Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In 1994 the Histiocyte Society initiated a prospective international collaborative therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected patients, intrathecal methotrexate), followed by bone marrow transplantation (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994, and June 30, 1998, 113 eligible patients aged no more than 15 years from 21 countries started HLH-94. All had either an affected sibling (n = 25) and/or fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of 3.1 years, the estimated 3-year probability of survival overall was 55% (95% confidence interval +/- 9%), and in the familial cases, 51% (+/- 20%). Twenty enrolled children were alive and off therapy for more than 12 months without BMT. For patients who received transplants (n = 65), died prior to BMT (n = 25), or were still on therapy (n = 3), the 3-year survival was 45% (+/- 10%). The 3-year probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly improved.
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PMID:Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. 1223 44

A 7-year-old previously healthy Czech boy was admitted due to fever, hepatosplenomegaly and pancytopenia. Aspiration of bone marrow revealed no signs of hemoblastosis (nor hemophagocytosis). He was treated with antibiotics and virostatics without effect. Progression of hepatosplenomegaly and pancytopenia induced suspicion of hemophagocytic lymphohistiocytosis (HLH). Five weeks later, bone marrow hemophagocytosis of erythrocytes, nuclear elements and platelets was detected. He was given corticoids and intravenous immunoglobulins and transferred to our haematology department. Laboratory findings of mild pancytopenia, hypofibrinogenaemia, hyperlipidaemia and elevated levels of ferritin, LDH and immunoglobulins were compatible to the diagnosis of HLH. Immunologic evaluation revealed T-lymphocyte activation. Appropriate immunosuppressive treatment with Dexamethasone, etoposide and Cyclosporine A was launched, followed by transient subside of fever and improvement of peripheral blood count, but not regression of hepatosplenomegaly. Four weeks later, relapse of fever and deterioration of blood count led to intensification of immunosuppression. However, no effect was evident. Moreover, hypertrophic cardiomyopathy with ventricular arrhythmia occurred. Treatment with antilymphocytic globulin for resistant course of HLH was planned. Before that, a fifth bone marrow aspiration was performed. Surprisingly, many Leishmania amastigotes were observed within marrow macrophages. Leishmania infection was confirmed by positive serology. Immunosuppressive treatment was withdrawn and changed for causal treatment with liposomal Amphotericin B. Positive clinical effect with subside of fever was evident in ten days, splenomegaly gradually resolved during three weeks, restoration of normal blood count lasted six weeks. No relapses of HLH nor leishmaniasis occurred. In control bone marrow aspirate performed three months later, the parasites were not detected. Ten months after the event, the patient is in complete remission of HLH with normal immunologic parameters. Most probably, he contracted visceral leishmaniasis during a visit of a Neapol area in Italy 3 months before the onset of the disease.
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PMID:[Hemophagocytic lymphohistiocytosis as a manifestation of visceral leishmaniasis]. 1242 69

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative option for primary hemophagocytic lymphohistiocytosis (HLH), a rare disease of infants and young children, characterized by recurrent fever, hepatosplenomegaly, and cytopenia. We report a case of successful engraftment and stable full-donor chimerism in a patient with HLH who underwent peripheral allogeneic CD34-selected HSCT. The donor was his 1-antigen-HLA-mismatched grandmother. After a conditioning regimen based on the combination of thiotepa, fludarabine, melphalan, and rabbit antilymphocyte serum, the patient received a megadose of 26.3 x 10(6)/kg of CD34(+) peripheral blood cells. Neutrophil (>0.5 x 10(9)/L) and platelet (>50 x 10(9)/L) engraftment was observed on days +16 and +12, respectively, and the patient was discharged home on day +24. No acute or chronic GVHD was observed. Infectious complications were the main causes of re-hospitalization in the first year after transplantation, but no significant morbidity was observed thereafter. Thirty-two months after HSCT, the patient is alive and well, still in complete clinical remission of his underlying disease with a durable engraftment, normal NK activity and full donor chimerism. This case suggests that a fludarabine-based conditioning regimen and CD34-selected peripheral allogeneic HSCT may be a feasible option in case of unavailability of a fully HLA-matched related or unrelated donor.
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PMID:Successful engraftment and stable full donor chimerism after myeloablation with thiotepa, fludarabine, and melphalan and CD34-selected peripheral allogeneic stem cell transplantation in hemophagocytic lymphohistiocytosis. 1255 20

A 66-year-old man was admitted to our hospital for fever on January 19, 1998. He began showing periodic high fever in June 1997 and an increased serum LDH in August 1997. His history included surgery for esophageal cancer in 1993. On admission, the patient's body temperature was 38.5 degrees C. Physical examination was negative for lymphadenopathy, hepatosplenomegaly, and skin rash. Peripheral blood revealed a hemoglobin level of 8.6 g/dl and a platelet count of 7.9 x 10(4)/microliter. Bone marrow examination showed hypocellularity with marked histiocytic hemophagocytosis. The various bacterial cultures were negative. Serum LDH was elevated to 1,606 IU/l, and ferritin was greater than 3,000 ng/ml. Antinuclear antibodies were negative. No significant elevation of viral antibody titers including that to Epstein-Barr virus was found. Hemophagocytic syndrome (HPS) was diagnosed, but no underlying diseases was identified. The patient's condition was complicated by interstitial pneumonia and pleural effusion. gamma-globulin and pulse methylprednisolone both proved ineffective for the HPS; however, complete remission was achieved with cyclic intravenous administration of etoposide (VP-16, 150 mg/day). Interestingly, the interstitial pneumonia resolved promptly with etoposide therapy. The patient relapsed, in July 2001, exhibiting high fever, cytopenia, and marrow hemophagocytosis. His condition was ameliorated by administration of etoposide. This was a rare case of chronic and recurrent HPS of unknown etiology accompanied by interstitial pneumonia. Etoposide should be considered as a primary therapy for HPS and its complications in cases such as our patients.
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PMID:[Successful use of etoposide in an elderly patient with chronic recurrent hemophagocytic syndrome]. 1270 51

Hemophagocytic syndrome (HPS) in systemic lupus erythematosus(SLE) patients has not commonly been reported. In this case study, we report the first case of Mycobacterium avium complex (MAC)-associated hemophagocytic syndrome in a patient with systemic lupus erythematosus (SLE). This SLE patient, a 15-year-old girl, had been on a high dose of prednisolone (> 0.5mg/kg/day) for more than 3 years. She presented with a spiking fever, hepatosplenomegaly, pancytopenia, hyperferritinemia and adult respiratory distress syndrome. Bone marrow examination revealed hemophagocytosis as well as non-caseating granulomatosis. There was no indication of SLE fare-up. She responded poorly to initial treatment with methyl-prednisolone, intravenous immumoglobulin, etoposide, and drugs for Mycobacterium tuberculosis including rifampin, ethambutol, isoniazid and pyramide. However, gastric lavage culture revealed MAC. Following treatment with clarithromycin, ciprofloxacin and amikacin, her condition gradually improved and she was discharged 3 months after admission. In SLE patients with pancytopenia and hyperferritinemia, MAC-associated HPS should be considered in the differential diagnosis.
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PMID:Mycobacterium avium complex-associated hemophagocytic syndrome in systemic lupus erythematosus patient: report of one case. 1272 56

Hemophagocytic lymphohistiocytosis is a rare and fatal disorder of early infancy, which affects predominantly the mononuclear phagocyte system and is characterized by the presence of fever, hepatosplenomegaly and cytopenia. Neurological symptoms can be extremely variable, ranging from irritability, and convulsions to focal neurological signs. They often develop during disease progression, but can also be the leading initial symptoms. Early diagnosis is mandatory, because new treatments, including bone marrow transplantation, appear to be promising. Here we present the clinical, neuroradiological and histopathological findings from two children with progressive CNS disease as the main clinical manifestation of hemophagocytic lymphohistiocytosis. Both children died and diagnosis was only obtained in retrospect after careful review of the histopathological material.
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PMID:CNS disease as the main manifestation of hemophagocytic lymphohistiocytosis in two children. 1500 52

Haemophagocytic syndrome is a rare disorder of immune regulation. Clinical features are fever, haemophagocytosis, hepatosplenomegaly, pancytopenia, lymph nodes enlargement, hypertriglyceridaemia and coagulopathy. Systemic findings may also include pulmonary infiltrates, renal failure and an inappropriate antidiuretic state. It has been described associated to many diseases, like lymphomas, most of them T-cell lymphomas, infections and systemic diseases, among other entities. Haemopoietic cells are actively ingested by monocytes and macrophages in lymph nodes, bone marrow, liver and spleen. This is a diagnostic criteria for haemophagocytic syndrome. The treatment of haemophagocytic syndrome is difficult and requires intensive supportive therapy, treatment of coagulopathy disorders, high-dose corticosteroids and immunosuppressive treatment, although in most cases there is no response to treatment and the evolution is fatal. The T-cell lymphomas that involve subcutaneous tissue and simulate panniculitis are classified recently as primary cutaneous T-cell lymphomas, and their presentation as inflammatory nodules of the legs are uncommon.
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PMID:[Haemophagocytic syndrome and cutaneous T-cell lymphoma]. 1504 94

We describe a 3 year-old male who presented with fever and cerebellar dysfunction after varicella. He developed transient hepatosplenomegaly, cytopenias, and progressive central nervous system involvement (coma, status epilepticus, and hydrocephalus). Despite normal initial cranial computed tomographic scan, diffuse swelling of the cerebellum with downward tonsillar herniation ensued. Diagnosis of hemophagocytic lymphohistiocytosis was difficult and delayed because of the relapsing course, and complete diagnostic criteria were not fulfilled at initial presentation. Central nervous system disease preceded the typical clinical picture of this disease; it dominated the clinical course and caused life-threatening complications and sequelae. The patient improved after treatment, according to the hemophagocytic lymphohistiocytosis protocol (HLH-94) of the Histiocyte Society, with dexamethasone, etoposide, and cyclosporine and unrelated cord blood stem cell transplantation. A mutation in the perforin gene confirmed the diagnosis of familial hemophagocytic lymphohistiocytosis.
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PMID:Near fatal cerebellar swelling in familial hemophagocytic lymphohistiocytosis. 1516 42

Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, fatal disorder of infancy. We report here a 17-day-old female infant who presented with high fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, thrombocytopenia, and liver failure. Leukocytosis was detected with circulating "atypical" lymphoid cells. Flow cytometric studies revealed expanded subpopulations of CD8+ T cells with unusual immunophenotypic features, including a subset that lacked CD5 expression. A liver biopsy showed hemophagocytic lymphohistiocytosis with exuberant infiltrates of CD8+ T cells that lacked perforin. Mutational studies revealed a 666C-->A (H222Q) missense mutation in the perforin gene. T-cell receptor studies on flow-sorted T-cell subpopulations revealed no evidence of monoclonality. Analysis of T-cell receptor excision circle levels indicated long proliferative history in the aberrant CD8+ T-cell subsets. This case provides an instructive example of uncontrolled reactive proliferation of CD8+ T cells in FHL, resulting in atypical morphology and unusual immunophenotypic features that might suggest malignancy in other clinical settings.
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PMID:Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis. 1520 66

Hemophagocytic syndrome (HPS) is an unusual acute syndrome presenting with fever, hepatosplenomegaly, and cytopenias. The hallmark of HPS is the accumulation of activated macrophages that engulf hematopoietic cells in the reticuloendothelial system. Most cases of HPS in adults are secondary to infection or malignancy, and thus investigation of the underlying disease is necessary. We describe a patient with prolonged fever, HPS, and chromosomal abnormalities in the bone marrow who underwent thorough evaluation for the cause of his symptoms. A final diagnosis of acute lymphoblastic leukemia (ALL) was established in a fourth, repeated bone marrow biopsy performed more than 2 months after the first presenting symptom appeared. This unusual case demonstrates the importance of cytogenetic abnormalities found in cases of HPS and the importance of repeated testing when an underlying disease is suspected.
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PMID:Prolonged fever of unknown origin and hemophagocytosis evolving into acute lymphoblastic leukemia. 1572 3


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