{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:17:37Z","timestamp":1788257857955,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Soonchunhyang University Research Fund"},{"id":[{"id":"https:\/\/ror.org\/03qjsrb10","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Histaglobulin (histamine\/immunoglobulin complex) has been used for decades as a non-allergen-specific immunotherapy for allergic diseases including allergic rhinitis, chronic urticaria, and atopic dermatitis. Despite growing clinical interest, no meta-analysis has synthesized the available evidence. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of histaglobulin across allergic diseases, with particular emphasis on implications for allergic rhinitis management. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to March 2026. Studies evaluating subcutaneous histaglobulin in patients with allergic diseases were included. For chronic urticaria studies reporting Urticaria Activity Score (UAS) as mean \u00b1 standard deviation, a random-effects meta-analysis was performed using the standardized mean difference (Hedges\u2019 g). Allergic rhinitis studies were synthesized narratively. Risk of bias was assessed using the National Institutes of Health (NIH) Quality Assessment Tools. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Fourteen studies (N = 754) met the inclusion criteria: six chronic urticaria studies with quantitative data (N = 190), three allergic rhinitis studies (N = 165), two atopic dermatitis\/chronic spontaneous urticaria case series (N = 8), and three chronic urticaria studies with incomplete data. Meta-analysis of six chronic urticaria studies, all of which used an uncontrolled before\u2013after design, demonstrated a large pooled within-group effect size (Hedges\u2019 g = 2.82; 95% confidence interval [CI] 1.75\u20133.88; p &lt; 0.00001), with high heterogeneity (I2 = 98.2%). UAS reduction ranged from 44% to 89% across studies. Complete remission rates ranged from 30% to 89%. Sensitivity analysis excluding one study with reporting concerns yielded consistent results (g = 2.34; 95% CI 1.83\u20132.85; I2 = 90.2%). All three allergic rhinitis studies reported significant symptom improvement (response rates 57\u201390%) with normalization of serum immunoglobulin E (IgE) and eosinophil counts. No serious adverse events were identified within the available literature; however, the cumulative sample size (N = 754) remains insufficient to exclude rare or long-term adverse effects. Available evidence suggests that histaglobulin may reduce disease activity in chronic urticaria; because the pooled estimate derives predominantly from uncontrolled before\u2013after studies with substantial heterogeneity, it reflects within-group improvement following treatment rather than a controlled estimate of treatment efficacy, and confidence in the effect remains limited. Preliminary evidence suggests that histaglobulin may also provide benefit in patients with allergic rhinitis; however, the available data are limited and heterogeneous, and larger, well-designed controlled studies are needed to confirm its effectiveness. Well-designed randomized controlled trials are needed, particularly for allergic rhinitis, to establish histaglobulin\u2019s role in evidence-based otorhinolaryngology practice.<\/jats:p>","DOI":"10.3390\/ijms27177753","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Histaglobulin in Allergic Diseases: A Systematic Review and Meta-Analysis with Implications for Allergic Rhinitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-057X","authenticated-orcid":false,"given":"Jayoung","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5194-930X","authenticated-orcid":false,"given":"Ji Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1398-9995.2007.01620.x","article-title":"Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update","volume":"63","author":"Bousquet","year":"2008","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/all.15090","article-title":"The international EAACI\/GA2LEN\/EuroGuiDerm\/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria","volume":"77","author":"Zuberbier","year":"2022","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1111\/j.1398-9995.2009.02178.x","article-title":"EAACI\/GA2LEN\/EDF\/WAO guideline: Management of urticaria","volume":"64","author":"Zuberbier","year":"2009","journal-title":"Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/cea.12494","article-title":"BSACI guideline for the management of chronic urticaria and angioedema","volume":"45","author":"Powell","year":"2015","journal-title":"Clin. 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