Abstract

While urticaria is quite common in childhood, it is less frequent as chronic condition. In this narrative review we have highlighted the causes of chronic urticaria (CU), indicating the diagnostic work-up according to age and characteristics of the patients, giving importante to the symptom presentations. The therapeutic options of CU even in children are also represented by the biologic drugs, which are usually recommended from the twelve years of life. Biologic option represents in case of CU an effective and safe intervention. Further molecules are indicated for this condition in the next future. In the review these options are discussed and experimental and registratory studies are indicated.

References

  1. Zuberbier T, Aberer W, Asero R, et al.; Endorsed by the following societies: AAAAI, AAD, AAIITO, ACAAI, AEDV, APAAACI, ASBAI, ASCIA, BAD, BSACI, CDA, CMICA, CSACI, DDG, DDS, DGAKI, DSA, DST, EAACI, EIAS, EDF, EMBRN, ESCD, GA²LEN, IAACI, IADVL, JDA, NVvA, MSAI, ÖGDV, PSA, RAACI, SBD, SFD, SGAI, SGDV, SIAAIC, SIDeMaST, SPDV, TSD, UNBB, UNEV and WAO. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy 2018;73:1393-1414. https://doi.org/10.1111/all.13397.
  2. Caffarelli C, Paravati F, El Hachem M, et al. Management of chronic urticaria in children: a clinical guideline. Ital J Pediatr 2019;45:101. https://doi.org/10.1186/s13052-019-0695-x.
  3. Cantarutti A, Donù D, Visentin F, et al. Epidemiology of frequently occurring skin diseases in Italian children from 2006 to 2012: a retrospective. Population-Based Study. Pediatr Dermatol 2015;32:668-678. https://doi.org/10.1111/pde.12568
  4. Buono EV, Giannì G, Scavone S, et al. Clinical Characteristics, Investigations and Treatment in Children with Chronic Urticaria: An Observational Study. Medicina (Kaunas) 2024;60:704. https://doi.org/10.3390/medicina60050704.
  5. Asero R, Ferrer M, Kocaturk E, et al. Chronic Spontaneous Urticaria: The Role and Relevance of Autoreactivity, Autoimmunity, and Autoallergy. J Allergy Clin Immunol Pract 2023;11:2302-2308. https://doi.org/10.1016/j.jaip. 2023.02.022.
  6. Pan X-F, Gu J-Q, Shan Z-Y. The prevalence of thyroid autoimmunity in patients with urticaria: a systematic review and meta-analysis: Springer 2015.
  7. Caminiti L, Passalacqua G, Magazzù G, et al. Chronic urticaria and associated coeliac disease in children: a case-control study. Pediatr Allergy Immunol 2005;16:428-432. https://doi.org/10.1111/j.1399-3038.2005.00309.x.
  8. Min J, Her Y, Moon KW, et al. Assessing Quality of Life in Patients with Chronic Urticaria Through Comparisons with Patients Having Other Common Chronic Diseases. J Allergy Clin Immunol Pract 2023;11:2426- 2431.e2. https://doi.org/10.1016/j.jaip.2023.03.047.
  9. Kim HA, Hyun MC, Choi BS. Natural History and Influencing Factors of Chronic Urticaria in Children. Allergy Asthma Immunol Res 2022;14:73-84. https://doi.org/10.4168/aair.2022.14.1.73.
  10. Puxeddu I, Pistone F, Pisani F, et al. Mast cell signaling and its role in urticaria. Ann Allergy Asthma Immunol 2024;133:374-379. https://doi.org/10.1016/j.anai.2024.04.023.
  11. Schoepke N, Asero R, Ellrich A, et al. Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study. Allergy 2019;74:2427-2436. https://doi.org/10.1111/all.13949.
  12. Powell RJ, Leech SC, Till S, et al; British Society for Allergy and Clinical Immunology. BSACI guideline for the management of chronic urticaria and angioedema. Clin Exp Allergy 2015;45:547-565. https://doi.org/10.1111/cea.12494.
  13. Agache I, Rocha C, Pereira AM, Song Y, Alonso-Coello P, Solà I, et al. Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines. Allergy 2021;76:59-70. https://doi.org/10.1111/all.14547
  14. Chipps BE, Farrell Garcia M, Murphy KR, Haselkorn T. Updated review of omalizumab to treat uncontrolled pediatric allergic asthma. J Allergy Clin Immunol 2025;155:12-23. https://doi.org/10.1016/j.jaci.2024.11.013
  15. Hanania NA, Chipps BE, Griffin NM, Iqbal A, Casale TB. Long-term effectiveness and safety of omalizumab in pediatric and adult patients with allergic asthma. Allergy Asthma Proc 2022;43:357-366. https://doi.org/10.2500/aap.2022.43.220042
  16. Anagnostou A, Turner PJ, Ebisawa M. Omalizumab for the treatment of food allergy: Recent FDA approval and future directions. J Allergy Clin Immunol 2025;155:963-965. https://doi.org/10.1016/j.jaci.2025.03.003.
  17. Wood RA, Kim JS, Lindblad R, Nadeau KC, Henning AK, Dawson P, et al. A randomized, placebo-controlled study of omalizumab combined with oral immunotherapy for multiple food allergies. N Engl J Med 2024;390:657-668. https://doi.org/10.1056/NEJMoa2306561.
  18. Goldstein S, Gabriel S, Kianifard F, Ortiz B, Skoner DP. Clinical features of adolescents with chronic idiopathic or spontaneous urticaria: Review of omalizumab clinical trials. Ann Allergy Asthma Immunol 2017;118:500-504. https://doi.org/10.1016/j.anai.2017.02.003.
  19. Saini SS, Bindslev-Jensen C, Maurer M, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study. J Invest Dermatol 2015;135:67-75. https://doi.org/10.1038/jid.2014.306. Erratum in: J Invest Dermatol 2015;135:925. https://doi.org/10.1038/jid.2014.512.
  20. Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol 2013;132:101-109. https://doi.org/10.1016/j.jaci.2013.05.013.
  21. Ben-Shoshan M, Grattan CE. Management of Pediatric Urticaria with Review of the Literature on Chronic Spontaneous Urticaria in Children. J Allergy Clin Immunol Pract 2018;6:1152-1161. https://doi.org/10.1016/j.jaip.2018.02.015.
  22. Alomari O, Ozceker D, Mokresh ME, et al. Omalizumab in pediatric chronic spontaneous urticaria: A systematic review and meta-analysis of efficacy and safety. Pediatr Allergy Immunol 2025;36:e70132. https://doi.org/10.1111/pai.70132.
  23. Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med 2013;368:924-35. https://doi.org/10.1056/NEJMoa1215372.
  24. Licari A, Marseglia A, Caimmi S, et al. Omalizumab in children. Paediatr Drugs 2014;16:491-502. https://doi.org/10.1007/s40272-014-0107-z.
  25. Ting SX, Huynh H, Chau C, et al. Efficacy and safety of omalizumab for chronic spontaneous urticaria in pediatric patients: Results from a multicenter study. Allergy 2021;76:3351-3359. https://doi.org/10.1111/all.14810.
  26. Dekkers C, de Koning H, Ziegler M, et al. Efficacy of omalizumab in children and adolescents with chronic spontaneous urticaria: a systematic review. Pediatr Allergy Immunol 2021;32:515-522. https://doi.org/10.1111/pai.13424.
  27. Corral-Magaña O, Sánchez-Borges M, González-Quevedo T, et al. Omalizumab in pediatric chronic spontaneous urticaria: A retrospective study. Pediatr Dermatol 2021;38:345-350. https://doi.org/10.1111/pde.14291
  28. Staubach P, Ehlers J, Fuchs T, et al. Long-term follow-up of pediatric patients with chronic spontaneous urticaria treated with omalizumab. J Dermatolog Treat 2022;33:895-902. https://doi.org/10.1080/09546634.2021.1923528
  29. Galletta F, Pucci S, Lodi M, et al. Omalizumab in children and adolescents with chronic spontaneous urticaria: A real-world experience from a single-center study. J Pers Med 2023;13:745-752. https://doi.org/10.3390/jpm13060745.
  30. Kahveci M, Demirsoy S, Demirkan S, et al. The role of omalizumab in treating pediatric patients with chronic spontaneous urticaria: A retrospective study in Turkey. Allergol Immunopathol (Madr) 2020;48:706-710. https://doi.org/10.1016/j.aller.2020.08.005.
  31. Ari A, Altunay İ, Çağlar E, et al. Omalizumab therapy in children with chronic spontaneous urticaria: A case series. Pediatr Dermatol 2020;37:540-544. https://doi.org/10.1111/pde.14001.
  32. Ben-Shoshan M, Grattan CE. Management of Pediatric Urticaria with Review of the Literature on Chronic Spontaneous Urticaria in Children. J Allergy Clin Immunol Pract 2018;6:1152-1161. https://doi.org/10.1016/j.jaip.2018.02.015.
  33. Kuo BS, Lin YJ, Hsu CL, et al. IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms. J Clin Invest 2022;132:e157765. https://doi.org/10.1172/JCI157765.
  34. Ye YM, Park JW, Kim SH, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of YH35324, a novel long-acting high-affinity IgE-Trap-Fc protein: first-in-human study. Int Immunopharmacol 2024;130:111706. https://doi.org/10.1016/j.intimp.2024.111706
  35. ClinicalTrials.gov. Mepolizumab for the Treatment of Chronic Spontaneous Urticaria. Identifier: NCT03494881. Available from: https://clinicaltrials.gov/ct2/show/NCT03494881.
  36. McLaren J, Chon Y, Gorski KS, et al. Tezepelumab for the treatment of chronic spontaneous urticaria: Results of the phase 2b INCEPTION study. J Allergy Clin Immunol 2025;155:1945-1956. https://doi.org/10.1016/j.jaci.2025.01.045.
  37. ClinicalTrials.gov. Dose Escalation Trial of Safety, Pharmacokinetics/Pharmacodynamics and Preliminary Clinical Activity of Briquilimab in Adults with Chronic Spontaneous Urticaria (BEACON). Identifier: NCT06162728. Available from: https://clinicaltrials.gov/ct2/show/NCT06162728. Accessed on: 1st october 2025.
  38. Giménez-Arnau AM, Salman A. Targeted therapy for chronic spontaneous urticaria: rationale and recent progress. Drugs 2020;80:1617-1634. https://doi.org/10.1007/s40265-020-01387-9.
  39. Maurer M, Ensina LF, Gimenez-Arnau AM, et al.; PEARL-1 and PEARL-2 trial investigators. Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials. Lancet 2024;403:147-159. https://doi.org/10.1016/S0140-6736(23)01684-7.
  40. Staubach P, Alvaro-Lozano M, Sekerel BE, et al. Ligelizumab in adolescents with chronic spontaneous urticaria: Results of a dedicated phase 2b randomized clinical trial supported with pharmacometric analysis. Pediatr Allergy Immunol 2023;34:e13982. https://doi.org/10.1111/pai.13982.
  41. Hershkovitz Y, Khanimov I, Rubin L, et al. Successful ligelizumab treatment of severe refractory solar urticaria. J Allergy Clin Immunol Pract 2023;11:2576-2577. https://doi.org/10.1016/j.jaip.2023.01.052.
  42. Maurer M, Casale TB, Saini SS, et al. Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, phase 3 trials. J Allergy Clin Immunol 2024;154:184-194. https://doi.org/10.1016/j.jaci.2024.01.028.
  43. Staubach P, Peveling-Oberhag A, Lang BM, et al. Severe chronic spontaneous urticaria in children - treatment options according to the guidelines and beyond - a 10 years review. J Dermatolog Treat 2022;33:1119-1122. https://doi.org/10.1080/09546634.2020.1782326.
  44. Arkwright PD. Anti-CD20 or anti-IgE therapy for severe chronic autoimmune urticaria. J Allergy Clin Immunol 2009;123:510-511; author reply 511. https://doi.org/10.1016/j.jaci.2008.11.043.
  45. Saini SS, Bindslev-Jensen C, Maurer M. Rituximab in refractory chronic spontaneous urticaria. Skin Pharmacol Physiol 2018;31:184-187. https://doi.org/10.1159/000488916.
  46. Mallipeddi R, Grattan CE. Lack of response of severe steroid-dependent chronic urticaria to rituximab. Clin Exp Dermatol 2007;32:333-334. https://doi.org/10.1111/j.1365-2230.2007.02365.x.
  47. Bergmann KC, Altrichter S, Maurer M. Benefit of benralizumab treatment in a patient with chronic symptomatic dermographism. J Eur Acad Dermatol Venereol 2019;33:e413-e415. https://doi.org/10.1111/jdv.15720.
  48. Magen E, Komarova I, Magen I, et al. Case of benralizumab-induced exacerbations of chronic spontaneous urticaria. Clin Case Rep 2022;10:e05930. https://doi.org/10.1002/ccr3.5930.
  49. Altrichter S, Giménez-Arnau AM, Bernstein JA, et al.; ARROYO Study Investigators. Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase IIb multinational randomized double-blind placebo-controlled ARROYO trial. Br J Dermatol 2024;191:187-199. https://doi.org/10.1093/bjd/ljae067.
  50. Wedner HJ, Fujisawa T, Guilbert TW, et al.; all TATE investigators. Benralizumab in children with severe eosinophilic asthma: Pharmacokinetics and long-term safety (TATE study). Pediatr Allergy Immunol 2024;35:e14092. https://doi.org/10.1111/pai.14092.
  51. Min TK, Kim JH, Kang SY, et al. Successful treatment of severe chronic spontaneous urticaria with mepolizumab: a case report. Allergy Asthma Immunol Res 2019;11:460-462. https://doi.org/10.4168/aair.2019.11.3.460.
  52. ClinicalTrials.gov. A study to investigate the effect of mepolizumab in adults with chronic spontaneous urticaria. Identifier: NCT03494881. Available online: https://clinicaltrials.gov/ct2/show/NCT03494881. Accessed on: 14 August 2022.
  53. Phillipps J, Bhasin A, Sluzevich J. Exploring mepolizumab use in chronic spontaneous urticaria: An open-label, single-arm, exploratory study. J Allergy Clin Immunol Pract 2025;13:2503-2505.e1. https://doi.org/10.1016/j.jaip.2025.06.014.
  54. Castagnoli R, Licari A, Brambilla I, et al. Mepolizumab in children with severe eosinophilic asthma: where do we stand? Curr Opin Allergy Clin Immunol 2023;23:162-168. https://doi.org/10.1097/ACI.0000000000000846.
  55. Sand FL, Thomsen SF. TNF-alpha inhibitors for chronic urticaria: experience in 20 patients. J Allergy (Cairo) 2013;2013:130905. https://doi.org/10.1155/2013/130905.
  56. Patrick E, Lyons JJ, Ishii M, et al. IL-1 pathway inhibition in refractory urticaria associated with autoinflammatory syndromes: experience with anakinra and canakinumab. Front Immunol 2021;12:734762. https://doi.org/10.3389/fimmu.2021.734762
  57. Del Giudice E, Sota J, Orlando F, et al. Off-label use of canakinumab in pediatric rheumatology and rare diseases. Front Immunol (Lausanne) 2022;9:998281. https://doi.org/10.3389/fmed.2022.998281.

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Giuliana Giannì - Department of Pediatrics, Section of Allergology, Livorno Hospital, Livorno, Italy

Enrico Vito Buono - Pediatric Clinic, Department of Medicine and Surgery, University of Parma, Parma, Italy

Diego Peroni - Pediatric Section, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Carlo Caffarelli - Pediatric Clinic, Department of Medicine and Surgery, University of Parma, Parma, Italy

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Giannì, G., Buono, E. V., Peroni, D., & Caffarelli, C. (2026). Update on Biologic Therapy of Chronic Spontaneous Urticaria. Italian Journal of Pediatric Allergy and Immunology, 39(4). https://doi.org/10.53151/2531-3916/2025-1760
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