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Allergic Rhinitis 高雄醫學大學附設醫院 耳鼻喉科 高雄市立小港醫院(委託高雄醫學大學經營) 耳鼻喉科 王凌峰 ARIA guideline 2001, Allergic Rhinitis and its Impact on Asthma in collaboration with the WHO To update clinician’s knowledge of allergic rhinitis To highlight the impact of allergic rhinitis on asthma To provide an evidence-based approach to diagnosis To provide an evidence-based approach to treatment To provide a stepwise approach to the management of the disease 2001. 10 Definition Rhinitis: a state of persistent nasal symptoms allergy, infection, structural anomalies in the nose, hormone, drug…. Allergic rhinitis: a symptomatic disorder of the nose, induced after allergen exposure, by an IgEmediated inflammation of the nasal membranes 1. Dykewicz. J Allergy Clin Immunol. 2003;111(suppl):S520. 2. Bauchau and Durham. Eur Respir J. 2004;24:758. 3. Linneberg. BMJ. 2005:331.352. Allergy and Atopy “Allergy“: 1906 von Pirquet Antigens induce changes in reactivity in both: protective immunity and hypersensitivity reactions. apply to the "uncommitted" biologic response, immunity (a beneficial effect) or allergic disease (a harmful effect). Allergy is an acquired potential to develop hypersensitivity reactions to a normally innocuous substance and is mediated by immunological mechanisms (but not exclusively IgE). Allergy and Atopy “Atopy”:Greek atopos, meaning out of place often used to describe IgE-mediated diseases. personal or familial (genetic) tendency to produce IgE antibodies in response to low doses of allergens, usually proteins, and to develop ‘classic’ allergic diseases such as asthma, rhinoconjunctivitis or eczemal dermatitis. Nonatopic allergic diseases: ★ IgE-independent mechanisms: ie. contact dermatitis and hypersensitivity pneumonitis ★ IgE responses to bee venom and drugs are not more frequent in atopic families. Epidemiology Prevalence Overall--10-25%, and increasing In Taiwan: 20~30% of child Hereditism One parent (+)--29%(~40%) Both parents (+)--47%(~75%) Age 11-20 y/o Triggers Allergens Aeroallergens Indoor Mites, dust, animals & insects Outdoor Pollens & moulds Occupational rhinitis Latex allergy Triggers Pollutants Indoor air pollutants >80% of time indoors Tobacco smoke Outdoor air pollutants Automobile--ozone, oxides of nitrogen & sulphur dioxide Triggers Aspirin (& NSAIDs) Classification Seasonal a. some specific season b. usually outdoor allergen: pollen, molds… c. rhinorrhea Perennial a. throughout the year b. usually indoor allergen: house dust, mite… c. nasal obstruction Occupational Classification Intermittent Symptoms Persistent Symptoms < 4 days per week or < 4 weeks Mild normal sleep normal daily activities, sport, leisure normal work and school no troublesome symptoms > 4 days per week and > 4weeks Moderate-Severe one or more items abnormal sleep impairment of daily activities, sport, leisure problems caused at work or school troublesome symptoms Symptoms & signs Symptoms a. rhinorrhea b. nasal obstruction c. nasal itching d. sneezing e. itchy or watery eye f. anosmia, nasal pain, headache Symptoms & Signs Signs a. Pale bluish turinates, frequently with edema “ hyperemia” --- acute infection or over use of topical medication b. Middle ear involvement: OME, eardrum retraction c. Prolonged mouth breathing (adenoid face) - Elevation of the upper lip - Over-bite - High arched palate Symptoms & Signs Signs d. Facial signs - “Allergic shiner” - Horizontal creases under the eyes (Dannie-Morgan line) - “Allergic salute” - supratip nasal crease e. Nasal polyposis f. signs of asthma, atopic dermatitis… Nasal salute Nasal itching Adenoid face Allergic shiners Skoner D, Urbach A, Fireman P. In: Atlas of Pediatric Physical Diagnosis. 3rd ed. 1997 Pathophysiology IgE Ab mediated, type I immune response Sensitization IgE adhered to mast cells & basophils Preformed (stored) mediators Histamine, kinins, proteases, platelet activating factor, heparin Newly formed mediators Prostaglandin, interleukins, leukotriene, cytokines Pathogenesis Early-phase (immediate) response - The onset of sneezing & itching may occur as early as ~30 sec, and usually peaks within minutes - Mast cell: the predominant cell - Histamine, leukotriene, prostaglandin, bradykinin, PAF (platelet activating factor) - Itching, sneezing, watery rhinorrhea, vasodilation (nasal congestion) Pathophysiology Late/delayed phase response 50% 4~12 Hours Priming Eosinophils infiltration TH2-type cytokines: IL-4, 5 & GM-CSF Other mediators: IL-8, RANTES, eotaxins & MCPs Nasal blockage, and nasal hyper-reactivity Allergy is more than histamine Minimal persistent inflammation “The united airways concept” (One airway, one disease) Link between rhinitis and other conditions Co-Morbidities --Asthma Asthma p’t--60-78% allergic rhinitis Allergic rhinitis p’t--19-38% asthma Bronchial challenge--nasal inflammation Nasal challenge--bronchial inflammation Co-Morbidities --Asthma Mechanism Nasal-bronchial reflex Mouth breathing caused by N-O Pulmonary aspiration of nasal contents Diagnosis Lung function test The reversibility of airflow obstruction Co-Morbidities --Asthma Medications Both effective--intranasal steroids, antihistamines, antileukotrienes Optimal management of rhinitis may improve coexisting asthma Diagnosis Routine tests - A typical history - General ENT examination i. Nose: boggy turbinate ii. Ear: OME, eardrum retraction iii. Eye: injected conjunctivitis with watery discharge, allergic shiner iv. Face: adenoid face, supratip nasal crease, Dannie-Morgan fold - Endoscope: rigid, flexible Diagnosis Allergic test - Skin test - Serum specific IgE Nasal cytology - Eosinophilia >20% Nasal challenge - Allergen, aspirin, lysine Radiology - usually unnecessary - X-ray, CT scan Diagnosis Optional tests (mainly for research) - Nasal biopsy - Nasal swab for bacteriology - Mucociliary function i. Nasal mucociliary clearance, ciliary beat frequency, electronmicroscope ii. Nasal inspiratory peak flow (NIPF), rhinomanometry, acoutic rhinometry iii. Olfaction, nitric oxide measurement iv. Testing for comobidities Diagnosis Total serum IgE test - a poorly predictive tool for allergy screening in rhinitis and should rarely be used as a diagnostic tool - In adult: 60~100 KU/L - 35~50% of allergic rhinitis have normal IgE level - 20% of nonatopic individuals have elevated total IgE Diagnosis Specific serum IgE - Phadiatop: for inhalation allergen (23 species) - MAST (Multiple Antigen Simultaneous Test) i. Semi-quantitative ii. 35 species - CAP i. CAP-1 ~ CAP-5 ii. 5 items each time “ Titer of serum IgE is usually unrelated with symptoms” Diagnosis Skin test - Scratch test - Prick-puncture test i. (+) in 15~35% of symptom-free persons - Intradermal test i. more sensitive, but less safe ii. Less correlate with symptoms iii. Positive control: histamine iv. Negative control: phenol, N/S, glycerin - Induration (wheal) & surrounding erythema (flare) Diagnosis Skin test VS specific IgE test Advantage i. greater sensitivity ii. rapid result iii. low cost Disadvantage i. inability in extensive eczema ii. multiple needle pricks iii. Influenced by drugs: antihistamine…. iv. maintain the potency of allergen extract v. anaphylaxis Diagnosis Nasal provocation test - In vivo and intranasal - For more stringent criteria are needed to incriminate the suspected allergen, such as occupational allergy - Non-specific reaction to pepper or other material Management Allergen avoidance indicated when possible Immunotherapy Pharmacotherapy Safety Effectiveness Easy administration Cost Effectiveness Specialist prescription May alter the nature course of the disease Patient education Always indicated Management Allergen avoidance Oral medication - Anti-histamine - Decongestant - Corticosteroid Intra-nasal spray - Intranasal steroid - Mast cell stabilizer (Cromolyn)(Intal) - Antihistamine: Azelastine - Decongestant - Anticholinergic Management Immunotherapy Newer agents - Anti-leukotrienes (zafirlukast®) - Monoclonal anti-IgE Ab (omalizumab ®) - Zileuton (Zyflo): 5-Lipoxygenase (LO) inhibitor Surgery - SMT(submucosal turbinectomy) - Inferior turbinate cauterization - Laser, cryotherapy, chemical agent, electrocautery…. Recommendations for Management of Allergic Rhinitis: ARIA Guidelines Moderate severe intermittent Mild intermittent Mild persistent Moderate severe persistent Intranasal steroid Local cromone Second-generation nonsedating H1 antihistamine Intranasal decongestant (<10 days) or oral decongestant Allergen and irritant avoidance ARIA = Allergic Rhinitis and its Impact on Asthma. Bousquet et al. Allergy. 2002;57:841. Bousquet et al. Allergy. 2003;58:192. Immunotherapy Management Allergen avoidance - Encase mattress, hot washing bedding, wooden floor - Pets, toys - Cockroaches - Aeration and heating ducts - HEPA cleaner a. Single avoidance intervention is fail to reduce allergen load b. Reduce allergen load ≠ symptoms relief Management Anti-histamine a. 1st generation Longifene, Homoclomin, Vena b. 2nd generation: 1st line agents for allergic rhinitis Loratadine(clarityne®), Cetirizine(Zyrtec®), Fexofenadine(allergra®), Clarinase® (clarityne+Peudo-E) c. Newer agent levocetirizine(Xyzal®), Desloratadine(Aerius®) d. Azelastine(Azela®)nasal spray “Inverse agonism” Management --Anti-histamine Side effect: (doparminergic, serotinergic, cholinergic receptor) CNS: sedation, sleepy, unable to concentrate Heart: arrhythmia(Torsades de pointes)Terfenadine, astemizole, especially in combination with macolides or ketoconazole Anti-cholinergic: urinary retention, dryness, precipitation of narrow-angle glaucoma GI upset Intranasal spray: bitter taste: 20% , sedation: 11% Astelin prescribibg information. Montvale, NJ: Med Pointe Pharmaceuticals: 2000. Management Decongestant - α1- adrenergic agonist (phenylephrine) - α2- adrenergic agonist (Oxymetazoline, xylometazoline, naphazoline) - Nonadrenaline releaser (ephedrine, peudoephedrine, amphetamine) - Block re-uptake of noradrenaline (coccaine, TCA, phenylpropanolamine) Management Decongestant - oral - Topical - Pay attention to patients with CV disease, poorly-controlled hypertension, glaucoma, older age, BPH, hyperthyroidism, pregnancy - > 10 days use of topical decongestant tachyphylaxis, rebound congestion (Rhinitis medicamentosa) Management Steroid -Oral -Intranasal corticosteroids :1st line for moderate/severe cases or persistent symptoms and when nasal obstruction is a major concern : Low Bioavailability : Local SE: crusting, dryness, and epistaxis : No Hypothalamic-pituitary-adrenal axis effect : Children growth delay in one report. : Pregnancy: safe for inhaled steroid in asthma woman Management Newer agents - Anti-leukotrienes (montelukast) - Monoclonal anti-IgE Ab (omalizumab ) - Zileuton (Zyflo): 5-Lipoxygenase (LO) inhibitor N Eng J Med 1999; 340(3): 197-208 Management -Immunotherapy Effective Indication Insufficiently controlled by conventional medications Do not wish to be on medications Medications produces undesirable S.E. Not recommended in children <5 y/o Management --Surgery An adjunctive intervention in a few highly selected patients Relief of nasal obstruction Management -- Others Homeopathy, herbalism, acupuncture No scientific & clinical evidence Allergic rhinitis in special conditions Pediatrics Pregnancy Elderly patients Allergies begin in children Evolution of sensitisation to grass pollen between the ages of 0 and 6 years % sensitised Evolution of sensitisation to house dust mite between the ages of 0 and 6 years % sensitised 15 25 20 10 15 10 5 5 0 1 2 3 5 6 Age (years) Bergmann RL et al. Clin Exp Allergy 1998;28:965-70. 0 1 2 3 Age (years) 5 6 “Allergic march” Children Allergic rhinitis: unusual < 2 y/o Allergy tests can be done at any age Medications Few medications have been tested in children < 2 y/o Avoid oral and intramuscular steroids in young children Intranasal steroid, intranasal Cromolyn Pregnancy Nasal obstruction may be aggravated Most medications cross the placenta FDA Pregnant Category: B: Cetirizine, loratadine, vena (Diphenhydramine) Budesonide nasal spray Cromolyn intranasal spray Immunotherapy: may be continued if initiated before pregnancy Initiating IT during pregnancy is not advised Pregnancy 1ST line: intranasal Cromolyn(Intal) Avoid pseudoephedrine in first trimester abortion or gastroschisis Aging Change in connective tissue and vasculature of the nose A less common cause in subjects >65 y/o Atrophic rhinitis is common Medications cause rhinitis (reserpine, guanethidine, phentolamine, methyldopa, prazosin, chlorpromazine or ACE inhibitors) Aging 2nd-generation antihistamine:1st choice Topical anticholinergic For isolated rhinorrhea (ipratropium bromide nasal spray) Specific S.E. Decongestants Drugs with anticholinergic activity, or sedative effect Cost per year in Taiwan 1st 2nd Intranasal Monteluk Omaluzim Zileuton antihistam steroid ast ab (Xolair) (Zyflo) anti(Singulair) histamine ine NT 730 NT 20005000 NT 36004000 NT 16000 NT 400000 NT 70000