Allergic Rhinitis: Update on Your Therapeutic Choices

March 31, 2010

Many pharmacological options exist for allergic rhinitis. Intranasal corticosteroids are the most effective medication class for patients with moderate to severe symptoms; those with milder intermittent symptoms can be treated with a second-generation oral or intranasal antihistamine.

ABSTRACT: Many pharmacological options exist for allergic rhinitis. Intranasal corticosteroids are the most effective medication class for patients with moderate to severe symptoms; those with milder intermittent symptoms can be treated with a second-generation oral or intranasal antihistamine. Allergen avoidance measures may also be helpful. In patients whose symptoms are refractory to standard pharmacological therapy, allergen immunotherapy can be effective. A 3- to 5-year treatment course of subcutaneous injection immunotherapy can produce lasting benefit years after completion of therapy. In the future, sublingual immunotherapy may emerge as an alternative approach in the United States as it has in Europe in recent years.

Key words: allergic rhinitis, nonallergic rhinitis, primary care

Allergic rhinitis is a common disorder that dramatically affects patients' quality of life and consumes billions of dollars each year in health care costs and lost productivity. Rhinitis may be allergic (IgE-mediated) or nonallergic. Pure allergic rhinitis is about 3 times more prevalent than pure nonallergic rhinitis; however, many patients have both types.

In this article, we review pharmacological treatments for the different types of rhinitis; we focus on their relative efficacy and the symptoms for which each is best employed (Table). We also discuss immunotherapy options for the treatment of allergic rhinitis. In a previous article ("Allergic Rhinitis: Update on Diagnosis"), we addressed issues related to the diagnosis of allergic rhinitis.

INTRANASAL CORTICOSTEROIDS

Intranasal corticosteroids are the most effective class of medication for allergic rhinitis, and they are effective for all of its symptoms.1 While a patient may prefer and/or respond better to a given agent, none of the currently available intranasal corticosteroids has known superior efficacy over another.1,2 Intranasal corticosteroids are also effective in nonallergic rhinitis,3 including vasomotor rhinitis4 and rhinitis medicamentosa.5 Even though symptoms may initially abate within approximately 12 hours,6 maximum efficacy requires several weeks of daily use.

In our experience, most patients who report that allergic rhinitis symptoms have not responded to an intranasal corticosteroid are not using the medication regularly. Advise patients to give the medication at least a 1-month trial. In addition, teach them to direct the spray laterally within the nasal vestibule; this technique minimizes the nasal irritation and bleeding that can be associated with intranasal corticosteroids. These strategies should improve adherence and consequently efficacy. Intranasal corticosteroids are generally free from significant systemic side effects, including growth suppression in children.1

ClassAgentTrade nameMechanismSymptom(s) treated

Second-generation oral antihistamineCetirizine, Fexofenadine, Levocetirizine, Loratadine, DesloratadineZyrtec, Allegra, Xyzal, Claritin, ClarinexStabilizes HItching, sneezing, rhinorrhea; not as effective for nasal congestion

Intranasal antihistamineAzelastine, OlopatadineAstelin, Astepro, PatanaseStabilizes HItching, sneezing, rhinorrhea and nasal congestion

Leukotriene receptor antagonistMontelukastSingulairLeukotriene receptor antagonistItching, sneezing, rhinorrhea; not as effective for congestion

Anticholinergic agentIpratropium nasal sprayAtrovent nasal sprayAnticholinergicRhinorrhea (only)

Intranasal corticosteroidFluticasone propionate, Fluticasone furoate, Mometasone, Budesonide, Triamcinolone, Flunisolide, CiclesonideFlonase, Veramyst, Nasonex, Rhinocort Aqua, Nasacort AQ, Nasarel, OmnarisMultiple anti-inflammatory effects (corticosteroid)Itching, sneezing, rhinorrhea and nasal congestion; the most effective class of agents

ANTIHISTAMINES

 

Second-generation oral antihistamines (loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine) are effective for pruritus and rhinorrhea in allergic rhinitis, although they are less effective for nasal congestion and are of no proven use in nonallergic rhinitis.7 They can be used as needed for rhinitis symptoms, but they generally are more effective with continuous use.8 As a group, the second-generation agents have fewer side effects than first-generation agents (diphenhydramine, chlorpheniramine, hydroxyzine, and others), which can cause sedation and anticholinergic side effects.9

 

In a double-blind study, the performance in a driving simulator of participants who took 50 mg of diphenhydramine was similar to or worse than that of persons with a blood alcohol concentration of 0.1%, whereas the performance of participants who took 60 mg of fexofenadine was not significantly different from that of those who received placebo.10 First-generation antihistamines have also been associated with impaired learning and school performance in children.

 

Among the second-generation oral agents, loratadine and desloratadine generally have somewhat less efficacy11-13 and slower onset of action11-14 than other agents. The intranasal antihistamines (azelastine, olopatadine) have rapid onset of action15 and may be more effective than oral antihistamines,16,17 but combining agents from the 2 classes may not be better than using the intranasal antihistamine by itself.17 Unlike oral antihistamines, intranasal antihistamines have proven utility for vasomotor rhinitis.18 The principal adverse effects of intranasal antihistamines include bad taste and somnolence.18

 

DECONGESTANTS

 

Intranasal decongestants, such as oxymetazoline, cause vasoconstriction and decrease nasal congestion, although they do not substantially affect itching, sneezing, and rhinorrhea.1 They can be useful in the short term in severely congested patients to allow other agents (eg, nasal corticosteroids or nasal antihistamines) to reach their site of action. While there is some evidence that intranasal decongestants can be safely tolerated for weeks,19 rebound congestion (rhinitis medicamentosa) may begin to develop within 3 days.20 Generally speaking, intranasal decongestants should not be recommended for longer than 3 days of continuous use.

 

Oral decongestants, such as pseudoephedrine and phenylephrine, are α-agonists and work similarly to topical agents. They alleviate congestion caused by both allergic and nonallergic rhinitis. Although they do not cause rhinitis medicamentosa, they have the potential for systemic adverse effects, including palpitations, irritability, and elevated blood pressure.1 However, the effect on blood pressure is probably overestimated: in a well-done meta-analysis, pseudoephedrine raised systolic blood pressure by an average of 1 mm Hg, increased pulse by 3 beats per minute, and did not affect diastolic blood pressure.21 Because of significant individual patient variability in these parameters, close monitoring remains important.

 

OTHER AGENTS

 

An intranasal preparation of the anticholinergic drug ipratropium is useful for the treatment of rhinorrhea in both allergic22 and nonallergic rhinitis23-25 as well as in rhinitis caused by the common cold.26

 

The efficacy of the leukotriene receptor antagonist montelukast in the treatment of allergic rhinitis is similar to that of oral antihistamines, and select studies suggest an additive benefit in combination with oral antihistamines. However, this combination is less effective than singleagent use of an intranasal corticosteroid for most patients.27 Montelukast is also useful in the treatment of asthma.28

 

Cromolyn, a mast cell stabilizer available as a nasal spray or eyedrops, is effective in preventing allergic rhinitis symptoms before allergen exposure. However, given a 4 times daily dosing regimen and limited efficacy following symptom onset, topical cromolyn preparations are of modest practical value for most patients.

INITIAL CHOICE OF AGENT

 

The selection of initial therapy involves several factors. In general, patients with moderate to severe allergic rhinitis symptoms should start with an intranasal corticosteroid, whereas those with milder intermittent symptoms can be treated with a second-generation oral or intranasal antihistamine.1 In patients with nonallergic rhinitis, either an intranasal corticosteroid or an intranasal antihistamine is appropriate; however, an oral antihistamine is not likely to be effective. Patients with prominent nasal congestion can be treated with an intranasal corticosteroid or perhaps an intranasal antihistamine. Patients whose most prominent symptom is clear anterior rhinorrhea, such as those with gustatory rhinitis, benefit most from intranasal ipratropium.

 

COMBINATION THERAPY

 

Frequently, a single agent does not sufficiently relieve the symptoms of allergic rhinitis. Because oral antihistamines treat all allergic rhinitis symptoms effectively except congestion, and oral decongestants treat only congestion, the combination makes pharmacological sense. Indeed, the evidence shows that this combination is superior to either agent alone for symptoms of allergic rhinitis.29 However, the adverse effects of oral decongestants make this combination untenable for sustained use in many patients.

 

An oral antihistamine plus montelukast may be superior to either agent alone for allergic rhinitis,30-32 but this combination is inferior to an intranasal corticosteroid by itself.32,33 Nevertheless, select patients may demonstrate marked clinical improvement, even the minority in whom intranasal corticosteroids have failed. For rhinorrhea, intranasal ipratropium and an intranasal corticosteroid are more effective than either agent alone.25

 

Other frequently used combinations, such as an oral antihistamine plus an intranasal corticosteroid33,34 and an oral antihistamine plus an intranasal antihistamine,17,35 are not supported by clearly convincing data that indicate additive benefit. However, from a practical standpoint, the combination of an intranasal corticosteroid used daily and an oral second-generation antihistamine used as needed is often quite effective. In patients who do not respond to this regimen, an intranasal antihistamine and an intranasal corticosteroid may be the most potent 2-agent combination.36

 

CLINICAL HIGHLIGHTS

Intranasal corticosteroids are the most effective medications for allergic rhinitis; they treat all of its symptoms. These agents are also effective in nonallergic rhinitis, including vasomotor rhinitis and rhinitis medicamentosa.
Most patients who report that allergic rhinitis symptoms have not responded to an intranasal corticosteroid are not using the medication regularly. Advise patients to give the medication at least a 1-month trial. In addition, teach them to direct the spray laterally within the nasal vestibule; this technique minimizes the nasal irritation and bleeding that can be associated with intranasal corticosteroids.
Second-generation oral antihistamines are effective for pruritus and rhinorrhea in allergic rhinitis, although they are less effective for nasal congestion and are of no proven use in nonallergic rhinitis.
To prevent the development of rebound congestion (rhinitis medicamentosa), advise patients not to use intranasal decongestants for more than 3 days.
In general, patients with moderate to severe allergic rhinitis symptoms should start with an intranasal corticosteroid, whereas those with milder intermittent symptoms can be treated with a second-generation oral or intranasal antihistamine.
Consider referral to an allergist for patients whose rhinitis remains symptomatic or whose quality of life remains impaired despite treatment.
Subcutaneous injection allergen immunotherapy has been shown to be effective in numerous randomized, controlled trials in children and adults. Immunotherapy also appears to prevent sensitization to new allergens and may reduce the risk of asthma in patients with allergic rhinitis.

ALLERGEN AVOIDANCE

 

For persons with allergic rhinitis, a number of allergen avoidance recommendations are advocated in practice parameters7 and reviews.37,38 For those with pollen allergy, these measures include wearing dust masks (although supporting data are limited,39 and even high-efficiency respirators, such as N95 respirators, do not perform well if not fitted properly40) and limiting time outdoors. For persons with mold allergy, avoidance measures include limiting soildisturbing activity or wearing masks while doing so, and for indoor mold, eliminating moisture sources, removing moisture-damaged materials, and cleaning nonporous surfaces with bleach.

 

To control dust mite antigen, reducing indoor humidity, using dust mite sheet covers, washing bedding in hot water, replacing carpeting with hard flooring, using acaricides, and using high-efficiency particulate air (HEPA) filters in vacuums and in heating/air conditioning units have all been advocated. However, the effectiveness of some of these measures is controversial.41-43

 

Roach antigen control focuses on extermination and good sanitation to prevent reinfestation. Pet allergen is most effectively avoided by removing the pet, after which time it can take months for allergen to disappear from the home.7,37,38

 

INDICATIONS FOR SPECIALTY REFERRAL

 

Consider referral to an allergist for patients whose rhinitis remains symptomatic or whose quality of life remains impaired despite treatment. Allergy skin testing may confirm suspected triggers or lead to the diagnosis of nonallergic rhinitis. Frequently, the combination of allergen avoidance and ongoing pharmacological therapy controls symptoms. For those patients with positive skin test results consistent with their symptoms (eg, peak symptoms in the fall in a patient with ragweed allergy) who remain uncontrolled with pharmacotherapy or who wish to limit the need for medication, consider allergen immunotherapy.

 

IMMUNOTHERAPY FOR ALLERGIC RHINITIS

 

Allergen immunotherapy involves exposing patients to initially escalating and then maintenance amounts of the allergens that cause the majority of their symptoms. Subcutaneous injection immunotherapy has been shown to be effective in numerous randomized, controlled trials in children and adults.44-71 Allergen immunotherapy also appears to prevent sensitization to new allergens and may reduce the risk of asthma in patients with allergic rhinitis.72-77 Further, allergen immunotherapy is the only treatment known to alter the natural history of allergic rhinitis, and the clinical benefits are usually sustained for years following a successful 3- to 5-year treatment period.

 

In the United States, immunotherapy is usually administered by subcutaneous injection, although sublingual immunotherapy may prove to be an effective alternative.78 While substantial positive data about European sublingual extracts have accumulated over the past several years, data about sublingual extracts in the United States are limited and results have been mixed.78,79 It is important to note that allergen extract potency is not uniformly standardized; different standardization methods are used in Europe. Thus, data from European sublingual immunotherapy trials (even with similar allergens) cannot be extrapolated directly for use with extracts manufactured in the United States. Currently, no form of sublingual immunotherapy is approved by the FDA.

References:

REFERENCES:

1.

Greiner AN, Meltzer EO. Pharmacologic rationale for treating allergic and nonallergic rhinitis.

J Allergy Clin Immunol

. 2006;118:985-998.

2.

Corren J. Intranasal corticosteroids for allergic rhinitis: how do different agents compare?

J Allergy Clin Immunol

. 1999;104(4, pt 1):S144-S149.

3.

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.

4.

Arikan OK, Koc C, Kendi T, et al. CT assessment of the effect of fluticasone propionate aqueous nasal spray treatment on lower turbinate hypertrophy due to vasomotor rhinitis.

Acta Otolaryngol

. 2006;126:37-42.

5.

Hallén H, Enerdal J, Graf P. Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa.

Clin Exp Allergy

. 1997;27:552-558.

6.

Meltzer EO, Rickard KA, Westlund RE, Cook CK. Onset of therapeutic effect of fluticasone propionate aqueous nasal spray.

Ann Allergy Asthma Immunol

. 2001;86:286-291.

7.

Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: an updated practice parameter.

J Allergy Clin Immunol

. 2008;122(2 suppl):S1-S84.

8.

Ciprandi G, Passalacqua G, Mincarini M, et al. Continuous versus on demand treatment with cetirizine for allergic rhinitis.

Ann Allergy Asthma Immunol

. 1997;79:507-511.

9.

Casale TB, Blaiss MS, Gelfand E, et al; Antihistamine Impairment Roundtable. First do no harm: managing antihistamine impairment in patients with allergic rhinitis.

J Allergy Clin Immunol

. 2003;111:S835-S842.

10.

Weiler JM, Bloomfield JR, Woodworth GG, et al. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance. A randomized, placebo-controlled trial in the Iowa driving simulator.

Ann Intern Med

. 2000;132:354-363.

11.

Van Cauwenberge P, Juniper EF. Comparison of the efficacy, safety and quality of life provided by fexofenadine hydrochloride 120 mg, loratadine 10 mg and placebo administered once daily for the treatment of seasonal allergic rhinitis.

Clin Exp Allergy

. 2000;30:891-899.

12.

Day JH, Briscoe M, Widlitz MD. Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: effects after controlled ragweed pollen challenge in an environmental exposure unit.

J Allergy Clin Immunol

. 1998;101:638-645.

13.

Passalacqua G, Canonica GW. A review of the evidence from comparative studies of levocetirizine and desloratadine for the symptoms of allergic rhinitis [published correction appears in

Clin Ther

. 2005;27:1669].

Clin Ther

. 2005;27:979-992.

14.

Meltzer EO. Evaluation of the optimal oral antihistamine for patients with allergic rhinitis.

Mayo Clin Proc.

2005;80:1170-1176.

15.

Patel D, Garadi R, Brubaker M, et al. Onset and duration of action of nasal sprays in seasonal allergic rhinitis patients: olopatadine hydrochloride versus mometasone furoate monohydrate.

Allergy Asthma Proc

. 2007;28:592-599.

16.

Berger W, Hampel F Jr, Bernstein J, et al. Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis.

Ann Allergy Asthma Immunol

. 2006;97:375-381.

17.

LaForce CF, Corren J, Wheeler WJ, Berger WE; Rhinitis Study Group. Efficacy of azelastine nasal spray in seasonal allergic rhinitis patients who remain symptomatic after treatment with fexofenadine.

Ann Allergy Asthma Immunol

. 2004;93:154-159.

18.

Banov CH, Lieberman P; Vasomotor Rhinitis Study Groups. Efficacy of azelastine nasal spray in the treatment of vasomotor (perennial nonallergic) rhinitis.

Ann Allergy Asthma Immunol

. 2001;86:28-35.

19.

Yoo JK, Seikaly H, Calhoun KH. Extended use of topical nasal decongestants.

Laryngoscope.

1997;107:40-43.

20.

Morris S, Eccles R, Martez SJ, et al. An evaluation of nasal response following different treatment regimes of oxymetazoline with reference to rebound congestion.

Am J Rhinol

. 1997;11:109-115.

21.

Salerno SM, Jackson JL, Berbano EP. Effect of oral pseudoephedrine on blood pressure and heart rate: a meta-analysis.

Arch Intern Med

. 2005;165:1686-1694.

22.

Meltzer EO, Orgel HA, Bronsky EA, et al. Ipratropium bromide aqueous nasal spray for patients with perennial allergic rhinitis: a study of its effect on their symptoms, quality of life, and nasal cytology.

J Allergy Clin Immunol

. 1992;90:242-249.

23.

Bronsky EA, Druce H, Findlay SR, et al. A clinical trial of ipratropium bromide nasal spray in patients with perennial nonallergic rhinitis.

J Allergy Clin Immunol

. 1995;95(5, pt 2):1117-1122.

24.

Bonadonna P, Senna G, Zanon P, et al. Coldinduced rhinitis in skiers-clinical aspects and treatment with ipratropium bromide nasal spray: a randomized controlled trial.

Am J Rhinol

. 2001;15:297-301.

25.

Dockhorn R, Aaronson D, Bronsky E, et al. Ipratropium bromide nasal spray 0.03% and beclomethasone nasal spray alone and in combination for the treatment of rhinorrhea in perennial rhinitis.

Ann Allergy Asthma Immunol

. 1999;82:349-359.

26.

Hayden FG, Diamond L, Wood PB, et al. Effectiveness and safety of intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo-controlled trial.

Ann Intern Med

. 1996;125:89-97.

27.

Rodrigo GJ, Yañez A. The role of antileukotriene therapy in seasonal allergic rhinitis: a systematic review of randomized trials.

Ann Allergy Asthma Immunol

. 2006;96:779-786.

28.

Price DB, Swern A, Tozzi CA, et al. Effect of montelukast on lung function in asthma patients with allergic rhinitis: analysis from the COMPACT trial [published correction appears in

Allergy

. 2006;61:1153].

Allergy

. 2006;61:737-742.

29.

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.

30.

Meltzer EO, Malmstrom K, Lu S, et al. Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial.

J Allergy Clin Immunol

. 2000;105:917-922.

31.

Ciebiada M, Górska-Ciebiada M, DuBuske LM, Górski P. Montelukast with desloratadine or levocetirizine for the treatment of persistent allergic rhinitis.

Ann Allergy Asthma Immunol

. 2006;97:664-671.

32.

Pullerits T, Praks L, Ristioja V, Lötvall J. Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis.

J Allergy Clin Immunol

. 2002;109:949-955.

33.

Di Lorenzo G, Pacor ML, Pellitteri ME, et al. Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis [published correction appears in

Clin Exp Allergy

. 2004;34:1329].

Clin Exp Allergy

. 2004;34:259-267.

34.

Barnes ML, Ward JH, Fardon TC, Lipworth BJ. Effects of levocetirizine as add-on therapy to fluticasone in seasonal allergic rhinitis.

Clin Exp Allergy

. 2006;36:676-684.

35.

Berger WE, White MV; Rhinitis Study Group. Efficacy of azelastine nasal spray in patients with an unsatisfactory response to loratadine.

Ann Allergy Asthma Immunol

. 2003;91:205-211.

36.

Ratner PH, Hampel F, Van Bavel J, et al. Combination therapy with azelastine hydrochloride nasal spray and fluticasone propionate nasal spray in the treatment of patients with seasonal allergic rhinitis.

Ann Allergy Asthma Immunol

. 2008;100:74-81.

37.

Bush RK. Indoor allergens, environmental avoidance, and allergic respiratory disease.

Allergy Asthma Proc

. 2008;29:575-579.

38.

Custovic A, Murray CS, Gore RB, et al. Controlling indoor allergens.

Ann Allergy Asthma Immunol

. 2002;88:432-443, 529.

39.

Gotoh M, Okubo K, Okuda M. Inhibitory effects of facemasks and eyeglasses on invasion of pollen particles in the nose and eye: a clinical study.

Rhinology

. 2005;43:266-270.

40.

Rengasamy A, Zhuang Z, Berryann R. Respiratory protection against bioaerosols: literature review and research needs.

RAm J Infect Control

. 2004;32:345-354.

41.

Gøtzsche PC, Johansen HK. House dust mite control measures for asthma.

Cochrane Database Syst Rev

. 2008;(2):CD001187. (Also published as "House dust mite control measures for asthma: systematic review" in

Allergy

. 2008;63:646-659.)

42.

Sheikh A, Hurwitz B, Shehata Y. House dust mite avoidance measures for perennial allergic rhinitis.

Cochrane Database Syst Rev

. 2007;(1):CD001563.

43.

Platts-Mills TA. Allergen avoidance in the treatment of asthma: problems with the meta-analyses.

J Allergy Clin Immunol

. 2008;122:694-696.

44.

Ariano R, Kroon AM, Augeri G, et al. Longterm treatment with allergoid immunotherapy with Parietaria: clinical and immunologic effects in a randomized, controlled trial.

Allergy

. 1999;54:313-319.

45.

Bousquet J, Becker WM, Hejjaoui A, et al. Differences in clinical and immunologic reactivity of patients allergic to grass pollens and to multiplepollen species, II: efficacy of a double-blind, placebocontrolled, specific immunotherapy with standardized extracts.

J Allergy Clin Immunol

. 1991;88:43-53.

46.

Bousquet J, Frank E, Soussana M, et al. Doubleblind, placebo-controlled immunotherapy with a high-molecular-weight, formalinized allergoid in grass pollen allergy.

Int Arch Allergy Appl Immunol

. 1987;82:550-552.

47.

Creticos PS, Marsh DG, Proud D, et al. Responses to ragweed-pollen nasal challenge before and after immunotherapy.

J Allergy Clin Immunol

. 1989;84:197-205.

48.

Creticos PS, Reed CE, Norman PS, et al. Ragweed immunotherapy in adult asthma.

N Engl J Med

. 1996;334:501-506.

49.

Dolz I, Martinez-Cócera C, Bartolomé JM, Cimarra M. A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy.

Allergy

. 1996;51:489-500.

50.

Lowell FC, Franklin W. A double-blind study of the effectiveness and specificity of injection therapy in ragweed hay fever.

N Engl J Med

. 1965;273:675-679.

51.

Malling HJ, Djurup R. Diagnosis and immunotherapy of mould allergy, VII: IgG subclass response and relation to the clinical efficacy of immunotherapy with Cladosporium.

Allergy

. 1988;43:60-70.

52.

Horst M, Hejjaoui A, Horst V, Michel FB, et al. Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract.

J Allergy Clin Immunol

. 1990;85:460-472.

53.

Malling HJ. Diagnosis and immunotherapy of mould allergy, IV: relation between asthma symptoms, spore counts and diagnostic tests.

Allergy

. 1986;41:342-350.

54.

Karlsson R, Agrell B, Dreborg S, et al. A double-blind, multicenter immunotherapy trial in children, using a purified and standardized

Cladosporium herbarum

preparation, II: in vitro results.

Allergy

. 1986;41:141-150.

55.

Dreborg S, Agrell B, Foucard T, et al. A doubleblind, multicenter immunotherapy trial in children, using a purified and standardized Cladosporium herbarum preparation, I: clinical results.

Allergy

. 1986;41:131-140.

56.

Ewbank PA, Murray J, Sanders K, et al. A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract.

J Allergy Clin Immunol

. 2003;111:155-161.

57.

Alvarez-Cuesta E, Cuesta-Herranz J, Puyana- Ruiz J, et al. Monoclonal antibody-standardized cat extract immunotherapy: risk-benefit effects from a double-blind placebo study.

J Allergy Clin Immunol

. 1994;93:556-566.

58.

Haugaard L, Dahl R. Immunotherapy in patients allergic to cat and dog dander, I: clinical results.

Allergy

. 1992;47:249-254.

59.

Hedlin G, Graff-Lonnevig V, Heilborn H, et al. Immunotherapy with cat- and dog-dander extracts, V: effects of 3 years of treatment.

J Allergy Clin Immunol

. 1991;87:955-964.

60.

Ohman JL Jr, Findlay SR, Leitermann KM. Immunotherapy in cat-induced asthma: double-blind trial with evaluation of in vivo and in vitro responses.

J Allergy Clin Immunol

. 1984;74(3, pt 1):230-239.

61.

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.

62.

Nanda A, O'Connor M, Anand M, et al. Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract.

J Allergy Clin Immunol

. 2004;114:1339-1344.

63.

Lent AM, Harbeck R, Strand M, et al. Immunologic response to administration of standardized dog allergen extract at differing doses.

J Allergy Clin Immunol

. 2006;118:1249-1256.

64.

Maestrelli P, Zanolla L, Pozzan M, Fabbri LM; Regione Veneto Study Group on the "Effect of immunotherapy in allergic asthma." Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite.

J Allergy Clin Immunol.

2004;113:643-649.

65.

Tabar AI, Echechipía S, García BE, et al. Double-blind comparative study of cluster and conventional immunotherapy schedules with

Dermatophagoides pteronyssinus. J Allergy Clin Immunol

. 2005;116:109-118.

66.

Pichler CE, Marquardsen A, Sparholt S, et al. Specific immunotherapy with

Dermatophagoides pteronyssinus

and D farinae results in decreased bronchial hyperreactivity.

Allergy

. 1997;52:274-283.

67.

Aas K. Hyposensitization in house dust allergy asthma: a double-blind controlled study with evaluation of the effect on bronchial sensitivity to house dust.

Acta Paediatr Scand

. 1971;60:264-268.

68.

Bousquet J, Hejjaoui A, Clauzel AM, et al. Specific immunotherapy with a standardized

Dermatophagoides pteronyssinus

extract, II: prediction of efficacy of immunotherapy.

J Allergy Clin Immunol

. 1988;82:971-977.

69.

Haugaard L, Dahl R, Jacobsen L. A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects.

J Allergy Clin Immunol

. 1993;91:709-722.

70.

McHugh SM, Lavelle B, Kemeny DM, et al. A placebo-controlled trial of immunotherapy with two extracts of

Dermatophagoides pteronyssinus

in allergic rhinitis, comparing clinical outcome with changes in antigen-specific IgE, IgG, and IgG subclasses.

J Allergy Clin Immunol

. 1990;86(4, pt 1):521-531.

71.

Kang BC, Johnson J, Morgan C, Chang JL. The role of immunotherapy in cockroach asthma. J Asthma. 1988;25:205-218.

72.

Purello-D'Ambrosio F, Gangemi S, Merendino RA, et al. Prevention of new sensitizations in monosensitized subjects submitted to specific immunotherapy or not: a retrospective study.

Clin Exp Allergy

. 2001;31:1295-1302.

73.

Pajno GB, Barberio G, De Luca F, Morabito L, et al. Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy: a six-year follow-up study.

Clin Exp Allergy

. 2001;31:1392-1397.

74.

Des Roches A, Paradis L, Menardo JL, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract, VI: specific immunotherapy prevents the onset of new sensitizations in children.

J Allergy Clin Immunol

. 1997;99:450-453.

75.

Jacobsen L. Preventive aspects of immunotherapy: prevention for children at risk of developing asthma.

Ann Allergy Asthma Immunol

. 2001;87: 43-46.

76.

Niggemann B, Jacobsen L, Dreborg S, et al; PAT Investigator Group. Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children.

Allergy

. 2006;61: 855-859.

77.

Möller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study).

J Allergy Clin Immunol

. 2002;109: 251-256.

78.

Frew AJ. Sublingual immunotherapy.

N Engl J Med

. 2008;358:2259-2264.

79.

Greenberger PA, Ballow M, Casale TB, et al. Sublingual immunotherapy and subcutaneous immunotherapy: issues in the United States.

J Allergy Clin Immunol

. 2007;120:1466-1468.

Therapeutic Agents in This Article

Azelastine (Astelin, Astepro)

Budesonide (Rhinocort Aqua)

Cetirizine (Zyrtec)

Chlorpheniramine (Chlor-Trimeton)

Ciclesonide (Omnaris)

Cromolyn (Nasalcrom)

Desloratadine (Clarinex)

Diphenhydramine (Benadryl)

Fexofenadine (Allegra)

Flunisolide (Nasarel)

Fluticasone furoate (Veramyst)

Fluticasone propionate (Flonase)

Hydroxyzine (Atarax)

Ipratropium (Atrovent)

Levocetirizine (Xyzal)

Loratadine (Claritin)

Mometasone (Nasonex)

Montelukast (Singulair)

Olopatadine (Patanase)

Oxymetazoline (Afrin, Dristan)

Phenylephrine (Neo-Synephrine)

Pseudoephedrine (Sudafed)

Triamcinolone (Nasacort AQ)