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Successful Treatment of Cardiac Sarcoidosis with Infliximab To the Editor: The clinical presentation of cardiac sarcoidosis may include arrhythmias, pericardial or valvular disease, congestive heart failure, or ventricular aneurysms1. Cardiac sarcoidosis is regarded as an indication for corticosteroid therapy2. Immunosuppressive agents are often combined with corticosteroids to reduce adverse effects. Anti-tumor necrosis factor-α (anti-TNF-α) therapy has been used to treat refractory sarcoidosis3, and TNF-α expression has been documented at sites where sarcoid granulomas are observed, and plays a critical role in granuloma formation4. Thus, anti-TNF-α therapy should result in suppression of disease manifestation and progression. The use of infliximab in patients with cardiac sarcoidosis has been described in 3 case reports. One patient had pericardial disease but the outcome of treatment was not included in the report5. A patient with severe ocular involvement developed a malignant arrhythmia and did not experience any further ectopy after infliximab treatment6. In another report, a patient with biopsy-proven sarcoidosis and multiple conduction blocks responded to infliximab therapy and no longer requires backup pacing7. We describe a patient with cardiac and muscle sarcoidosis who responded to infliximab. Cardiac status improved symptomatically and on magnetic resonance imaging (MRI). A 58-year-old woman was initially assessed in October 2003 for management of biopsy-proven sarcoidosis in the right gastrocnemius muscle. Her history included refractory atrial fibrillation treated with amiodarone, type 2 diabetes mellitus, coronary artery disease, hypertension, celiac disease, glaucoma, and esophageal reflux. Initially no therapy was indicated as she was asymptomatic. In April 2005, she reported episodes of tachycardia lasting up to 1 hour occurring once per week. An electrocardiogram showed first-degree atrioventricular block. She underwent a cardiac MRI, which showed normal cardiac chamber size and ejection fraction, without regional wall abnormalities. There was delayed enhancement of the mid-left ventricle cavity wall, particularly in the inferolateral segment, consistent with myocardial fibrosis of nonischemic origin and the diagnosis of cardiac sarcoidosis. Cardiac MRI markers of inflammation included an early enhancement ratio of 5.8 (normal < 4.0)8 and a T2 ratio for myocardial edema of 2.3 (normal < 2.0)9 (Figure 1).
She had developed extensive nodularity and pain in the extensor muscles of the forearms and calves. She was treated with prednisone 50 mg per day. Her muscle pain and palpitations improved, but blood glucose management deteriorated and she became markedly cushingoid. She also developed proximal muscle weakness and pain with distal paresthesias. These symptoms were initially ascribed to corticosteroid therapy and the prednisone was tapered to 10 mg per day. Nerve conduction studies, however, showed her symptoms to be due to diabetic amyotrophy and a peripheral neuropathy. Repeat cardiac MRI in March 2006 showed inferolateral wall abnormalities with loculated organizing pericardial fluid over the right ventricle. Infliximab therapy was initiated in May 2006 at 3 mg/kg at Weeks 0, 2, and 6, and then every 8 weeks. She continues to receive prednisone 5 mg per day (due to adrenal insufficiency). The nodularity in her extremities has improved clinically and on imaging. Repeat cardiac MRI showed improvement of the early enhancement ratio to 2.4 and the T2 ratio to 1.9, consistent with resolution of active inflammation and no progression in fibrosis (Figure 2).
We report this case to show that infliximab may be effective in the treatment of cardiac sarcoidosis in patients in whom corticosteroids are either ineffective or are associated with unacceptable adverse effects. We recognize that there may be issues concerning infliximab use in patients with heart failure, as increased mortality has been reported10. Such patients would require close monitoring if a decision is made to use infliximab. Further study of infliximab in treating sarcoidosis is also required to determine the appropriate dose and duration of therapy. A high index of suspicion is required to diagnose cardiac sarcoidosis. Preliminary investigations of patients with sarcoidosis should include a thorough evaluation of the cardiovascular system for conduction defects and valvular and pericardial abnormalities. Cardiac MRI holds promise in the diagnosis and monitoring of patients with cardiac sarcoidosis. However, the prognostic significance of changes in markers of myocardial inflammation identified on cardiac MRI remains to be determined. CHERYL BARNABE, MD, FRCPC, Resident, Division of Rheumatology, University of Calgary; JAMES McMEEKIN, MD, FRCPC, Clinical Professor of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary; ANDREW HOWARTH, MD, PhD, FRCPC, Assistant Professor, Libin Cardiovascular Institute of Alberta, University of Calgary; LIAM MARTIN, MB, MRCPI, FRCPC, Professor of Medicine, Division of Rheumatology, Department of Medicine, University of Calgary, Room 410, Heritage Medical Research Building, 3350 Hospital Drive NW, Calgary, Alberta T2N 2T9, Canada. Address reprint requests to Dr. Martin. E-mail: lmartin@ucalgary.ca 2. Chapelon-Abric C, de Zuttere D, Duhaut P, et al. Cardiac sarcoidosis: a retrospective study of 41 cases. Medicine Baltimore 2004;83:315-34. [MEDLINE] 3. Ulbricht KU, Stoll M, Bierwirth J, Witte T, Schmidt RE. Successful tumor necrosis factor alpha blockade treatment in therapy-resistant sarcoidosis. Arthritis Rheum 2003;48:3542-3. [MEDLINE] 4. Moller DR. Treatment of sarcoidosis -- from a basic science point of view. J Intern Med 2003;253:31-40. [MEDLINE] 5. Doty JD, Mazure JE, Judson MA. Treatment of sarcoidosis with infliximab. Chest 2005;127:1064-71. [MEDLINE] 6. Roberts SD, Wilkes DS, Burgett RA, Knox KS. Refractory sarcoidosis responding to infliximab. Chest 2003;124:2028-31. [MEDLINE] 7. Uthman I, Touma Z, Khoury M. Cardiac sarcoidosis responding to monotherapy with infliximab. Clin Rheumatol 2007;26:2001-3. [MEDLINE] 8. Walker PM, Marie PY, Danchin N, Bertrand A. Comparison of T1 estimation techniques in cardiac MRI. Magn Reson Imaging 1994;12:43-50. [MEDLINE] 9. Marie PY, Angioi M, Carteaux JP, et al. Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by black blood magnetic resonance imaging sequence. J Am Coll Cardiol 2001;37:825-31. [MEDLINE] 10. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate to severe heart failure: results of the Anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 2003;107:3133-40. [MEDLINE]
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