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Allen P Kaplan - One of the best experts on this subject based on the ideXlab platform.
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pathogenesis of Chronic Urticaria
Clinical & Experimental Allergy, 2009Co-Authors: Allen P Kaplan, M W GreavesAbstract:Summary Chronic Urticaria is defined as the presence of Urticaria (hives) for at least 6 weeks with the assumption that it occurs daily or close to it. If we eliminate physical Urticarias and Urticarial vasculitis from consideration, the remainder can be divided into autoimmune Chronic Urticaria (45%) and idiopathic Chronic Urticaria (55%). The autoimmune subgroup is associated with the IgG anti-IgE receptor α subunit in 35–40% of patients and IgG anti-IgE in an additional 5–10%. These autoantibodies have been shown to activate blood basophils and cutaneous mast cells in vitro with augmentation of basophil activation by complement and release of C5a, in particular. Binding methods (immunoblot and ELISA) yield positives in many autoimmune diseases as well as occasional normal subjects or patients with other forms of Urticaria but most such sera are non-functional. Activation of basophils or mast cells causing histamine release is quite specific for Chronic Urticaria and defines the autoimmune subgroup. Although pathogenicity is not formally proven, the antibodies cause wealing upon intradermal injection, and removal of the autoantibody leads to remission. A cellular infiltrate is seen to be characterized by mast cell degranulation and infiltration of CD4+ T lymphocytes, monocytes, neutrophils, eosinophils, and basophils. The intensity of the infiltrate and clinical severity of the disease (including accompanying angio-oedema) is more severe in the autoimmune subpopulation. This latter group also has a higher evidence of human leucocyte antigen DR alleles associated with autoimmunity and a 25% incidence of antithyroid antibodies with diagnosed hypothyroidism in some. Hypo-responsiveness of patients' basophils to anti-IgE and hyperresponsiveness to serum defines another subpopulation (at least 50%) that overlaps the idiopathic and autoimmune subgroups. Hypo-responsiveness to anti-IgE has been shown to be associated with elevated levels of cytoplasmic phosphatases that inhibit degranulation. Reversal of the abnormality is seen with disease remission. Further work will be needed to distinguish whether this is a cause or a consequence of persistent Urticaria and to further assess the relationship (or lack thereof) of altered responsiveness (decreased or increased) with the presence or absence of activating autoantibodies.
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Chronic Urticaria pathogenesis and treatment
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Allen P KaplanAbstract:Patients previously designated as having Chronic idiopathic Urticaria are now divided into 2 groups: 40% to 50% with Chronic autoimmune Urticaria, and the remainder with Chronic idiopathic Urticaria. Patients in both groups may have concomitant angioedema (approximately 40%). The autoimmune subgroup has an association with antithyroid antibodies and is caused by IgG antibody to the alpha subunit of the IgE receptor (35% to 40%), usually reactive with unoccupied IgE receptors, or IgG antibody to IgE (5% to 10%). Complement activation augments histamine secretion by release of C5a. The IgG subclasses that appear to be pathogenic are IgG(1), IgG(3), and, to a lesser degree, IgG(4), but not IgG(2). Histology of Chronic Urticaria (both subtypes) reveals a perivascular non-necrotizing infiltrate of CD4(+) lymphocytes consisting of a mixture of T(H)1 and T(H)2 subtypes, plus monocytes, neutrophils, eosinophils, and basophils. These cells are recruited as a result of interactions with C5a, cell priming cytokines, chemokines, and adhesion molecules. Suggested therapy for patients with severe disease involves the use of high-dose hydroxyzine or diphenhydramine when nonsedating antihistamines are ineffective, supplemented by H-2 antagonists and leukotriene antagonists. The most severe patient may require protracted treatment with low-dose alternate-day steroid or cyclosporine. Cyclosporine can be steroid-sparing when side effects are encountered or when use of steroids is relatively contraindicated. Careful monitoring of blood pressure, BUN, creatinine, and urinalysis is required.
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a role for c5a in augmenting igg dependent histamine release from basophils in Chronic Urticaria
The Journal of Allergy and Clinical Immunology, 2002Co-Authors: Yoko Kikuchi, Allen P KaplanAbstract:Abstract Background: Histamine release in Chronic Urticaria is initiated by cross-linking of the α subunit of FceRI by means of IgG antibody, followed by complement activation. Objective: We sought to further elucidate the mechanism by which complement augments histamine release and to assess the role of C5a. Methods: We first quantitated the ability of purified C5a to initiate basophil histamine release and to be inhibited by antibody directed to the C5a receptor. Using this antibody, we quantitated its ability to inhibit histamine release induced by sera from patients with Chronic Urticaria. We also compared the ability of normal serum, C5-depleted serum, and C5-depleted serum after reconstitution with C5 to augment histamine release by IgG isolated from patients with Chronic Urticaria. Results: As the concentration of C5a was increased up to 50 ng/mL, the percentage of histamine release increased and reached a plateau of 40% to 50%; this was inhibited by antibody to the C5a receptor. Preincubation of basophils with antibody to the C5a receptor inhibited basophil histamine release from 15 sera tested, with a range of 4% to 39%. Histamine release caused by patient IgG was augmented when normal serum was added but not when C5-depleted serum was substituted for normal serum. Augmentation of histamine release by patient IgG was again obtained when C5-depleted serum was reconstituted with C5. Conclusion: Our conclusion is that pathogenic IgG cross-links the IgE receptor directly to cause histamine release, and activation is augmented by complement. C5a is the complement agonist that is responsible for the augmented histamine release. (J Allergy Clin Immunol 2002;109:114-8.)
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a role for c5a in augmenting igg dependent histamine release from basophils in Chronic Urticaria
The Journal of Allergy and Clinical Immunology, 2002Co-Authors: Yoko Kikuchi, Allen P KaplanAbstract:Abstract Background: Histamine release in Chronic Urticaria is initiated by cross-linking of the α subunit of FceRI by means of IgG antibody, followed by complement activation. Objective: We sought to further elucidate the mechanism by which complement augments histamine release and to assess the role of C5a. Methods: We first quantitated the ability of purified C5a to initiate basophil histamine release and to be inhibited by antibody directed to the C5a receptor. Using this antibody, we quantitated its ability to inhibit histamine release induced by sera from patients with Chronic Urticaria. We also compared the ability of normal serum, C5-depleted serum, and C5-depleted serum after reconstitution with C5 to augment histamine release by IgG isolated from patients with Chronic Urticaria. Results: As the concentration of C5a was increased up to 50 ng/mL, the percentage of histamine release increased and reached a plateau of 40% to 50%; this was inhibited by antibody to the C5a receptor. Preincubation of basophils with antibody to the C5a receptor inhibited basophil histamine release from 15 sera tested, with a range of 4% to 39%. Histamine release caused by patient IgG was augmented when normal serum was added but not when C5-depleted serum was substituted for normal serum. Augmentation of histamine release by patient IgG was again obtained when C5-depleted serum was reconstituted with C5. Conclusion: Our conclusion is that pathogenic IgG cross-links the IgE receptor directly to cause histamine release, and activation is augmented by complement. C5a is the complement agonist that is responsible for the augmented histamine release. (J Allergy Clin Immunol 2002;109:114-8.)
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mechanisms of autoimmune activation of basophils in Chronic Urticaria
The Journal of Allergy and Clinical Immunology, 2001Co-Authors: Yoko Kikuchi, Allen P KaplanAbstract:Abstract Background: Approximately 35% to 40% of patients with Chronic Urticaria possess a circulating antibody directed to the α subunit of the high-affinity type I IgE receptor (FcϵRI), which is detectable by using histamine release assays or immunoblotting. Prior reports suggest that purified IgG may not directly activate basophils but rather does so through complement activation. Objective: We sought to further elucidate the mechanism by which this antibody causes basophil histamine release, including the role of complement, and to reassess the relationship of functional versus binding assays. Methods: We incubated human basophils with patient serum, patient IgG, or patient IgG plus normal serum as a complement source and measured histamine release for each condition. IgG fractions were neutralized with cloned α subunit to determine whether histamine release decreased proportionately. We also screened sera from 260 patients to compare histamine release with immunoblotting results. Results: We initially tested 35 sera from patients with Chronic Urticaria by using basophils from 2 atopic donors and one nonreleaser with rabbit anti-IgE. No histamine was released from the nonreleaser, yet all donors responded identically to monocyte chemotactic protein 1, indicating a requirement for IgE or the IgE receptor. Basophil histamine release was markedly augmented by complement if release by IgG alone was low. Incubation of purified IgG with an increasing concentration of cloned α subunit gradually reduced the histamine-releasing capability in patients with positive or negative immunoblot results. Of 260 patients tested, 43% had positive histamine release results, and 47% had positive immunoblot results, yet there was no correlation when individual patients were assessed. Conclusion: A subpopulation of patients with Chronic Urticaria possess IgG antibody directed to the α subunit of FcϵRI. This IgG activates basophils, which is dependent on or augmented by complement. Binding assays for the FcϵRI α subunit, such as immunoblotting, are not currently feasible as a screening method. A functional assay is required. (J Allergy Clin Immunol 2001;107:1056-62.)
Riccardo Asero - One of the best experts on this subject based on the ideXlab platform.
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Chronic Urticaria: a focus on pathogenesis [version 1; referees: 3 approved]
F1000 Research Ltd, 2017Co-Authors: Riccardo Asero, A. Tedeschi, A.v. Marzano, M. CugnoAbstract:Chronic Urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6 weeks. These are rather frequent conditions that may severely affect patients' quality of life and sometimes represent a challenge for doctors as well. The causes of Chronic Urticaria are still poorly defined, although there is growing evidence that different biologic systems including immunity, inflammation, and coagulation may take part in the pathomechanism eventually leading to mast cell and basophil degranulation and hence to wheal formation. This review will discuss the main findings that are (slowly) shedding light on the pathogenesis of this disorder
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expression of tissue factor by eosinophils in patients with Chronic Urticaria
International Archives of Allergy and Immunology, 2009Co-Authors: M. Cugno, Angelo V Marzano, A Tedeschi, Daniele Fanoni, Luigia Venegoni, Riccardo AseroAbstract:Background: Although several cases of Chronic Urticaria (CU) are currently regarded as autoimmune in origin, associated with histamine-releasing autoantibodies, an activation of blo
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leukotriene receptor antagonists may prevent nsaid induced exacerbations in patients with Chronic Urticaria
Annals of Allergy Asthma & Immunology, 2000Co-Authors: Riccardo AseroAbstract:Background About 30% of patients with Chronic Urticaria experience flares of hives and/or angioedema after ingesting either aspirin or nonsteroidal anti-inflammatory drugs. In such patients, cross-reactivity to all NSAIDs seems to occur suggesting a mechanism dependent on cyclooxygenase inhibition. Objective To evaluate the preventive effect of leukotriene receptor antagonists on Urticaria exacerbations induced by NSAIDs in a patient with Chronic Urticaria. Methods A 59-year-old woman with a 2-year history of recurrent Urticaria exacerbated by different NSAIDs including aspirin 500 mg (2 episodes), piroxicam 20 mg, and nimesulide 100 mg (1 episode each) was studied. Acetaminophen 375 mg and floctafenine 50 mg induced a marked flare of Urticaria/angioedema in a single-blind, placebo-controlled challenge. Results The patient was totally Urticaria free during a 3-week course of montelukast 10 mg once a day. After montelukast withdrawal, a gradual relapse of Urticaria/angioedema occurred along with a further acute Urticaria/angioedema episode after a single piroxicam, 20-mg tablet. Zafirlukast 20 mg twice daily was started. After some days the patient was Urticaria-free again, and after 3 weeks she tolerated a 6-day course of injective piroxicam (20 mg once a day) without any problem. To date the patient is still Urticaria-free. Conclusion Leukotriene receptor antagonists may prevent the severe Urticaria/angioedema exacerbations which follow the use of NSAIDs in some patients with Chronic Urticaria.
Alexander Kapp - One of the best experts on this subject based on the ideXlab platform.
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Chronic Urticaria serum induces histamine release leukotriene production and basophil cd63 surface expression inhibitory effects of anti inflammatory drugs
The Journal of Allergy and Clinical Immunology, 2000Co-Authors: B Wedi, Vera Novacovic, Michael Koerner, Alexander KappAbstract:Abstract Background: A role of potential histamine-releasing autoantibodies against the high-affinity IgE receptor on the surface of basophils and mast cells is discussed in the pathogenesis of Chronic Urticaria. This so-called autoimmune Urticaria may be diagnosed by a positive intracutaneous autologous serum skin test, which is found in about 30% of patients with Chronic Urticaria. Objective: Our purpose was, first, to compare the effect of complement-inactivated sera of 20 patients with Chronic Urticaria and positive autologous serum skin tests, 20 patients with Chronic Urticaria and negative skin tests, and 20 control subjects without Chronic Urticaria (10 atopic and 10 nonatopic subjects) and, second, to analyze the effect of anti-inflammatory drugs on the serum activity. Methods: The following assay systems were used: release of histamine in whole blood samples, surface expression of the activation marker CD63 on basophils, and sulfidoleukotriene de novo production in leukocyte suspensions. Whole blood, basophils, and leukocyte suspensions were obtained from a nonatopic and an atopic donor. Results: Sera of patients with autologous serum skin test positive Chronic Urticaria resulted not only in significantly increased histamine release compared with skin test–negative Chronic Urticaria sera but also in a significant higher induction of basophil CD63 surface expression and sulfidoleukotriene de novo production. However, serum activity was neither characteristic for Chronic Urticaria nor for Chronic Urticaria with a positive autologous serum skin test. Preincubation with dapsone, chloroquine, and lidocaine dose dependently resulted in a significant reduction of all histamine release, CD63 expression, and sulfidoleukotriene production. In addition, mizolastine was able to inhibit serum-induced sulfidoleukotriene production. Conclusion: Further studies investigating the in vivo effect of these drugs will have to clarify their role in the management of the subset of patients with Chronic Urticaria demonstrating serum-induced inflammatory effects. (J Allergy Clin Immunol 2000;105:552-60.)
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prevalence of helicobacter pylori associated gastritis in Chronic Urticaria
International Archives of Allergy and Immunology, 1998Co-Authors: Bettina Wedi, S Wagner, Thomas Werfel, Michael P Manns, Alexander KappAbstract:Background: Chronic Urticaria and concurrent angioedema are frustrating problems for both physicians and patients. Methods: 100 patients with Chronic Urticaria (m
Jonathan A Bernstein - One of the best experts on this subject based on the ideXlab platform.
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the addition of zafirlukast to cetirizine improves the treatment of Chronic Urticaria in patients with positive autologous serum skin test results
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Scott E Bagenstose, Linda Levin, Jonathan A BernsteinAbstract:Abstract Background Because leukotrienes have potent local effects on cutaneous vasculature, leukotriene antagonists might be effective in the treatment of Chronic Urticaria. Objective A double-blinded, placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with Chronic Urticaria benefit from add-on therapy with a leukotriene-modifying agent. Methods Patients 12 years or older with a history of Chronic Urticaria (more than 6 weeks in duration) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H 1 -antagonist therapy for enrollment. At baseline, all subjects were skin tested to autologous serum to assess for the potential presence of FcϵRI or IgE autoantibodies. Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week. Those patients with persistent hives were randomized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo. At each successive weekly visit, physician and patient treatment effectiveness score (TES) and visual analog scale (VAS) ratings were recorded. Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings. Results were adjusted for baseline rating, recruiting center, and autologous serum skin test (ASST). A separate analysis evaluated patients with positive ASST results receiving combination therapy versus monotherapy. Results Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 ( P Conclusion The results of this study indicate that only patients with autoimmune (ASST positive) Chronic Urticaria refractory to H 1 -antagonist monotherapy might benefit from the addition of the leukotriene D 4 –receptor antagonist zafirlukast to their treatment regimen. These results also suggest that routine screening of patients with Chronic Urticaria with the ASST might be useful in formulating therapeutic algorithms in the management of Chronic Urticaria.
Scott E Bagenstose - One of the best experts on this subject based on the ideXlab platform.
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the addition of zafirlukast to cetirizine improves the treatment of Chronic Urticaria in patients with positive autologous serum skin test results
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Scott E Bagenstose, Linda Levin, Jonathan A BernsteinAbstract:Abstract Background Because leukotrienes have potent local effects on cutaneous vasculature, leukotriene antagonists might be effective in the treatment of Chronic Urticaria. Objective A double-blinded, placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with Chronic Urticaria benefit from add-on therapy with a leukotriene-modifying agent. Methods Patients 12 years or older with a history of Chronic Urticaria (more than 6 weeks in duration) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H 1 -antagonist therapy for enrollment. At baseline, all subjects were skin tested to autologous serum to assess for the potential presence of FcϵRI or IgE autoantibodies. Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week. Those patients with persistent hives were randomized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo. At each successive weekly visit, physician and patient treatment effectiveness score (TES) and visual analog scale (VAS) ratings were recorded. Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings. Results were adjusted for baseline rating, recruiting center, and autologous serum skin test (ASST). A separate analysis evaluated patients with positive ASST results receiving combination therapy versus monotherapy. Results Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 ( P Conclusion The results of this study indicate that only patients with autoimmune (ASST positive) Chronic Urticaria refractory to H 1 -antagonist monotherapy might benefit from the addition of the leukotriene D 4 –receptor antagonist zafirlukast to their treatment regimen. These results also suggest that routine screening of patients with Chronic Urticaria with the ASST might be useful in formulating therapeutic algorithms in the management of Chronic Urticaria.