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      Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria

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          Abstract

          Purpose

          Patients with chronic spontaneous urticaria (CSU) have an increased risk for comorbid autoimmune diseases. In this retrospective multicenter study of CSU patients, we evaluated clinical and laboratory features of CSU associated with a higher risk of comorbid autoimmune diseases.

          Methods

          We analyzed records of CSU patients (n = 1,199) for a history or presence of autoimmune diseases. Patients were diagnosed with type IIb autoimmune CSU (aiCSU) if all 3 tests were positive: autologous serum skin test (ASST), basophil histamine release assay (BHRA) and/or basophil activation test (BAT), and IgG autoantibodies against FcεRIα/IgE detected by immunoassay.

          Results

          Twenty-eight percent of CSU patients had at least 1 autoimmune disease. The most prevalent autoimmune diseases were Hashimoto's thyroiditis (HT) (≥ 21%) and vitiligo (2%). Two percent of CSU patients had ≥ 2 autoimmune diseases, most frequently HT plus vitiligo. Comorbid autoimmune diseases, in patients with CSU, were associated with female sex, a family history of autoimmune diseases, and higher rates of hypothyroidism and hyperthyroidism ( P < 0.001). Presence of autoimmune diseases was linked to aiCSU ( P = 0.02). The risks of having autoimmune diseases were 1.7, 2.9 and 3.3 times higher for CSU patients with a positive ASST, BHRA and BAT, respectively. In CSU patients, markers for autoimmune diseases, antinuclear antibodies and/or IgG anti-thyroid antibodies were associated with non-response to omalizumab treatment ( P = 0.013).

          Conclusions

          In CSU, autoimmune diseases are common and linked to type IIb autoimmune CSU. Our results suggest that physicians assess and monitor all adult patients with CSU for signs and symptoms of common autoimmune diseases, especially HT and vitiligo.

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          Most cited references53

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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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            Autoimmune thyroid disorders.

            Autoimmune thyroid diseases (AITD) result from a dysregulation of the immune system leading to an immune attack on the thyroid. AITD are T cell-mediated organ-specific autoimmune disorders. The prevalence of AITD is estimated to be 5%; however, the prevalence of antithyroid antibodies may be even higher. The AITD comprise two main clinical presentations: Graves' disease (GD) and Hashimoto's thyroiditis (HT), both characterized by lymphocytic infiltration of the thyroid parenchyma. The clinical hallmarks of GD and HT are thyrotoxicosis and hypothyroidism, respectively. The mechanisms that trigger the autoimmune attack to the thyroid are still under investigation. Epidemiological data suggest an interaction among genetic susceptibility and environmental triggers as the key factor leading to the breakdown of tolerance and the development of disease. Recent studies have shown the importance of cytokines and chemokines in the pathogenesis of AT and GD. In thyroid tissue, recruited T helper 1 (Th1) lymphocytes may be responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates CXCL10 (the prototype of the IFN-γ-inducible Th1 chemokines) secretion from the thyroid cells, therefore creating an amplification feedback loop, initiating and perpetuating the autoimmune process. Associations exist between AITD and other organ specific (polyglandular autoimmune syndromes), or systemic autoimmune disorders (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, cryoglobulinemia, sarcoidosis, psoriatic arthritis). Moreover, several studies have shown an association of AITD and papillary thyroid cancer. These data suggest that AITD patients should be accurately monitored for thyroid dysfunctions, the appearance of thyroid nodules, and other autoimmune disorders.
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              Subclinical Hypothyroidism

              Subclinical hypothyroidism, defined as an elevated serum thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine (FT4) affects up to 10% of the adult population.
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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
                July 2021
                16 February 2021
                : 13
                : 4
                : 545-559
                Affiliations
                [1 ]Dermatological Allergology, UCARE Charité, 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 ]Division of Immune-Mediated Skin Diseases, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.
                [3 ]Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano (MI), Italy.
                [4 ]Servicio de Alergia. Instituto de Investigación Sanitaria (IIS)- Hospital Universitario de la Princesa, Madrid, Spain.
                [5 ]Department of Allergy, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra Pamplona IDISNA, RETIC de Asma, Reacciones Adversas y Alérgicas (ARADyAL), Pamplona, Spain.
                [6 ]Department of Dermatology, Hospital del Mar, IMIM, Universitat Autònoma Barcelona, Spain.
                [7 ]Department of Dermatology and Allergy, University Medical Center (UKGM), Justus Liebig University, Giesen, Germany.
                [8 ]Department of Dermatology, Medical University of Vienna, Vienna, Austria.
                [9 ]Bioagilytix Europe GmbH, Hamburg, Germany.
                [10 ]Institute of Immunology, University of Kiel, Kiel, Germany.
                [11 ]Department of Allergy and Clinical Immunology, 424 General Military Training Hospital, Thessaloniki, Greece.
                [12 ]Allergy Unit, 2nd Dpt. of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, University General Hospital “Attikon”, Athens, Greece.
                [13 ]RefLab ApS, Copenhagen, Denmark.
                [14 ]Odense Research Center of Anaphylaxis, ORCA, Odense, Denmark.
                [15 ]Department of Dermatology, University Medical Center Mainz, Mainz, Germany.
                [16 ]Division of Clinical Immunology and Allergy, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
                [17 ]Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
                Author notes
                Correspondence to Marcus Maurer, MD. 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, 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/0000-0001-5380-8132
                https://orcid.org/0000-0001-9955-385X
                https://orcid.org/0000-0002-8277-1700
                https://orcid.org/0000-0001-7725-981X
                https://orcid.org/0000-0001-8495-1302
                https://orcid.org/0000-0001-9548-5423
                https://orcid.org/0000-0001-9990-1332
                https://orcid.org/0000-0002-3124-9998
                https://orcid.org/0000-0002-8238-2561
                https://orcid.org/0000-0002-6058-869X
                https://orcid.org/0000-0003-1371-6764
                https://orcid.org/0000-0003-2713-2380
                https://orcid.org/0000-0002-4070-9976
                https://orcid.org/0000-0002-2481-4549
                https://orcid.org/0000-0002-2276-0284
                https://orcid.org/0000-0002-2202-2513
                https://orcid.org/0000-0003-4347-337X
                https://orcid.org/0000-0002-4121-481X
                Article
                10.4168/aair.2021.13.4.545
                8255350
                34212543
                53a79a30-7205-4516-9c75-6a25413f8f1c
                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
                : 16 September 2020
                : 10 November 2020
                : 23 November 2020
                Funding
                Funded by: GA2LEN stipend
                Categories
                Original Article

                Immunology
                chronic urticaria,autoimmune diseases,autoimmune thyroiditis,autoantibodies,autoimmunity,omalizumab,vitiligo,immunoassay

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