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      Total IgE as a Marker for Chronic Spontaneous Urticaria

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          Abstract

          Objective

          Immunoglobulin E (IgE) and its receptor, FcɛRI, importantly contribute to the pathophysiology of chronic spontaneous urticaria (CSU). Recent findings point to a possible role of total IgE as a marker of CSU disease activity, endotypes, and responses to treatment. The evidence in support of total IgE included in the diagnostic workup of patients with CSU has not yet been reviewed.

          Methods

          Publications were searched via PubMed. The search terms used were “chronic urticaria” and “total IgE.” Studies were screened by titles and abstracts, and 141 were used in the review.

          Results

          CSU patients frequently had elevated total IgE serum levels (up to 50%), but normal or very low total IgE levels also occurred. High total IgE may represent high disease activity, longer disease duration, high chance of responding to omalizumab treatment, quick relapse after stopping omalizumab, and lower chance of responding to cyclosporine. Low IgE, in contrast, may suggest Type IIb autoimmune CSU, poor response to treatment with omalizumab and a better chance to benefits from cyclosporine treatment. Furthermore, IgE in different CSU cohorts may have different physicochemical properties that could explain differences in treatment responses to IgE-directed therapies.

          Conclusion

          The results of our review suggest that total IgE is a valuable marker for CSU, and we recommend its assessment in the routine diagnostic workup of CSU patients.

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          Most cited references76

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          The EAACI/GA²LEN/EDF/WAO Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. The 2017 Revision and Update

          This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
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            Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta‐analysis

            Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population-based studies worldwide.
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              Regulation of mast-cell and basophil function and survival by IgE.

              Mast cells and basophils are important effector cells in T helper 2 (T(H)2)-cell-dependent, immunoglobulin-E-associated allergic disorders and immune responses to parasites. The crosslinking of IgE that is bound to the high-affinity receptor Fc epsilon RI with multivalent antigen results in the aggregation of Fc epsilon RI and the secretion of products that can have effector, immunoregulatory or autocrine effects. This response can be enhanced markedly in cells that have been exposed to high levels of IgE, which results in the increased surface expression of Fc epsilon RI. Moreover, recent work indicates that monomeric IgE (in the absence of crosslinking) can render mast cells resistant to apoptosis induced by growth-factor deprivation in vitro and, under certain circumstances, can induce the release of cytokines. So, the binding of IgE to Fc epsilon RI might influence mast-cell and basophil survival directly or indirectly, and can also regulate cellular function.
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                Author and article information

                Journal
                Allergy Asthma Immunol Res
                Allergy Asthma Immunol Res
                AAIR
                Allergy, Asthma & Immunology Research
                The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
                2092-7355
                2092-7363
                March 2021
                04 January 2021
                : 13
                : 2
                : 206-218
                Affiliations
                [1 ]Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
                [2 ]Department of Respiratory Medicine, Box Hill Hospital, Melbourne, Victoria, Australia.
                [3 ]Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
                [4 ]Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China.
                [5 ]Division of Immune-Mediated Skin Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.
                [6 ]Department of Dermatology and Venereology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.
                [7 ]Freie Universität Berlin, Berlin, Germany.
                Author notes
                Correspondence to Marcus Maurer, MD. Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité – Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany. Tel: +49-30-450-518042; Fax: +49-30-450-518972; marcus.maurer@ 123456charite.de
                Author information
                https://orcid.org/0000-0001-9955-385X
                https://orcid.org/0000-0002-3450-0877
                https://orcid.org/0000-0001-6278-2608
                https://orcid.org/0000-0001-5380-8132
                https://orcid.org/0000-0001-5520-2900
                https://orcid.org/0000-0003-3775-2989
                https://orcid.org/0000-0002-9365-3785
                https://orcid.org/0000-0003-4532-1644
                https://orcid.org/0000-0001-5661-3613
                https://orcid.org/0000-0001-9411-8998
                https://orcid.org/0000-0003-3432-6837
                https://orcid.org/0000-0002-1639-9410
                https://orcid.org/0000-0002-4121-481X
                Article
                10.4168/aair.2021.13.2.206
                7840871
                33474856
                8c02d8fd-3fc3-4328-8164-b50be58739bb
                Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 October 2020
                : 13 November 2020
                : 14 November 2020
                Funding
                Funded by: GA2LEN
                Funded by: Russian Academic Excellence Project 5-10
                Funded by: Darrell Gwynn Foundation, CrossRef https://doi.org/10.13039/100002955;
                Award ID: KFO 339
                Categories
                Review

                Immunology
                urticaria,chronic spontaneous urticaria,immunoglobulin e,biomarkers,omalizumab,cyclosporine,therapeutics,diagnosis,receptor

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