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)

Macrophage activation syndrome is a rare and potentially fatal complication of many childhood pathological settings, most frequently reported in systemic onset-juvenile idiopathic arthritis. The disruption of the macrophage-lymphocyte interaction leads to uncontrolled proliferation of highly activated macrophages and T lymphocytes. The syndrome comprises a heterogeneous group of disorders featuring sepsis-like characteristics typically combined with impaired function of natural killer cells and cytotoxic T-cells, haemophagocytosis and hypercytokinemia, often resulting in fatal multiple organ failure. The clinical picture shows high grade fever, hepatosplenomegaly, pancytopenia, lymphoadenopathy, central nervous system involvement and consumptive coagulopathy. Macrophage activation syndrome is associated with high mortality: even though diagnostic criteria have been proposed, definite diagnosis can be a challenge for clinicians, especially in early phases. There is no standardized therapeutic protocol for macrophage activation syndrome, but it is widely recognized that aggressive treatment strategies might strongly influence prognosis. First line-therapy is usually represented by parenteral administration of high dose-corticosteroids, whilst cyclosporine is added in the steroid-resistant cases. In this paper we provide clinical clues and summarize the most recent studies about pathophysiology and management suggestions for macrophage activation syndrome.
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PMID:The clinical spectrum and treatment options of macrophage activation syndrome in the pediatric age. 1670 49

Reactive hemophagocytic syndrome (HS) occurs mainly in the setting of serious infections and lymphomas. HS can occur in the course of 2 active systemic diseases, without simultaneous infection: adult Still disease and systemic lupus erythematosus (SLE). Observations of specific lupus-associated HS are rare, and the long-term outcome of these patients with active SLE is unknown. We retrospectively studied 15 episodes of SLE-associated HS in 12 patients (10 women, 2 men) and noted the long-term outcome. HS occurred at a mean age of 25 years. All patients were febrile with >or=2 cytopenias, and bone marrow aspiration indicated hemophagocytosis. HS revealed SLE in 9 patients and recurred in 3. The main features of SLE-associated HS were a low frequency of hepatosplenomegaly, a high frequency of heart involvement (5 pericarditis, 4 myocarditis requiring transfer to intensive care unit), and a low C-reactive protein level (mean, 15 mg/L). Cutaneous-mucous symptoms of SLE, arthritis, and nephritis were present respectively in 8 (53%), 6 (40%), and 4 (27%) episodes, but symptoms of SLE were absent in 4 episodes at admission. All patients had anti-nuclear antibodies when the HS occurred. Anti-double-stranded DNA antibodies were present in 12 episodes. Treatment was steroids in 14 cases but cyclophosphamide was the only treatment able to control HS in 2 cases. All the cases of SLE-associated HS were controlled by the immunosuppressive regimen. Intravenous immunoglobulins seemed poorly effective. No infectious agent was found. Clinical presentations of the 23 patients with SLE-associated HS described in the literature were reviewed and were similar to those of the current series. The mean follow-up was 88 months (range, 7-240 mo). One patient died at 15 months (sepsis). Among the 5 patients with a follow-up >8 years, 4 always had active disease. During the follow-up of SLE, immunosuppressive drugs were added in 8 patients (cyclophosphamide in 7, azathioprine in 3, mycophenolate mofetil in 2) with significant adverse drug reactions. In the long-term, SLE-associated HS seems to define a severe SLE form with frequent flares, possible HS recurrences, and the need for prolonged immunosuppression.
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PMID:Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome. 1672 Dec 59

Classical galactosaemia (McKusick 230400) is an: autosomal recessive disorder of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712). Most patients present in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycaemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. The gold standard for diagnosis of classical galactosaemia is measurement of GALT activity in erythrocytes. Gas-chromatographic determination of urinary sugars and sugar alcohols demonstrates elevated concentrations of galactose and galactitol. The only therapy for patients with classical galactosaemia is a galactose-restricted diet, and initially all galactose must be removed from the diet as soon as the diagnosis is suspected. After the neonatal period, a lactose-free diet is advised in most countries, without restriction of galactose-containing fruit and vegetables. In spite of the strict diet, long-term complications such as retarded mental development, verbal dyspraxia, motor abnormalities and hypergonadotrophic hypogonadism are frequently seen in patients with classical galactosaemia. It has been suggested that these complications may result from endogenous galactose synthesis or from abnormal galactosylation. Novel therapeutic strategies, aiming at the prevention of galactose 1-phosphate production, should be developed. In the meantime, the follow-up protocol for patients with GALT deficiency should focus on early detection, evaluation and, if possible, early intervention in problems of motor, speech and cognitive development.
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PMID:Classical galactosaemia revisited. 1683 75

In this case report we describe the first case of hemophagocytic lymphohistiocytosis with concurrent cutis marmorata telangiectatica congenita. She had pancytopenia and hepatosplenomegaly, hemophagocytic cells in spleen necropsy, and she died with respiratory failure and pseudomonas induced septicemia.
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PMID:Hemophagocytic lymphohistiocytosis in a neonate with cutis marmorata telangiectatica congenita. 1710 57

Gaucher disease (GD) is a progressive macrophage lipidosis capable of causing disabling and life-threatening complications. Anecdotal experiences suggest that GD may go undiagnosed for many years, leading to severe complications that are preventable or reversible by enzyme replacement therapy (ERT) with imiglucerase. We conducted surveys of patients and Hematology-Oncology specialists to assess the frequency of diagnostic delays. Additionally, we report a series of patients who suffered diagnostic delays and as a result developed disabilities including potentially life-threatening manifestations of GD. Of 136 patients surveyed, the average time from first appearance of GD symptoms to final diagnosis was 48.7 +/- 123.6 months. More than two-thirds were evaluated and managed by a hematologist-oncologist (Hem-Onc). A global survey of 406 Hem-Oncs found that only 20% considered GD in the differential diagnosis for all of its classic symptoms (cytopenia, hepatosplenomegaly, bone pain); the diagnosis considered most likely included leukemia, lymphoma, and multiple myeloma. To illustrate actual consequences of diagnostic delays, we describe 14 patients with GD who suffered from symptoms for up to 10 years before correct diagnosis. Diagnostic delays led to complications that are preventable or reversible with ERT (i.e., avascular necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure, liver pathology). Patients homozygous for N370S mutation in this series were vulnerable to diagnostic delays. In conclusion, prolonged diagnostic delays occur in GD and may result in severe disease manifestations. Our findings suggest that physician education will increase the likelihood of prompt detection of GD and improve its management with ERT with imiglucerase when indicated.
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PMID:Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention. 1880 77

We present a case of Budd-Chiari syndrome (BCS) having two risk factors, Behcet's disease (BD) and oral contraceptive (OC) usage. A 33-year-old woman with BD was admitted to the Emergency Unit with nausea, vomiting, abdominal pain, abdominal distention, and confusion started 12 days ago before admission. Since the patient was in a shock state, she was taken to the Intensive Care Unit (ICU) with the suspicion of abdomen-originated sepsis. Abdominal ultrasound showed massive hepatosplenomegaly and moderate ascites. Abdominal MRI revealed an inferior vena cava (IVC) obstruction starting above the renal veins and diffuse thrombosis of the right and medial hepatic veins. An extensive thrombosis of the IVC and the hepatic veins (BCS) which led to shock was diagnosed. In addition to BD, the unnotified OC usage for a year by the patient without her doctor's knowledge was recognized as possible precipitating factor of BCS. Pulse methylprenisolone was started for three consecutive days to treat active BD-induced vasculitis. IVC digital subtraction angiography (DSA) showed occlusion of the IVC below the hepatic veins with extensive collateral circulation originating at the occlusion level suggesting that obliteration had a subacute or chronic course. Since intralesional thrombolytic therapy failed, the patient was transferred to a liver transplantation center. While waiting for an appropriate donor, the patient died due to hepatic failure. Since BCS is mortal and deemed multi-factorial, every patient with a thrombotic risk factor such as BD should be questioned for other possible causes of thrombosis.
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PMID:A case of Budd-Chiari syndrome with Behcet's disease and oral contraceptive usage. 1757 62

Systemic mastocytosis results in the accumulation of mast cells in various tissues. We report a rare case of systemic mastocytosis presenting with cholestatic liver disease. Our patient was a 60-year-old African-American woman who presented with diarrhea, weight loss, hepatosplenomegaly and cholestatic pattern of serum liver chemistry tests. Immunohistological stains with mast-cell tryptase and CD117 antibodies performed on the liver-biopsy tissue showed prominent mast cells. Subsequently, bone-marrow biopsy and small-bowel biopsies also showed mast-cell infiltration confirming the diagnosis of systemic mastocytosis. The patient underwent treatment with imatinib mesylate without response. Her disease transformed into acute myeloid leukemia and she ultimately died from sepsis. This case underscores the importance of including rare conditions like systemic mastocytosis in the differential diagnosis of cholestatic disorders.
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PMID:Aggressive systemic mastocytosis presenting with hepatic cholestasis. 1787 16

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition with high mortality. We report an extremely premature girl, born in the 24th gestational week (BW 732 g), that during her second month developed a severe HLH subsequent to a Serratia marcescens septicemia, with hepatosplenomegaly, cytopenias, hyperbilirubinemia (mostly conjugated, total bilirubin 916 mumol/L), hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia (21266 mug/L), and elevated sIL-2 receptor levels. Genetic analysis revealed no PRF1, STX11 or UNC13D gene mutations. Treatment was provided according to the HLH-2004 protocol with etoposide, dexamethasone, and immunoglobulin, but no cyclosporin because of immature kidneys. She recovered fully from the HLH but developed a severe retinopathy as well as green teeth secondary to the hyperbilirubinemia. We conclude that secondary, bacteria-associated HLH can develop in premature infants, and that HLH can be treated with cytotoxic therapy also in premature infants. It is important to be aware of HLH in premature infants, since it is treatable.
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PMID:Severe bacteria-associated hemophagocytic lymphohistiocytosis in an extremely premature infant. 1788 50

We report a Japanese case of human herpes virus-8 (HHV-8)-associated multicentric Castleman disease(MCD) complicated by hemophagocytic syndrome(HPS). A 60-year-old man presented with persistent fever and progressive pancytopenia in June 2004. On physical examination, anemia, icterus, hepatosplenomegaly, and generalized lymphadenopathy were detected. Laboratory findings showed elevated levels of serum ferritin and soluble interleukin-2 receptor. Anti-human immunodeficiency virus (HIV) antibody was negative. Bone marrow aspiration revealed a normocellular marrow with an increased number of hemophagocytic histiocytes. Biopsy of cervical lymph node disclosed pathological features compatible with the plasmablastic variant of Castleman disease. HHV-8 DNA was detected in the specimen from lymph node by polymerase chain reaction. Thus, the diagnosis of HHV-8-associated MCD complicated by HPS was made. The patient was treated with immunotherapy and subsequent chemotherapy. However, he died of bacterial sepsis after one-month therapy. This case report provides some evidence that HHV-8 may be a causative agent of MCD even in HIV-seronegative Japanese patients.
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PMID:[A Japanese case of human herpes virus-8-associated multicentric castleman disease complicated by hemophagocytic syndrome]. 1870 66

We present a 22-year-old male diagnosed with pro T-acute lymphoblastic leukemia (ALL). His laboratory test showed 181,900/microL of WBC complicated with lymphoadenopathy, pleural effusion, pericardial effusion and hepatosplenomegaly at the onset. Flow cytometry analysis of the leukemic cells showed cCD3+, CD7+, CD2+, CD1a-, CD3-, CD5-, CD4-, CD8-, CD34+, and HLA-DR+ as a pro T-cell phenotype. The patient was treated with induction therapy followed by 3 courses of consolidation therapy and achieved his first complete remission. He underwent up-front stem cell transplantation (SCT) from an HLA-full matched sibling, with early relapse just before transplantation. The conditioning regimen consisted of fludarabine (100 mg/m2) and melphalan (180 mg/m2). He relapsed with an extramedullary mass (gingival, testis, and femoral muscles) 1 year after transplantation. Since bone marrow involvement was not apparent, he received involved field radiation therapy (25.2 Gy/14 frequencies) in each mass. Six months after extramedullary relapse, bone marrow relapse occurred, and the patient died of sepsis due to Pseudomonas aeruginosa during re-induction therapies. Based on the immature T cell phenotype frequently with myeloid markers, a graft-versus- leukemic effect might be expected after allogeneic SCT for Pro T-ALL and a positive indication of SCT for this disease should be considered.
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PMID:[Limited but potential efficacy by graft-versus-leukemia (GVL) for Pro T-ALL]. 1901 41


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