Heart Vessels (1992) 7:104-106
Heart
andVesselS
© Springer-Verlag1992
Acute hemorrhagic myocarditis in systemic lupus erythematosus Paul Dickens 1, John Nicholls 1, and Chu-Pak Lau 2 1Departments of Pathology and 2Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
Abstract. We report a 46-year-old patient with longstanding systemic lupus erythematosus (SLE) who developed rapidly progressive heart failure and died. At postmortem, there was a unique picture of hemorrhage and mild inflammation present in the myocardium causing the heart failure. As far as we are aware, this picture has not been described before in SLE and is similar to that seen in the cardiac allograft hyperacute rejection.
Key words: Hemorrhagic myocarditis - Lupus erythematosus - Hyperacute rejection
Case report The patient was a 46-year-old female who presented in 1983 with symmetrical polyarthritis of the hands and lower limbs for 20 years. A diagnosis of systemic lupus erythematosus was made based on a positive antinuclear antibody (1/50), positive anti-DNA antibody and reduced complements 3 and 4. Apart from joint involvement she had had bilateral hip replacements for avascular femoral head necrosis. Her renal function remained normal apart from mild proteinuria (0.69 g over 24 h). There were no symptoms referrable to her cardiovascular system. The patient was seen 2 weeks prior to the final presentation. Routine blood test showed a hypochromic anemia (10.0 g/dl, MCV = 78) with normal white cell and platelet counts. Upper gastrointestinal endoscopy was planned. At this time, her medication included prednisone 5 mg on alternate days, sulindac 200mg twice daily, and hydroxychloroquine 400mg Address correspondence to: J Nicholls
Received August 30, 1991; revision received November 25, 1991; accepted December 21, 1991
twice daily. The last anti-nuclear antibody titer was 1/1080 and C3 and C4 were reduced (37 and 6mg/dl respectively). She was admitted initially to a local hospital, 3 days prior to her transferral to our hospital, with fever, cough and blood-streaked sputum. Chest X-ray showed a normal-sized heart and normal lung fields. The white cell count was 3.5 x 109/1 with a relative predominance of lymphocytes (60%). Her platelet count was 49 x 109/1. Renal and liver function tests were normal. After transferral, her condition became unstable with rapidly progressive pulmonary edema and an enlarging cardiac shadow. There was no electrocardiographic evidence of myocardial infarction. The platelet count dropped to 19 x 109/1 but there was no evidence of disseminated intravascular coagulation as assayed by prothrombin time and activated partial thromboplastin time. The C-reactive protein was 127mg/dl (normal < 8mg/dl). Blood cultures were negative. She deteriorated rapidly and arrested within 12h of transferral due to rapidly progressive heart failure. A full postmortem was performed 25 h after death. No external abnormality was present. The main abnormalities were in the lungs and the heart. The lungs were both heavy (left = 742 g, right = 711 g) with edema fluid easily expressed. No areas of consolidation were present. The visceral pericardium was adherent to the parietal pericardium and the two layers separated with difficulty. The heart weighed 304 g and on sectioning the myocardium was a deep plum red color affecting all chambers (Fig. 1). The valves were normal with no evidence of endocarditis or vegetations. Minimal atheroma was identified in the coronary arteries. No infarction was identified grossly. Histological sections of the heart showed florid extravasation of red blood cells into the interstitium with separation of the myocytes (Fig. 2). The architecture of the heart was preserved with no significant
P. Dickens et al.: Hemorrhagic myocarditis
105 cardial vessels were patent with no inflarnmation or platelet thrombi identified. The endothelial cells lining the arterioles showed a rnoderate degree of swelling but electron microscopy and silver staining failed to demonstrate disruption of the vessel wall or immune cornplex deposition. No infarction was present on routine hernatoxylin and eosin staining and a special stain (Hernatoxylin/basic fuschin/picric acid) showed no areas of ischemia. Within the areas of hemorrhage there was a mild mononuclear cellular infiltrate cornposed rnainly of lymphocytes. Postmortern viral cultures were negative. The kidney showed mild mesangial enlargernent but there was no evidence of a vasculitic process or crescentic glomerulonephritis. Irnrnunofluorescent staining showed a weak mesangial C3 hut no other findings. There was pulmonary edema with no evidence of vascular pathology. All other organs were normal histologically.
Discussion
Fig. 1. Opened view of the left side of the heart showing aa intensely hemorrhagic left ventricle increase in fibrous tissue, as demonstrated by trichrome staining. The coronary arteries were free of atherosclerotic changes or vasculitis. The intrarnyo-
The cardiac lesions in SLE are many and varied. [1] As SLE is a systemic disease, all layers of the heart may be affected. Pericarditis is the most comrnon manifestation of SLE and may be focal or diffuse. Myocarditis and endocarditis are reported to be less cornmon clinically, though Libman-Sacks endocarditis vegetations may be seen in 4 0 % - 5 0 % of hearts at autopsy. Cardiac arrhythrnias and conduction disturbances are rare, except in neonates of rnothers with SLE but coronary atherosclerosis is reported to be increased when cornpared to controls. [1] In 1951 Griffiths and Vural [2] correlated clinical and postrnortem findings in 18 cases of SLE and found 12 cases had endocardial lesions and that most of the cases
Fig. 2. Section of myocardium showing interstitial hemorrhage with no vasculitic changes (H & E ×200)
106 showed some focal myocarditis characterized by the presence of focal collections of inflammatory cells containing small lymphocytes, and mononuclear and plasma cells in the myocardial interstitium. In 9 cases a serofibrinous pericarditis was present. The myocardial changes consisted of fine scars and focal fibrinoid metamorphosis of the collagenous fibers which resulted in fragmentation and swelling of these elements and increased density of the ground substance. A mild perivascular infiltration of lymphocytes and polymorphs was present. In 1975, Bulkley and Roberts [3] examined the hearts of patients with SLE who had been treated with steroids. They identified a fibrinous pericarditis in 53% of patients but myocarditis was present in only 3 out of 36 patients, each of whom also had endocarditis and pericarditis and who presented with congestive cardiac failure and electrocardiographic abnormalities. Cardiac disorders accounted for only 20% of the deaths in these steroid-treated patients. The patient in this report had a unique histological picture for SLE of intramyocardial hemorrhage in association with mild fibrosis and mild inflammation. We initially considered other possible causes for hemorrhage including catecholamine myocarditis [4] and thrombotic thrombocytopenic purpura [5] but there was no evidence of the microangiopathic hemolytic anemia, renal dysfunction or thrombi seen in the latter condition and the histological appearances did not support the former. Furthermore, there was no histological evidence of vasculitis present in any of the organs sampled. The appearances, however, are similar to those seen in hyperacute rejection in cardiac transplants due to ABO blood type mismatch [6]. There was evidence of a pericarditis, as is commonly seen in patients with SLE, although no cardiac tamponade was present. Unlike other reports of the
P. Dickens et al.: Hemorrhagic myocarditis cardiac manifestations of SLE, [1, 2] there was no evidence of myocardial infarction or ischemia and the coronary vessels were free of atheroma and vasculitis. The very low dose of steroid therapy would not normally lead to opportunistic infection and organisms were not identified by culture. We have only been able to identify minor non-specific vascular changes but attribute the hemorrhage to a combination of a low platelet count together with an immune-mediated angiopathic process. We conclude that hemorrhagic myocarditis should be considered in patients with active lupus and thrombocytopenia presenting with acute heart failure without evidence of ischemia.
Acknowledgements. We would like to thank Dr. Margaret Billingham of Stanford University who reviewed the sections and commented on them.
References 1. Ansari A, Larson PH, Bates HD (1985) Cardiovascular manifestations of systemic lupus erythematosus: Current perspectives. Prog Cardiovasc Dis 27:421-434 2. Griffiths GC, Vural IL (1951) Acute and subacute disseminated lupus erythematosus, a correlation of clinical and postmortem findings in 18 cases. Circulation 3:492-500 3. Bulkley BH, Roberts WC (1975) The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapy. Am J Med 58:243-264 4. Nino AF, Berman MM, Gluck EH, Conway MM, Fisher JP, Dougherty JE, Rossi MA (1987) Drug induced left ventricular failure in patients with pulmonary disease. Endomyocardial biopsy demonstration of catecholarnine myocarditis. Chest 92:732-736 5. Webb JG, Butany J, Langer G, Scott JG, Liu PP (1990) Myocarditis and myocardial hemorrhage associated with thrombotic thrombocytopenic purpura. Arch Int Med 150:1535-1537
Heart
andVesselS
© Springer-Verlag1992
Acute hemorrhagic myocarditis in systemic lupus erythematosus Paul Dickens 1, John Nicholls 1, and Chu-Pak Lau 2 1Departments of Pathology and 2Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
Abstract. We report a 46-year-old patient with longstanding systemic lupus erythematosus (SLE) who developed rapidly progressive heart failure and died. At postmortem, there was a unique picture of hemorrhage and mild inflammation present in the myocardium causing the heart failure. As far as we are aware, this picture has not been described before in SLE and is similar to that seen in the cardiac allograft hyperacute rejection.
Key words: Hemorrhagic myocarditis - Lupus erythematosus - Hyperacute rejection
Case report The patient was a 46-year-old female who presented in 1983 with symmetrical polyarthritis of the hands and lower limbs for 20 years. A diagnosis of systemic lupus erythematosus was made based on a positive antinuclear antibody (1/50), positive anti-DNA antibody and reduced complements 3 and 4. Apart from joint involvement she had had bilateral hip replacements for avascular femoral head necrosis. Her renal function remained normal apart from mild proteinuria (0.69 g over 24 h). There were no symptoms referrable to her cardiovascular system. The patient was seen 2 weeks prior to the final presentation. Routine blood test showed a hypochromic anemia (10.0 g/dl, MCV = 78) with normal white cell and platelet counts. Upper gastrointestinal endoscopy was planned. At this time, her medication included prednisone 5 mg on alternate days, sulindac 200mg twice daily, and hydroxychloroquine 400mg Address correspondence to: J Nicholls
Received August 30, 1991; revision received November 25, 1991; accepted December 21, 1991
twice daily. The last anti-nuclear antibody titer was 1/1080 and C3 and C4 were reduced (37 and 6mg/dl respectively). She was admitted initially to a local hospital, 3 days prior to her transferral to our hospital, with fever, cough and blood-streaked sputum. Chest X-ray showed a normal-sized heart and normal lung fields. The white cell count was 3.5 x 109/1 with a relative predominance of lymphocytes (60%). Her platelet count was 49 x 109/1. Renal and liver function tests were normal. After transferral, her condition became unstable with rapidly progressive pulmonary edema and an enlarging cardiac shadow. There was no electrocardiographic evidence of myocardial infarction. The platelet count dropped to 19 x 109/1 but there was no evidence of disseminated intravascular coagulation as assayed by prothrombin time and activated partial thromboplastin time. The C-reactive protein was 127mg/dl (normal < 8mg/dl). Blood cultures were negative. She deteriorated rapidly and arrested within 12h of transferral due to rapidly progressive heart failure. A full postmortem was performed 25 h after death. No external abnormality was present. The main abnormalities were in the lungs and the heart. The lungs were both heavy (left = 742 g, right = 711 g) with edema fluid easily expressed. No areas of consolidation were present. The visceral pericardium was adherent to the parietal pericardium and the two layers separated with difficulty. The heart weighed 304 g and on sectioning the myocardium was a deep plum red color affecting all chambers (Fig. 1). The valves were normal with no evidence of endocarditis or vegetations. Minimal atheroma was identified in the coronary arteries. No infarction was identified grossly. Histological sections of the heart showed florid extravasation of red blood cells into the interstitium with separation of the myocytes (Fig. 2). The architecture of the heart was preserved with no significant
P. Dickens et al.: Hemorrhagic myocarditis
105 cardial vessels were patent with no inflarnmation or platelet thrombi identified. The endothelial cells lining the arterioles showed a rnoderate degree of swelling but electron microscopy and silver staining failed to demonstrate disruption of the vessel wall or immune cornplex deposition. No infarction was present on routine hernatoxylin and eosin staining and a special stain (Hernatoxylin/basic fuschin/picric acid) showed no areas of ischemia. Within the areas of hemorrhage there was a mild mononuclear cellular infiltrate cornposed rnainly of lymphocytes. Postmortern viral cultures were negative. The kidney showed mild mesangial enlargernent but there was no evidence of a vasculitic process or crescentic glomerulonephritis. Irnrnunofluorescent staining showed a weak mesangial C3 hut no other findings. There was pulmonary edema with no evidence of vascular pathology. All other organs were normal histologically.
Discussion
Fig. 1. Opened view of the left side of the heart showing aa intensely hemorrhagic left ventricle increase in fibrous tissue, as demonstrated by trichrome staining. The coronary arteries were free of atherosclerotic changes or vasculitis. The intrarnyo-
The cardiac lesions in SLE are many and varied. [1] As SLE is a systemic disease, all layers of the heart may be affected. Pericarditis is the most comrnon manifestation of SLE and may be focal or diffuse. Myocarditis and endocarditis are reported to be less cornmon clinically, though Libman-Sacks endocarditis vegetations may be seen in 4 0 % - 5 0 % of hearts at autopsy. Cardiac arrhythrnias and conduction disturbances are rare, except in neonates of rnothers with SLE but coronary atherosclerosis is reported to be increased when cornpared to controls. [1] In 1951 Griffiths and Vural [2] correlated clinical and postrnortem findings in 18 cases of SLE and found 12 cases had endocardial lesions and that most of the cases
Fig. 2. Section of myocardium showing interstitial hemorrhage with no vasculitic changes (H & E ×200)
106 showed some focal myocarditis characterized by the presence of focal collections of inflammatory cells containing small lymphocytes, and mononuclear and plasma cells in the myocardial interstitium. In 9 cases a serofibrinous pericarditis was present. The myocardial changes consisted of fine scars and focal fibrinoid metamorphosis of the collagenous fibers which resulted in fragmentation and swelling of these elements and increased density of the ground substance. A mild perivascular infiltration of lymphocytes and polymorphs was present. In 1975, Bulkley and Roberts [3] examined the hearts of patients with SLE who had been treated with steroids. They identified a fibrinous pericarditis in 53% of patients but myocarditis was present in only 3 out of 36 patients, each of whom also had endocarditis and pericarditis and who presented with congestive cardiac failure and electrocardiographic abnormalities. Cardiac disorders accounted for only 20% of the deaths in these steroid-treated patients. The patient in this report had a unique histological picture for SLE of intramyocardial hemorrhage in association with mild fibrosis and mild inflammation. We initially considered other possible causes for hemorrhage including catecholamine myocarditis [4] and thrombotic thrombocytopenic purpura [5] but there was no evidence of the microangiopathic hemolytic anemia, renal dysfunction or thrombi seen in the latter condition and the histological appearances did not support the former. Furthermore, there was no histological evidence of vasculitis present in any of the organs sampled. The appearances, however, are similar to those seen in hyperacute rejection in cardiac transplants due to ABO blood type mismatch [6]. There was evidence of a pericarditis, as is commonly seen in patients with SLE, although no cardiac tamponade was present. Unlike other reports of the
P. Dickens et al.: Hemorrhagic myocarditis cardiac manifestations of SLE, [1, 2] there was no evidence of myocardial infarction or ischemia and the coronary vessels were free of atheroma and vasculitis. The very low dose of steroid therapy would not normally lead to opportunistic infection and organisms were not identified by culture. We have only been able to identify minor non-specific vascular changes but attribute the hemorrhage to a combination of a low platelet count together with an immune-mediated angiopathic process. We conclude that hemorrhagic myocarditis should be considered in patients with active lupus and thrombocytopenia presenting with acute heart failure without evidence of ischemia.
Acknowledgements. We would like to thank Dr. Margaret Billingham of Stanford University who reviewed the sections and commented on them.
References 1. Ansari A, Larson PH, Bates HD (1985) Cardiovascular manifestations of systemic lupus erythematosus: Current perspectives. Prog Cardiovasc Dis 27:421-434 2. Griffiths GC, Vural IL (1951) Acute and subacute disseminated lupus erythematosus, a correlation of clinical and postmortem findings in 18 cases. Circulation 3:492-500 3. Bulkley BH, Roberts WC (1975) The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapy. Am J Med 58:243-264 4. Nino AF, Berman MM, Gluck EH, Conway MM, Fisher JP, Dougherty JE, Rossi MA (1987) Drug induced left ventricular failure in patients with pulmonary disease. Endomyocardial biopsy demonstration of catecholarnine myocarditis. Chest 92:732-736 5. Webb JG, Butany J, Langer G, Scott JG, Liu PP (1990) Myocarditis and myocardial hemorrhage associated with thrombotic thrombocytopenic purpura. Arch Int Med 150:1535-1537
