The role of substance P in the pathogenesis of chronic urticaria in children

Introduction. Chronic urticaria (CU) in children remains a serious clinical problem, especially in cases of resistance to antihistamine therapy, indicating the involvement of non-histaminergic mechanisms, in particular the Substance P (SP) / neurokinin-1 receptor (NK-1R) axis. The chronic form of urticaria occurs in children under 15 years of age with a frequency of up to 1.1%, with the highest prevalence observed in the adolescent group, approaching that of the adult population.
Materials and methods. A non-systematic review of the literature was conducted. Publications were searched in PubMed, Google Scholar, CyberLeninka and eLibrary databases for the period 2000-2024 using the keywords: “substance P”, “chronic urticaria”, “children”, “neurogenic inflammation”, “NK-1 receptor”. 49 relevant sources were selected, including original studies, systematic reviews, clinical guidelines and case series. Due to the limited number of pediatric studies (n = 8), the data were extrapolated with caution, with the main focus on describing pathogenetic mechanisms and identifying gaps in the evidence base.
Results. SP has been shown to play a multifaceted role in the pathogenesis of CU in both adults and, presumably, children, acting as a mediator linking the nervous, immune and vascular systems. Via the NK-1R receptor, SP directly causes mast cell degranulation, mediates neurogenic inflammation, increases vascular permeability, has an immunomodulatory effect (chemotaxis of neutrophils and eosinophils, polarization of the Th2 response) and is a central link in stress-induced exacerbations. Elevated plasma levels of SP and NK-1R expression in the skin correlate with disease severity and resistance. At the same time, most studies have been performed on adult patients, while pediatric data are limited, which does not allow all mechanisms to be unequivocally extrapolated to the pediatric population.
Conclusions. The SP/NK-1R axis may be considered as one of the possible pathogenetic links in antihistamine-resistant CU in children. Despite the theoretical rationale for NK-1R blockade, NK-1R antagonists cannot currently be recommended for pediatric practice due to the lack of efficacy and safety data, as well as conflicting results in adults

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