Adults, children with chronic spontaneous urticaria differ in clinical features, response
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Key takeaways:
- Pediatric patients had less angioedema and shorter disease duration than adult patients.
- Adult patients had elevated C-reactive protein and more skin prick test positivity than pediatric patients.
Pediatric and adult chronic spontaneous urticaria exhibit distinct features, with adolescent presentations resembling those of adults more than those of younger children, according to a study published in Pediatric Allergy and Immunology.
Younger children with chronic spontaneous urticaria (CSU) also have better responses to antihistamines than adolescents and adults, suggesting more severe and refractory disease as patients age, Deniz Özçeker, MD, specialist, department of pediatric immunology and allergy, SBU Istanbul Cemil Tascioglu City Hospital, and colleagues wrote.
The retrospective analysis comprised 162 pediatric patients aged younger than age 18 years (mean age, 10.7 years ± 4.2) and 589 adults aged 18 years and older (mean age, 40.3 years ± 13.8). The pediatric population was 48.8% girls, and the adult population was 69.6% women (P < .001).
Disease durations included 12 months for adults and 5 months for the pediatric patients (P < .001). Also, 59.8% of the adults and 19.1% of the pediatric patients had angioedema (P < .001). Both figures showed a clear tendency toward increases with age, the researchers said.
When the researchers divided the cohort into those patients aged 12 years and older (n = 91) and those aged younger than 12 years (n = 660), they said they found similar results for sex, disease duration and angioedema.
Compared with pediatric patients, adults more frequently experienced autoimmune thyroiditis (9.4% vs. 3.4%; P = .02), antithyroid peroxidase antibody (IgG-anti-TPO) positivity (24.7% vs. 9%; P < .001), elevated C-reactive protein (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).
Pediatric patients more frequently had low total IgE levels than adults (29.5% vs. 17.5%; P = .004). Additionally, the researchers said, IgG-anti-TPO positivity and eosinopenia rates increased with age.
When the researchers compared these traits between cohorts divided at age 12 years, they said the results again were similar with those found with a cutoff of age 18 years.
Specifically, IgG-anti-TPO positivity percentages included 2.6% for patients aged younger than 12 years and 18.5% for adolescents aged 12 to 17 years (P = .002). SPT positivity percentages similarly included 23.8% for patients younger than age 12 years and 39.6% for adolescents (P = .049).
Treatments included standard doses of H1-antihistamines for 57.3% of pediatric patients and 40.1% of adults (P < .001), high doses of H1-antihistamines or combinations of antihistamines and leukotriene antagonists (LTRA) for 33.9% of pediatric patients and 25% of adults (P < .001) and omalizumab (Xolair; Genentech, Novartis) for 7% for pediatric patients and 20.5% for adults (P < .001).
The researchers said they did not see any significant differences in treatment distributions when they compared patients aged 0 to 7 years with those aged 8 to 11 years and when they compared those aged 12 to 17 years with those aged 18 years and older.
However, treatments among patients aged younger than 12 years included standard doses of H1-antihistamines (60.2%), high doses of H1-antihistamines or LTRA (37.3%) and omalizumab (2.4%). Percentages of these treatments among adolescents included 41.4% for standard doses of H1-antihistamines, 25.6% for high doses of H1-antihistamines of LTRA and 32.1% for omalizumab (P < .001).
Patients who did not respond to first-step and second-step treatments included 8.6% of the pediatric group and 35% of the adult group.
Response rates to standard doses of antihistamines included 68% of patients aged 0 to 7 years, 60% for patients aged 7 to 11 years, 48% for those age 12 to 17 years and 40% for the adult patients.
Among pediatric patients, indicators of antihistamine refractoriness included eosinopenia (13.6% in responders vs. 62.5% in nonresponders; P < .001), angioedema (19.4% in responders vs. 46.7% in nonresponders; P = .01) and IgG-anti-TPO positivity (7.3% in responders vs. 27.3% in nonresponders; P = .002).
In adults, angioedema (56.7% in responders and 65.6% in nonresponders; P = .004) and eosinopenia (32% in responders and 51.1% in nonresponders; P = .003) were indicators of antihistamine refractoriness.
Only two of the 14 pediatric patients who were unresponsive to antihistamines were aged younger than 12 years. Indicators of antihistamine refractoriness among patients aged 12 to 17 years included elevated CRP, angioedema, duration of disease, SPT positivity and eosinopenia.
Only SPT positivity had a negative impact on antihistamine response in patients aged 12 years and older based on a logic regression analysis (beta = 0.23; 95% CI, 0.07-0.82; P = .02).
Based on these findings, the researchers concluded that pediatric patients with CSU had distinct clinical presentation, disease duration, associated conditions, laboratory findings and treatment responses compared with adults, possibly reflecting different disease endotypes.
Perspective
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There are limited data on pediatric CSU in comparison with adults, and this study provides new information about differences between CSU markers in children and adults as well as in severity and response to treatment support.
In my clinical experience, we rarely see intractable refractory CSU in children, as most pediatric cases respond to oral antihistamines.
The results of this study may suggest that there is no need to perform an extensive battery of tests for autoimmunity in pediatric patients with CSU, as autoimmune markers such as TPO antibodies, CRP and eosinopenia are clearly less common than they are in adults.
It is also important to emphasize to parents of children with CSU that with the high rate of response to oral antihistamines, there often is no need to start biologics such as omalizumab, which we often use in adults, and there is less likelihood to develop angioedema as well.
More research is required to understand the biomarkers of CSU in children. Interestingly, a recent study presented at the American Academy of Dermatology Annual Meeting in March demonstrated that serum tryptase, which is a proteolytic enzyme secreted by mast cells (which were not examined in the current study), was a good biomarker of severity of CSU in children and response to treatment.
Reference:
Nguyen A, et al. Association of biomarkers with treatment and disease resolution of chronic spontaneous urticaria in children. Presented at: 2023 American Academy of Dermatology Annual Meeting; March 17-21, 2023; New Orleans.
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