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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune regulation. HLH consists of two forms: familial and acquired, the latter which occurs in association with infection, malignancy, rheumatic disease and acquired immune deficiency. Herein, we report a case of acquired HLH in a child who had received allogeneic hematopoietic stem cell transplantation for familial HLH with UNC13D mutation. Based on microbiology, only rotavirus was identified as a possible organism triggering HLH. The patient's fulminant clinical course included acute respiratory failure, a sepsis-like pattern, disseminated intravascular coagulopathy, and rhabdomyolysis, leading to multiorgan failure and death from septic shock.
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PMID:Rotavirus-associated hemophagocytic lymphohistiocytosis (HLH) after hematopoietic stem cell transplantation for familial HLH. 2571 13

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening extreme whole body inflammatory state. It results from the pathological hyperactivation of the immune system, because of congenital or acquired abnormalities of cytotoxicity and NK or T cells. Uncontrolled stimulation of lymphocytes and macrophages lead to hypercytokinemia, organ infiltration by these cells and multiple organ failure. There are genetic HLH and secondary HLH, associated with infections, autoimmune disorders, malignancies. The frequency of the secondary form is difficult to estimate because of the wrong and difficult diagosis. The clinical course is often insidious and nonspecific. Symptoms are varied. The most important are: unremitting fever, hepatosplenomegaly. Generalized edema, rash, lymphadenopathy may occur. Liver failure, respiratory, circulatory and multiple organ failure could develop in a very short time. Most common abnormalities in additional tests are: cytopenias, hypofibrinogenaemia, hypertriglyceridaemia, hyperferritinaemia, hypertransaminasaemia, elevated parameters of inflammation (excepting lowering erythrocyte sedimentaion rate). Criteria for diagnosis and therapeutic protocols referto the genetic forms of HLH. Currently, there are no guidelines for secondary HLH. Diagnostic and therapeutic difficulties also arise from clinical picture, similar as in the systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome. We present the clinical presentation, diagnostic pitfalls and treatment of secondary HLH, based on a review of the current literature and our own observations.
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PMID:[Secondary hemophagocytic syndromes]. 2577 10

Hemophagocytic lymphohistiocytosis is a clinic pathologic entity characterized by increased proliferation and activation of benign macrophages with hemophagocytosis throughout the reticuloendothelial system. It is a potentially lethal disorder due to an uncontrolled immune response to a triggering agent. HPS may be primary, or secondary to malignancy, infections, auto-immune diseases, and pharmacotherapy. HPS is a rare, but life-threatening complication. Herein, we described a female patient with HPS with secondary sepsis. Our objective was to raise the importance of early diagnosis of HFS by presenting a representative case.
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PMID:Sepsis of unknown origin with multiorgan failure syndrome: Think of hemophagocytic lymphohistiocytosis. 2618 Apr 36

Macrophage activation syndrome (MAS) is a potentially life-threatening complication of rheumatic diseases such as systemic juvenile idiopathic arthritis (sJIA) and systemic lupus erythematosus. It is often considered a type of secondary hemophagocytic lymphohistiocytosis (HLH) and results from over-activation of T lymphocytes and macrophages leading to a "cytokine storm". Characteristic features are persistent fever, lymphadenopathy, hepatosplenomegaly, cytopenias (anemia, leucopenia, thrombocytopenia), raised C-reactive protein, falling erythrocyte sedimentation rate, hypofibrinogenemia, transaminitis, hypertriglyceridemia and extreme hyperferritinemia often associated with multi-organ impairment. Key to its management is early recognition of MAS which may be difficult due to similarity to systemic sepsis or flares of the underlying rheumatic disease. To aid with this process, criteria for the diagnosis of MAS in patients with sJIA derived by international consensus have been published. Although bone marrow biopsy showing hemophagocytosis is strongly supportive it is not essential for diagnosis. Together with appropriate supportive care, first-line treatment is high-dose intravenous corticosteroids with cyclosporin or intravenous immunoglobulin (IVIg) added if there is not initial response. Although etoposide is used by hematologists in treatment of HLH, there are concerns regarding organ toxicity and bone marrow suppression which weigh against its use in initial management of MAS. With increasing understanding of the pathogenesis of MAS, use of drugs targeting specific cytokines has been reported in case series. The relatively rapid effectiveness of anakinra, a recombinant IL-1 receptor antagonist, has been documented. Further studies of this and other biologic agents are required to identify the most effective and safest treatment option for refractory MAS.
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PMID:Macrophage Activation Syndrome. 2640 31

Although graft failure (GF) is a fatal and life-threatening complication of umbilical cord blood transplantation (CBT), the standard treatment has not been established. We describe the case of a 28-year-old man diagnosed with acute myelogenous leukemia with myelodysplasia-related changes harboring a normal karyotype. This patient underwent 2 courses of idarubicin and cytosine arabinose therapy, and 3 courses of high-dose cytosine arabinose therapy. Subsequently, he underwent high-dose chemotherapy (total body irradiation and cyclophosphamide) followed by first CBT. Primary GF occurred after post-immunological reaction and hemophagocytic lymphohistiocytosis, and was diagnosed on day 27 after the first CBT. Therefore, the patient underwent secondary CBT for GF treated with a modified one-day conditioning regimen consisting of fludarabine (30 mg/m(2), 3 days), cyclophosphamide (2 g/m(2)), and total body irradiation (2 Gy), and graft-versus-host disease prophylaxis consisting of mycophenolate and tacrolimus. Consequently, the patient achieved neutrophil engraftment on day 17 after the second CBT. During the clinical course of the second CBT, the main complications were sepsis, BK virus-associated cystitis, and acute graft-versus-host disease (skin, grade 2, stage 3). After these treatments, the patient was disease-free for 39 months. Our case suggests that these treatments may be feasible, safe, and effective for the treatment of patients with GF. This case study may be helpful to physicians who directly care for GF patients, and may provide a future direction for a more efficient treatment modality.
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PMID:Successful Secondary Umbilical Cord Blood Transplantation for Graft Failure in Acute Myelogenous Leukemia, Treated with Modified One-Day Conditioning Regimen, and Graft-Versus-Host Disease Prophylaxis Consisting of Mycophenolate and Tacrolimus. 2649 May 21

We report a case of several autoimmune disorders eventually presenting as severe multi organ dysfunction syndrome caused by adult hemophagocytic lymphohistiocytosis (HLH). Clinical and laboratory tests might lead to fatal misinterpretation without awareness of its diagnostic evaluation, as HLH shares common features with sepsis and immune-mediated systemic inflammatory response syndromes.
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PMID:Adult hemophagocytic lymphohistiocytosis causing multi organ dysfunction in a patient with multiple autoimmune disorders: when the immune system runs amok. 2686 16

Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyperinflammatory syndrome characterized by excessive activation of macrophages and T cells resulting from defective cytotoxicity. Severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes (macrophages) secreting high amounts of inflammatory cytokines threatens the life of the patient and may lead to death unless arrested by appropriate treatment. HLH can be caused either by certain underlying genetic diseases (familial HLH), or may also occur due to particular triggers in patients with no known inherited disorder (acquired HLH). Due to life threatening nature of the disease, early diagnosis and initiation of immunosuppressive therapy is extremely important. HLH diagnosis is based on constellation of clinical manifestations and laboratory parameters which often overlap with those of severe infection or sepsis. Identification of patients with familial HLH and their underlying genetic defects requires specialized laboratory tests and is important for predicting relapses and planning early therapeutic hematopoietic stem cell transplantation (HSCT). A high suspicion and thorough clinical, immunological and genetic work-up is required for diagnosis of HLH. Prompt initiation of adequate treatment is essential for the survival. Substantial progress has been made in exploring the complex cause and pathophysiology of HLH and also in management of HLH patients.
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PMID:Current Updates on Classification, Diagnosis and Treatment of Hemophagocytic Lymphohistiocytosis (HLH). 2687 83

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disease caused by excessive immune activation. Acquired HLH is seen in adults and is often caused by infection or malignancy. Diagnosis is difficult and usually missed as clinical and laboratory findings are nonspecific. Moreover, the pathophysiology of the systemic inflammatory response syndrome and/or sepsis is remarkably similar to HLH. Thus, in patients presenting with presumed severe sepsis or septic shock complicated by multiorgan failure without a clear infectious source, HLH should be considered. A disproportionately high ferritin may be one of the earlier laboratory findings to suggest HLH. We discuss a case of a young male who presented with presumed septic shock with multiorgan failure who was eventually found to have Epstein-Barr virus-induced HLH.
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PMID:Weathering a Cytokine Storm: A Case of EBV-Induced Hemophagocytic Lymphohistiocytosis. 2720 Mar 81

Haemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathological immune activation characterised by extreme inflammation. We present a case of a young Filipino man consulting for non-specific symptoms of fever, body malaise and weight loss. Prominent physical examination findings included gross pallor, cachexia and hepatosplenomegaly. Laboratory results revealed pancytopaenia, while bone marrow examination revealed haemophagocytosis. Further workup for HLH showed hypertriglyceridaemia, hypofibrinogenaemia and hyperferritinaemia (fulfilling 6 of 8 diagnostic criteria). Exhaustive serological and haematological examinations showed chronic hepatitis B virus infection and past evidence of Epstein-Barr virus infection as possible triggers. The patient was started on antiviral therapy, high-dose steroids and chemotherapy. He initially improved, but eventually succumbed to severe fungal sepsis and pulmonary haemorrhage. An autopsy confirmed the diagnosis of HLH.
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PMID:Virus-associated haemophagocytic lymphohistiocytosis in a young Filipino man. 2728 96

IL-6 contributes to host defense against infections and tissue injuries. However, exaggerated, excessive synthesis of IL-6 while fighting environmental stress leads to an acute severe systemic inflammatory response known as 'cytokine storm', since high levels of IL-6 can activate the coagulation pathway and vascular endothelial cells but inhibit myocardial function. Remarkable beneficial effects of IL-6 blockade therapy using a humanized anti-IL-6 receptor antibody, tocilizumab were recently observed in patients with cytokine release syndrome complicated by T-cell engaged therapy. In this review we propose the possibility that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis.
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PMID:Immunotherapeutic implications of IL-6 blockade for cytokine storm. 2738 87


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