A Practical Approach to Diagnosing and Managing Chronic Spontaneous Urticaria

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Abstract

Chronic spontaneous urticaria (CSU) is an unpredictable inflammatory skin condition characterized by the spontaneous onset of itchy wheals, angioedema, or both, which occurs for longer than 6 weeks overall. Despite the relatively straightforward diagnostic algorithm for CSU, relying primarily on a detailed medical history and only limited laboratory tests, patients often wait years to be diagnosed, with many cycling through different healthcare practitioners before a diagnosis is made. Even then, current treatment options for CSU are limited, with approximately half of patients resistant to standard-of-care second-generation antihistamines at standard or higher doses. As such, there is an unmet need for improved, streamlined management for patients with CSU. Here, we review the evidence-based diagnostic algorithm for CSU, consider the required steps of the diagnostic workup, and provide practical, real-world advice on the management of CSU to improve the timely diagnosis and care of patients with this debilitating disease.

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Most cited references 83

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Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria.

Marcus Maurer, Karin Rosén, Hsin-Ju Hsieh … (2013)

Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H-antihistamines, even at high doses. In phase 2 trials, omalizumab, an anti-IgE monoclonal antibody [corrected] that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients. In this phase 3, multicenter, randomized, double-blind study, we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H-antihistamine therapy (licensed doses). We randomly assigned 323 patients to receive three subcutaneous injections, spaced 4 weeks apart, of omalizumab at doses of 75 mg, 150 mg, or 300 mg or placebo, followed by a 16-week observation period. The primary efficacy outcome was the change from baseline in a weekly itch-severity score (ranging from 0 to 21, with higher scores indicating more severe itching). The baseline weekly itch-severity score was approximately 14 in all four study groups. At week 12, the mean (±SD) change from baseline in the weekly itch-severity score was -5.1±5.6 in the placebo group, -5.9±6.5 in the 75-mg group (P=0.46), -8.1±6.4 in the 150-mg group (P=0.001), and -9.8±6.0 in the 300-mg group (P<0.001). Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg group (1% for each). Omalizumab diminished clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of approved doses of H-antihistamines. (Funded by Genentech and Novartis Pharma; ClinicalTrials.gov number, NCT01292473.).

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The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria

Torsten Zuberbier, Amir Hamzah Abdul Latiff, Mohamed Abuzakouk … (2021)

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

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Mast Cell Mediators: Their Differential Release and the Secretory Pathways Involved

Tae Chul Moon, A. Befus, Marianna Kulka (2014)

Mast cells (MC) are widely distributed throughout the body and are common at mucosal surfaces, a major host–environment interface. MC are functionally and phenotypically heterogeneous depending on the microenvironment in which they mature. Although MC have been classically viewed as effector cells of IgE-mediated allergic diseases, they are also recognized as important in host defense, innate and acquired immunity, homeostatic responses, and immunoregulation. MC activation can induce release of pre-formed mediators such as histamine from their granules, as well as release of de novo synthesized lipid mediators, cytokines, and chemokines that play diverse roles, not only in allergic reactions but also in numerous physiological and pathophysiological responses. Indeed, MC release their mediators in a discriminating and chronological manner, depending upon the stimuli involved and their signaling cascades (e.g., IgE-mediated or Toll-like receptor-mediated). However, the precise mechanisms underlying differential mediator release in response to these stimuli are poorly known. This review summarizes our knowledge of MC mediators and will focus on what is known about the discriminatory release of these mediators dependent upon diverse stimuli, MC phenotypes, and species of origin, as well as on the intracellular synthesis, storage, and secretory processes involved.

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Author and article information

Contributors

Adam Friedman:

ORCID: http://orcid.org/0000-0001-8925-1620

ajfriedman@mfa.gwu.edu

Journal

Journal ID (nlm-ta): Dermatol Ther (Heidelb)

Journal ID (iso-abbrev): Dermatol Ther (Heidelb)

Title: Dermatology and Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 2193-8210

ISSN (Electronic): 2190-9172

Publication date (Electronic): 17 May 2024

Publication date PMC-release: 17 May 2024

Publication date Collection: June 2024

Volume: 14

Issue: 6

Pages: 1371-1387

Affiliations

[1 ]Department of Dermatology, George Washington University School of Medicine and Health Sciences, ( https://ror.org/00y4zzh67) Washington, DC USA

[2 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Department of Dermatology, , University of Maryland School of Medicine, ; Baltimore, MD USA

[3 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Maryland Itch Center, , University of Maryland School of Medicine, ; Baltimore, MD USA

[4 ]Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, ( https://ror.org/02dgjyy92) Coral Gables, FL USA

Author information

Adam Friedman http://orcid.org/0000-0001-8925-1620

Shawn G. Kwatra http://orcid.org/0000-0003-3736-1515

Gil Yosipovitch http://orcid.org/0000-0001-6303-1822

Article

Publisher ID: 1173

DOI: 10.1007/s13555-024-01173-5

PMC ID: 11169305

PubMed ID: 38758422

SO-VID: ade61d39-e72a-4df1-9720-0810b994c432

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 23 February 2024

Date accepted : 17 April 2024

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100008272, Novartis Pharmaceuticals Corporation;

Custom metadata

ScienceOpen disciplines: Dermatology

Keywords: chronic spontaneous urticaria,chronic urticaria,diagnosis,angioedema,wheals

Data availability:

ScienceOpen disciplines: Dermatology

Keywords: chronic spontaneous urticaria, chronic urticaria, diagnosis, angioedema, wheals

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