Fulminant Childhood Hemophagocytic Syndrome Mimicking Histiocytic Medullary Reticulosis: An Atypical Form of Epstein-Barr Virus Infection

Abstract

Ten cases of pediatric fulminant hemophagocytic syndrome, encountered between 1986 and 1989, are described. They occurred in the summer, and the patients presented with fever, jaundice, hepatosplenomegaly, pancytopenia, coagulopathy, and abnormal liver function. Bone marrow studies revealed infiltration by atypical T-lymphoid cells, rare B immunoblasts, and mature histiocytes with hemophagocytosis. Initially, histiocytic medullary reticulosis was suspected in six cases. The clinical course was characterized by rapid deterioration, with a mean period of 16 days from onset of fever to death. The main causes of death were coagulopathy with multiple organ failure and opportunistic infection. In seven of eight cases studied by serologic assay and Southern blot hybridization, acute or active Epstein-Barr virus (EBV) infection was documented. It is suggested that an atypical or fulminant form of primary EBV infection distinct from classic infectious mononucleosis was prevalent in previously healthy children in Taiwan. Younger age involvement and seasonal clustering were characteristic of the disorder described.

Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome

“…37,38 Tissues or freshly frozen cells were available for DNA and RNA extraction in 7 cases, including lymph nodes in 2 cases, spleen in 1 case, skin in 1 case, and bone marrow in 3 cases. As controls, 10 specimens of reactive lymphoid hyperplasia (5 cases), IM (2 cases), and nasal type NK/T-cell lymphoma (3 cases) were included.…”

Functional analysis of C-terminal deletion mutants of Epstein--Barr virus thymidine kinase

“…It is the aetiological agent of adult infectious mononucleosis (Henle et al, 1968;Henle & Henle, I979) and is closely associated with African Burkitt's Iymphoma (Epstein ef a]., 1964;de Th6 et al, 1978), nasopharyngea] carcinoma (Old et aI., 1966), B cell neoplasia in immunocompromised patients (Hanto et al, 1985), T cell lymphoma (Su & Hsieh, 1992) and childhood virus-associated haemophagocytic syndrome (Chen et a]., 1991).…”

Haemophagocytosis in Bone Marrow Aspirate – A Review of the Clinical Course of 10 Cases

“…In 1979, Risdall et al [16] first described 19 cases of VAHS, the majority being due to CMV, with VZV, HSV and EBV being the other viruses implicated. Other reports [17,18] were mainly due to EBV infection. Chen et al [17] reported 10 cases of fatal paediatric haemophagocytic syndrome where EBV infection was proven by either serology or molecular method in 7 of them.…”

“…Other reports [17,18] were mainly due to EBV infection. Chen et al [17] reported 10 cases of fatal paediatric haemophagocytic syndrome where EBV infection was proven by either serology or molecular method in 7 of them. Our case 6 was particu larly puzzling in that no bacteriological or virological cause was found and postmortem did not reveal any evi dence of lymphoma.…”

“…In their series, 13 patients were on immunosuppressants after renal trans plant, and reduction in immunosuppressants was thought to be critical in the successful management of these cases. On the other hand, there were many subsequent cases of VAHS reported which are not in the context of immuno compromised host, and a fatal outcome was observed in some of them [17,18], The only way to prevent mistreat ment of cases of VAHS with chemotherapy is an active search for viral infection including viral culture in every suspected case, together with an aggressive attempt to obtain tissue for histology to detect the presence of lym phoma, as far as the clinical state of patient permits. The decision to start chemotherapy should be individualised and depend on the overall judgement based on all avail able clinical, laboratory and pathological information, as well as the urgency of the situation.…”