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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemophagocytic lymphohistiocytosis, terminology that designates a syndrome that may be familial or sporadic, with or without an associated viral infection, is presented as the prototype of a hemophagocytic syndrome, a condition in which there is uncontrolled activation of the cellular immune system. Diagnostic criteria include idiopathic fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, and the presence of hemophagocytosis. The surgical and autopsy pathology features infiltrates composed of lymphocytes and ordinary, but activated, histiocytes and hemophagocytosis. The chronic hepatitis-like hepatic lesion is noted to be characteristic, if not unique, in this age group and setting. Current concepts of pathophysiology focus on the role of cytokines, particularly interleukin (IL)-1, IL-2, soluble IL-2 receptor, plasminogen activator, and prostaglandins. The clinicopathologic features of the syndrome can be accounted for by the uncontrolled and unopposed production and release of these mediators. Nosology places hemophagocytic lymphohistiocytosis in the position of the most important of the "benign" histiocytosis syndromes that involve ordinary histiocytes of the mononuclear phagocytic system in contrast to Langerhans cell histiocytosis (histiocytosis X) in which pathological dendritic histiocytes are operative. Features that distinguish hemophagocytic lymphohistiocytosis from other disorders, such as malignant histiocytosis, X-linked lymphoproliferative disorder, congenital immunodeficiency states, the accelerated phase of Chediak-Higashi syndrome, and cytophagic histiocytic panniculitis, which may be associated with a hemophagocytic syndrome, are presented.
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PMID:Hemophagocytic lymphohistiocytosis: a hemophagocytic syndrome. 156 89

We retrospectively studied the incidence of familial hemophagocytic lymphohistiocytosis (FHL) in children during the 16-year period 1971-86. First, all departments of pediatrics, pathology, and infectious diseases were enquired for children with FHL or disorders resembling FHL. Secondly, the causes of death of all children who died during the study period in Sweden (n = 19,542) were also investigated. Files and histological specimens were further studied in selected children. By using a set of inclusion/exclusion criteria, we found 32 children with FHL. The incidence was 1.2/1,000,000 children per year. One child per 50,000 live borns developed FHL during this period. The sex ratio was close to 1:1. Prominent early clinical signs were fever (91%), splenomegaly (84%), hepatomegaly (90%), rash (43%), and lymph node enlargement (42%). Neurological symptoms, which developed in 47%, could totally dominate the clinical picture and develop prior to other symptoms and signs. Common laboratory findings were pancytopenia, hypertriglyceridemia, hypofibrinogenemia, elevated serum transaminases, hyperbilirubinemia, hyponatremia, hypoalbuminemia, and a moderate spinal fluid pleocytosis. Chest X-ray often revealed mostly discrete pulmonary infiltrates. FHL is an underdiagnosed disease and in only 11/32 children was diagnosis made during their lifetime. It is important to be aware of the disorder as potential therapy now exists.
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PMID:Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. 205 92

A male patient, aged 23 years, with no notable previous history, was admitted to hospital because of fever, splenomegaly, and pancytopenia. The bone marrow was infiltrated by mature looking histiocytes displaying erythrophagocytosis. Other findings included polyclonal hypergammaglobulinemia, elevated transaminases, hypofibrinogenemia, and hypertriglyceridemia. A diagnosis of virus-associated hemophagocytic syndrome was made and virology studies attributed it to herpes simplex virus type 1. Therapy with acyclovir, high dose i.v. immunoglobulins, and vinblastine was unsuccessful. With the addition of prednisone, a remission, with disappearance of histiocytic marrow involvement, was obtained but was of short duration, and the outcome was fatal.
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PMID:[Hemophagocytic syndrome associated with herpes simplex virus. Apropos of a case with a fatal outcome]. 380 39

In a 41-year-old woman who had suffered from hypofibrinogenemia, thrombocytopenia, leukopenia and splenomegaly for several years a causative hamartoma of the spleen (splenoma) was removed surgically. The results of a preoperative therapeutic trial with heparin, the marked accumulation of 125I-activity in the splenoma following intravenous injection of radioiodinated fibrinogen, the immunohistochemical demonstration of extensive fibrinogen deposits in the splenoma, and normalization of fibrinogen levels and blood cell counts after surgery point to the pathogenetic role of this rare splenic tumor. The salient clinical and pathological features of 41 splenoma cases in the literature are briefly reviewed. Hematologic signs were observed in only 9 splenoma patients.
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PMID:[Chronic defibrination syndrome and thrombocytopenia in splenic hamartoma (splenoma)]. 711 62

Described here is an autopsy case of a 30-year-old woman with systemic hemangiomatosis accompanied by coagulopathy and microangiopathic hemolytic anemia. She had hepato-splenomegaly, anemia, thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, and fibrinogenopenia. A splenectomy was performed and a diffuse angioma of the spleen was found. Postmortem examination revealed cavernous hemangiomas and hemangioendotheliomatous lesions in the liver, bone marrow, intestine, and lymph nodes. Coagulation studies suggested that exacerbation of coagulopathy occurred due to Liniac (10MV X-ray) irradiation. Our observation raised the possibility that the irradiation might lead to chronic localized consumption coagulopathy, which was confined to the hemangioma, to acute disseminated types of intravascular coagulation.
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PMID:Diffuse hemangiomatosis, coagulopathy and microangiopathic hemolytic anemia. 723 17

Hemophagocytic lymphohistiocytosis (HLH) is a rare, often fatal, disease of early infancy. The diagnosis of HLH is frequently delayed or made at autopsy because no genetic or biologic marker has been identified. To improve the classification and treatment of HLH, the Histiocyte Society has established an 'International Registry for HLH'. Data collected included family history, clinical and laboratory features at the onset of illness, and treatment outcome. Stringent diagnostic criteria (ie fever, splenomegaly, cytopenia, hypertriglyceridemia, and/or hypofibrinogenemia, and hemophagocytosis without evidence of malignancy) were used for patient selection. One hundred and twenty-two patients (61 males, 61 females) were enrolled from 17 centers in 11 countries. The rate of parental consanguinity was 24%. A positive family history was reported in 49% of cases including two pairs of affected male twins. The median age at disease onset was 2.9 months, with no difference between familial and sporadic cases. Age at onset was similar in affected sibs from 10 of 14 families, but in four up to 3-year differences were observed. Hemophagocytosis was present at diagnosis in 75%. An associated infection (usually by common viral pathogens) was reported in 50 of the 122 (41%) cases, of which 25 had familial disease. Natural killer activity was impaired in 36 of 37 patients studied. Chromosome analysis was normal in all tested patients. A decreased frequency of HLA-B7 and B8 alleles and increased frequency of HLA-B21 and DQ3 were observed. The estimated 5-year survival (SE) was 21% (18.7) for all patients. It was 66% (37.8) for patients who received allogeneic bone marrow transplant and 10.1% (9.6) for patients treated with chemotherapy alone (P=0.0001). None of the previously proposed prognostic indicators (age, associated infection, cerebrospinal fluid pleocytosis, family history) correlated with treatment outcome.
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PMID:Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. 863 26

Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by proliferation and non-malignant activation of histiocytes and T lymphocytes in the reticuloendothelial system. Diagnostic guidelines include fever, splenomegaly, cytopenia, hypertriglyceridemia and/or hypofibrinogenemia with hemophagocytosis in the bone marrow, spleen or lymph nodes. In many patients diagnosis is difficult due to the lack of diagnostic criteria, hemophagocytosis, variability of clinical presentation, spontaneous improvement and the absence of a specific marker of the disease. When there is strong clinical suspicion of FHL, chemotherapy and immunosuppressor treatment should be started early to achieve complete cure and should be followed by hematopoietic stem cell transplantation. We present the case of a 2-month-old girl who presented fever, anemia and thrombocytopenia, enlarged liver and spleen, hyperferritinemia, hypertriglyceridemia, and hypertransaminasemia without the finding of hemophagocytosis in bone marrow. Two of the girl's relatives had died of fulminant hepatic failure of unknown etiology. The patient improved spontaneously but presented reactivation of the disease 3 weeks later and died after splenic biopsy.
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PMID:[Difficulties in the diagnosis of familial hemophagocytic lymphohistiocytosis]. 1182 68

The hemophagocytic syndrome (HPS) is an uncommon, often misdiagnosed life-threatening disorder of immune regulation, characterized by a widespread proliferation and multisystemic infiltration of non-malignant histiocytes that undergo uncontrolled hemophagocytosis in bone marrow and/or reticulo-endothelial system. The HPS immune dysfunction consists in a low or absent cytotoxic T and natural killercell activity and in hyperactivation of T lymphocytes and macrophages, with consequent proinflammatory cytokine storm. Clinically, HPS is characterized by high fever, lymphadenopathies, hepato-splenomegaly, liver dysfunction, (pan)cytopenia, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, as well as coagulopathy and neurological manifestations in many cases. A hereditary/primary variant (familial hemophagocytic lymphohistiocytosis) and an acquired/secondary form (reactive HPS) are known. This latter may occur in several disorders, including infections, immunodeficiency states, malignancies, lymphoproliferative and autoimmune diseases. Without treatment, HPS fatally has an unfavourable prognosis. Recently, outcome improvements have been reported, due to better therapeutic strategies. The clinical and pathological features of this syndrome are reviewed.
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PMID:[The hemophagocytic syndrome (macrophage activation syndrome)]. 1271 99

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder with familial and acquired forms. The familial form is associated with mutations in the perforin gene and both forms are associated with severe defects in lymphocyte cytotoxic function. We examined perforin-deficient mice as a model of HLH in order to gain insight into this poorly understood disorder. While these mice do not spontaneously develop HLH-like symptoms, we found that they manifest all of the features of HLH after infection with lymphocytic choriomeningitic virus (LCMV). Following LCMV infection, perforin-deficient mice develop fever, splenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevation of multiple serum cytokine levels, and hemophagocytosis is evident in many tissues. Investigation into how this phenotype develops has revealed that CD8+ T cells, but not natural killer (NK) cells, are necessary for the development of this disorder. Cytokine neutralization studies have revealed that interferon gamma (IFNgamma) is uniquely essential as well. Finally, the excessive amount of IFNgamma seen in affected mice appears to be driven by increased antigen presentation to CD8+ T cells. These studies provide insight into the pathophysiology of HLH, and provide new targets for specific therapeutic intervention in this fatal disorder.
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PMID:An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. 1506 16

In HLH-94, the first prospective international treatment study for hemophagocytic lymphohistiocytosis (HLH), diagnosis was based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). In HLH-2004 three additional criteria are introduced; low/absent NK-cell-activity, hyperferritinemia, and high-soluble interleukin-2-receptor levels. Altogether five of these eight criteria must be fulfilled, unless family history or molecular diagnosis is consistent with HLH. HLH-2004 chemo-immunotherapy includes etoposide, dexamethasone, cyclosporine A upfront and, in selected patients, intrathecal therapy with methotrexate and corticosteroids. Subsequent hematopoietic stem cell transplantation (HSCT) is recommended for patients with familial disease or molecular diagnosis, and patients with severe and persistent, or reactivated, disease. In order to hopefully further improve diagnosis, therapy and biological understanding, participation in HLH studies is encouraged.
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PMID:HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. 1693 60


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