Nonallergic rhinitis with eosinophilia syndrome

Abstract

Nonallergic rhinitis with eosinophilia syndrome (NARES) is a clinical syndrome comprising symptoms consistent with allergic rhinitis in which an absence of atopy has been demonstrated by allergen skin testing, and nasal cytology analysis demonstrates more than 20% eosinophils. Anosmia is a prominent feature not shared with allergic rhinitis. The pathophysiology of NARES is poorly understood, but a key component involves a self-perpetuating, chronic eosinophilic nasal inflammation with development of nasal micropolyposis and polyposis. Mast cells likely play an important role as well. NARES is a risk factor for the development of nasal polyposis and aspirin sensitivity, as well as obstructive sleep apnea. Treatment consists mainly of intranasal corticosteroids with or without the addition of second-generation antihistamines and/or leukotriene-receptor antagonists.

This is a preview of subscription content, log in to check access.

References and Recommended Reading

  1. 1.

    World Health Organisation Initiative, Bousquet J, van Cauwenberge P: Allergic Rhinitis and Its Impact on Asthma (ARIA). Geneva: WHO; 2000.

  2. 2.

    Jacobs RL, Freedman PM, Boswell RN: Nonallergic rhinitis with eosinophilia (NARES syndrome). Clinical and immunologic presentation. J Allergy Clin Immunol 1981, 67:253–262.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Settipane RA, Lieberman P: Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 2001, 86:494–507.A recent and thorough review on the topic of nonallergic rhinitis

    PubMed  CAS  Google Scholar 

  4. 4.

    van Cauwenberge P, Wang D-Y, Ingels KJAO, Bachert C: Rhinitis: the spectrum of the disease. In Asthma and Rhinitis. Edited by Busse WW, Holgate ST. Oxford: Blackwell Science; 2000:6–13.

    Google Scholar 

  5. 5.

    Schiavano D, Nucera E, Milani A, et al.: Nasal lavage cytometry in the diagnosis of nonallergic rhinitis with eosinophilia syndrome (NARES). Allergy Asthma Proc 1997, 18:363–366.

    Article  Google Scholar 

  6. 6.

    Mygind N, Dirkasen A, Johnsen NJ, Weeke B: Perennial rhinitis: an analysis of skin testing, serum IgE and blood and smear eosinophilia in 201 patients. Clin Otolarygol 1978, 3:189–196.

    CAS  Google Scholar 

  7. 7.

    Mullarkey MF, Hill JS, Webb DR: Allergic and non-allergic rhinitis: their characterization with attention to the meaning of nasal eosinophilia. J Allergy Clin Immunol 1980, 65:122–126.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Settipane GA, Klein DE: Non allergic rhinitis: demography of eosinophils in nasal smear, blood total eosinophil counts and IgE levels. N Engl Reg Allergy Proc 1985, 6:363–366.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Crobach M, Hermans J, Kaptein A, et al.: Nasal smear eosinophilia for the diagnosis of allergic rhinitis and eosinophilic non-allergic rhinitis. Scand J Prim Health Care 1996, 14:116–121.

    PubMed  CAS  Google Scholar 

  10. 10.

    Moneret-Vautrin DA, Hsieh V, Wayoff M, et al.: Nonallergic rhinitis with eosinophilia syndrome a precursor of the triad: nasal polyposis, intrinsic asthma, and intolerance to aspirin. Ann Allergy 1990, 64:513–518.

    PubMed  CAS  Google Scholar 

  11. 11.

    Kramer MF, de la Chaux R, Fintelmann R, Rasp G: NARES: A risk factor for obstructive sleep apnea? Am J Otolaryngol 2004, 25:173–177.

    PubMed  Article  Google Scholar 

  12. 12.

    Fokkens WJ: Thoughts on the pathophysiology of nonallergic rhinitis. Curr Allergy Asthma Rep 2002, 2:203–209.

    PubMed  Article  Google Scholar 

  13. 13.

    Leone C, Teodoro C, Pelucchi A, et al.: Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with eosinophilia syndrome. J Allergy Clin Immunol 1997, 100:775–780.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Marshall KG, Attia EL, Danoff D: Vasomotor rhinitis. In Disorders of the Nose, Paranasal Sinuses. Edited by Marshall KG, Attia EL. Littleton: PSG Publishing; 1987:195–203.

    Google Scholar 

  15. 15.

    Moneret-Vautrin DA, Jankowski R, Wayoff M: [Clinical and pathogenic aspects of NARES (non-allergic rhinitis with eosinophilic syndrome)]. Rev Laryngol Otol Rhinol (Bord ) 1991, 112:41–44.

    CAS  Google Scholar 

  16. 16.

    Di Lorenzo G, Drago A, Pellitteri ME, et al.: Measurement of inflammatory mediators of mast cells and eosinophils in native nasal lavage fluid in nasal polyposis. Int Arch Allergy Immunol 2001, 125:164–175.

    Article  Google Scholar 

  17. 17.

    Craig SS, Schwartz LB: Tryptase and chymase, markers of distinct types of human mast cells. Immunol Res 1989, 8:130–138.

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Schwartz LB, Kawahara MS, Hugli TE, et al.: Generation of C3a anaphylatoxin from human C3 by human mast cell tryptase. J Immunol 1983, 130:1891–1895.

    PubMed  CAS  Google Scholar 

  19. 19.

    Togias A, Naclerio RM, Proud D, et al.: Studies on the allergic and nonallergic nasal inflammation. J Allergy Clin Immunol 1988, 81:782–790.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Kramer MF, Rasp G: Nasal polyposis: eosinophils and interleukin-5. Allergy 1999, 54:669–680.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Klimek L, Rasp G: Norm values for eosinophil cationic protein in nasal secretions: influence of specimen collection. Clin Exp Allergy 1999, 29:367–374.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Kramer MF, Burow G, Pfrogner E, Rasp G: In vitro diagnosis of chronic nasal inflammation. Clin Exp Allergy 2004, 34:1086–1092. The most recent evaluation into differences in pathophysiology between NARES, nasal polyposis, allergic rhinitis, and sinusitis; provides useful insights into the same.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Bousquet J, Chanez P, Lacoste JY, et al.: Eosinophilic inflammation in asthma. N Engl J Med 1990, 333:1033–1039.

    Article  Google Scholar 

  24. 24.

    Flavahan NA, Slifman NR, Gleich GJ, Vanhoutte PM: Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Am Rev Respir Dis 1988, 138:685–688.

    PubMed  CAS  Google Scholar 

  25. 25.

    Venge P, Dahl R, Fredens K, Peterson CG: Epithelial injur y by human eosinophils. Am Rev Respir Dis 1988, 138:S54-S57.

    PubMed  CAS  Google Scholar 

  26. 26.

    Hastie AT, Loegering DA, Gleich GJ, Kueppers F: The effect of purified human eosinophil major basic protein on mammalian ciliary activity. Am Rev Respir Dis 1987, 135:848–853.

    PubMed  CAS  Google Scholar 

  27. 27.

    Davidson AE, Miller SD, Settipane RJ, et al.: Delayed nasal mucociliary clearance in patients with nonallergic rhinitis and nasal eosinophilia. Allergy Proc 1992, 13:81–84.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Baraniuk J: Neuroregulation. Proceedings of the St.Thomas Aventis Meeting, 1-14. 2000.

  29. 29.

    Baraniuk J, Silver PB, Kaliner MA, Barnes PJ: Perennial rhinitis subjects have altered vascular, glandular, and neural responses to bradykinin nasal provocation. Int Arch Allergy Immunol 2005, 103:202–208.

    Article  Google Scholar 

  30. 30.

    Ricchio MM, Reynolds CJ, Hay DW, Proud D: Effects of intranasal administration of endothelin-1 to allergic and non-allergic individuals. Am J Respir Crit Care Med 1995, 152:1757–1764.

    Google Scholar 

  31. 31.

    Ricchio MM, Proud D: Evidence that enhanced neural reactivity to bradykinin in patients with symptomatic allergy is mediated by neural reflexes. J Allergy Clin Immunol 1996, 97:1252–1253.

    Article  Google Scholar 

  32. 32.

    Wilde AD, Cook JA, Jones AS: The nasal response to isometric exercise in non-eosinophilic intrinsic rhinitis. Clin Otolaryngol 1996, 21:84–86.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Powe DG, Huskisson RS, Carney AS, et al.: Evidence for an inflammatory pathophysiology in idiopathic rhinitis. Clin Exp Allergy 2001, 31:864–872.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Romero JN, Scadding GK: Eosinophilia in nasal secretions compared to skin prick test and nasal challenge test in the diagnosis of nasal allergy. Rhinology 1992, 30:169–175.

    PubMed  CAS  Google Scholar 

  35. 35.

    Powe DG, Jagger C, Kleinjan A, et al.: "Entopy": localized mucosal allergic disease in the absence of systemic responses for atopy. Clin Exp Allergy 2003, 33:1374–1379. Further evidence to support the hypothesis that perhaps "non-allergic" rhinitis is actually allergic but with only local manifestations (ie, local IgE production).

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Carney AS, Powe DG, Huskisson RS, Jones NS: Atypical nasal challenges in patients with idiopathic rhinitis: More evidence for the existence of allergy in the absence of atopy? Clin Exp Allergy 2002, 32:1436–1440.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Scadding GK: Non-allergic rhinitis: diagnosis and management. Curr Opin Allergy Clin Immunol 2001, 1:15–20.

    PubMed  CAS  Google Scholar 

  38. 38.

    Keith P, Dolovich J: Allergy and nasal polyposis. In Nasal polyposis-An Inflammatory Disease and Its Treatment. Edited by Mygind N, Lildholdt T. Copenhagen: Munksgaard; 1997:68–77.

    Google Scholar 

  39. 39.

    Redegeld F, van der Heijden M, Kool M, et al.: Immunoglobulin-free light chains elicit immediate hypersensitivity- like responses. Nature Med 2002, 8:694–701.

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Kraneveld A, Kool M, van Houwelingen A, et al.: Elicitation of allergic asthma by immunoglobulin free light chains. PNAS 2005, 102:1578–1583.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Webb DR, Meltzer EO, Finn AF Jr, et al.: Intranasal fluticasone propionate is effective for perennial nonallergic rhinitis with or without eosinophilia. Ann Allergy Asthma Immunol 2002, 88:385–390.

    PubMed  CAS  Article  Google Scholar 

  42. 42.

    Mygind N: Effects of corticosteroid therapy in non-allergic rhinosinusitis. Acta Otolaryngol 1996, 116:164–166.

    PubMed  CAS  Google Scholar 

  43. 43.

    Mygind N, Lildholdt T: Nasal polyps treatment: medical management. Allergy Asthma Proc 1996, 17:275–282.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Purello-D’Ambrosio F, Isola S, Ricciardi L, et al.: A controlled study on the effectiveness of loratadine in combination with flunisolide in the treatment of nonallergic rhinitis with eosinophilia (NARES). Clin Exp Allergy 1999, 29:1143–1147.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Peters-Golden M, Henderson WR Jr: The role of leukotrienes in allergic rhinitis. Ann Allergy Asthma Immunol 2005, 94:609–618.

    PubMed  CAS  Google Scholar 

  46. 46.

    Berges-Gimeno MP, Simon RA, Stevenson DD: The effect of leukotriene-modifier drugs on aspirin-induced asthma and rhinitis reactions. Clin Exp Allergy 2002, 32:1491–1496.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Bachert C, Watelet JB, Gevaert P, Van Cauwenberge P: Pharmacological management of nasal polyposis. Drugs 2005, 65:1537–1552.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Saito H, Morikawa H, Howie K, et al.: Effects of a cysteinyl leukotriene receptor antagonist on eosinophil recruitment in experimental allergic rhinitis. Immunology 2004, 113:246–252.

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Menzies-Gow A, Flood-Page P, Sehmi R, et al.: Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J Allergy Clin Immunol 2003, 111:714–719.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Paul K. Keith MD, MSc, FRCPC.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ellis, A.K., Keith, P.K. Nonallergic rhinitis with eosinophilia syndrome. Curr Allergy Asthma Rep 6, 215–220 (2006). https://doi.org/10.1007/s11882-006-0037-0

Download citation

Keywords

  • Obstructive Sleep Apnea
  • Rhinitis
  • Allergic Rhinitis
  • Allergic Rhinitis
  • Allergy Clin Immunol