Chronic nonallergic rhinitis

INTRODUCTION — Chronic nonallergic rhinitis (NAR) is not a specific disease but rather a syndrome diagnosed by excluding other specific types of rhinitis. The pathogenesis, incidence, clinical manifestations, diagnosis, and treatment of chronic NAR are presented in this topic review. Allergic rhinitis and an overview of other forms of rhinitis are presented separately:

●(See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)

●(See "Pharmacotherapy of allergic rhinitis".)

●(See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis".)

●(See "An overview of rhinitis".)

DEFINITION — NAR is best defined by the chronic presence of one or more of the four following cardinal symptoms of rhinitis, in the absence of a specific etiology (such as an immunologic, infectious, pharmacologic, structural, hormonal, vasculitic, metabolic, or atrophic cause):

●Sneezing

●Rhinorrhea

●Nasal congestion

●Postnasal drainage

Although there is no consensus about how long symptoms should be present to establish chronicity, some studies have utilized a minimum duration of over one year [1,2].

The lack of clarity regarding the pathogenesis of this condition has led to an imprecise terminology and a number of synonyms used to refer to this entity. These include:

●Idiopathic rhinitis

●Nonallergic, noninfectious rhinitis

●Intrinsic rhinitis

●Vasomotor rhinitis or nonallergic vasomotor rhinitis

Some experts use the term "nonallergic rhinitis" to refer more generally to any form of rhinitis that is noninfectious and nonallergic [3]. However, in this topic review, NAR is used more narrowly, as defined above.

THEORIES OF PATHOGENESIS — There is no single unifying theory of pathogenesis for chronic NAR, and it may represent a group of incompletely defined disorders [4-6]. However, NAR can be broadly divided into noninflammatory and inflammatory forms [7-34], with the inflammatory form being further divided into cases that are either eosinophilic or noneosinophilic processes [1,2,7-34]. With all forms of chronic NAR, there is also a variable component of autonomic dysregulation. In the noninflammatory form, these neurologic abnormalities are the only demonstrable findings.

Patients with NAR often exhibit a clinical hypersensitivity to odors, which is usually manifested by the production of rhinitis symptoms. One group of researchers evaluated the neurogenic responses to chemical/olfactory stimuli in patients with NAR using functional magnetic resonance imaging (MRI) [35]. Subjects underwent MRI during exposure to different types of odors. They exhibited increased blood flow to several odor-sensitive regions of the brain in response to both pleasant (vanilla) and unpleasant (hickory smoke) odors. The neurologic responses were associated with the production of symptoms upon exposure to hickory smoke. (See 'Clinical features' below.)

Noninflammatory — With the noninflammatory form (as defined by biopsies negative for inflammation), it has been postulated that the disease results from an abnormality in the autonomic nervous system, including the adrenergic, cholinergic, and/or nonadrenergic-noncholinergic (NANC) innervation of the nose [9-12]. However, such abnormalities have also been demonstrated in some inflammatory cases and, in this context, have been proposed to be secondary to a primary inflammatory process [7,8,12,29]. Thus, the pathogenic role of these abnormalities is unclear.

"Gustatory rhinitis" is a term applied to the development of profuse, watery rhinorrhea or congestion in association with eating hot or spicy foods [36] (see 'Prominent rhinorrhea without other symptoms' below). It is most likely a subtype of noninflammatory NAR.

Patients with noninflammatory NAR may display the following abnormal neurologic findings:

●Abnormal responses to various neurogenic stimulation, including heightened responses (in the form of rhinitis symptoms) to histamine, cold stimulation of the extremities and nasal mucosa, methacholine, and other stimuli designed to activate cholinergic responses [7,10,29]

●Diminished responses to vasoconstrictive stimuli [37]

●Increased concentrations of intranasal neuropeptides, such as vasoactive intestinal peptide (VIP) and substance P [16]

In addition to these neural processes, nasal secretory abnormalities may also be important to the pathogenesis of NAR. In one study, subjects with allergic rhinitis secreted higher amounts of albumin and an unidentified 26 kilodalton protein than did those with NAR [38]. Since production of the latter protein could be stimulated by pilocarpine, it was thought to occur in secretory mucosal glands. This implies that there is a qualitative difference in the glandular mucosa, which may distinguish patients with allergic rhinitis from those with NAR.

Inflammatory — Nonallergic rhinitis with nasal eosinophilia syndrome (NARES) is the most common type of inflammatory NAR. The clear nasal secretions in these patients contain greater than 25 percent eosinophils. Nasal biopsies from these patients commonly show increased eosinophils, as well as increased numbers of mast cells and prominent mast cell degranulation [2,19]. The presence of eosinophils in nasal secretions can be assessed in the office by having the patient blow the nose into a piece of "wax paper" and applying the secretions onto a glass slide. Once dried, the secretions are stained with Wright's stain and examined under a light microscope. Although not considered essential for the diagnosis, the author has performed this examination for years and has found that the presence of abundant eosinophils usually predicts a good response to intranasal corticosteroids (INCS).

The cellular inflammatory infiltrate may have dominant cells other than eosinophils. Nasal cytology, in some cases, shows a predominance of mast cells and neutrophils [39,40]. There may also be an increase in mucus-producing cells [41]. These histologic findings may be associated with different clinical manifestations [39]. In one study, the burden of inflammatory cells correlated with impaired quality of life [41]. As noted above, the presence of eosinophilia can indicate responsiveness to corticosteroids. It may also be associated with a higher incidence of asthma and more severe symptoms than when the predominant pattern is characterized by neutrophilia. When mast cells are the predominant cell type, nasal itching is often a characteristic feature [39].

The inflammatory cytokine pattern in chronic NAR differs from normals. A study comparing patients with allergic rhinitis, NAR, and controls found that both patient groups had increased levels of interleukin 16 and interleukin 17 compared with controls [42]. Significantly higher serum levels of the costimulatory molecule sCD48 occurred in the nonallergic group, and significant correlations were noted between the serum level of sCD48 and the number and percentage of eosinophils and eosinophilic cationic protein. Eotaxin-1/CCL11 serum levels were also found to be significantly higher in the nonallergic group [43].

Patients with allergic rhinitis and NAR had significantly different microbiota profiles compared with healthy controls [44]. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of allergic and nonallergic phenotypes, providing us with new ideas for the therapy of these disorders.

Evidence for a localized allergic response — Patients with chronic NAR have negative skin and in vitro tests for allergen-specific immunoglobulin E (IgE) by definition and thus lack evidence of increased systemic production of allergen-specific IgE. However, IgE production may occur locally in the nasal tissue in patients with negative skin tests, as well as in patients with typical allergic rhinitis [2,45-52]. One group of investigators has shown that up to one-half of patients with chronic NAR react to nasal challenge with allergen, especially dust mite allergen, with symptoms and signs similar to those in patients with typical allergic rhinitis and significantly different from controls without rhinitis [46,53,54]. Local IgE production in the nasal mucosa has been demonstrated to additional allergens, including pollens, animal epithelia, molds (Alternaria), and others. Basophils from peripheral blood may be activated by the involved allergens, suggesting spillover of locally synthesized specific IgE into the circulation. Because of these findings, some authors have suggested performing an allergen-specific nasal challenge and/or measuring the (local) nasal-specific IgE levels in addition to standard allergy tests in this subgroup of patients. In addition, they recommend repeating allergy skin testing "after a time interval" since patients formerly diagnosed with NAR may develop allergic disease [55-57].

It is possible that the production of local allergen-specific IgE in patients with symptoms of rhinitis is simply a precursor to the development of the systemic production of these IgE antibodies. A prospective 10-year follow-up study with initial cohorts of 194 patients with local allergic rhinitis and 130 healthy controls was designed to answer this question. After 10 years of follow-up, 176 patients remained, and skin prick tests and/or serum-specific IgE became positive in only 9.7 percent of those with local allergic rhinitis and in 7.8 percent of controls. The authors interpreted these findings as indicating that local allergic rhinitis is a separate condition from classic allergic rhinitis and not simply a precursor phase of this disorder [58,59].

On the other hand, other researchers (using similar techniques) were either unable to demonstrate consistent responses to nasal allergen challenge in patients with NAR [60] or found the same responses in healthy controls [61]. These findings challenge the concept that NAR results from a localized, IgE-mediated mechanism. An alternative explanation could be nonspecific hyperreactivity of the nasal mucosa due to inflammation from another etiology.

PREVALENCE — Rhinitis, in both its allergic and nonallergic forms, affects 10 to 40 percent of the population in industrialized countries [62]. Pure chronic NAR may be responsible for anywhere from 17 to 52 percent of all cases of rhinitis in adults [4,63-70]. The prevalence of NAR in children is less well studied [71-74]. Much of the data utilized to establish the prevalence of chronic NAR have been gathered from allergy specialty practices, although there have been some community-based epidemiologic surveys [63-67,75,76].

The prevalence of pure NAR underestimates the impact of this condition since it coexists with allergic rhinitis in a substantial subset of patients [68]. Patients with both conditions have been described as having "mixed" rhinitis, although they are generally classified as allergic since there is no established United States diagnostic code for "mixed" allergic and nonallergic disease.

In addition, in the presence of allergen-specific IgE, it is difficult to establish the existence of concomitant NAR. The Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology has estimated that, taking this underestimation into account, approximately 50 percent of patients presenting with rhinitis may have the nonallergic form (alone or as mixed disease) [68]. Based upon a survey of American allergists, 34 percent of 975 rhinitis patients were identified as having the "mixed" form of rhinitis [67]. Extrapolating these data to the overall incidence of rhinitis in the United States revealed that NAR may affect as many as 17 million Americans and that an additional 22 million may suffer from the "mixed form" of rhinitis [67].

EPIDEMIOLOGY — NAR presents later in life than allergic rhinitis, with 70 percent of patients presenting after 20 years of age [66,77]. In comparison, the onset of allergic rhinitis usually occurs before age 20 (and often in childhood).

Women make up the majority of patients in most studies, so there may be a female predominance [64,78].

Rhinitis of older adults (also called senile rhinitis) is a term used to describe NAR in older patients. It is characterized by prominent rhinorrhea and aggravated by eating and environmental factors [79]. (See 'Prominent rhinorrhea without other symptoms' below.)

CLINICAL FEATURES — The clinical history is the most important tool used to make the distinction between NAR and other forms of rhinitis.

Compared with allergic rhinitis — Compared with allergic rhinitis, features that are helpful in correctly identifying NAR include the following:

●The most frequent and prominent clinical manifestations of NAR are nasal blockage and postnasal drip [80]. In contrast, patients with allergic rhinitis report prominent eye symptoms, sneezing, and rhinorrhea.

●Patients with NAR often cannot readily identify triggers, such as times of year when specific pollens are prevalent or exposure to animals. In contrast, most patients with allergic rhinitis can identify one or more triggers. (See 'Characteristic triggers' below.)

●Symptoms most commonly occur throughout the year (eg, perennial), although the condition may be exacerbated by weather conditions, particularly during the spring and fall [81]. Symptoms in those with allergic disease usually show seasonal patterns, although some have perennial symptoms.

●Patients with NAR suffer from comorbidities, including asthma, chronic rhinosinusitis, otitis media, sleep disturbance, and declines in quality of life, similar to those with allergic rhinitis [41,82]. Studies examining the relationship between NAR and asthma are reviewed in more detail below. (See 'Relationship with asthma' below.)

Characteristic triggers

●Respiratory irritants (eg, cigarette smoking, strong scents, and fragrances) are prominent inducers of symptoms, although this may be true for patients with longstanding allergic rhinitis also. Nonallergic rhinitis due to irritants in the workplace is a frequent (but sometimes overlooked) cause of occupational rhinitis [83]. (See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis", section on 'Increasing sensitivity over time'.)

●Weather changes (eg, fluctuations in temperature, humidity, and/or barometric pressure) affect many patients with NAR. In a study using a unique environmental exposure chamber designed to simulate various weather conditions, 37 subjects were challenged with cold, dry air, and temperature changes [84]. Nasal patency was assessed with acoustic rhinometry and rhinorrhea by measurement of nasal secretions. In addition, subjective measures of nasal symptoms were also evaluated. Significant symptoms with objective confirmation were induced in response to these simulated weather changes.

●Heated or spicy foods induce watery rhinorrhea in patients with the syndrome of gustatory rhinitis, which can be considered a subtype of NAR. Food triggers are more common in older adults, and gustatory rhinitis and rhinitis of older adults overlap [79]. (See 'Prominent rhinorrhea without other symptoms' below.)

Relationship with asthma — NAR, like allergic rhinitis, is associated with asthma and is a significant risk factor for the development of asthma. Some studies have found that NAR confers a lower risk of asthma compared with allergic rhinitis [85], while others have found similar rates of asthma development [86,87].

There may be subsets of patients with NAR that are at particularly elevated risk for asthma. Those with inflammatory NAR with increased nasal eosinophilia appear to be at greater risk for the development of asthma than patients with NAR without eosinophilia [13,88,89]. Those with eosinophilia not only have a comparatively elevated risk for asthma but also a greater risk for the development of chronic rhinosinusitis with nasal polyposis and aspirin sensitivity. (See "Aspirin-exacerbated respiratory disease".)

PHYSICAL EXAM — The nasal turbinates can appear boggy and edematous in both allergic rhinitis and NAR. The mucosal tissue is more often erythematous in nonallergic disease as compared with the pale-bluish hue or pallor seen with allergic rhinitis. However, none of these findings are diagnostic, and the mucosa can even appear relatively normal, particularly in older patients.

DIAGNOSIS — The diagnosis of chronic NAR is based on a characteristic history and physical examination, combined with the absence of evidence for clinical allergy to aeroallergens. It is therefore a diagnosis of exclusion. However, in practical terms, allergy testing is not essential to making a presumptive initial diagnosis of NAR and beginning therapy. In addition, allergic rhinitis and NAR can coexist, and, in such cases, it may only become clear that the patient has both disorders in retrospect once an effective combination of medications is found.

Referral for allergy testing — It is not necessary to perform allergy testing before making a presumptive diagnosis of NAR and initiating treatment as previously mentioned. However, if the patient is not experiencing adequate improvement, then testing for allergy is indicated to clarify the etiology.

Allergy testing can be accomplished either through skin testing or with blood tests. In general, skin testing with aeroallergens is the more sensitive and specific of the two methods, but it should only be performed by an allergy expert, and, thus, referral is required. (See "Overview of skin testing for IgE-mediated allergic disease".)

The other method of identifying allergic sensitivities is immunoassays to detect allergen-specific IgE antibodies in the serum. These tests are widely available and require no patient preparation (such as discontinuation of medications). IgE immunoassays provide similar information as that obtained with allergen skin tests, although they are variably more expensive and less sensitive for the diagnosis of allergy to inhalant allergens compared with skin tests. (See "Overview of in vitro allergy tests", section on 'Accuracy'.)

In evaluating patients for allergy, clinicians should be mindful that a positive skin test for allergy or a positive in vitro test by itself does not prove that the patient is allergic to that substance. The result must be consistent with the clinical history, with symptoms occurring during the appropriate season, or upon exposure. (See "Overview of skin testing for IgE-mediated allergic disease" and "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis".)

The use of limited panels of IgE immunoassays in the primary care setting has been evaluated in the diagnosis and management of rhinitis. Such testing can improve diagnostic accuracy and/or management when skin testing is not easily obtained [90-92]. These panels typically test for IgE antibodies to common seasonal and perennial allergens [91,93]. Some perennial allergens are relevant to almost all populations (eg, dust mites, animal danders). However, other allergens (pollens and molds) are relevant to specific geographic areas. A logical approach for determining which allergens should be included would involve consulting a local allergy expert initially to identify a limited number of allergens that are important in that area [94].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of chronic NAR includes several other forms of rhinitis, as well as laryngopharyngeal reflux.

Other forms of rhinitis — Various other causes of rhinitis should be excluded (table 1):

●Rhinitis medicamentosa (due to topical decongestants) and nasal dysfunction related to systemic medications, such as some erectile dysfunction drugs, medications for prostatic hypertrophy, and some antihypertensives (table 1) (see 'Management of rhinitis medicamentosa' below)

●Occupational rhinitis (allergic and irritant) (see "Occupational rhinitis")

●Atrophic rhinitis, which is characterized by chronic nasal congestion, crusting of secretions, halitosis, and a thin, erythematous mucosa on nasal examination (see "Atrophic rhinosinusitis")

●Nasal polyposis, which is often characterized by severe congestion or obstruction and reduced or absent sense of smell (see "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'CRS with nasal polyposis')

●Rhinitis in association with hormonal changes of pregnancy, lactation, hypothyroidism, and acromegaly (see "An overview of rhinitis", section on 'Other causes of rhinitis')

Management of rhinitis medicamentosa — Physical examination in patients with rhinitis medicamentosa often reveals swollen, red nasal mucous membranes. Diagnosis most heavily relies upon the history of use of a causative medication. In some patients, even several days of regular use of decongestant sprays leads to rebound nasal congestion as the medication wears off, prompting patients to administer the medicine more frequently to obtain relief. This begins a vicious cycle of nasal congestion both caused and temporarily relieved by the medication with escalating use and eventual dependency [95].

Treatment of rhinitis medicamentosa begins with withdrawal of the causative medication. In addition, an intranasal corticosteroid (INCS) is usually required to reduce symptoms while patients discontinue the culprit decongestant [96-99]. It is important to counsel patients that nasal congestion will probably worsen temporarily as the offending medication is stopped so that this is not interpreted as treatment failure. Intranasal fluticasone was shown in a small randomized trial of 19 patients to be effective in countering rebound nasal congestion in this setting [95]. Topical INCS achieve high concentrations of the drug in the affected mucosa and are the most appropriate long-term therapy. Complete recovery can take as long as one year in cases of long-term overuse [100,101].

A brief course of oral glucocorticoids (eg, prednisone, 0.5 mg per kg for five days) has also been proposed for treatment during withdrawal in some case reports. This is helpful when nasal congestion is sufficiently severe that topical therapies cannot penetrate up into the nose. However, this is not necessary in most patients.

Laryngopharyngeal reflux — Isolated postnasal irritation and excessive phlegm can also result from reflux of gastric fluids with or without esophageal symptoms noticeable to the patient, which is a condition referred to as laryngopharyngeal reflux. In a randomized trial of 75 patients with isolated postnasal drip, sinus disease and allergic rhinitis were excluded with a sinus computed tomography (CT) and either skin testing or in vitro test allergy testing, respectively [102]. Patients were assigned to either lansoprazole (30 mg twice daily) or placebo for 16 weeks. There was statistically significant improvement in symptoms in the group receiving lansoprazole at 8 and 16 weeks, which persisted at least to two months. The responders were not distinguishable from nonresponders either by pH or impedance monitoring at the start of the study. (See "Laryngopharyngeal reflux in adults: Evaluation, diagnosis, and management".)

MANAGEMENT

Overview — Patients with chronic NAR are generally less responsive to pharmacologic therapy than those with allergic rhinitis [8,103]. Specifically, most find oral antihistamines unhelpful [104,105]. However, two classes of medications are useful in treating the total symptom complex of chronic NAR [67,106-116]:

●Intranasal corticosteroids (INCS)

●Intranasal antihistamines

Patients with mild disease may be adequately treated with either INCS or intranasal antihistamine monotherapy. There are no studies specifically comparing the two therapies in a head-to-head manner.

Patients who are very symptomatic tend to respond better to combination therapy [117]. We generally use full-strength dosing for both agents and emphasize to patients that the medications should be used on a daily basis regardless of the presence or absence of symptoms. (See 'Combination therapy' below.)

In addition to these agents, ipratropium has been approved specifically to treat the symptom of rhinorrhea in chronic NAR [118,119].

Combination therapy — It has been our clinical experience that the combination of INCS and intranasal antihistamines is more effective than either agent alone. This has been demonstrated in patients with seasonal allergic rhinitis [120], although it has not been specifically studied in chronic NAR:

●A combination spray containing azelastine-fluticasone is available in the United States and is approved for children six years of age and older and adults for seasonal allergic rhinitis. The dose is one actuation per nostril, twice daily. This combination product has been studied in patients with seasonal allergic rhinitis and has been shown to be superior to single treatment with either agent alone [120].

●Another combination is olopatadine-mometasone, which is approved for patients ≥12 years of age. The dose is two sprays per nostril twice daily. Combination therapy can also be achieved with two separate sprays.

●For the INCS component, we usually begin with full-strength dosing. Multiple preparations are available (table 2).

Options for an intranasal antihistamine spray include:

●Azelastine 0.15%, one to two actuations per nostril twice daily and decreasing the dose as symptoms improve. Many patients' symptoms are controlled with once-daily dosing. Azelastine is also available in a 0.1% preparation, as well as a generic preparation that is dosed two actuations each nostril twice daily in adults and one actuation twice daily in children.

●Olopatadine hydrochloride nasal spray (0.06%) that is dosed two actuations twice daily in adults and children >12 and one actuation twice daily for children ≤11 years.

Efficacy of corticosteroid sprays — In a systematic review of 18 trials comparing monotherapy with INCS to placebo for all types of NAR, the strength of the evidence for benefit beyond the first few months was low to very low [121]. Individual trials that demonstrated benefit estimated the effect size to be small to moderate.

It is possible that specific subtypes of NAR are more or less responsive to INCS than others. A multicenter, randomized trial assessed the effects of fluticasone furoate on a subset of patients with symptoms that were triggered predominantly by changes in weather and temperature and found no difference compared with placebo [122]. Thus, although patients with NAR as a group derive some benefit from INCS, there are clearly important subgroups of nonresponders that require further study.

Efficacy of antihistamine sprays — As monotherapy, azelastine has been shown to be effective in prospective studies [110,123]. As an example, in two multicenter, randomized, open-label trials, approximately 80 to 85 percent of more than 200 subjects with chronic NAR responded favorably to azelastine [110].

The improvement in symptoms with azelastine is likely due to antiinflammatory actions. Azelastine reduces eosinophil activation and adhesion molecule expression and suppresses inflammatory cytokine generation [114,115,124]. Azelastine may also reduce neurogenic excitation from olfactory stimuli. In the previously mentioned study in which subjects with NAR were exposed to pleasant and unpleasant odors, the administration of azelastine significantly attenuated exaggerated blood flow to odor-sensitive regions of the brain as assessed by magnetic resonance imaging (MRI) [35].

Olopatadine and azelastine (0.1%) were compared for the treatment of NAR in a multicenter, randomized parallel group study lasting 14 days [125]. Both reduced congestion, rhinorrhea, postnasal drip, and sneezing, and there were no statistically significant differences between their effects. In addition, there was no difference in the side effect profile of the two agents, although both medicines have a bitter taste. In another placebo-controlled study, olopatadine reduced the response to hyperosmolar challenge in patients with prominent vasomotor symptoms [126].

Prominent rhinorrhea without other symptoms — When rhinorrhea is the dominant symptom or the only symptom, as in gustatory rhinitis or rhinitis of older adults, ipratropium (0.03%) nasal spray is recommended [3,36,127]. Ipratropium is usually employed at a dose of two sprays to each nostril three times per day. Alternatively, it can also be used as needed or prior to exposures that cause rhinorrhea, such as before cold air exposure or eating. This medication is also available in a concentration of 0.06%, although this strength is intended for short-term use only (eg, treatment of rhinorrhea associated with the common cold). Two multicenter, placebo-controlled trials demonstrated the effectiveness of ipratropium to control rhinorrhea [118,119]:

●The administration of ipratropium nasal spray (0.03%) for one year among 285 patients with perennial NAR resulted in significant improvement in rhinorrhea, as well as a decreased need for additional medications to control symptoms [118].

●In a study of 253 patients with perennial NAR, ipratropium nasal spray significantly reduced rhinorrhea versus that observed with placebo [119].

Adjunctive therapies — Adjunctive therapies that are helpful in some patients include oral decongestants, nasal saline sprays and irrigations, and oral antihistamines. Studies of antileukotriene drugs and intranasal chromones in the treatment of NAR are lacking.

●Oral decongestants – An oral decongestant, such as pseudoephedrine, can be added to the treatment regimen, unless symptoms related to prostatic hyperplasia or hypertension preclude their use. The usual dosing of pseudoephedrine is 30 or 60 mg orally, up to three times daily on symptomatic days.

Phenylephrine hydrochloride is also widely available, but it is less effective for the treatment of rhinitis symptoms and may not be superior to placebo at the 10 mg dose that is commonly available without prescription [128,129].

There are no specific studies examining the clinical efficacy of decongestants for this NAR. Such agents are employed as needed only for congestion not responsive to the use of either the nasal corticosteroid, azelastine, or a combination of both.

●Nasal saline irrigation – Daily nasal lavage or nasal saline sprays can also be useful. These interventions are particularly helpful for symptoms of postnasal drainage. They can be used immediately prior to INCS or azelastine so that the mucosa is freshly cleansed when the medications are applied (table 3).

Nasal lavage is associated with improvement in a variety of rhinitis conditions and carries little risk if properly performed. A large body of observational reports and one prospective, controlled clinical study has found that nasal lavage is effective in NAR as well as chronic rhinosinusitis [130]. In the only prospective study, the use of nasal irrigation significantly improved 23 of 30 nasal symptoms [131].

A variety of over-the-counter devices including bulb syringes and bottle sprayers are effective, provided the system delivers an adequate volume of solution (>200 mL per side) into the nose. Patients can make their own solutions or buy commercially prepared kits. Nasal lavage with warmed saline can be performed as needed only, daily at baseline, or twice daily for increased symptoms.

One nasal lavage device, Navage (brand name), combines a forceful automatic spray into one nostril with simultaneous suction from the opposite nostril. We have found this device to be effective, and we employ it regularly in our practice.

Intranasal saline sprays have also been found effective for symptoms of chronic NAR, including relieving postnasal drip, sneezing, and congestion [67,132]. Saline sprays are somewhat less effective than larger-volume nasal lavage, although they may be more convenient for some patients [133].

●Oral antihistamines – Clinical experience and limited data suggest that the newer, nonsedating H1 antihistamines are not as effective in NAR compared with allergic rhinitis [104,105].

Older, first-generation H1 antihistamines (eg, chlorpheniramine) have anticholinergic properties that can be helpful to some patients with persistent and bothersome postnasal drip and/or anterior rhinorrhea despite the above therapies [134]. However, these medications are sedating and have other disadvantages that are reviewed separately. (See "Pharmacotherapy of allergic rhinitis", section on 'Oral antihistamines'.)

Role of surgery — Several surgical approaches have been used in patients with severe chronic NAR [127,135-138]. These have been reported as uncontrolled case series. Such interventions may be helpful in patients with difficult symptoms that are refractory to multiple therapies (eg, corticosteroid nasal spray in combination with azelastine and/or decongestants and/or ipratropium nasal spray). Six to 12 months of medical management should be allowed before surgical options are considered. Studies of efficacy are lacking.

●Kinetic oscillation stimulation (KOS) appears to stabilize the autonomic dysregulation characteristic of many forms of NAR. It utilizes a balloon placed in the nasal cavity. The balloon is pulsed with air and vibrated for 10 minutes per side. In one study, a single treatment could provide subjective relief for several months, and there were no major adverse effects [139].

●A turbinectomy can be performed when congestion is predominant. With this technique, there has been concern about the destruction and/or elimination of the mucosal surface. However, laser turbinectomy has been reported to preserve normal nasal cytology as well as normal ciliary activity [137].

●A number of other surgical procedures have been tried in the past, including vidian nerve resection, electrocoagulation of anterior ethmoidal nerve, sphenopalatine ganglion block, and others [138,140,141]. None of these techniques have been shown to have long-term benefits, and the potential risks (eg, persistent pain) have to be considered carefully since they may outweigh any possible benefits. However, this is an area of ongoing research, and future therapies may emerge. For example, temperature-controlled radiofrequency neurolysis has been successfully employed for ablation of the posterior nasal nerve area to produce a significant reduction in symptoms in a group of patients deemed refractory to medication treatment. Relief persisted for 52 weeks, and there were no significant side effects [142].

Alternative therapies — Topical capsaicin has been shown to reduce the symptoms of NAR, but irritation of the nasal mucosa was a limiting factor [143-145]. Subsequently, a randomized trial of 42 patients with a significant component of NAR evaluated the effects of a diluted capsaicin nasal spray to which eucalyptol was added to reduce the burning sensation caused by capsaicin [146]. After two weeks of therapy with this preparation (dosed up to 12 actuations daily), patients reported significant improvements in total nasal symptom scores compared with placebo and good tolerability. This preparation is available without a prescription [147]. A 2015 Cochrane review concluded that "capsaicin may be an option in the treatment of idiopathic nonallergic rhinitis" based on low-quality evidence [148]. We do not have extensive experience with this product.

Other alternative and complementary therapies have been evaluated, such as acupuncture and topical silver nitrate, although they cannot be recommended at this time.

Follow-up care — We follow patients receiving chronic therapy for rhinitis every 3 to 12 months, depending upon the severity and nature of the symptoms. The medications regimen can be reduced in some patients over time. However, in most patients, some medication is usually needed on a daily and long-term basis.

PROGNOSIS — Chronic NAR is a persistent condition in the majority of patients. In one study, 180 patients with NAR were reevaluated three to seven years after diagnosis [149]. Fifty-two percent reported worsening symptoms. There was a statistically significant increase in the percentage of patients who had developed asthma (32 to 55 percent), and 11 percent had decrements in lung function compared with their initial evaluation. The relationship between NAR and asthma is reviewed above. (See 'Relationship with asthma' above.)

In addition, 24 percent had developed allergen-specific IgE (most commonly to dust mite and animal epithelia). Thus, over time, chronic NAR may involve the lower airways in some patients, leading to asthma, and can also progress to allergic rhinitis.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Rhinitis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Nonallergic rhinitis (runny or stuffy nose) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition and pathogenesis – Chronic nonallergic rhinitis (NAR) is a syndrome in which some combination of sneezing, rhinorrhea, nasal congestion, and postnasal drainage is present over time in the absence of a specific allergic etiology. The pathogenesis is not well characterized. Other terms for this condition include vasomotor rhinitis, idiopathic rhinitis, nonallergic-noninfectious rhinitis, and intrinsic rhinitis. (See 'Introduction' above and 'Definition' above and 'Theories of pathogenesis' above.)

●Prevalence – As many as 50 percent of patients presenting with rhinitis may have NAR, either alone or in combination with allergic rhinitis or other forms of rhinitis. (See 'Prevalence' above.)

●Clinical features – Compared with allergic rhinitis, NAR has a later age of onset (usually after age 20 years) and more prominent nasal congestion and postnasal drainage. Symptoms of allergic conjunctivitis are absent. Patients often identify weather conditions or nonspecific respiratory irritants (eg, cigarette smoke) as exacerbating factors. Gustatory rhinitis is a subtype of NAR that presents as watery rhinorrhea in response to eating, particularly upon ingestion of heated or spicy foods (See 'Clinical features' above.)

●Diagnosis – Diagnosis is based upon characteristic historic features, physical exam findings, and the absence of evidence of sensitivity to aeroallergens. It is a diagnosis of exclusion, although it may coexist with other forms of rhinitis. (See 'Diagnosis' above and 'Differential diagnosis' above.)

●Differential diagnosis – The differential diagnosis of NAR includes several other forms of rhinitis (table 1), as well as laryngopharyngeal reflux. (See 'Differential diagnosis' above.)

●Treatment options:

•For patients with mild symptoms of NAR, we suggest monotherapy with either an intranasal corticosteroid (INCS) or an intranasal antihistamine spray (Grade 2C). (See 'Management' above.)

•For patients with moderate-to-severe symptoms, we suggest combination therapy with both INCS (table 2) and intranasal antihistamines, rather than monotherapy with either agent (Grade 2C). We find that most patients require both agents daily for adequate symptom control. We start with full-strength doses of both agents and reduce the doses over time as symptoms improve. Combination sprays containing both corticosteroid and antihistamine are also available (ie, azelastine-fluticasone and olopatadine-mometasone). (See 'Combination therapy' above.)

•For patients with NAR and prominent nasal congestion that is refractory to INCS (table 2), intranasal antihistamines, or a combination of both, we suggest adding over-the-counter oral decongestants on an as-needed basis (Grade 2C). Pseudoephedrine is commonly employed but should be used with caution in patients with hypertension. (See 'Adjunctive therapies' above.)

•Daily nasal saline irrigation is a helpful adjunctive therapy for patients with NAR and other forms of rhinitis who find the maneuver comfortable (table 3). Regular use of over-the-counter nasal saline sprays may also benefit some patients. (See 'Adjunctive therapies' above.)

•For patients with prominent watery rhinorrhea without other symptoms, we suggest ipratropium nasal spray (Grade 2C). Isolated rhinorrhea is typical of gustatory rhinitis and rhinitis of older adults. (See 'Prominent rhinorrhea without other symptoms' above.)

●Prognosis – NAR tends to be a persistent condition. Over time, it may involve the lower airways in some patients, leading to asthma, and can also progress to allergic rhinitis. (See 'Prognosis' above and 'Evidence for a localized allergic response' above.)