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Vasomotor Rhinitis
Introduction
Nonallergic rhinitis (NAR) describes a syndrome of chronic symptoms of nasal congestion and rhinorrhea, unrelated to a specific allergen. Nonallergic rhinitis can subdivide into numerous different subtypes with vasomotor rhinitis (VMR) being the most common type. Vasomotor rhinitis is a term often used to describe rhinitis symptoms associated with nonallergic, noninfectious triggers with no clear etiology after the conclusion of an exhaustive search for a diagnosis. The pathophysiology of nonallergic rhinitis is complex, with still much to be discovered. It is partly due to an imbalance between parasympathetic and sympathetic inputs on the nasal mucosa.[1] The most critical factor in attaining a proper diagnosis of vasomotor rhinitis is a comprehensive history and physical. The best overall treatment is the avoidance of the known trigger with medical therapy as an adjunct. When all other options fail, surgical intervention becomes a viable therapy.
Etiology
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Etiology
Although the etiology of vasomotor rhinitis is not well understood, it is thought to be associated with the dysregulation of sympathetic, parasympathetic, and nociceptive nerves innervating the nasal mucosa.[1] The imbalance among mediators results in increased vascular permeability and mucus secretion from the submucosal nasal glands.[2][3] Mucous secretion is regulated primarily by the parasympathetic nervous system, whereas the sympathetic nervous system controls vascular tone.[4] Acetylcholine is the primary parasympathetic neurotransmitter that regulates mucus secretion and rhinorrhea. Norepinephrine and neuropeptide Y are sympathetic neurotransmitters that control the vascular tone of vessels in the nasal mucosa and modulate the parasympathetic system-initiated secretions.[5] Sensory neuropeptides and nociceptive type C fibers of the trigeminal nerve contribute to mast cell degranulation as well as the itching/sneezing reflexes.[1]
Epidemiology
Rhinitis, whether allergic or nonallergic, affects roughly 20% of the population in industrialized countries.[6] An estimated 20 to 40 million people are affected by allergic rhinitis, costing over $1.9 billion annually.[1] An estimated 17 to 19 million Americans experience nonallergic rhinitis.[7] Nonallergic rhinitis presents later in life, with patients developing symptoms most commonly between the ages of 30 and 60.[6] Females are more affected by nonallergic rhinitis than men. 70% of women aged 50 to 64 experience some form of nonallergic rhinitis in any given year.[8]
History and Physical
Vasomotor rhinitis is clinically diagnosed. An exhaustive history, complete head and neck examination, and diagnostic testing will rule out infections, allergic, and inflammatory causes.[9] Headache, facial pressure, postnasal drip, coughing, and throat clearing are common symptoms among both allergic and nonallergic rhinitis.[10] Patients with vasomotor rhinitis tend to categorize into two groups depending on predominant symptomatology: “blockers” with congestion and “runners” with rhinorrhea. Patients with rhinorrhea tend to have an enhanced cholinergic response. Those with nasal obstruction tend to have nociceptive neurons with a heightened response to harmless stimuli.[9][10] Vasomotor rhinitis is generally perennial. However, seasonal exacerbation of vasomotor rhinitis from shifts in barometric pressure, temperature, and humidity may get misconstrued as allergic rhinitis. Environmental triggers that affect vasomotor rhinitis patients may include strong odors, cold air exposure, alcohol ingestion, and/or spicy foods. Physical exam often reveals boggy edematous mucosa with clear mucoid secretions. Mucosal injection and lymphoid hyperplasia involving the tonsils, adenoids, and lingual tonsils may be present. There are reports of an area of blanched mucosa surrounds prominent vessels in chemical sensitivities.[11] Examination of the nasal cavity and nasopharynx may help to identify primary or secondary causes of rhinitis. An example: the presence of purulent drainage from the middle meatus on nasal endoscopy would indicate an infectious process essentially ruling out vasomotor rhinitis.
Evaluation
The workup for vasomotor rhinitis should include skin testing and/or serum-specific IgE antibodies. As a diagnosis of exclusion, vasomotor rhinitis will typically have a negative skin test and serum antibodies for relevant allergens. Nasal cytology can provide information about cell types composing the mucosa and helps to identify the presence of inflammatory markers. Scrapings from the inferior turbinate, nasal lavage, or nose blowing can provide epithelial cells for analysis. The presence of 5 to 25 eosinophils in high-powered fields is compatible with the diagnosis of nonallergic rhinitis with eosinophilia syndrome (NARES), a subset of nonallergic rhinitis.[12] Brandt and Bernstein developed a validated questionnaire to aid in the diagnosis of vasomotor rhinitis through a series of questions. Their results revealed that patients with onset of symptoms after the age of 35 years, a negative family history of allergies or atopy, no outdoor or cat-related symptoms, and symptoms associated with exposure to perfumes and fragrances had a 96% likelihood of having vasomotor rhinitis.[13] Nasal provocation testing has become standardized via commercially available products. Provocation testing involves exposing a patient to a respective allergen, assessing the clinical response, and collecting objective data with rhinomanometry and acoustic rhinometry.[14] A computed tomography scan of the paranasal sinuses is a diagnostic option for patients with suspected sinus disease, and magnetic resonance imaging can assist with suspected mass lesions of the head and neck. However, in cases of vasomotor rhinitis, imaging will rarely reveal pathology and is not particularly useful.
Distinguishing vasomotor rhinitis from allergic rhinitis can be challenging. Symptomatology and physical exam findings are often very similar. Allergic rhinitis is a nasal disorder associated with an allergen exposure that induces an IgE-mediated inflammatory response. The timing of symptoms provides clues into differentiating between non-allergic rhinitis and allergic rhinitis. Seasonal peaks of pollen, places with pet dander and/or mold spores, geographical relocation leading to symptoms can point to a diagnosis of allergic rhinitis. The patient’s history provides essential information for diagnosis. Allergy testing is a clinically useful tool to identify a specific allergen and treat the condition. Allergy testing alone can be nonspecific, but in conjunction with a thorough history and physical exam is valuable in distinguishing between vasomotor rhinitis and allergic rhinitis.[15]
A detailed history will often elucidate an infectious process from an allergic or nonallergic one. Infectious rhinitis also presents with similar symptomatology to nonallergic rhinitis: nasal purulence, postnasal drip, facial pressure and pain, fever, sore throat, etc. The three cardinal symptoms of infectious rhinitis include purulent nasal discharge, nasal obstruction, and facial pressure, and are often present for ten days or longer. A fever may or may not be present depending on the acuity of the infection, and is only 50% sensitive and specific.[16] A physical exam will often reveal purulence in the region of the middle meatus with hyperemia, edema, or crusting along the middle turbinate.
Treatment / Management
Upon determining a diagnosis of vasomotor rhinitis, educating the patient on avoiding environmental triggers is critical.[10] Evading or limiting exposure to inciting factors such as perfumes, tobacco smoke, and cleaning supplies can significantly reduce symptoms. Avoidance of triggers is generally not very difficult. However, when inciting exposures are unavoidable, medications are an option.[1]
A stepwise pharmacologic approach is often implemented, with the initial intervention targeted toward the predominant symptom.[10] Topical nasal corticosteroids are considered first-line in vasomotor rhinitis, especially for congestion and obstructive symptoms. Topical steroids work on the nasal mucosa resulting in decreased neutrophil and eosinophil chemotaxis, reduced mast cell and basophil mediator release, and ultimately decreased edema and inflammation.[17] Topical steroids are generally well-tolerated, and side effects are infrequent. The most commonly reported side effects are nasal dryness, crusting, and septal irritation.[18] Multiple studies have shown the effectiveness of topical nasal steroids in the treatment of vasomotor rhinitis. Integrated analysis of three double-blinded randomized controlled trials demonstrated that fluticasone 200 or 400 mcg was significantly more effective than a placebo.[19] Fluticasone propionate and beclomethasone are currently the only topical steroid preparations approved by the FDA for vasomotor rhinitis.[1][19][20] Budesonide has also shown to be efficacious and is currently the only topical steroid agent with a pregnancy category B rating.[21][22](A1)
Anticholinergic medications can provide relief from unrelenting rhinorrhea. However, the oral preparations have disturbing systemic side effects such as blurred vision, dry mouth, and thickened secretions. A topical anticholinergic like ipratropium bromide is the first choice for rhinorrhea. Two separate randomized controlled trials demonstrated the effectiveness of ipratropium bromide in controlling rhinorrhea.[23][24] Topical anticholinergics act locally and block parasympathetic input to the nasal mucosa glands only.[23] Systemic side effects are uncommon. Epistaxis and nasal dryness may occur.[24] Ipratropium bromide also carries a pregnancy category B rating and can be used in children as young as six.(A1)
Oral antihistamines have a limited role in vasomotor rhinitis, with no specific formulation approved. They tend only to benefit those patients with a sneezing and itching component. Topical antihistamines such as azelastine have approval for both allergic and nonallergic rhinitis. Azelastine is helpful in patients with rhinorrhea and nasal congestion. Azelastine is an H1-receptor antagonist. It also inhibits the synthesis of leukotrienes, kinins, cytokines, and adhesion molecule expression, while providing anti-inflammatory effects unrelated to histamine.[25][26] This characteristic makes it effective in vasomotor rhinitis. Azelastine provides a significant reduction in vasomotor symptomatology, including nasal obstruction, rhinorrhea, and nasal edema, as demonstrated in two randomized control trials.[27][28] These trials demonstrated significant improvement in all symptoms within the first week of treatment. Azelastine is well tolerated with low cessation rates.[27][28] Patients with chronic vasomotor rhinitis are generally less responsive to pharmacologic therapy than those with allergic rhinitis. The combination of intranasal steroids and topical antihistamines has been effective in treating the symptomatology of chronic nonallergic rhinitis.[29] Topical capsaicin has also demonstrated efficacy as an adjunct therapy for those with rhinorrhea and nasal congestion.[30] The mechanism is thought to center around the modulation of the C fibers associated with nociceptive neurons. Capsaicin targets transient receptor potential vanilloid type 1 (TRPV1), an ion channel that present on epithelial cells, submucosal glands, and nerves in the human nasal mucosa and assists in regulating nasal secretions and congestion. Repeated intranasal applications of capsaicin can desensitize TRPV1 make it less sensitive to physical and chemical nociceptive stimuli. However, the limiting factor with capsaicin use is a patient’s ability to tolerate its irritant quality.[31](A1)
Sympathomimetic medications, specifically topical decongestants, can provide short-term symptomatic relief. Topical decongestants work primarily by stimulating alpha-1 and alpha-2 adrenoreceptors on the vasculature of the nasal mucosa. This action leads to vasoconstriction, decreased blood flow, and subsequently decreased congestion and rhinorrhea of the nasal cavity. To date, no study has determined the effectiveness of topical decongestants on chronic non-allergic rhinitis. Long-term use of topical decongestants can lead to rebound vasodilation and increased congestion. This condition is termed rhinitis medicamentosa, a form of drug-induced rhinitis. By limiting the use of nasal decongestants to five days and not exceeding the recommended dosing, rhinitis medicamentosa and addiction are avoidable.[32]
Botulinum toxin has also demonstrated a potential role in the treatment of vasomotor rhinitis through its anticholinergic effects.[4] Botulinum toxin (BTX) inhibits acetylcholine release from the presynaptic nerve terminal. Injecting BTX into the inferior and middle turbinates decreases rhinorrhea and nasal mucous gland secretion in patients with vasomotor rhinitis. The improvement is usually short-lived, lasting roughly four weeks.[33] BTX is considered a safe treatment without significant side effects. However, temporary symptom relief may not be a practical option for most patients.[5](B3)
When medical management alone does not adequately control vasomotor rhinitis symptoms, surgical interventions may be employed. Mucosal sparing inferior turbinate reduction surgery improves obstruction symptoms and acts synergistically with medical therapies.[34] By improving the nasal airway, decreasing mucosal edema, preserving turbinate function, and reducing obstructive nasal symptoms, which also allows for topical steroids and histamines to reach further into the nasal cavity, a greater reduction of symptoms is provided.[1](A1)
The therapeutic transection of the vidian nerve is a well-known surgical option for vasomotor rhinitis. The technique aims to disrupt the autonomic nerve supply of the nasal cavity, thus decreasing nasal secretions.[1] The vidian nerve forms from the confluence of the greater superficial petrosal and deep petrosal nerves. The deep petrosal contains sympathetic fibers. The greater superficial petrosal nerve contains preganglionic parasympathetic secretomotor fibers for the lacrimal, palatine, and nasal mucus glands, as well as the nerves responsible for vasodilating the vessels of the nasal mucosa.[35] The first vidian neurectomy was described by Golding-Wood in 1961 using a transantral approach and carried significant morbidity due to facial numbness, postoperative bleeding, and ocular injuries.[36][37] With the advent of endoscopic techniques, improved visualization of the pterygopalatine fossa has decreased complications associated with neurectomy. Rates of successful control of rhinitis and patient satisfaction following endoscopic vidian neurectomy have been reported as high as 91%.[38] A systematic review performed by Marshak et al. reported that all published case series associated with vidian neurectomy improved rhinorrhea and nasal congestion.[35] The most notable complication associated with neurectomy includes postoperative dry eyes from decreased lacrimation with a reported aggregate rate of 48%, dysesthesia, and mucosal engorgement when supine.[3][37] Most symptoms were temporary, with dry eyes resolving in 1 to 6 months.[1][35](A1)
Treating nonallergic rhinitis in pregnancy and the pediatric population presents its own challenges. Management should center around conservative therapy first. Nasal saline irrigations have essentially no risk and may be helpful. If medications are necessary, several options exist. Diphenhydramine may be an option when needed, although with caution in children less than two and in the first trimester of pregnancy. Ipratropium bromide carries a category B rating and is safe in children as young as six. As discussed above, budesonide is the only topical nasal steroid with a category B rating. Fluticasone is safe to use in patients as young as four years of age. Topical decongestants can be used on a limited basis in children as young as 6. Oxymetazoline is the decongestant of choice in both pregnancy and pediatric populations.[39][40]
Differential Diagnosis
Primary and secondary causes of nonallergic rhinitis exist. Primary causes include eight subtypes: drug-induced rhinitis; gustatory rhinitis; hormonal induced rhinitis; nonallergic rhinitis with eosinophilia syndrome; senile rhinitis; atrophic rhinitis; cerebral spinal fluid leak; and idiopathic nonallergic rhinitis.[9] Secondary causes include granulomatosis with polyangiitis; Churg-Strauss syndrome, relapsing polychondritis, systemic lupus erythematosus, Sjogren syndrome, autoimmune rhinitis, hypothyroidism, pregnancy, acromegaly, metabolic syndromes, cystic fibrosis, Kartagener syndrome, sarcoidosis, immunodeficiency, amyloidosis, laryngopharyngeal reflux, and chronic fatigue syndrome.[41]
Drug-induced rhinitis is often further divided into three categories: neurogenic, inflammatory, and idiopathic. Numerous medications list rhinitis as a side effect. The most notable offenders are antihypertensive medications, erectile dysfunction medications, and some psychiatric medications. Overuse of topical decongestants leads to rhinitis medicamentosa by a different mechanism. Systemic anti-hypertensive drugs cause rhinitis through neurogenic mechanisms. They induce a parasympathetic dominance of the nasal mucosa by inhibiting norepinephrine release, which leads to congestion and rhinorrhea.[42]
Hormone-induced rhinitis is associated with nasal congestion secondary to elevated estrogen and progesterone. Up to 65% of women self-report nasal congestion at some time during their pregnancy.[43] The mechanism is still under investigation. It appears that a cyclic hormonal pattern or slowly increasing plasma levels can affect the nasal mucosa. The decrease in estrogen and progesterone after delivery correlates with a rapid resolution of rhinitis symptoms postpartum.[44]
Occupational rhinitis (OR) is a nasal irritation and inflammation that occurs from workplace exposures. Causes of rhinitis in the workplace can classify as either allergic, irritant, or a combination. Occupational rhinitis causes often get subdivided into high molecular weight compounds such as plant or animal-derived proteins and low molecular weight compounds, which are often hapten associated. Certain occupations are at an increased risk: bakers, livestock breeders, industry workers, veterinarians, etc.[45] The diagnosis of OR requires both documentation of rhinitis and causation related to workplace exposure. IgE-specific antibodies are often seen in the high molecular weight compound exposures but are less sensitive in the low molecular weight compounds. Reproduction of nasal symptoms from nasal provocation challenge testing remains the standard of care in diagnosing occupational rhinitis.[46]
Prognosis
Nonallergic rhinitis is a persistent condition that is usually present lifelong. One study by Rondon and colleagues,[47] reexamined 180 patients with nonallergic rhinitis 3 to 7 years after initial diagnosis. As high as 52% of patients experienced worsening disease, with a 12% increase in persistence, and a 9% increase in the severity of nasal symptoms. Additionally, patients with nonallergic rhinitis went on to develop new comorbidities, with the most common being asthma. The development of chronic sinusitis also increased.[48]
Complications
Chronic vasomotor rhinitis symptoms often interfere with work performance and school attendance due to loss of productivity and frequent doctor visits. Chronic nonallergic rhinitis places considerable physical and economic burdens on sufferers. In a survey of rhinitis patients, 25% endorsed limiting their choice of occupation or place of residence to reduce rhinitis symptoms.[49] Also, medical treatments to control symptoms may prompt undesirable side effects such as nasal dryness, palpitations, epistaxis, and drowsiness. These side effects compound the negative impact of nonallergic rhinitis on patients.[50] Chronic nonallergic rhinitis is often associated with other conditions such as headaches, eustachian tube dysfunction, nasal polyps, obstructive sleep apnea, and chronic cough. These symptoms can significantly complicate management and impair quality of life.[41]
Deterrence and Patient Education
Patient education is critical in managing vasomotor rhinitis. Patients with known environmental, non-immunologic, and irritant triggers should be reminded to avoid exposure to these offending agents. Avoidance of irritating stimuli is the mainstay of treatment. Avoidance measures and medical therapy are often enough to decrease most of the symptomatology and mucosal disease associated with nonallergic rhinitis. If stimuli are unavoidable, educating the patient on pretreating with topical nasal steroids or histamines can limit symptoms.[1][10]
Enhancing Healthcare Team Outcomes
Vasomotor rhinitis is a diagnosis of exclusion after performing an exhaustive investigation into a patient’s history. Vasomotor rhinitis is the most commonly diagnosed nonallergic rhinitis, not because of high prevalence, but often from healthcare professionals resorting to diagnosis without performing an extensive workup. Allergic rhinitis and nonallergic rhinitis have very similar symptomatology, such as congestion, rhinorrhea, facial pressure, and headache. They are often differentiated by whether an immunoglobulin E (IgE) response assessment is positive. However, not all allergic rhinitis patients are affected by an IgE inflammatory process. Skin and serum allergy tests are often inadequate in their ability to describe local allergic rhinitis.
Clinicians are almost always involved in the care of patients with allergic and nonallergic rhinitis. Whether it is an allergist, otolaryngologist, and/or primary clinician, rhinitis is very common with most providers encountering the disease in their practice. When the diagnosis becomes more complex, consultation with a rhinologist or specialist may be warranted. As will all aspects of healthcare, interprofessional coordination is critical for the effective management of patients with nonallergic and allergic rhinitis. The laboratory technicians collect serum samples for IgE testing and analyze the results. The allergy technicians perform the appropriate allergen skin testing and interpret results. The nurses are vital members of the interprofessional group as they monitor the patient's vital signs, review patients’ medications, assess therapeutic effectiveness, and triage symptom severity. The pharmacists ensure proper dosing for intranasal steroids and histamines and other medical management of rhinitis while screening for interactions amongst medications. Pharmacists can also discuss alternative agents with the prescriber in the event of inadequate therapeutic response or adverse events. The radiologists also play a vital role in analyzing nasal anatomic obstructions on imaging. As with any condition, an interprofessional team approach to diagnosis and management ensures the best potential for positive results for the patient. [Level 5]
Patients with negative systemic allergy assessments and negative imaging are often categorized into a nonallergic rhinitis subtype but have a clinical picture congruent with local allergic rhinitis. A recent cross-sectional study was performed to assess the clinical characteristics of patients with nonallergic rhinitis. Older patients who denied a history of asthma and lacked an inhalant allergy trigger were more likely to have true nonallergic rhinitis. Environmental triggers were not considered a distinguishing feature between local allergic rhinitis and nonallergic rhinitis. The results of this research study may help guide differentiation between truly nonallergic etiologies and those with falsely negative systemic allergy testing. [Level 4][51]
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