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Endocarditis and extrinsic coronary compression
Letters to the Editor
The second patient was a 39-yearold man who was admitted because of a fever of 39°C that lasted 1 month, fatigue, and weight loss of 3 kg. Clinical findings on admission included hepatomegaly and gross splenomegaly. The laboratory workup showed a hemoglobin level of 9.4 g/dL, a white blood cell count of 2700/L, a platelet count of 136,000/L, a Creactive protein level of 227 mg/L, and polyclonal elevation of gamma globulins (4.1 g/dL). As with the imaging studies for our first patient, cultures and serology did not yield significant findings. Bone marrow aspiration showed increased number of macrophages with hemophagocytosis (⬎10%) and Leishmania amastigotes both intra- and extracellularly. Leishmania antibodies were positive at a titer of 1/320. Liposomal amphotericin B was administered (total dose, 20 mg/kg), with prompt clinical and laboratory response. The association of visceral leishmaniasis and hemophagocytic syndrome is rare. A MEDLINE search yielded 16 articles reporting 27 patients with the association. Only 3 of these patients were adults (4 – 6); age was not provided on 4 patients. Our patients fulfilled the diagnostic criteria for primary hemophagocytic syndrome (7), which have also been applied to reactive hemophagocytic syndrome, and therefore could be classified as hemophagocytic syndrome reactive to leishmaniasis. In the reactive form of the syndrome, underlying disease may cause a dysfunction of cellular cytotoxicity with lymphocyte hyperactivation (8). A Th1-Th2 imbalance in favor of Th1, and an inappropriate activation of cytotoxic CD8 T cells, have been suggested. Activated T cells stimulate the phagocytic activity and proliferation of macrophages, releasing cytokines such as tumor necrosis factor–␣, interleukin (IL)-1, IL-6, and macrophage colony-stimulating factor, which are responsible for the clinical manifestations of hemophagocytic syndrome (8). 440
October 1, 2002
In visceral leishmaniasis, active disease is associated with a Th2 response, whereas a Th1 response is necessary for the resolution of infection (9). Other nonviral infections, which have been associated with reactive hemophagocytic syndrome (e.g., Mycobacterium tuberculosis and Salmonella typhi), also elicit a Th1 response (3). Therefore, an unregulated or inappropriate Th1 response in visceral leishmaniasis may have caused the hemophagocytic syndrome in our patients. Theano Kontopoulou, MD, PhD George Tsaousis, MD Emmanouel Vaidakis, MD Panagiotis Fanourgiakis, MD Elias Michalakeas, MD Evangelia Trigoni, MD Michael Samarkos, MD, MSc Fifth Department of Internal Medicine and Hematology Department Evangelismos Hospital Athens, Greece 1. Jaffe R. The histiocytoses. Clin Lab Med. 1999;19:135–155. 2. Favara BE, Feller AC, Pauli M. Contemporary classification of histiocytic disorders. The WHO committee on histiocytic/reticulum cell proliferation. The Reclassification Group of the Histiocyte Society. Med Pediatr Oncol. 1997;29:157–166. 3. Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000;6:601– 608. 4. Matzner Y, Bear A, Beeri E, et al. Systemic leishmaniasis mimicking malignant histiocytosis. Cancer. 1979;43:398 –402. 5. Bessis D, Sotto A, Taib J, Ciurana AJ. Visceral leishmaniasis with hemophagocytic syndrome. Clin Infect Dis. 1993;17:611. 6. Rodriguez-Cuartero A, Salas-Galan A, Perez-Galvez MN, Perez-Blanco FZ. Haemophagocytic visceral kala-azar [letter]. Infection. 1991;3:184. 7. Elinder G, Hender JI, Ost A, and the FHL Study Group of the Histiocyte Society. Diagnostic guidelines for hemophagocytic histiocytosis. Semin Oncol. 1991;18:29 –33. 8. Janka G, Imasuku S, Elinder G, et al. Infection and malignancy associated hemophagocytic syndromes. Hematol Oncol Clin North Am. 1998;12:435–444. 9. Scharton-Kersten T, Scott P. The role of innate immune responses in Th1 cell development following Leishmania major infection. J Leukocyte Biol. 1995;57:515–522.
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113
ENDOCARDITIS AND EXTRINSIC CORONARY COMPRESSION To the Editor: Occlusion of the coronary arteries is almost invariably a sequel to atherosclerosis and associated plaque rupture. However, other causes should be considered in patients with typical symptoms and electrocardiographic (ECG) signs who do not have evidence of atherosclerosis. In addition to coronary atherosclerosis, other conditions such as syphilis, rheumatic fever, infectious diseases, vasculitis, coronary embolism, coronary aneurysms, traumatic lesions, congenital conditions, thromboangiitis obliterans, or medial calcification involving fibroplastic proliferation may be present (1). These conditions, however, seemed unlikely in our patient, a 43-year-old woman with a previous diagnosis of multiple sclerosis. Three weeks before admission, the patient developed fever, night sweats, cough, and progressive dyspnea, which did not resolve with antibiotic treatment. On admission, bilateral pneumonia and pleural effusions were observed. Physical examination revealed tachycardia, bibasilar rales, and a diastolic murmur. Echocardiography revealed aortic valvular vegetations, and she was referred to the cardiology intensive care unit. Bacterial endocarditis was suspected, and a blood culture revealed coagulasepositive Staphylococcus aureus. Despite treatment with penicillin G, gentamicin, and vancomycin, her condition did not improve. Her aortic insufficiency worsened. Eight days after admission, she developed substernal chest pain and showed acute signs of ischemia. Troponin T and creatine kinase-MB con-centrations were elevated. During coronary arteriography, the left main coronary artery showing a smooth, concentric narrowing was observed in the oblique view (Figure,
Letters to the Editor
Figure. Panel A. Coronary arteriogram showing smooth, concentric narrowing of the left main coronary artery (LCA) and abrupt closure of the left circumflex (LCX) (arrow). Panel B. Magnetic resonance tomography in a long-axis view showing the abscess (Ab) adjacent to the aortic root (white arrows) and the LCA (black arrow) adjacent to the abscess. Ao ⫽ aorta; LA ⫽ left atrium; LAD ⫽ left anterior descending coronary artery; LV ⫽ left ventricle; PA ⫽ pulmonary artery.
panel A ). The left circumflex branch was closed, and there was limited blood supply to the left anterior descending coronary artery. The reasons for the coronary constriction and closure of the left circumflex branch were not immediately obvious. No intraluminal defect, as would be expected with plaque rupture or coronary artery emboli, was apparent. The patient was referred for emergent operation. A transesophageal echocardiogram revealed large vegetation in the aortic valve. The structure above the aortic valve suggested a paravalvular abscess. Magnetic resonance tomography (MRT)
showed that the left main coronary artery was close to the abscess (Figure, panel B). The operation revealed a large vegetation emanating from the left coronary valvular cusp and a large abscess involving the posterior aortic annulus. The aortic valve was excised and replaced with a homograft. The left main coronary artery was reconstructed, and the abscess cavity was cleansed and closed. Circulation through the left circumflex coronary artery was restored. The adventitia showed inflammation with proliferation and sheets of round cell infiltrate involving the vasa vasorum. The di-
October 1, 2002
agnosis was adventitial inflammation of the aorta with bacterial endocarditis and paravalvular myocardial abscess. The patient recovered gradually. During an examination 1 year later, her ECG and chest radiograph were normal, while MRT showed a patent left main coronary artery. The homograft valve was moderately incompetent. Aortic valve abscesses are relatively uncommon but can lead to aneurysms, with rupture into the pericardium, or perforation into the right atrium, right ventricle, or left ventricle (2). In our patient, transesophageal echocardiography offered important additional information that facilitated her subsequent operative care. Ralf Dechend, MD Bernhard Pilz, MD Matthias Friedrich, MD Friedrich C. Luft, MD Rainer Dietz, MD Franz Volhard Clinic HELIOS Klinikum-Berlin Medical Faculty of the Charite´ Humboldt University of Berlin, Berlin, Germany 1. Friedberg CK. Diseases of the Heart. 3rd ed. Philadelphia, Pennsylvania/London, United Kingdom: W. B. Saunders; 1966. 2. Pilz B, Dietz R, Luft FC. Coronary artery-toleft ventricular fistula. Am J Med. 1999;107: 640 –641.
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113 441
The second patient was a 39-yearold man who was admitted because of a fever of 39°C that lasted 1 month, fatigue, and weight loss of 3 kg. Clinical findings on admission included hepatomegaly and gross splenomegaly. The laboratory workup showed a hemoglobin level of 9.4 g/dL, a white blood cell count of 2700/L, a platelet count of 136,000/L, a Creactive protein level of 227 mg/L, and polyclonal elevation of gamma globulins (4.1 g/dL). As with the imaging studies for our first patient, cultures and serology did not yield significant findings. Bone marrow aspiration showed increased number of macrophages with hemophagocytosis (⬎10%) and Leishmania amastigotes both intra- and extracellularly. Leishmania antibodies were positive at a titer of 1/320. Liposomal amphotericin B was administered (total dose, 20 mg/kg), with prompt clinical and laboratory response. The association of visceral leishmaniasis and hemophagocytic syndrome is rare. A MEDLINE search yielded 16 articles reporting 27 patients with the association. Only 3 of these patients were adults (4 – 6); age was not provided on 4 patients. Our patients fulfilled the diagnostic criteria for primary hemophagocytic syndrome (7), which have also been applied to reactive hemophagocytic syndrome, and therefore could be classified as hemophagocytic syndrome reactive to leishmaniasis. In the reactive form of the syndrome, underlying disease may cause a dysfunction of cellular cytotoxicity with lymphocyte hyperactivation (8). A Th1-Th2 imbalance in favor of Th1, and an inappropriate activation of cytotoxic CD8 T cells, have been suggested. Activated T cells stimulate the phagocytic activity and proliferation of macrophages, releasing cytokines such as tumor necrosis factor–␣, interleukin (IL)-1, IL-6, and macrophage colony-stimulating factor, which are responsible for the clinical manifestations of hemophagocytic syndrome (8). 440
October 1, 2002
In visceral leishmaniasis, active disease is associated with a Th2 response, whereas a Th1 response is necessary for the resolution of infection (9). Other nonviral infections, which have been associated with reactive hemophagocytic syndrome (e.g., Mycobacterium tuberculosis and Salmonella typhi), also elicit a Th1 response (3). Therefore, an unregulated or inappropriate Th1 response in visceral leishmaniasis may have caused the hemophagocytic syndrome in our patients. Theano Kontopoulou, MD, PhD George Tsaousis, MD Emmanouel Vaidakis, MD Panagiotis Fanourgiakis, MD Elias Michalakeas, MD Evangelia Trigoni, MD Michael Samarkos, MD, MSc Fifth Department of Internal Medicine and Hematology Department Evangelismos Hospital Athens, Greece 1. Jaffe R. The histiocytoses. Clin Lab Med. 1999;19:135–155. 2. Favara BE, Feller AC, Pauli M. Contemporary classification of histiocytic disorders. The WHO committee on histiocytic/reticulum cell proliferation. The Reclassification Group of the Histiocyte Society. Med Pediatr Oncol. 1997;29:157–166. 3. Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000;6:601– 608. 4. Matzner Y, Bear A, Beeri E, et al. Systemic leishmaniasis mimicking malignant histiocytosis. Cancer. 1979;43:398 –402. 5. Bessis D, Sotto A, Taib J, Ciurana AJ. Visceral leishmaniasis with hemophagocytic syndrome. Clin Infect Dis. 1993;17:611. 6. Rodriguez-Cuartero A, Salas-Galan A, Perez-Galvez MN, Perez-Blanco FZ. Haemophagocytic visceral kala-azar [letter]. Infection. 1991;3:184. 7. Elinder G, Hender JI, Ost A, and the FHL Study Group of the Histiocyte Society. Diagnostic guidelines for hemophagocytic histiocytosis. Semin Oncol. 1991;18:29 –33. 8. Janka G, Imasuku S, Elinder G, et al. Infection and malignancy associated hemophagocytic syndromes. Hematol Oncol Clin North Am. 1998;12:435–444. 9. Scharton-Kersten T, Scott P. The role of innate immune responses in Th1 cell development following Leishmania major infection. J Leukocyte Biol. 1995;57:515–522.
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113
ENDOCARDITIS AND EXTRINSIC CORONARY COMPRESSION To the Editor: Occlusion of the coronary arteries is almost invariably a sequel to atherosclerosis and associated plaque rupture. However, other causes should be considered in patients with typical symptoms and electrocardiographic (ECG) signs who do not have evidence of atherosclerosis. In addition to coronary atherosclerosis, other conditions such as syphilis, rheumatic fever, infectious diseases, vasculitis, coronary embolism, coronary aneurysms, traumatic lesions, congenital conditions, thromboangiitis obliterans, or medial calcification involving fibroplastic proliferation may be present (1). These conditions, however, seemed unlikely in our patient, a 43-year-old woman with a previous diagnosis of multiple sclerosis. Three weeks before admission, the patient developed fever, night sweats, cough, and progressive dyspnea, which did not resolve with antibiotic treatment. On admission, bilateral pneumonia and pleural effusions were observed. Physical examination revealed tachycardia, bibasilar rales, and a diastolic murmur. Echocardiography revealed aortic valvular vegetations, and she was referred to the cardiology intensive care unit. Bacterial endocarditis was suspected, and a blood culture revealed coagulasepositive Staphylococcus aureus. Despite treatment with penicillin G, gentamicin, and vancomycin, her condition did not improve. Her aortic insufficiency worsened. Eight days after admission, she developed substernal chest pain and showed acute signs of ischemia. Troponin T and creatine kinase-MB con-centrations were elevated. During coronary arteriography, the left main coronary artery showing a smooth, concentric narrowing was observed in the oblique view (Figure,
Letters to the Editor
Figure. Panel A. Coronary arteriogram showing smooth, concentric narrowing of the left main coronary artery (LCA) and abrupt closure of the left circumflex (LCX) (arrow). Panel B. Magnetic resonance tomography in a long-axis view showing the abscess (Ab) adjacent to the aortic root (white arrows) and the LCA (black arrow) adjacent to the abscess. Ao ⫽ aorta; LA ⫽ left atrium; LAD ⫽ left anterior descending coronary artery; LV ⫽ left ventricle; PA ⫽ pulmonary artery.
panel A ). The left circumflex branch was closed, and there was limited blood supply to the left anterior descending coronary artery. The reasons for the coronary constriction and closure of the left circumflex branch were not immediately obvious. No intraluminal defect, as would be expected with plaque rupture or coronary artery emboli, was apparent. The patient was referred for emergent operation. A transesophageal echocardiogram revealed large vegetation in the aortic valve. The structure above the aortic valve suggested a paravalvular abscess. Magnetic resonance tomography (MRT)
showed that the left main coronary artery was close to the abscess (Figure, panel B). The operation revealed a large vegetation emanating from the left coronary valvular cusp and a large abscess involving the posterior aortic annulus. The aortic valve was excised and replaced with a homograft. The left main coronary artery was reconstructed, and the abscess cavity was cleansed and closed. Circulation through the left circumflex coronary artery was restored. The adventitia showed inflammation with proliferation and sheets of round cell infiltrate involving the vasa vasorum. The di-
October 1, 2002
agnosis was adventitial inflammation of the aorta with bacterial endocarditis and paravalvular myocardial abscess. The patient recovered gradually. During an examination 1 year later, her ECG and chest radiograph were normal, while MRT showed a patent left main coronary artery. The homograft valve was moderately incompetent. Aortic valve abscesses are relatively uncommon but can lead to aneurysms, with rupture into the pericardium, or perforation into the right atrium, right ventricle, or left ventricle (2). In our patient, transesophageal echocardiography offered important additional information that facilitated her subsequent operative care. Ralf Dechend, MD Bernhard Pilz, MD Matthias Friedrich, MD Friedrich C. Luft, MD Rainer Dietz, MD Franz Volhard Clinic HELIOS Klinikum-Berlin Medical Faculty of the Charite´ Humboldt University of Berlin, Berlin, Germany 1. Friedberg CK. Diseases of the Heart. 3rd ed. Philadelphia, Pennsylvania/London, United Kingdom: W. B. Saunders; 1966. 2. Pilz B, Dietz R, Luft FC. Coronary artery-toleft ventricular fistula. Am J Med. 1999;107: 640 –641.
THE AMERICAN JOURNAL OF MEDICINE威
Volume 113 441