Getting allergic rhinitis under control: Part 2

May 1, 2005
William E. Berger, MD, MBA
William E. Berger, MD, MBA

Volume 5, Issue 5

Most of the symptoms of allergic rhinitis, including nasal obstruction, rhinorrhea, sneezing, and nasal itching, respond to intranasal corticosteroids administered once or twice daily. However, many patients also need to take an antihistamine for adequate control of symptoms. While an antihistamine/decongestant combination can provide symptomatic relief, it fails to address the inflammatory component of allergic rhinitis. Thus, combining an intranasal corticosteroid or oral leukotriene modifier with an antihistamine might be a more effective strategy. Factors that can facilitate treatment adherence include minimizing the number of daily doses, allowing patients to select their own dosing schedules, and providing written instructions. Specific immunotherapy can be beneficial in select patients whose allergic rhinitis symptoms are not sufficiently controlled by pharmacotherapy. (J Respir Dis. 2005;26(5):188-194)

Allergic rhinitis is a common medical condition, and numerous pharmacologic agents are available for the management of symptoms. Because many of the medications used to treat allergic rhinitis are available over-the-counter (OTC), patients frequently attempt treatment without consulting a physician. As a result, many of those who do visit a doctor have already experienced treatment failure. Because the various treatment options may overlap or complement one another, the development of an effective treatment plan requires a thoughtful appraisal of the patient's symptoms.

In the April 2005 issue of The Journal of Respiratory Diseases, I reviewed the use of antihistamines, decongestants, and cromolyn for the management of allergic rhinitis. In this article, I will focus on intransasal corticosteroids, leukotriene modifiers, and combination therapy. I will also discuss immunotherapy and patient education.

Intranasal corticosteroids

Since corticosteroids have broad anti-inflammatory and immunosuppressant activity, they are effective as monotherapy for allergic rhinitis when applied topically (Table 1). The anti-inflammatory potential of corticosteroid therapy was demonstrated in a nasal cytology study of patients with allergic rhinitis who were treated with intranasal fluticasone.1 The proportion of patients with nasal eosinophils and basophilic cells significantly decreased after fluticasone treatment.

One 8-week clinical trial compared fluticasone aqueous nasal spray, budesonide in a reservoir powder device, and placebo.2 In weeks 1 to 4, fluticasone effectively lowered total nasal symptom scores, compared with budesonide and placebo, at all time points. Over weeks 1 to 8, it effectively lowered individual scores for sneezing and itching, compared with budesonide, and lowered all individual symptom scores, compared with placebo.2

Most of the symptoms associated with seasonal allergic rhinitis, including nasal obstruction, rhinorrhea, sneezing, and nasal itching, respond to intranasal corticosteroids administered once or twice daily.3 In comparison trials, intranasal corticosteroids were significantly more effective than cromolyn in relieving symptoms of allergic rhinitis.4 Once-daily use of an intranasal corticosteroid has also been shown to be more effective than use of an oral antihistamine in reducing symptoms of seasonal allergic rhinitis and improving quality of life.5,6

A meta-analysis of 9 randomized, controlled, single- or double-blind studies involving 648 patients with allergic rhinitis indicated that total nasal symptom scores were reduced significantly more for those who received intranasal corticosteroids than for those who received oral antihistamines.7 Overall reductions in total individual symptom scores for sneezing, rhinorrhea, itching, and nasal blockage were also significantly greater with intranasal corticosteroids; however, for all symptoms except nasal blockage, individual results varied substantially among the trials.7

While corticosteroids are clearly effective, one study found that at least 50% of patients with allergic rhinitis who were treated with fluticasone still needed to take an antihistamine for adequate control of symptoms.8 In addition, achieving relief of symptoms with intranasal corticosteroids may take several days, and sustaining this relief requires long-term administration.

Corticosteroids can have a prophylactic effect when given to patients with seasonal allergic rhinitis before the start of an allergy season. In a randomized study, intranasal triamcinolone acetonide administered preseasonally was found to prevent nasal symptoms and reduce the severity of subsequent symptoms in patients with allergic rhinitis.9 Patients received triamcinolone once daily for 6 weeks; treatment was started at least 1 week before significant ragweed pollen was detected.

Intranasal corticosteroids are generally safe; they have few systemic adverse effects and few effects on plasma cortisol levels.10 However, in 2000, aqueous beclomethasone nasal spray was reported to cause growth inhibition in children.11 A 1-year study of 100 prepubertal children who had perennial allergic rhinitis indicated that those treated with aqueous beclomethasone, 168 µg twice daily, had a significantly lower over- all growth rate than did placebo-treated children.11

However, subsequent studies and several published analyses of the relevant literature indicate that intranasal corticosteroids, used in prescribed doses, are not associated with restricted skeletal growth in children.12-16 Because some children may be particularly at risk, careful attention to height measurements should be maintained throughout therapy.

Leukotriene antagonists

The recognized role of cysteinyl leukotrienes (CysLT) in the pathophysiology of allergic and inflammatory diseases provides a rationale for the use of leukotriene antagonists in the treatment of allergic rhinitis. Leukotrienes released during the allergic response play a role in chemotaxis, and they increase vascular permeability in the nose. Key synthetic and signaling proteins of the CysLT pathway have been identified in eosinophils and mast cells recovered from nasal washes of patients who have active seasonal allergic rhinitis.17

The efficacy of oral leukotriene antagonists in the treatment of allergic rhinitis has been confirmed in clinical trials. In a study of more than 1300 adults with active allergic rhinitis symptoms, montelukast, administered once daily at bedtime for 2 weeks, significantly improved daytime nasal symptoms and quality-of-life scores; montelukast was comparable in efficacy to once-daily loratadine.18 Leukotriene receptor antagonists have also been reported to improve quality of life significantly, when compared with placebo, in patients with rhinoconjunctivitis.18,19

However, a meta-analysis of randomized controlled trials, which included 11 studies of seasonal allergic rhinitis, found that leukotriene receptor antagonists, while effective, were outperformed by antihistamines and intranasal corticosteroids.19 Although leukotriene receptor antagonists reduced mean daily symptom scores compared with placebo, antihistamines reduced those scores by an additional 2%, and intranasal corticosteroids produced reductions that were 12% greater still. In general, leukotriene modifiers may be most appropriate for patients who would prefer not to take corticosteroids.

Combination therapy

When the symptoms of allergic rhinitis are severe or do not respond adequately to monotherapy, combination therapy has proved useful. One of the most commonly used combinations is a nasal decongestant plus an oral antihistamine. Such formulations, which usually include a first-generation antihistamine, are available OTC.

The use of a combination of pseudoephedrine and a second-generation, nonsedating antihistamine can be effective against the entire spectrum of seasonal allergic rhinitis symptoms. Importantly, this combination therapy is reported to have fewer adverse effects on daily activity and work productivity than monotherapy with either drug has.20

While an antihistamine/decongestant combination can provide symptomatic relief, it fails to address the inflammatory component of allergic rhinitis. Therefore, combining an anti-inflammatory, such as a corticosteroid or leukotriene antagonist, with an antihistamine might be a more effective strategy, especially since anti-inflammatory drugs can have prophylactic effects.

In fact, the combination of an oral antihistamine and an intranasal corticosteroid is one of the options included in the 1994 guidelines of the International Consensus Reprt on Rhinitis.21 In one trial, 85% to 90% of patients treated with the combination of loratadine and beclomethasone reported symptomatic improvement and 39% to 46% required no additional medication for allergic rhinitis.22

In one study, combination therapy with montelukast and cetirizine, initiated 6 weeks before the beginning of grass pollen season, was highly effective in controlling symptoms of allergic rhinitis.23 This pretreatment significantly reduced in-season symptom scores for sneezing, eye and nasal itching, rhinorrhea, and congestion. The combination was more effective than cetirizine alone in preventing eye and nasal itching as well as rhinorrhea, and pretreatment delayed the onset of symptoms.

Another study that compared the combination of a nonsedating antihistamine with montelukast or pseudoephedrine found the 2 combinations to be similarly effective in treating symptoms and nasal obstruction in patients with seasonal allergic rhinitis.24 The only noteworthy difference was a lack of improvement in sleep quality among patients who received pseudoephedrine (a drug that is known to disturb sleep quality).

The combination of cetirizine and montelukast has been reported to be as effective as intranasal corticosteroid monotherapy for patients with seasonal allergic rhinitis.25 However, a 2-week study found a significantly greater reduction in nasal symptoms reported on questionnaires by patients who received intranasal fluticasone compared with those who received a loratadine/montelukast combination.26 Eosinophil counts and levels of eosinophil cationic protein, a marker of eosinophil activation, were significantly reduced in the fluticasone group compared with the combination-therapy group. Nevertheless, patients in both treatment groups experienced dramatic improvement in symptoms.26

Specific immunotherapy

The use of specific immunother-apy has proved effective at controlling symptoms in patients with allergic rhinitis who are sensitive to a variety of aeroallergens, including house dust mites, grass and ragweed pollen, and cat dander.27-30 It is recommended when symptoms cannot be adequately controlled with drug therapy or when allergen avoidance is impracticable. Injection is the most common method used to administer the antigen preparations.

Specific immunotherapy has been shown to induce a variety of therapeutic effects in patients with ragweed allergy. In one study, patients who received immunotherapy had a decreased response after allergen challenge--they needed higher pollen doses to elicit sneezing or mediator release from mast cells or basophils in the nose.29 Also, mediator release (at any dose) occurred in significantly fewer patients in the immunotherapy group.

Specific immunotherapy can induce important changes in cell- mediated responses to nasal allergens. In one study, nasal biopsy specimens following grass pollen challenge revealed reduced numbers of infiltrating CD4+ T lymphocytes and eosinophils in patients who received immunotherapy.28

When administered long-term, specific immunotherapy can produce profound changes in specific and nonspecific responses. In patients with house dust mite allergy who received immunotherapy for 3 years, improvements in allergen-specific immune parameters were associated with decreased nonspecific bronchial hyperreactivity; use of medication to control symptoms was also reduced.31

It is important to note that certain potential risks are associated with specific immunotherapy. However, a large retrospective survey of more than 6000 patients found that systemic reactions to specific immunotherapy were infrequent, occurring at a rate of only 0.06%; no cases of anaphylaxis were reported.32 Specific immunotherapy is safe when administered by competent specialists who are trained to manage any adverse systemic reactions that may occur (Table 2).

Patient education

The probability of a successful treatment outcome is increased if the patient enthusiastically participates in therapy. One way of ensuring this is to establish a therapeutic partnership with the patient. This requires educating the patient about his or her disease, the different treatments available, and the likelihood of success associated with those treatments.33

Informing the patient about the causes of allergic rhinitis and providing instructions on the proper use of medications are important steps in encouraging adherence to a therapeutic program. The patient should be made aware of the value of allergen avoidance and should be told about potential drug side effects.

Failed treatment might be an indication of poor adherence or improper use of medication; these are possibilities the health care provider should investigate.21 Factors that contribute to maintaining treatment adherence include minimizing the number of daily doses, allowing patients to select their own dosing schedules, providing written instructions, and maintaining a well-designed reminder chart for the timing of dosing intervals.33

The importance of patient education in the treatment of allergic rhinitis was demonstrated in a study of 90 adults who were treated with beclomethasone nasal spray and given detailed information about the drug and its proper dosing.34 This intervention resulted in successful management of symptoms in more than 80% of patients (They said that they were satisfied with their therapy.)

Patients who had poorer symptom control used significantly less of the corticosteroid than did those who had good control.34 The main reasons reported by patients for lack of adherence were the desire to minimize medication use and the inability to remember to take the medication. In addition, symptoms and trust in the clinician were the major factors that determined the patient's treatment choices.34

Good communication between patient and clinician is essential, since it encourages adherence to therapy, which, in turn, is a predictor of treatment success. Such communication, along with periodic follow-up and appropriate adjustments to treatment, ensures that for most patients, the symptoms of allergic rhinitis can be successfully controlled over the long term.

References:

REFERENCES


1. Meltzer EO, Orgel HA, Rogenes PR, Field EA. Nasal cytology in patients with allergic rhinitis: effects of intranasal fluticasone propionate.

J Allergy Clin Immunol.

1994;94:708-715.
2. Kivisaari E, Baker RC, Price MJ. Comparison of once daily fluticasone propionate aqueous nasal spray with once daily budesonide reservoir powder device in patients with perennial rhinitis.

Clin Exp Allergy.

2001;31:855-863.
3. Ratner PH, Paull BR, Findlay SR, et al. Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily.

J Allergy Clin Immunol.

1992;90(3 pt 1):285-291.
4. Welsh PW, Stricker WE, Chu CP, et al. Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed allergy.

Mayo Clin Proc.

1987;62:125-134.
5. Gehanno P, Desfougeres JL. Fluticasone propionate aqueous nasal spray compared with oral loratadine in patients with seasonal allergic rhinitis.

Allergy.

1997;52:445-450.
6. Condemi J, Schulz R, Lim J. Triamcinolone acetonide aqueous nasal spray versus loratadine in seasonal allergic rhinitis: efficacy and quality of life.

Ann Allergy Asthma Immunol.

2000;84:533-538.
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. Juniper EF, Guyatt GH, Ferrie PJ, Griffith LE. First-line treatment of seasonal (ragweed) rhinoconjunctivitis. A randomized management trial comparing a nasal steroid spray and a nonsedating antihistamine.

CMAJ.

1997;156:1123-1131.
9. Munk ZM, Gross GN, Hampel FC Jr, Ratner PH. Preseasonal, once daily triamcinolone acetonide nasal aerosol for seasonal allergic rhinitis.

Ann Allergy Asthma Immunol.

1997;78:325-331.
10. Storms WW. Treatment of seasonal allergic rhinitis with fluticasone propionate aqueous nasal spray: review of comparator studies.

Allergy.

1995;50(23 suppl):25-29.
11. Skoner DP, Rachelefsky GS, Meltzer EO, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate.

Pediatrics.

2000;105:E23.
12. 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.
13. Mansfield LE, Mendoza CP. Medium and long-term growth in children receiving intranasal beclomethasone dipropionate: a clinical experience.

South Med J.

2002;95:334-340.
14. Waddell AN, Patel SK, Toma AG, Maw AR. Intranasal steroid sprays in the treatment of rhinitis: is one better than another?

J Laryngol Otol.

2003;117:843-845.
15. 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.
16. Benninger MS, Ahmad N, Marple BF. The safety of intranasal steroids.

Otolaryngol Head Neck Surg.

2003;129:739-750.
17. Figueroa DJ, Borish L, Baramki D, et al. Expression of cysteinyl leukotriene synthetic and signalling proteins in inflammatory cells in active seasonal allergic rhinitis.

Clin Exp Allergy.

2003; 33:1380-1388.
18. Philip G, Malmstrom K, Hampel FC, et al. Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled trial performed in the spring.

Clin Exp Allergy.

2002;32:1020-1028.
19. Wilson AM, O'Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis.

Am J Med.

2004;116:338-344.
20. Sussman GL, Mason J, Compton D, et al. The efficacy and safety of fexofenadine HCl and pseudoephedrine, alone and in combination, in seasonal allergic rhinitis.

J Allergy Clin Immunol.

1999;104:100-106.
21. International Consensus Report on the diagnosis and management of rhinitis. International Rhinitis Management Working Group.

Allergy.

1994;49(19 suppl):1-34.
22. Berger WE, Fineman SM, Lieberman P, Miles RM. Double-blind trials of azelastine nasal spray monotherapy versus combination therapy with loratadine tablets and beclomethasone nasal spray in patients with seasonal allergic rhinitis. Rhinitis Study Groups.

Ann Allergy Asthma Immunol.

1999;82:535-541.
23. Kurowski M, Kuna P, Gorski P. Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation.

Allergy.

2004;59:280-288.
24. Moinuddin R, deTineo M, Maleckar B, et al. Comparison of the combinations of fexofenadine-pseudoephedrine and loratadine-montelukast in the treatment of seasonal allergic rhinitis.

Ann Allergy Asthma Immunol.

2004;92:73-79.
25. Wilson AM, Orr LC, Sims EJ, Lipworth BJ. Effects of monotherapy with intra-nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis.

Clin Exp Allergy.

2001;31:61-68.
26. Saengpanich S, deTineo M, Naclerio RM, Baroody FM. Fluticasone nasal spray and the combination of loratadine and montelukast in seasonal allergic rhinitis.

Arch Otolaryngol Head Neck Surg.

2003;129:557-562.
27. Varney VA, Tabbah K, Mavroleon G, Frew AJ. Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial.

Clin Exp Allergy.

2003; 33:1076-1082.
28. Durham SR, Ying S, Varney VA, et al. Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4

+

T lymphocytes and eosinophils in the nasal mucosa and increases the number of cells expressing messenger RNA for interferon-gamma.

J Allergy Clin Immunol.

1996; 97:1356-1365.
29. Creticos PS, Adkinson NF Jr, Kagey-Sobotka A, et al. Nasal challenge with ragweed pollen in hay fever patients. Effect of immunotherapy.

J Clin Invest.

1985;76:2247-2253.
30. Varney VA, Edwards J, Tabbah K, et al. Clinical efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial.

Clin Exp Allergy.

1997;27:860-867.
31. Pichler CE, Helbling A, Pichler WJ. Three years of specific immunotherapy with house-dust-mite extracts in patients with rhinitis and asthma: significant improvement of allergen-specific parameters and of nonspecific bronchial hyperreactivity.

Allergy.

2001;56:301-306.
32. Luigi A, Senna G, Mezzelani P, Pappalardo G. Safety of specific immunotherapy: a retrospective study.

J Investig Allergol Clin Immunol.

1994;4:250-254.
33. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. American Academy of Allergy, Asthma and Immunology.

Ann Allergy Asthma Immunol.

1998; 81:478-518.
34. Juniper EF, Willms DG, Guyatt GH, Ferrie PJ. Aqueous beclomethasone dipropionate nasal spray in the treatment of seasonal (ragweed) rhinitis.

CMAJ.

1992;147:887-892.