{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:40:44Z","timestamp":1789094444068,"version":"build-2803163510"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic spontaneous urticaria (CSU) is a burdensome dermatological condition with a complex, multifactorial pathogenesis involving intricate immune, neurological, and psychological interactions. While traditional models primarily emphasize auto-allergic mechanisms, evidence highlights the critical role of neuroimmune interaction in the chronicity and exacerbation of disease. This review examines the neuroimmune contributions to CSU pathogenesis, focusing on mast cell (MC)\u2013sensory neuron interactions, autonomic nervous system dysregulation, neuroinflammatory pathways, and psychological comorbidities that perpetuate disease activity. A comprehensive narrative review of the literature was undertaken, evaluating mechanisms such as MC activation through immunoglobulin-E (IgE)-independent pathways, neuropeptide-mediated inflammation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and psychiatric associations with CSU. Findings indicate that beyond the classical IgE-mediated MC degranulation, neurogenic inflammation via Mas-Related G-Protein Coupled Receptor X2 (MRGPRX2) receptors\u2014triggered by neuropeptides such as substance P and vasoactive intestinal peptide\u2014plays a pivotal role. Chronic psychological stress activates the HPA axis, contributing to MC hyperactivity and reinforcing the pruritus-stress cycle. Furthermore, a high prevalence of psychiatric comorbidities, including anxiety and depression, contributes to central sensitization and worsens disease severity. The interplay of T cells, basophils, eosinophils, and endothelial cells further amplifies the neuroimmune-inflammatory network. These insights suggest that optimal CSU management requires an integrated approach encompassing dermatological, immunological, and psychological interventions. Emerging therapies targeting neuroimmune pathways, such as MRGPRX2 antagonists, beta-adrenergic blockers, and cognitive-behavioral strategies, show promise. Future research should prioritize the development of personalized neuroimmune-directed therapies to enhance disease control in CSU.<\/jats:p>","DOI":"10.4103\/idoj.idoj_415_25","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T08:00:20Z","timestamp":1766736020000},"page":"3-9","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["The Neuropsychological Dimensions to Pathogenesis of Chronic Spontaneous Urticaria Beyond Autoallergy \u2013 A Brief Narrative Review"],"prefix":"10.4103","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8091-101X","authenticated-orcid":false,"given":"M. Sendhil","family":"Kumaran","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahibpreet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davinder","family":"Parsad","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarun","family":"Narang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"R1-20251229","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/164_2021_506","article-title":"The classification, pathogenesis, diagnostic workup, and management of urticaria: An update","volume":"268","author":"Maurer","year":"2022","journal-title":"Handb Exp Pharmacol"},{"key":"R2-20251229","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.iac.2024.03.004","article-title":"Chronic spontaneous urticaria: Quality of life and economic impacts","volume":"44","author":"Keller","year":"2024","journal-title":"Immunol Allergy Clin North Am"},{"key":"R3-20251229","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.alit.2023.05.003","article-title":"Chronic urticaria and the pathogenic role of mast cells","volume":"72","author":"Elieh-ali-komi","year":"2023","journal-title":"Allergol Int"},{"key":"R4-20251229","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.jid.2020.06.030","article-title":"MRGPRX2 activation causes increased skin reactivity in patients with chronic spontaneous urticaria","volume":"141","author":"Shtessel","year":"2021","journal-title":"J Invest Dermatol"},{"key":"R5-20251229","doi-asserted-by":"crossref","first-page":"498","DOI":"10.4168\/aair.2021.13.3.498","article-title":"Elevated MRGPRX2 levels related to disease severity in patients with chronic spontaneous urticaria","volume":"13","author":"Cao","year":"2021","journal-title":"Allergy Asthma Immunol Res"},{"key":"R6-20251229","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.neuron.2018.03.023","article-title":"Peripheral and central mechanisms of itch","volume":"98","author":"Dong","year":"2018","journal-title":"Neuron"},{"key":"R7-20251229","first-page":"1280","article-title":"Skin and psychosomatics-psychodermatology today","volume":"18","author":"Gieler","year":"2020","journal-title":"J Dtsch Dermatol Ges"},{"key":"R8-20251229","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.3390\/jcm12093134","article-title":"Neuro-immuno-psychological aspects of chronic urticaria","volume":"12","author":"Tomaszewska","year":"2023","journal-title":"J Clin Med"},{"key":"R9-20251229","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1111\/exd.13705","article-title":"Possible roles of basophils in chronic itch","volume":"28","author":"Hashimoto","year":"2019","journal-title":"Exp Dermatol"},{"key":"R10-20251229","doi-asserted-by":"crossref","first-page":"879754","DOI":"10.3389\/fimmu.2022.879754","article-title":"The role of crosstalk of immune cells in pathogenesis of chronic spontaneous urticaria","volume":"13","author":"Zhou","year":"2022","journal-title":"Front Immunol"},{"key":"R11-20251229","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12974-025-03397-4","article-title":"Beyond the itch: The complex interplay of immune, neurological, and psychological factors in chronic urticaria","volume":"22","author":"Yang","year":"2025","journal-title":"J Neuroinflammation"},{"key":"R12-20251229","doi-asserted-by":"crossref","first-page":"100835","DOI":"10.1016\/j.waojou.2023.100835","article-title":"Occurrence and risk factors of mental disorders in patients with chronic urticaria","volume":"16","author":"Ghazanfar","year":"2023","journal-title":"World Allergy Organ J"},{"key":"R13-20251229","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1046\/j.1365-2133.2000.03831.x","article-title":"Psychiatric morbidity in dermatological outpatients: An issue to be recognized","volume":"143","author":"Picardi","year":"2000","journal-title":"Br J Dermatol"},{"key":"R14-20251229","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jaad.2005.11.1103","article-title":"Prevalence and correlates of suicidal ideation among patients with skin disease","volume":"54","author":"Picardi","year":"2006","journal-title":"J Am Acad Dermatol"},{"key":"R15-20251229","first-page":"104","article-title":"Psychiatric evaluation of patients with psoriasis vulgaris and chronic urticaria","volume":"10","author":"Mehta","year":"2007","journal-title":"German J Psychiatry"},{"key":"R16-20251229","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2340\/00015555-1109","article-title":"High prevalence of mental disorders and emotional distress in patients with chronic spontaneous urticaria","volume":"91","author":"Staubach","year":"2011","journal-title":"Acta Derm Venereol"},{"key":"R17-20251229","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1365-2133.2005.06976.x","article-title":"Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity","volume":"154","author":"Staubach","year":"2006","journal-title":"Br J Dermatol"},{"key":"R18-20251229","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.jaci.2014.02.036","article-title":"The diagnosis and management of acute and chronic urticaria: 2014 update","volume":"133","author":"Bernstein","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"R19-20251229","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13601-019-0278-3","article-title":"Psychiatric comorbidity in chronic urticaria patients: A systematic review and meta-analysis","volume":"9","author":"Konstantinou","year":"2019","journal-title":"Clin Transl Allergy"},{"key":"R20-20251229","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/01.EWX.0000503397.22746.bd","article-title":"Psychiatric disorders associated with some chronic dermatologic diseases among a group of Egyptian dermatology outpatient clinic attendants","volume":"14","author":"Sorour","year":"2017","journal-title":"J Egyptian Womens Dermatol Soc"}],"container-title":["Indian Dermatology Online Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/idoj.idoj_415_25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:57:16Z","timestamp":1786647436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/idoj.idoj_415_25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/idoj.idoj_415_25","relation":{},"ISSN":["2229-5178","2249-5673"],"issn-type":[{"value":"2229-5178","type":"print"},{"value":"2249-5673","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]},"assertion":[{"value":"2025-04-14","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}