Chronic urticaria is associated with a low resolution rate, but researchers writing in JAMA point to biomarkers that may help predict the likelihood of resolution.
The study found that the resolution rate of chronic urticaria is low in children at around 10%, but that certain biomarkers may influence the likelihood of resolution. In particular, the condition was more likely to resolve in children with positive basophil activation test (BAT) results (using CD63 activation marker) and the absence of basophils.
To learn more about the course of chronic urticaria in children, the Canadian researchers followed 139 under-18 years olds who had presented between 2013 and 2015 with hives lasting at least 6 weeks. Thirty-one of the children (20%) had inducible urticaria, most commonly cold induced, 6 had autoimmune comorbidity, such as thyroiditis and type 1 diabetes, and 24 (17%) had autoimmune disorders. Seventeen children (12%) had family members who had experienced the condition.
Chronic urticaria was found to be twice as likely to resolve within one year in children who returned positive BAT results (CD63 level >1.8%) compared to in children with negative BAT results (hazard ratio [HR], 2.33; 95%CI, 1.08-5.05). In contrast, presence of basophils decreased the likelihood of resolution (HR, 0.40; 95%CI, 0.20-0.99). The age of the child did not affect the likelihood of resolution.
Over the course of the study chronic urticaria resolved in 43 patients, which represents a rate of resolution of 10.3% per year. Levels of CD63 higher than 1.8% and absence of basophils were associated with earlier disease resolution.
Moshe Ben-Shoshan, MD, from the Division of Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Centre, Montréal, Canada, said: "We have followed the largest cohort of children to date, to our knowledge, with chronic urticaria and have shown that the resolution rate is low (10 per 100 patient-years) and that basophil count and CD63 levels can help predict resolution."
The researchers estimated that the cost of using BAT to be roughly Can$55 per sample. "Our findings suggest that such a cost may be justified to predict the risk of a more chronic course," Ben-Shoshan said.
The favorable prognosis associated with autoimmunity and CD63 level higher than 1.8% could be related to the presence of transient viral and bacterial infections that induce autoantibody production, he suggested. "Infections, especially viruses, are common in children and are well accepted pathogenic players in up to 80% of cases of acute urticaria. Furthermore, acute viral infections in children and adults have been proposed to be able to induce transient autoantibodies against self, owing to mimicry between the virus and self or virus-induced cell apoptosis revealing a self neoantigen."
Marcus Maurer, MD, from the Department of Dermatology and Allergy, at Charité–Universitätsmedizin Berlin in Germany, said that the findings, when taken together with the results of previous studies, would "allow physicians provide children with chronic urticaria and their parents with an educated guess on how long it will take until the disease goes away by itself".
"While we still do not have good predictors for the duration of chronic urticaria in individual children, we are beginning to understand that clinical features (e.g., good response to antihistamine treatment) and laboratory markers (e.g., basophil numbers and serum autoreactivity) can help to distinguish between subpopulations of pediatric patients with chronic urticaria that differ in the duration of their disease," he wrote in an accompanying editorial.
In adults laboratory markers and clinical features, such as higher age at onset, being female, long disease duration, hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs, comorbid inducible urticaria, or concomitant recurrent angioedema, have been linked to longer duration of chronic spontaneous urticaria. But, surprisingly, basophil-activating serum activity and basopenia, which are both linked to the presence of mast cell–activating autoantibodies and high disease activity, are associated with earlier, not later, disease resolution in children with chronic urticaria.
"This seems to contradict the findings that high disease activity, that is, failure to respond to a standard-dosed antihistamine or high urticaria activity scores, predict longer disease duration," Maurer said. "That both basopenia and autoreactive serum are linked to shorter times to remission in children with chronic urticaria may point to the possibility that type 2 autoimmune urticaria (driven by IgG autoantibodies) is of shorter duration than type 1 autoimmune urticaria (driven by IgE autoantibodies), in children as well as in adults with chronic spontaneous urticaria."
He said studies are now needed to assess basopenia, basophil-activating serum activity, and other markers of "autoimmune" chronic spontaneous urticaria for their link to the duration of disease.
Dermatologists treating patients with chronic urticaria are encouraged to add their data to the global chronic urticaria registry, CURE, which allows for the identification, characterization, and comparison of subgroups of chronic urticaria. It currently holds data from around 1,000 patients, including many pediatric patients.
Chronic urticaria can be brought on by a specific physical trigger such as cold, but most cases in children have no identifiable trigger and are classified as chronic spontaneous urticaria (CSU). At least half of children with chronic spontaneous urticaria have an autoimmune etiology that can be determined in vitro using the basophil activation test (BAT).
Chronic urticaria affects 0.1% to 0.3% of children and is characterized by the occurrence of wheals, angioedema, or both lasting more than 6 weeks. While 30% to 55% of cases resolve spontaneously within 5 years in adults, the natural history and predictors of resolution in children has been more of a mystery.
This article originally appeared on our partner's website Dermatology Times, which is a part of UBM Medica. (Free registration is required.)