Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of systemic lupus erythematosus (SLE) and B-cell malignancy is widely reported in the literature. Here we report nine cases of concurrent of SLE or discoid lupus erythematosus (DLE) and lymphoma or plasma cell disorder. A MEDLINE search was done using the keywords, 'SLE' and 'lymphoma' and the characteristics of all identified cases were summarized and analyzed, along with data from our own cases. Numerous variants of B-cell malignancies were encountered in these patients. B-cell malignancy occurs after the diagnosis and treatment of SLE in most reported cases, although it may precede SLE, or occur synchronously with it. The age at onset of the B-cell neoplasm in SLE patients is similar to that in the general population. Mortality in patients with both diseases is associated with progressive B-cell neoplasm, sepsis secondary to either disease, or both. B-cell malignancy and SLE seem to run independent clinical courses rather than being affected by each other. The use of immunosuppressive drugs is common in patients with SLE diagnosed prior to B-cell lymphoma, arguing that the effect of immunosuppression on the pathogenesis of lymphoma can not be excluded. Three areas worthy of study regarding the probable mechanisms for the occurrence of SLE and B-cell malignancies are discussed. A tumor suppressor gene PTEN may link the two disorders via a defective apoptosis pathway to eliminate hyperactive B and T cells in SLE. The accumulation of clonally expanded hyperactive B-cells that recognize self-antigens in the lymph nodes of SLE may predispose these B-cells to DNA breaks, facilitating tumorigenesis. Lastly, EBV infection, found to have a high prevalence in SLE patients, may serve as a common etiological factor in both disorders.
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PMID:Systemic lupus erythematosus and B-cell hematologic neoplasm. 1178 71

We describe the case of a young woman with a known history of thrombocytopenia, who developed respiratory and circulatory failure thought to be caused by sepsis. She subsequently was shown to have high titres of anticardiolipin antibodies as well as lupus anticoagulant. Serological tests for various connective tissue diseases were negative. Multiple cerebral ischaemic lesions led to a poor outcome. This case highlights the potential difficulties in differentiating catastrophic anti-phospholipid syndrome from disseminated intravascular coagulation.
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PMID:Multi-organ failure secondary to catastrophic anti-phospholipid syndrome. 1193 48

Infections are common in systemic lupus erythematosus (SLE), and remain a source of mortality. The types of infections (such as pneumonia, urinary tract infection, cellulitis, and sepsis) in SLE patients are similar to the general population and include the same pathogens (Gram-positive and Gram-negative). SLE patients may also develop opportunistic infections, especially when treated with immunosuppressive agents. As a high-risk population, identification and treatment of chronic infections such as tuberculosis, hepatitis B, or human immunodeficiency virus (HIV), are important prior to the institution of immunosuppression to prevent reactivation or exacerbation of the infection. A common caveat is to distinguish between a lupus flare and an acute infection; judicious use of corticosteroids and cytotoxic drugs is critical in limiting infectious complications. The risk factors associated with susceptibility to disease include severe flares, active renal disease, treatment with moderate or high doses of corticosteroids and/or immunosuppressive agents, and others. Genetic factors (complement deficiencies, mannose-binding lectin, Fcgamma III, granulocyte macrophage colony-stimulating factor [GM-CSF], osteopontin) may predispose certain SLE patients to develop infections. Parameters including C-reactive protein (CRP) and adhesion molecules may help to differentiate an infectious disease from an exacerbation of the disease. Finally, the mechanism of molecular mimicry by specific microbial agents may play a role in the induction of SLE.
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PMID:SLE and infections. 1279 59

Roles for Toll-like receptors (TLRs) are emerging in conditions such as sepsis syndrome, systemic lupus erythromatosis, rheumatoid arthritis and asthma, suggesting that the selective targeting of TLRs might be useful therapeutically. TLRs are defined by the presence of extracellular leucine-rich repeats and an intracellular Toll/interleukin-1 receptor domain, and play a role in host defence and inflammation. Signalling pathways activated by TLRs show remarkable similarity to those activated by the pro-inflammatory cytokine interleukin-1 (the receptor for which also has a Toll/interleukin-1 receptor domain), although adaptor proteins specific for certain TLRs are starting to emerge (e.g. Mal and Trif). The common signalling pathways used by all members of the TLR superfamily are being targeted, with drugs that block nuclear factor-kappaB and p38 mitogen-activated protein kinase in clinical development for diseases such as rheumatoid arthritis and psoriasis. As we learn more about TLR signal transduction, more options are presenting themselves for pharmacological targeting.
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PMID:Therapeutic targeting of Toll-like receptors for inflammatory and infectious diseases. 1290 49

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder, characterised by a loss of self-tolerance to endocrine tissues, chronic candidiasis and ectodermal disorders. APECED is associated with mutations of a single gene, designated autoimmune regulator (AIRE). We describe a 31-year-old APECED patient with non-traumatic, cutaneous ulcers on both forearms with features of a lupus-like panniculitis. On admission to the ICU in September 2001, the patient suffered from a ketoacidotic, hyperglycemic coma and adrenal crisis due to an Enterobacter-cloacae sepsis, originating from multiple, necrotising deep cutaneous ulcers. These ulcers spontaneously developed on both forearms, some of which were just emerging, full blown or healing with scars. Histological examination showed signs of a scarring panniculitis and vasculitis. Immunohistochemistry and direct immunofluorescence with characterisation of immunoglobulin and complement-factor binding pattern revealed features of a lupus-like panniculitis. Sequence analysis of all 14 exons of the AIRE gene revealed a R257 X mutation in exon 6 resulting in a nonsense mutation at codon 257 confirming the diagnosis of APECED. Oral treatment with 60 mg/day corticosteroids for two weeks led to complete resolution of all ulcers. In conclusion, mutations in the AIRE gene may provide the genetic background against which additional factors can initiate an autoimmune process. Here, autoimmune panniculitis appears to be an associated feature of the APECED syndrome. Our findings support the use of immunosuppressive therapy for autoimmune disease components of the APECED syndrome.
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PMID:Lupus-like panniculitis in a patient with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). 1295 36

Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors, antiphospholipid antibodies (e.g., lupus anticoagulant) can produce a prolonged aPTT that does not correct with normal plasma but is overcome by adding excess phospholipid or platelets. Paradoxically, a tendency to thrombosis, not bleeding, accompanies lupus anticoagulants and the antiphospholipid antibody syndrome. Transfusion of red blood cells, platelets, or plasma products is sometimes warranted, but clinicians must carefully weigh potential benefits against known risks. In critically ill patients, administering RBCs can enhance oxygen delivery to tissues. Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion. The use of rHuEPO to increase erythropoiesis offers an alternative to RBC transfusion, assuming normal, responsive progenitor cells and adequate iron, folate, and cobalamin stores. Future research should examine whether clinical outcomes from rHuEPO use in critically ill patients are important and cost-effective. Because platelets play an instrumental role in primary hemostasis, platelet transfusions are often important in managing patients who are bleeding or at risk of bleeding with thrombocytopenia or impaired platelet function. Platelet transfusions carry risks, and decisions to transfuse platelets must consider clinical circumstances. Most important, platelet transfusions are generally contraindicated if the underlying disorder is TTP or type II HIT, because platelet transfusion in these settings may fuel thrombosis and worsen clinical signs and symptoms. Plasma products can correct hemostasis when bleeding arises from malfunction, consumption, or underproduction of plasma coagulation proteins. Choice of plasma product for transfusion depends on clinical circumstances. FFP is the most commonly used plasma product to correct clotting factor deficiencies, particularly coagulopathies that are attributable to multiple clotting factor deficiency states as in liver disease, DIC, or warfarin anticoagulation. PCC or rFVIIa that is administered in small volumes may provide advantages over FFP when coagulopathies require quick reversal without risk of volume overload. Factor concentrates can replace specific factor deficiencies. Recombinant FVIIa bypasses inhibitors to factors VIII and IX and vWF. Use of rFVIIa in managing hemostatic abnormalities from severe liver dysfunction; extensive surgery, trauma, or bleeding; excessive warfarin anticoagulation; and certain platelet disorders requires further study to determine optimal and cost-effective dosing regimens. Recombinant activated protein C reduces mortality from severe sepsis that is associated with organ dysfunction in adults who are at high risk for death (APACHE scores of at least 25). In severe sepsis, levels of protein C decrease, as do fibrinogen and platelet levels. Because of its anticoagulant effect, however, drotrecogin alfa may induce bleeding. Guidelines for drotrecogin alfa use must take into account bleeding risks.
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PMID:Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. 1471 Jun 93

Lymphohistiocytic activation syndromes are characterized by activation and proliferation of T cells and macrophages usually reflecting an inappropriate response of the host to an infection. The clinical manifestations are often alarming symptoms suggestive of severe sepsis. Most patients have a known underlying disease (hemopathy, lupus, Still's disease, HIV infection, bone marrow or organ transplantation). In the few cases that occur apparently without any risk factors, investigations should be done to look for a predisposing inherited disease such as familial lymphohistiocytosis or Purtilo syndrome in boys. The treatment relies on immunosuppressive agents followed by bone marrow transplantation, which can provide a definitive cure in genetics forms.
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PMID:[Hemophagocytic syndromes and primary immunodeficiencies]. 1476 36

We examined the demography, reasons for admission and cause of death in systemic lupus erythematosus (SLE) patients admitted to a medical intensive care unit (ICU) over a 7-year period. Fourteen patients were admitted during this period-all were female, 13 were of mixed ethnic ancestry and one a black South African. Of the 14 patients, 12 were admitted as a result of lupus activity, 2 had sepsis as the major cause of admission, although 5 other patients developed infection during their admission. Five patients had a generalised flare of their disease or progressive renal failure. Seven patients were admitted with a variety of lupus-related pathologies. In general the precise cause of death was difficult to determine. Of the 14 patients, 9 had impaired renal function on admission including 1 with sepsis and 1 of the survivors. Three patients (21%) survived, one with respiratory failure due to shrinking lung, a second with an acute flare of SLE and a third with pulmonary emboli. This study demonstrates that lupus in our community may produce life-threatening flares. Although cause of death was not always definitely identified, admission to the ICU was primarily due to active SLE and not sepsis or iatrogenic disease.
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PMID:Survival of patients with SLE admitted to an intensive care unit-a retrospective study. 1556 99

Viral and bacterial infections may serve as an environmental trigger for the development or exacerbation of systemic lupus erythematosus (SLE) in the genetically predetermined individual. In addition, SLE patients are more prone to develop common (pneumonia, urinary tract infection, cellulitis, sepsis), chronic (tuberculosis), and opportunistic infections possibly due to inherit genetic and immunologic defects (complement deficiencies, mannose-binding lectin [MBL] polymorphisms, elevated Fcgamma III and GM-CSF levels, osteopontion polymorphism), but also due to the broad spectrum immunosuppressive agents that are part of therapy for severe manifestations of the disease. Hence, SLE patients are considered a high-risk population, where identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression so as to prevent reactivation or exacerbation of the infection. Infections in SLE patients remain a source of morbidity and mortality. A caveat often encountered is to distinguish between a lupus flare and an acute infection; in such cases parameters including elevated CRP (and adhesion molecules) may aid in the diagnosis of infection. Recent research has provided convincing evidence that EBV infection may play a major role not only in molecular mimicry but also in aberrations of B cells and apoptosis leading to a state of perpetual heightened immune response in SLE.
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PMID:Infections and SLE. 1637 52

Neopterin is a low-molecular mass substance synthesized from guanosine triphosphate (GTP) in monocytes/macrophages due to IFNgamma stimulation. The cellular immune system is involved in or affected by the disease process in various conditions such as viral infections (AIDS), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosis, Crohn's disease), malignancy and monitoring after solid organ transplants. Similar to procalcitonin, neopterin determination can assist in the differential diagnosis between viral and bacterial infection and as an indicator for impending septic complications (MODS vs. sepsis). Because of fact that reduced glamerular filtration rate neopterin accumulates in the blood, neopterin determination in multiorgan failure or sepsis patients are limited. The aim of this study was to evaluate the usefulness of neopterin in clinical diagnostics.
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PMID:[Role of neopterin in clinical diagnostics]. 1646 8


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