Association between serological indicators of past contacts with Herpesviridae and a slower resolution of chronic spontaneous urticaria in children

Abstract

To evaluate the relationship between serological indicators of Herpesviridae infection and evolution of symptoms in children with chronic spontaneous urticaria (CSU).In this observational study, consecutive children with CSU underwent, at presentation, clinical and laboratory work-up, autologous serum skin test (ASST) to identify autoimmune urticaria (CAU), disease severity assessment (urticaria activity score 7, UAS7), serological diagnostics for Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus-6 (HHV-6), and parvovirus B19, as well as for Mycoplasma pneumoniae and Chlamydia pneumoniae. Children were re-assessed at 1, 6, and 12 months after the commencement of antihistamine/antileukotriene treatment.None of the 56 included children had an acute CMV/EBV or HHV-6 infection, but 17 (30.3%) had IgG antibodies against CMV, EBV, or HHV-6 (five were also seropositive for parvovirus B19); 24 (42.8%) suffered from CAU; and 9 (16.1%) were seropositive for Mycoplasma/Chlamydia pneumoniae. The initial symptom severity was moderate-to-severe (UAS7 quartiles 18-32) and comparable between Herpesviridae-seropositive and Herpesviridae-seronegative patients. At 1, 6, and 12 months, UAS7 was consistently higher in seropositive children. In a multivariable analysis (adjusted for age, baseline UAS7, ASST, mean platelet volume, and other serology), Herpesviridae seropositivity was associated with higher UAS scores: mean difference 4.2 score points (95% confidence interval 0.5-7.9; Bayes estimate 4.2, 95% credible interval 1.2-7.3) in a mixed model for repeated measures. This estimate was comparable between children with positive (CAU) and negative (CSU) ASST.A history of CMV/EBV/HHV-6 infection might contribute to a slower-resolving CSU in children.