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      Stress, pseudoallergens, autoimmunity, infection and inflammation in chronic spontaneous urticaria

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          Abstract

          Chronic spontaneous urticaria (CSU) is often associated with organ specific autoimmunity but is rarely caused by food allergy. Colourings and preservatives in pre-packaged foods, so called pseudoallergens, have also been implicated. Factors that promote inflammation or reduce anti-inflammatory mechanisms may however, predispose susceptible individuals to CSU. Chronic underlying infection and mental and emotional stress can sometimes precede the onset of CSU and once established can exacerbate the symptoms. There is early evidence of dysbiosis within the gastrointestinal tract in people with CSU and reduced levels of vitamin D are also evident. The latter may be related to the importance of vitamin D3 in increasing T regulatory function which can control a tendency to autoimmunity. It is quite possible that a state of on-going chronic inflammation with reduced anti-oxidant mechanisms may underlie the not infrequent association between CSU and metabolic syndrome. Effective treatment of CSU should involve the use of anti-histamines, intermittent steroids and anti-IgE therapy. For recalcitrant disease immune modulatory therapy has a place. However, talking therapies that reduce stress and anxiety, vitamin D3 supplementation, correction of intestinal dysbiosis and treatment of any chronic infection should also be considered.

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          Most cited references110

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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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            Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases.

            Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity, and wound healing. However, MCs are best known for their roles in allergic and inflammatory diseases, such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis, and asthma. In addition to the high-affinity IgE receptor (FcεRI), MCs express numerous G protein-coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and the most common targets of drug therapy. Antimicrobial host defense peptides, neuropeptides, major basic protein, eosinophil peroxidase, and many US Food and Drug Administration-approved peptidergic drugs activate human MCs through a novel GPCR known as Mas-related G protein-coupled receptor X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on the plasma membrane and intracellular sites and their selective expression in MCs. In this article we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch, and chronic inflammatory diseases, such as urticaria and asthma. We propose that host defense peptides that kill microbes directly and activate MCs through MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, mAbs or small-molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders.
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              Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria.

              Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy.
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                Author and article information

                Contributors
                Amolak.Bansal@nhs.net
                Journal
                Allergy Asthma Clin Immunol
                Allergy Asthma Clin Immunol
                Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology
                BioMed Central (London )
                1710-1484
                1710-1492
                11 September 2019
                11 September 2019
                2019
                : 15
                : 56
                Affiliations
                [1 ]ISNI 0000 0001 2171 1133, GRID grid.4868.2, St Barts, Queen Mary’s University, ; London, UK
                [2 ]GRID grid.416404.3, St Helier Hospital, ; Carshalton, Surrey SM5 1AA UK
                Article
                372
                10.1186/s13223-019-0372-z
                6737621
                31528163
                3afd0696-0805-4870-8b56-a49720a8c729
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 May 2019
                : 4 September 2019
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Immunology
                chronic urticaria,pseudoallergens,stress,infections,autoimmunity,cofactors,vitamin d3
                Immunology
                chronic urticaria, pseudoallergens, stress, infections, autoimmunity, cofactors, vitamin d3

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