Intranasal corticosteroids for the treatment of perennial allergic rhinitis.

Allergic rhinitis is a one of the most common chronic diseases, affecting 10 to 30% of adults and up to 40% of children. (1) Allergic rhinitis is typically categorized based on the timing of the rhinitis symptoms as either seasonal or perennial. One problem with this description is that certain allergens that are seasonal in some areas may be perennial in others. The recent ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines reclassified allergic rhinitis based on a patient's symptom frequency (intermittent and persistent) and severity (mild and moderate/severe). (2)

In this issue of the Southern Medical Journal, Bruton and Fromer give an excellent overview of the current treatment options available for perennial allergic rhinitis (PAR) with a focus on intranasal corticosteroids. In this editorial, I will expand on the key points which Drs. Bruton and Fromer discuss.

The first step in allergic rhinitis therapy is allergen avoidance. The diagnosis of allergic rhinitis can be made presumptively based on the history, but confirmation testing (by skin testing or IgE RAST) is often necessary to differentiate between allergic and nonallergic rhinitis and identify the specific allergic triggers. Typical allergens associated with PAR include dust mites, animal dander, cockroach and indoor molds. Most US homes have dust mite allergens present with levels in bedrooms associated with allergic sensitization. (3) In addition, dog and cat allergens are universally found in homes, even in homes without animals. (4) Several allergens may be contributing to the perennial symptoms, thus reduction in levels of one allergen may offer no clinical improvement. When extensive environmental interventions are applied, indoor allergen levels decrease and allergic symptoms improve. (5)

Pharmacologically, the most effective treatments for allergic rhinitis are intranasal corticosteroids, oral antihistamines, and leukotriene receptor antagonists. Characteristic symptoms of PAR include year-round nasal congestion and postnasal drainage with less rhinorrhea and sneezing than in seasonal allergic rhinitis. Intranasal corticosteroids reduce individual nasal symptoms (sneezing, rhinorrhea, itching, postnasal drip, and nasal blockage) and total nasal symptom score better than with antihistamines. (6,7) Leukotriene receptor antagonists are no more effective than antihistamines and are less effective than intranasal corticosteroids in the treatment of allergic rhinitis. (8)

Current preparations of intranasal corticosteroids have potential differences based upon the individual corticosteroid compound. Mometasone furoate and fluticasone propionate are highly lipophilic, allowing greater uptake and retention into the nasal mucosa. (9) In addition, several different measurements of corticosteroid potency also favor mometasone furoate and fluticasone propionate. (9) The estimated systemic bioavailability by intranasal administration varies greatly from 49% (flunisolide) to less than 1% (both mometasone furoate and fluticasone propionate). (9) Despite these differences, all nasal preparations are considered equally efficacious in the treatment of allergic rhinitis. (10)

Side effects of intranasal corticosteroids are typically local. While regular topical corticosteroid use in atopic dermatitis may lead to skin atrophy, no evidence exists that the proper chronic use of intranasal corticosteroids leads to nasal mucosal atrophy. (11) When used at recommended doses, intranasal corticosteroids do not effect the hypothalamic-pituitary-adrenal (HPA) axis. (9) In children, the effect of corticosteroids on linear growth may be an early manifestation of systemic absorption. The first study to evaluate the effect of intranasal corticosteroids on growth was a one year study of children 6 to 9 years old with PAR treated with beclomethasone dipropionate 168 [micro]g twice daily. (12) The children treated with beclomethasone dipropionate grew 0.9 cm less compared with the placebo-treated children despite having no measurable effect on the HPA axis. Factors that may have played a role in this result include twice daily dosing with a relatively high intranasal bioavailability of 44%. No effect on growth rate has been demonstrated with other intranasal corticosteroids when used for 1 to 2 years, including budesonide, triamcinolone acetonide, fluticasone propionate, and mometasone furoate. (13-16)

Allergen immunotherapy and omalizumab (anti-IgE antibodies) treatment are considered immunomodulating therapies, altering the allergic pathway. Allergen immunotherapy is effective for pollen, mold, animal dander, dust mite, and cockroach allergies. Symptomatic patients with allergic rhinitis despite allergen avoidance and pharmacotherapy are candidates for immunotherapy. Other candidates include allergic rhinitis patients having undesirable adverse reactions to medications, or those wishing to reduce or eliminate long-term pharmacotherapy. In addition to reducing symptoms to current allergens, immunotherapy may prevent the development of sensitization to new allergens or progression of allergic rhinitis to asthma, especially in children. (17) Although newer pharmacological agents continue to become available, immunotherapy is still the only available treatment that alters the natural course of allergic rhinitis.

Omalizumab binds to free serum IgE, decreasing expression of IgE on the surface of allergic effector cells. The U.S. Food and Drug Administration approved omalizumab for the treatment of moderate to severe persistent perennial allergic asthma in patients 12 or older. Studies have demonstrated that omalizumab is also effective in reducing symptoms and improving quality of life in patients with PAR. (18) The benefits of omalizumab may not be long-term as serum IgE levels return to baseline when the therapy is discontinued.

With many options available for treatment, intranasal corticosteroids are still the backbone of therapy for perennial allergic rhinitis, or moderate-severe persistent symptoms when using the ARIA guidelines. With newer intranasal formulations available, physicians have many choices to fit each patient's individual needs or preferences.

References

1. Newacheck PW, Stoddard JJ. Prevalence and impact of multiple childhood chronic illnesses. J Pediatr 1994;124:40-48.

2. Bousquet J, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108(5 Suppl):S147-S334.

3. Arbes SJ Jr, Cohn RD, Yin M, et al. House dust mite allergen in US beds: results from the First National Survey of Lead and Allergens in Housing. J Allergy Clin Immunol 2003;111:408-414.

4. Arbes SJ Jr, Cohn RD, Yin M, et al. Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: results from the National Survey of Lead and Allergens in Housing. J Allergy Clin Immunol 2004;114:111-117.

5. Morgan WJ, Crain EF, Gruchalla RS, et al. Results of a home-based environmental intervention among urban children with asthma. N Engl J Med 2004;351:1068-1080.

6. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral HI receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998;317:1624-1629.

7. Yanez A, Rodrigo GJ. Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Ann Allergy Asthma Immunol 2002;89:479-484.

8. Nathan RA. Pharmacotherapy for allergic rhinitis: a critical review of leukotriene receptor antagonists compared with other treatments. Ann Allergy Asthma Immunol 2003;90:182-191.

9. Allen DB. Systemic effects of intranasal steroids: an endocrinologist's perspective. J Allergy Clin Immunol 2000;106:S179-190.

10. Corren J. Intranasal corticosteroids for allergic rhinitis: how do different agents compare? J Allergy Clin Immunol 1999;104(4 Pt 1):S144-149.

11. Holm AF, Fokkens WJ, Godthelp T, et al. A 1-year placebo-controlled study of intranasal fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis: a safety and biopsy study. Clin Otolaryngol Allied Sci 1998;23:69-73.

12. Skoner DP, Rachelefsky GS, Meltzer EO, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics 2000;105:E23.

13. Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics 2000; 105:E22.

14. Ober S, Gentile D, Kairis E, et al. Growth velocity and HPA axis function during 1-year treatment with triamcinolone acetonide aqueous (TAA) nasal spray in children with allergic rhinitis. J Allergy Clin Immunol 2005;115:S267.

15. Allen DB, Meltzer EO, Lemanske RF Jr, et al. No growth suppression in children treated with the maximum recommended dose of fluticasone propionate aqueous nasal spray for one year. Allergy Asthma Proc 2002; 23:407-413.

16. Moller C, Ahlstrom H, Henricson KA, et al. Safety of nasal budesonide in the long-term treatment of children with perennial rhinitis. Clin Exp Allergy 2003;33:816-822.

17. Joint Task Force on Practice Parameters. Allergen immunotherapy: a practice parameter. American Academy of Allergy, Asthma and Immunology. American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol 2003;90:1-40.

18. Chervinsky P, Casale T, Townley R, et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2003;91:160-167.

Jeff Stokes, MD, FAAAAI, FACAAI

From the Allergy/Immunology Division, Department of Medicine, Creighton University Medical Center, Omaha. NE.

Reprint requests to Jeff Stokes, MD, FAAAAI, FACAAI, Assistant Professor, Department of Medicine, Allergy/Immunology Division, Creighton University Medical Center, 601 North 30th Street, Omaha, NE 68131. Email: [e-mail]