Abstract
Background: Migraine is a condition characterized by recurrent episodes of unilateral headache. Allergic rhinitis (AR) is an IgE-mediated inflammatory condition of the nasal mucosa that is triggered by exposure to allergens. Migraine and AR may share underlying immunological mechanisms, including histamine release and mast cell activation. Despite the growing interest in the immunological interplay between allergic conditions and neurological symptoms, the specific relationship between AR and migraine remains underexplored.
Methods: PubMed, Scopus, and Web of Science were systematically searched to identify relevant studies. Pooled odds ratio (OR) and pooled risk ratio (RR) were calculated with 95% confidence intervals (CI) using a random-effects model. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. Heterogeneity assessment and subgroup analysis were also performed.
Results: Eleven studies involving 4,704,591 participants were included. The pooled OR for migraine in individuals with AR was 2.94 (95% CI: 2.02–4.29; p < 0.0001; I² = 95.62%). The pooled RR from two cohort studies was 2.27 (95% CI: 1.10–4.65; p = 0.026; I² = 99.72%). Subgroup analysis revealed significant differences in the pooled OR regarding the source of individuals with AR and the method of AR assessment, with a higher pooled OR in hospital patients (OR = 7.32) and when using skin tests (OR =6.93), respectively.
Conclusion: Migraine headaches are significantly associated with AR, particularly in hospital settings and when objectivemethodsareusedforARdiagnosis.Thefindingsofthisstudyshouldbeinterpreted cautiously owing to the high heterogeneity.
References
1. Amiri P, Kazeminasab S, Nejadghaderi SA, Mohammadinasab R, Pourfathi H, Araj-Khodaei M, Sullman MJM, Kolahi AA, Safiri S. Migraine: A Review on Its History, Global Epidemiology, Risk Factors, and Comorbidities. Front Neurol. 2021: 800605 [PMID: 35281991, https://doi.org/10.3389/fneur.2021.800605]
2. Ozge A, Ozge C, Ozturk C, Kaleagasi H, Ozcan M, Yalcinkaya DE, Ozveren N, Yalcin F. The relationship between migraine and atopic disorders-the contribution of pulmonary function tests and immunological screening. Cephalalgia. 2006: 172 [PMID: 16426272, https://doi.org/10.1111/j.1468-2982.2005.01021.x]
3. Leonardi M, Raggi A. A narrative review on the burden of migraine: when the burden is the impact on people's life. J Headache Pain. 2019: 41 [PMID: 31023226, https://doi.org/10.1186/s10194-019-0993-0]
4. Steiner TJ, Stovner LJ. Global epidemiology of migraine and its implications for public health and health policy. Nat Rev Neurol. 2023: 109 [PMID: 36693999, https://doi.org/10.1038/s41582-022-00763-1]
5. Dong L, Dong W, Jin Y, Jiang Y, Li Z, Yu D. The Global Burden of Migraine: A 30-Year Trend Review and Future Projections by Age, Sex, Country, and Region. Pain Ther. 2025: 297 [PMID: 39661241, https://doi.org/10.1007/s40122-024-00690-7]
6. Bousquet J, Van Cauwenberge P, Khaltaev N, Aria Workshop G, World Health O. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001: S147 [PMID: 11707753, https://doi.org/10.1067/mai.2001.118891]
7. Savoure M, Bousquet J, Jaakkola JJK, Jaakkola MS, Jacquemin B, Nadif R. Worldwide prevalence of rhinitis in adults: A review of definitions and temporal evolution. Clin Transl Allergy. 2022: e12130 [PMID: 35344304, https://doi.org/10.1002/clt2.12130]
8. Martin VT, Taylor F, Gebhardt B, Tomaszewski M, Ellison JS, Martin GV, Levin L, Al-Shaikh E, Nicolas J, Bernstein JA. Allergy and immunotherapy: are they related to migraine headache? Headache. 2011: 8 [PMID: 21054364, https://doi.org/10.1111/j.1526-4610.2010.01792.x]
9. Lv H, Liu K, Xie Y, Wang Y, Chen S, Liu P, Guan M, Cong J, Xu Y. No causal association between allergic rhinitis and migraine: a Mendelian randomization study. Eur J Med Res. 2024: 78 [PMID: 38281051, https://doi.org/10.1186/s40001-024-01682-1]
10. Yang W, Dai H, Xu XF, Jiang HY, Ding JY. Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses. Front Neurol. 2024: 1383832 [PMID: 38576533, https://doi.org/10.3389/fneur.2024.1383832]
11. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hrobjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021: n71 [PMID: 33782057, https://doi.org/10.1136/bmj.n71]
12. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010: 603 [PMID: 20652370, https://doi.org/10.1007/s10654-010-9491-z]
13. Gao Y, Huang YB, Liu XO, Chen C, Dai HJ, Song FJ, Wang J, Chen KX, Wang YG. Tea consumption, alcohol drinking and physical activity associations with breast cancer risk among Chinese females: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2013: 7543 [PMID: 24460331, https://doi.org/10.7314/apjcp.2013.14.12.7543]
14. Huedo-Medina TB, Sanchez-Meca J, Marin-Martinez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods. 2006: 193 [PMID: 16784338, https://doi.org/10.1037/1082-989X.11.2.193]
15. Thompson SG, Turner RM, Warn DE. Multilevel models for meta-analysis, and their application to absolute risk differences. Stat Methods Med Res. 2001: 375 [PMID: 11763548, https://doi.org/10.1177/096228020101000602]
16. Aamodt AH, Stovner LJ, Langhammer A, Hagen K, Zwart JA. Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT Study. Headache. 2007: 204 [PMID: 17300360, https://doi.org/10.1111/j.1526-4610.2006.00597.x]
17. Derebery J, Meltzer E, Nathan RA, Stang PE, Campbell UB, Corrao M, Stanford R. Rhinitis symptoms and comorbidities in the United States: burden of rhinitis in America survey. Otolaryngol Head Neck Surg. 2008: 198 [PMID: 18656715, https://doi.org/10.1016/j.otohns.2008.05.019]
18. Graif Y, Shohat T, Machluf Y, Farkash R, Chaiter Y. Association between asthma and migraine: A cross-sectional study of over 110 000 adolescents. Clin Respir J. 2018: 2491 [PMID: 30004178, https://doi.org/10.1111/crj.12939]
19. Han JH, Lee HJ, Yook HJ, Han K, Lee JH, Park YM. Atopic Disorders and Their Risks of Migraine: A Nationwide Population-Based Cohort Study. Allergy Asthma Immunol Res. 2023: 55 [PMID: 36693358, https://doi.org/10.4168/aair.2023.15.1.55]
20. Ku M, Silverman B, Prifti N, Ying W, Persaud Y, Schneider A. Prevalence of migraine headaches in patients with allergic rhinitis. Ann Allergy Asthma Immunol. 2006: 226 [PMID: 16937756, https://doi.org/10.1016/S1081-1206(10)60018-X]
21. Ozturk A, Degirmenci Y, Tokmak B, Tokmak A. Frequency of migraine in patients with allergic rhinitis. Pak J Med Sci. 2013: 528 [PMID: 24353570, https://doi.org/10.12669/pjms.292.3148]
22. Saberi A, Nemati S, Shakib RJ, Kazemnejad E, Maleki M. Association between allergic rhinitis and migraine. J Res Med Sci. 2012: 508 [PMID: 23626624,
23. Tsiakiris G, Neely G, Lind N, Nordin S. Comorbidity in allergic asthma and allergic rhinitis: functional somatic syndromes. Psychol Health Med. 2017: 1163 [PMID: 28034321, https://doi.org/10.1080/13548506.2016.1276606]
24. Wang IC, Tsai JD, Lin CL, Shen TC, Li TC, Wei CC. Allergic rhinitis and associated risk of migraine among children: a nationwide population-based cohort study. Int Forum Allergy Rhinol. 2016: 322 [PMID: 26446370, https://doi.org/10.1002/alr.21654]
25. Zencir M, Ergin H, Sahiner T, Kilic I, Alkis E, Ozdel L, Gurses D, Ergin A. Epidemiology and symptomatology of migraine among school children: Denizli urban area in Turkey. Headache. 2004: 780 [PMID: 15330824, https://doi.org/10.1111/j.1526-4610.2004.04145.x]
26. Mortimer MJ, Kay J, Gawkrodger DJ, Jaron A, Barker DC. The prevalence of headache and migraine in atopic children: an epidemiological study in general practice. Headache. 1993: 427 [PMID: 8262782, https://doi.org/10.1111/j.1526-4610.1993.hed3308427.x]
27. Levy D, Burstein R, Strassman AM. Mast cell involvement in the pathophysiology of migraine headache: A hypothesis. Headache. 2006: S13 [PMID: 16927959, https://doi.org/10.1111/j.1526-4610.2006.00485.x]
28. Agnihotri NT, McGrath KG. Allergic and nonallergic rhinitis. Allergy Asthma Proc. 2019: 376 [PMID: 31690374, https://doi.org/10.2500/aap.2019.40.4251]
29. Mehle ME. Allergy and migraine: is there a connection? Curr Opin Otolaryngol Head Neck Surg. 2008: 265 [PMID: 18475083, https://doi.org/10.1097/MOO.0b013e3282f6a629]
30. Gazerani P, Pourpak Z, Ahmadiani A, Hemmati A, Kazemnejad A. A correlation between migraine, histamine and immunoglobulin e. Scand J Immunol. 2003: 286 [PMID: 12641658, https://doi.org/10.1046/j.1365-3083.2003.01216.x]
31. Theodoropoulos DS, Katzenberger DR, Jones WM, Morris DL, Her C, Cullen NA, Morrisa DL. Allergen-specific sublingual immunotherapy in the treatment of migraines: a prospective study. Eur Rev Med Pharmacol Sci. 2011: 1117 [PMID: 22165671,
32. Heatley RV, Denburg JA, Bayer N, Bienenstock J. Increased plasma histamine levels in migraine patients. Clin Allergy. 1982: 145 [PMID: 6176358, https://doi.org/10.1111/j.1365-2222.1982.tb01633.x]
33. Krabbe AA, Olesen J. Headache provocation by continuous intravenous infusion of histamine. Clinical results and receptor mechanisms. Pain. 1980: 253 [PMID: 7402688, https://doi.org/10.1016/0304-3959(88)90012-7]
34. Lassen LH, Thomsen LL, Olesen J. Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of migraine. Neuroreport. 1995: 1475 [PMID: 7579128, https://doi.org/10.1097/00001756-199507310-00003]
35. Nelson HS, Rosloniec DM, McCall LI, Ikle D. Comparative performance of five commercial prick skin test devices. J Allergy Clin Immunol. 1993: 750 [PMID: 8227867, https://doi.org/10.1016/0091-6749(93)90019-c]
36. Onore C, Careaga M, Ashwood P. The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun. 2012: 383 [PMID: 21906670, https://doi.org/10.1016/j.bbi.2011.08.007]
37. Perry BF, Login IS, Kountakis SE. Nonrhinologic headache in a tertiary rhinology practice. Otolaryngol Head Neck Surg. 2004: 449 [PMID: 15100642, https://doi.org/10.1016/j.otohns.2004.01.005]
38. Kristensen P. [Bias from dependent errors in observational studies]. Tidsskr Nor Laegeforen. 2005: 173 [PMID: 15665891,
39. Wynne AM, Henry CJ, Godbout JP. Immune and behavioral consequences of microglial reactivity in the aged brain. Integr Comp Biol. 2009: 254 [PMID: 21665818, https://doi.org/10.1093/icb/icp009]
40. Cady RK, Schreiber CP. Sinus headache: a clinical conundrum. Otolaryngol Clin North Am. 2004: 267 [PMID: 15064062, https://doi.org/10.1016/S0030-6665(03)00181-6]
41. Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C. Prevalence of migraine in patients with a history of self-reported or physician-diagnosed "sinus" headache. Arch Intern Med. 2004: 1769 [PMID: 15364670, https://doi.org/10.1001/archinte.164.16.1769]

This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 ASIDE Internal Medicine