Chronic Spontaneous Urticaria: Studying Age-Specific Therapies
Overview
Chronic spontaneous urticaria (CSU) presents differently in pediatric and adult populations. A retrospective analysis of 751 CSU patients (162 pediatrics and 589 adults) revealed shorter disease duration and lower angioedema rates in pediatric cases. Adults showed higher prevalence of anti-thyroid peroxidase positivity, elevated CRP, eosinopenia, and skin prick test reactivity. Pediatric patients exhibited better response to antihistamines, while only 7% used omalizumab compared to 20.8% in adults. The study highlights distinct clinical and treatment aspects in CSU between pediatric and adult cohorts.
Introduction
Chronic urticaria (CU) is divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), depending on eliciting factors. CU affects a significant portion of the population worldwide, with prevalence rates around 1.4%. The approach to CU treatment involves histamine-mediated symptom relief using antihistamines, often second-generation H1 antihistamines (sg-AH). Omalizumab and cyclosporine are considered for non-responsive cases. While guidelines exist, pediatric CU management lacks specific algorithms. Limited evidence-based knowledge on pediatric CU hinders clear guidance, especially regarding differences in clinical features, laboratory parameters, comorbidities, treatment response, and indicators compared to adults. This study addresses these gaps.
Method
The study involved a retrospective analysis of patients diagnosed with chronic spontaneous urticaria (CSU) who sought treatment at the Pediatric Allergy Clinic and Dermatology Clinic of Istanbul Okmeydanı Training and Research Hospital between 2013 and 2019. The clinics were renowned centers for chronic spontaneous urticaria treatment and catered to a substantial number of outpatients. Referrals to the clinics were not contingent on treatment refractoriness or disease duration; all CSU patients were considered eligible for referral.
Inclusion Criteria
- Patients diagnosed with chronic spontaneous urticaria (CSU).
- Patients who sought treatment at the Pediatric Allergy Clinic and Dermatology Clinic of Istanbul Okmeydanı Training and Research Hospital between 2013 and 2019.
- Patients of all ages, including pediatric (<18 years), adolescent (12–17 years), and adult (≥18 years) patients.
- Patients who received treatment in accordance with the International Urticaria Guideline recommendations.
- Patients with available data on demographic features (age, gender, atopy, family history of atopy, disease duration, and angioedema) and laboratory values (serum eosinophil count, serum total IgE levels, C-reactive protein levels, antithyroid peroxidase antibody levels, IgG-anti-TPO positivity, skin prick test results, and autologous serum skin test results).
Exclusion Criteria
- Patients with chronic inducible urticaria or other types of urticaria.
- Patients seeking treatment for reasons other than chronic spontaneous urticaria.
- Patients with incomplete or insufficient medical records.
- Patients with a history of significant medical conditions that could confound the study results.
- Patients who did not receive treatment in accordance with the International Urticaria Guideline recommendations.
- Patients with missing data on key demographic features or laboratory values necessary for analysis.
The study was ethically approved by the Ethics Committee of Istanbul Okmeydanı Training and Research Hospital. Data on relevant patient characteristics and treatment responses were extracted from patient files. The analysis aimed to determine differences between pediatric, adolescent, and adult chronic spontaneous urticaria patients in terms of clinical features, laboratory parameters, comorbidities, and treatment response indicators.
Statistical Analysis
The statistical analysis was conducted using the SPSS package program (Version 22 for Windows, SPSS Inc). Continuous variables’ suitability for normal distribution was assessed using the “Kolmogorov–Smirnov Test,” and the results were presented as a median along with the minimum and maximum values. Frequency data were presented as percentages (%). Gender, atopy, IgG-anti-TPO positivity, low IgE, elevated CRP, eosinopenia, ASST positivity, skin prick test positivity, and autoimmune thyroiditis rates were compared between groups using Pearson’s chi-squared test or Fisher’s exact test. For comparisons involving age, disease duration, and laboratory parameter levels, Kruskal–Wallis test (with Bonferroni correction) and Mann–Whitney U tests were employed.
To determine the factors influencing treatment responses for patients aged ≥12 years, binary logistic regression analysis was performed. The statistical significance level was established as p < .05. This rigorous analytical approach aimed to reveal meaningful differences, associations, and predictors within the studied parameters and treatment responses among the various patient groups.
Results
A retrospective analysis of 751 CSU patients (162 pediatric and 589 adults) revealed distinct demographic and laboratory variations. Pediatric patients had a mean age of 10.7 ± 4.2, while adults had a mean age of 40.3 ± 13.8. Females accounted for 48.8% of pediatric patients and 69.6% of adult patients (p < .001). Disease duration was longer in adults (12 vs. 5 months), and angioedema was more prevalent (59.8% vs. 19.1%, p < .001). These trends persisted when analyzing age groups <12 years and ≥12 years
Autoimmune thyroiditis was more common in adults (9.4% vs. 3.4%, p = .02), and certain laboratory indicators exhibited age-associated differences. Specifically, IgG-anti-TPO positivity (24.7% vs. 9%, p < .001), elevated CRP (46.5% vs. 11.1%, p < .001), eosinopenia (38.5% vs. 18.1%, p < .001), and skin prick test positivity (39.3% vs. 28.8%, p = .03) were more frequent in adults. Conversely, low total IgE levels were more common in pediatric patients (29.5% vs. 17.5%, p = .004). Similar trends were observed in comparisons involving age subgroups.
Treatment and Refractoriness in Pediatric and Adult CSU Patients
Treatment distribution varied between pediatric and adult chronic spontaneous urticaria patients. In the pediatric group, standard H1-antihistamines were given to 57.3%, high doses of H1-antihistamines or combinations of H1-antihistamines and LTRA were administered to 33.9%, and omalizumab was used for 7%. Corresponding figures for adults were 40.1%, 25%, and 20.5%, respectively (p < .001). Similar treatment distributions were noted across different age groups.
Regarding refractoriness, only 8.6% of pediatric patients were unresponsive to first- and second-step treatments, while 35.0% of adults showed unresponsiveness. Indicators of refractoriness varied between pediatric and adult patients. For pediatric patients, eosinopenia (62.5% vs. 13.6%, p < .001), angioedema (46.7% vs. 19.4%, p = .01), and IgG-anti-TPO positivity (27.3% vs. 7.3%, p = .002) were associated with refractoriness. In adults, markers included angioedema (65.6% vs. 56.7%, p = .004) and eosinopenia (51.1% vs. 32%, p = .003). When focusing on ≥12 years of age, elevated CRP, angioedema, prick test positivity, and eosinopenia were linked to refractoriness. Logistic regression analysis demonstrated that prick test positivity negatively affected AH response in patients ≥12 years (beta = 0.23; B = -1.4, p = .02, 95% CI = 0.07–0.82). These findings provided insights into the differences in treatment response between pediatric and adult CSU patients.
Conclusion
This study highlights notable differences between pediatric and adult patients with chronic spontaneous urticaria (CSU) regarding clinical presentation, disease characteristics, associated conditions, laboratory findings, and treatment responses. An intriguing observation is the emergence of distinctive features in patients aged 12 and above, aligning adolescent chronic spontaneous urticaria with adult chronic spontaneous urticaria.
Female predominance in adult CSU patients (69.6%) contrasts with the less pronounced trend in pediatric cases (48.8%). This gender difference escalates with age, suggesting a potential hormonal influence on autoimmune and inflammatory processes. Angioedema, a marker of severe chronic spontaneous urticaria, is less prevalent in pediatric patients (19.1% vs. 59.8% in adults), with a rise by age (0–7 years: 8.9%, 8–11 years: 19.7%, 12–17 years: 26.8%). Angioedema correlates with antihistamine refractoriness in both pediatric and adolescent/adult groups.
Autoimmunity is increasingly recognized as a driver of CSU. Adult patients exhibit higher rates of autoimmune thyroiditis, IgG-anti-TPO positivity, eosinopenia, high CRP levels, and skin prick test positivity compared to pediatric patients. Conversely, low IgE levels are more frequent in pediatrics. Adolescent patients (12–17 years) exhibit increased IgG-anti-TPO positivity. Such findings suggest a possible type 2b autoimmune chronic spontaneous urticaria profile in adults, but further study is required to ascertain the pediatric endotype.
Treatment response patterns also vary. While pediatric chronic spontaneous urticaria responds well to standard antihistamine doses, adult cases often necessitate higher doses or alternate treatments. Omalizumab usage is less prevalent in pediatric cases (7% vs. 20.5% in adults). Response to standard antihistamines declines with age, with adolescents (12–17 years) requiring omalizumab treatment more frequently (17.9%).
Biomarkers linked to antihistamine refractoriness include eosinopenia, angioedema, IgG-anti-TPO positivity, elevated CRP, disease duration, and skin prick test positivity. These factors may guide treatment decisions. Notably, this study sheds light on distinct CSU profiles in pediatric and adult patients, suggesting evolving autoimmune mechanisms and potential hormonal contributions to disease pathogenesis. Further investigation is warranted to elucidate the intricate interplay of these factors across age groups in CSU patients.
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