Pharmacotherapy for Nonallergic Rhinitis

Updated: Aug 16, 2017
  • Author: Vijay R Ramakrishnan, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Overview

Overview

Nonallergic rhinitis is a syndrome resulting from nasal inflammation that encompasses several distinct diagnoses. [1, 2] This syndrome should be distinguished from allergic rhinitis, a syndrome that immunoglobulin E (IgE) is thought to mediate. Nonallergic rhinitis may be diagnosed by means of clinical evaluation or by means of allergen skin testing or radioallergosorbent testing (RAST).

Both allergic and nonallergic rhinitis may have persistent and equally severe symptoms. Depending on its etiology, nonallergic rhinitis may resemble allergic rhinitis in terms of rhinorrhea, sneezing, pruritus, and congestion. These symptoms may vary temporally, ranging from transient to nearly continuous. Inflammation in either type of rhinitis may induce an episode of acute rhinosinusitis in a patient predisposed because of blockages in functionally important intranasal passages.

Quality of life studies have demonstrated that the burden of rhinitis is not simply sinonasal but may be associated with impaired sleep, excessive daytime sleepiness, concentration problems, and increased irritability. [3] The "unified airway" theory applies to nonallergic patients as well; patients with nonallergic rhinitis have been show to be at a higher risk of asthma, and vice versa.

According to a 2007 Danish study, nonallergic rhinitis affects up to 25% of the population, and nearly half of these individuals seek treatment for relief of their symptoms. [4]

Nonallergic rhinitis has 7 basic subclassifications, as follows: (1) infectious rhinitis, (2) vasomotor rhinitis, (3) occupational rhinitis, (4) hormonal rhinitis, (5) drug-induced rhinitis, (6) gustatory rhinitis, and (7) nonallergic rhinitis with eosinophilia syndrome (NARES). A thorough history and physical examination aid the clinician in identifying the etiology and help direct the appropriate therapeutic course.

Patients with allergic rhinitis typically present with rhinorrhea, sneezing, pruritus, and conjunctivitis. Physical examination may demonstrate the "allergic shiner" (dark circles under the eyes that resemble bruises from a black eye), a transverse nasal crease, and boggy-appearing nasal mucosa. The diagnosis can be made clinically on the basis of a helpful history or skin testing.

In 1975, Huggins and Brostoff described a subset of patients with a history suggestive of dust mite allergy but negative skin prick testing who were found to have positive reactions to nasal provocation testing and specific IgE antibodies to dust mites in their nasal secretions. More recently, Powe et al coined the term “entopy” to describe this phenomenon of a localized nasal allergic response with local IgE production in the absence of systemic atopy. Nasal biopsy showed specific IgE to grass pollen in 3 of 11 patients who had been diagnosed with nonallergic rhinitis. [5] In another study, 35% of patients diagnosed with nonallergic rhinitis with negative skin prick testing were found to have positive nasal provocation testing to common allergens. [6] These patients may benefit from standard allergic rhinitis medical therapy, and early data suggest they may also benefit from immunotherapy.

Elevated concentrations of immunoglobulin G subclass 1 (IgG1) and immunoglobulin G subclass 4 (IgG4) anti-IgE autoantibodies have been found in patients with nonallergic rhinitis compared with control subjects. However, these elevations are far lower than those found in patients with allergic rhinitis. In addition, concentrations of serum-soluble Fas (inherent signals for cell death) are substantially elevated in patients with allergic rhinitis compared with patients with nonallergic rhinitis. Therapy for allergic rhinitis is focused on desensitization and use of decongestants, antihistamines, and mast-cell mediators.

Autonomic stimuli have a greater effect on patients with nonallergic rhinitis than on those with allergic rhinitis. Autonomic imbalance favoring the parasympathetic system increases nasal blood flow, edema, and secretions, creating an overall presentation of rhinorrhea and nasal obstruction. Patients can reduce nasal airway resistance up to 50% with isotonic exercise, which increases in sympathetic tone mediate. Changes in body posture from erect to supine can increase nasal airway resistance. In the supine position, pressure is lower in the right nostril than in the left nostril when the patient lies on the right side. Temperature can also affect nasal blood flow and compliance, both of which decrease in cold environments.

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Distinguishing Types of Nonallergic Rhinitis

Infectious rhinitis

Infectious rhinitis is usually caused by an upper respiratory tract infection, usually of viral origin. The most common causes are infections due to rhinovirus, coronavirus, adenovirus, parainfluenza virus, respiratory syncytial virus, or enterovirus. Viral infections are generally self-limited and resolve within 7-10 days. Patients with infectious rhinitis typically present with clear-to-mucopurulent nasal discharge rather than watery rhinorrhea; this discharge is accompanied by facial pain and pressure, an altered sense of smell, and postnasal drainage with cough. Persistent facial pain and edema, purulent drainage, and fevers suggest a secondary bacterial infection.

Therapy should be directed at symptomatic care.

Vasomotor rhinitis

Vasomotor rhinitis is believed to result from disturbed regulation of the parasympathetic and sympathetic systems in which the parasympathetic system dominates, resulting in vasodilation and edema of the nasal vasculature. Resulting symptoms are rhinorrhea, sneezing, and congestion. Cold air, strong odors, stress, or inhaled irritants may exacerbate symptoms. Rates of anxiety and depression are higher in women with vasomotor rhinitis than in healthy women without rhinitis. [7] Patients with profuse rhinorrhea and those with predominant nasal congestion are sometimes distinguished by using the terms "runners" and "blockers," respectively.

Occupational rhinitis

Patients with occupational rhinitis have symptoms of rhinitis only in the workplace. These symptoms are usually due to an inhaled irritant (eg, metal salts, animal dander, latex, wood dusts, chemicals). Patients with occupational rhinitis frequently present with concurrent occupational asthma. Indeed, rates of both noninfectious rhinitis and adult-onset asthma were found to be higher among welders in a study by Storaas et al encompassing multiple areas of northern Europe. The report, drawn from the international, multicenter, population-based Respiratory Health in Northern Europe (RHINE) study, found the hazard ratio for noninfectious rhinitis in welders to be 1.4, with the results consistent for men and women and across the surveyed centers (although the incidence of adult-onset asthma was found to be higher only in men). [8]

The diagnosis is based on the history or the results of nasal provocation or skin testing. Avoidance is preferable, but this is often not achievable. In the situations, nasal corticosteroids or second-generation antihistamines have been of use.

Hormonal rhinitis

Patients may have symptoms of rhinitis during periods of known hormonal imbalance. Estrogens are known to affect the autonomic nervous system by means of several mechanisms. Central parasympathetic activity, acetylcholine content, and activity of acetyl choline transferase are increased. Feedback inhibition of sympathetic neurons mediated by alpha-2 receptors is also increased in hyperestrogen states. In addition, estrogens are believed to increase levels of hyaluronic acid in the nasal mucosa.

The most common hormonal causes of rhinitis are pregnancy, menstruation, puberty, use of exogenous estrogen, and known or occult hypothyroidism. Hormonal rhinitis in pregnancy usually manifests during the second month; it continues throughout pregnancy and ceases after delivery. In patients with hypothyroidism, edema increases in the turbinates as a result of thyrotropic hormone release. Nasal congestion and rhinorrhea are the chief manifesting symptoms of hormonal rhinitis.

Therapy is guided at symptomatic care and treatment of the underlying disease.

Drug-induced rhinitis

Several medications are implicated in rhinitis, including angiotensin-converting enzyme inhibitors, reserpine, guanethidine, phentolamine, methyldopa, beta-blockers, chlorpromazine, gabapentin, penicillamine, aspirin, nonsteroidal anti-inflammatory drugs, inhaled cocaine, exogenous estrogens, and oral contraceptives.

Rhinitis medicamentosa represents a different etiology. This is a drug-induced rhinitis resulting from prolonged use (ie, >5-10 d) of nasal sympathomimetics. During this process, alpha-receptors in the nose are gradually desensitized to endogenous and exogenous stimulation. Patients with this disease typically present with extensive nasal congestion and rhinorrhea resulting from loss of adrenergic tone rather than from the original cause of rhinitis. Normal nasal function should recover within 7-21 days after sympathomimetics are discontinued. Topical nasal steroid spray may ease the transition from the sympathomimetic agents, and some suggest allowing the patient to continue using the offending agent at night for a few days or weaning one nostril at a time.

Gustatory rhinitis

Gustatory rhinitis occurs after eating, particularly hot and spicy foods. The end result, ie, profuse watery rhinorrhea secondary to nasal vasodilation, is vagally mediated and generally occurs within a few hours of oral ingestion. Symptoms of rhinitis are rarely secondary to ingestion of specific preservatives or dyes in food.

Nonallergic rhinitis with eosinophilia syndrome

NARES, or eosinophilic rhinitis (ie, perennial intrinsic rhinitis) accounts for as many as 20% of rhinitis diagnoses. Some researchers believe that this condition may be a precursor to the aspirin triad of intrinsic asthma, nasal polyposis, and aspirin intolerance. Abnormal prostaglandin metabolism has been implicated as a cause of NARES. Eosinophil counts are elevated in approximately 20% of nasal smears in the general population; however, not everyone with eosinophilia has symptoms of rhinitis. A distinguishing feature of NARES is the presence of eosinophils, usually 10-20% on nasal smears. In general, patients with NARES present with nasal congestion, sneezing, rhinorrhea, nasal pruritus, and hyposmia.

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Pharmacotherapy

A wide variety of etiologies are involved in nonallergic rhinitis. Therefore, treatment options should not be implemented randomly. Instead, they should be primarily aimed at resolving the underlying causative physiology. It is also valuable to distinguish between allergic and nonallergic rhinitis before a treatment method is chosen.

Anticholinergics

Ipratropium bromide is the only topical anticholinergic medication for nasal application available in the United States. In addition to the basic structure of atropine, ipratropium contains an isopropyl group, resulting in a quaternary ammonium structure. This ammonium addition limits the systemic absorption of ipratropium (< 10%) through mucous membranes. This limitation, in turn, diminishes the frequency of adverse effects.

Ipratropium is ideal for patients presenting with only rhinorrhea. It is best used in combination if patients present with rhinorrhea and other symptoms because it possesses no activity for treating or preventing sneezing, itching, or nasal congestion. Clinical studies showed that ipratropium reduces the duration and severity of rhinorrhea by 33% and 29%, respectively, compared with placebo. Less than 10% of patients have headache, epistaxis, pharyngitis, nasal dryness, nausea, or nasal irritation.

Ipratropium nasal spray is formulated in concentrations of 0.03% and 0.06%. The 0.03% concentration is specifically intended for the treatment of rhinitis. The 0.06% nasal spray is intended for managing rhinorrhea without a specific diagnosis of rhinitis (eg, common cold). Each actuation of the 0.03% formulation delivers 21 mcg. An ideal dose for patients older than 6 years is 168-252 mcg daily or 2 actuations to each nostril 2-3 times per day. Doses for children younger than 6 years have not been established.

Nasal corticosteroids

Nasal corticosteroids follow the same pathway of reducing inflammation as that of medications taken systemically, but their anti-inflammatory activity is localized to the upper airway. Nasal corticosteroids are believed to permit smooth-muscle relaxation, reduce airway hyperresponsiveness, and reduce the quantity and activity of inflammatory mediators. This class of medications is particularly useful for managing rhinorrhea, sneezing, pruritus, and congestion. Nasal corticosteroids are also useful in patients with NARES, as evidence suggests that they inhibit inactivation of eosinophils and the resultant cascade leading to inflammation.

A study by Kirtsreesakul et al, however, found that although patients with nonallergic rhinitis experienced improvement from nasal steroid therapy, it was to a lesser extent than in patients with allergic rhinitis. The study, in which 149 patients underwent a 28-day course of treatment with triamcinolone acetonide (220 μg once daily), also reported that the therapy proved least effective in cases of noninflammatory noninfectious rhinitis. [9]

Because of the local activity of nasal corticosteroids, adverse reactions are limited to nasal irritation and nasal bleeding, which can be reduced with the use of an aqueous formulation. Many formations are available, and several trials may be needed to discover one the patient will easily comply with. A trial of regular, daily use for at least 1 month is advised, and patients should be counseled that it may take several weeks to achieve a noticeable improvement.

The main difference in the activity of various inhaled corticosteroids is in their binding affinities. Among flunisolide, triamcinolone, beclomethasone, budesonide, and fluticasone, fluticasone is most potent in binding affinity to human glucocorticoid receptors. The clinical relevance of this finding is a magnified response relative to that of other inhaled corticosteroids.

Comparative data in the form of clinical trials between nasal corticosteroids, specifically in patients with nonallergic rhinitis, are scarce. A study of budesonide compared with beclomethasone demonstrated that budesonide was superior regarding total nasal symptom score at the midpoint (ie, 6 mo) and at the conclusion (ie, 12 mo) of the study. [10] The total nasal symptom score was composed of sneezing, nasal congestion, and rhinorrhea. The influencing factor was that patients treated with budesonide had improved resolution of sneezing episodes relative to patients treated with beclomethasone.

In another study, investigators compared the outcomes of 317 patients who had allergic or nonallergic rhinitis and who had received treatment with fluticasone 200 mcg twice daily, beclomethasone 200 mcg twice daily or placebo for 12 weeks. All patients were given terbinafine to cover rhinitis symptoms not relieved by the randomized therapy. No statistically significant differences were demonstrated between the fluticasone and beclomethasone groups regarding nasal blockage on waking, nasal blockage throughout the day, sneezing, rhinorrhea, overall assessment of symptoms, or terbinafine usage. When the data were analyzed, no difference in responses was demonstrated between patients with allergic rhinitis and those with nonallergic rhinitis.

Antihistamines

Antihistamines are useful in relieving rhinorrhea, sneezing, and nasal pruritus. However, as the name implies, they block histamine, a factor most common to patients with allergic rhinitis. Therefore, unless the symptoms result from histamine release, antihistamines have limited benefit. All antihistamines competitively and reversibly block type 1 histamine receptors (H1). In addition, newer antihistamines (second-generation) may inhibit the release of certain inflammatory mediators, specifically mast cells and basophils.

The 2 generations of antihistamines can be distinguished regarding their lipid-penetrating ability. First-generation agents are lipophilic and readily cross the blood-brain barrier, increasing the frequency of CNS adverse effects (eg, sedation). A decreased affinity for cholinergic and 5-hydroxytryptaminergic receptors and an increased affinity for peripheral H1 receptors decrease CNS adverse events with second-generation agents relative to first-generation agents. With the exception of cetirizine, which is cleared renally, antihistamines pass through the cytochrome P450 system. The 2 generations do not differ in efficacy. Furthermore, antihistamines are broken down into subclassifications based on similarities in their chemical structure.

Some nasal antihistamines, such as azelastine, have a labeled indication for the treatment of vasomotor rhinitis. Two multicenter clinical trials showed that azelastine was more effective than placebo in patients' perceptions of rhinorrhea, sneezes, nasal congestion, and postnasal drip. [11] Before the blinding was lifted, nearly twice as many patients randomly selected to receive azelastine stated that they would continue taking the study medication. In addition to its antihistamine actions, azelastine has been shown to possess anti-inflammatory actions that may be responsible for its efficacy in patients with vasomotor rhinitis. Functional MRI examining neurogenic response to odorants in 12 patients with nonallergic rhinitis found treatment with azelastine attenuated blood flow to relevant areas of the brain and may reduce brain response to odorants. [12] Whether this efficacy is specific to azelastine or whether it can be applied to the entire class of antihistamines is not clear.

A newer nasal antihistamine, olopatadine, which is approved for allergic rhinitis, was found to have similar efficacy and safety when compared with azelastine in a multicenter, randomized, double-blind clinical trial. [13]

Sympathomimetics

Nasally applied sympathomimetics are imidazoline derivatives that cause local vasoconstriction through alpha 2-adrenergic agonistic properties, ultimately reducing nasal edema and obstruction. This alpha 2-receptor specificity reduces blood flow to nasal mucosa by approximately 30-40% rather than exerting a direct decongestant effect.

Pseudoephedrine and phenylpropanolamine, systemically administered sympathomimetics were recalled from United States market. These drugs are beta-phenylethylamine derivatives pharmacologically similar to ephedrine. Both medications possess combined alpha-adrenergic stimulation while augmenting the release of norepinephrine. However, pseudoephedrine additionally stimulates beta-adrenergic receptors. Although this combined adrenergic stimulation makes pseudoephedrine strikingly similar to ephedrine, its potency and degree of CNS stimulation are less than those of ephedrine. Both local and systemic types of sympathomimetics are useful for the short-term treatment of nasal obstruction. If the topical formulations are used beyond 5-10 days, patients may develop rhinitis medicamentosa, a condition in which the alpha-adrenergic receptors become downregulated secondary to constant stimulation. Systemic accumulation may leadtoinsomnia, anorexia, and nervousness.

Use extreme caution in patients with glaucoma, benign prostatic hypertrophy, or hypertension because sympathomimetics may exacerbate these conditions.

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Investigational or International Drug Therapy

Capsaicin

Capsaicin is a phenolic chemical contained within the oil of the Capsicum pepper. Capsaicin is initially irritating to its targeted area. However, the area becomes desensitized to the irritation after repeated use. Nerve endings responsible for rhinorrhea, sneezing, and congestion become desensitized when capsaicin is applied to the nasal mucosa. Capsaicin use has been targeted to patients presenting with congestion, rhinorrhea, sneezing, or a combination of these symptoms.

Clinical studies revealed a 60% reduction in nasal airway resistance. In most patients, effectiveness continued for more than 4 months after study completion. In most patients, scores on visual analog scales significantly improved. However, no significant difference was documented for nasal blockage, rhinorrhea, sneezing, coughing, mucous production, or eye irritation before, during, or after study completion. Documented adverse reactions were limited to initial nasal irritation and increased nasal airway resistance.

No consensus is reported for dosages of capsaicin. Suggested regimens range from 3.3 x 10-3 mol capsaicin dissolved in 70% ethanol sprayed into each nostril once a week for 5 weeks to a solution containing capsaicin 0.15 mg/0.5 mL applied to each nostril every 2 or 3 days for 7 treatments. A recent randomized, double-blinded trial of capsaicin versus placebo also found success with twice daily administration for 2 weeks. [14] A capsaicin formulation called Sinol Nasal Spray is available over the counter at pharmacies.

Bacterially derived immunostimulant

Many patients with infectious rhinitis develop recurrent episodes year after year. The bacterially derived immunostimulant ribomunyl is aimed at preventing infectious rhinitis in predisposed patients. It is composed of ribosomal fractions from Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae, as well as membrane fractions of K pneumoniae. The production of humoral-specific and secretory-specific antibodies with this therapy occurs by means of an unidentified mechanism.

In 1 study, more than 38% of patients treated with ribomunyl were free of infectious rhinitis compared with 29.6% of those receiving placebo. In addition, significantly more patients assigned to the placebo group than those assigned to the treatment group required antibiotics. Patients receiving antibiotics in the placebo group required prolonged treatment with antibiotics. Ribomunyl continued protection from infectious rhinitis throughout the peak season (ie, autumn to winter). Although adverse reactions occurred in some patients, they were not specifically reported. Patients were initially given 1 tablet (strength and quantity of individual components not stated) 4 times per week for 3 weeks; this dosage then was reduced to 4 consecutive days per month for a total of 5 months.

To date, ribomunyl is not available in the United States, but it is widely marketed in Europe.

Silver nitrate

Although not widely implemented in clinical practice, topically applied silver nitrate is believed to downregulate nasal mucous membranes to stimuli by means of a local astringent action of coagulated albumin. Patients presenting with rhinorrhea, sneezing, and congestion are most likely to benefit from silver nitrate. In clinical trials, silver nitrate significantly improved nasal symptoms and significantly changed nasal mucosal pathology compared with both flunisolide and placebo after 6 months of treatment. Most patients had no reoccurrence for as long as 6 months after study completion. However, some patients may have signs of reoccurrence at 1 month. Most patients have not reported any adverse effects, with the exception of local irritation and a case of anosmia.

A dose-escalating trial was conducted to determine the most effective concentration (range tested, 5-25%). A 20% solution was the most effective concentration that did not cause harmful nose irritation. Each dose is applied with a cotton-tip held in place for 1 minute once a week for 5 weeks.

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Rhinitis Pharmacotherapy in Special Patient Populations

Pregnant patients

Patients who are pregnant and who present with symptoms of rhinitis are not limited to the specific diagnosis of hormonal rhinitis. Rather, if the cause is rhinitis medicamentosa, beclomethasone nasal inhalation may be beneficial to treat symptoms while the patient is weaned from topical sympathomimetics. Infectious rhinitis may complicate pregnancy, and antibiotics may be required. In addition, some patients may present with vasomotor rhinitis. Nasal saline solution, exercise, and pseudoephedrine are usually beneficial in these patients.

Ipratropium is safe for use in humans, without evidence of teratogenicity. Although ipratropium is excreted in human breast milk, it has not been identified as a harmful agent to infants.

As a class, inhaled corticosteroids are rated as pregnancy category C, implying documented teratogenicity in animals but not in humans. Some experts recommend the use of beclomethasone over other corticosteroids because of its consistent track record. This comment has not been formally evaluated. To the authors' knowledge, no conclusive data have been published regarding the use of any inhaled corticosteroids during lactation and breastfeeding.

The US Food and Drug Administration (FDA) has given a pregnancy category rating of B to all antihistamines with the exceptions of brompheniramine, fexofenadine, and tripelennamine, which are category C. Women should exercise caution if they take antihistamines while breastfeeding. On the basis of a case report of increased crying, irritability, and disturbed sleep in an infant, the manufacturer has recommended that brompheniramine be contraindicated during breastfeeding. Antihistamines are also likely to reduce the volume of milk in lactating women.

Both topical and systemic sympathomimetics are rated as pregnancy category C. Because of the nature of these drugs as powerful vasoconstrictors, they could potentially reduce uterine blood flow. However, human teratogenicity is not specifically reported. These drugs are excreted in breast milk; however, the clinical significance of this excretion is unknown.

Pediatric patients

Nonallergic rhinitis of all types is rare in children, and is poorly understood. The true incidence in children is unknown. Children presenting with NARES account for less than 2% of children with nasal eosinophilia. Second-generation oral antihistamines may be used to control symptoms of rhinitis. If possible, first-generation oral antihistamines should be avoided to prevent adverse reactions, particularly paroxysmal hyperactivity. Nasal corticosteroids may be beneficial in pediatric patients presenting with rhinorrhea, sneezing, pruritus, and congestion. Although growth delay has not been observed in long-term studies, the FDA recommends routine monitoring of height in children treated with corticosteroids. Effects of laryngopharyngeal reflux (LPR) have been implicated in some sinonasal diseases in children and should be considered by the clinician. [15, 16]

A randomized, double-blind, placebo-controlled study by Veskitkul et al indicated that in children with nonallergic rhinitis suffering from recurrent acute rhinosinusitis (RAR), azithromycin can successfully be used prophylactically to decrease the number of RAR episodes. The annual number of RAR episodes in the patients receiving prophylaxis were reduced from 5 to 0.5, according to the report. [17]

Patients with renal and/or hepatic insufficiency

Patients with renal insufficiency, hepatic insufficiency, or both are prone to augmentation of adverse events, resulting from a reduced clearance through renal and/or hepatic pathways. Fortunately, many of the drugs recommended for use in nonallergic rhinitis are administered intranasally. Therefore, subsequent systemic absorption is minimal. Still, antihistamines and some sympathomimetics are administered systemically.

Cetirizine and fexofenadine are largely excreted unchanged in the urine at rates of 50% and 95%, respectively. Although this route of metabolism is advantageous in hepatically impaired patients, the dose should be reduced to cetirizine 5 mg/day and fexofenadine 60 mg/day in patients with renal impairment.

Loratadine passes through the cytochrome P450 isoenzyme system, specifically involving 2D6 and 3A4. Therefore, an initial regimen of loratadine 10 mg every other day is recommended in patients with hepatic insufficiency.

Diphenhydramine, clemastine, brompheniramine, chlorpheniramine, and tripelennamine are metabolized extensively in the liver. However, no dosage adjustments are required in patients with renal or hepatic impairment.

Pseudoephedrine and phenylpropanolamine both are metabolized in the liver, where they form active metabolites. Dosage reduction is not necessary in patients with hepatic impairment. However, a large percentage of these drugs are eliminated unchanged in the urine. Therefore, dosages of pseudoephedrine should be reduced in patients with renal impairment.

Elderly patients

Cholinergic and alpha-adrenergic hyperactivity are common causes of rhinitis in elderly patients. The increased cholinergic response may partly be the result of activation by various foods (ie, gustatory rhinitis). Although ipratropium may be the obvious choice for this type of watery rhinorrhea, some elderly patients may be concerned by unwanted adverse effects, particularly loss of bladder control. Therefore, antihistamines (eg, fexofenadine, cetirizine, loratadine) are preferable.

Athletes

Athletes with nonallergic rhinitis who actively compete on the state and national levels may be difficult to treat. Strict compliance with guidelines US Olympic Committee and International Olympic Committee have established must be observed. Athletes are not permitted to use any oral decongestants. However, the Olympic committee does permit the use of oral antihistamines. Nasal corticosteroids may be permitted for use as approved on a case-by-case basis. Each sporting event is likely to have its own regulations. The prescribing practitioner should verify accepted medications in advance by writing to the appropriate supervising committees.

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Surgical Therapy

Patients whose condition is refractory to medical therapy may seek additional treatment. Surgical therapy should be considered a possible adjuvant to continued medical therapy. Intranasal examination may demonstrate a deviated septum and/or pronounced turbinate hypertrophy. In these cases, it is reasonable to expect septoplasty and/or inferior turbinate reduction to alleviate some of the nasal obstruction and congestion. Many surgical techniques are available to treat inferior turbinate hypertrophy, including submucous resection with or without outfracture, cryotherapy, laser cauterization, electrocauterization, and/or turbinectomy. A randomized control trial of 382 patients with 6-year follow-up was conducted to evaluate submucous resection with lateral displacement (outfracture) in terms of efficacy and complications, and found outcomes to be statistically better than turbinectomy, laser or cryotherapy, or electrocautery.

The vidian nerve contains contributions from the greater and deep petrosal nerves and supplies autonomic input to nasal mucosa. Electrical stimulation of the vidian nerve leads to nasal vasodilation and increased secretions. Vidian neurectomy has been used in the past to manage severe vasomotor rhinitis secondary to medical management. As medical therapy has improved over the past 2 decades, use of this procedure has declined due to difficulties with surgical technique and previously published unsatisfactory long-term results. However, as endoscopic techniques improve, vidian neurectomy has been revisited, and a retrospective study of 14 procedures demonstrated benefit in regards to rhinorrhea and nasal obstruction. [18]

Another series of 178 procedures followed for 1.5 years found 90% of patients were satisfied with their surgical results. [19] A long-term study of patients with persistent allergic rhinitis treated with endoscopic vidian neurectomy found 64.7% and 24.7% of patients reported “much improvement” or “improvement” at 3 years respectively. [20] Complications of endoscopic vidian neurectomy are typically mild and include dry eyes, nasal crusting, and transient cheek and dental numbness.

Additionally, cadaver studies of the parasympathetic innervation of the nose have revealed projections from the pterygopalatine ganglion that innervate the nasal mucosa. Surgery targeting these individual postganglionic nerve fascicles may find a role as new procedure to benefit patients with vasomotor rhinitis while avoiding the morbidity associated with vidian neurectomy. [21]

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Summary

Nonallergic rhinitis is a distinct disease classification, separate from allergic rhinitis, which is characterized by an IgE-mediated response. The diagnosis of nonallergic rhinitis encompasses several individual classifications, including NARES, as well as vasomotor, occupational, hormonal, infectious, drug-induced, and gustatory conditions. A wide variety of medications are available for the treatment of associated symptoms. However, no individual class of medications or single medication is ideal for managing the entire spectrum of symptoms. Surgical therapy may be warranted in particular patients with nonallergic rhinitis refractory to proper medical management. Patients are best treated to manage their unique symptoms and to correct the causes.

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Tables

Table 1. Nasal Corticosteroids (Open Table in a new window)

Generic Name Trade Names Concentration Per Actuation (mcg) Daily Dose (mcg)
Low Medium High
Beclomethasone dipropionate Beconase



Beconase AQ*



Vancenase Pockethaler



Vancenase AQ Double Strength*



42, 84 (double strength) 168-504 504-840 840+
Budesonide Rhinocort



Rhinocort AQ



200 200-400 600-400 600+
Flunisolide Nasarel



Nasalide



250 500-1000 1000-2000 2000+
Fluticasone propionate Flonase* 44, 110, 220 88-264 264-660 660+
Mometasone Nasonex 50 < 200 200 200+
Triamcinolone acetonide Nasacort



Nasacort AQ*



100 400-1000 1000-2000 2000+
* Aqueous formulations.

Table 2. Distinctions Among Classifications of Antihistamines (Open Table in a new window)

Class Distinction
Ethanolamines High degree of antimuscarinic activity, sedation
Ethylenediamines Highest specificity for the H1 receptor
Alkylamines Highest potency
Piperazines No major distinctions
Phenothiazines High degree of anticholinergic activity, sedation
Piperidines Poor CNS penetration, highly selective, low anticholinergic activity

Table 3. Dosing of Available Antihistamines (Open Table in a new window)

Class Generic Name Trade Name Prescription Status Daily Dosage
First generation
Alkylamines Brompheniramines Dimetane* OTC 4 mg q4-6h; not to exceed 24 mg/d
Chlorpheniramines†‡ Chlor-Trimeton* OTC 4 mg q4-6h; not to exceed 24 mg/d
Ethanolamines Clemastine* Tavist OTC 1.34 mg bid or 2.68 mg tid; not to exceed 8.04 mg/d
Diphenhydramine Benadryl OTC 25-50 mg q6-8h
Ethylenediamines Tripelennamine PBZ Rx 25-50 mg q4-6h or 100 mg bid; not to exceed 300 mg/d
Phenothiazines Promethazine Phenergan Rx Not routinely used for rhinitis
Piperazine Hydroxyzine†§ Atarax Rx Not routinely used for rhinitis
Meclizine Antivert, Bonine Rx, OTC Not routinely used for rhinitis
Second generation
Alkylamines Acrivastine|| Semprex-D Rx 1 capsule tid-qid
Piperazines Cetirizine Zyrtec Rx 5-10 mg/d
Levocetirizine Xyzal Rx 5 mg/d
Piperidines Fexofenadine* Allegra Rx 60 mg bid
Loratadine Claritin Rx 10 mg/d
Desloratadine** Clarinex Rx 5 mg/d
Note.—bid = twice daily; OTC = over the counter; q = every; qid = 4 times daily; Rx = prescription; tid = 3 times daily.



* Available as a liquid formation.



Also available with a decongestant (pseudoephedrine).



Available as a generic drug.



§ Active metabolite possesses more activity than parent compound.



|| Available only in combination with pseudoephedrine.



Active metabolite of hydroxyzine.



** Major metabolite of loratadine.



 

Table 4. Dosing of Sympathomimetic Agents (Open Table in a new window)

Type Generic Name Trade Name Daily Dosage
Systemic Phenylpropanolamine Propagest and various generics 25 mg q4h or 50 mg q8h; not to exceed 150 mg/d
Pseudoephedrine Sudafed and various generics 30-60 mg q4-6h OR 120 mg q12h; not to exceed 240 mg/d
Topical Oxymetazoline Afrin 2-3 sprays in each nostril bid
Xylometazoline Otrivin 2-3 sprays in each nostril q8-10h
Note: bid = twice daily; q = every

Table 5. Choosing a Class of Medications for a Specific Symptom of Nonallergic Rhinitis (Open Table in a new window)

Medications Presenting Symptoms
Rhinorrhea Sneezing Pruritus Obstruction Congestion
Corticosteroids X X X   X
Antihistamines X X X    
Anticholinergics X        
Sympathomimetics       X  
Capsaicin* X X     X
Ribomunyl*          
Silver nitrate* X X     X
* Investigational or international drug therapy.

Table 6. Choosing a Class of Medications for a Particular Type of Nonallergic Rhinitis (Open Table in a new window)

Medications Type of Nonallergic Rhinitis
NARES Vasomotor Occupational* Hormonal Infectious Drug Induced* Gustatory
Corticosteroids X   X X   X  
Antihistamines     X X      
Anticholinergics   X   X     X
Sympathomimetics X X   X      
Capsaicin   X          
Ribomunyl         X    
Silver nitrate   X          
* Avoidance of the irritant is the most successful treatment.



Investigational or international drug therapies.



 

Table 7. Treatment Options for Nonallergic Rhinitis in Pregnant Patients (Open Table in a new window)

Medication Pregnancy Class
Antihistamines



Brompheniramine



Chlorpheniramine



Clemastine



Diphenhydramine



Tripelennamine



Acrivastine



Cetirizine



Levocetirizine



Fexofenadine



Loratadine



Desloratadine



 



C



B



B



B



C



B



B



B



C



B



C



Sympathomimetics



Phenylpropanolamine



Pseudoephedrine



Oxymetazoline



Xylometazoline



 



C



C



C



C



Corticosteroids



Beclomethasone



Flunisolide



Fluticasone



Mometasone



Dexamethasone



Budesonide



 



C



C



C



C



C



C



Anticholinergics



Ipratropium



 



B



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