This article reviews a uniform way to describe nonallergic rhinitis in its various forms. The insights into its pathophysiology are briefly reviewed. A classification scheme for the different forms is provided. This is followed by descriptions of the diagnosis, evaluation, and management of nonallergic rhinitis.
An estimated 17 to 19 million Americans are affected by NAR. Women seem to be more affected by rhinitis, with 70% of women aged 50 to 64 experiencing some form of rhinitis during a 1-year period. Chronic rhinitis symptoms often interfere with school and/or work performance, and a lack of productivity is worsened by the need for frequent doctor visits. In a recent survey of rhinitis patients, 25% noted restricting their choice of occupation or residence to reduce their symptoms. In addition, medications—although usually helpful—may elicit undesirable side effects such as drowsiness, epistaxis, palpitations, and nasal dryness, which compound the overall impact of NAR.
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A patient with rhinitis symptoms should be fully evaluated from a rhinologic standpoint before nasal surgery is undertaken.
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If diagnosed with rhinitis, the patient should be aware that his or her complaints may not be improved with surgery alone; maintenance medical therapy may be required postoperatively.
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Although a common reason for nonallergic rhinitis (NAR), vasomotor rhinitis is a diagnosis of exclusion.
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Systemic diseases and local factors can contribute to NAR and should be recognized by the facial plastic surgeon caring for her or his patients.
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Patient education and awareness of symptom triggers are key factors in the management of NAR.
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Although there are few medications specifically for NAR, it can usually be reasonably managed with a combination of medical therapy and avoidance measures.
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Allergic rhinitis (AR) and NAR may coexist in the same patient. The facial plastic surgeon should be ready to address these entities.
NAR and AR have similar presentations, manifestations, treatments, and impacts on school and work performance. Thus, statistics for AR can be used to infer the economic impact of NAR. In many instances, AR and NAR are often indistinguishable and co-exist. Twenty to 40 million Americans are affected by AR, and the direct costs for doctor visits and medication expenses are at least $1.9 billion annually. The cost of lost productivity approaches $3.8 billion annually.
Of the patients who present to the otolaryngologist’s office, 50% are diagnosed with a form of NAR, and the rest are diagnosed with AR. In a survey of 975 patients visiting allergists’ offices for chronic rhinitis, the National Classification Task Force found that 43% were diagnosed with pure AR, 23% with NAR, and 34% with mixed AR and NAR. Thus, 57% of chronic rhinitis patients have some component of NAR.
Despite the health care burden of NAR, defining it is difficult. Symptom presentation is nonspecific, and patients may present in a variety of ways. Historically, vasomotor rhinitis was the term used to describe chronic, NAR; however, motor nerve or vascular dysfunction has not been well-described. Other terms used include perennial rhinitis, idiopathic rhinitis, perennial NAR, and nonallergic, noninfectious perennial rhinitis. Nonallergic rhinitis is the term used in this article to describe the various forms of the symptom complex of nasal congestion, obstruction, intermittent rhinorrhea as well as occasional itching and sneezing unrelated to an identifable allergen sensitivity by skin or serum testing.
In many cases of NAR, treatment is often indiscriminate, with varied responses seen among patients. The results are often unsatisfactory and frustrating for both the physician and the patient. Because there have been no unifying criteria for this broad class of problems, further investigation and work-up are generally abandoned by many clinicians, especially since there are no clear diagnostic tests. This article will review a uniform way to describe nonallergic rhinitis in its various forms. The insights into it pathophysiology is briefly reviewed. A classification scheme for the different forms is provided. This is followed by descriptions of the diagnosis, evaluation and management of NAR.
Insights into the pathophysiology of NAR
Attempting to understand the pathophysiology of NAR requires an appreciation of nasal function. The upper and lower respiratory tracts are lined with pseudostratified ciliated columnar epithelium, which contains goblet cells, ciliated cells, and basal cells. This lining serves in the important regulatory functions for the nose, including the filtration and humdification of inspired air, temperature regulation, olfaction, and preparation of the inspired air for the lower airways.
The mucosa produces mucus secretions that provide lubrication. Additionally, these secretions contain lysozyme, glycoproteins, lactoferrin, and secretory immunoglobulin A, providing protection for the airway. The cilia propel the mucous blanket and their trapped contents toward the natural sinus ostia and toward the nasopharynx.
The mucosa has a rich vascular supply with abundant venous sinusoids. The nasal cycle is comprised of a normal physiologic phenomenon during which time the nasal mucosa will alternately engorge and decongest. This is regulated by the autonomic nervous system, which controls the vasculature as well as glandular secretions.
Sensation primarily originates from the trigeminal nerve. Afferent ethmoidal nerves provide sensory innervation to the epithelium, vessels, and glands. Unspecified afferent sensory nerves called C-fibers react to pain and changes in temperature and osmolarity; they are the most relevant type of sensory fibers in NAR. These sensory fibers are stimulated by inflammatory mediators such as histamine and bradykinin and are involved in centrally mediated reflexes. Once stimulated, C-fibers depolarize, leading to increased vascular permeability and submucosal gland release. There is also acute stimulation of nasal mucosal endothelial cells and epithelial cells, with the resultant sensation of itching and/or burning, and the production of mucoid rhinorrhea.
The sympathetic portion of the autonomic nervous system comprises 50% of the efferent nasal reflex arc, which causes vasoconstriction of the nasal vasculature. The parasympathetic nerves form the other half of the efferent nasal reflex arc, with relaxation of the blood vessels and stimulation of the serous glands of the nasal mucosa. Notably, unilateral stimulation of the efferent reflex arc leads to a bilateral response.
In essence, a derangement of any component of the nasal mucosa may lead to the symptoms of NAR. The nonspecific and variable symptoms of NAR are confounding; this compounds the difficult task of identifying the exact pathophysiologic source. Various possible etiologies for NAR have been investigated:
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Inflammation
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Hyperreactivity of the parasympathetic limb of the autonomic nervous system and/or hyporeactivity of the sympathetic arm
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Glandular hyper-reactivity
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Hypersensitivity of the sensory input via by C-fibers.
Recent research on patients with NAR has begun to evaluate the role of mucosal immunoglobulin E (IgE) and inflammatory cell production. A subgroup of patients with NAR has been found to demonstrate an increased local prodcution of IgE upon nasal provocation testing. A separate study indicates that a subgroup of NAR patients, who by definition are not systemtically atopic, may display a local allergic disease pathway. This group could possibly be those classically described as possessing NAR with eosinophilia syndrome, or NARES.
In the case of potential autonomic problems, hyper-responsiveness of the afferent sensory limb leads to an exaggerated efferent response with resultant oversecretion of mucus and increased nasal congestion due to capillary plasma exudation. The same symptoms are seen with normal afferent input and a hyper-reactive efferent arc. Less commonly, an intrinsic epithelial problem or a problem with central nervous system regulation can be the source of disordered responsiveness. Unfortunately, given the complex interaction of sinonasal mucosal regulation, it has been difficult to develop an accurate study model.
The inhalation of irritants is linked to the stimulation of the C-fibers, afferent sensory nerves in nasal mucosa, which innervate the epithelium, vessels, and glands. This results in the activation of the parasympathetic nerves and subsequent sneezing, rhinorrhea, and congestion. This reaction may be induced by histamine and possibly lead to an immunomodulatory response and local cellular events. Glandular hypersecretion can also occur independent of sensory nerve stimulation, as has been shown in methacholine challenge tests. Such findings indicate increased mucosal sensitivity and reactivity in patients with NAR.
Nasal provocation testing using various stimulants has been performed in attempts to characterize NAR. In addition to methacholine, histamine, cold dry air, and capsaicin have all been studied. However, no one study model has provided definitive information regarding the physiologic mechanisms involved in NAR. In many of the studies, the stimulant evaluated induced nasal symptoms greater than seen in controls, but symptom response often overlapped with those patients diagnosed AR. Unfortunately, studies exist with contrary results. Additionally, comparison between studies is difficult, as study methods have not been uniform. Furthermore, provocation studies have shown that upon stimulation, multiple reactions may occur simultaneously (eg, release of inflammatory mediators as well as an exagerrated autonomic response). As a result, there are many examples of how to study the many facets of the pathophysiology of NAR, but there is currently no specific model.
Types of NAR
NARES
NARES was first described in 1981. Patients were described as having perennial nasal complaints, rhinorrhea, epiphora, sneezing, and pruritis typical for AR. Cytologic examination of nasal secretions showed marked eosinophilia. However, the patients lacked immunologic reaction to common inhalant allergens. Most of the patients denied a specific trigger, although some reported reactions to weather changes, odors, or chemical irritants. Other studies demonstrated that mast cells, IgE-positive cells, and eosinophils are increased in the nasal mucosa of both AR and NAR patients, possiby as a consequence of localized IgE-mediated reactions. In these patients, epithelial damage was seen in the presence of high local eosinophil counts. Nasal neural dysfunction has also been described to contribute to the symptomatology in NARES-type patients.
Hormone-Related Rhinitis
Rhinitis during pregnancy is a probably one of the best known forms of NAR. Rhinorrhea and congestion are prominent, and a review of the patient’s history frequently elicits a prior history of chronic rhinitis, either allergic or nonallergic. The etiology of this condition is considered to be due in part to direct effects on the nasal mucosa from changes in estrogen, progesterone, prolactin, and placental growth hormone levels. Vascular changes and physiologic expansion of circulating blood volume may also contribute to increased nasal vascular pooling and progesterone-induced vascular smooth muscle relaxation.
Hormones may act directly on the nasal mucosa, causing mucus gland hyper-reactivity and increased rhinorrhea. As such, nasal symptoms may be associated with systemic conditions that result from hormone imbalance such as hypothyroidism and acromegaly. Rhinitis may arise as a result of changing blood hormone concentrations during puberty. Fluctuating serum hormone levels during menstruation and perimenopause are also associated with nasal symptoms.
Medication-Associated Rhinitis
Rhinitis is a common adverse effect of the chronic use decongestant medications. Obtaining a patient history about medication overuse of topical nasal decongestants and cocaine abuse is critical. Frequent or prolonged use can result in rebound congestion that induces dependency on medication use for relief of nasal airway mucosal obstruction.
Rhinitis is an adverse effect of a myriad of other medications. Medications that affect the vasculature for the treatment of hypertension and cardiac conditions can also affect the nasal mucosa. The suspected patient should be queried about the use of beta-blockers, angiotensin-converting enzyme inhibitors, alpha-blockers, and vasodilators. As mentioned earlier, hormones are associated with nasal symptoms, so a history of the use of hormone replacement and oral contraceptives should also be sought. Psychotropic agents are also associated with congestion (eg, thioridazine, amitriptyline, perphenazine). The use of selective seritonin reuptake inhibitors may be associated with rhinitis-type adverse effects as well. Nonsteroidal anti-inflammatory medications are well known for their potential association with rhinosinusitis, sinonasal polyps, and asthma.
Irritant Rhinitis
The production of profuse, mucoid rhinorrhea is known to be stimulated by cold, dry air. Facial pressure and headaches as well as nasal symptoms can be brought on by altitude shifts in some patients such as pilots and flight attendants. Alterations in barometric pressure and temperature can be other inciting causes of this form of NAR.
Gustatory rhinitis occurs when the ingestion of foods leads to mucoid or watery rhinorrhea that lasts for as long as the food is ingested. Hot, spicy foods are a common culprit, but sometimes just the act of eating can lead to runny nose. Other nasal symptoms are often absent; however, sweating and epiphora may accompany the reaction. The likely pathophysiologic mechanism is the stimulation of afferent sensory nerves with resultant activation of the parasympathetic nerves supplying the nasal mucosal and sweat glands.
Tobacco smoke, perfumes, floral fragrances, and cleaning chemicals produce annoyance reactions and are known triggers in patients with a heightened sense of olfaction. Also, some foods and alcohol are triggers for many patients. Patients are often sensitive to multiple irritants that are part of their environment. Air pollution and ozone levels are discussed daily in susceptible areas and times of the year.
Occupational Forms of Rhinitis
The occupational form of rhinitis is a special form of irritant rhinitis that represents a complex form of inhalant-induced rhinitis. Various types of chemical exposure have been classifeid by Baraniuk and Kaliner and consist of immunologic, annoyance, irritational, and corrosive forms. Airway reactions can occur with suprathreshold exposure to chemicals and fumes in the workplace. Oftentimes, reactions are a result of exposure to respiratory inhalant irritants beyond threshold levels. Paint fumes, formaldehyde, oxides of nitrogen, and toluene are also examples of this problem.
Although the pathophysiology is not well understood, there is support that many forms of irritant rhinitis are mediated by neurogenic mechanisms, particularly those that are related to chemical exposures. Neurogenic inflammation is considered a pathway model in chemical sensitivity syndromes, including some forms of chronic rhinitis and asthma. As discussed earlier, the proposed mechanism is the stimulation of irritant receptors on sensory nerves (ie, C-fibers), which induces neuropeptide mediator release. The mediator release then produces vasodilation and edema associated with inflammation independent of immune-mediated inflammation.
Unfortunately, along with typical NAR symptoms, victims of occupational rhinitis may also develop nasal mucosal hyper-reactivity, and problems with an impaired sense of smell, nosebleeds, nasal crusting, and reduced mucociliary function. Nasal and oral mucosal contact with high concentrations of soluble chemical gases can cause inflammation, burns and ulcerations, as well as skin and eye reactions. Examples of such corrosive reactions include those associated with exposures to ammonium, chloride, hydrochloric acid, vinyl chloride, organophosphates, and acrylamide.
The prevalence of occupational rhinitis is estimated to be 5% to 15%. Nonallergic forms should be differentiated from occupationally induced allergic or immunologic rhinitis. Immunologic aeroallergens associated with rhinitis in the workplace include animal proteins, wheat, latex, pyrethrum in the insecticide and garden industries, acid anhydrides in the adhesive industry, and toluene in auto body spray paints. As such, a detailed workplace history is essential.
Idiopathic
A diagnosis of idiopathic or vasomotor rhinitis is given when other identifiable causes of NAR have been excluded. Unfortunately, it is the most common form of NAR. Speculated as an entity more than 50 years ago, vasomotor rhinitis was historically considered to be due to an imbalance of the autonomic nerve supply to the nasal mucosa. Studies since then have demonstrated a possible relationship between vasomotor rhinitis and autonomic nervous system dysfunction. Hypoactivity of the sympathetic nervous system relative to the parasympathetic nervous system results in the diversity of local and systemic symptoms that may be seen in vasomotor rhinitis and autonomic dysfunction.
Associated Local and Systemic Problems
Local factors affecting the nose can result in nasal symptoms. Anatomic findings such as the presence of a septal deviation or nasal valve collapse affect nasal airflow and may give a sense of congestion. Hypertrophic turbinates may be a result of chronic rhinitis but also cause physical alterations in the nasal airway. The presence of a septal perforation alters the natural lamellar airflow of the nasal cavities and may be perceived as congestion or obstruction by the patient.
The nasal symptoms that result from obstruction from inflammatory disease such as polyps or neoplasms are sometimes diagnosed as rhinitis or sinus problems before the correct diagnosis is made. Rhinitis may be the first sign of inflammatory sinonasal disease or infection. Systemic problems such as autoimmune disorders or vasculitides such as Sjogren syndrome, lupus, sacoidosis, Wegener syndrome, and Churg-straus syndrome are associated with chronic rhinitis. Congenital problems associated with ciliary dysmotility must also be kept in mind. Cystic fibrosis is also part of the differential diagnosis in chronic rhinitis.
Types of NAR
NARES
NARES was first described in 1981. Patients were described as having perennial nasal complaints, rhinorrhea, epiphora, sneezing, and pruritis typical for AR. Cytologic examination of nasal secretions showed marked eosinophilia. However, the patients lacked immunologic reaction to common inhalant allergens. Most of the patients denied a specific trigger, although some reported reactions to weather changes, odors, or chemical irritants. Other studies demonstrated that mast cells, IgE-positive cells, and eosinophils are increased in the nasal mucosa of both AR and NAR patients, possiby as a consequence of localized IgE-mediated reactions. In these patients, epithelial damage was seen in the presence of high local eosinophil counts. Nasal neural dysfunction has also been described to contribute to the symptomatology in NARES-type patients.
Hormone-Related Rhinitis
Rhinitis during pregnancy is a probably one of the best known forms of NAR. Rhinorrhea and congestion are prominent, and a review of the patient’s history frequently elicits a prior history of chronic rhinitis, either allergic or nonallergic. The etiology of this condition is considered to be due in part to direct effects on the nasal mucosa from changes in estrogen, progesterone, prolactin, and placental growth hormone levels. Vascular changes and physiologic expansion of circulating blood volume may also contribute to increased nasal vascular pooling and progesterone-induced vascular smooth muscle relaxation.
Hormones may act directly on the nasal mucosa, causing mucus gland hyper-reactivity and increased rhinorrhea. As such, nasal symptoms may be associated with systemic conditions that result from hormone imbalance such as hypothyroidism and acromegaly. Rhinitis may arise as a result of changing blood hormone concentrations during puberty. Fluctuating serum hormone levels during menstruation and perimenopause are also associated with nasal symptoms.
Medication-Associated Rhinitis
Rhinitis is a common adverse effect of the chronic use decongestant medications. Obtaining a patient history about medication overuse of topical nasal decongestants and cocaine abuse is critical. Frequent or prolonged use can result in rebound congestion that induces dependency on medication use for relief of nasal airway mucosal obstruction.
Rhinitis is an adverse effect of a myriad of other medications. Medications that affect the vasculature for the treatment of hypertension and cardiac conditions can also affect the nasal mucosa. The suspected patient should be queried about the use of beta-blockers, angiotensin-converting enzyme inhibitors, alpha-blockers, and vasodilators. As mentioned earlier, hormones are associated with nasal symptoms, so a history of the use of hormone replacement and oral contraceptives should also be sought. Psychotropic agents are also associated with congestion (eg, thioridazine, amitriptyline, perphenazine). The use of selective seritonin reuptake inhibitors may be associated with rhinitis-type adverse effects as well. Nonsteroidal anti-inflammatory medications are well known for their potential association with rhinosinusitis, sinonasal polyps, and asthma.
Irritant Rhinitis
The production of profuse, mucoid rhinorrhea is known to be stimulated by cold, dry air. Facial pressure and headaches as well as nasal symptoms can be brought on by altitude shifts in some patients such as pilots and flight attendants. Alterations in barometric pressure and temperature can be other inciting causes of this form of NAR.
Gustatory rhinitis occurs when the ingestion of foods leads to mucoid or watery rhinorrhea that lasts for as long as the food is ingested. Hot, spicy foods are a common culprit, but sometimes just the act of eating can lead to runny nose. Other nasal symptoms are often absent; however, sweating and epiphora may accompany the reaction. The likely pathophysiologic mechanism is the stimulation of afferent sensory nerves with resultant activation of the parasympathetic nerves supplying the nasal mucosal and sweat glands.
Tobacco smoke, perfumes, floral fragrances, and cleaning chemicals produce annoyance reactions and are known triggers in patients with a heightened sense of olfaction. Also, some foods and alcohol are triggers for many patients. Patients are often sensitive to multiple irritants that are part of their environment. Air pollution and ozone levels are discussed daily in susceptible areas and times of the year.
Occupational Forms of Rhinitis
The occupational form of rhinitis is a special form of irritant rhinitis that represents a complex form of inhalant-induced rhinitis. Various types of chemical exposure have been classifeid by Baraniuk and Kaliner and consist of immunologic, annoyance, irritational, and corrosive forms. Airway reactions can occur with suprathreshold exposure to chemicals and fumes in the workplace. Oftentimes, reactions are a result of exposure to respiratory inhalant irritants beyond threshold levels. Paint fumes, formaldehyde, oxides of nitrogen, and toluene are also examples of this problem.
Although the pathophysiology is not well understood, there is support that many forms of irritant rhinitis are mediated by neurogenic mechanisms, particularly those that are related to chemical exposures. Neurogenic inflammation is considered a pathway model in chemical sensitivity syndromes, including some forms of chronic rhinitis and asthma. As discussed earlier, the proposed mechanism is the stimulation of irritant receptors on sensory nerves (ie, C-fibers), which induces neuropeptide mediator release. The mediator release then produces vasodilation and edema associated with inflammation independent of immune-mediated inflammation.
Unfortunately, along with typical NAR symptoms, victims of occupational rhinitis may also develop nasal mucosal hyper-reactivity, and problems with an impaired sense of smell, nosebleeds, nasal crusting, and reduced mucociliary function. Nasal and oral mucosal contact with high concentrations of soluble chemical gases can cause inflammation, burns and ulcerations, as well as skin and eye reactions. Examples of such corrosive reactions include those associated with exposures to ammonium, chloride, hydrochloric acid, vinyl chloride, organophosphates, and acrylamide.
The prevalence of occupational rhinitis is estimated to be 5% to 15%. Nonallergic forms should be differentiated from occupationally induced allergic or immunologic rhinitis. Immunologic aeroallergens associated with rhinitis in the workplace include animal proteins, wheat, latex, pyrethrum in the insecticide and garden industries, acid anhydrides in the adhesive industry, and toluene in auto body spray paints. As such, a detailed workplace history is essential.
Idiopathic
A diagnosis of idiopathic or vasomotor rhinitis is given when other identifiable causes of NAR have been excluded. Unfortunately, it is the most common form of NAR. Speculated as an entity more than 50 years ago, vasomotor rhinitis was historically considered to be due to an imbalance of the autonomic nerve supply to the nasal mucosa. Studies since then have demonstrated a possible relationship between vasomotor rhinitis and autonomic nervous system dysfunction. Hypoactivity of the sympathetic nervous system relative to the parasympathetic nervous system results in the diversity of local and systemic symptoms that may be seen in vasomotor rhinitis and autonomic dysfunction.
Associated Local and Systemic Problems
Local factors affecting the nose can result in nasal symptoms. Anatomic findings such as the presence of a septal deviation or nasal valve collapse affect nasal airflow and may give a sense of congestion. Hypertrophic turbinates may be a result of chronic rhinitis but also cause physical alterations in the nasal airway. The presence of a septal perforation alters the natural lamellar airflow of the nasal cavities and may be perceived as congestion or obstruction by the patient.
The nasal symptoms that result from obstruction from inflammatory disease such as polyps or neoplasms are sometimes diagnosed as rhinitis or sinus problems before the correct diagnosis is made. Rhinitis may be the first sign of inflammatory sinonasal disease or infection. Systemic problems such as autoimmune disorders or vasculitides such as Sjogren syndrome, lupus, sacoidosis, Wegener syndrome, and Churg-straus syndrome are associated with chronic rhinitis. Congenital problems associated with ciliary dysmotility must also be kept in mind. Cystic fibrosis is also part of the differential diagnosis in chronic rhinitis.
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