Anne Janin MD, PhD ERM 0220, Department of Pathology Hospital Saint Louis 75475 Paris, France Reply to the letter of Dr A. Janin To the Editor, We thank Dr Janin for her interest in our paper on eosinophilic myocarditis in idiopathic hypereosinophilic syndrome (HES) [1]. In the manuscript, we analyzed 2 endomyocardial biopsies taken before and after steroid therapy in a young patient with cardiac involvement due to HES. In the first biopsy, we found a prominent eosinophilic infiltration, areas of myocardial necrosis, and evidence of apoptotic cell death involving myocytes and scattered blood vessel walls. In the second biopsy, after 1 year of steroid therapy, the cellular inflammatory component was absent, and the histological picture dramatically changed into a severe myocardiosclerosis, which we mainly ascribed to a postnecrotic reparative process. The main purpose of our paper was to show that both necrotic and apoptotic processes, most likely induced by infiltrating eosinophils, could have contributed to myocardial cell death [1]. Dr Janin suggests that myocardial interstitial fibrosis might result not only from a reparative process induced by necrosis but also from the direct local effects of eosinophilic cationic proteins. We agree with Dr Janin’s comment; however, we believe that the postnecrotic mechanism quantitatively contributed more than the direct local one in promoting myocardial fibrosis. In the first endomyocardial biopsy (performed 8 months after the onset of HES), despite the presence of a remarkable eosinophilic infiltration, evidence of eosinophilic degranulation, and areas of necrosis, there were no signs of interstitial fibrosis. This was only evident in the second biopsy, when necrosis had disappeared. It has been well established that myocardial necrosis, independently of the underlying cause (eg, ischemic, inflammatory, or infectious diseases), is a major determinant of the development of myocardial sclerosis [2-4]. A limitation of our study must be acknowledged: only small amounts of endomyocardial tissue were available for the histological analysis, and unfortunately, autopsy was not performed; thus, we could not investigate further aspects of the disease. In conclusion, we agree with the view that a direct local effect of eosinophilic products on myocardial tissue may be a cause of interstitial fibrosis, but we suggest that in conditions characterized by large areas of necrosis, a postnecrotic reparative process might be the quantitatively predominant mechanism. References [1] Corradi D, Vaglio A, Maestri R, et al. Eosinophilic myocarditis in a patient with idiopathic hypereosinophilic syndrome: insights into mechanisms of myocardial cell death. Hum Pathol 2004;9:1160- 3. [2] Anversa P, Leri A, Beltrami CA, et al. Myocyte death and growth in the failing heart. Lab Invest 1998;7:767 - 86. [3] Fenoglio Jr JJ, Ursell PC, Kellogg CF, et al. Diagnosis and classification of myocarditis by endomyocardial biopsy. N Engl J Med 1983;1:12 - 8. [4] Leon JS, Wang K, Engman DM. Captopril ameliorates myocarditis in acute experimental Chagas disease. Circulation 2003;17:2264 - 9. Domenico Corradi MD Roberta Maestri PhD Pathology Section Department of Pathology and Laboratory Medicine University of Parma 43100 Parma, Italy Augusto Vaglio MD Carlo Buzio MD Department of Clinical Medicine Nephrology and Health Science University of Parma 43100 Parma, Italy Correspondence 593