adairАллергология и Иммунология в ПедиатрииAllergology and Immunology in Paediatrics2500-11752712-7958Ассоциация детских аллергологов и иммунологов России10.53529/2500-1175-2026-2-4-14adair-247Research ArticleОБЗОРREVIEWРоль субстанции Р в патогенезе хронической крапивницы у детейThe role of substance P in the pathogenesis of chronic urticaria in childrenhttps://orcid.org/0000-0003-0383-5006КрасиловаЕ. В.KrasilovaE. V.

Красилова Елена Владимировна — к. м. н., доцент кафедры клинической иммунологии с курсом последипломного образования

414000, г. Астрахань, ул. Бакинская, д. 121

Krasilova Elena Vladimirovna — Cand. Sci., Associate Professor, Department of Clinical Immunology with a Postgraduate Course

121 Bakinskaya Str., Astrakhan, 414000

el25kv@mail.ruhttps://orcid.org/0000-0002-8172-2421ШелеповаТ. Н.ShelepovaT. N.

Шелепова Татьяна Николаевна — к. м. н., доцент кафедры клинической иммунологии с курсом последипломного образования

414000, г. Астрахань, ул. Бакинская, д. 121

Shelepova Tatiana Nikolaevna — Cand. Sci., Associate Professor, Department of Clinical Immunology with a Postgraduate Course

121 Bakinskaya Str., Astrakhan, 414000

shelepovatn@yandex.ruhttps://orcid.org/0000-0001-6766-079XВоронинаЛ. П.VoroninaL. P.

Воронина Людмила Петровна — д. м. н., заведующий кафедрой клинической иммунологии с курсом последипломного образования

414000, г. Астрахань, ул. Бакинская, д. 121

Voronina Lyudmila Petrovna — Doc. Sci., Head of Department of Clinical Immunology with a Postgraduate Course

121 Bakinskaya Str., Astrakhan, 414000

voroninaluda74@mail.ruhttps://orcid.org/0000-0003-4168-4851БашкинаО. А.BashkinaO. A.

Башкина Ольга Александровна — д. м. н., заведующий кафедрой факультетской педиатрии

414000, г. Астрахань, ул. Бакинская, д. 121

Bashkina Olga Alexandrovna — Doc. Sci., Head of Department of Faculty Pediatrics

121 Bakinskaya Str., Astrakhan, 414000

bashkina1@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Астраханский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияAstrakhan State Medical UniversityRussian Federation20263107202602414Copyright © Красилова Е.В., Шелепова Т.Н., Воронина Л.П., Башкина О.А., 20262026Красилова Е.В., Шелепова Т.Н., Воронина Л.П., Башкина О.А.Krasilova E.V., Shelepova T.N., Voronina L.P., Bashkina O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://adair.elpub.ru/jour/article/view/247

Актуальность. Хроническая крапивница (ХК) у детей остается серьезной клинической проблемой, особенно в случаях резистентности к антигистаминной терапии, что указывает на вовлеченность негистаминергических механизмов, в частности оси субстанция Р (SP) / нейрокинин-1 рецептор (NK-1R). Хроническая форма крапивницы встречается у детей до 15 лет с частотой до 1,1%, при этом максимальная распространенность отмечается в подростковой группе, приближаясь к показателям взрослой популяции.Материалы и методы. Проведен несистематический обзор литературы. Поиск публикаций выполнялся в базах данных PubMed, Google Scholar, CyberLeninka и eLibrary за период 2000–2024 гг. с использованием ключевых слов: «субстанция Р», «хроническая крапивница», «дети», «нейрогенное воспаление», «рецептор NK-1R». Отобрано 49 релевантных источников, включая оригинальные исследования, систематические обзоры, клинические рекомендации и серии клинических случаев. В связи с ограниченным числом педиатрических исследований (n = 8) данные экстраполировались с осторожностью, основной акцент сделан на описании патогенетических механизмов и выявлении пробелов в доказательной базе.Результаты. Установлено, что SP играет многогранную роль в патогенезе ХК как у взрослых, так и, предположительно, у детей, выступая медиатором, связывающим нервную, иммунную и сосудистую системы. SP через рецептор NK-1R напрямую вызывает дегрануляцию тучных клеток, опосредует нейрогенное воспаление, повышает сосудистую проницаемость, обладает иммуномодулирующим действием (хемотаксис нейтрофилов и эозинофилов, поляризация Th2-ответа) и является центральным звеном в реализации стресс-индуцированных обострений. Повышенные уровни SP в плазме и экспрессия NK-1R в коже коррелируют с тяжестью и резистентностью заболевания. Вместе с тем большинство исследований выполнено на взрослых пациентах, а педиатрические данные ограниченны, что не позволяет однозначно экстраполировать все механизмы на детскую популяцию.Выводы. Ось SP/NK-1R может рассматриваться как одно из возможных патогенетических звеньев антигистаминорезистентной ХК у детей. Несмотря на теоретическую обоснованность блокады NK-1R, в настоящее время антагонисты NK-1R не могут быть рекомендованы для педиатрической практики из-за отсутствия данных об эффективности и безопасности, а также из-за противоречивых результатов у взрослых.

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

крапивницадетисубстанция Рнейрокинин-1 рецепторнейрогенное воспалениепатогенезтерапияchronic urticariachildrensubstance Pneurokinin-1 receptorneurogenic inflammationpathogenesistherapyReferencesZuberbier T., Aberer W., Asero R., Abdul Latiff A.H., Baker D., Ballmer-Weber B., Bernstein J.A., Bindslev-Jensen C., Brzoza Z., Buense Bedrikow R. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018; 73 (7): 1393–1414.Zuberbier T., Aberer W., Asero R., Abdul Latiff A.H., Baker D., Ballmer-Weber B., Bernstein J.A., Bindslev-Jensen C., Brzoza Z., Buense Bedrikow R. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018; 73 (7): 1393–1414.Kulthanan K., Jiamton S., Thumpimukvatana N., Pinkaew S. Chronic idiopathic urticaria: prevalence and clinical course. J Dermatol. 2007; 34 (5): 294–301.Kulthanan K., Jiamton S., Thumpimukvatana N., Pinkaew S. Chronic idiopathic urticaria: prevalence and clinical course. J Dermatol. 2007; 34 (5): 294–301.Balp M.M., Weller K., Carboni V., Chirilov A., Papavassilis C., Severin T., Hua L., Maurer M. Prevalence and clinical characteristics of chronic spontaneous urticaria in pediatric patients. Pediatr Allergy Immunol. 2018; 29 (6): 630–636.Balp M.M., Weller K., Carboni V., Chirilov A., Papavassilis C., Severin T., Hua L., Maurer M. Prevalence and clinical characteristics of chronic spontaneous urticaria in pediatric patients. Pediatr Allergy Immunol. 2018; 29 (6): 630–636.Asero R., Tedeschi A., Marzano A.V., Cugno M. Chronic urticaria: a focus on pathogenesis. F1000Res. 2017; 6: 1095.Asero R., Tedeschi A., Marzano A.V., Cugno M. Chronic urticaria: a focus on pathogenesis. F1000Res. 2017; 6: 1095.Konstantinou G.N., Asero R., Maurer M., Sabroe R.A., Schmid-Grendelmeier P., Grattan C.E. EAACI/GA²LEN task force consensus report: the autologous serum skin test in urticaria. Allergy. 2009; 64 (9): 1256–1268.Konstantinou G.N., Asero R., Maurer M., Sabroe R.A., Schmid-Grendelmeier P., Grattan C.E. EAACI/GA²LEN task force consensus report: the autologous serum skin test in urticaria. Allergy. 2009; 64 (9): 1256–1268.Church M.K., Kolkhir P., Metz M., Maurer M. The role and relevance of mast cells in urticaria. Immunol Rev. 2018; 282 (1): 232–247.Church M.K., Kolkhir P., Metz M., Maurer M. The role and relevance of mast cells in urticaria. Immunol Rev. 2018; 282 (1): 232–247.Maurer M., Eyerich K., Eyerich S., Ferrer M., Gutermuth J., Hartmann K., Jakob T., Kappen J.H., Navarini A., Schäkel K. Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020. Int Arch Allergy Immunol. 2020; 181 (5): 321–333.Maurer M., Eyerich K., Eyerich S., Ferrer M., Gutermuth J., Hartmann K., Jakob T., Kappen J.H., Navarini A., Schäkel K. Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020. Int Arch Allergy Immunol. 2020; 181 (5): 321–333.Mlynek A., Magerl M., Hanna M., Lhachimi S., Baiardini I., Canonica G.W., Maurer M. The neuropeptide substance P is a key mediator in the pathogenesis of urticaria. J Eur Acad Dermatol Venereol. 2008; 22 (5): 565–571.Mlynek A., Magerl M., Hanna M., Lhachimi S., Baiardini I., Canonica G.W., Maurer M. The neuropeptide substance P is a key mediator in the pathogenesis of urticaria. J Eur Acad Dermatol Venereol. 2008; 22 (5): 565–571.Theoharides T.C., Zhang B., Kempuraj D., Tagen M., Vasiadi M., Angelidou A., Alysandratos K.D., Kalogeromitros D., Asadi S., Stavrianeas N. IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin. Proc Natl Acad Sci U S A. 2010; 107 (9): 4448–4453.Theoharides T.C., Zhang B., Kempuraj D., Tagen M., Vasiadi M., Angelidou A., Alysandratos K.D., Kalogeromitros D., Asadi S., Stavrianeas N. IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin. Proc Natl Acad Sci U S A. 2010; 107 (9): 4448–4453.Peters E.M. Stressed skin? — A molecular psychosomatic update on stress-causes and effects in dermatologic diseases. J Dtsch Dermatol Ges. 2016; 14 (3): 233–252.Peters E.M. Stressed skin? — A molecular psychosomatic update on stress-causes and effects in dermatologic diseases. J Dtsch Dermatol Ges. 2016; 14 (3): 233–252.Moher D., Liberati A., Tetzlaff J., Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6 (7): e1000097.Moher D., Liberati A., Tetzlaff J., Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6 (7): e1000097.Higgins J.P.T., Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration; 2011.Higgins J.P.T., Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration; 2011.Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71.Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71.Liberati A., Altman D.G., Tetzlaff J., Mulrow C., Gøtzsche P.C., Ioannidis J.P.A., Clarke M., Devereaux P.J., Kleijnen J., Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009; 6 (7): e1000100.Liberati A., Altman D.G., Tetzlaff J., Mulrow C., Gøtzsche P.C., Ioannidis J.P.A., Clarke M., Devereaux P.J., Kleijnen J., Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009; 6 (7): e1000100.Siebenhaar F., Degener F., Zuberbier T., Martus P., Maurer M. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria. J Allergy Clin Immunol. 2009; 123 (3): 672–679.Siebenhaar F., Degener F., Zuberbier T., Martus P., Maurer M. High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria. J Allergy Clin Immunol. 2009; 123 (3): 672–679.Özçeker D., Can P.K., Terzi Ö., Tamay Z., Güler N., Ensina L.F. Differences between adult and pediatric chronic spontaneous urticaria from a cohort of 751 patients: clinical features, associated conditions and indicators of treatment response. Pediatr Allergy Immunol. 2023; 34 (2): e13925.Özçeker D., Can P.K., Terzi Ö., Tamay Z., Güler N., Ensina L.F. Differences between adult and pediatric chronic spontaneous urticaria from a cohort of 751 patients: clinical features, associated conditions and indicators of treatment response. Pediatr Allergy Immunol. 2023; 34 (2): e13925.Ahanchian H., Farid R., Moghaddam Z.A., Jabbari F., Kianifar H.R., Khoshakhlagh M. Evaluation of serum substance P level in chronic urticaria and correlation with disease severity. Iran J Allergy Asthma Immunol. 2020; 19 (1): 89–94.Ahanchian H., Farid R., Moghaddam Z.A., Jabbari F., Kianifar H.R., Khoshakhlagh M. Evaluation of serum substance P level in chronic urticaria and correlation with disease severity. Iran J Allergy Asthma Immunol. 2020; 19 (1): 89–94.Ensina L.F., Brandão L.S., Neto H.C., Cardoso T., Solé D., Ben-Shoshan M. Chronic urticaria treatment challenges in children. Rev Paul Pediatr. 2025; 43: e2024107.Ensina L.F., Brandão L.S., Neto H.C., Cardoso T., Solé D., Ben-Shoshan M. Chronic urticaria treatment challenges in children. Rev Paul Pediatr. 2025; 43: e2024107.O’Connor T.M., O’Connell J., O’Brien D.I., Goode T., Bredin C.P., Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol. 2004; 201 (2): 167–180.O’Connor T.M., O’Connell J., O’Brien D.I., Goode T., Bredin C.P., Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol. 2004; 201 (2): 167–180.Zhao Z.Q., Huo F.Q., Jeffry J., Hampton L., Demehri S., Kim S., Liu X.Y., Barry D.M., Wan L., Liu Z.C. Chronic itch: emerging treatments following new research concepts. Br J Pharmacol. 2021; 178 (12): 2455–2468.Zhao Z.Q., Huo F.Q., Jeffry J., Hampton L., Demehri S., Kim S., Liu X.Y., Barry D.M., Wan L., Liu Z.C. Chronic itch: emerging treatments following new research concepts. Br J Pharmacol. 2021; 178 (12): 2455–2468.Steinhoff M.S., von Mentzer B., Geppetti P., Pothoulakis C., Bunnett N.W. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev. 2014; 94 (1): 265–301.Steinhoff M.S., von Mentzer B., Geppetti P., Pothoulakis C., Bunnett N.W. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev. 2014; 94 (1): 265–301.Almeida T.A., Rojo J., Nieto P.M., Pinto F.M., Hernandez M., Martin J.D., Candenas M.L. Tachykinins and tachykinin receptors: structure and activity relationships. Curr Med Chem. 2004; 11 (15): 2045–2081.Almeida T.A., Rojo J., Nieto P.M., Pinto F.M., Hernandez M., Martin J.D., Candenas M.L. Tachykinins and tachykinin receptors: structure and activity relationships. Curr Med Chem. 2004; 11 (15): 2045–2081.Kulka M., Sheen C.H., Tancowny B.P., Grammer L.C., Schleimer R.P. Neuropeptides activate human mast cell degranulation and chemokine production. Immunology. 2008; 123 (3): 398–410.Kulka M., Sheen C.H., Tancowny B.P., Grammer L.C., Schleimer R.P. Neuropeptides activate human mast cell degranulation and chemokine production. Immunology. 2008; 123 (3): 398–410.Joos G.F., Germonpre P.R., Pauwels R.A. Role of tachykinins in asthma. Allergy. 2000; 55 (4): 321–337.Joos G.F., Germonpre P.R., Pauwels R.A. Role of tachykinins in asthma. Allergy. 2000; 55 (4): 321–337.Zhong J., Minikes A.M., Wang Y., Song Y., Li J., Chen X., Zhang M., Li H., Liu Z., Zhao Z. Substance P and its receptor neurokinin 1 expression in chronic spontaneous urticaria. J Dermatol Sci. 2019; 94 (2): 304–311.Zhong J., Minikes A.M., Wang Y., Song Y., Li J., Chen X., Zhang M., Li H., Liu Z., Zhao Z. Substance P and its receptor neurokinin 1 expression in chronic spontaneous urticaria. J Dermatol Sci. 2019; 94 (2): 304–311.DeFea K.A., Vaughn Z.D., O’Bryan E.M., Nishijima D., Déry O., Bunnett N.W. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta-arrestin-dependent scaffolding complex. Proc Natl Acad Sci U S A. 2000; 97 (20): 11086–11091.DeFea K.A., Vaughn Z.D., O’Bryan E.M., Nishijima D., Déry O., Bunnett N.W. The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta-arrestin-dependent scaffolding complex. Proc Natl Acad Sci U S A. 2000; 97 (20): 11086–11091.Russell F.A., King R., Smillie S.J., Kodji X., Brain S.D. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014; 94 (4): 1099–1142.Russell F.A., King R., Smillie S.J., Kodji X., Brain S.D. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014; 94 (4): 1099–1142.Steinhoff M., Buddenkotte J., Lerner E.A. Role of neuropeptides in pruritus. In: Itch: Mechanisms and Treatment. CRC Press; 2014: 75–94.Steinhoff M., Buddenkotte J., Lerner E.A. Role of neuropeptides in pruritus. In: Itch: Mechanisms and Treatment. CRC Press; 2014: 75–94.Burnstock G. Purinergic mechanisms and pain. Curr Opin Pharmacol. 2016; 32: 70–77.Burnstock G. Purinergic mechanisms and pain. Curr Opin Pharmacol. 2016; 32: 70–77.Babina M., Guhl S., Artuc M., Zuberbier T. Allergic FcepsilonRI- and pseudo-allergic MRGPRX2-triggered mast cell activation routes are independent and inversely regulated by SCF. Allergy. 2018; 73 (1): 256–260.Babina M., Guhl S., Artuc M., Zuberbier T. Allergic FcepsilonRI- and pseudo-allergic MRGPRX2-triggered mast cell activation routes are independent and inversely regulated by SCF. Allergy. 2018; 73 (1): 256–260.Gonçalves N.P., Vægter C.B., Pallesen L.T., Joca S.R. The role of substance P in the central nervous system. Neurosci Biobehav Rev. 2021; 131: 1025–1043.Gonçalves N.P., Vægter C.B., Pallesen L.T., Joca S.R. The role of substance P in the central nervous system. Neurosci Biobehav Rev. 2021; 131: 1025–1043.Pavlovic S., Daniltchenko M., Tobin D.J., Hagen E., Hunt S.P., Klapp B.F., Arck P.C., Peters E.M. Further exploring the brainskin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice. J Invest Dermatol. 2008; 128 (2): 434–446.Pavlovic S., Daniltchenko M., Tobin D.J., Hagen E., Hunt S.P., Klapp B.F., Arck P.C., Peters E.M. Further exploring the brainskin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice. J Invest Dermatol. 2008; 128 (2): 434–446.Chang J., Cote C., Netchiporouk E., Leung J., Gooderham M., Vender R., Prajapati V.H. Management of pediatric chronic spontaneous urticaria: a review of current evidence and guidelines. J Asthma Allergy. 2021; 14: 187–199.Chang J., Cote C., Netchiporouk E., Leung J., Gooderham M., Vender R., Prajapati V.H. Management of pediatric chronic spontaneous urticaria: a review of current evidence and guidelines. J Asthma Allergy. 2021; 14: 187–199.Votto M., Castagnoli R., Bertozzi M., Brambilla I., Caimmi S., Licari A., Marseglia A., Marseglia G.L. Pediatric chronic spontaneous urticaria: a brief clinician’s guide. Expert Rev Clin Immunol. 2022; 18 (9): 889–899.Votto M., Castagnoli R., Bertozzi M., Brambilla I., Caimmi S., Licari A., Marseglia A., Marseglia G.L. Pediatric chronic spontaneous urticaria: a brief clinician’s guide. Expert Rev Clin Immunol. 2022; 18 (9): 889–899.Arck P.C., Slominski A., Theoharides T.C., Peters E.M., Paus R. Neuroimmunology of stress: skin takes center stage. J Invest Dermatol. 2006; 126 (8): 1697–1704.Arck P.C., Slominski A., Theoharides T.C., Peters E.M., Paus R. Neuroimmunology of stress: skin takes center stage. J Invest Dermatol. 2006; 126 (8): 1697–1704.Theoharides T.C., Donelan J.M., Papadopoulou N., Cao J., Kempuraj D., Conti P. Mast cells as targets of corticotropin-releasing factor and related peptides. Trends Pharmacol Sci. 2004; 25 (11): 563–568.Theoharides T.C., Donelan J.M., Papadopoulou N., Cao J., Kempuraj D., Conti P. Mast cells as targets of corticotropin-releasing factor and related peptides. Trends Pharmacol Sci. 2004; 25 (11): 563–568.Steinhoff M., Ständer S., Seeliger S., Ansel J.C., Schmelz M., Luger T. Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol. 2003; 139 (11): 1479–1488.Steinhoff M., Ständer S., Seeliger S., Ansel J.C., Schmelz M., Luger T. Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol. 2003; 139 (11): 1479–1488.Kocatürk E., Podder I., Zenclussen A.C., Kasperska-Zajac A., Elieh-Ali-Komi D., Church M.K., Maurer M. Role of substance P and its receptor neurokinin 1 in chronic urticaria: a systematic review. Int J Mol Sci. 2021; 22 (20): 11127.Kocatürk E., Podder I., Zenclussen A.C., Kasperska-Zajac A., Elieh-Ali-Komi D., Church M.K., Maurer M. Role of substance P and its receptor neurokinin 1 in chronic urticaria: a systematic review. Int J Mol Sci. 2021; 22 (20): 11127.Metz M., Krull C., Hawro T., Saluja R., Groffik A., Stangerup M., Maurer M. Substance P is upregulated in the serum of patients with chronic spontaneous urticaria. J Invest Dermatol. 2014; 134 (11): 2833–2836.Metz M., Krull C., Hawro T., Saluja R., Groffik A., Stangerup M., Maurer M. Substance P is upregulated in the serum of patients with chronic spontaneous urticaria. J Invest Dermatol. 2014; 134 (11): 2833–2836.Herberth G., Daegelmann C., Weber A., Röder S., Krämer U., Schins R.P.F., Behrendt H., Borte M., Heinrich J., Herbarth O. Association of neuropeptides with Th1/Th2 balance and allergic sensitization in children. Clin Exp Allergy. 2006; 36 (11): 1408– 1416.Herberth G., Daegelmann C., Weber A., Röder S., Krämer U., Schins R.P.F., Behrendt H., Borte M., Heinrich J., Herbarth O. Association of neuropeptides with Th1/Th2 balance and allergic sensitization in children. Clin Exp Allergy. 2006; 36 (11): 1408– 1416.Frieri M. Neurokinin-1 receptor antagonists: a new frontier in the treatment of chronic refractory urticaria. J Allergy Clin Immunol Pract. 2019; 7 (4): 1101–1103.Frieri M. Neurokinin-1 receptor antagonists: a new frontier in the treatment of chronic refractory urticaria. J Allergy Clin Immunol Pract. 2019; 7 (4): 1101–1103.Frieri M. Neurokinin-1 receptor antagonists for the treatment of chronic urticaria. Ann Allergy Asthma Immunol. 2021; 126 (5): 487–488.Frieri M. Neurokinin-1 receptor antagonists for the treatment of chronic urticaria. Ann Allergy Asthma Immunol. 2021; 126 (5): 487–488.Guo L., Jin H.Z. Advances in small molecule and biological drugs for the treatment of pruritus. Chin J Dermatol. 2023; 56 (5): e20210582.Guo L., Jin H.Z. Advances in small molecule and biological drugs for the treatment of pruritus. Chin J Dermatol. 2023; 56 (5): e20210582.Kolkhir P., Altrichter S., Asero R., Daschner A., Ferrer M., Giménez-Arnau A., Hawro T., Jakob T., Kosma P., Makris M. Chronic urticaria: new insights into pathophysiology and treatment. Lancet. 2022; 399 (10321): 363–376.Kolkhir P., Altrichter S., Asero R., Daschner A., Ferrer M., Giménez-Arnau A., Hawro T., Jakob T., Kosma P., Makris M. Chronic urticaria: new insights into pathophysiology and treatment. Lancet. 2022; 399 (10321): 363–376.Maurer M., Rosen K., Hsieh H.J., Saini S., Grattan C., Gimenéz-Arnau A., Agarwal S., Doyle R., Canvin J., Kaplan A. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013; 368 (10): 924–935.Maurer M., Rosen K., Hsieh H.J., Saini S., Grattan C., Gimenéz-Arnau A., Agarwal S., Doyle R., Canvin J., Kaplan A. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013; 368 (10): 924–935.Metz M., Altrichter S., Buttgereit T., Fluhr J.W., Fok J.S., Hawro T., Kolkhir P., Krause K., Magerl M., Pyatilova P. Omalizumab in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. J Allergy Clin Immunol. 2019; 143 (2): AB236.Metz M., Altrichter S., Buttgereit T., Fluhr J.W., Fok J.S., Hawro T., Kolkhir P., Krause K., Magerl M., Pyatilova P. Omalizumab in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. J Allergy Clin Immunol. 2019; 143 (2): AB236.Ensina L.F., Caminati M., Crisci M., Nunes I.C., Ribeiro M.R., Silva D.A.O., Solé D., Ben-Shoshan M. Omalizumab in pediatric chronic spontaneous urticaria: a real-life study. Pediatr Allergy Immunol. 2021; 32 (5): 1042–1049.Ensina L.F., Caminati M., Crisci M., Nunes I.C., Ribeiro M.R., Silva D.A.O., Solé D., Ben-Shoshan M. Omalizumab in pediatric chronic spontaneous urticaria: a real-life study. Pediatr Allergy Immunol. 2021; 32 (5): 1042–1049.Sultan N., Cheema W., Hashmi T., Ch A.A., Rehman S., Butt G. To compare the added effectiveness of ketotifen along with traditional H1 anti histamines for the symptomatic improvement of chronic idiopathic urticaria. J Pak Assoc Dermatol. 2022; 31 (4): 665–671.Sultan N., Cheema W., Hashmi T., Ch A.A., Rehman S., Butt G. To compare the added effectiveness of ketotifen along with traditional H1 anti histamines for the symptomatic improvement of chronic idiopathic urticaria. J Pak Assoc Dermatol. 2022; 31 (4): 665–671.Gleich G.J. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol. 2000; 105 (4): 651–663.Gleich G.J. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol. 2000; 105 (4): 651–663.

The authors declare that there are no conflicts of interest present.