaine GH, Frank R, et al: Clinical pharmacology and therapeutic applications of the antiarrhythmic agent, amiodarone. Am Heart J 1981;101:480-493.Crossref 2. Rosenbaum MB, Chiale PA, Halpern MS, et al: Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol 1976;38:934-944.Crossref 3. Waxman HL, Groh WC, Marchlinski FE, et al: Amiodarone for control of sustained ventricular tachyarrhythmia: Clinical and electrophysiologic effects in 51 patients. Am J Cardiol 1982;50:1066-1074.Crossref 4. Vos AK, van Ramshorst AGS, Grosfeld JCM, et al: A peculiar cutaneous pigmentation from Cordarone. Dermatologica 1972;145:297-303.Crossref 5. Delage C, Lagacé R, Huard J: Pseudocyanotic pigmentation of the skin induced by amiodarone: A light and electron microscopic study. Can Med Assoc J 1975;112:1205-1208. 6. D'Amico DJ, Kenyon KR, Ruskin JN: Amiodarone keratopathy: Druginduced lipid storage disease. Arch Ophthalmol 1981;99:275-261.Crossref 7. Greene HL, Graham EL, Werner JA, et al: Toxic and therapeutic effects of amiodarone in the treatment of cardiac arrhythmias. J Am Coll Cardiol 1983;2:1114-1128.Crossref 8. Harris L, McKenna WJ, Rowland E, et al: Side effects of long-term amiodarone therapy. Circulation 1983;67:45-51.Crossref 9. Burger A, Dinichert D, Nicod P, et al: Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. J Clin Invest 1976;58:255-259.Crossref 10. Saal AK, Werner JA, Greene HL, et al: Effect of amiodarone on serum quinidine and procainamide levels. Am J Cardiol 1984;53:1264-1267.Crossref 11. Oetgen WJ, Sobol SM, Tri TB, et al: Amiodarone-digoxin interaction: Clinical and experimental observations. Chest 1984;86:75-79.Crossref 12. McKenna WJ, Rowland E, Krikler DM: Amiodarone: The experience of the past decade. Br Med J 1983;287:1654-1656.Crossref 13. McGovern B, Garan H, Ruskin JN: Serious adverse effects of amiodarone. Clin Cardiol 1984;7:131-137.Crossref 14. Kory RC, Callahan R, Boren HG, et al: The Veterans Administration-Army cooperative study of pulmonary function: I. Clinical spirometry in normal men. Am J Med 1961;30:243-258.Crossref 15. Colgan T, Simon GT, Kay JM, et al: Amiodarone pulmonary toxicity. Ultrastruct Pathol 1984;6:199-207.Crossref 16. Rotmensch HH, Liron M, Tupilski M, et al: Possible association of pneumonitis with amiodarone therapy. Am Heart J 1980;100:412-413.Crossref 17. Sobol SM, Rakita L: Pneumonitis and pulmonary fibrosis associated with amiodarone treatment: A possible complication of a new antiarrhythmic drug. Circulation 1982;65:819-824.Crossref 18. Marchlinski FE, Gansler TS, Waxman HL, et al: Amiodarone pulmonary toxicity. Ann Intern Med 1982;97:839-845.Crossref 19. Gefter WB, Epstein DM, Pietra GG, et al: Lung disease caused by amiodarone, a new antiarrhythmic agent. Radiology 1983;147:339-344.Crossref 20. Darmanata J, van Zandwijk N, Duren DR, et al: Amiodarone pneumonitis: Three further cases with a review of published reports. Thorax 1984;39:57-64.Crossref 21. Kudenchuk PJ, Pierson DJ, Greene HL, et al: Prospective evaluation of amiodarone pulmonary toxicity. Chest 1984;86:541-548.Crossref 22. Raeder EA, Podrid PJ, Lown B: Side effects and complications of amiodarone therapy. Am Heart J 1985;109:975-983.Crossref 23. Rotmensch HH, Belhassen B, Swanson BN, et al: Steady-state serum amiodarone concentrations: Relationships with antiarrhythmic efficacy and toxicity. Ann Intern Med 1984;101:462-469.Crossref 24. Olson LK, Forrest JV, Friedman PJ, et al: Pneumonitis after amiodarone therapy. Radiology 1984;150:327-330.Crossref 25. Hunt D, Kertes P, Venables S, et al: Exacerbation of bronchial asthma following treatment with amiodarone: Demonstration of an antiadrenergic effect in vitro. Chest 1984;86:492-494.Crossref 26. Van Zandwijk N, Darmanata JI, Duren DR, et al: Amiodarone pneumonitis. Eur J Respir Dis 1983;64:313-317. 27. Pollak PT, Sami M: Acute necrotizing pneumonitis and hyperglycemia after amiodarone therapy. Am J Med 1984;76:935-939.Crossref 28. Farmakis M, Litos G, Melissinos C, et al: Diffuse interstitial pulmonary disease during amiodarone treatment. Arzneimittelforsch 1984;34: 223-225. 29. Jirik FP, Henning H, Huckell VF, et al: Diffuse alveolar damage syndrome associated with amiodarone therapy. Can Med Assoc J 1983;128: 1192-1195. 30. Riley SA, Williams SE, Cooke NJ: Alveolitis after treatment with amiodarone. Br Med J 1982;284:161-162.Crossref 31. Zaher C, Hamer A, Peter T, et al: Low-dose steroid therapy for prophylaxis of amiodarone-induced pulmonary infiltrates. N Engl J Med 1983;308:779.Crossref 32. Dan M, Greif J: Amiodarone and pneumonitis. Ann Intern Med 1983;99:732.Crossref 33. Joelson J, Kluger J, Cole S, et al: Possible recurrence of amiodarone pulmonary toxicity following corticosteroid therapy. Chest 1984;85:284-286.Crossref

Journal

Archives of Internal Medicine – American Medical Association

Published: Jan 1, 1987

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