Fatal degeneration of specialized cardiac muscle associated with chronic active Epstein–Barr virus infection

Abstract

Key words ATG, CAEBV, cardiac muscle, Epstein-Barr virus, hematopoietic stem cell transplantation.Chronic active Epstein-Barr virus infection (CAEBV) is a lifethreatening disorder characterized by prolonged fever, wasting, hepatosplenomegaly, and cytopenia, in addition to abnormal EBV antibody titers and the presence of EBV antigens or EBV-DNA in tissue. 1 The ultimate prognosis of CAEBV is very poor, and patients with CAEBV often develop a progressive cellular and humoral immunodeficiency with pancytopenia and hypoglobulinemia that renders them susceptible to opportunistic infections or B-or T-cell lymphoproliferative disease. 2 An effective treatment for CAEBV has yet to be established, although allogeneic hematopoietic stem cell transplantation (HSCT) was recently reported to be effective in eradicating EBV-infected lymphocytes. 3,4 Allogeneic HSCT is, however, accompanied by a considerable risk of therapy-related death. Kimura et al. reported that approximately one-half of patients with CAEBV who underwent HSCT died within 60 days. 5 We here report a patient with CAEBV who developed fatal acute circulatory failure during the preconditioning of HSCT, and in whom autopsy showed degeneration of specialized cardiac muscle and severe large-vessel arteritis associated with CAEBV. Case reportA 12-year-old boy was admitted to a regional hospital with a 2 year history of fever, wasting, and a short stature (-3.0 SD). He was diagnosed with CAEBV on clinical signs and the presence of EBV genome in peripheral blood, and was admitted to hospital in April 2005. He was allergic to mosquito bites. On examination, lymph node adenopathy was noted. No skin lesion was observed. On brain CT, bilateral calcification of the basal ganglia was noted. Echocardiography showed dilatation of the lumens of the coronary arteries. The leukocyte count was 2.2 ¥ 10 9 /L; hemoglobin, 12.5 g/dL; and platelet count, 61 ¥ 10 9 /L. Biochemical analysis was as follows: aspartate aminotransferase, 28 IU/L; alanine aminotransferase, 14 IU/L; lactate dehydrogenase, 265 IU/L; C-reactive protein, 0.63 mg/dL; soluble interleukin-2 receptor, 1200 U/mL (normal, <519 U/mL); viral capsid antigen (VCA)-IgG, ¥320; EA-IgG, ¥10; EBNA, ¥10. Natural killer activity was 55%. The quantity of EBV genome DNA was increased (2.6 ¥ 10 3 copies/mg DNA) on polymerase chain reaction in peripheral blood mononuclear cell (PBMC), particularly in CD4+T cells (4.3 ¥ 10 4 copies/mg DNA), but not in CD8+T cells or CD56+NK cells. Southern blot of the peripheral blood cells using an EBV terminal probe indicated monoclonal proliferation of EBV-infected lymphocytes. Flow cytometry showed the expression of the perforin protein in PBMC. Chromosome analysis of peripheral blood showed the normal male karyotype.The high load of EBV genome DNA had persisted for over 6 months. Therefore, HSCT from a human leukocyte antigen (HLA)-matched sibling donor was planned in October 2005. Just before bone marrow transplantation, the quantity of EBV-DNA was consistently high in peripheral blood. No che...

Mortality in Schizophrenia: Clinical and Serological Predictors

“…EBV can cause myocarditis 29 and has been associated with fatal or near-fatal consequences in some cases. [30][31][32][33][34] The mechanisms underlying the occurrence of serious effects of EBV infection in some individuals are not known with certainty but may be related to the underlying immune state of the host, as well as the timing of infection and the infectious dose. The effect of EBV exposure on a population of immune competent individual has not been previously reported.…”

From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

“…In addition, EBV has been implicated in a wide variety of diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome, multiple sclerosis (MS), myasthenia gravis (MG), rheumatoid arthritis (RA), autoimmune thyroid disorders, inflammatory bowel disease, celiac diseases, diabetes, Parkinson's disease, myopericarditis, dilated cardiomyopathy, and even death. [9][10][11][12][13][14] At the same time, anti-EBV antibody level was found to be higher in BL patients than in control subjects. 3,[15][16][17] High level of anti-EBV immunoglobulin G antibodies were also found in subjects with NPC, [18][19][20][21] with IgG reactivity increasing significantly with tumor stage 21 ; Hodgkin and non-Hodgkin lymphomas [22][23][24] ; precancerous gastric lesions 25 ; MS [26][27][28][29] ; RA [30][31][32] ; MG 33,34 ; and SLE, 29,31,34 among others.…”

“…In addition, EBV has been implicated in a wide variety of diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome, multiple sclerosis (MS), myasthenia gravis (MG), rheumatoid arthritis (RA), autoimmune thyroid disorders, inflammatory bowel disease, celiac diseases, diabetes, Parkinson's disease, myopericarditis, dilated cardiomyopathy, and even death. 9 10 11 12 13 14 …”