ABSTRACT
A virus-associated hemophagocytic syndrome is characterized by high fever, liver dysfunction, coagulation abnormalities, pancytopenia, and a benign histiocytic proliferation with prominent hemophagocytosis in bone marrow, lymph node, spleen, and liver. Three phases of disease progression can be defined. In the first week, there is mild leukocytosis and myeloid hyperplasia in the marrow and the fever is resistant to antipyretics and antibiotics. In the second phase, usually corresponding to the 2nd to 3rd week of the illness, the fever persists and jaundice and hepatosplenomegaly may develop and the marrow now reveals the presence of atypical or transformed T lymphocytes and a scattering of histiocytes with hemophagocytosis. In the third phase, the disease progresses to a full-blown hemophagocytic syndrome with coagulopathy and lung infiltrates. The marrow in this stage is usually hypoplastic with florid histiocytic proliferation and hemophagocytosis and the patients usually die within 1-2 months. We describe a pregnant woman with fatal hemophagocytic syndrome. Virologic study strongly suggests that Epstein-Barr virus implicated in the pathogenesis of this patient.
Subject(s)
Female , Humans , Pregnancy , Anti-Bacterial Agents , Antipyretics , Bone Marrow , Disease Progression , Fever , Herpesvirus 4, Human , Histiocytes , Hyperplasia , Jaundice , Leukocytosis , Liver , Liver Diseases , Lung , Lymph Nodes , Lymphohistiocytosis, Hemophagocytic , Pancytopenia , Pregnant Women , Spleen , T-LymphocytesABSTRACT
BACKGROUND: A virus-associated hemophagocytic syndrome(VAHS) is a non-neoplastic, generalized histiocytic proliferation with prominent hemophagocytosis associated with a systemic viral infection. Although VAHS is generally a benign process, Epstein-Barr virus- associated hemophagocytic syndrome(EBV-AHS) is often fatal and has a high mortality rate. Therefore, clinical and laboratory findings, virology studies, treatment and prognosis in EBV- AHS are reviewed. METHODS: We retrospectively analyzed various clinical datas of 7 patients who were diagnosed as EBV-AHS by EBV panel test, mRNA in situ hybridization(1 case) and diagnostic guidelines of Histiocyte Society and followed up to the Department of Pediatrics, Severance Hospital, Yonsei University Medical College from January 1990 to December 1997. RESULTS: The mean age at diagnosis was 2.8 years(range; 0.8~5.4). EBV-AHS was caused by reactivation of EBV in 6 cases and primary infection in 1 case. Persistent fever and hepatosplenomegaly were observed in all cases. Hyperferritinemia was detected in 5 cases. Hypertriglyceridemia was noted in 4 cases among 5 cases tested and hypofibrinogenemia was detected in 5 cases among 5 cases tested. Benign histiocytic infiltration(at least above 5% of all nucleated marrow cells), hemophagocytosis and normocellularity in bone marrow were observed in all cases. The mortality rate was 57%, the main causes of death were bleeding and sepsis. In analysis of prognostic factors associated with death, there was a correlation between hypofibrinogenemia, hepatomegaly, hypoalbuminemia and death, although insignificant statistically. CONCLUSION: In our study, EBV-AHS was caused by reactivation of EBV in most cases. The mortality rate was 57% and the main causes of death were bleeding and sepsis. In analysis of prognostic factors associated with death, there was a correlation between hypofibrinogenemia, hepatomegaly and hypoalbuminemia to a certain degree. But, further study of larger numbers of patients and longer follow-up is needed to clarify the prognostic factors.
Subject(s)
Humans , Bone Marrow , Cause of Death , Diagnosis , Fever , Follow-Up Studies , Hemorrhage , Hepatomegaly , Herpesvirus 4, Human , Histiocytes , Hypertriglyceridemia , Hypoalbuminemia , Lymphohistiocytosis, Hemophagocytic , Mortality , Pediatrics , Prognosis , Retrospective Studies , RNA, Messenger , Sepsis , VirologyABSTRACT
Virus associated hemophagocytic syndrome, class ll histiocytoses, characterized by high fever, severe constitutional symptoms, abnormal liver function and coagulation, perigheral blood pancytopenia and histiocytic hyperplasis with prominent hemophagocytosis in bone marrow and lymph nodes has been reported and associated with active viral infection. It is non-malignant and reversible. It must be differentiated from histiocytic medullary reticulosis because of the inappopriateness of immunosuppressive of cytotozic therapy which is the therapeutic method for HMR, but is contraindicated in the treatment of VAHS. This paper describes two patients whose clinicopathology was compatible with the diagnosis of virus associated hemophagocytic syndrome.