Allergic rhinitis (AR) is a common, often chronic, health condition associated with significant morbidity.1 Approximately 20% of adults and 40% of children have symptoms consistent with the disease, which can range in severity from mild to moderate-severe.2 For its sufferers, AR can have a consequential impact on quality of life, direct medical costs, and productivity. This article aims to provide an overview of AR, its management principles, and the role of the pharmacist in providing care for patients with AR.
Rhinitis is an inflammation of the nasal mucosa.1 When associated with allergens, rhinitis encompasses an even broader spectrum of signs and symptoms, including rhinorrhea, nasal congestion, pruritus, sneezing, postnasal drip, and sometimes nasal pain. Other upper respiratory organs, including the eyes, ears, sinuses, and oropharynx may be involved, as characterized by symptoms of ocular pruritus and watering, ear pain, recurrent sinusitis, and chronic cough. Patients may also display characteristic physical exam findings such as a darkening below the eyes ("allergic shiners") or a nasal crease caused by constant rubbing ("allergic salute").1,3-7 The symptoms of AR may be difficult to distinguish from nonallergic forms; however, more prominent nasal pruritus and conjunctival irritation, as seen with AR, may help differentiate. Additionally, when skin-prick testing is performed, the presence of an immunoglobulin E (IgE)-mediated allergic reaction would lend itself to a diagnosis of AR in the presence of symptoms and may aid in allergen avoidance as a nonpharmacologic management strategy.6 Other types of rhinitis, such as hormonal and infectious, should also be ruled out. The use of a patient diary to record rhinitis symptoms, their triggers, and when they occur may help with diagnosis.
Depending on the temporal relationship of allergy symptoms, AR may be further classified into two types. Seasonal AR, sometimes called hay fever, manifests at a particular time of the year, usually when allergens such as fungi and tree, grass, and weed pollens are at the highest levels. Perennial AR is associated with year-round symptoms and is typically related to indoor allergen exposure to dust mites, animal proteins, cockroaches, and molds.1,5,6 AR may also be classified by symptom frequency, either as intermittent (symptoms lasting <4 days/wk for <4 wk) or persistent (symptoms lasting >=4 days/wk for >=4 wk regardless of symptoms).8
Describing rhinitis symptoms according to mild or moderate-severe disease may also be helpful for treatment. Moderate-severe disease is associated with a minimum of one of the following: sleep disturbance; impairment of school or work performance; impairment of daily leisure or sports activities; or troublesome symptoms, which may have a significant emotional impact due to their severity.9 Moderate-severe AR generally requires more intensive medical management.
Although more children and adolescents suffer from symptoms of AR, symptoms tend to have a bimodal peak during childhood and middle age, but can begin at any time.10 In addition to allergen exposure, several risk factors predispose a person to developing AR (Table 1). AR commonly occurs in the presence of other allergic-type disorders as well, including sinusitis, asthma, eczema, and allergic conjunctivitis, and can exacerbate their severity. AR can also cause otitis media as a result of eustachian tube dysfunction and may result in migraine headaches or anosmia if improperly managed.10
The goal of AR treatment is to reduce or eliminate inflammation-associated allergy symptoms. Additionally, improving quality of life and productivity are equally important, as is minimizing medication-related adverse effects.
AR can be treated by employing both nonpharmacologic and pharmacologic modalities for symptom management, as well as immunotherapy. Nonpharmacologic therapy should be implemented in all patients with AR to help decrease symptom severity; however, most patients will not receive complete resolution of symptoms with nondrug therapies alone.
Allergen avoidance is recommended as one of the main nonpharmacologic strategies for managing symptoms of AR, although for most patients it is impractical. Reducing environmental exposure to allergens by keeping windows closed and minimizing outdoor activities during the pollen season may help reduce symptoms. Minimizing mold growth through proper cleaning and dehumidification can help patients with a mold allergy. Other indoor allergens, such as house dust mites, animal dander, and insects should be minimized or avoided through proper cleaning measures, selecting allergen-proof covers and construction materials, and by utilizing high-efficiency particulate air (HEPA) filters.6
Pharmacologic therapy and immunotherapy can help patients achieve symptom resolution to improve their quality of life. Patients who experience seasonal AR may be able to anticipate the onset of symptoms and use pharmacologic therapy immediately prior to and during allergy season.
Medication classes used to treat AR include intranasal corticosteroids, oral antihistamines, topical antihistamines, leukotriene modifiers, topical mast cell stabilizers, topical anticholinergics, and decongestants. The following discussion and Table 2 provide an overview of these drugs.
Intranasal corticosteroids are first line for the treatment of AR.1,2,4,11-15
This class of medications is the most effective compared to other drugs for
controlling the symptoms associated with AR, including nasal congestion, nasal
discharge, pruritus, sneezing, and postnasal drip.11-12,16
Available by prescription only, specific agents include beclomethasone
(Beconase AQ), ciclesonide (Omnaris), budesonide (Rhinocort, Rhinocort Aqua),
mometasone (Nasonex), triamcinolone (Nasacort AQ), and fluticasone furoate
(Veramyst), as well as flunisolide (Nasarel, Nasalide) and fluticasone
propionate (Flonase), both of which are now available as generics. Veramyst,
the newest FDA-approved intranasal corticosteroid for the treatment of AR,
treats both nasal and ocular symptoms.17 In regard to efficacy, no
significant difference exists between agents; however, steroids do differ in
potency. When comparing intranasal corticosteroids to oral antihistamines,
intranasal corticosteroids provide better overall relief of symptoms, which is
supported by numerous studies and meta-analyses.2,12
Intranasal corticosteroids work by decreasing inflammation associated with AR. Ideally, they should be started before the onset of seasonal symptoms and used every day.1 Most of the intranasal corticosteroids are dosed one to two sprays in each nostril once or twice daily. If the medication is dosed once daily, it should be administered at night, due to the fact that nasal inflammation is greater during the night than during the day. Optimally, therapy should be started at the maximum dose for the patient's age, then stepped down at one-week intervals to the lowest effective dose.12 Some patients may even experience relief of symptoms with administration every other day. This concept is especially useful for children, who may benefit from use of intranasal corticosteroids as needed.12
The most common adverse effects of intranasal corticosteroids include transient burning after application, epistaxis, nasal pruritus, headache, and pharyngitis.1,4,12 Systemic adverse effects, including insomnia, nervousness, increased appetite, indigestion, headache, hyperglycemia, and diaphoresis, can occur, especially if the steroid is used at high doses for an extended period of time.12,18
The intranasal steroids are divided into three generations depending on their bioavailability. Beclomethasone and flunisolide, two first-generation intranasal corticosteroids, are more bioavailable and tend to produce more systemic adverse effects than other intranasal corticosteroids.12 The other steroids fall into second- and third-generation categories and tend to have limited systemic adverse effects. Hypothalamic-pituitary-adrenal (HPA) axis suppression and effects on growth in children are potential concerns with topical corticosteroids. These effects have been evaluated in various studies, and the second- and third-generation intranasal steroids, at recommended doses, show no or limited effects on HPA axis suppression and decreased vertical growth of children. Furthermore, agents that are dosed once daily are preferred in children in order to minimize the amount of steroid the child receives.12
Oral Antihistamines: Oral antihistamines are effective at reducing most, but not all, symptoms of AR.4,11 This class of medications specifically treats pruritus, sneezing, rhinorrhea, and watery eyes.4,11,13,15 The drugs do not combat the nasal congestion associated with AR.1,4,11-13
Oral antihistamines are divided into two generations, which differ by their adverse-effect profile and dosing. All of the agents are equally efficacious when compared to each other.12 The first-generation oral antihistamines include diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), hydroxyzine (Atarax), and bromphenir amine (Dimetapp Allergy). These agents are dosed every four to six hours and cause significant sedation, their limiting adverse effect.12,18 Anticholinergic adverse effects, most commonly dry mouth, dry eyes, urinary retention, and confusion, can occur when taking a first-generation oral antihistamine.12 Confusion is prevalent when used in the elderly and can be detrimental to their overall well-being. When children take these medications, they can experience a paradoxical stimulation reaction; therefore, it is not recommended that these agents be used in children less than 2 years of age.18
Second-generation oral antihistamines have all of the benefits of first-generation agents without the sedation and anticholinergic adverse effects. Second-generation agents are generally dosed once or twice daily and do not cross the blood brain barrier; therefore, they do not cause sedation to the extent of the first-generation agents. Second-generation antihistamines are well tolerated and, before generic and OTC versions were introduced, were significantly more expensive than first-generation medications. Agents include cetirizine (Zyrtec) and loratadine (Claritin), available OTC, and fexofenadine (Allegra), desloratadine (Clarinex), and levocetirizine (Xyzal), available by prescription only. Some of these medications are also found in combination with pseudoephedrine to treat nasal congestion (e.g., Allegra-D, Claritin-D, Zyrtec-D).14 Patients with mild-to-moderate symptoms may achieve adequate relief by using only oral antithistamines.12
Topical Antihistamines: Azelastine (Astelin), an intranasal antihistamine, has the same properties of oral antihistamines. It does not treat nasal congestion equally to intranasal corticosteroids or decongestants; however, it may provide some relief of nasal congestion.12 Azelastine is dosed twice daily and can be used in children 5 years of age and older.18 Common adverse effects include headache, sedation, and bitter taste after administration. This medication does not offer any benefits over oral antihistamines and intranasal corticosteroids.1,18
Leukotriene Modifiers: Antileukotriene agents are available to treat allergies and asthma. Montelukast (Singulair) is the only agent in this class approved for treatment of AR. A review of randomized clinical trials has shown that montelukast is comparable to loratadine in relieving symptoms associated with AR and may be equally efficacious to a combination of an intranasal corticosteroid with a second-generation oral antihistamine.12,15 Montelukast can be used in children as young as 2 years for AR and may be most beneficial in patients who also have asthma.12,18 Furthermore, patients who do not tolerate intranasal corticosteroids may receive relief of symptoms from either montelukast alone or in combination with an oral antihistamine.12
Topical Mast Cell Stabilizers: Cromolyn (Nasalcrom) nasal spray is a mast cell stabilizer available OTC that is effective in decreasing symptoms of AR if used regularly.15 Mast cell stabilizers decrease inflammation associated with allergies by inhibiting the mast cell release of histamine and other inflammatory mediators.1,12 This medication can be dosed 30 minutes prior to exposure; therefore, it may be particularly useful for patients with a specific known allergy who plan on coming in contact with that allergen. More efficacious than placebo, cromolyn is less effective when compared to intranasal corticosteroids and oral antihistamines.12,15 One drawback to its use is that cromolyn must be dosed four times daily to achieve symptom relief.1,12 Nasal pruritus, irritation, sneezing, and epistaxis are the most common adverse effects associated with use of cromolyn.1,4 Overall, the medication is well tolerated, which makes it especially useful for treating children with AR.12
Topical Anticholinergics: Topical anticholinergics, specifically ipratropium (Atrovent) nasal spray, may be effective in the treatment of rhinorrhea associated with AR.13 It generally does not relieve nasal pruritus or nasal congestion and therefore may be most beneficial in the treatment of nonallergic rhinitis or postnasal drip.1,15 Common adverse effects associated with its use include headache and epistaxis.4 To achieve maximum effectiveness, ipra tropium should be dosed two sprays in each nostril two to four times daily and initiated before symptom onset.4,11
Decongestants: Decongestants, medications marketed specifically to relieve nasal congestion, are available in both oral and topical dosage forms.11 Oral decongestants include pseudoephedrine (e.g., Sudafed), available behind the counter or by prescription, and phenylephrine (e.g., Sudafed PE), available OTC. Common adverse effects associated with the use of decongestants include insomnia, anorexia, tachycardia, and nervousness.11
The most common topical OTC decongestant is oxymetazoline (Afrin) nasal spray. Nasal decongestants are not recommended for the long-term treatment of AR and can only be used for a short period of time before rebound congestion occurs.12 Patients are at risk for developing rebound congestion, also known as rhinitis medicamentosa, if topical decongestants are used incorrectly. The maximum duration of continued use of a topical decongestant is less than 72 hours (3 days). Patients using topical decongestants should understand that if the agents are used longer than three days, rebound congestion will develop. Furthermore, if an intranasal corticosteroid is started, the topical decongestant should be discontinued.11 If extreme nasal congestion occurs, relief may be found with short-term use of nasal decongestants. Overall, decongestants have no role in the chronic treatment of AR.
Immunotherapy, or hyposensitization, may be used in the treatment of moderate-severe AR in those who do not receive adequate relief with combination therapy including an intranasal corticosteroid, and in patients who have coexisting diseases such as asthma or sinusitis.1,4,13,15 Immunotherapy is directed toward a specific known allergen and involves weekly subcutaneous injections of increasing doses of an allergen until a maintenance dose is found, after which it is administered at two- to six-week intervals.1,4,13,15 Although this disease-modifying treatment takes several years to complete, patients may experience relief for years following therapy.1,16
Immunotherapy can be quite dangerous, as the risk of an anaphylactic reaction is high.16 Systemic reactions occur in approximately 5% to 10% of patients receiving immuno therapy.4 However, the efficacy of immunotherapy for AR is well documented; patients receiving this treatment will experience improvement in their symptoms.1
A new approach to immunotherapy is to administer the allergen sublingually.4 This method is currently being used in Europe with no reports of systemic reactions recorded to date.4 Sublingual immunotherapy is not available in the United States. Immunotherapy is contraindicated in patients with severe cardiovascular disease and severe asthma.13 Agents discussed earlier can be used in combination with immunotherapy for complete relief of symptoms.
Children: Children may experience symptoms of AR due to a variety of other conditions. To be sure that AR is the correct diagnosis, children should be evaluated by a health care provider before initiating any pharmacologic therapy, including OTC medications. Overall, oral antihistamines and cromolyn are first-line agents for the treatment of AR in children. When choosing an oral antihistamine, comparing the adverse-effect profiles of the generations will lead one to select a second-generation oral antihistamine. As discussed earlier, second-generation antihistamines are associated with less drowsiness and can be dosed once to twice daily for most individuals.11 Cetirizine has recently gained OTC status and is approved for use in children aged 6 months and older, although its labeling states that drowsiness may occur.19 Cromolyn is considered first line in children and is approved for use in children 2 years and older.13 Cromolyn may have to be used for two to four weeks before maximum benefit is seen.18
As with the treatment of AR in adults, intranasal corticosteroids are an excellent treatment option for children with severe symptoms. Intranasal corticosteroids control sneezing, rhinorrhea, nasal pruritus, and congestion; however, with the exception of Veramyst, they have no effect on ocular symptoms.11,17 The intranasal corticosteroids approved for use in children are listed in Table 3.
Controversy continues about the use of corticosteroids in children. Current evidence suggests that the use of long-term intranasal corticosteroids in children has an excellent risk-benefit profile. The FDA states that the benefit of using intranasal corticosteroids in children for AR clearly outweighs the risk of children not attaining their perceived height. Children should be continually monitored while using intranasal corticosteroids, and other therapeutic options should also be implemented in order to use the lowest effective dose of steroid as possible.11
Parents should be cautioned on the use of OTC products for symptom relief in children. The FDA recently released a warning regarding the use of cold, cough, flu, and allergy products in this population, and currently does not recommend the use of these products in children and infants under the age of 2.20 The appropriateness of these agents in children aged 2 to 11 years is under investigation. Inappropriate use has resulted in potentially dangerous and life-threatening adverse effects. Specific products that were marketed toward this age group have been voluntarily withdrawn from the market. Parents who use these products in their children should only do so as specifically directed by a health care provider, and under close supervision.
Pregnancy: Treating chronic illness during pregnancy always presents a challenge. Choosing not to treat symptoms of AR during pregnancy will not harm the woman or her developing fetus. However, treatment can improve a pregnant woman's quality of life, and the decision to treat should be left up to the woman and her health care provider. Symptoms of AR often worsen during pregnancy partly due to increased blood flow to nasal turbinates; however, some women may experience resolution of their chronic symptoms of AR during pregnancy.15 As with all patients with AR, nonpharmacologic therapy should be implemented first, and if symptoms do not resolve, pharmacologic therapy can then be added.
Cromolyn, an intranasal mast cell stabilizer, is first line for the treatment of AR during pregnancy.16 This medication has been given a Pregnancy Risk Category B, which means that no fetal harm has been demonstrated in animal or human studies.18 Oral antihistamines can also be used during pregnancy. Chlorpheniramine, a first-generation antihistamine, has the most safety data supporting its use during pregnancy. This medication is dosed every four hours to provide 24-hour relief. Second-generation oral antihistamines that are Category B are loratadine, cetirizine, and levocetirizine. These antihistamines are generally chosen ahead of chlorpheniramine because they are less sedating and dosed once daily.
Intranasal corticosteroids can also be used during pregnancy if the above options are not providing enough relief. Most of the steroids are Category C, which means that no studies have been performed in humans or animals or that studies in animals have demonstrated fetal harm. The exception is budesonide nasal spray, which is Category B.18 Controversy remains about using intranasal corticosteroids during pregnancy. Even though these medications have been proven safe during pregnancy, recommendations still point women to using possibly less-effective medications that have a better-established history in terms of safety during pregnancy.16
The Pharmacist's Role
Pharmacists provide care to patients suffering from AR and are in a position to help patients maximize the use of medications, minimize adverse effects, and improve quality of life. Nonpharmacologic modalities should be recommended to all patients with AR to lessen symptoms. Pharmacists should use their expertise in selecting a product to treat symptoms of AR and to counsel on the proper technique of using a nasal spray (Table 4). Furthermore, pharmacists can recommend therapies for children and pregnant women so they are treated successfully and safely. AR is a common condition that impacts its sufferers greatly. Pharmacists can offer medication options and nondrug therapies to help manage the disease.
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