Allergic Rhinitis in Children Alfred Tam MBBSHK FRCPEdin

Allergic Rhinitis in Children Alfred Tam MBBS(HK), FRCP(Edin. , London, Glasg. ) FHKCPaed, FHKAM(Paediatrics) Department of Paediatrics and Adolescent Medicine, University of Hong Kong

Allergic Rhinitis in Children • • • What is allergic rhinitis? Diagnosis and differential diagnosis Assessment and classification of AR What can make AR worse or better? Health effects of AR What can we do to make AR better?

What is allergic rhinitis? • • • Rhinorhoea Nasal blockage Postnasal drip Itchiness Sneezing Associated health effects ‼ Ig. E mediated

Allergic rhinitis is increasing Lee SL et al. Pediatr Allergy Immunol 2004; 15: 72 -8.

AR prevalence varies in different cities Wong G et al. Clin Exp Allergy 2001; 31: 1225. Past 12 mths %(95%CI) HK BJ GZ Numbers 3110 4227 3565 Wheeze 5. 8(5. 0 -6. 7) 3. 8(3. 3 -4. 4) 3. 4(2. 8 -4. 1) 15. 0(13. 9 -16. 4) 6. 7(5. 9 -7. 5) 7. 4(6. 6 -8. 3) 3. 8(3. 1 -4. 5) 2. 2(1. 8 -2. 7) 1. 8(1. 4 -2. 3) Rhinoconjunctivitis Flexural eczema

Atopic sensitization is not that different! Wong G et al. BMJ 2004; 329: 486 -9. %(95%CI) HK BJ GZ Numbers 1341 1044 1098 Atopic 41. 2(38. 5 -43. 8) 23. 9(21. 3 -26. 4) 30. 8(28. 1 -33. 5) D. pter 34. 1(31. 5 -36. 6) 7. 5(5. 9 -9. 1) 20. 0(17. 6 -22. 4) D. far 25. 9(23. 5 -28. 2) 5. 7(4. 3 -7. 1) 17. 9(15. 6 -20. 2) 3. 7(2. 7 -4. 7) 5. 6(4. 2 -6. 9) 4. 3(3. 1 -5. 5) 11. 5(9. 8 -13. 2) 13. 3(11. 3 -15. 4) 17. 8(14. 8 -19. 2) Cat Cockroach

Allergic Rhinitis in Hanoi Nguyen et al. Pediatr Allergy Immunol 2003; 14: 272 -9. Symptoms % n Ever allergic rhinitis 34. 9 338 Allergic rhinitis in past 12 months 27. 6 267 Allergic rhinoconjunctivitis in past 12 months 10. 7 104 AR limiting activities 17 165 Ever hay fever 7. 8 76 Doctor diagnosed hay fever 11. 2 109

Diagnosis of Allergic Rhinitis 1. Clinical symptoms of recurrent or persistent rhinitis and/or associated health effects 2. Signs of atopy and recurrent or persistent rhinitis 3. Demonstration of Ig. E allergy 4. Exclusion of other causes of rhinitis

Diagnosis of Allergic Rhinitis 1. Clinical symptoms of recurrent or persistent rhinitis and/or associated health effects – – – Rhinorhoea Nasal blockage Postnasal drip Itchiness Sneezing Others: conjunctivitis, eczema, asthma, chronic rhinosinusitis, otitis media with effusion, sleep obstruction…

Diagnosis of Allergic Rhinitis 2. Signs of atopy and recurrent or persistent rhinitis

Diagnosis in Primary Care Setting

Diagnosis of Allergic Rhinitis 3. Demonstration of Ig. E allergy

Immunoassay vs Skin Test for Diagnosis of Allergy Immunoassay • Not influenced by medication • Not influenced by skin disease • Does not require expertise • Quality control possible • Expensive Skin test • • Higher sensitivity Immediate results Requires expertise Cheaper

Other Causes of Rhinitis in Children • Infection – Viral, bacterial, – Rhinosinusitis • Foreign body in the nose • Rhinitis associated with physical or chemical factors • Drug, food induced rhinitis • NARES, aspirin sensitivity • Vasomotor rhinitis

Health Effects of Allergic Rhinitis • • Social inconvenience Sleep disturbances/obstruction Learning difficulties Impaired maxillary growth Dental problems Infection: nose and sinuses Co-morbidities: conjunctivitis, asthma, rhinosinusitis, otitis media

Short Form Health Survey (SF-36) Profiles of Patients with Allergic Rhinitis controls (n=139) 90 allergic rhinitis (n=312) 85 * † scale: 0 to 100 80 Declining health status * 75 * 70 * * 65 60 * 55 50 Physical Functioning Role– Physical Bodily Pain General Health Vitality Domains Adapted from Meltzer EO et al. J Allergy Clin Immunol. 1997; 99: S 815 Social Functioning Role– Emotional Mental Health Change in Health

Perennial Rhinitis: an Independent Risk Factor for Asthma (European Community Respiratory Health Survey) 25 20 OR=11 no rhinitis, N=5198 rhinitis, N=1412 15 Asthma (%) OR=17 10 5 0 Atopic Adapted from Leynaert B et al. J Allergy Clin Immunol 1999; 104: 301 Non atopic

Looking for asthma…

In Patients with Rhinitis: • Routinely ask for symptoms suggestive of asthma • Perform chest examination • Consider lung function testing • Consider tests for bronchial hyperresponsiveness in selected cases

ARIA Classification Intermittent. Š 4 days per week. or Š 4 weeks Mild normal sleep & no impairment of daily activities, sport, leisure & normal work and school & no troublesome symptoms in untreated patients Persistent. > 4 days per week. and > 4 weeks Moderatesevere one or more items. abnormal sleep. impairment of daily activities, sport, leisure. abnormal work and school. troublesome symptoms

Medications for Allergic Rhinitis ARIA sneezing obstruction H 1 -antihistamines oral +++ intranasal intraocular Corticosteroids Cromones intranasal intraocular Decongestants rhinorrhea nasal itch symptoms nasal +++ ++ 0 +++ 0 to + +++ 0 +++ + 0 ++ ++ ++ 0 +++ + + 0 + 0 0 ++ intranasal 0 0 ++ 0 0 oral 0 0 + 0 0 Anti-cholinergics 0 +++ 0 0 0 Anti-leukotrienes 0 + ++ 0 ++ eye

Oral Antihistamines • First generation agents • Newer agents Chlorpheniramine Acrivastine Brompheniramine Azelastine Diphenydramine Cetirizine Promethazine Desloratadine Fexofenadine Tripolidine Levocetirizine Loratadine Hydroxyzine Mizolastine Azatadine

Nasal Antihistamines • Azelastine • Levocabastine • Olopatadine

Efficacy of an Antihistamine over 6 Months in Persistent Allergic Rhinitis Sneezing * 0. 8 Pruritus Nose Pruritus Eyes * * 1. 0 mean Individual symptom score improvement Rhinorrhea * * * * 0. 6 Congestion * 0. 4 0. 2 0 * P<0. 05 1 wk 6 mo 4 wk 1 wk 6 mo 4 wk Baseline total symptom score: 8. 95 Levocetirizine, 5 mg, N = 276 Placebo, N = 271 Bachert C et al. J Allergy Clin Immunol 2004: 114: 838

Efficacy of an Antihistamine in the Treatment of Allergic Rhinitis with Perennial Symptoms (n= 337) (n= 339) Simons FER et al. , J Allergy Clin Immunol 2003; 111: 617

Newer Generation Oral Antihistamines Somnolence/Drowsiness Active Placebo Data Source Cetirizine 10 mg qd 13. 7% 6. 3% www. PDR. net Desloratadine 5 mg qd 2. 1% 1. 8% www. PDR. net Fexofenadine 60 mg bid 1. 3% 0. 9% www. PDR. net Levocetirizine 5 mg qd 6. 8% 1. 8% Bachert et al JACI 2004; 114: 838 Loratadine 10 mg qd 8% 6% www. PDR. net

Newer Generation Oral Antihistamines • First line treatment for mild allergic rhinitis • Effective for – Rhinorrhea – Nasal pruritus – Sneezing • Less effective for – Nasal blockage • Possible additional anti-allergic and anti-inflammatory effect • In-vitro effect > in-vivo effect • Minimal or no sedative effects • Once daily administration • Rapid onset and 24 hour duration of action

Decongestants: Alpha-2 Adrenergic Agonists • Oral Pseudoephedrine • Nasal Phenylephrine Oxymetazoline Xylometazoline

Decongestants: Alpha-2 Adrenergic Agonists nasal septum nasal turbinates nasal airway lumen vasoconstriction

Decongestants EFFICACY: • Oral decongestants: moderate • Nasal decongestants: high ADVERSE EFFECTS: • Oral decongestants: insomnia, tachycardia, hyperkinesia tremor, increased blood pressure, stroke (? ) • Nasal decongestants: tachyphylaxis, rebound congestion, nasal hyperresponsiveness, rhinitis medicamentosa

Cysteinyl-Leukotriene Production and the Cys. LT 1 Receptor Cys. LT 1 receptor cytosolic phospholipase A 2 leukotriene C 4 arachidonic nucleus acid + 5 -lipoxygenase activating protein 5 -lipoxygenase leukotriene A 4 leukotriene C 4 leukotriene D 4 leukotriene E 4 leukotriene C 4 synthase mast cells basophils eosinophils macrophages

Efficacy of a Cys. LT 1 Receptor Antagonist in Allergic Rhinitis with Seasonal Symptoms Daytime Nasal Symptoms Score (0 -3 point scale) 0 Change from baseline (mean, 95% CI) -0. 2 -0. 4 -0. 6 * * placebo, N=149 montelukast, N=155 mean baseline=2. 0 *p<0. 01 vs placebo Adapted from Nayak, et al. Ann Allergy Asthma Immunol. 2002; 88: 592 loratadine, N=301

Anti-Leukotriene Treatment in Allergic Rhinitis Efficacy • • • Equipotent to H 1 receptor antagonists but with onset of action after 2 days Reduce nasal and systemic eosinophilia May be used for simultaneous treatment of allergic rhinitis and asthma Safety • Dyspepsia (approx. 2%)

Nasal Corticosteroids Beclomethasone dipropionate Budesonide Ciclesonide* Flunisolide Fluticasone propionate Mometasone furoate Triamcinolone acetonide * Currently only approved for asthma

Nasal Corticosteroids 1 2 3 reduction of mucosal mast cells reduction of mucosal inflammation • suppression of reduction of late phase reactions priming nasal hyperresponsiveness reduction of acute allergic reactions reduction of symptoms and exacerbations glandular activity and vascular leakage • induction of vasoconstriction

Efficacy of Nasal Corticosteroid Sprays in Children with Allergic Rhinitis and Seasonal Symptoms Meltzer E. et al. J Allergy Clin Immunol. 1999; 104: 107.

Comparative Efficacy of Nasal Corticosteroids Mandl M. et al. Ann Allergy Asthma Immunol 1997; 79: 370

Nasal Corticosteroids • Most potent anti-inflammatory agents • Effective in treatment of all nasal symptoms including obstruction • Superior to anti-histamines and anti-leukotienes • First line pharmacotherapy for persistent allergic rhinitis

Nasal Corticosteroids • Overall safe to use • Adverse Effects – Nasal irritation – Epistaxis – Septal perforation (extremely rare) – HPA axis suppression (inconsistent and not clinically significant) – Suppressed growth (only in one study with beclomethasone)

Nasal Corticosteroid vs Placebo: Effects on 12 -Hour Urinary Free Cortisol in 2 -3 Year-Old Children 6 -week treatment Value of 1 indicates no change from baseline 1. 0 0. 8 0. 6 Adjusted Geometric Mean of the Change from Baseline 0. 4 0. 98 0. 94 SE=1. 15 N=31 N=29 0. 2 0 Fluticasone Proprionate Nasal Spray 200 µg daily Adapted from Galant, S. P. et al. Pediatrics 2003; 112: 96 Placebo

Other Management Aspects • Manage other co-morbidities: – Allergic conjunctivitis – Asthma – Sinusitis… • Environmental manipulations: – allergen avoidance – Pollution treatment • Nutritional support • Activities and sports

Environmental Control 1. Allergens • • • House dust mites Pets Cockroaches Molds Pollen 2. Pollutants and Irritants

House dust mite allergen avoidance – Provide adequate ventilation to decrease humidity – Wash bedding regularly at 60°C – Encase pillow, mattress and quilt in allergen impermeable covers – Use vacuum cleaner with HEPA filter – Dispose of feather bedding – Remove carpets – Remove curtains, pets and stuffed toys from bedroom

Allergen Avoidance • Pets • Remove pets from bedrooms and, even better, from the entire home • Vacuum carpets, mattresses and upholstery regularly • Wash pets regularly (±) • Molds • Ensure dry indoor conditions • Use ammonia to remove mold from bathrooms and other wet spaces • Cockroaches • Eradicate cockroaches with appropriate gel-type, non-volatile, insecticides • Eliminate dampness, cracks in floors, ceilings, cover food; wash surfaces, fabrics to remove allergen • Pollen • Remain indoors with windows closed at peak pollen times • Wear sunglasses • Use air-conditioning, where possible • Install car pollen filter

To Conclude… • Allergic rhinitis is very common and causes considerable morbidity • Adequate and appropriate treatment leads to significant improvement in quality of life • Co-morbid conditions are common and warrants special attention and treatment for optimal results • Environmental manipulations is also important in the control of disease

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