Evaluating Comorbidities, Natural History, and Predictors of Early Resolution in a Cohort of Children With Chronic Urticaria

Abstract

IMPORTANCE Chronic urticaria (CU) affects 0.1% to 0.3% of children. Most cases have no identifiable trigger and are classified as chronic spontaneous urticaria (CSU). At least half of patients with CSU may have an autoimmune etiology that can be determined in vitro using the basophil activation test (BAT). While 30% to 55% of CU cases resolve spontaneously within 5 years in adults, the natural history and predictors of resolution in children are not known.OBJECTIVE To assess the comorbidities, natural history of CU, and its subtypes in children and identify predictors of resolution. DESIGN, SETTING, AND PARTICIPANTSWe followed a pediatric cohort with chronic urticaria that presented with hives lasting at least 6 weeks between 2013 and 2015 at a single tertiary care referral center.EXPOSURES Data were collected on disease activity, comorbidities, physical triggers, BAT results, complete blood cell count, C-reactive protein levels, thyroid-stimulating hormone levels, and thyroid peroxidase antibodies. MAIN OUTCOMES AND MEASURESWe assessed the rate of resolution (defined as absence of hives for at least 1 year with no treatment) and the association with clinical and laboratory markers. RESULTSThe cohort comprised 139 children younger than 18 years old. Thirty-one patients (20%) had inducible urticaria, most commonly cold induced. Six children had autoimmune comorbidity, such as thyroiditis and type 1 diabetes. Autoimmune disorders (24 patients [17%]) and CU (17 patients [12%]) were common in family members. Positive BAT results (CD63 levels > 1.8%) were found in 58% of patients. Patients with positive BAT results (CD63 level >1.8%) were twice as likely to resolve after 1 year compared 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). No correlation with age was found. Chronic urticaria resolved in 43 patients, with 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.CONCLUSIONS AND RELEVANCE Resolution rate in children with CU is low. The presence of certain biomarkers (positive BAT result and basophil count) may help to predict the likelihood of resolution.

Urticaria in children and adolescents: An updated review of the pathogenesis and management

“…Recently, it was found that positive CD63 basophil activation test is common in PcsU and is associated with high disease activity . Low blood basophil counts on the contrary were linked to earlier symptoms resolution …”

“…20 Low blood basophil counts on the contrary were linked to earlier symptoms resolution. 21 Patients suffering from cU can simultaneously have another autoimmune pathology. 22 Thus, antithyroid antibodies can be found in 4.3%-17.3% of children and 27% of adults diagnosed with CSU.…”

Anaphylaxis in atypical cold urticaria: case report and review of literature

“…If urticaria lasts more than 6 weeks, it is defined as chronic urticaria. The prevalence of chronic urticaria in children is about 0.1–0.3% [ 6 ] and it has been found to be more common among atopic patients or patients with familiarity for autoimmune diseases [ 7 ]. In about 80% of cases, chronic urticaria is idiopathic, even if almost half of these patients presents autoantibodies, whose presence could be demonstrated by an autologous skin test [ 8 ].…”

“…The remaining patients present inducible forms of urticaria, that can be caused by many different stimuli: physical (such as cold urticaria, dermographic urticaria, delayed pressure urticaria, heat urticaria, solar urticaria, aquagenic urticaria, vibratory angioedema), or by exercise and hot bath (cholinergic urticaria) [ 5 ]. Physical urticarias account for 22% of chronic urticaria in children, and among these dermatographism is the most common [ 7 ]. Recently, European and US guidelines for the diagnosis and the management of CU have been published; the two guidelines are mostly similar even if some differences, especially about treatment, are still present [ 11 ].…”

Reply to “Comment on: ‘Children with chronic urticaria can be effectively controlled with updosing second-generation antihistamines’”

“…In a previous analysis of a larger well-defined CU registry, the natural resolution rate in Canadian children was relatively low, at 10% per year. 4 Further, Canadian and European Academy of Allergy and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum/World Allergy Organization urticaria guidelines 5,6 recommend that if there is no improvement in the control of symptoms in 2 to 4 weeks of treatment with second-generation antihistamines, the dose should be increased up to 4 times the standard dose, and if inadequate control occurs after 2 to 4 weeks, omalizumab should be added to the treatment. The guidelines do not support waiting 3 months to determine whether resolution occurs.…”