Allergic rhinitis (AR) is an atopic disease characterized by symptoms of nasal congestion, clear rhinorrhea, sneezing, and nasal pruritis. It can affect one in every six individuals and has associations with significant morbidity, loss of productivity, and health-care costs. Historically, the belief was that AR was a condition of the nasal passages only, but treatment of AR is now as a systemic disease due to its close association with asthma and atopic dermatitis. AR can classify as either seasonal (intermittent) or perennial (chronic), with approximately 20% of cases being seasonal, 40% perennial, and 40% with features of both. Outside of nasal symptoms, patients suffering from untreated AR can also have allergic conjunctivitis, post-nasal drip, non-productive cough, Eustachian tube dysfunction, and chronic sinusitis. Once diagnosed, AR is treatable with a variety of modalities, with intra-nasal glucocorticoids being first-line therapy.
Allergic rhinitis is an immunoglobulin (Ig)E-mediated response against inhaled allergens that cause inflammation driven by type 2 helper (Th2) cells. There is a considerable genetic component to the allergic reaction, classified into early and late phase reactions. Initial response occurs within minutes of exposure to allergens and characteristically manifests degranulation of host mast cells. This releases a variety of pre-formed and newly synthesized mediators, with histamine (H) being one of the primary mediators of allergic rhinitis. Histamine induces sneezing via the trigeminal nerve and also plays a role in rhinorrhea by stimulating mucous glands. Other immune mediators such as leukotrienes and prostaglandins are also implicated as they act on blood vessels to cause nasal congestion. Four to six hours after initial response, an influx of cytokines, such as interleukins (IL)-4 and IL-13, from mast cells occurs, signifying the development of the late phase response. These cytokines, in turn, facilitate infiltration of eosinophils, T-lymphocytes, and basophils into the nasal mucosa and produce nasal congestion.
In long-standing AR, due to eosinophilic infiltration and nasal mucosa obliteration, a non-IgE mediated hyperresponsiveness develops. The nasal mucosa now becomes hyperreactive to normal stimuli (such as tobacco smoke, cold air) and causes symptoms of sneezing, rhinorrhea, and nasal pruritis.
There are data to suggest there may be a genetic component to the development of allergic rhinitis, but studies are generally lacking. Monozygotic twins show 45 to 60% concordance, and dizygotic twins have a concordance rate of approximately 25% in the development of AR. Specific regions on chromosomes 3 and 4 also correlate with allergic responses.
Prevalence of allergic rhinitis based on physician diagnosis is approximately 15%; however, the prevalence is estimated to be as high as 30% based on patients with nasal symptoms. AR is known to peak in the second to fourth decades of life and then gradually decline. The incidence of AR in the pediatric population is also quite high, making it one of the most common chronic pediatric disorders. According to data from the International Study for Asthma and Allergies in Childhood, 14.6% in the 13 to 14 year age group and 8.5% in the 6 to 7 year age group display symptoms of rhinoconjunctivitis linked to allergic rhinitis.  Seasonal allergic rhinitis seems to be more common in the pediatric age group, whereas chronic rhinitis is more prevalent in adults.
A systematic review from 2018 estimated that 3.6% of adults had missed work and 36% had impaired work performance due to allergic rhinitis. Economic evaluations have shown that indirect costs associated with lost work productivity account for the majority of the cost-burden for AR.
Risk factors for developing AR include a family history of atopy, male sex, a presence of allergen-specific IgE, a serum IgE greater than 100 IU/mL before age 6, and/or higher socioeconomic status. Studies in young children have shown a higher risk of AR in those with early introduction of foods or formula and/or heavy exposure to cigarette smoking in the first year of life. Although many recent studies have evaluated the link between pollution and development of AR, no significant correlation yet exists definitively. Interestingly, there are several factors identified that may have a protective effect on the development of AR. The role of breastfeeding in the development of AR is often debated, but it is still recommended due to its many other known benefits and no associated harms. There is no evidence that pet avoidance in childhood prevents AR; however, it is hypothesized that early pet exposure may induce immune tolerance. There is growing interest in the "farm effect" on the development of allergies, and a metanalysis of 8 studies showed a 40% lower risk in subjects who had lived on a farm during their first year of life.
Taking a thorough, detailed history is an essential part of the evaluation of AR, so questions should focus on types of symptoms, the time, duration, and frequency of symptoms, suspected exposures, and exacerbating factors. Patients with intermittent or seasonal allergic rhinitis have symptoms of sneezing, rhinorrhea, and watery eyes. On the other hand, patients with persistent, chronic AR complain of postnasal drip and chronic nasal congestion and obstruction. These patients will often have a family history of allergic rhinitis or a personal history of asthma. Patients with intermittent rhinitis may report triggers such as pollens, animal dander, flooring/upholstery, mold, humidity, and/or tobacco smoke.
On physical examination, clinicians may notice mouth breathing, frequent sniffling and/or throat clearing, transverse supra-tip nasal crease, and dark circles under eyes (allergic shiners). Otoscopic examination of the nose typically reveals swelling of the nasal mucosa and thin, clear secretions. Whenever possible, an internal endoscopic examination of the nasal cavity should be conducted to assess for nasal polyps and structural abnormalities. Pneumatic otoscopy can be used to assess for eustachian tube dysfunction, which can be a common finding in patients with allergic rhinitis. Palpation of sinuses may elicit tenderness in patients with chronic symptoms. These patients should also undergo careful examination for signs of asthma or dermatitis.
Allergic rhinitis is largely a clinical diagnosis made based on a thorough history and physical. A positive response to empiric treatment with a nasal glucocorticoid can help clinch the diagnosis. A formal diagnosis is possible with either serum testing for allergen-specific IgE or allergy skin testing. As stated by the American Academy of Otolaryngology guidelines, allergy testing should be reserved for patients who are unresponsive to empiric treatment or require identification of a specific allergen to target therapy. Serum testing does not require trained technicians, and the patient does not need to stop taking antihistamines in advance. On the other hand, skin allergy testing requires a trained professional to perform testing and results are available immediately. In patients with seasonal symptoms, testing should is preferable when symptoms are present to be able to best identify the triggers. Skin testing is known to have slightly better sensitivity than serum testing and is more cost-effective. Contraindications to skin allergy testing include patients with uncontrolled or severe asthma, unstable cardiovascular disease, pregnancy, and/or concurrent beta-blocker therapy. H2-receptor antagonists, tricyclic antidepressants and anti-IgE monoclonal antibody omalizumab can interfere with allergy skin test response; therefore, cessation is advisable before testing.
Radiographic imaging is not routinely recommended for the diagnosis of AR and is mostly used to rule out other conditions such as rhinosinusitis.
Avoidance of triggers, especially in those with seasonal symptoms, is encouraged, although it is not always practical, such as in the case of allergy to pollens. Precautions can be taken to avoid dust mites, animal dander, and upholstery. If removal of a pet from the home is not feasible, isolating the pet to a single room in the house may be an option. It is important to note that it may take up to 20 weeks to completely eliminate cat dander from a home even after removal. It is also recommended to use allergen-impermeable bedding covers, wash sheets in hot water, and use a vacuum cleaner with high-efficiency particulate air (HEPA) filters.
Pharmacological options include antihistamines, intranasal steroids, leukotriene receptor antagonists (LTRAs), and immunotherapy. First-generation antihistamines include diphenhydramine, chlorpheniramine, and hydroxyzine; whereas, fexofenadine, loratadine, desloratadine, and cetirizine are examples of second-generation antihistamines. Both first- and second-generation antihistamines are effective at controlling symptoms of AR, but first-generation antihistamines can be quite sedating due to their ability to cross the blood-brain barrier. These agents also act on muscarinic receptors, causing side effects of dry mouth, urinary retention, constipation, and/or tachycardia. Second-generation antihistamines have improved H1 selectivity, are less sedating, and have longer half-lives (12 to 24 hours) compared to those of the first-generation. Fexofenadine has no sedating effects, but loratadine and desloratadine may be sedating at higher doses. Cetirizine has the most potential for sedation of all second-generation antihistamines. In terms of symptom relief, there is no one agent recommended over others. Intranasal antihistamines, such as azelastine, have a rapid onset and are more efficacious than oral antihistamines in relieving nasal symptoms. They are recommended as first or second-line therapies for AR.
Intranasal corticosteroid therapy can be as monotherapy or in combination with oral antihistamines in patients in patients with mild, moderate, or severe symptoms. Studies have shown intranasal corticosteroids are superior to antihistamines in effectively reducing nasal inflammation and improving mucosal pathology. Commonly available nasal sprays in the United States include beclomethasone, budesonide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. Proper administration of nasal spray is critical in achieving an optimal clinical response; therefore, patients should always receive counsel on the appropriate use of devices. They should be used regularly, as their peak effect may take multiple days to develop. The most common side effect reported is nasal irritation, which can be prevented by spraying away from the nasal septum. Oral and injectable steroids have been shown to alleviate symptoms of AR but are not recommended for routine use due to their significant side-effect profile.
Leukotriene receptor antagonists (LTRAs) such as montelukast and zafirlukast can be beneficial in patients with AR, but they are not as efficacious as intranasal corticosteroids. Their use is often in combination therapy with other agents. For patients in whom avoidance measures and combination pharmacotherapy are not effective, allergen immunotherapy should be considered. Subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) are commonly used therapies. Weekly incremental doses are given for 6 to 8 months, followed by maintenance doses for 3 to 5 years. Typically, patients experience a prolonged, protective effect, and therapy can be ceased.
Oral decongestants such as pseudoephedrine are useful in relieving symptoms but are not recommended for extended daily use due to their side-effect profile. Intranasal decongestants such as xylometazoline are alpha-agonists that are delivered directly to nasal tissue to produce vasoconstriction. Prolonged use of intranasal decongestants have a risk of causing rebound nasal congestion (rhinitis medicamentosa) and, therefore, should not be used for more than a week. Sodium cromoglycate (Cromolyn) is effective in reducing sneezing, rhinorrhea, and nasal pruritis, so it is a reasonable option. Surgical treatment is reserved for patients with rhinitis, polyposis, or chronic sinus disease refractory to medical treatment. Budesonide is the only FDA approved agent for pregnant patients experiencing symptoms of allergic rhinitis. Omalizumab, a monoclonal antibody, has shown to be beneficial in patients with AR, although the cost associated with therapy is a limiting factor in its use. Nasal saline can be another option in conjunction with other treatment modalities. Isotonic solutions have shown to be more beneficial in adults, whereas hypertonic solutions may be more effective in children.
The differential diagnosis for AR includes other forms of rhinitis that are not allergic. Children, particularly those under the age of 2 years, should also be assessed for congenital causes of nasal obstruction, such as choanal atresia and immunodeficiencies.
In studies comparing the effects of intranasal corticosteroids to topical antihistamines and oral antihistamines, intranasal steroids were proven to be more beneficial in relieving symptoms of sneezing, rhinorrhea, and nasal pruritis and blockage and are, therefore, recommended as first-line therapy for all patients with AR. There is great evidence for the efficacy of immunotherapy for AR and allergic asthma, and it is the only disease-modifying intervention in allergic conditions.
Anti-H3 and H4 antihistamines are currently under study for use in AR, but no agents have received approval yet. Roflumilast, a phosphodiesterase-4 (PDE4) inhibitor approved for patients with COPD, has been proven to be beneficial in AR in one small study, but further studies to confirm results are lacking. A new route of administration for immunotherapy is the injection of allergen directly into lymph nodes. It has been proven to induce a 10-fold higher allergen-specific IgG response that is demonstrated by improved efficacy and safety. Dapilumab, a fully humanized monoclonal antibody, improved AR-related nasal symptoms in a recent randomized, double-blind, placebo-controlled trial. It works by inhibiting signaling of IL-4 and IL-13, which are both key drivers of immune diseases. Novel therapeutic approaches such as these are in development or clinical trials and look promising in the treatment of AR.
The belief is that the prevalence of allergic rhinitis peaks in adolescence and gradually decreases with advancing age. In a longitudinal study, at the time of the 23-year follow up, 54.9% of patients showed improvement in symptoms with 41.6% of those being symptom-free. Patients who had an onset of symptoms at a younger age were more likely to show improvement. The severity of AR can vary over time and depends on a variety of factors such as location and season. Approximately 50% of patients receiving grass allergy immunotherapy noted improvement in symptoms that continued 3 years after discontinuation of therapy.
Chronic rhinosinusitis, although distinct from allergic rhinitis, can be a complication of AR. It is characterized by nasal inflammation with symptoms of nasal congestion or discharge, ongoing for longer than 3 months. Chronic rhinosinusitis may also demonstrate findings of nasal polyps (nasal polyposis), which form as a result of chronic inflammation of the paranasal sinus mucosa. Nasal polyps are typically benign and present bilaterally. Unilateral nasal polyps should raise concern for malignancy. The incidence of nasal polyps in the general population is approximately 4% and more common in males. Treatment options include topical steroids and saline irrigation. Surgical removal is reserved for patients who do not respond to medical therapy.
It is also a known fact that sensitization to allergens in AR can alter immunological parameters of the adenoids, resulting in adenoid hypertrophy. Eustachian tube dysfunction commonly manifests in patients with AR and presents as ear fullness, otalgia, and ear popping. Approximately 10 to 40% of patients with AR also have concurrent asthma, and some studies suggest asthma is more common in moderate to severe persistent rhinitis. Many studies have demonstrated AR to be an independent risk factor for asthma, especially in patients diagnosed with AR during infancy. Some other associated complications include otitis media with effusion, persistent cough, and eosinophilic esophagitis, although there is a need to define the link more clearly.
Patients undergoing allergen desensitization (allergy shots) can experience an acute exacerbation of rhinitis or asthma, or, in a worst-case scenario, the patient could progress to anaphylaxis. Therefore, staff members in offices that provide this therapy should be well-versed in the diagnosis and management of such severe reactions and have the appropriate emergency medications (especially epinephrine) and airway management equipment immediately available.
Allergic rhinitis is most often diagnosed and managed by primary care physicians/providers. However, patients who fail traditional therapies for AR are eligible for referral to a specialist, such as an allergist or an otolaryngologist (ENT) with an allergy focus. Patients who are deemed candidates for immunotherapy typically obtain a referral to allergists for therapy. Specific findings on the physical exam should also prompt a referral, such as multiple nasal polyps in a pediatric patient, which is highly suggestive of cystic fibrosis. Patients who present with bloody or unilateral nasal discharge (not basic epistaxis) should be urgently referred to an ENT to rule out malignancy. Any concern for cerebrospinal fluid leak causing rhinorrhea also warrants referral to an ENT specialist.
Patients often underestimate the severity of this condition and fail to seek medical therapy. It is important to get rhinitis under control, especially due to the link between AR and asthma, and poor control of rhinitis typically predicts poor control of asthma. Patient compliance with the treatment regimen is key in proper management and alleviation of symptoms. Patients should receive educational materials with information about allergic rhinitis and its implications. Moreover, patient education on proper administration of nasal sprays also plays an essential role in a patient's response to therapy. Patients should be advised to look down and squirt nasal spray just inside nostril aiming toward the outer walls on both sides. It should be stressed that the patient should not take a deep breath or sniff hard after spraying. Counseling patients on avoidance of known allergens is a necessary but time-consuming task.
According to the "ecology of medical care" model, only a minority of patients seek medical care for their symptoms; and most of these are managed by their primary care physician/provider (PCP). Therefore, it is crucial to provide patients information on self-management and when to contact their PCP. Involvement of community pharmacists and nurse practitioners can play a vital role in achieving these goals. PCPs and allergy specialists often work closely in co-managing patients with AR. Access to healthcare and specialists vary globally; but, when available, PCPs, pediatricians, allergists, and/or ENT specialists may be involved in caring for these patients.
|||Kakli HA,Riley TD, Allergic Rhinitis. Primary care. 2016 Sep; [PubMed PMID: 27545735]|
|||Skoner DP, Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. The Journal of allergy and clinical immunology. 2001 Jul; [PubMed PMID: 11449200]|
|||Pawankar R,Mori S,Ozu C,Kimura S, Overview on the pathomechanisms of allergic rhinitis. Asia Pacific allergy. 2011 Oct; [PubMed PMID: 22053313]|
|||Min YG, The pathophysiology, diagnosis and treatment of allergic rhinitis. Allergy, asthma [PubMed PMID: 20358020]|
|||Tran NP,Vickery J,Blaiss MS, Management of rhinitis: allergic and non-allergic. Allergy, asthma [PubMed PMID: 21738880]|
|||Wheatley LM,Togias A, Clinical practice. Allergic rhinitis. The New England journal of medicine. 2015 Jan 29; [PubMed PMID: 25629743]|
|||Mir E,Panjabi C,Shah A, Impact of allergic rhinitis in school going children. Asia Pacific allergy. 2012 Apr; [PubMed PMID: 22701858]|
|||Varshney J,Varshney H, Allergic Rhinitis: an Overview. Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2015 Jun; [PubMed PMID: 26075169]|
|||Vandenplas O,Vinnikov D,Blanc PD,Agache I,Bachert C,Bewick M,Cardell LO,Cullinan P,Demoly P,Descatha A,Fonseca J,Haahtela T,Hellings PW,Jamart J,Jantunen J,Kalayci �,Price D,Samolinski B,Sastre J,Tian L,Valero AL,Zhang X,Bousquet J, Impact of Rhinitis on Work Productivity: A Systematic Review. The journal of allergy and clinical immunology. In practice. 2018 Jul - Aug; [PubMed PMID: 29017832]|
|||Wise SK,Lin SY,Toskala E,Orlandi RR,Akdis CA,Alt JA,Azar A,Baroody FM,Bachert C,Canonica GW,Chacko T,Cingi C,Ciprandi G,Corey J,Cox LS,Creticos PS,Custovic A,Damask C,DeConde A,DelGaudio JM,Ebert CS,Eloy JA,Flanagan CE,Fokkens WJ,Franzese C,Gosepath J,Halderman A,Hamilton RG,Hoffman HJ,Hohlfeld JM,Houser SM,Hwang PH,Incorvaia C,Jarvis D,Khalid AN,Kilpel�inen M,Kingdom TT,Krouse H,Larenas-Linnemann D,Laury AM,Lee SE,Levy JM,Luong AU,Marple BF,McCoul ED,McMains KC,Mel�n E,Mims JW,Moscato G,Mullol J,Nelson HS,Patadia M,Pawankar R,Pfaar O,Platt MP,Reisacher W,Rond�n C,Rudmik L,Ryan M,Sastre J,Schlosser RJ,Settipane RA,Sharma HP,Sheikh A,Smith TL,Tantilipikorn P,Tversky JR,Veling MC,Wang Y,Westman M,Wickman M,Zacharek M, International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. International forum of allergy [PubMed PMID: 29438602]|
|||Small P,Kim H, Allergic rhinitis. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2011 Nov 10; [PubMed PMID: 22166009]|
|||Y��ez A,Rodrigo GJ, Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis. Annals of allergy, asthma [PubMed PMID: 12452206]|
|||Ratner PH,Howland WC 3rd,Arastu R,Philpot EE,Klein KC,Baidoo CA,Faris MA,Rickard KA, Fluticasone propionate aqueous nasal spray provided significantly greater improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis compared with montelukast. Annals of allergy, asthma [PubMed PMID: 12775135]|
|||Masieri S,Cavaliere C,Begvarfaj E,Rosati D,Minni A, Effects of omalizumab therapy on allergic rhinitis: a pilot study. European review for medical and pharmacological sciences. 2016 Dec; [PubMed PMID: 28051241]|
|||Scadding GK, Optimal management of allergic rhinitis. Archives of disease in childhood. 2015 Jun; [PubMed PMID: 25838332]|
|||Heffler E,Brussino L,Del Giacco S,Paoletti G,Minciullo PL,Varricchi G,Scadding G,Malvezzi L,De Virgilio A,Spriano G,Puggioni F,Fornero M,Rolla G,Canonica GW, New drugs in early-stage clinical trials for allergic rhinitis. Expert opinion on investigational drugs. 2019 Jan 24; [PubMed PMID: 30676119]|
|||Greisner WA 3rd,Settipane RJ,Settipane GA, Natural history of hay fever: a 23-year follow-up of college students. Allergy and asthma proceedings. 1998 Sep-Oct; [PubMed PMID: 9801740]|
|||Durham SR,Emminger W,Kapp A,Colombo G,de Monchy JG,Rak S,Scadding GK,Andersen JS,Riis B,Dahl R, Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. The Journal of allergy and clinical immunology. 2010 Jan; [PubMed PMID: 20109743]|
|||Rodríguez Del Río P,Vidal C,Just J,Tabar AI,Sanchez-Machin I,Eberle P,Borja J,Bubel P,Pfaar O,Demoly P,Calderón MA, The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2017 Feb [PubMed PMID: 27637414]|
|||Cingi C,Wallace D,Bayar Muluk N,Ebisawa M,Castells M,Şahin E,Altıntoprak N, Managing anaphylaxis in the office setting. American journal of rhinology & allergy. 2016 Jul [PubMed PMID: 27456586]|
|||Ryan D,van Weel C,Bousquet J,Toskala E,Ahlstedt S,Palkonen S,van den Nieuwenhof L,Zuberbier T,Wickman M,Fokkens W, Primary care: the cornerstone of diagnosis of allergic rhinitis. Allergy. 2008 Aug; [PubMed PMID: 18691300]|
|||Lipworth B,Newton J,Ram B,Small I,Schwarze J, An algorithm recommendation for the pharmacological management of allergic rhinitis in the UK: a consensus statement from an expert panel. NPJ primary care respiratory medicine. 2017 Jan 23; [PubMed PMID: 28115736]|
|||Rosenwasser LJ, Treatment of allergic rhinitis. The American journal of medicine. 2002 Dec 16; [PubMed PMID: 12517578]|