Non-Skin-Related Symptoms are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results from CURE

https://www.sciencedirect.com/science/article/pii/S2213219824004124

The Journal of Allergy and Clinical Immunology: In Practice, Available online 24 April 2024

Polina Pyatilova, Yana Hackler, Felix Aulenbacher, Riccardo Asero, Andrea Bauer, Mojca Bizjak, Cascia Day, Joachim Dissemond, Aurélie Du-Thanh, Daria Fomina, Ana M. Giménez-Arnau, Clive Grattan, Stamatis Gregoriou, Tomasz Hawro, Alicja Kasperska-Zajac, Maryam Khoshkhui, Emek Kocatürk, Elena Kovalkova, Kanokvalai Kulthanan, Elizaveta Kuznetsova, Michael Makris, Olga Mukhina, David Pesqué, Jonny Peter, Pascale Salameh, Frank Siebenhaar, Agnieszka Sikora, Petra Staubach, Papapit Tuchinda, Mateusz Zamłyński, Karsten Weller, Marcus Maurer, Pavel Kolkhir

Highlights

• What is already known about this topic?

Patients with chronic spontaneous urticaria (CSU) often have recurrent, unexplained, non-skin-related symptoms, such as fever, joint/bone/muscle pain, and malaise. The rate of these symptoms and causes (urticaria or other conditions manifesting in wheals) are unknown.

• What does this article add to our knowledge?

One-third of patients had ≥1 non-skin-related symptoms, correlating with infection and food as trigger factors. These symptoms were associated with wheals of ≥24 hours duration, higher disease activity, longer disease duration, angioedema, worse quality of life, and poorer disease control.

• How does this study impact current management guidelines?

In patients with CSU and non-skin-related symptoms, disease control should be evaluated. Additional investigations such as skin biopsy, evaluation of inflammatory markers, and rarely genetic testing should be considered to rule out urticarial vasculitis and urticarial autoinflammatory disorders. Furthermore, it is important to consider and address any comorbidities early on.

ABSTRACT

Background

Chronic spontaneous urticaria (CSU) can present with non-skin-related symptoms (NSRS), including recurrent unexplained fever, joint/bone/muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (e.g., urticarial vasculitis or autoinflammatory disorders) or without wheals (e.g., 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 (CURE) of 2,521 patients with CSU who were ≥16 years old.

Results

One-third of CSU patients (31.2%, 786/2,521) had ≥1 NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having ≥1 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 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 (UAS7, median: 21 vs. 14, p=0.009), longer disease duration (years, median: 2 vs. 1, p=0.001), presence of angioedema (74.6% vs. 58.7%, p<0.001), worse quality of life (CU-Q2oL, median: 42 vs. 29, p<0.001) and more frequent poor control of CSU (78% vs. 69%, p<0.001).

Conclusion

The presence of NSRS in a subpopulation of CSU patients points to a need for better control of the disease, exclusion of comorbid conditions and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

Keywords: Chronic spontaneous urticarial non-skin-related symptoms malaise fever joint/bone/muscle pain

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