In CSU, Non-Dermal Conditions Impact Disease Control and Quality of Life
—A recent study showed that up to one-third of patients with chronic spontaneous urticaria had non-skin-related symptoms, and these are tied to increased disease activity, poorer disease control, and poorer quality of life.
The diagnosis of chronic spontaneous urticaria (CSU) requires an outbreak of hives lasting >6 weeks with no identifiable physical trigger.1 However, patients also may have recurrent noncutaneous symptoms that further diminish quality of life.2,3 Patient outcomes could be improved with better understanding of the type and prevalence of such symptoms in those with CSU.2
A new study, using data from the multinational Chronic Urticaria Registry (CURE), finds that “one in three patients diagnosed with chronic spontaneous urticaria have additional non-skin-related symptoms such as fever; joint, bone and muscle pain; and/or malaise,” according to Pavil Kolkhir, MD, Institute of Allergology, Charité—Universitätsmedizin Berlin, Berlin Institute of Health, and the Fraunhofer Institute for Translational Medicine and Pharmacology in Germany. “Our study shows that CSU patients with any of these symptoms are more likely to have longer wheal duration, higher disease activity, longer disease duration, worse quality of life, and poorer disease control,” added Polina Pyatilova, MD, lead author and colleague of Dr. Kolkhir.
The approach
To determine the prevalence and impact of noncutaneous symptoms, researchers reviewed data from 2521 patients aged 16 or older enrolled in CURE. CURE is an ongoing, prospective, observational registry that includes patients from around the world on all continents except North America and Antarctica. The median age of the patients included in this study was 44 years, with a median duration of CSU of 1 year. Three-quarters of patients were female.2
Enrolled patients and their physicians completed questionnaires every 6 months that included demographics and questions on symptoms, urticaria triggers, risk factors and comorbid conditions, and type of treatment and response. Disease control was measured semi-annually using the Urticaria Control Test (UCT) and weekly in some patients using the Urticaria Activity Score. Noncutaneous symptoms assessed were fever; pain in joints, bone, or muscle (JBMP); and malaise, and were obtained from patient-reported questionnaires. Quality of life was assessed using standardized general (Dermatology Life Quality Index) and urticaria-specific (Chronic Urticaria Quality of Life) instruments. Data were included for baseline age and other demographic factors, comorbid conditions, and laboratory values.2
Descriptive analyses were done for categorical values (using frequency and percentage) and quantitative values (using median and interquartile ranges). Mann-Whitney (two-group comparisons) and Kruskal-Wallis (three-group comparisons) were used for bivariate analysis. Outcomes were reported as adjusted odds ratio (OR) with 95% confidence intervals (CI).2
What the investigators found
The findings showed that 31.2% (n=786) of patients had ≥1 noncutaneous symptom, including 8.2% (n=208) with 2 and 1.8% (n=46) with 3 concurrent symptoms. Recurrent fever was reported by 5.3% (n=134), JBMP by 19.1% (n=482), and otherwise unexplained malaise by 18.6% (n=470).2
Factors that correlated with having ≥1 noncutaneous symptoms in multivariable analysis included food (OR=1.7, 95% CI: 1.08-2.78; P=.022) or infection (OR=1.5, 95% CI: 1.02-2.28; P=.039) triggers and wheal duration of 24 hours or more (OR=2.5, 95% CI: 1.89-3.32; P=.000). Wheal duration showed significant correlation with each of the individual symptoms as well. Medication triggers were correlated with symptoms of JBMP (OR=2.29, 95% CI: 1.26-4.15; P=.006) or malaise (OR=2.19, 95% CI: 1.21-3.95; P=.015).2
Patients reporting noncutaneous symptoms had higher disease activity (P=.009), a longer median duration of CSU (P=.001), and higher prevalence of concurrent angioedema (P<.001).2 Sleep disturbances, poorer quality of life (versus those without symptoms), and concurrent conditions of anxiety, atopic dermatitis, and gastrointestinal or thyroid disease also correlated with noncutaneous symptoms. On laboratory tests, patients with noncutaneous symptoms had elevated levels of inflammatory biomarkers (leukocytes, erythrocyte sedimentation rates, and C-reactive protein). Finally, more patients reporting noncutaneous symptoms than those without such symptoms had poor disease control as measured by the UTC (78% vs 69%, respectively; P<.001).2
Conclusions and some limitations
Patients with CSU tend to be women between the ages of 20 and 40, and CSU may persist for up to 5 years in some individuals.4 Both cutaneous and noncutaneous symptoms negatively impact quality of life, and may impair performance at work or school.4 To improve these patients’ lives, a better understanding of CSU presentation and new treatment alternatives are needed. “Up to 30% of patients with CSU have insufficient response to urticaria guideline-recommended therapy with antihistamines and omalizumab, with considerable quality of life impairment,” noted Drs. Kolkhir and Pyatilova. “A better understanding of the pathophysiology of CSU and new target molecules is needed for better treatment.”
A few limitations to this study were noted by the authors. First is that only 3 types of noncutaneous symptoms were included in the data, and those were subject to patient bias or opinion. Severity data were also lacking, and it was not possible to track changes over time nor to establish causation. In short, the data were subject to self-reporting biases that could introduce overall weaknesses, thus establishing the need for further studies.
A key takeaway of this study is that these symptoms worsen patients’ experience of CSU and leave them with worse control and quality of life. This emphasizes the importance of recognizing and (where possible) treating all symptoms of CSU. “Our findings indicate the need for better diagnosis and management of CSU when non-skin-related symptoms are present, including differential diagnosis of urticarial vasculitis and urticarial autoinflammatory diseases and early diagnosis and treatment of concomitant disorders,” Dr. Kolkhir said. Dr. Pyatilova added that, “CSU patients should be asked about the presence of any systemic symptoms at every visit.”
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