This activity is supported by an educational grant from Chattem, Inc.
Making Sense of Allergic Rhinitis: A Comprehensive Look at Causes, Comorbidities, and Effective Treatment Strategies
Rupal Patel Mansukhani, PharmD
Clinical Assistant Professor
Ernest Mario School of Pharmacy
Piscataway, New Jersey
Lucio Volino, PharmD
Clinical Assistant Professor
Ernest Mario School of Pharmacy
Piscataway, New Jersey
The following contributors have no relevant financial relationships with commercial interests to disclose.
Rupal Patel Mansukhani, PharmD
Lucio Volino, PharmD
Pharmacy Times Office of Continuing Professional Education
Planning Staff—David Heckard; Maryjo Dixon, RPh; Steve Lin, PharmD, RPh; and Donna Fausak
Editorial Staff—Bea Riemschneider and Kirk McKay
An anonymous peer reviewer is used as part of content validation and conflict resolution. The peer reviewer has no relevant financial relationships with commercial inter-ests to disclose.
At the conclusion of this knowledge-based CPE activity, pharmacists should be bet-ter prepared to:
Release date: February 12, 2014
Expiration date: February 12, 2016
Target audience: Pharmacists
Type of activity: Knowledge
Estimated time to complete activity: 2 hours
Review the incidence and basic pathophysiology of allergic rhinitis (AR).
Describe the common symptoms, presentation, and complications of AR.
Discuss current management of AR, including allergen avoidance, immunother-apy, and pharmacotherapy, including new and emerging dosage formulations.
Apply counseling strategies to help address common patient questions and mis-conceptions to achieve optimal symptom relief.
Pharmacy Times Office of Continuing Professional Education is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 2.0 contact hours (0.2 CEUs) under the ACPE universal activity number 0290-0000-14-004-H01-P. The activity is available for CE credit through February 12, 2016.
Rhinitis, classified as allergic or nonallergic, involves the presence of at least 1 of the following symptoms: nasal congestion, anterior and posterior rhinorrhea, sneezing, and itching. Nonallergic forms of rhinitis, such as infectious or drug induced, do not involve IgE-dependent events and are different from allergic rhinitis (AR).1
Allergy causes approximately 50% of all rhinitis cases,2
and based on reports from physicians, AR is the primary diagnosis for roughly 11.1 million office visits.3
AR is a common, chronic, inflammatory condition of the upper respiratory tract, and particularly the nasal mucosa, that causes significant socioeconomic and quality-of-life (QOL) burden.4-6
Although the exact prevalence of AR is difficult to ascertain, it is estimated that the disease affects approximately 30 to 60 million Americans1
and 400 million individuals worldwide.4,7
Further, up to 30% of adults and 40% of children suffer from AR annually.1
Education plays an important role in promoting adherence and optimizing therapeutic outcomes in AR.1
Focus can be placed on factors such as AR as a disease, its progression, potential pharmacologic and nonpharmacologic management options, its impact on other disease states, and other general concerns.1,4
As accessible health care providers, pharmacists are in an excellent position to answer questions and counsel patients with respect to these elements, with the intention of improving adherence and maximizing outcomes.
This article addresses some of the most common patient questions encountered during practice and/or when discussing AR with patients. These questions and responses apply counseling strategies to help address common queries and misconceptions and to empower patients with the information they need to achieve optimal symptom relief.
What are the different types of allergic rhinitis?
AR has 3 classifications: seasonal AR (SAR), perennial AR (PAR), and mixed AR. SAR, which is also referred to as hay fever, and PAR account for 20% and 40% of all AR cases, respectively, but are associated with different causative allergens and symptomatology throughout the year. SAR commonly results from an immunologic response to outdoor allergens, such as pollens or mold spores, with levels of exposure that may fluctuate throughout the year. PAR, on the other hand, is associated with a year round exposure to indoor allergens, such as animal dander, dust mites, cockroaches, and molds. Roughly 40% of patients with AR suffer from mixed AR, which consists of baseline PAR with exacerbations of SAR, depending on the time of year and extent of pollen exposure.2
Why do people develop allergic rhinitis?
People develop AR in response to allergens such as dust mites, animal dander, cockroaches, pollen, and mold.7
AR is mediated by allergen specific IgE produc-tion and presence that transitions through 3 main phases of allergic response: (1) allergic sensitization, (2) early-phase response, and (3) late-phase response.2
During the allergic sensitization period, threshold concentrations of allergens initiate a complex immune response that involves T lymphocyte activation, interleukin and cytokine release, and B-cell differentiation.2,8
This cascade of events culminates in the formation and release of allergen-specific IgE.2,8
The binding of this complex to mast cells and basophils produces allergen priming, sensitizing these mediators for future activation and/ or degranulation on allergen re-exposure.8
After priming has occurred, further allergen exposure produces an early-phase response within minutes. This response is led primarily by mast cell degranulation that releases preformed inflammatory mediators, such as histamine, proteases (ie, chymase, kininogenase, tryptase), tumor necrosis factor, leukotrienes, and other enzymes. Through nasal sensory nerve stimulation, these components initiate the development of early-phase symptoms, consisting of sneezing, nasal pruritus, and watery rhinorrhea, with minimal nasal congestion involvement.8
Shortly thereafter, additional mediators such as prostaglandins and leukotrienes are produced de novo and contribute to the early-phase response symptoms.2,5,8
The presence of additional cellular mediators such as eosinophils, basophils, neutrophils, T lymphocytes, macrophages, and monocytes leads to the late-phase response.2,8
This cell-mediated process, occurring approximately 4 to 8 hours after allergen exposure, presents similarly to the early-phase response, but with more pronounced congestion.2
Leukotrienes contribute to the early and late-phase response symptoms of sneezing and rhinorrhea, while being one of the main factors for developing nasal congestion.9
What increases my risk for allergic rhinitis and how can I reduce the risk?
Many factors can increase the risk for allergic rhinitis. Some risk factors (eg, family history, genetics, ethnicity, being born in the spring or summer) are not modifiable, but some factors can be addressed.2,10
Because AR is the body’s response to what the body considers foreign substances, reducing exposure to and/or avoiding allergens may help decrease the occurrence and worsening of symptoms. Table 1 lists the common risk factors that are associated with the development of AR.2,10
Symptoms of AR may be caused or aggravated by a wide range of indoor and outdoor allergen sources, such as dust mites, pets, cockroaches, pollen, and mold. Discovered in the 1990s, allergen avoidance is the least complex nonpharmacologic approach to AR symptom control and to improving patient QOL. Allergen avoidance will not harm a patient with AR, but studies on it have not been able to consistently demonstrate reduction in symptoms and medication use.1
There are many ways to avoid triggers for indoor allergens. For patients allergic to dust mites, covering pillows and mattresses with water vaporpermeable fabrics may drastically reduce the allergen levels.11
Removing carpets and rugs, washing bedding in hot water (120o
F), and vacuuming or using air filtration with high efficiency particulate air (HEPA) filters may also reduce dust mite exposure.1,12
Patients who are allergic to pet allergens may reduce symptoms by removing the animal from the home or taking the proper precautions to decrease pet dander exposure in the household. Some studies show that pet dander can be reduced by confining animals to an uncarpeted room with HEPA filtration and/or washing animals weekly or biweekly. Patients allergic to cockroaches may use physical or chemical control measures, such as keeping the home clean, keeping food in airtight containers, and using chemicals such as hydramethylnon and abamectin. Further, sealing cracks in flooring and caulking may reduce cockroach access into a household.12
Eliminating moisture sources, followed by cleaning nonporous surfaces with a diluted bleach solution, can help remove and prevent indoor, mold related allergic rhinitis.1
Keeping moisture levels at less than 50% and using air conditioners and/or dehumidifiers may also assist in reducing mold exposure.12
If outdoor allergens, such as pollen or mold spores, are the problem, closing windows and doors when counts are high can help reduce exposure.12
In addition, patients allergic to pollen may avoid the outdoors on sunny, windy days with low humidity, when the pollen count is high-est. Outdoor mold spore exposure can be reduced by using a face mask when gardening and lawn mowing.1
Other measures include avoiding the use of window or attic fans and drying clothes with a dryer rather than hanging them outside.13
It is important to remember that using more than 1 method of allergen avoidance may be necessary. Also, complete avoid-ance may be difficult or impossible.7
What are some potential problems associated with allergic rhinitis?
AR is associated with numerous short-and long-term complications that impact the patient’s overall QOL, and AR con-tributes to the development of other medical conditions or health issues. Complications and comorbidities tied to AR are listed in Table 2.6,7,14
AR has been reported to cause sinus problems, interfere with work by increasing presenteeism and absenteeism, and affect academic performance through the disruptive effect of nasal-related symptoms.4,7,15
In addition, the inconvenience of practical issues (eg, constantly having to rub the eyes, blowing or rubbing the nose, carrying tissues) also contributes to reduced QOL and to social challenges.6,14
Cognitive impairment, either independently or in affiliation with sleep disturbance, is also a significant complication of AR.6
It should be noted that asthma and AR are closely related, with AR identified as a risk factor for asthma7
that has been associated with the worsening and/or development of asthma symptoms7,14
; approximately 10% to 40% of patients with rhinitis also suffer from asthma, while more than 80% of patients with asthma have rhinitis.7
What are allergy shots, and do they really work?
If allergy avoidance is insufficient, pharmacotherapy or allergy immunotherapy may be beneficial. Allergy immunotherapy (ie, “allergy shots”) entails the repeated administration of specific allergens to patients with IgE-mediated conditions in an effort to provide immune protection against the allergic symptoms and inflammatory reactions associated with natural exposures to these allergens, thereby gradually “desensitizing” the patient to specific allergens. Immunotherapy may only be considered in patients who have specific IgE antibodies to the specific allergen. If the patient has IgE antibod-ies but the specific allergen cannot be determined, immunotherapy is not recommended.16
Currently, there are 2 predominant modes of allergen immunotherapy: subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT); however, other routes of administration for immunotherapy are currently being explored (eg, epicutaneous, intranasal). Europe currently has 2 SLIT and 1 SCIT grass pollen products for allergic rhinitis. In the United States, there are no specific medications that are FDA approved for use as SLIT or SCIT. Formulations used in the United States are patient specific, created by physicians’ offices.17
Randomized, clinical trials show little or no statistical difference between SLIT and SCIT at reducing symptom scores or medication use scores; however, the lack of significant differences between the 2 treatment strategies does not necessarily indicate equivalent efficacy. The data available were difficult to interpret due to multiple study designs—some were open label, and others were placebo controlled. To detect minor differences, large head-to-head studies are needed.17
The treatment route of SLIT is considered investigational, as is immunotherapy related to food hypersensitivities.16
Additional studies will be needed to determine appropriate dosing and to further evaluate treatment efficacy and safety. Currently, immunotherapy can be effective for management of allergic asthma, allergic rhinitis/conjunctivitis, and stinging insect hypersensitivity. Some evidence also suggests that immunotherapy may be effective in managing atopic dermatitis.16
Immunotherapy is not routinely recommended for the treatment of allergic symptoms unless the patient (1) has symptoms that are not adequately controlled by allergen avoidance or medication, (2) has adverse reactions to medications, (3) wants to reduce long-term use of medications, or (4) has a severe and/or prolonged condition.17
Other candidates for immunotherapy are those who have a history of systemic reactions to stings by insects of the order Hymenoptera, such as bees, wasps, yellow jackets, and hornets.16
Once an appropriate treatment candidate has been identified, the patient should be educated on the risks and benefits of therapy, treatment duration, and realistic expectations for outcomes related to the immunotherapy. The benefits of immunotherapy are decreased symptoms or medication use; however, the risk of systemic side effects such as angioedema, cough, wheezing, hypotension, and anaphylaxis still exists, with 86% of systemic reactions occurring less than 30 minutes after SCIT administration.16,18
Therefore, patients should be monitored for at least 30 minutes after treatment.
Typically, the 2 phases of immunotherapy treatment are the buildup phase and the maintenance phase. During the buildup phase, patients receive injections with increasing amounts of the allergens 1 to 3 times per week, generally for 3 to 6 months, depending on the number of injections needed.16
“The efficacy of immunotherapy depends on an appropriate dose, which would be defined as an optimal therapeutic dose of each of the constituents in the allergen immunotherapy extract.”16
Typically, the physician will determine the concentration of allergen in the specific allergen containing extract, which complicates the design of well controlled clinical trials, as each manufacturer/physician may have its own in-house standard. During the build-up phase, allergic symptoms may improve marginally, but the patient must enter the maintenance phase of treatment to observe the full benefits of immunotherapy.17
The maintenance vial is considered to have the highest concentration of allergen used in the course of allergy immunotherapy.16
This concentration is determined by the physician prior to initiation of therapy. The maintenance phase of allergen immunotherapy begins when a therapeutic dose for the maintenance vial is achieved. During the maintenance phase, the intervals between treatments increase to allow less allergen in the patient’s system while maintaining allergy symptom control. Generally, the interval ranges from every 4 to 8 weeks for venom, and every 2 to 4 weeks for inhalant allergens. If symptoms are improving and immunotherapy is working, the maintenance treatment should be reevaluated after 3 to 5 years of therapy. Since treatment may take many years, adherence can be an issue and should be discussed with patients. If symptoms seem to be getting worse or remain the same, there is no use in continuing treatment because the formulation is not showing benefit.16
How is allergic rhinitis treated?
Many different treatment options are available for AR. Pharmacotherapy is usually chosen based on the type of AR (ie, SAR, PAR, mixed type), symptoms, severity, age, and comorbid conditions.1
Depending on the drug class, treatments are available over the counter or with a prescription. Currently, oral antihistamines, decongestants, and mast cell stabilizers are available over the counter. Corticosteroids, leukotriene receptor antagonists, intranasal anticholinergics, and antihistamines are available by prescription only.
Antihistamine products are the most common drug class used for the treatment of AR, with oral, intranasal, and ocular formulations that are indicated for use in AR. Antihistamines bind to histamine1
) receptors to prevent the inflammatory action of histamine at the receptor sites in the respiratory tract, decreasing symptoms of allergic rhinitis, such as sneezing and nasal discharge. Currently, 2 classes of oral antihistamines are available: first generation (nonselective) and second-generation (selective). Selective agents (eg, cetirizine [Zyrtec], fexofenadine [Allegra], levocetirizine [Xyzal], loratadine [Claritin], desloratadine [Clarinex]) are preferred over nonselective agents (eg, chlorpheniramine [Chlorphen-12], diphenhydramine [Benadryl]) because selective agents bind to the peripheral H1
receptors versus the central H1
receptors found in the central nervous system. Selective binding produces less sedation, performance impairment, constipation, dry mouth, blurred vision, and dizziness. Second-generation agents are also preferred because they can be taken once daily. Among the newer, nonsedating antihistamines, no single agent has been conclusively found to achieve superior over-all response rates compared with older agents.1
Oral antihistamines are effective against symptoms including rhinorrhea, sneezing, nasal itching, and eye symptoms.19
Oral antihistamine formulations are associated with several side effects, most commonly constipation, dry mouth, and somnolence.1,20
However, if the oral formulation is causing unwanted adverse effects, it may be beneficial for a patient to try an intranasal formulation; these formulations are available by prescription only and include olopatadine (Patanase) and azelastine (Astelin). Further, patients may benefit from an intranasal spray if they have tried oral antihistamine products without success, with 1 study demonstrating that intranasal azelastine showed a benefit in patients who had not achieved relief with oral loratadine.21
Finally, ocular antihistamines may be used in patients with ocular symptoms that are not relieved by oral antihistamine formulations. Ocular antihistamines are available over the counter (eg, ketotifen [Zaditor, Zyrtec Itchy Eye]) or by prescription (eg, azelastine [Optivar]). Naphazoline and pheniramine (Naphcon-A)—an antihistamine (pheniramine component) and decongestant (naphazoline component) combination product—is also available over the counter.
Corticosteroids are the most effective class used to treat moderate to severe AR, and the nasal formulation is associated with minimal adverse effects while providing relief of sneezing, runny nose, and nasal congestion.1,22,23
Examples of intra-nasal corticosteroids include mometasone (Nasonex), fluticasone (Flonase), triamcinolone (Nasacort), beclomethasone (Beconase), and flunisolide (Nasalide). The FDA recently approved Nasacort Allergy 24HR as an OTC treatment. Nasacort OTC is expected to be released in spring 2014. Corticosteroids work by inhibiting the inflammatory response, reducing intracellular edema, and causing mild vasoconstriction. The most common adverse effects associated with intranasal corticosteroids are sneezing and nosebleeds.1
On the other hand, the use of oral corticosteroids is limited due to potentially serious adverse effects, such as peptic ulceration, alteration of glucose level, and depression with suicidal intent. Therefore, oral corticosteroid products are typically reserved for short-term treatment of patients with severe AR experiencing no relief from other agents.1,20
Cromolyn sodium (NasalCrom) is a mast cell stabilizer that prevents the degranulation of mast cells and release of allergic mediators such as histamine. It is available as an OTC nasal spray for the self-management of AR. Its most common side effect is sneezing after administration. Although cromolyn sodium causes minimal side effects, it requires multiple doses throughout the day, which makes the medication less convenient than other treatment options, such as second-generation oral antihistamines.24
Intranasal ipratropium bromide (Atrovent), a prescription anticholinergic agent, provides symptomatic relief of runny nose or rhinorrhea20
but does not help to relieve symptoms of nasal congestion, sneezing, or postnasal drip; therefore, its use in patients with AR is often limited. Further, ipratropium requires multiple daily doses and therefore is not preferred over other treatment options that offer a more convenient dosing schedule. Side effects of ipratropium bromide are similar to those of other nasal formulations, including dryness and nosebleeds.25
Nasal decongestants are available in systemic or topical formulations and act on adrenergic receptors in the nasal mucosa to improve ventilation.20
Nasal decongestant spray is available as an OTC product, is widely used due to its established efficacy, and may include the following active ingredients: naphazoline (Privine), oxymetazoline (Afrin; Neo-Synephrine Nighttime12 hour), or phenylephrine (Neo-Synephrine). However, it should be noted that if a nasal decongestant is used for more than 3 to 5 days, rebound congestion or rhinitis medicamentosa may occur; therefore, patients should be instructed to avoid the use of topical decongestants for more than 5 days.20
Oral decongestants (ie, pseudoephedrine and phenylephrine) may cause systemic adverse effects, such as insomnia and increased blood pressure; therefore, patients should be advised to take these products during waking hours, and the use of decongestants should be avoided in patients with hypertension, hyperthyroidism, prostatic hypertrophy, glaucoma, and psychiatric disorders. Caution should also be used in patients taking beta blockers and monoamine oxidase inhibitors.19,20,25
Lastly, leukotriene receptor antagonists, such as montelukast (Singulair), may be used for the treatment of PAR, either alone or in combination with an antihistamine. Other agents in the class, such as zafirlukast (Accolate), are not FDA approved for the treatment of allergic rhinitis. “Leukotriene receptor antagonists were better than placebo, equivalent to oral H1
antagonists, and inferior to intranasal corticosteroids for treating seasonal allergic rhinitis.”26
Montelukast is available with once daily dosing, but as a prescription agent, the medication may cost significantly more compared with OTC products. To determine optimal treatment options for any individual patient with AR, it is important to evaluate all factors, such as efficacy, side effects, and cost.
Education and counseling may help address potential patient concerns and clarify misconceptions. The following are common misconceptions that patients may have during AR discussions.
Prescription medications are always more effective than OTC medications.
Many OTC medications for treating AR were once approved as prescription medications. For a prescription to OTC switch to occur, a prescription product must demonstrate its appropriateness for self-administration, with studies that show the average patient’s ability to read and follow the directions found on the package labeling. Further, the FDA must approve the request for making the switch. Many allergy medications are now available without a prescription, which does not indicate less efficacy than prescription counterparts; rather, a medication’s OTC status indicates that the medication is “safe and effective for use by the general public without seeking treatment by a health professional.”27
You only need to take medication when showing allergy symptoms.
Some patients have SAR associated with very specific allergens. Primarily, patients should be educated about avoiding allergen triggers to prevent symptoms and exacerbations.1
Of course, because triggers may sometimes be unavoidable, patients should also be advised to initiate their medication for AR 1 to 2 weeks prior to the time they expect their allergies to begin.
Pollen counts can predict “bad” days.
Allergic response to allergens is highly dependent on the individual and is contingent on the amount and type of allergen exposure. Although pollen counts have been found to affect AR symptoms and medication use, some individuals have a persistent allergic response after an allergy season, even when pollen counts have decreased, which may be caused by a process referred to as priming. As the allergy season progresses and pollen levels increase, the nasal passages become more sensitive to the allergen, meaning that less allergen may be required to cause an allergic response. Although pollen counts may be decreasing, there is still enough allergen to cause a response due to the heightened sensitivity of the nasal passages.1
This process may also lead to an exaggerated response toward irritant triggers, such as tobacco smoke, temperature changes, unpleasant odors, and even exercise, resulting in AR symptoms.2
An individual can outgrow his or her seasonal or perennial allergies.
The frequency of allergic rhinitis increases with age until an individual becomes an adult. In 80% of cases, AR develops before 20 years of age. Depending on the type of AR (eg, SAR, mixed), symptoms may also come and go throughout the year. PAR happens more frequently in adults, whereas SAR tends to be more common in children and adolescents.1
Overall, remission of AR symptoms occurs relatively infrequently.7
Rain washes away pollen.
Rain is actually one of the ways that pollen is moved for pollination between plants. Rain can capture and disperse airborne allergens to the ground or scatter settled allergens.28
However, allergy symptoms may improve on rainy, cloudy days with little or no wind, because pollen is less likely to disperse freely under these conditions.29
It is still important to use proper allergen avoidance practices to reduce allergen exposure and minimize allergy symptoms during this time.
If you use 1 brand of allergy medication, you build a tolerance, and it will stop working.
Tolerance to allergy medications does not occur. Depending on the type of allergy the patient has, the symptoms may worsen over time due to patient and/or environmental factors. For example, the first time someone presents with allergies may be during a mild pollen season, but the patient’s symptoms may be worse the following year if the pollen count is higher. Although the patient may feel as though the medication is no longer working, the cause for increased allergic symptoms may be the increased allergen exposure.
Pharmacists are in an excellent position to assist patients in managing their seasonal and PAR symptoms. Reviewing basic principles such as allergen avoidance and the use of preventive pharmacologic options can help patients prevent and/or reduce the severity of symptom progression. Pharmacologic therapy should be individualized to optimize therapy.
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.
Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol. 2001;108(1 suppl):S2-S8.
National ambulatory medical care survey: 2010 sum-mary tables. Centers for Disease Control and Prevention website. www.cdc.gov/nchs/data/ahcd/namcs_summary/2010_namcs_web_tables.pdf.AccessedNovember 25, 2013.
Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet. 2011;378(9809):2112-2122.
Howarth PH, Salagean M, Dokic D. Allergic rhinitis: not purely a histamine related disease. Allergy. 2000;55(suppl 64):7-16.
Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(1):3-9.
Bousquet J, Khaltaev N, Cruz AA, et al. ARIA (allergic rhinitis and its impact on asthma) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy. 2008;63(suppl 86):8-160.
Rosenwasser LJ. Current understanding of the pathophysiology of allergic rhinitis. Immunol Allergy Clin North Am. 2011;31(3):433-439.
Borish L. Allergic rhinitis: systemic inflammation and implications for management. J Allergy Clin Immunol. 2003;112(6):1021-1031.
Jones N. Allergic rhinitis: aetiology, predisposing and risk factors. Rhinology. 2004;42(2):49-56.
Owen S, Morgenstern M, Hepworth J, et al. Control of house dust mite in bedding. Lancet. 1990;335:396-397.
Woodcock A, Custovic A. Allergen avoidance: does it work? Br Med Bull. 2000;56(4):1071-1086.
Pollen. National Institute of Environmental Health Scienceswebsite.www.niehs.nih.gov/health/topics/conditions/asthma/allergens/pollen/. Updated April 2012. Accessed December 7, 2013.
Settipane RA. Complications of allergic rhinitis. Allergy Asthma Proc. 1999;20(4):209-213.
Blaiss MS, Meltzer EO, Derebery MJ, Boyle JM. Patient and healthcare provider perspectives on the burden of allergic rhinitis. Allergy Asthma Proc. 2007;28(suppl 1):S4-S10.
Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 suppl):S1-S15.
Calderon MA, Casale TB, Togias, et al. Allergen specific immunotherapy for respiratory allergies:from metaanalysis to registration and beyond. J Allergy Clin Immunol. 2011;127(1):30-38.
Epstein TG, Liss GM, Murphy Berendts K, et al. Immediate and delayed onset systemic reactions after subcutaneous immunotherapy injections: ACAAI/ AAAAI surveillance study of subcutaneous immunotherapy year 2. Ann Allergy Asthma Immunol. 2011;107(5):426-431.
Price D, Bond C, Bouchard J, et al. International Primary Care Respiratory Group (IPCRG) Guidelines: management of allergic rhinitis. Prim Care Respir J. 2006;15(1):58-70.
May JR, Smith PH. Allergic rhinitis. In: Wells BG, ed. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw Hill; 2011. www.accesspharmacy.com/content.aspx?aID=7998284.AccessedDecember 13, 2013.
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(2):205-211.
Riccio AM, Saverino D, Pesce G, et al. Effects of different up dosing regimens for hymenoptera venom immunotherapy on serum CTLA-4 and IL-10. PLoS One. 2012;7(6):e37980.
Spector SL, Nicklas RA, Chapman JA, et al. Symptom severity assessment of allergic rhinitis: part 1. Ann Allergy Asthma Immunol. 2003;91:105-116.
Why NasalCrom Nasal Allergy Spray. Nasalcrom website. www.nasalcrom.com/en/Why_Nasalcrom.aspx. Accessed January 17, 2014.
DailyMed National Institutes of Health. Ipratropium bromide. dailymed.nlm.nih.gov/dailymed/archives/fdaDru-gInfo.cfm?archiveid=6690. Accessed January 17, 2014.
Rodrigo GJ, Yanez A. The role of antileukotriene therapy in seasonal allergic rhinitis: a systematic review of randomized trials. Ann Allergy Asthma Immunol. 2006;96:779-786.
Drug application for over-the-counter (OTC) drugs. FDA website.www.fda.gov/drugs/developmentapprovalpro-cess/howdrugsaredevelopedandapproved/approvalap-plications/over-the-counterdrugs/default.htm.Accessed December 8, 2013.
Burge HA, Rogers CA. Outdoor allergens. Environ Health Perspect. 2000;108(suppl 4):653-659.
Outdoorallergens:tipstoremember.AmericanAcademy of Allergy Asthma & Immunology website. www.aaaai. org/conditions-and-treatments/library/at-a-glance/out-door-allergens.aspx. Accessed December 7, 2013.