Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In a 30-year-old male patient systemic lupus erythematosus was diagnosed based on the presence of 8 out of 11 ARA criteria. Disease onset was acute and included renal function impairment with biopsy-proven lupus nephritis (WHO class IV) requiring renal replacement therapy. Although conventional immunosuppressive therapy regimens proved effective in controlling disease activity, all of the administered drugs were accompanied by serious side effects: bilateral femur head necrosis with corticosteroids, allergic skin reaction in response to azathioprine, nephrotoxicity with cyclosporine, nausea and abdominal pain with mycophenolate mofetil and life-threatening septicemia with cyclophosphamide treatment. In search for alternative treatment options, tacrolimus (FK506, trough serum levels 3-6 ng/ml) was started. FK506 was well-tolerated and lupus activity completely resolved within 7 months after initiation of therapy. During 36 months of follow-up no arthritic complaints occurred and renal function stabilized at a serum creatinine of 2.1 mg/dl with negative anti-ds-DNA antibodies and ANA titers. In conclusion, FK506 may be considered as alternative immunosuppressive for maintenance treatment in patients with severe lupus erythematosus and side effects to conventional regimens.
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PMID:Tacrolimus- (FK 506) based immunosuppression in severe systemic lupus erythematosus. 1526 13

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

The genetic predisposition to many autoimmune diseases is inherited as a polygenic trait. It is conceivable that some of the causative alleles in these diseases became prevalent in the population by conferring a survival benefit against environmental assaults, such as infections. We used mice cogenic for genetic loci predisposing to systemic lupus erythomatosus to test the hypothesis that some of these genetic loci protect the host from bacterial infections. Mice with the Sle3 lupus-susceptibility locus on a wild-type background were found to have enhanced antibacterial responses in the context of pneumonia and intra-abdominal sepsis than wild-type animals. This was associated with markedly augmented accumulation of neutrophils in infected tissues, and was bone marrow transferable and dependent on the presence of neutrophils, but not lymphocytes. There was no difference in in vitro leukocyte killing of bacteria nor influx of phagocytes between lupus-susceptible and wild-type animals, but neutrophils from lupus-susceptible mice displayed markedly reduced rate of apoptosis, associated with altered expression of Bcl-2 family proteins, contributing to their greater accumulation. Importantly, deliberate inhibition of apoptosis in wild-type animals significantly boosted the accumulation of neutrophils at the site of infection and resulted in an enhanced antimicrobial response. These observations support the concept that some of the genetic loci that mediate autoimmunity may also confer augmented antimicrobial innate immunity.
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PMID:The lupus-susceptibility locus, Sle3, mediates enhanced resistance to bacterial infections. 1649 84

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

It is generally accepted that antiphospholipid syndrome remains a major medical problem characterised by hypercoagulability, arterial and venous thrombosis and thrombocytopenia. It is unclear how best to treat these patients should they require emergency surgery. If a lupus anticoagulant is present, hypercoagulability may occur de novo but surgical interventions along with sepsis are two important predisposing factors. We describe three patients with primary antiphospholipid syndrome and discuss the implications for surgery.
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PMID:Antiphospholipid syndrome: a series of surgical emergencies and the current evidence for its management. 1683 58


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