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2002 Selected Articles

Recognizing and Treating Nonallergic Rhinitis

Michael A. Kaliner, MD

Nonallergic rhinitis (NAR), by itself or in combination with allergic rhinitis, occurs more frequently than commonly recognized, especially in women. Recent data suggest that about 40 million Americans have either "pure" NAR or mixed rhinitis, in which at least some symptoms are not immunoglobulin E (IgE)-mediated.¹ The few studies that report incidence by gender suggest that women are disproportionately affected by NAR or mixed rhinitis.

Diagnosing nonallergic rhinitis can be confusing because the primary symptoms–rhinorrhea, nasal congestion, sneezing, postnasal drip–may be indistinguishable from allergic rhinitis (AR). Diagnosis of NAR is made by a combination of careful history-taking and exclusion: A history of symptoms triggered by environmental irritants suggests a diagnosis of NAR, and negative or irrelevant skin test findings can further help to rule out IgE-mediated rhinitis. However, positive skin test results do not rule out mixed rhinitis.

Differentiating AR from NAR and identifying mixed rhinitis in patients with skin test results that are positive for allergens is critical to optimal patient management. This is because oral antihistamines, the drugs most commonly used in AR, may not be beneficial for patients with NAR. Only 26% of allergy patients say that their symptoms are well-controlled or completely controlled with their present therapy² indicating that many patients may have a component of NAR that is not currently addressed by treatment.

CLASSIFICATION

Nonallergic rhinitis includes a diverse group of nasal diseases unified by a common symptomatology. More than 30 different conditions comprise this group; some of these disorders are poorly defined, many are of unknown etiology, and most lack incidence data. In addition, NAR can be subclassified on the basis of relative frequency (Table 1) or etiologic/cytologic findings (Table 2).

There are limited data on the incidence and frequency of distinct NAR subtypes. A 1985 study of 78 patients with NAR found that vasomotor rhinitis (VMR) was the most prevalent type of NAR, affecting about 61% of subjects.³ Another study reported that VMR was present in 37% of 142 rhinitis patients followed prospectively.⁴

Vasomotor rhinitis deserves special attention because of its high incidence in clinical practice. It has an estimated prevalence of 5% to 10%, while the prevalence of AR is estimated at 15% to 17%.⁵ The possibility of VMR should be suspected in patients presenting with symptoms such as chronic nasal congestion, rhinorrhea, and/or postnasal drip. These classic symptoms are sometimes accompanied by a reduced sense of taste or smell, sinus headache, and chronic cough and throat-clearing.⁵ Table 3 summarizes the key distinguishing features of VMR and other common types of NAR; frequency data are included when available.

EPIDEMIOLOGY

Whereas the prevalence and epidemiology of AR are well defined, only a few studies have investigated the frequency of NAR. In its 1998 report, the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology estimated that about 50% of patients presenting with rhinitis do not have AR.⁶ A 1999 retrospective analysis of 975 patients in 15 allergy practices by the National Rhinitis Classification Task Force (NRCTF) found that 57% of patients presenting with chronic rhinitis had either pure (23%) or mixed (34%) NAR, whereas 43% had pure AR (Figure 1).¹

Figure 1. Relative incidence of AR, NAR, and mixed rhinitis1

Based on prevalence data about AR and estimates that the ratio of AR to NAR is about 3:1, the results of the NRCTF survey suggest that 17 million US patients have NAR, and an additional 22 million have mixed rhinitis.¹ A nationwide epidemiologic survey of patients in the outpatient setting is underway as a follow-up to the NRCTF survey, using the same screening tool to define AR, NAR, and mixed rhinitis (Figure 2). Interim data on 3,500 patients shows a breakdown of 32% with AR, 22% with NAR, and 46% with mixed rhinitis.⁷

Figure 2. Patient Screening Tool*

*The Patient Rhinitis Screen is being used in ongoing nationwide epidemiologic study to investigate incidence of AR, NAR, and mixed rhinitis [Copyright 1999, Wallace Laboratories, Inc.].

Prior to the NRCTF research, four studies had estimated frequency rates for NAR. One study found 52% of 142 patients who presented with nasal congestion and rhinorrhea had nasal diseases other than AR.⁴ A retrospective review of 564 patients’ charts diagnosed NAR in 17%.⁸ The European Community Respiratory Health Survey (ECRHS) reported a 25% incidence of NAR among 1,412 patients selected on the basis of history suggesting AR.⁹ Finally, 30% of 152 rhinitis patients proved to meet research criteria for perennial NAR compared with 54% who had AR and 16% with "undetermined" rhinitis.¹⁰

THE FEMALE FACTOR

Female gender appears to be a significant risk factor for NAR. The NRCTF found that female patients comprised 71% of those with NAR, 62% of those with mixed rhinitis, and 55% of those with AR.¹ Earlier studies reported that women make up 58%³ to 74%¹⁰ of NAR patients. The author’s clinical experience suggests a ratio of female to male patients with NAR of 9:1.

In women, rhinitis symptoms may, in some cases, be attributable to hormonal influences–ie, pregnancy, use of oral contraceptives (OCs) or hormone replacement therapy (HRT), hormone fluctuations during the menstrual cycle, or other endocrine-mediated syndromes. Rhinitis during pregnancy may be primarily congestive in nature, resulting from the combination of hormonally induced intranasal vascular engorgement, mucosal hypersecretion,¹¹ and increased blood volume normally associated with pregnancy.⁷ The use of OCs or conjugated estrogens for HRT can also lead to nasal obstruction and/or hypersecretion.⁶ There is limited evidence linking nasal pathology with thyroid disease, and increased nasal secretion has been reported anecdotally in patients with hypothyroidism.⁶

DIAGNOSIS

The diagnosis of NAR depends on history and exclusion, on ruling out all other possible causes of rhinitis, and linking specific environmental triggers with nasal symptoms. A careful patient history correlated with skin tests for allergens can usually differentiate between AR and NAR. However, positive skin test results do not rule out the possibility that some component of the patient’s symptoms are nonallergic in origin, and the clinician should determine whether nonallergic causes may play a role. Mixed rhinitis may occur in 33% or more of rhinitis patients. Table 4 shows the differential diagnosis of rhinitis.

Age, Seasonality, and Family History

It has been reported that 70% of patients diagnosed with NAR developed the condition after age 20, whereas 70% of patients diagnosed with AR developed the condition before age 20.⁸ Patients with perennial symptoms are more likely to have pure NAR: Fifty-percent of patients with perennial rhinitis had negative skin test findings, compared with 32% of those with combined perennial/seasonal rhinitis and 22% of those with purely seasonal rhinitis.¹² However, many patients with VMR have seasonal exacerbations due to variations in temperature, humidity, and/or barometric pressure. A family history of rhinitis tends to suggest an allergic basis for symptoms.

Exacerbating Factors

Symptoms triggered by known allergens (eg, pollen, pets, dust) support a diagnosis of AR, while symptoms triggered by environmental irritants, alcoholic beverages (beer and wine), or changes in weather suggest NAR (Figure 2). Generally, a patient describing nasal symptoms in response to cold air, strong smells (eg, perfumes, tobacco, paint, cleaning solutions), alcohol consumption, emotional stress, and changes in temperature, humidity, and/or barometric pressure has VMR, although concomitant AR should be considered as well.

Presenting Symptoms

While NAR symptoms may follow the classic rhinitis model–including rhinorrhea, nasal congestion, sneezing, and postnasal drip¹³–VMR symptoms tend to be more obstructive/congestive than secretory, and sneezing and nasal pruritus are less common.¹⁴ If nasal blockage is the predominant symptom, a diagnosis of VMR should be considered.¹⁵ More intense nasal symptoms may be a sign that nonallergic rhinitis with eosinophils syndrome (NARES), the second most common type of NAR, is the cause.¹⁶

Physical Examination

Proper examination of the nasal cavity must take into account the color of the nasal mucosa, the texture of the mucous layer, and the anatomy of the turbinates, nasal septum, and posterior valve area. If the inferior turbinates are pale and boggy, AR is likely. Pink to reddish mucosa with clear discharge, some congestion, and moderate postnasal drainage may be indicative of VMR. Anatomic abnormalities, which might include a deviated septum or enlarged turbinates, point toward a structural cause of rhinitis.⁵ Nonnasal manifestations (eg, atopic symptoms, asthma, dermatitis, conjunctivitis) suggest AR.

Diagnostic Tests

Because of the similarity of symptoms between NAR and AR, a diagnosis of pure NAR is usually associated with negative allergy skin test results. Negative results from radioallergosorbent testing (RAST) to analyze serum IgE levels in response to specific allergens also rule out AR, but positive findings do not rule out concomitant NAR. A nasal smear for eosinophils may distinguish NARES from other types of NAR, but expert consensus is lacking on its usefulness in routine practice.⁶ Thus, patients are presumed to have VMR when there is a positive history of responses to triggers, while the diagnosis of AR requires a history of symptoms triggered by allergens and significantly positive skin reactions to those allergens.

TREATMENT

Evolving Management Strategies

While rhinitis is often treated empirically with oral antihistamines, clinical data suggest that these agents are not useful for controlling symptoms of VMR or other types of NAR,^6,17 and are only partially beneficial in treating mixed rhinitis.¹⁸ The high incidence of mixed rhinitis suggests that empiric treatment should include agents that are effective in both AR and NAR when there is any indication of a nonallergic component to the rhinitis (Figure 3). Intranasal azelastine (Astelin) is the only antihistamine therapy currently approved by the US Food and Drug Administration (FDA) for both AR and NAR. In double-blind clinical trials of patients with VMR, 82% to 85% of patients responded to azelastine with reductions in congestion, postnasal drip, rhinorrhea, and sneezing.¹⁹ Topical corticosteroids are also useful in the management of NAR, and three are FDA-approved for this indication: beclomethasone (Beconase, Vancenase), budesonide (Rhinocort), and fluticasone (Flonase). These agents may be advantageous when nasal mucosal inflammation is present.¹⁴ The author’s clinical experience has shown that azelastine and nasal corticosteroids work well together.

Figure 3. Products Indicated for Rhinitis Relief

Symptom-specific Treatment

For NAR patients with primarily blockage/congestion symptoms and little rhinorrhea or sneezing, oral or topical decongestants can be helpful. Side effects of oral decongestants (eg, insomnia, nervousness, loss of appetite, hypertension) restrict their long-term use. The use of decongestant nasal sprays should be limited to a maximum of 3 to 10 days because of the risk of developing "rebound" congestion (rhinitis medicamentosa).²⁰ Both azelastine and topical nasal corticosteroid sprays reduce nasal congestion with few side effects.

Anticholinergic agents are useful for NAR patients with predominantly anterior secretory/rhinorrhea symptoms. The only intranasal anticholinergic drug approved for use in the United States is ipratropium bromide (Atrovent), which is available in 0.03% and 0.06% solutions. Ipratropium may be used alone or in combination with corticosteroid sprays or azelastine. In a large, double-blind, controlled, randomized clinical trial,²¹ the combined use of ipratropium and beclomethasone nasal sprays was found to be more effective than either agent alone for the treatment of rhinorrhea from perennial rhinitis, and did not result in potentiation of adverse drug reactions. This study further proposed that ipratropium alone be used for patients in whom rhinorrhea is the primary symptom, and in combination with a nasal corticosteroid for patients with several symptoms or symptoms resistant to ipratropium treatment.²¹ A saline nasal spray may also be useful for relieving sneezing, congestion, rhinorrhea, and postnasal drip in patients with VMR.⁷

Other Therapeutic Approaches

In cases where environmental factors may trigger rhinitis, patients should be counseled regarding avoidance of these triggers. Patients whose nasal smear is strongly positive for eosinophils, suggesting a diagnosis of NARES, usually respond well to intranasal corticosteroids. Rhinitis medicamentosa requires withdrawal from the overused agent (usually a decongestant nasal spray), using a 1-week tapering course with an oral or intranasal glucocorticoid, and gradual discontinuation of the decongestant nasal spray beginning on the second or third day.⁷ Surgical procedures to reduce nasal secretions or turbinectomy to relieve congestion or obstruction may also be considered in recalcitrant cases.

Pregnancy

Treating rhinitis during pregnancy can be particularly challenging, and there are scant data to guide pharmacologic management for these patients. In general, nonpharmacologic approaches should be used, including intranasal saline spray, steam inhalation, devices designed to open the nasal passages (eg, Breathe Right® nasal strips), and avoidance of triggers. Pregnancy-related rhinitis is often recalcitrant, however, and may respond only to topical corticosteroids.⁷

CONCLUSION

Nonallergic rhinitis is a common condition that often goes un- or underrecognized, especially in women. An estimated 17 million Americans have "pure" NAR, and an additional 22 million have mixed rhinitis. The "umbrella" of NAR includes more than 30 diverse subtypes of nasal disease, some of which are poorly defined and characterized. Perennial nonallergic rhinitis–ie, VMR–is the most common type.

Differentiating NAR from AR is particularly difficult because symptoms of the two disorders overlap. Skin tests for allergens, combined with a careful history with particular attention to key differentiating factors, aids diagnosis. Positive skin tests do not rule out NAR, and a significant proportion of patients have both AR and NAR. A definitive diagnosis is critical to optimal care. Oral antihistamines, the drugs most often used to treat rhinitis, have not proved effective for either pure NAR or mixed rhinitis. Broad-based therapeutic options that can effectively address both NAR and AR include topical antihistamine sprays and intranasal corticosteroids.

Michael A. Kaliner, MD, is a clinical professor of Medicine at George Washington University School of Medicine in Washington, DC, and medical director of the Institute for Asthma & Allergy in Wheaton, Md.

REFERENCES

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