Biomarkers may predict chronic urticaria resolution

“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 and laboratory markers can help to distinguish between subpopulations of pediatric patients with chronic urticaria that differ in the duration of their disease,” Elena Netchiporouk, et al. JAMA Dermatology.

Chronic urticaria is associated with a low resolution rate in children, but researchers writing in JAMA Dermatology point to biomarkers that may help predict the likelihood of resolution.

The study, published in December, 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. 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, researchers led by Mosh Ben-Shoshan, M.D., of McGill University Health Center in Montreal, followed 139 pediatric patients who presented between 2013 and 2015 with hives lasting at least six weeks. Thirty-one of the children (20%) had inducible urticaria, most commonly cold induced, six 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.

“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,” Dr. Shoshan said.

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,” he 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.

“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,” Dr. Shoshan said.

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,” wrote Marcus Maurer, M.D., Charité–Universitätsmediz, Germany, in an accompanying editorial.

“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 (eg, good response to antihistamine treatment) and laboratory markers (eg, 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.

CHRONIC URTICARIA IN ADULTS

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,” Dr 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 (http://www.urticaria-registry.com), which allows for the identification, characterization, and comparison of subgroups of chronic urticaria. It currently holds data from around 1000 patients, including many pediatric patients.

DISEASE PROFILE

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 (CU) affects 0.1% to 0.3% of children and is characterised 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.

REFERENCES

Elena Netchiporouk, MD; Denis Sasseville, MD; Linda Moreau, MD; et al. "Evaluating Comorbidities, Natural History, and Predictors of Early Resolution in a Cohort of Children With Chronic Urticaria," JAMA Dermatology. December 2017. DOI:10.1001/jamadermatol.2017.3182

Maurer M, Church MK, Weller K. "Chronic Urticaria in Children: Still Itching for Insight," editorial published in JAMA Dermatology, Dec. 1, 2017. DOI: 10.1001/jamadermatol.2017.3183