Allergic rhinitis (AR) may be defined as an inflammation of the nasal mucous membranes caused by an immunoglobulin (Ig) E-mediated (allergic) reaction to aeroallergens.

The first recorded case of AR (catarrhus aestivus) was described in 1819 by Sir John Bostock, who presented himself as a case report to the Medical and Surgical Society of London.¹ At the dawn of the 20th century, there were only several thousand members of the US Ragweed Association (now defunct). One hundred years later, AR has become the most common allergic/immunologic disorder in the US population^2-4 and now affects an estimated one in every seven Americans. AR is acknowledged as a significant health challenge on a global scale.³ It is a major cause of patient visits to physicians in the United States, frequently complicates management of other conditions (eg, asthma, chronic sinusitis) and, if untreated or undertreated, can lead to considerable morbidity including missed work or school, sleep disruption, diminished daytime performance, and impaired quality of life.^2,5 The economic burden of AR is substantial.⁴

The rising prevalence of AR has been found not only in children⁴ but also in adults.⁵ The peak incidence of AR occurs during young adult years. Although AR prevalence declines with age, it is also an important health concern in older adults.⁶ There is an equal incidence of AR in males and females.

Epidemiologic studies have consistently demonstrated that AR and asthma commonly coexist.² AR is frequently associated with asthma and is a risk factor for developing asthma; in addition, many patients with AR demonstrate increased bronchial hyperresponsiveness to inhalation challenge with histamine or methacholine.

Individuals who have inherited the potential to develop IgE-mediated, or "allergic," responses to otherwise innocuous inhalant allergens, with sufficient exposure will generate allergen-specific IgE after T-cell release of interleukins 4 and 13, and B-cell "switching" to produce IgE antibody-thereby becoming "sensitized." The allergic reaction that underlies AR results from subsequent exposure to the allergen to which sensitization has occurred, which cross-links at least two IgE antibodies bound to the high-affinity IgE receptor on presensitized effector cells: mast cells or basophils.⁷ The allergic response includes both an early and a late phase.^2,7 The early phase occurs promptly, and has a duration of approximately 1 hour. The late phase typically begins in 3 to 6 hours, peaks at 6 to 8 hours, and subsides in 12 to 24 hours. Almost one-half of subjects studied in laboratory settings will exhibit this "dual" response.⁸ The symptoms of the early phase generally include sneezing, pruritus, and clear rhinorrhea; symptoms characterizing the late phase may be indistinguishable, but typically entail more prominent congestion.^2,7 The late phase is promoted by factors generated in the early phase that encourage release of inflammatory mediators and the activation and recruitment of cells to the nasal mucosa.^2,3,8 Whereas histamine appears to be the major mediator of the early phase, the late phase is more closely associated with other mediators, chemokines, and cytokines that have both inflammatory and proinflammatory effects, leading to recruitment of inflammatory cells such as eosinophils and basophils. Eosinophils play an important role in the late phase⁷ by release of leukotrienes, which data suggest are of greater importance than histamines for nasal congestion.^9,10 During a clinically relevant exposure in a sensitized individual (eg, outdoors during the ragweed season, or indoors in cat-infested environments), aeroallergens enter the nasal passages on a virtually continual basis; for this reason, it is frequently difficult to separate the early and late phases of the allergic response in the real-world setting. One can imagine that, based on the incessant nature of aeroallergen exposure, affected individuals experience a perpetual late-phase response.

There are four major symptoms of AR: sneezing, pruritus, congestion, and drainage; however, many patients with AR may not complain of the entire symptom complex.¹¹ Patients with AR commonly experience concomitant ocular symptoms, so much so that the term "allergic rhinoconjunctivitis" is frequently used as an alternative to AR.² An appropriate history for AR includes questions to elicit information regarding onset and duration of symptoms, provoking factors or situations, concomitant ocular symptoms, and associated pruritus of other facial structures (eg, throat, ears, palate). Of the four major symptoms, pruritus and sneezing are more specific for AR than for other conditions in the differential diagnosis of chronic rhinitis (Table 1). The propensity for sneezing may entail paroxysms of 5 to 10 or more in rapid succession. Congestion is a bothersome symptom, as commonly described by patients, and compared with other symptoms tends to be less responsive to currently available medications. Rhinorrhea is typically clear; purulent discharge may reflect the presence of secondary infection.

Physical examination may reveal pale, boggy nasal mucous membranes and infraorbital congestion ("allergic shiners"), but can be relatively unremarkable unless the patient is seen when symptoms are prominent. At such times, subtotal or complete nasal obstruction may be present, along with suffusion of conjunctivae.

Proper recognition of individuals with AR requires a careful history and physical examination. The key components of the history that favor AR as opposed to other causes of rhinitis (Table 1) include seasonality of symptoms, occurrence of symptoms with certain exposures or situations (eg, walking into a pet store), improvement of symptoms during spring, summer, or fall seasons when in air-conditioned environments (buildings or automobiles), and the experience of prominent itching of nose, eyes, ears, throat, or palate. As opposed to AR in younger patients with chronic rhinitis, AR in older adults is less frequently confirmed, and alternative diagnoses for perennial rhinitis, including cholinergic hyperactivity, pharmacologic causes (eg, alpha-adrenergic effects of antihypertensive drugs), and chronic sinusitis are found more frequently.⁶

The diagnosis of AR requires (1) positive history, (2) demonstration of IgE-mediated potential to inhalant allergens by cutaneous (or in vitro) testing, and (3) correlation between history and cutaneous (or in vitro) test findings. Immediate hypersensitivity skin testing is recommended as the preferred diagnostic study, as it is associated with reduced cost, is more sensitive, and entails no delay in obtaining results.^2,12 Individuals with skin disorders or who are unable to suspend antihistamine medications such that skin testing would be uninterpretable, are candidates for in vitro testing to detect elevated levels of specific IgE to inhalant allergens.^2,12

Once a diagnosis of AR is confirmed, treatment strategies include avoidance, medications, and allergen immunotherapy.

Avoidance
Avoidance of clinically relevant allergens can lead to substantial reduction of symptoms and medication reliance,² and is arguably the most important aspect of AR management. The inhalant allergens that may account for AR are listed in Table 2. Note that individuals with AR are frequently sensitive to more than one allergen.

The occurrence and severity of symptoms among patients with seasonal AR due to outdoor pollens and mold spores will parallel exposure to and levels of these factors in ambient air. For this reason, monitoring pollen and mold counts in one's vicinity is frequently of benefit (Figure 1), as the knowledge of these counts can be useful for planning outdoor activities. A predictable sequence of pollination is observed each year: trees predominate in the spring, grasses in the summer, and weeds in the late summer and early fall. Ragweed pollen (Figure 2) is the dominant weed in the midwestern and northeastern United States. Ragweed typically appears in ambient air during the second week of August, peaks in early September (usually Labor Day weekend), and then persists until frost. Mold spore counts are shown as an example in (Figure 3), along with pollen counts recorded simultaneously for 3 days each week throughout the 2004 season in Ohio. Molds are present in samples of ambient air at much higher levels than pollens; however, pollens can be regarded as more "efficient" aeroallergens because grass counts in single digits may be sufficient to provoke symptoms in sensitized individuals who are exposed, whereas mold counts of several thousand are still considered "low."

For individuals who are allergic to outdoor pollens, air conditioning can lead to dramatic symptom relief.² By reducing indoor relative humidity, it also significantly reduces mold spore and dust mite (see below) allergen levels.¹³ We now spend most of our time indoors;¹⁴ for this reason, the utility of air conditioning for reducing symptoms should not be underestimated.

Dust mites are a major source of allergens in house dust.^2,13 Dust mites have been isolated in dust samples taken from all five major continents. They are microscopic and rely on heat and humidity to survive and proliferate.² Allergy to dust mites is common in patients with AR. Recommended avoidance measures to reduce exposure to dust mites include encasement of the mattress, box spring, and pillow in impermeable covers, reducing indoor relative humidity, washing bedding weekly in a hot cycle (>130° F) and, if possible, removal of carpets in favor of tiled or hardwood flooring.¹³

For individuals allergic to cat or dog dander who are themselves pet owners, no avoidance strategy can approach the benefit that will be gained with elimination of the pet from the home.¹⁵ In view of the emotional attachments that commonly occur with pet ownership as well as the potential therapeutic value of pets,¹⁶ advising removal of a pet from the home must be discussed openly with allergic patients and considered carefully from an individualized risk/benefit standpoint. If a cat or dog is removed from the home, it must be recognized that, due to persistence of the allergen for periods of several months, clinical benefit may not occur promptly. When elimination of pets from the home is not possible, second-best measures include restricting the pet from the allergic person's bedroom, use of high-efficiency particulate or electrostatic air cleaners, and removal of carpets and other upholstered items that otherwise serve as reservoirs for allergens.¹⁵ Although allergen reduction may be transient and the potential for clinical benefit has not been clearly established, bathing the pet (cat or dog) may also be attempted as a second-best alternative to removing the pet from the home.

Pharmacotherapy
Because avoidance measures will likely be incomplete and patients with AR will continue to be exposed to clinically relevant levels of aeroallergens, virtually all patients with AR will benefit from medication.

The most commonly prescribed medications for AR are H₁-antihistamines.² These drugs antagonize the action of histamine by blocking receptor sites on target cells. Antihistamines were introduced more than 50 years ago and continue to be widely used. Although conventional or first-generation antihistamines are efficacious, they can be associated with drowsiness and performance impairment.² Impaired driving performance has been documented with use of conventional antihistamines, even in persons with no subjective awareness of drowsiness.¹⁷ Older adults may be more sensitive to the psychomotor impairment promoted by antihistamines and are at increased risk for complications such as fractures and subdural hematomas caused by falls.⁶ Prominent anticholinergic effects, including dryness of mouth and eyes, constipation, inhibition of micturition, and potential provocation of narrow-angle glaucoma may occur. Because of comorbid conditions (eg, increased intraocular pressure, benign prostatic hypertrophy, preexisting cognitive impairment, and so forth) that may increase the potential risk of regular or even intermittent use, first-generation antihistamines should be prescribed or recommended cautiously in older adults. Use of second-generation antihistamines (Table 3), which lack the prominent central nervous system or anticholinergic properties of conventional antihistamines, are preferred.² Second-generation antihistamines include oral fexofenadine, oral loratidine (available over the counter), oral desloratidine, oral cetirizine, and intranasal azelastine.

Oral decongestants primarily reduce nasal congestion and may attenuate drainage but do not affect sneezing or itching; they are frequently helpful taken in combination with an antihistamine. Once again, use of these drugs may be problematic,² especially in older adults,⁶ in view of their propensity for promoting central nervous system (eg, tremor, irritability, insomnia, nervousness) and cardiovascular (palpitations, blood pressure elevation) adverse effects. These drugs may also raise intraocular pressure and provoke obstructive urinary symptoms. Although topical decongestants are highly efficacious for congestion, use should be avoided for longer than 4 days because of the risk of rhinitis medicamentosa.²

Intranasal cromolyn is also available over the counter. This medication is well tolerated, but appears to be more efficacious for preventing inflammation than for reversing it once it occurs.² Although its frequency of use limits its utility, it has no risk for systemic adverse effects and may be preferred for selected patients (eg, pregnant women and older adults) based on this safety advantage.

AR can be managed successfully with a regimen of avoidance measures and regular medication. In properly selected patients, allergen immunotherapy can be administered to reduce symptoms and medication reliance. Much of the morbidity associated with untreated or undertreated AR can be prevented with proper diagnosis and management.

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