SYSTEMATIC REVIEW Allergen-specific immunotherapy for local allergic rhinitis: a systematic review and meta-analysis* Abstract Background: Local allergic rhinitis (LAR) is a phenotype of chronic rhinitis exhibiting a local Th2-driven inflammation without positive clinical markers of atopy. Immunomodulatory effects of allergen-specific immunotherapy (AIT) induce allergen-specific tolerance. However, AIT is not well-recognized as a treatment for LAR. Methodology: Systematic search on six electronic databases and registries was performed. Experimental and observational studies of AIT for LAR patients were retrieved. The primary outcomes were symptom score, medication score, combined symptom medication score, and disease-specific quality of life. Secondary outcomes were serum specific(s) IgG4, sIgE, and adverse events. Results: Four double-blind randomized controlled trials (156 patients) from two research units assessed the effects of subcuta- neous immunotherapy (SCIT). Compared with placebo, SCIT showed significant reductions in symptom score, medication score, combined symptom medication score, disease-specific quality of life, and an increase in serum sIgG4. There was no significant change in serum sIgE. Likewise, two observational studies (one using SCIT and one using sublingual immunotherapy) improved post-therapeutic symptom score. No studies assessed the effects after discontinuation of treatment. AIT was safe without serious adverse events. Conclusion: AIT has beneficial effects and safe for LAR. Its effects are restricted to studies with short-term follow-up. AIT may be considered in LAR patients. Key words: allergen, local allergic rhinitis, immunotherapy, subcutaneous, sublingual Minh P. Hoang 1,2,3 , Jompol Samuthpongtorn 4 , Wirach Chitsuthipakorn 5,6 , Kachorn Seresirikachorn 1,2 , Kornkiat Snidvongs 1,2 1 Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 2 Endoscopic Nasal and Sinus Surgery Excellent Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand 3 Department of Otolaryngology, Hue University of Medicine and Pharmacy, Hue University, Vietnam 4 Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand 5 Center of Excellence in Otolaryngology-Head & Neck Surgery, Rajavithi Hospital, Bangkok, Thailand 6 Department of Otolaryngology, College of Medicine, Rangsit University, Bangkok, Thailand Rhinology 60: 1, 11 - 19, 2022 https://doi.org/10.4193/Rhin21.193 *Received for publication: June 4, 2021 Accepted: September 2, 2021 11 Introduction Chronic rhinitis is an inflammatory condition of the nasal mucosa, which is classified into allergic rhinitis (AR) and non- allergic rhinitis (NAR) (1) . AR is associated with immunoglobulin E (IgE)-mediated response via the Th2 inflammatory pathway after exposure to inhalant allergens (2) . Clinical tests for atopy are used to confirm the diagnosis of AR, including skin prick test (SPT) and serum specific(s) IgE. At least one of these two markers of atopy are positive in AR patients (2) . Chronic rhinitis patients with negative for both markers are diagnosed with NAR. One-quarter of NAR patients have positive nasal allergen provocation test (NAPT) (3) . This condition indicates a localized allergic condi- tion or entopy (3-6) . Although the concept of local allergy in the absence of systemic atopy was postulated for the first time in 1975 (7) , the term local allergic rhinitis (LAR) was recognized after better understanding of local mucosal allergic immune reaction without systemic response (5,8,9) . However, there are controversies regarding the inconsistency of local sIgE detection in patients with NAR (10) . In addition, some studies found the transformation from LAR to AR after years of follow-up. As a result, the concept