Non -Allergic Rhinitis Non-Allergic

Leo Martinez, MD Patricia Maeso , MD Maeso, University of Texas Medical Branch Department of Otolaryngology Grand Rounds Presentation December 16, 2009

Outline
Define and Introduction Etiologies Diagnosis Prognosis Treatments

Define
Rhinitis - Two or more nasal symptoms of: Nasal congestion Rhinorrhea Sneezing/Itching Impairment of Smell for more than 1 hr a day

Define
Noninfectious rhinitis has been classified as either allergic or non-allergic. Allergic rhinitis is defined as immunologic nasal response, primary mediated by immunoglobulin E (IgE). Non-allergic rhinitis is defined as rhinitis symptoms in the absence of identifiable allergy, structure abnormality or sinus disease.

Define

Non-allergic rhinitis has been described in many terms Vasomotor rhinitis, vascular rhinitis, perennial, chronic rhinitis and noninfectious perennial rhinitis.

Introduction
Nasal function includes Temperature regulation Olfaction Humidification Filtration and Protection

Introduction
Nasal lining contains secretion of IgA, proteins and enzymes Nasal Cilia propel the matter toward the natural ostia at frequency of 10-15 beats per minute Mucous move at a rate of 2.5-7.5 ml per minute

Introduction
Up to10% of the population affected by rhinitis 58 million American with allergic rhinitis and another 19 million with non-allergic rhinitis In the patient population that presents to ENT clinic, 50% diagnosed with allergic rhinitis and 50% diagnosed with non-allergic rhinitis.2

Introduction
Problems that arise from non-allergic rhinitis (NAR) are similar to allergic rhinitis which include development of sinusitis, eustachian tube dysfunction, chronic otitis media, anosmia, This leads to a lack of productivity at work and frequent doctor visits Medical treatment side effects can cause drowsiness, epistaxis, and nasal dryness on top of the normal symptom of NAR

Table -- Causes of non-allergic rhinitis

Occupational Drug induced Rhinitis medicamentosa NARES Hormonal Idiopathic or vasomotor Atrophic and other mimickers

Occupational
Arises from airborne agents at workplace. Agents do not act through immunemediated mechanism. They are direct irritants to the nasal mucosa and cause non-allergic hyper-responsive reactions.

Occupational Irritants

Occupational Irritants
Over 205 different chemicals entities identified, including cigarette smoke and chemicals and solvents like chlorine, metal salts, latex, glues and wood dusts. Patients usually present with concurrent occupational asthma. Diagnosis is based on history or results of nasal provocation with stimulus. About 70% of patient improve in symptoms when triggers are avoided.

Drug Induced Rhinitis

Drug Induced Rhinitis

Several common medications may induce rhinitis when administered topically or orally. Drugs can be divided into pharmacologic or aspiring hypersensitivity.

MEDICATIONS CONTRIBUTING TO RHINITIS

Cocaine Cocaine Topical Topical nasal nasal decongestants decongestants phosphodiesterase phosphodiesterase type-5 type-5 inhibitors inhibitors (PDE-5)-(PDE-5)-Sildenafi Sildenafi Alpha-adrenoceptor Alpha-adrenoceptor antagonists antagonists Reserpine Reserpine Hydralazine Hydralazine Angiotensin-converting Angiotensin-converting enzyme enzyme inhibitors inhibitors Beta-blockers Beta-blockers Methyldopa Methyldopa Guanethidine Guanethidine Phentolamine Phentolamine Oral Oral contraceptives contraceptives Non steroidal anti-inflammatory medications Aspirin Psychotropic agents Thioridazine Chlordiazepoxide Chlorpromazine Amitriptyline Perphenazine Alprazolam

Drug Induced Rhinitis

Intolerance to aspirin and/or NSAIDS is unpredictable. It is predominately produces rhinorrhea but may be a part of a ASA triad complex involving hyperplastic rhinosinusitis, nasal polyps and asthma.

Drug Induced Rhinitis

Pharmacologic rhinitis is infrequent and a predicable side effect. Usually lead to nasal congestion, but watery secretions and PND can be accompanying symptoms.

Rhinitis Medicamentosa
Rhinitis medicamentosa (RM) is a drug induced non-allergic rhinitis associated with prolonged use of topical nasal decongestants. Also called rebound or chemical rhinitis Incidence is btw 1-9%, equal sex distribution and more common in young to middle age adults and pregnant women.

Rhinitis Medicamentosa
Nasal mucosa innervated predominately by sympathetic fibers. They release Norepinephrine, that stimulate alpha 1 and alpha 2 receptors that cause vasoconstriction. Sympathomimetic amines (phenylephrine) and imidazoline derivatives (oxymetazoline) both produce vasoconstriction by endogenous release of norepinephrine.

Rhinitis Medicamentosa
Prolong use leads to reduced production of presynaptic norepinephrine and also leads to decrease sensitivity of alpha receptors causing need for larger dose for shorter acting time. This leads to a cycle of excessive dose which worsens their original symptoms.

Rhinitis Medicamentosa
Risk of RM is accepted to be greatest after 10 day use of medication. Treatment is gradual stopping of decongestant with introduction of topical corticosteroid. Pt should be warned of temporary worsening symptoms. Pt should be off nasal decongestants for 3 month before any other treatment, medical or surgical, can be used for original nasal disorder.

NARES

NARES
NARES, non-allergic rhinitis with eosinophilia syndrome, is characterized on the basis of 20-25% or greater eosinophils in nasal smears of pt with rhinitis. There is lack of allergy by skin test, or IgE antibodies. Prevalence ranges from 13-33% of nonallergic rhinitis.

Numerous eosinophils on nasal mucosa

NARES
Etiology is unknown, however, NARES is believed to be associated with ASA triad. This is due to the fact that NARES patients frequently develop nasal polyps and asthma later in life. Also, abnormal prostaglandin metabolism has been implicated as cause of NARES However, eosinophil counts are elevated in 20% of nasal smears of general population and not everyone with eosinophilias has symptoms of rhinitis.

NARES
Studies by Powe Et al. (2001) suggest that NARES is a local IgE mediated response that does not result in a systemic response. Epithelium of full thickness turbinates were compared from non-allergic rhinitis, allergic rhinitis and control group, which revealed local IgE in nonallergic and allergic population, and not the controlled group. It was found that the 50% of nonallergic rhinitis pt who had negative response to skin prick tests, had a positive result to nasal allergy challenge.

NARES
Other studies(Romero et al.) have also shown positive nasal allergen challenges to skin prick test negative patients. Therefore, skin prick test negative pt with eosinophilia may require allergen challenge before diagnosis of non-allergic rhinitis. NARES as a subgroup responds better to nasal corticosteroids than other non-allergic rhinitis.

Hormonal Rhinitis

Hormonal Rhinitis
Defined as rhinitis during periods of known hormonal imbalance Estrogens are know to affect the autonomic nervous system by increasing central parasympathetic activity, acetyl choline transferase and acetycholine content. Also, increased inhibition of sympathetic neurons of alpha-2 receptors noted in pregnancy. Estrogen also believed to increase hyaluronic acid in nasal mucosa.

Hormonal Rhinitis
Therefore, the most common causes are pregnancy, menstruation, puberty and exogenous estrogen. Hormonal rhinitis in pregnancy usually manifest in the second month and continues throughout the pregnancy. Cumulative incidence of pregnancy rhinitis was 22%, 69% in women who were smokers.

Hormonal Rhinitis
Hypothyroidism may also be a known cause of hormonal rhinitis. In pt with hypothyroidism, edema increases in the turbinates as a result of TSH release. However, evidence is inconclusive at this time. Nasal congestion and rhinorrhea are the most common symptoms of hormonal rhinitis.

Idiopathic rhinitis
Also known as vasomotor rhinitis is characterized by nasal blockage and rhinorrhea, but sneezing and pruritus is lower than allergic rhinitis. Etiology is unknown, however attempts have been made to differentiate idiopathic rhinitis on basis hyperactivity to histamine, methacholine, cold dry air or capsaicin. None of the test have been able to differentiate it from other forms of rhinitis

Idiopathic Rhinitis

Idiopathic rhinitis (IR) is usually diagnosis of exclusion. Therefore, it is solely diagnosed on patient complaints.

Idiopathic Rhinitis
Exclusion criteria for IR Positive allergy test Smoking Nasal polyps Pregnancy Medications affecting nasal function Beneficial effects of nasal corticosteroid spray (NARES)

Idiopathic Rhinitis
IR have no significant difference in nasal mucosal lymphocytes, antigen-presenting cells, eosinophils, macrophages, mast cells or IgE positive cells compared to controls. A significant reduction of immunocompetent cells in nasal mucosa of IR pt treated with nasal steroids did not reduce nasal complaints. Therefore IR is believed not be causes by inflammation.

Idiopathic Rhinitis

Studies have suggested autonomic dysregulation, neuropeptide or nitric oxide hyperactivity. However, non of these studies have been conclusive

Atrophic rhinitis et al
A number of conditions can produce the same signs and symptoms of rhinitis. Structural conditions mimic rhinitis include deviated septum, nasal tumors, enlarged adenoids, hypertrophic turbinates, and atrophic rhinitis. Immunologic conditions include Wegeners granulomatosis, sarcoidosis, and polychondritis.

Diagnosis

PATIENT HISTORY QUESTION

What What are are your your nasal nasal and and sinus sinus symptoms? symptoms? Do Do they they include: include: Nasal Nasal discharge discharge Congestion/blockage Congestion/blockage Postnasal Postnasal drainage drainage Episodes Episodes of of sneezing sneezing Nasal Nasal itching itching Itchy Itchy eyes eyes Epiphora Epiphora
Did your environment change before the onset of your symptoms Do you have environmental allergies (e.g., hayfever)? Have you undergone allergy testing? Have you been treated for allergies? Are there certain situations or environments in which your symptoms are worse or in which they are better? For example, home, work, indoors, or outdoors? Are there certain times of the day or year during which your symptoms are worse or better?

PATIENT HISTORY QUESTION

What type of work do you do? Are you exposed to chemicals in your occupation? Have you noticed an increase in nasal or sinus symptoms around certain chemicals/aromas? Did your symptoms begin when you started taking certain medications? What medications have you tried for your symptoms Of the medications you have tried, have any resulted in the improvement of your symptoms? Do you have a history of chronic sinusitis? Do you have a history of nasal and/or sinus polyps? Are you sensitive or allergic to aspirin? Have you undergone sinus surgery? Do you have asthma?

A comprehensive head and neck examination includes nasal endoscopy. Boggy and edematous mucosa with clear mucoid secretions suggest noninfectious rhinitis. Inflammation and purulent discharge from middle meatus suggest active infection. Areas of blanched mucosa with prominent vessels suggest chemical exposure Atrophy of mucosa is seen in aging, prior surgery or drug abuse Look for septal deviations, choanal stenosis, polyps.

Treatment

Patient education is key for initial treatment. Pt are frequently not aware of triggers that incites their congestion Avoidance of inciting factors, change in environment, using mask and protective equipment Associated medications can be discontinued or changed If exposure and medications cannot be changed, then medical therapy is next line of treatment.

Treatment
Immunologic therapy has no benefit to nonallergic rhinitis and therefore it is important to distinguish the disease before considering starting immunotherapy. Nasal saline lavage has minor decongestant benefits and improves mucociliary function in both allergic and non-allergic rhinitis.

Topical nasal steroids are widely used for treatment of NAR. They work on the nasal mucosa by decreasing neutrophils and eosinophil chemotaxis, reduced mast cell release and thus decrease edema and inflammation.

Topical Nasal Steroids

Treatment
Fluticasone propionate, budesonide and beclomthasone are the only topical steroids approved for NAR. Efficacy is inconsistent. They must be tried for a minimum of 6 wks. With the exception of NARES, topical steroids sprays do not provide the same reliefs as they do to allergic rhinitis

Treatment
Antihistamines have been shown to have inconsistent results. Histamine release is the pathophysiology indicated for AR. For this reason, they are considered a poor choice for NAR.

Commonly Prescribed Antihistamines

Treatment
Of the antihistamines, Azelastine intranasally has been efficacious for all forms of NAR, including Idiopathic Rhinitis. It is an H1 receptor antagonist, that also inhibits synthesis of leukotrienes, kinins, cytokines and free radicals. However, the exact mechanism of action for relief of symptoms is unknown.

Treatment
The anticholinergic drug Ipratropium bromide, which is mainly used for treatment of asthma, has been shown to be effective in reducing the severity and duration of rhinorrhea in NAR. The strength of 0.03% is the dose for NAR, initially two sprays TID. Once symptoms abate, the dose should be lowered slowly until one spray BID.

Treatment
Mast cell stabilizers such as cromolyn, are effective only for allergic rhinitis and have no benefit with non-allergic disease. No studies to date have been identified looking at the efficacy of leukotriene modifiers in treatment of non-allergic rhinitis

Treatment
Capsaicin has been shown to be of benefit to Idiopathic Rhinitis. Nasal Capsaicin, the pungent agent of hot red peppers, results in rhinorrhea, nasal blockage and sneezing through c-fibers (pain receptors). Repeated application of capsaicin, however, lead to desensitization and degeneration of C-fibers.

Treatment
Dosage is five high dose treatments of intranasal capsaisin over 1 day at 1 hr intervals after local anesthesia or five treatments spread out over 2 wks. Up to 75% of patients will show long lasting (from 4 month to over 1 yr.) relief of symptoms. Even after symptom free period is over, a repeat dose of capsaisin will most likely repeat itself. A lower dose capsaicin formulations nasal sprays can be found OTC at pharmacies and used in higher frequencies.

Treatment
Surgery is reserved for failed medical therapy only. Nasal polyps, inferior turbinate hypertrophy and septal spurs may obstruct nasal cavity and block the action of topical medications.

Treatment
Silver nitrate has been studied as therapy Topically it has been shown to down-regulate nasal mucous membranes stimuli. Clinical trials show improvement over placebo at 6 month interval for most patients. Local irritation and anosmia was rare side effect. A 20% solution was most effective dose that did not cause harmful irritation. Applied by cotton tip applicator for 1 minute once a wk for 5 wks.

Treatment

Submucosal resection, vidian neurectomy or the combination of the two have been shown to be efficacious in treatment of symptoms.

Treatment
Since 1961, vidian neurectomy has demonstrated as treatment for persistent rhinorrhea. Initially done as transantral, recently endoscopic transnasal approaches are used, which have less morbidity (decreased lacrimation and dysesthesia) Efficacy has been documented up to 88% with symptoms ceasing.

Treatment
Many surgical techniques are available to treat inferior turbinate hypertrophy. A randomized control trial of 382 pt with 6 yr. follow up found sub-mucous resection with lateral displacement to be statistically better in terms of efficacy to turbinectomy, laser or cryotherapy or electrocautery

Treatment
Recently Ikeda et al (2006) showed benefit to combined vidian neurectomy and inferior turbinate resection for intractable chronic rhinitis. Fifty-six pt enrolled showed improvement of >80% in symptomatic nasal obstruction, discharge, sneezing, and quality of life. Four pt had complication of anosmia, one showed hyperesthesia.

Follow up
Rondon et al (2009) showed allergen sensitization in subjects diagnosed with nonallergic rhinitis. A sample of 180 pt diagnosed with NAR during 2000-2004 was reevaluated in 2007 by questionnaires, spirometery, skin prick testing and IgE testing Pt with NAR experienced worsening disease (52%), increased persistence and severity (912%), and new comorbidities (24%) of asthmas and conjunctivitis.

Follow up
Sensitization to allergens not present at initial evaluation was detected by skin prick or IgE measurement in 24% of the patients initially diagnosed with NAR This suggested that sensitization of allergens is likely to appear at a later date in adults.

Follow up
Sanders et al (2009) also noticed variability in allergen content in 5 different skin prick test ( up to 10 fold difference in concentration). Therefore it is possible that many apparent cases of non-allergic rhinitis may be misdiagnosed allergic rhinitis.

Conclusion
Non-allergic Rhinitis is diagnosis of exclusion of allergic IgE mediated causes. NAR is typically given diagnoses when no identifiable cause is given, which is up to 50% of cases seen in ENT practices History and physical exam findings are as important an allergy testing in diagnoses

Conclusion
Avoidance of irritative substance, medication changes and monitor of hormonal balance are important initial steps to treatment Topical nasal steroids and topical H-1 receptor antagonist Azelastine are FDA approve medications for use of non-allergic rhinitis Anticholinergic medications and capsaisin treatment have been proven beneficial, where as mast cell stabilizers and leukotriene modifiers have not.

References
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