AimTo evaluate the relationship between serological indicators ofHerpesviridaeinfection and evolution of symptoms in children with chronic spontaneous urticaria (CSU).MethodsIn 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 forMycoplasma pneumoniaeandChlamydia pneumoniae. Children were re-assessed at 1, 6, and 12 months after the commencement of antihistamine/antileukotriene treatment.ResultsNone 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 forMycoplasma/Chlamydia pneumoniae. The initial symptom severity was moderate-to-severe (UAS7 quartiles 18-32) and comparable betweenHerpesviridae-seropositive andHerpesviridae-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),Herpesviridaeseropositivity 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.ConclusionA history of CMV/EBV/HHV-6 infection might contribute to a slower-resolving CSU in children.