Thoughts on the pathophysiology of nonallergic rhinitis
Open accessAbstract
Nonallergic noninfectious rhinitis is a diagnosis by exclusion, meaning that a number of poorly defined nasal conditions that have in common allergy and infection as a cause of the rhinitis have been excluded. The etiology of some subgroups of nonallergic noninfectious rhinitis, like nonallergic rhinitis with eosinophilia (NARES) and drug-induced rhinitis, are quite well defined, but in the majority of the patients, the etiology and pathophysiology are unknown. These patients are classified as idiopathic rhinitis patients. A careful determination of the intensity of the symptoms combined with modern diagnostic tools enables us to discriminate idiopathic rhinitis patients from normal controls. This review discusses the possible pathophysicologic mechanisms of nonallergic noninfectious rhinitis, with emphasis on idiopathic rhinitis.
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BackgroundSelf-citationDifferences between allergic and nonallergic rhinitis in a large sample of adolescents and adults
Mølgaard, E., Thomsen, S. F., Lund, T. K., Pedersen, L., Nolte, H., & Backer, V. (2007) · Allergy · doi:10.1111/j.1398-9995.2007.01355.x · Cited by 133 · see citing works
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Persistent rhinitis – allergic or nonallergic?
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“endotoxin and beta(1,3)-glucan) in compost workers (16), and vanadium pentoxide, a respiratory irritant constituent of fuel oil ash, in boilermakers (17), have demonstrated Figure 1.”
BackgroundIdiopathic rhinitis, the ongoing quest
van Rijswijk, J. B., Blom, H. M., & Fokkens, W. J. (2005) · Allergy · doi:10.1111/j.1398-9995.2005.00975.x · Cited by 104 · see citing works
“The exact figures are unknown but most ear nose and throat (ENT) clinics report a 50–50% division between allergic and nonallergic patients in perennial rhinitis (4).”
BackgroundSelf-citationNon-Allergic Rhinitis with Eosinophils and Mast Cells Constitutes a New Severe Nasal Disorder
Gelardi, M., Giudice, A. M. D., Fiorella, M. L., Fiorella, R., Russo, C., Soleti, P., Gioacchino, M. D., & Ciprandi, G. (2008) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200802100209 · Cited by 91 · see citing works
Nonallergic rhinitis with eosinophilia syndrome
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“The syndrome appears to have a female predominance [1,10, 12 ].”
BackgroundLocal allergic rhinitis: concept, clinical manifestations, and diagnostic approach.
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“However, mismatch of clinical disease and sensitization often occurs (2, 3).”
BackgroundMethodInfluentialCapsaicin for non-allergic rhinitis
Gevorgyan, A., Segboer, C., Gorissen, R., van Drunen, C. M., & Fokkens, W. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010591.pub2 · Cited by 52 · see citing works
Self-citationMechanisms of vasomotor rhinitis
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“, hypo-reactivity of the sympathetic system and hyper-reactivity of the parasympathetic system; resulting in functional abnormality of the nasal end organs in these patients (4).”
BackgroundIntranasal corticosteroids for non-allergic rhinitis
Segboer, C. L., Gevorgyan, A. M., Avdeeva, K. S., Chusakul, S., Kanjanaumporn, J., Aeumjaturapat, S., Reeskamp, L. F., Snidvongs, K., & Fokkens, W. J. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010592.pub2 · Cited by 48 · see citing works
Self-citationDiagnosis of Obstructive Sleep Apnea in Patients with Allergic and Non-Allergic Rhinitis
Pace, A., Iannella, G., Rossetti, V., Visconti, I. C., Gulotta, G., Cavaliere, C., Vito, A. D., Maniaci, A., Cocuzza, S. G., Magliulo, G., et al. (2020) · Medicina · doi:10.3390/medicina56090454 · Cited by 37 · see citing works
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Diagnosis and treatment of non-allergic rhinitis: focus on immunologic mechanisms
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“choice for NARES due to underlying eosinophilic inflammation [40,41].”
BackgroundLocal mucosal immunoglobulin E production: does allergy exist in non‐allergic rhinitis?
Powe, D. G., & Jones, N. S. (2006) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2006.02593.x · Cited by 31 · see citing works
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Schwellnus, M. P., Adami, P. E., Bougault, V., Budgett, R., Clemm, H. H., Derman, W. E., Erdener, U., Fitch, K. D., Hull, J. H., McIntosh, C., et al. (2022) · British Journal of Sports Medicine · doi:10.1136/bjsports-2022-105567 · Cited by 32 · see citing works
“corticosteroid is the treatment of choice.(76, 77) In cases where there is no suspected inflammatory component, ipratropium is the preferred treatment for e.”
BackgroundLieberman, P., & Pattanaik, D. (2014) · Current Allergy and Asthma Reports · doi:10.1007/s11882-014-0439-3 · Cited by 26 · see citing works
“, hyporeactivity of the sympathetic system and hyperreactivity of the parasympathetic system, resulting in functional abnormalities of the nasal end organs in these patients [61].”
BackgroundRole of inflammation in non-allergic rhinitis
Corso, E. D., Battista, M., Pandolfini, M., Liberati, L., Baroni, S., Romanello, M., Passàli, G. C., Fetoni, A. R., Sergi, B., Nardo, W. D., et al. (2014) · Rhinology Journal · doi:10.4193/rhino13.102 · Cited by 25 · see citing works
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Prevalence and determinants of allergic diseases in a Congolese population
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Intranasal Flunisolide Treatment in Patients with Non-Allergic Rhinitis
Varricchio, A., Capasso, M., Lucia, A. D., Avvisati, F., Varricchio, A., Bettoncelli, G., & Ciprandi, G. (2011) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201102400213 · Cited by 21 · see citing works
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“Nonallergic rhinitis (NAR) is currently considered as a condition that must be diagnosed by exclusion [1–3].”
Tantilipikorn, P., Thanaviratananich, S., Chusakul, S., Benjaponpitak, S., Fooanant, S., Chintrakarn, C., Jirapongsananuruk, O., Visitsunthorn, N., Toler, T., Sutton, L., et al. (2010) · The Open Respiratory Medicine Journal · doi:10.2174/1874306401004010092 · Cited by 17 · see citing works
Inflammatory Cell Patterns in the Nasal Mucosa of Patients with Idiopathic Rhinitis
Çomoğlu, Ş., Keles, N., & Değer, K. (2012) · American Journal of Rhinology & Allergy · doi:10.2500/ajra.2012.26.3725 · Cited by 15 · see citing works
Non Allergic Rhinitis: Prevalence, Clinical Profile and Knowledge Gaps inLiterature
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Meng, Y., Yan, B., Wang, Y., Wu, D., Zhang, L., & Wang, C. (2020) · World Allergy Organization Journal · doi:10.1016/j.waojou.2020.100134 · Cited by 12 · see citing works
“These results are not in full agreement with those of previous studies, in which NARES was demonstrated to display female predominance.(11,31,32) It was interesting to note that there was no significant difference between the AR and NARES groups, which were highly associated with eosinophilic airway inflammation, comp…”
ResultAllergic and Non-allergic Rhinitis
Al-Ahmad, M. S., Hassab, M., & Ansari, A. A. (2020) · Springer eBooks · doi:10.1007/978-3-030-54088-3_22 · Cited by 11 · see citing works
Levin, M., Tan, L. W., Baker, L., Wormald, P. J., Greiff, L., & Ohlin, M. (2011) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2011.03724.x · Cited by 10 · see citing works
Clinically relevant outcome measures of novel pharmacotherapy for nonallergic rhinitis
Brown, K. R., & Bernstein, J. A. (2015) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000166 · Cited by 11 · see citing works
“of dysautonomia is secondary to overactivity of the parasympathetic nervous system that causes vasodilation and increases mucous secretion resulting in nasal congestion and anterior or posterior drainage [14].”
BackgroundNejad, M. M., Salehi, E., Mesdaghi, M., Atarod, L., Movahedi, M., Gheflati, Z., Aboufazeli, T., & Vodjgani, M. (2013) · PubMed · Cited by 9 · see citing works
Joe, S. A. (2011) · Facial Plastic Surgery Clinics of North America · doi:10.1016/j.fsc.2011.10.003 · Cited by 8 · see citing works
“Other terms used include perennial rhinitis, idiopathic rhinitis, perennial NAR, and nonallergic, noninfectious perennial rhinitis.(2,8,11,12) Nonallergic rhinitis is the term used in this article to describe the various forms of the symptom complex of nasal congestion, obstruction, intermittent rhinorrhea as well as…”
BackgroundInfluentialDie (ausschließlich) lokale IgE-Produktion in der Nasenschleimhaut
Klimek, L., von Bernus, L., & Pfaar, O. (2012) · HNO · doi:10.1007/s00106-012-2584-0 · Cited by 9 · see citing works
The Role of Nasal Cytology and Serum Atopic Biomarkers in Paediatric Rhinitis
Dodi, G., Filippo, P. D., Ciarelli, F., Porreca, A., Cazzato, F., Matonti, L., Pillo, S. D., Neri, G., Chiarelli, F., & Attanasi, M. (2023) · Diagnostics · doi:10.3390/diagnostics13030555 · Cited by 8 · see citing works
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The Diagnosis of Non-Allergic Rhinitis
van Waterschoot, J., Gerven, L. V., Pfirrman, S., Greiwe, J. C., & Bernstein, J. A. (2025) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2025.09.003 · Cited by 6 · see citing works
Mari, A. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2004.04.016 · Cited by 6 · see citing works
“Several papers which addressed and reviewed clinical [55–58] and immunopathological features [59–64] of IgE and non-IgE-mediated forms at different organ levels have underlined that much more similarities rather than differences can be found between these two conditions [65,66].”
BackgroundDeveloping nomograms for identifying allergic rhinitis among chronic rhinitis: A real-world study
Huang, Y., Wang, C., Zhang, Y., & Zhang, L. (2021) · World Allergy Organization Journal · doi:10.1016/j.waojou.2021.100534 · Cited by 6 · see citing works
Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis
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“An increase in nasal epithelial permeability might contribute to the disease development by enabling irritants, infection and cellular components such as eosinophil MBP/ECP to reach sensory nerve endings, vessels and secretory glands (6).”
BackgroundCapsaicin for non-allergic rhinitis
Gevorgyan, A. M., Segboer, C. L., Gorissen, R., van Drunen, C. M., & Fokkens, W. J. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010591 · Cited by 6 · see citing works
Self-citationDifferential Diagnosis in Allergy
Stachler, R. J., & Al‐Khudari, S. (2011) · Otolaryngologic Clinics of North America · doi:10.1016/j.otc.2011.03.017 · Cited by 5 · see citing works
Intranasal corticosteroids for non-allergic rhinitis
Gevorgyan, A. M., Segboer, C. L., Chusakul, S., Kanjanaumporn, J., Aeumjaturapat, S., Reeskamp, L. F., Fokkens, W. J., & Snidvongs, K. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010592 · Cited by 5 · see citing works
Self-citationThe effect of single kinetic oscillation stimulation treatment on nonallergic rhinitis
Sainio, S., Blomgren, K., Laulajainen‐Hongisto, A., & Lundberg, M. (2023) · Laryngoscope Investigative Otolaryngology · doi:10.1002/lio2.1048 · Cited by 4 · see citing works
“Increased parasympathetic activity leads to increased mucus production, whereas decreased sympathetic activity leads to increased vascular permeability and, hence, mucosal edema.(2) The mechanism of KOS is believed to stem in the short term from KOS mimicking naturally occurring air turbulence in the nasal cavity, and…”
BackgroundJoe, S. A., & Patel, S. (2010) · Elsevier eBooks · doi:10.1016/b978-0-323-05283-2.00047-1 · Cited by 4 · see citing works
Physiology of the Aging Nose and Geriatric Rhinitis
Eliyan, Y., Varga-Huettner, V. E., & Pinto, J. M. (2023) · Springer eBooks · doi:10.1007/978-3-031-12386-3_14 · Cited by 3 · see citing works
[Non-allergic chronic rhinitis].
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A high school gym-induced disease
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“whereas there are no sound data to support this notion.(3) The disease is ‘‘non-allergic’’ when allergy has not been proven by”
Association between Vasomotor Rhinitis and Irritable Bowel Syndrome
Lauriello, M., Eibenstein, A., Angelone, A. M., Pasqua, M. B., Tucci, C., Giacomo, C. D., Salerno, A., Frieri, G., & Fusetti, M. (2016) · Allergy & Rhinology · doi:10.2500/ar.2016.7.0184 · Cited by 3 · see citing works
“Periodic obstruction 8 (16) 18 (36) 6 (12) Alternating obstruction 6 (12) 5 (10) 9 (18) Persistent obstruction 36 (72) 15 (30) 3 (6) No obstruction — 12 (24) — Persistent rhinorrhea 35 (70) 7 (14) 1 (2) Periodic rhinorrhea 15 (30) 22 (44) 10 (20) No rhinorrhea — 21 (42) 39 (78) Normal turbinates — 7 (14) 33 (66) Hyper…”
Physiology of the Aging Nose and Geriatric Rhinitis
Varga-Huettner, V. E., & Pinto, J. M. (2013) · Springer eBooks · doi:10.1007/978-3-642-37250-6_13 · Cited by 2 · see citing works
New Findings in Nonallergic Rhinitis and Local Allergic Rhinitis
Segboer, C. L., van Drunen, C. M., Terreehorst, I., Rondón, C., Hellings, P. W., & Fokkens, W. J. (2013) · Current Otorhinolaryngology Reports · doi:10.1007/s40136-013-0013-x · Cited by 2 · see citing works
“occupational rhinitis [12, 13].”
Self-citationMometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study
Rizzi, A., Parrinello, G., Corso, E. D., Tricarico, L., Centrone, M., Rienzo, A. D., Laface, C., Passàli, G. C., Cadoni, G., Inchingolo, R., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12071179 · Cited by 2 · see citing works
Cochrane corner: Intranasal corticosteroids for non‐allergic rhinitis
Gregory, I., & Grewal, A. (2022) · Clinical & Experimental Allergy · doi:10.1111/cea.14151 · Cited by 2 · see citing works
KASSEM, M. S. E. M. K. S. M. S. M., & Aglan, Y. I. (2019) · The Medical Journal of Cairo University/The Medical Journal of Cairo University · doi:10.21608/mjcu.2019.52321
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- Authors
- Fokkens, W. J.
- Affiliations
- Erasmus MC (NL)
- Corresponding author
- Fokkens, Wytske J.
- ORCID
- Fokkens, Wytske J.
- Venue
- Current Allergy and Asthma Reports
- Published
- 2002-05
- Volume
- 2
- Issue
- 3
- Pages
- 203-209
- ISSN
- 1529-7322 (ISSN-L)
- 1534-6315
- PMC
- PMC7089100
- OpenAlex
- W2033104308
- Cited by
- 65
- References
- 66
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 5 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 0.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Allergy and Asthma Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Otorhinolaryngology › Sinusitis and nasal conditions
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- non-allergic rhinitis, vasomotor rhinitis, pathophysiology, diagnosis of exclusion, drug-induced rhinitis, nasal symptoms
- MeSH terms
- Diagnosis, Differential, Humans, Nervous System, Nose, Rhinitis, Respiratory Mucosa
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