Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0042109 (urticaria)
6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic urticaria (CU), defined as recurrence of wheals with or without angioedema for more than 6 weeks, is a quite common disease that may severely worsen the quality of life. Studies carried out during the last 2 decades have demonstrated an autoimmune pathogenesis mediated by functionally active autoantibodies to the high affinity IgE receptor (FcepsilonRI) or to IgE which are able to induce histamine release from basophils and mast cells. However, such mechanism can be detected in less than 50% of patients only. The present article reviews recent findings showing an additional pathogenic mechanisms in CU patients: activation of the coagulation cascade resulting in thrombin production. Thrombin is a serine protease which may play a key role in urticaria, being able to induce edema through an increase in vascular permeability, mast cell activation and degranulation, and to induce the production of the anaphylotoxin C5a. Such mechanism seems to be active in the majority of CU patients, however their relationship with anti-FcepsilonRI or anti-IgE autoantibodies is still matter of research.
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PMID:Chronic urticaria: a disease at a crossroad between autoimmunity and coagulation. 1796 29

The association between chronic urticaria (CU) and autoimmune disease has been recognized for some time, especially with autoimmune thyroid disease. More recently, functional IgG autoantibodies against FcepsilonRIalpha and less commonly against IgE have been reported in a subset of patients with CU. These patients have been described as having more severe and difficult-to-control urticaria. The autologous serum skin test has been proposed as a surrogate test to define presence of these autoantibodies, although it identifies presence of histamine releasing factor, not necessarily antibody. Basophil histamine release and basophil activation assays using flow cytometry to measure CD63 and, more recently, CD203c expression have been used to identify patients with autoimmune urticaria. New research suggests that in some patients with CU, the activation of the extrinsic coagulation pathway with thrombin generation might play an important role in their CU.
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PMID:The autoimmune nature of chronic urticaria. 1892 50

Urticaria is a skin disease characterised by short-lived surface swellings of the dermis (wheals) frequently accompanied by itching. It is classified as acute or chronic depending on whether the wheal recurrence occurs for less or more than six weeks. Acute urticaria is often due to a hypersensitivity reaction, whereas about 50% of the cases of chronic urticaria are regarded as autoimmune. Urticaria may occur alone or in association with a deeper swelling (angioedema) involving the subcutaneous and/or submucosal tissues, and last from hours to a few days. Angioedema can also develop alone, and may be idiopathic or be caused by allergies, inherited or acquired deficiencies of C1-inhibitor protein, or adverse drug reactions. An interplay between inflammation and coagulation has been proposed as a pathomechanism in urticaria and urticaria-associated angioedema (in which histamine and thrombin are involved), as well as in angioedema due to C1-inhibitor deficiency, which involves various biological systems. An increase in the plasma markers of thrombin generation, fibrinolysis and inflammation has been documented during exacerbations of urticaria and angioedema, with the marker levels decreasing to normal during remission. However, the hypercoagulable state in chronic urticaria and angioedema has not been reported to be associated with any increased risk of thrombosis, although there have been a number of reports of cardiovascular events occurring during episodes of acute urticaria. These observations have provided the rationale for the clinical evaluation of anticoagulant and antifibrinolytic drugs, the efficacy of which has sometimes been demonstrated.
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PMID:Inflammation and coagulation in urticaria and angioedema. 2227 13

Chronic spontaneous urticaria is a common condition, with a lifetime prevalence of 0.5-1.0%. It has a significant effect on quality of life, comparable to having triple-vessel coronary artery disease. Warfarin and nicoumalone are synthetic derivatives of the plant toxin coumarin. We report the first case of successful response to both warfarin and nicoumalone in the same patient, thereby demonstrating a class action of synthetic coumarins in the disease. Complete response with both coumarins occurred once an INR above 2.0 was achieved, and was maintained during a 12-month follow-up. The mechanism of action of coumarins on urticaria is not known, but may be related to decrease in thrombin production or to interference of activation of other inflammatory proteins produced during the coagulation process. Side-effects of anticoagulation can be catastrophic, and coumarin treatment currently remains reserved for restricted severe recalcitrant cases only.
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PMID:Class action of oral coumarins in the treatment of a patient with chronic spontaneous urticaria and delayed-pressure urticaria. 2243 98

Asparaginase (ASNase) is one of the most important key drugs in the treatment of acute lymphoblastic leukemia (ALL). However, clinical hypersensitivity reactions often occur and lead to the discontinuation of ASNase treatment. Here, we report a retrospective study of 68 Erwinia ASNase (Erw-ASNase) administrations in 11 patients with childhood ALL who developed allergic reactions to E.coli-ASNase in our hospital between 2006 and 2012. The median age of the patients was 6 (range, 0 to 14). Erw-ASNase purchased overseas by the patients' guardians had already been administered when we obtained informed consent from the guardians. In all patients, fibrinogen and/or anti-thrombin III levels were decreased, but thrombosis did not develop. There was only one mild adverse event (grade 2 urticaria) in one patient, in whom Erw-ASNase could be continued after increasing the doses of premedication with antihistamine and prednisolone. Erw-ASNase could be safely administered to all patients.
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PMID:[The feasibility of Erwinia asparaginase for pediatric patients who developed an allergic reaction to E.coli asparaginase during treatment of acute lymphoblastic leukemia]. 2366 19

Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1-antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.
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PMID:Chronic urticaria and coagulation: pathophysiological and clinical aspects. 2467 28

Thrombin, a key player in coagulation, is widely held to induce and promote inflammation. As of now, the features, kinetics and control of thrombin's proinflammatory effects on the skin remain to be characterized in detail. We, therefore, injected thrombin into the ear skin of mice and observed strong, dose-dependent and transient ear swelling responses as well as mast cell (MC) degranulation. Unexpectedly, thrombin induced even stronger, not reduced, ear swelling in MC-deficient Kit^W-sh/W-sh mice. Prior local reconstitution of Kit^W-sh/W-sh mice with MCs inhibited this effect, indicating that MCs may contribute to the control of thrombin-induced skin inflammation. In line with previous studies, we found that MCs express the thrombin receptors PAR1, PAR3 and PAR4, thrombin induces direct and dose-dependent MC degranulation, and that degranulated MCs inactivate thrombin. Further findings suggested that MC-mediated protection from thrombin-induced inflammation is likely to rely on the effects of MC proteases. We show for the first time that MC-deficient mice and MC protease 4-deficient mice with normal numbers of MCs show markedly increased ear swelling in response to thrombin as compared to wild-type mice. Taken together, these results suggest that thrombin-induced skin inflammation is controlled, in part, by MC protease 4 released from activated MCs. For MC-driven diseases such as chronic spontaneous urticaria, which has been linked to increased thrombin generation, this might mean that MCs may contribute to the resolution of skin inflammatory responses.
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PMID:Mast cells are critical for the limitation of thrombin-induced skin inflammation. 2878 94

Intraoperative bovine-derived topical thrombin is still widely used for hemostasis during surgery. A 38-year-old woman with chronic spontaneous urticaria was referred to the orthopedic surgery department for herniated disk and myelopathy. During the first stage of operation, bovine-derived thrombin powder soaked in Gelfoam was used as a hemostatic aid. After 30 minutes, the patient developed anaphylactic shock with systemic skin rash and angioedema. Repeated intravenous bolus and infusion of vasopressor were carried out, and her blood pressure normalized. Skin test and specific immunoglobulin E test showed positive results for bovine thrombin and beef, respectively. During the second stage of operation (After 10 days from first stage of operation), bovine-derived thrombin powder was excluded and the operation was successful without any unexpected events. Therefore, bovine thrombin should be used with caution because it might cause anaphylaxis.
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PMID:A Case of Intraoperative Anaphylaxis Caused by Bovine-Derived Thrombin. 2941 61

Several lines of evidence indicate that the immune system, inflammation, and coagulation are simultaneously activated in autoimmune and immune-mediated skin diseases. Pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha induce the expression of the main initiator of coagulation, i.e., tissue factor. The proteases of coagulation in turn act on protease-activated receptors inducing the expression of various pro-inflammatory cytokines triggering inflammation. The cross-talk among immune system, inflammation, and coagulation amplifies and maintains the activation of all three pathways. This review focuses on three skin disorders as chronic spontaneous urticaria (CSU), angioedema, and bullous pemphigoid (BP), in which the relationships among the three systems have been investigated or their clinical consequences are relevant. Markers of thrombin generation, fibrinolysis, and inflammation have been reported to be increased in the plasma during flares of CSU and angioedema, as well as in the active phase of BP, with the marker levels reverting to normal during remission. The coagulation activation seems to be important only at local level in CSU and angioedema while both at local and systemic levels in BP which is the only condition associated with an increased thrombotic risk. The prothrombotic state in autoimmune skin diseases raises the question of the indication of anticoagulant treatment, particularly in the presence of other cardiovascular risk factors.
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PMID:Coagulation and Skin Autoimmunity. 3128 19

Chronic spontaneous urticaria (CSU) is considered to be primarily a mast cell-driven disease. However, recent evidence suggests that eosinophils may also have an axial role in symptomology. Histologic studies have demonstrated the presence of both eosinophils and eosinophil granules, indicative of activation, in CSU lesions. Although many allergic and inflammatory conditions are associated with a peripheral blood eosinophilia, the converse appears to be the case in CSU, with a peripheral blood eosinopenia being observed in many patients. Possible mechanisms include the depletion of blood eosinophils by recruitment into the skin during active disease and immunologic destruction in the blood. We also address in some detail the interactions between eosinophils and mast cells, particularly the cytokine cross-talk of these cells and mediator release possibly leading to clinical symptoms. Also, activation by eosinophil proteins of the coagulation pathway leads to the generation of thrombin and increased mast cell degranulation. Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. Clearly, a new picture of an important role of eosinophils in the pathogenesis of CSU is emerging.
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PMID:The role of eosinophils in chronic spontaneous urticaria. 3222 75


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