Allergic rhinitis

The treatment goal for allergic rhinitis is relief of symptoms. Therapeutic options available to achieve this goal include avoidance measures, nasal saline irrigation, oral antihistamines, intranasal corticosteroids, combination intranasal corticosteroid/antihistamine sprays; leukotriene receptor antagonists (LTRAs), and allergen immunotherapy (see Fig. 2). Other therapies that may be useful in select patients include decongestants and oral corticosteroids. If the patient’s symptoms persist despite appropriate treatment, referral to an allergist should be considered. As mentioned earlier, allergic rhinitis and asthma appear to represent a combined airway inflammatory disease and, therefore, treatment of asthma is also an important consideration in patients with allergic rhinitis.

A simplified, stepwise algorithm for the treatment of allergic rhinitis. Treatments can be used individually or in any combination

The first-line treatment of allergic rhinitis involves the avoidance of relevant allergens (e.g., house dust mites, moulds, pets, pollens) and irritants (e.g., tobacco smoke). Patients allergic to house dust mites should be instructed to use allergen-impermeable covers for bedding and to keep the relative humidity in the home below 50% (to inhibit mite growth). Pollen and outdoor mould exposure can be reduced by keeping windows closed, using window screen filters, using an air conditioner, and limiting the amount of time spent outdoors during peak pollen seasons. For patients allergic to animal dander, removal of the animal from the home is recommended and usually results in a significant reduction in symptoms within 4–6 months. However, compliance with this recommendation is poor and, therefore, the use of high-efficiency particulate air (HEPA) filters and restricting the animal from the bedroom or to the outdoors may be needed to attempt to decrease allergen levels. Measures for reducing exposure to mould allergens include cleaning with fungicides, dehumidification to less than 50%, remediation of any water damage, and HEPA filtration. These avoidance strategies can effectively improve the symptoms of allergic rhinitis, and patients should be advised to use a combination of measures for optimal results [1].

The second-generation oral anti-histamines (e.g., desloratadine [Aerius], fexofenadine [Allegra], loratadine [Claritin], cetirizine [Reactine]) are the first-line pharmacological treatments recommended for all patients with allergic rhinitis. Recently, two new second-generation antihistamines—Bilastine (Blexten) and rupatadine (Rupall)—have been introduced in Canada. At present, these antihistamines are available by prescription only (see Table 3 for a list of second-generation antihistamines and their recommended dosing regimens).

The second-generation oral anti-histamines have been found to effectively reduce sneezing, itching and rhinorrhea when taken regularly at the time of maximal symptoms or before exposure to an allergen. Although the older (first-generation) sedating antihistamines (e.g., diphenhydramine, chlorpheniramine) are also effective in relieving symptoms, they have been shown to negatively impact cognition and functioning and, therefore, they are not routinely recommended for the treatment of allergic rhinitis [1, 14].

Intranasal corticosteroids are also first-line therapeutic options for patients with mild persistent or moderate/severe symptoms and they can be used alone or in combination with oral antihistamines. When used regularly and correctly, intranasal corticosteroids effectively reduce inflammation of the nasal mucosa and improve mucosal pathology. Studies and meta-analyses have shown that intranasal corticosteroids are superior to antihistamines and leukotriene receptor antagonists in controlling the symptoms of allergic rhinitis, including nasal congestion, and rhinorrhea [19,20,21,22]. They have also been shown to improve ocular symptoms and reduce lower airway symptoms in patients with concurrent asthma and allergic rhinitis [23,24,25].

The intranasal corticosteroids available in Canada are shown in Table 3 and include fluticasone furoate (Avamys), beclomethasone (Beconase), fluticasone propionate (Flonase), triamcinolone acetonide (Nasacort), mometasone furoate (Nasonex), ciclesonide (Omnaris) and budesonide (Rhinocort). Since proper application of the nasal spray is required for optimal clinical response, patients should be counseled on the appropriate use of these intranasal devices. Ideally, intranasal corticosteroids are best started just prior to exposure to relevant allergens and, because their peak effect may take several days to develop, they should be used regularly [4].

The most common side effects of intranasal corticosteroids are nasal irritation and stinging. However, these side effects can usually be prevented by aiming the spray slightly away from the nasal septum [1]. Evidence suggests that intranasal beclomethasone and triamcinolone, but not other intranasal corticosteroids, may slow growth in children compared to placebo. However, long-term studies examining the impact of usual doses of intranasal beclomethasone on growth are lacking [26,27,28,29].

It is important to note that most patients with allergic rhinitis presenting to their primary-care physician have moderate-to-severe symptoms and will require an intranasal corticosteroid. Bousquet et al. [30] noted improved outcomes in patients with moderate-to-severe symptoms treated with a combination of these agents.

If intranasal corticosteroids are not effective, a combination corticosteroid/antihistamine spray can be tried. Combination fluticasone propionate/azelastine hydrochloride (Dymista) is now available in Canada. This combination spray has been shown to be more effective than the individual components with a safety profile similar to intranasal corticosteroids [31,32,33,34].

The LTRAs montelukast and zafirlukast are also effective in the treatment of allergic rhinitis; however, they do not appear to be as effective as intranasal corticosteroids [35,36,37]. Although one short-term study found the combination of LTRAs and antihistamines to be as effective as intranasal corticosteroids [38], longer-term studies have found intranasal corticosteroids to be more effective than the combination for reducing nighttime and nasal symptoms [20, 39]. It is important to note that in Canada, montelukast is the only LTRA indicated for the treatment of allergic rhinitis in adults.

LTRAs should be considered when oral antihistamines, intranasal corticosteroids and/or combination corticosteroid/antihistamine sprays are not well tolerated or are ineffective in controlling the symptoms of allergic rhinitis. If combination pharmacological therapy with oral antihistamines, intranasal corticosteroids, combination corticosteroid/antihistamine sprays and LTRAs is not effective or is not tolerated, then allergen immunotherapy should be considered [1, 14].

Allergen immunotherapy involves the subcutaneous administration of gradually increasing quantities of the patient’s relevant allergens until a dose is reached that is effective in inducing immunologic tolerance to the allergen (see Allergen-specific Immunotherapy article in this supplement). Allergen immunotherapy is an effective treatment for allergic rhinitis, particularly for patients with intermittent (seasonal) allergic rhinitis caused by pollens, including tree, grass and ragweed pollens [40,41,42,43]. It has also been shown to be effective for the treatment of allergic rhinitis caused by house dust mites, Alternaria, cockroach, and cat and dog dander (although it should be noted that therapeutic doses of dog allergen are difficult to attain with the allergen extracts available in Canada). Allergen immunotherapy should be reserved for patients in whom optimal avoidance measures and pharmacotherapy are insufficient to control symptoms or are not well tolerated. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy and who are equipped to manage possible life-threatening anaphylaxis [1].

Evidence suggests that at least 3 years of allergen-specific immunotherapy provides beneficial effects in patients with allergic rhinitis that can persist for several years after discontinuation of therapy [44, 45]. In Canada, most allergists consider stopping immunotherapy after 5 years of adequate treatment. Immunotherapy may also reduce the risk for the future development of asthma in children with allergic rhinitis [41].

Typically, allergen immunotherapy is given on a perennial basis with weekly incremental increases in dose over the course of 6–8 months, followed by maintenance injections of the maximum tolerated dose every 3–4 weeks for 3–5 years. After this period, many patients experience a prolonged, protective effect and, therefore, consideration can be given to stopping therapy. Pre-seasonal preparations that are administered on an annual basis are also available [1, 14].

Sublingual immunotherapy is a way of desensitizing patients and involves placing a tablet of allergen extract under the tongue until it is dissolved. It is currently available for the treatment of grass and ragweed allergy, as well as house dust mite-induced allergic rhinitis (with or without conjunctivitis). At present, four sublingual tablet immunotherapy products are available in Canada: Oralair®, Grastek®, Ragwitek® and Acarizax™ [46,47,48,49]. The sublingual route of immunotherapy offers multiple potential benefits over the subcutaneous route including the comfort of avoiding injections, the convenience of home administration, and a favourable safety profile. Like subcutaneous immunotherapy, sublingual immunotherapy is indicated for those with allergic rhinitis who have not responded to or tolerated conventional pharmacotherapy, or who are adverse to the use of these conventional treatments.

The most common side effects of sublingual immunotherapy are local reactions such as oral pruritus, throat irritation, and ear pruritus [42]. These symptoms typically resolve after the 1st week of therapy. There is a very small risk of more severe systemic allergic reactions with this type of immunotherapy and, therefore, some allergists may offer the patient an epinephrine auto-injector in case a reaction occurs at home. The risk of systemic allergic reactions is much lower with sublingual immunotherapy compared to traditional injections [42].

Similar to subcutaneous immunotherapy, sublingual immunotherapy is contraindicated in patients with severe, unstable or uncontrolled asthma. It should ideally be avoided in patients on beta-blocker therapy as well as in those with active oral inflammation or sores [46,47,48,49,50]. Sublingual immunotherapy should only be administered using the Health Canada approved products discussed above.

A simplified, stepwise algorithm for the treatment of allergic rhinitis is provided in Fig. 2. Note that mild, intermittent allergic rhinitis can generally be managed effectively with avoidance measures and oral antihistamines. However, as mentioned earlier, most patients presenting with allergic rhinitis have moderate-to-severe symptoms and, therefore, will require a trial of intranasal corticosteroids.

Oral and intranasal decongestants (e.g., pseudoephedrine, phenylephrine) are useful for relieving nasal congestion in patients with allergic rhinitis. However, the side-effect profile associated with oral decongestants (i.e., agitation, insomnia, headache, palpitations) may limit their long-term use. Furthermore, these agents are contraindicated in patients with uncontrolled hypertension and severe coronary artery disease. Prolonged use of intranasal decongestants carries the risk of rhinitis medicamentosa (rebound nasal congestion) and, therefore, these agents should not be used for more than 3–5 days [51]. Oral corticosteroids have also been shown to be effective in patients with severe allergic rhinitis that is refractory to treatment with oral antihistamines and intranasal corticosteroids [1, 4].

Although not as effective as intranasal corticosteroids, intranasal sodium cromoglycate (Cromolyn) has been shown to reduce sneezing, rhinorrhea and nasal itching and is, therefore, a reasonable therapeutic option for some patients. The anti-IgE antibody, omalizumab, has also been shown to be effective in seasonal allergic rhinitis and asthma [1], however, it is not currently approved for the treatment of allergic rhinitis.

Surgical therapy may be helpful for select patients with rhinitis, polyposis, or chronic sinus disease that is refractory to medical treatment. Most surgical interventions can be performed under local anesthesia in an office or outpatient setting [1].

It is important to note that allergic rhinitis may worsen during pregnancy and, as a result, may necessitate pharmacologic treatment. The benefit-to-risk ratio of pharmacological agents for allergic rhinitis needs to be considered before recommending any medical therapy to pregnant women. Intranasal sodium cromoglycate can be used as a first-line therapy for allergic rhinitis in pregnancy since no teratogenic effects have been noted with the cromones in humans or animals. Antihistamines may also be considered for allergic rhinitis in pregnancy. Starting or increasing allergen immunotherapy during pregnancy is not recommended because of the risk of anaphylaxis to the fetus. However, maintenance doses are considered to be safe and effective during pregnancy [1].

Given the popularity of complementary and alternative medicines (CAM) in the general population, it is reasonable for physicians to ask patients about their use of CAM in a nonjudgmental manner. Given the limited number of well-designed clinical trials examining the efficacy of CAM in allergic rhinitis, it is difficult for clinicians to evaluate these therapies and provide guidance. Nonetheless, since there will be patients who wish to pursue CAM for the management of allergic rhinitis, it is advisable to provide some information about these therapies including a discussion of the lack of high-quality studies evaluating some of these therapies.

Various CAM have been used for the management of allergic rhinitis, including traditional Chinese medicines, acupuncture, homeopathy, and herbal therapies [52]. In a number of studies, acupuncture has been shown to provide modest benefits for patients with allergic rhinitis [52, 53]. However, acupuncture is time consuming.