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Table of Contents

Published October 31, 2005

  

David M.
Lang, MD

David M. Lang, MD

Department of
Pulmonary, Allergy,
and Critical Care
Medicine

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Copyright 2005
The Cleveland Clinic Foundation

  
DEFINITION

 

Chapter Outline

Definition

Prevalence

Pathophysiology

Signs and
Symptoms

Diagnosis

Treatment
and Outcomes

References

National Guidelines

Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology
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.
PREVALENCE

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 population2-4 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.
PATHOPHYSIOLOGY
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.
SIGNS AND SYMPTOMS

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.

Table 1:
Differential Diagnosis of Allergic Rhinitis
  • Vasomotor/Irritant Rhinitis
  • Chronic Sinusitis
  • Nonallergic rhinitis with eosinophilia
  • Gustatory rhinitis
  • Atrophic Rhinitis
  • Rhinitis Medicamentosa
  • Rhinitis associated with Drugs
    (eg, antihypertensive agents, oral contraceptives)
  • Rhinitis associated with systemic disease
    (eg, Hypothyroidism, Wegener's Granulomatosis, Sjögren's Syndrome)
  • Structural Factors
    (Septal Deviation, Nasal Polyposus,
    Nasopharyngeal Carcinoma)

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.
DIAGNOSIS

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

TREATMENT AND OUTCOMES

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.

Table 2:
Inhalent Allergens
  • Dust Mites
  • Cockroaches
  • Pets (dogs, cats, etc)
  • Mold Spores
  • Trees
  • Grasses
  • Weeds
  • Mold Spores

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."

Ragweed is the dominant weed pollen in the Midwestern United States.
Figure 2

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.

Table 3:
Second-Generation Antihistamines
Generic
(Proprietary Drug)
Daily Dose
Azelastine (Astelin)
2 sprays in each nostril BID
Cetirizine (Zyrtec)
5 or 10 mg daily
Fexofenadine (Allegra)
180 mg daily or 60 mg BID
Loratidine (Claritin)
10 mg daily
Desloratidine (Clarinex)
5 mg daily
  

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.

Intranasal corticosteroids (ICs) are the most efficacious agents for management of AR.2 Given that symptoms of AR reflect an inflammatory response promoted by aeroallergen exposure (see above), an agent that has a broad range of anti-inflammatory effects and acts through multiple mechanisms would be expected to offer maximal relief of AR symptoms compared with other agents. The therapeutic effects of ICs include vasoconstriction and reduction of mucosal edema, inhibition of mediator release, suppression of cytokine production, and inhibition of inflammatory cell infiltration.2 ICs are effective for reducing nasal congestion, rhinorrhea, and sneezing, and also may relieve ocular symptoms.11 Systemic effects are minimal at recommended doses.2 The major adverse effect of ICs is local irritation or epistaxis; patients should be instructed to suspend IC use at the first sign of bleeding or irritation, and to direct the nasal spray laterally, away from the nasal septum.

Intranasal ipratropium is efficacious for rhinorrhea but has little benefit for other AR symptoms.2 This medication may be helpful if rhinorrhea is refractory to other medications listed above or for persons with vasomotor/irritant rhinitis.2 Adverse effects include the potential for local irritation or epistaxis.

Table 4 shows the therapeutic utility of the above agents for addressing the four major symptoms of AR in addition to ocular symptoms.2,11,18 In clinical practice, combination treatment with more than one of these agents is frequently required to achieve and maintain control of AR.

Evidence-based medicine has been increasingly utilized to aid in data-driven treatment decisions. The number needed to treat (NNT) and number needed to harm (NNH) calculations have recently been derived to estimate the magnitude of treatment effects of these medications for AR.18 NNT is the average number of patients who need to receive a treatment for one to benefit, and the NNH is the average number of patients who need to receive a treatment for one to be harmed. The lower the NNT and the higher the NNH, respectively, the more effective and favorable the treatment. The NNT and NNH calculations for the above medications are also displayed in Table 4.

Allergen Immunotherapy
Allergen immunotherapy is well established as efficacious for patients with AR2,19 and for those with asthma.20

Allergen immunotherapy entails the incremental administration of inhalant allergens to induce immune system changes in host response to natural exposure to these allergens.19 Numerous randomized, double-blinded, placebo-controlled trials have shown that allergen immunotherapy can reduce levels of symptoms and medication reliance.19 A 3-year trial of allergen immunotherapy21 in which 37 of 44 patients were randomized to injections of timothy grass pollen or placebo found a significant reduction in symptoms and medication use for rhinitis and asthma with allergen immunotherapy. The NNH was 416.7, which indicates that approximately 417 allergen immunotherapy injections were given for one person to experience a systemic reaction. Because of the risk of anaphylaxis, injections should be given only in a setting where adequate precautions are taken and life-threatening anaphylaxis can be treated.19

A trial of immunotherapy merits consideration for the following patients with AR: those with secondary complications (eg, sinusitis, otitis); those with concomitant (mild to moderate) asthma for which inhalant allergy is relevant; or those for whom a program of optimal avoidance measures and medications is not effective, practicable, nor preferred.2,19 Allergen immunotherapy also may be desirable for patients with AR who do not tolerate or are disinclined to take regular medications.

The decision to begin allergen immunotherapy should be individualized, and is based on symptom severity, relative benefit with pharmacotherapy, and whether comorbid conditions such as cardiovascular disease or beta-blocker exposure are present.22 The latter conditions are associated with heightened risk for (more serious) anaphylaxis-the major hazard of allergen immunotherapy.19
SUMMARY
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.
REFERENCES
  1. Bostock J. Case of a periodical affection of the eyes and chest. Ann Allergy. 1960;18:894-5.

  2. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. American Academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1998;81:478-518.

  3. Bachert C, van Cauwenberge P, Khaltaev N, Bousquet J, World Health Organization. Allergic rhinitis and its impact on asthma. In collaboration with the World Health Organization. Executive summary of the workshop report. 7-10 December 1999, Geneva, Switzerland. Allergy. 2002;57:841-55; erratum in Allergy. 2002;57:1208.

  4. Meltzer EO. The prevalence and medical and economic impact of allergic rhinitis in the United States. J Allergy Clin Immunol. 1997;99:S805-S828.

  5. Linneberg A, Nielsen NH, Madsen F, Frolund L, Dirksen A, Jorgensen T. Increasing prevalence of specific IgE to aeroallergens in an adult population: two cross-sectional surveys 8 years apart: The Copenhagen Allergy Study. J Allergy Clin Immunol. 2000;106:247-252.

  6. Lang DM. Management of allergic rhinitis. Geriatric Times. 2002;3.
  7. Naclerio RM. Pathophysiology of perennial allergic rhinitis. Allergy. 1997;52:7-13.

  8. Pelikan Z. Late and delayed responses of the nasal mucosa to allergen challenge. Ann Allergy. 1978;41:37-47.

  9. Okuda M, Watase T, Mezawa A, Liu CM. The role of leukotriene D4 in allergic rhinitis. Ann Allergy. 1988;60:537-540.

  10. Donnelly AL, Glass M, Minkwitz MC, Casale TB. The leukotriene D4 receptor antagonist, ICI 204,219, relieves symptoms of acute seasonal allergic rhinitis. Am J Respir Crit Care Med. 1995;151:1734-1739.

  11. Spector S, Nicklas RA, Chapman J, et al, for the Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; Joint Council of Allergy, Asthma, and Immunology. Symptom severity assessment of allergic rhinitis: part 1. Ann Allergy Asthma Immunol. 2003;91:105-114.

  12. Allergy testing. American College of Physicians. Ann Intern Med. 1989;110:317-320.

  13. Arlian LG, Platts-Mills TA. The biology of dust mites and the remediation of mite allergens in allergic disease. J Allergy Clin Immunol. 2001;107:S406-S413.

  14. Samet JM, Marbury MC, Spengler JD. Health effects and sources of indoor air pollution. Part I. Am Rev Respir Dis. 1987;136:1486-1508.

  15. Chapman MD, Wood RA. The role and remediation of animal allergens in allergic diseases. J Allergy Clin Immunol. 2001;107(suppl):S414-S421.

  16. Fitzgerald F. The therapeutic value of pets. West J Med. 1986;144:103-105.

  17. O'Hanlon JF, Ramaekers JG. Antihistamine effects on actual driving performance in a standard test: a summary of Dutch experience, 1989-94. Allergy. 1995;50:234-242.

  18. Portnoy JM, Van Osdol T, Williams PB. Evidence-based strategies for treatment of allergic rhinitis. Curr Allergy Asthma Rep. 2004;4:439-466.

  19. Allergen immunotherapy: a practice parameter. American Academy of Allergy, Asthma and Immunology. American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 2003;90(suppl 1):1-40.

  20. Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2003;4:CD001186.

  21. Walker SM, Pajno GB, Lima MT, Wilson DR, Durham SR. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. J Allergy Clin Immunol. 2001;107:87-93.

  22. Lang DM. Anaphylactoid and anaphylactic reactions: hazards of beta-blockers. Drug Saf. 1995;12:299-304.

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