Onset Of Hemophagocytic Syndrome Research Articles

Infectious causes and management of Japanese spotted fever and severe fever thrombocytopenia syndrome in Ehime prefecture

Objectives We investigated the infectious causes and management of Japanese spotted fever (JSF) and severe fever thrombocytopenia syndrome (SFTS), which are usually tick-borne infections, at a public health center in Ehime prefecture.Methods The doctor diagnosing JSF and SFTS at the public health center reported the infectious cases using the questionnaire based on the Ehime Epidemiological Surveillance of Infectious Diseases Program.Results There were 91 cases of JSF reported from August 2003, accounting for 56.5% of the whole Ehime prefecture. Since 67.0% of the JSF patients resided near the mountains with citrus cultivations, there were high chances of contact with ticks during farm work or their daily routine even if they did not visit the mountain areas. The distribution of the occupations of the JSF patients was as follows: citrus cultivator, 31.9%; farmer, 14.3%; and retired, 26.4%. The incidence of various clinical symptoms in the JSF patients was as follows: fever and systemic erythema, 100%; tick bite, 73.6%; liver dysfunction, 69.2%; disseminated intravascular coagulation (DIC), 14.3%; and neurological symptoms, 11.0%. The mortality rate was 1.1%. The incidence of DIC, which was considered a severe condition, was significantly low in patients with confirmed tick bites. There were 14 cases of SFTS reported from December 2013, accounting for 42.4% of the whole Ehime prefecture. Notably, 85.7% of the SFTS patients resided in the mountains. Moreover, 85.7% of the SFTS patients were retired. The incidence of various clinical symptoms in the SFTS patients was as follows: fever and marked leucopenia and thrombocytopenia, 100%; tick bite, 57.1%; diarrhea, 71.4%; neurological symptoms, 57.1%; and bleeding tendency, 42.9%. The mortality rate was 35.7%, and the average number of days from onset to death was 11.2 days.Conclusion Since this region is one of the leading citrus producing areas in Ehime prefecture, JSF is considered an occupational disease. It is frequently caused by tick bites while working in the mountain areas of citrus cultivations. Hence, citrus growers should be cautious of tick-borne infections. Recently, the number of JSF cases has been gradually decreasing due to awareness and education of the inhabitants. Currently, SFTS is considered a category IV infection disease, but it can rapidly lead to death after the onset of hemophagocytic syndrome. Therefore, doctors should immediately transfer the patients diagnosed with SFTS to a hospital with an intensive care unit.

Long-term prognosis of human herpesvirus 6 reactivation following allogeneic hematopoietic stem cell transplantation.

Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently have HHV-6 reactivation typically during the early phase following HSCT. The long-term clinical complications and prognosis, however, remain unclear. Between September 2010 and October 2012, whole blood samples from 105 patients collected weekly from prior to 6weeks after HSCT underwent multiplex polymerase chain reaction (PCR) to screen for viral DNA, followed by real-time PCR for quantitative estimation. In 48 patients, only HHV-6 was detected in at least one sample. In 30 patients, no viral DNA was detected. Long-term clinical records were reviewed in March 2016. All 48 HHV-6-positive patients, and 24 patients in whom no viral DNA detected, were followed up. Median maximum HHV-6 DNA load in the blood of the HHV-6 reactivation group (n=48) was 11800copies/μg peripheral blood leukocyte DNA (range, 52-310000000). Hemophagocytic syndrome (HPS) was diagnosed in two subjects with HHV-6 reactivation. Acute graft-versus-host disease (GVHD) developed more frequently in patients with HHV-6 reactivation than in patients without viral reactivation (P=0.002), but there was no difference in incidence of chronic GVHD. There was no difference in engraftment of neutrophils and platelets between groups. There was also no difference in overall survival between groups. Onset of HPS, however, was associated with lower overall survival (P=0.009). Human herpesvirus 6 reactivation was associated with acute GVHD, but not with chronic GVHD, engraftment or overall survival. Onset of HPS, however, predicts lower overall survival.

Plasma Levels of Presepsin (Soluble CD14-subtype) as a Novel Prognostic Marker for Hemophagocytic Syndrome in Hematological Malignancies

Objective Recent studies suggest that presepsin (soluble CD14-subtype) is a useful diagnostic and prognostic marker for sepsis, with secretion by activated macrophages potentially dependent on phagocytosis of microorganisms. As "hemophagocytosis" is one of the major characteristics in patients with hemophagocytic syndrome (HPS), we hypothesized that presepsin may reflect the phagocytic activity and be a useful prognostic marker for HPS. Therefore, we aimed to assess the prognostic potential of presepsin in secondary HPS in adult patients with hematological malignancies. Methods Between April 2006 and August 2014, we retrospectively examined consecutive patients with HPS whose blood samples were available at our institution and compared the prognostic value of the following in HPS, singly and in combination: plasma presepsin, serum soluble interleukin (IL)-2 receptor (sIL-2R), ferritin, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-6 and IL-10. Results A total of 14 patients were enrolled. The median age of the patients was 46.5 years (range, 22-65). In univariable Cox models, there were no significant variables associated with the prognosis. However, in 12 evaluable patients, only the combination of higher median values of presepsin (>1,935 pg/mL) and sIL-2R (>4,585 U/mL) at the onset of HPS was significantly associated with the 90-day mortality (hazard ratio 14.5; 95% CI, 1.47-143.36; p=0.02). Conclusion These results suggest that a composite model of plasma presepsin and serum sIL-2R levels at the onset of HPS might be a novel predictor of the prognosis of patients with hematological malignancies and secondary HPS.

Anesthetic management for cesarean delivery in a parturient with exacerbated hemophagocytic syndrome

Hemophagocytic syndrome is an uncommon disease characterized by cytokine dysfunction and uncontrolled hemophagocytosis. It arises rarely during pregnancy, in which case maternal and fetal mortality are relatively high. It has some similarities with HELLP syndrome. Poor maternal condition increases the risk of preterm labor and the possibility of emergency cesarean delivery in non-optimal conditions, presenting a great challenge to the anesthesiologists. We report a 28-year-old primigravida with the onset of hemophagocytic syndrome and cyopenia at 23 weeks of gestation. A further exacerbation at 28 weeks of gestation brought on preterm labor. General anesthesia was provided successfully for cesarean delivery. The patient recovered completely after this episode. We suggest that early diagnosis, multi-disciplinary intervention, pre-operative correction of the hematological abnormalities, general anesthesia and close postoperative monitoring are necessary.

Three patients with hemophagocytic syndrome who developed acute organic brain syndrome

Introduction We describe three patients with hemophagocytic syndrome (HPS) who developed acute organic brain syndrome. All three presented with high-grade fever and twilight state, and were admitted to our hospital. After admission, delirium developed in all three. As delirium improved, various other psychiatric symptoms, including hallucinations, agitation, hypoactivity, affective lability and insomnia, were noted. Discussion When treated with steroid hormones, immunoglobulin and neuroleptics, all patients demonstrated improvement in their psychiatric symptoms, as well as in their general condition and laboratory findings. Ultimately, they all recovered and were discharged. Conclusion It needs to be noted that organic brain syndrome might be observed at the onset of HPS. Consequently, early diagnosis and treatment for psychiatric symptoms, as well as for HPS, are crucial.

Défaut d’exocytose des granules lytiques

An in vivo disturbance of lymphocyte homeostasis occurs during the course of the hemophagocytic syndrome (HS). HS is a severe and often fatal syndrome resulting from potent and uncontrolled activation and proliferation of T-lymphocytes, mainly polyclonal CD8 lymphocytes, leading to excessive macrophage activation, high level of proinflammatory cytokine production and multiple deleterious effects. The onset of HS characterizes several inherited disorders in humans. In most of these conditions, the molecular defect impairs the granule-dependent cytotoxic activity of lymphocytes, thus highlighting the determinant role of this function in driving back the immune system to a state of equilibrium following infection. Several lines of evidence suggest that an increase in the expansion phase rather than a decrease in the contraction phase of the CD8+ T cells population characterizes the HS. Failure to kill antigen presenting cells through a transaction mechanism of cytotoxic cells should favor a sustained response, although the mechanism may be more complex than simple decrease of antigen load. Defect in the granule dependent cytotoxic function of lymphocytes result from perforin mutation in familial hemophagocytic lymphohistiocytosis type 2, from Munc13-4 (UNC13D) mutation in familial hemophagocytic lymphohistiocytosis type 3, from Rab27a mutation in Griscelli syndrome type 2, and from CHS/LYST mutation in Chediak-Higashi syndrome. The characterization of the molecular causes leading to these conditions identified Rab27a and Munc13-4 as two critical effectors of the exocytic machinery, required for the terminal transport/docking or priming of the cytotoxic granules, respectively. Different members of the Rab and Munc13 family of proteins are also used in neurotransmitter release at the neurological synapse, highlighting the similarity of the mechanisms regulating both secretory pathways. Future investigations regarding HS will continue to elucidate this exocytic pathway machinery and improve our understanding of how it finely regulates the immune response, an area that is likely to be useful for therapeutic intervention.

Hemophagocytic syndrome as one of main manifestations in untreated systemic lupus erythematosus: two case reports and literature review

Hemophagocytic syndrome (HPS) is an unusual but fatal disorder characterized by pancytopenia and activation of macrophages. We describe two cases of untreated systemic lupus erythematosus (SLE) with HPS that presented as one of the manifestations of SLE. The onset of HPS was after parturition for one patient, and after abortion for the other. Bone marrow examination revealed severe hemophagocytosis in both patients. One patient responded to pulsed methylprednisone alone, and the other responded to pulsed methylprednisone plus intravenous immunoglobulin (IVIG). We believe accurate diagnosis, intensive therapy, and sufficient supportive cares are essential in improving patients' prognosis.

Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis

Hemophagocytic syndrome (HS) is a severe and often fatal syndrome resulting from potent and uncontrolled activation and proliferation of T-lymphocytes, leading to excessive macrophage activation and multiple deleterious effects. The onset of HS characterizes several inherited disorders in humans. In each condition, the molecular defect impairs the granule-dependent cytotoxic activity of lymphocytes, thus highlighting the determinant role of this function in driving the immune system to a state of equilibrium following infection. It has also been shown that some of the proteins required for lytic granule secretion are required for melanocyte function, leading to associated hypopigmentation in these conditions. This review focuses on several effectors of this secretory pathway, recently identified, because their defects cause these disorders, and discusses their role and molecular interactions in granule-dependent cytotoxic activity.

A clinical analysis of 52 adult patients with hemophagocytic syndrome: the prognostic significance of the underlying diseases.

We retrospectively analyzed 52 adult patients with hemophagocytic syndrome (HPS). The underlying diseases were heterogeneous, including malignant lymphoma (lymphoma-associated hemophagocytic syndrome [LAHS]) in 26 patients, systemic lupus erythematosus in 3 patients, viral infections in 7 patients, and bacteria] or fungal infections in 6 patients. More than 83% of patients received prednisolone as an initial treatment. Multiple-agent chemotherapies (cyclophosphamide, doxorubicin, and vincristine) were administered to 96% of LAHS patients after a histopathological diagnosis of lymphoma. HPSs were controllable and remissions were achieved except for those patients with LAHS, fulminant Epstein-Barr virus-associated HPS, and an immunosuppressive state. Twenty-one (81%) of the LAHS patients had uncontrollable HPS and died of multiple organ failure and disseminated intravascular coagulation. The median survival time of LAHS patients was 83 days. In contrast, 3 (12%) of the other HPS patients died of multiple organ failure within 44 days.The clinical manifestations and the laboratory findings of LAHS and the other HPSs were too variable to establish the prognosis based only on the findings at the onset of HPS. The prognostic factors of adult HPS were found to be the underlying diseases, notably malignant lymphoma and infections, accompanied by the immunosuppressive state.

Cutaneous lesions of hemophagocytic syndrome in a patient with T-cell lymphoma and active Epstein-Barr infection

The hemophagocytic syndrome (HPS) was first described in immune-compromised patients with secondary viral infections. Immunodeficiency has not always been diagnosed before the onset of HPS, but most patients who develop HPS have known immune deficits. HPS has also been reported in association with lymphoreticular malignancies. In HPS the most prominent histologic change is phagocytosis of red blood cells and other bone marrow-derived elements by cytologically benign histiocytes. Considerable confusion exists about the similarities and differences between HPS and other conditions in which hemophagocytosis may occur, for example, histiocytic medullary reticulosis, T-gamma lymphoma, malignant histiocytic lymphoma, and cytophagic histiocytic panniculitis. We report a patient with HPS and cutaneous lesions of cytophagic histiocytic panniculitis who also had an active Epstein-Barr virus infection, and a CD8+ T-cell lymphoma.