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Basophil count associated with spontaneous chronic urticaria resolution

A positive basophil activation test result may be a prognostic factor of pediatric chronic urticaria resolution, according to new research published in JAMA Dermatology.

Because the etiology of chronic urticaria remains unknown and little is understood about why as many as half of cases resolve spontaneously within 5 years in adults, the researchers followed a cohort of 139 children (aged, < 18 years) with the disease to gain further understanding of the comorbidities, natural history and subtypes, and predictors of resolution.

Eligible participants were accrued at a single tertiary center between 2013 and 2015. Criteria included hives lasting at least 6 weeks. Factors undergoing assessment included disease activity, comorbidities, physical triggers, basophil activation test results, complete blood cell count, C-reactive protein levels, thyroid-stimulating hormone levels and thyroid peroxidase antibodies, according to study background.

Inducible urticaria was reported in 20% of the cohort, which the researchers suggested was most commonly induced by cold.

An autoimmune comorbidity was observed in six children. These cases included thyroiditis and type 1 diabetes.

Family members of the patients frequently reported autoimmune disorders (17%) and chronic urticaria (12%).

The researchers defined a positive basophil activation test as CD63 levels > 1.8% and observed this outcome in 58% of the cohort. Resolution after 1 year occurred more than twice as frequently in children with a positive basophil activation test result than in those with a negative result (HR = 2.33; 95% CI, 1.08-5.05).

However, the presence of basophils carried a negative association with resolution (HR = 0.40; 95% CI, 0.20-0.99).

Age carried no association with resolution.

There were 43 cases of chronic urticaria resolution, according to the findings. The yearly resolution rate was 10.3%.

In an accompanying editorial, Marcus Maurer, MD, Martin K. Church, PhD, DSc, and Karsten Weller, MD, of the department of dermatology and allergy at Charité–Universitätsmedizin Berlin, wrote that the findings by Netchiporouk et al. may allow clinicians to provide an educated guess to parents and children about the likelihood and timing of spontaneous 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 (eg, good response to antihistamine treatment) and laboratory markers (eg, basophil numbers and serum auto reactivity) can help to distinguish between subpopulations of pediatric patients with [chronic urticaria] that differ in the duration of their disease,” they wrote. “Although this observation is new, it is hardly surprising.”

The editorialists suggested that a number of factors have long been known to predict spontaneous response in adults. “What comes as a surprise is that, in children with [chronic urticaria], 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,” they wrote. “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.”

Another take-home message from the paper, according to the editorialists, is 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],” they wrote.

They suggested that basopenia, as well as other markers of autoimmune chronic spontaneous urticaria, should be directions of future study. “Such studies should be performed in children and adults with [chronic spontaneous urticaria],” they wrote. “They should include, aside from blood basophil levels and serum auto reactivity, clinical features of [chronic spontaneous urticaria] previously linked to ‘autoimmune’ [chronic spontaneous urticaria], such as comorbid autoimmune disorders, concomitant angioedema, and levels of disease activity, impact and control, as well as blood levels of IgG-anti-FceRI, IgG-anti-IgE, IgE-anti-self, other autoantibodies (e.g., IgG-anti-TPO), autologous serum skin testing, total IgE, and response to antihistamines and omalizumab.”

Disease severity, age at onset and gender information also should undergo clinical study, the editorialists added.

“Other questions that emerge from the present findings include the following,” they wrote. “What is the reason for the basopenia seen in some but not all patients with [chronic spontaneous urticaria]? How is this linked to basophil activating serum activity? Do basopenia and serum auto-reactivity precede the development of clinical signs and symptoms, or do they result from them? Both antihistaminic therapy and treatment with omalizumab have been shown to normalize blood basophil levels in patients who benefit from these treatments. Is the same true for serum auto-reactivity, and is spontaneous remission in patients with [chronic spontaneous urticaria] linked to the loss of serum auto-reactivity?” – by Rob Volansky

Disclosures: The authors report no relevant financial disclosures.