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Hemophagocytic Syndrome (hemophagocytic + syndrome)
Selected AbstractsMycophenolate Mofetil: A Possible Cause of Hemophagocytic Syndrome Following Renal Transplantation?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010L. Raffray No abstract is available for this article. [source] Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasisIMMUNOLOGICAL REVIEWS, Issue 1 2005Gael Ménasché Summary:, 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. [source] Soluble hemoglobin,haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndromeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2005Dominik J. Schaer Abstract:, Reactive hemophagocytic syndrome (RHS) is a disease of overwhelming macrophage activity triggered by infection, malignancy or autoimmune disorders. Currently used laboratory markers for the quantitative assessment of monocyte/macrophage activation lack lineage-restricted expression patterns and thus specificity. Serum levels of the macrophage specific scavenger receptor CD163 were detemined by enzyme-linked immunosorbent assay (ELISA) and were found to be highly increased in patients with RHS (median 39.0 mg/L). Significantly lower levels were determined in patients with sepsis (median 9.1 mg/L), acute mononucleosis (median 8.2 mg/L), Leishmania infection (median 6.7 mg/L) and healthy controls (median 1.8 mg/L). Follow-up of patients with a relapsing course of the disease revealed close correlations of sCD163 with clinical disease activity, serum ferritin and other markers of macrophage activity. Large sinusoidal accumulations of CD163 expressing macrophages actively engaged in phagocytosis of blood cells were detected in spleen sections of RHS patients. Our data suggests sCD163 to be a macrophage-specific marker in patients with disorders of inappropriate macrophage activation. [source] Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysisHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2004Gwi Eon Kim MD Abstract Background. The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas. Methods. Eighty patients with localized non-Hodgkin's lymphoma involving the nasal cavity and/or paranasal sinuses were divided into three subtypes on the basis of their immunohistochemical findings: (A) B-cell lymphoma (n = 19), (B) T-cell lymphoma (n = 27), and (C) natural killer (NK)/T-cell lymphoma (n = 34). The clinicopathologic profiles, immunophenotypic data, patterns of treatment failure, and survival data among the three patient groups were retrospectively compared. Results. The nasal cavity was the predominant site of involvement in T-cell and NK/T-cell lymphoma, whereas sinus involvement without nasal disease was common in B-cell lymphoma. Systemic B symptoms were frequently observed in NK/T-cell lymphoma. Almost all patients with NK/T-cell lymphoma showed a strong association with the Epstein-Barr virus by in situ hybridization studies. Sixty-five patients (81%) patients achieved complete remission after initial treatment, but 36 (55%) of these subsequently experienced treatment failure. Although there were no significant differences in locoregional failure rates among the patients of the three groups, distant failure was far more common in B-cell or NK/T-cell lymphoma than in T-cell lymphoma (p = .005). Most B-cell lymphoma cases showed a predilection for sites of systemic failure in the nodal and extranodal sites below the diaphragm, such as the paraaortic lymph nodes or the gastrointestinal (GI) tract, whereas patients with NK/T-cell lymphoma showed an increased risk of systemic dissemination to the skin, testes, or GI tract, including the development of hemophagocytic syndrome. The 5-year actuarial and disease-free survival rates for all patients were 57% and 51%, respectively. Of the three subtypes of primary sinonasal lymphomas, T-cell lymphoma seemed to carry the most favorable prognosis and NK/T-cell lymphoma the worst. (The 5-year actuarial survival rate was 57% for B-cell lymphoma, 80% for T-cell lymphoma, 37% for NK/T-cell lymphoma; p = .02, log-rank.) By univariate and multivariate analyses, immunophenotype was identified as the most important prognostic factor. Conclusions. Our data indicate that the three subtypes of primary sinonasal lymphomas classified by immunohistochemical studies exhibit different clinical profiles, different patterns of failure, and different treatment outcomes. Given these observations, it is concluded that the recognition of these distinct subsets, diagnosed on the basis of immunophenotypic study, is very important and clinically relevant in predicting their potential behavior and prognosis. © 2004 Wiley Periodicals, Inc. Head Neck26: 584,593, 2004 [source] Intravascular lymphoma: a neoplasm of ,homeless' lymphocytes?HEMATOLOGICAL ONCOLOGY, Issue 3 2006Maurilio Ponzoni Abstract Intravascular lymphoma (IVL) is an extremely rare form of non-Hodgkin lymphoma characterized by almost exclusive growth of neoplastic lymphocytes within blood vessel lumen. IVL is morphologically characterized in most instances by large cells with B-cell lineage. IVL is an aggressive and usually disseminated disease that predominantly affects elderly patients, resulting in poor PS, B-symptoms, anemia, and high lactate dehydrogenase serum level. The brain and skin are the most commonly involved sites; nodal disease is rare. Survival after conventional chemotherapy is disappointing, with a relevant impact of diagnostic delay and lethal complications. Notwithstanding these results, IVL limited to the skin (cutaneous variant) is a favorable presentation with distinctive clinical characteristics. Moreover, differences in clinical presentation with Eastern Countries IVL cases, mostly associated with hemophagocytic syndrome, do exist. Intensive combinations containing drugs with higher central nervous system bioavailability are needed in cases with brain involvement; the role of high-dose chemotherapy with autologous stem cell transplantation should be investigated in younger patients with unfavorable features. The present review will discuss the most recent acquisitions related either to diagnosis and immunophenotypic/biologic characteristics as well as clinical/therapeutic issues of IVL. Copyright © 2006 John Wiley & Sons, Ltd. [source] Extranodal NK/T-cell lymphoma, nasal type, presenting after 5 years of remissionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Tomonobu Ito MD A 76-year-old woman with multiple edematous erythemas, erosions, and ulcers on the breast and abdomen was admitted to our hospital in June 2005. She had developed granulomatous bleeding lesions in the right nostril 6 years prior to her visit to our dermatology unit. She had been observed at the otorhinolaryngology department of our hospital, and a biopsy was taken from the nasal lesion. Computerized tomography and gallium scintigraphy (67Ga single-photon emission computed tomography) did not reveal any lesions corresponding to the diagnosis of malignant lymphoma. The histologic examination of the nasal specimen rendered a diagnosis of natural killer (NK)/T-cell lymphoma, nasal. Because imaging analysis indicated a small-sized tumor without metastases, oral prednisolone at 20 mg/day was administered for 1 month. The tumor decreased in size and disappeared after 19 months of low-dose steroid therapy. ,Five years after the initial treatment, the patient developed a fever of 38 °C with infiltrated erythemas and erosions on her breast. Erysipelas was initially suspected, but the antimicrobial agent did not show any effect and the multiple infiltrated erythemas and ulcers spread throughout her chest and abdomen (Fig. 1). The lymph nodes were not palpable. The right nasal cavity showed no granulomatous lesions or other signs of abnormality. The peripheral white blood cell count (3000/µL), red blood cell count (3.54 × 106/µL), and platelet count (112 × 103/µL) were reduced. Atypical lymphocytes were not observed. The serum lactic dehydrogenase (LDH; 1770 U/L; normal, 224,454 U/L), aspartate aminotransferase (AST; 140 U/L; normal, 10,30 U/L), and alanine aminotransferase (ALT; 57 U/L; normal, 3,29 U/L) levels were elevated. The soluble interleukin-2 (IL-2) receptor level was high (25,300 U/mL; normal, 167,497 U/mL). Epstein,Barr virus (EBV) serologic examination showed the immunoglobulin G (IgG) viral capsid antigen (VCA) at 1 : 320 and the EBV nuclear antigen (EBNA) at 1 : 40. IgM VCA and EBV early antigen-diffuse restricted antibody (EA) IgA and IgG were not detectable. Histologic findings from the left chest skin showed a distribution of atypical lymphocytes from the upper dermis to the subcutaneous tissue, and many foamy cells which had phagocytosed the hemocytes (Fig. 2a,b). Immunohistochemical analysis showed that the atypical lymphocytes were sCD3,, CD4,, CD8,, CD20,, CD56+, granzyme B+, and T-cell intracellular antigen (TIA-1) positive. Furthermore, EBV-encoded small RNAs (EBER), detected by in situ hybridization, exhibited a strong signal. The nasal lesions biopsied 6 years previously showed an identical staining pattern with the skin lesions immunohistochemically. Analysis of the T-cell receptor-, (TCR-,), TCR-,, and TCR-, gene did not reveal any clonal rearrangements, but the EBV gene was detected from the skin specimens by Southern blotting. Our patient's condition was diagnosed as a case of extranodal NK/T-cell lymphoma, nasal type, but the patient had concomitantly developed hemophagocytic syndrome (HPS). She was treated with a combination of steroid pulse therapy and chemotherapy (pirarubicin hydrochloride 30 mg/m2, cyclophosphamide 500 mg/m2, vincristine 1 mg/m2, prednisolone 30 mg/m2, etoposide 80 mg/m2). After the first session of chemotherapy, the lesions on the chest and abdomen diminished, but, 2 weeks later, the skin lesions recurred, and disseminated intravascular coagulation (DIC) induced by HPS supervened. The patient died as a result of multiple organ failure induced by HPS. Figure 1. Multiple infiltrated erythemas, erosions, and ulcers on the breast and abdomen Figure 2. Histologic findings of a skin biopsy specimen from the left chest (hematoxylin and eosin staining). (a) Dense infiltration of atypical lymphocytes from the upper dermis to the subcutaneous tissue (×40). (b) Many foamy cells had phagocytosed the hemocytes (×400) [source] Paraneoplastic Sweet's syndrome in a patient with hemophagocytic syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Wan-Lung Lin MD No abstract is available for this article. [source] Intravascular lymphoma associated with systemic lupus erythematosusINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2004Masanao Naya Abstract We report a case of systemic lupus erythematosus (SLE) associated with intravascular (angiotropic) lymphoma. A 27-year-old woman had been suffering from uncontrolled severe eruptions for a long time and was admitted because of high fever due to hemophagocytic syndrome (HPS). As her SLE had not been well-controlled by moderate doses of steroids and azathioprine, autoimmune associated HPS was first considered. She was initially treated with steroid pulses and ,-globulin for HPS. However, chromosomal analysis of bone marrow cells revealed severe abnormalities. After malignant lymphoma-associated HPS was diagnosed, chemotherapy was commenced in the intensive care unit with artificial respiration and continuous hemodiafiltration. The patient died of cerebral infarction at day 45. It is suggested that the SLE itself was associated with the development of the intravascular lymphoma rather than due to the azathioprine. [source] Fatal Subcutaneous Panniculitis-Like T-Cell Lymphoma (Sptcl) with Interface Change and Dermal Mucin, A Dead-Ringer for Lupus ErythematosusJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005L. Ma We report a 48-year-old male who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition. The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3+CD4,CD8+/,CD56+. Monoclonal rearrangements of T-cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow. This case is amongst rare reports of subcutaneous panniculitis-like T-cell Lymphoma (SPTCL) with systemic involvement. [source] A Retrospective Study of the Incidence and the Classification of Bone Marrow Disorders in the Dog at a Veterinary Teaching Hospital (1996,2004)JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2006Douglas J. Weiss Background: An 8-year retrospective study was conducted to evaluate the prevalence and the classification of canine bone marrow disorders in a clinical pathology service at a university referral hospital. Animals: Dogs evaluated for bone marrow disorders at a veterinary teaching hospital. Hypothesis: A better understanding of the spectrum and the prevalence of canine bone marrow disorders can be achieved with a multiyear retrospective study. Methods: Bone marrow aspirate smears, core biopsy specimens, and case records from 717 dogs were reviewed. Results: Bone marrow specimens were first categorized based on the presence or the absence of a primary bone marrow disorder. Nondysplastic and nonmalignant pathologic changes were placed into 14 subcategories. Frequently observed pathologic disorders included nonregenerative immune-mediated anemia, pure red cell aplasia, bone marrow necrosis, myelofibrosis, and hemophagocytic syndrome. Dysmyelopoiesis (n = 61) was subcategorized into myelodysplastic syndromes (n = 27), and congenital (n = 1) and secondary (n = 33) dysmyelopoiesis. One hundred twenty-six cases of neoplasia were divided into acute leukemia (n = 46), chronic leukemia (n = 7), stage 5 malignant lymphoma (n = 28), multiple myeloma (n = 25), malignant histiocytosis (n = 11), metastatic mast-cell tumor (n = 3), sarcoma (n = 5), and carcinoma (n = 1). Conclusions and Clinical Importance: This study provides a general indication of the spectrum and the prevalence of canine bone marrow disorders at a referral center in North America. [source] Fatal infectious mononucleosis with evidence suggestive of the development of B cell lymphomaPATHOLOGY INTERNATIONAL, Issue 9 2003Kenzo Hiroshima A 4-year-old girl presented to a local hospital in August 1999 with fever and cervical lymphadenopathy. A diagnosis of Epstein,Barr virus (EBV) infection was made and the patient was treated with corticosteroids. One month later she developed dyspnea secondary to tonsilar swelling, and underwent tonsillectomy and adenoidectomy. Her dyspnea increased, however, and by mid September she required mechanical ventilation. Six weeks later, she was transferred to Chiba Children's Hospital (Chiba, Japan). Despite vigorous treatment, she died within four weeks of admission. At autopsy, microscopic examination revealed numerous histiocytes with frequent hemophagocytosis in her lungs, liver, spleen, thymus, and lymph nodes. The tentative diagnosis was EBV-associated hemophagocytic syndrome (EBVAHS). A proliferation of atypical lymphocytes was observed in the lymph nodes, the majority of which stained positive with CD79a antibody. A whitish nodule, 8 mm in diameter, was noted in her right ovary. It consisted of a proliferation of pleomorphic lymphoid cells expressing CD79a antigen. In situ hybridization detected EBV RNA within CD79a antigen-positive cells in the lungs, spleen, thymus, bone marrow, lymph nodes, and the right ovary. Polymerase chain reaction analysis of DNA from the ovarian nodule demonstrated a monoclonal rearrangement of the immunoglobulin heavy chain gene indicating that it consisted of a clone of B lymphocytes. We suggest that EBVAHS develops into polyclonal and monoclonal lymphoproliferative disorder in a short period, and that EBVAHS is a preneoplastic condition that may result in B cell lymphoma. [source] Anaplastic large cell lymphoma presenting as hemophagocytic syndrome in an adolescentPEDIATRIC BLOOD & CANCER, Issue 7 2007P. Sovinz MD No abstract is available for this article. [source] Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: A report from the HLH studyl centerPEDIATRIC BLOOD & CANCER, Issue 2 2003Shinsaku Imashuku MD Abstract Background Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), also known as EBV-associated hemophagocytic syndrome, develops mostly in children and young adults and may be fatal. Early etoposide treatment has been confirmed to be effective in children. However, it is unclear whether the same treatment is useful in adults. Procedure To assess whether etoposide is effective in treating young adult cases, we retrospectively studied the therapeutic measures taken and outcomes in 20 young adult cases of EBV-HLH. Eleven cases were registered in our HLH study center in Kyoto and nine derived from the literature. The patients were between 17 and 33 years old and eight were males. The influence of gender, cell lineage (T- or natural killer-), EBV serology pattern, jaundice and treatment on the outcome was assessed. Results and Conclusions Patients receiving etoposide within four weeks after diagnosis had a good prognosis as five of the seven patients survived compared to one of 13 not treated with etoposide or treated late (chi-square test for survival, P,=,0.0095). The Kaplan,Meier analysis showed the 2.5-year survival of 85.7,±,13.2% in the early etoposide-treated patients, compared to 10.3,±,9.4% in the remaining patients (log-rank test, P,=,0.0141). Thus, early etoposide treatment is effective in treating EBV-HLH in young adults as well as in children. Med Pediatr Oncol 2003;41:103,109. © 2003 Wiley-Liss, Inc. [source] Low glycosylated ferritin, a good marker for the diagnosis of hemophagocytic syndromeARTHRITIS & RHEUMATISM, Issue 5 2008Laurence Fardet Objective A very low percentage of glycosylated ferritin (<20%) has only been reported in association with adult-onset Still's disease (AOSD), a disease classically associated with hemophagocytic syndrome. We undertook this study to determine whether hemophagocytic syndrome outside the context of AOSD is also associated with a very low percentage of glycosylated ferritin. Methods From October 2006 to September 2007, the serum level of glycosylated ferritin was determined in all consecutive patients seen in 3 departments and for whom the diagnosis of hemophagocytic syndrome was suspected. The level of glycosylated ferritin in these patients was compared with that in age- and sex-matched controls with a marked inflammatory syndrome not associated with hemophagocytic syndrome. We assessed the value of glycosylated ferritin as a marker for the diagnosis of hemophagocytic syndrome. Results Forty-two patients were included in the study (14 with confirmed hemophagocytic syndrome, 7 with suspected but unconfirmed hemophagocytic syndrome, and 21 controls). The median level (interquartile range [IQR]) of total serum ferritin was significantly higher in patients with confirmed hemophagocytic syndrome (3,344 ,g/liter [2,074,7,334]) than in patients with suspected but unconfirmed hemophagocytic syndrome (555 ,g/liter [464,1,420]) (P = 0.02) or in controls (451 ,g/liter [126,929]) (P < 0.001). The median (IQR) percentage of glycosylated ferritin was significantly lower in patients with confirmed hemophagocytic syndrome (10% [3,14]) than in patients with suspected but unconfirmed hemophagocytic syndrome (40% [36,47]) (P < 0.001) or in controls (36% [26,49]) (P < 0.001). The diagnostic performance of glycosylated ferritin tended to be higher than that of total serum ferritin for the diagnosis of hemophagocytic syndrome (area under the receiver operating characteristic curve [95% confidence interval] 0.97 [0.92,1.00] versus 0.79 [0.59,1.00]; P = 0.10). Conclusion These results suggest that glycosylated ferritin may be a helpful marker for the diagnosis of hemophagocytic syndrome. [source] Pathogenesis and mechanism of disease progression from hemophagocytic lymphohistiocytosis to Epstein,Barr virus-associated T-cell lymphoma: Nuclear factor-,B pathway as a potential therapeutic targetCANCER SCIENCE, Issue 9 2007Huai-Chia Chuang Epstein,Barr virus (EBV) can infect T lymphocytes and manifests as hemophagocytic lymphohistiocytosis (HLH), a distinct entity of hemophagocytic syndrome (HPS) characterized by fever, hepatosplenomegaly, cytopenia, hypercytokinemia, and systemic macrophage activation with hemophagocytosis. In a substantial percentage of HLH patients, the disease may relapse or progress to T-cell lymphoma in months to years. In the present review, the authors summarize the previous studies on the pathogenesis of HLH and the potential mechanism for the progression of disease from HLH to T-cell lymphoma. The infection of T cells by EBV could activate T cells to secrete proinflammatory cytokines, particularly tumor necrosis factor-, (TNF-,), which subsequently activate macrophages. EBV latent membrane protein-1 (LMP-1) is the viral product responsible for the activation of the TNF receptor (TNFR) associated factors/nuclear factor-,B (NF-,B)/ERK pathway to enhance cytokine secretion mediated through the suppression of the SAP/SH2D1A gene. The activation of NF-,B will confer resistance to TNF-,-induced apoptosis on EBV-infected T cells through the down-regulation of TNFR-1. Consistent with in vitro observations, EBV-associated T or natural killer/T-cell lymphoma showed constitutive activation of NF-,B, explaining its drug resistance, hypercytokinemia, and poor prognosis. Therefore, similar to other inflammation-associated cancers, HLH provides a unique model to study the mechanism of disease progression from a benign virus-infected disorder (HLH) to T-cell lymphoma. Inhibition of the NF-,B signal pathway should provide a potential target for the treatment of HLH and EBV-associated T-cell lymphoma. (Cancer Sci 2007; 98: 1281,1287) [source] Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasisIMMUNOLOGICAL REVIEWS, Issue 1 2005Gael Ménasché Summary:, 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. [source] Life-threatening hemophagocytic syndromes: Current outcomes with hematopoietic stem cell transplantationPEDIATRIC TRANSPLANTATION, Issue 2005Alexandra H. Filipovich Abstract:, Life-threatening hemophagocytic syndromes represent a subset of genetic disorders of inflammation. Many are rapidly lethal and can only be definitively treated at the present time with allogeneic hematopoietic stem cell transplantation (HSCT). In this report, current results with allogeneic transplantation for Hemophagocytic Lymphohistiocytosis (HLH) are described. HLH typically presents symptomatically during infancy and early childhood and can be identified by a constellation of numerous physical findings and laboratory tests indicative of overwhelming inflammation. The majority of patients with familial HLH lack natural killer (NK) cell function; in approximately 50% of cases the specific underlying genetic cause can now be discerned. Effective treatment consists of initial combination therapy with proapoptotic chemotherapy (typically etoposide) and anti-inflammatory therapies (principally steroids) in addition to aggressive supportive care, followed by allogeneic HSCT from the best available donor. Over the past 25 yr, through collaborative worldwide efforts, survival of children with HLH and related disorders has improved from 5% at 1 yr after diagnosis to greater than 50% 3,5 yr after diagnosis. [source] | |||||||||||||||||||||||||