Patients suffering from chronic spontaneous urticaria (CSU) and chronic inducible urticaria often experience a profound decline in their overall quality of life. David Lang, MD, from the Cleveland Clinic and former president of the American Academy of Allergy, Asthma, and Immunology, highlighted this during a session at the American College of Allergy, Asthma, and Immunology meeting in November. He emphasized the extensive effects of chronic urticaria on various aspects of daily living, including physical functioning, social interactions, mental well-being, and energy levels, as demonstrated in a 2007 study that compared affected individuals to healthy controls across all domains of the SF-36 health survey.
Sleep Abnormalities With Urticaria
When clinicians assess patients with dermatological conditions like CSU, inquiries about insomnia and sleep quality are standard due to the obvious connection between intense itching and disrupted rest. However, Caroline Mann, MD, from Johannes-Gutenberg University in Mainz, Germany, and her research team argue that the true extent of sleep disturbances in chronic pruritic skin disorders remains underappreciated.
In their 2020 pilot investigation published in Acta Dermato-Venereologica, the team observed elevated scores on the Insomnia Severity Index (ISI) among patients with a variety of chronic inflammatory skin conditions. Specifically, for the 36 participants diagnosed with chronic urticaria, the average ISI score stood at 6.8 during periods without flares, suggesting no clinically significant insomnia. In contrast, scores jumped to 14.9 during active flares, approaching the cutoff for moderate clinical insomnia. Concurrently, these patients recorded a mean Dermatology Life Quality Index (DLQI) score of 8.5 out of 30, reflecting a moderate level of impairment in their quality of life attributable to the disease. The study revealed that insomnia symptoms worsened significantly during flares, with statistically significant correlations between ISI and DLQI scores (P=0.029) as well as between pruritus intensity scores and DLQI scores (P>0.001).
Participants commonly described difficulties in initiating sleep, staying asleep throughout the night, awakening prematurely, disruptions to daytime activities, general dissatisfaction with their sleep routines, and heightened anxiety over their sleep problems. In this cohort of chronic urticaria patients, compromised sleep appeared to alter their subjective perception of disease severity. Elevated pruritus levels were linked to reduced satisfaction with sleep patterns.
Further evidence from a Spanish study involving 75 CSU patients indicated that those with suboptimal sleep quality faced a 1.62 times higher likelihood of experiencing anxiety and a 3.93 times greater risk of depression. Prior research has also connected insomnia to diminished pain tolerance in various chronic illnesses. Interestingly, in Mann’s analysis, patient-reported insomnia did not escalate proportionally with pruritus intensity. The authors pointed out that, contrary to expectations from other investigations, itch alone did not emerge as the primary driver of sleep disruption. This suggests the involvement of other contributing elements in the poor sleep experienced by these patients.
A survey of 160 chronic urticaria patients, shared at the 2024 American Academy of Allergy, Asthma, and Immunology meeting, revealed that 29% dealt with insomnia, with the figure climbing to 45% among those whose condition remained uncontrolled. Obstructive sleep apnea affected 28% of the group overall and 35% of those with uncontrolled urticaria. Bruxism, or teeth grinding, was reported by 18% of participants, predominantly among those whose urticaria was well-managed. The researchers stressed that these results underscore the critical need to integrate sleep disorder evaluation into the comprehensive care of chronic urticaria patients, advocating for multifaceted strategies that tackle both the primary disease and its sleep-related complications.
Treatment Impact
Effective management of the underlying CSU through sustained therapy demonstrably alleviates the associated sleep disturbances. A pooled evaluation of the phase III GLACIAL, ASTERIA I, and ASTERIA II randomized controlled trials demonstrated that omalizumab (Xolair), used for chronic idiopathic or spontaneous urticaria, produced substantially greater reductions in sleep impairment than placebo. These benefits became evident after the initial omalizumab dose and peaked within the first four weeks of treatment, only to wane following cessation of therapy, according to Evgeniya Antonova, PhD, from Genentech in South San Francisco, California, and her collaborators in their publication in Clinical and Translational Allergy.
The researchers observed that conventional approaches to sleep issues in skin disorders typically emphasize sedative agents like hypnotics, rather than addressing the root cause. Sedating H1 antihistamines are frequently prescribed at bedtime for symptom relief and sleep aid. It is therefore noteworthy that improvements in sleep were achieved by directly targeting the dermatological condition itself.
Comparable advantages emerged from the REMIX-1 and REMIX-2 clinical trials evaluating remibrutinib (Rhapsido), an oral Bruton’s tyrosine kinase inhibitor approved in October for adult CSU patients who continue to have symptoms despite H1 antihistamine therapy. Data from these trials, presented at the November American College of Allergy, Asthma, and Immunology meeting, examined impacts on quality of life and sleep. Remibrutinib outperformed placebo in enhancing DLQI scores and the weekly Sleep Interference Score (SIS7).
Improvements in SIS7 with remibrutinib versus placebo were apparent by week 1 (7.4 compared to 10.3 on the 0-21 scale), with progressive gains sustained up to week 24 (2.9 versus 4.8). Notably, enhancements in urticaria severity scores closely paralleled sleep improvements, exhibiting a robust correlation between the metrics.
Dupilumab (Dupixent), an injectable monoclonal antibody targeting the interleukin-4 receptor alpha and approved in April as an adjunctive option for CSU patients aged 12 and older refractory to H1 antihistamines, similarly reduced the burden of sleep impairment. This was evidenced in a post-hoc analysis of the phase III LIBERTY-CSU CUPID-A trial.
Looking ahead, biologics are poised for an expanded prominence in CSU management, with forthcoming updates to the chronic urticaria practice parameters anticipated in 2026 likely to broaden therapeutic recommendations, as Lang indicated. He advocated for greater patient involvement in treatment choices, allowing them to weigh options based on personal priorities. Lang likened this to asthma care, where multiple biologics may be suitable, a scenario increasingly applicable to CSU as well. Patients deserve full transparency to make informed decisions aligned with their needs and preferences.
