Non–Skin Related Symptoms Are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results From the Chronic Urticaria Registry

Pyatilova P. Hackler Y. Aulenbacher F. Asero R. Bauer A. Bizjak M. Day C. Dissemond J. Du-Thanh A. Fomina D. Giménez-Arnau A.M. Grattan C. Gregoriou S. Hawro T. Kasperska-Zajac A. Khoshkhui M. Kocatürk E. Kovalkova E. Kulthanan K. Kuznetsova E. Makris M. Mukhina O. Pesqué D. Peter J. Salameh P. Siebenhaar F. Sikora A. Staubach P. Tuchinda P. Zamłyński M. Weller K. Maurer M. Kolkhir P.
July 2024 American Academy of Allergy, Asthma and Immunology

Journal of Allergy and Clinical Immunology: In Practice
2024 #12 Issue 7 1890 - 1899.e3 pp.

Background: Chronic spontaneous urticaria (CSU) can present with non–skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection). Objective: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. Methods: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older. Results: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001). Conclusions: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

and muscle pain , bone , Chronic spontaneous urticaria , Fever , Joint , Malaise , Non–skin related symptoms

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Institute of Allergology, Charité–Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Fraunhofer Institute for Translational Medicine and Pharmacology, Immunology and Allergology, Berlin, Germany
Ambulatorio di Allergologia, Clinica san Carlo, Paderno Dugnano, Italy
Department of Dermatology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
Division of Allergy, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia
Urticaria Center of Reference and Excellence, Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa
Urticaria Center of Reference and Excellence, Allergy and Immunology Unit, University of Cape Town, Lung Institute, Cape Town, South Africa
Department of Dermatology, Venerology, and Allergology, University of Essen, Essen, Germany
University of Montpellier and University Hospital of Montpellier, Dermatology Department, Montpellier, France
Moscow City Research and Practical Center of Allergology and Immunology, Moscow Healthcare Department, City Clinical Hospital 52, Moscow, Russian Federation
Department of Clinical Immunology and Allergology, I.M., Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
Department of Pulmonology, Astana Medical University, Astana, Kazakhstan
Department of Dermatology, Hospital del Mar and Research Institute, Barcelona, Universitat Pompeu Fabra, Barcelona, Spain
St Johns Institute of Dermatology, Guys Hospital, London, United Kingdom
Faculty of Medicine, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Athens, Greece
Department of Dermatology, Allergology, and Venereology, Institute and Comprehensive Center for Inflammation Medicine, University Medical Center Schleswig-Holstein, Lübeck, Germany
LEN Urticaria Centers of Reference and Excellence Network), Medical University of Silesia in Katowice, Katowice, Poland
Allergy Research Center, Mashhad University of Medical Science, Mashhad, Iran
Department of Dermatology, Koç University School of Medicine, Istanbul, Turkey
Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Allergy Unit, Second Department of Dermatology and Venereology, National and Kapodistrian University of Athens, University General Hospital “Attikon,”, Athens, Greece
Department of Dermatology, Hospital del Mar Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
Research Department, School of Medicine, Lebanese American University, Byblos, Lebanon
Institut National de Santé Publique dÉpidémiologie Clinique et de Toxicologie-Liban, Beirut, Lebanon
Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus
Faculty of Pharmacy, Lebanese University, Hadat, Lebanon
Department of Dermatology, Johannes Gutenberg University, Mainz, Germany

Institute of Allergology
Fraunhofer Institute for Translational Medicine and Pharmacology
Ambulatorio di Allergologia
Department of Dermatology
Division of Allergy
Urticaria Center of Reference and Excellence
Urticaria Center of Reference and Excellence
Department of Dermatology
University of Montpellier and University Hospital of Montpellier
Moscow City Research and Practical Center of Allergology and Immunology
Department of Clinical Immunology and Allergology
Department of Pulmonology
Department of Dermatology
St Johns Institute of Dermatology
Faculty of Medicine
Department of Dermatology
LEN Urticaria Centers of Reference and Excellence Network)
Allergy Research Center
Department of Dermatology
Department of Dermatology
Allergy Unit
Department of Dermatology
Research Department
Institut National de Santé Publique dÉpidémiologie Clinique et de Toxicologie-Liban
Department of Primary Care and Population Health
Faculty of Pharmacy
Department of Dermatology

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