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

IgE mediated

Allergic rhinitis is increasing

Lee SL et al. Pediatr Allergy Immunol 2004; 15: 72-8.

Prevelance Rates 1995-2001 45 40 35 30 25 % 20 15 10 5 0

Ever rhinitis Current rhinitis Current rhinoconjunctivitis Ever eczema 1995 (3618) 2001(4448)

AR prevalence varies in different cities

Wong G et al. Clin Exp Allergy 2001; 31: 1225.

Past 12 mths %(95%CI)

Numbers

HK
3110

BJ
4227

GZ
3565

Wheeze
Rhinoconjunctivitis

5.8(5.0-6.7)
15.0(13.9-16.4)

3.8(3.3-4.4)
6.7(5.9-7.5)

3.4(2.8-4.1)
7.4(6.6-8.3)

Flexural eczema

3.8(3.1-4.5)

2.2(1.8-2.7)

1.8(1.4-2.3)

Atopic sensitization is not that different!

Wong G et al. BMJ 2004; 329:486-9.

%(95%CI) Numbers

HK 1341

BJ 1044

GZ 1098

Atopic
D. pter D. far Cat Cockroach

41.2(38.5-43.8)
34.1(31.5-36.6) 25.9(23.5-28.2) 3.7(2.7-4.7) 11.5(9.8-13.2)

23.9(21.3-26.4)
7.5(5.9-9.1) 5.7(4.3-7.1) 5.6(4.2-6.9) 13.3(11.3-15.4)

30.8(28.1-33.5)
20.0(17.6-22.4) 17.9(15.6-20.2) 4.3(3.1-5.5) 17.8(14.8-19.2)

Allergic Rhinitis in Hanoi

Nguyen et al. Pediatr Allergy Immunol 2003; 14:272-9.

Symptoms
Ever allergic rhinitis Allergic rhinitis in past 12 months Allergic rhinoconjunctivitis in past 12 months AR limiting activities Ever hay fever Doctor diagnosed hay fever

%
34.9 27.6 10.7 17 7.8 11.2

n
338 267 104 165 76 109

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 IgE 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 IgE 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
90 85 80 controls (n=139) allergic rhinitis (n=312)

* *

scale: 0 to 100

Declining health status

75
70 65 60 55 50
Physical Functioning

* * *

*
Role Physical Bodily Pain General Health Vitality Social Functioning Role Emotional Mental Health Change in Health

Domains Adapted from Meltzer EO et al. J Allergy Clin Immunol. 1997;99:S815

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 (%)
10

OR=17

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

. 4 days per week . or 4 weeks

Persistent
. > 4 days per week . and > 4 weeks

Mild
normal sleep & no impairment of daily activities, sport, leisure & normal work and school & no troublesome symptoms

Moderatesevere
one or more items . abnormal sleep . impairment of daily activities, sport, leisure . abnormal work and school . troublesome symptoms

in untreated patients

Medications for Allergic Rhinitis ARIA

sneezing rhinorrhea eye symptoms
H1-antihistamines oral intranasal intraocular Corticosteroids Cromones intranasal intraocular Decongestants intranasal oral +++ ++ 0 +++ +++ +++ +++ 0 +++

nasal obstruction

nasal itch

0 to + + 0 ++

+++ ++ 0 ++

++ 0

+
0 0 0

+
0 0 0

+
0 ++ +

+
0 0 0

0
++ 0 0

Anti-cholinergics Anti-leukotrienes

0 0

+++ +

0 ++

0 0

0 ++

Oral Antihistamines
First generation agents
Chlorpheniramine
Brompheniramine Diphenydramine Promethazine Tripolidine Hydroxyzine Azatadine

Newer agents
Acrivastine Azelastine Cetirizine Desloratadine Fexofenadine Levocetirizine Loratadine

Mizolastine

Nasal Antihistamines
Azelastine Levocabastine Olopatadine

Efficacy of an Antihistamine over 6 Months in Persistent Allergic Rhinitis

Sneezing Rhinorrhea Pruritus Nose Pruritus Eyes Congestion 1.0

* * * * *

*
* *

* * *

0.8 mean Individual symptom score improvement

0.6

0.4

0.2

* P<0.05

1 wk 4 wk

6 mo

1 wk 4 wk

6 mo

1 wk 4 wk

6 mo

1 wk 4 wk

6 mo

1 wk 4 wk

6 mo

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 Cetirizine 10 mg qd Desloratadine 5 mg qd Placebo Data Source

13.7%

6.3%

www.PDR.net

2.1%

1.8%

www.PDR.net

Fexofenadine 60 mg bid
Levocetirizine 5 mg qd Loratadine 10 mg qd

1.3%

0.9%

www.PDR.net

6.8%

1.8%

Bachert et al JACI 2004;114:838

www.PDR.net

8%

6%

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 Nasal

Pseudoephedrine

Phenylephrine
Oxymetazoline Xylometazoline

Decongestants: Alpha-2 Adrenergic Agonists

nasal septum nasal airway lumen

nasal turbinates

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 CysLT1 Receptor

CysLT1 receptor

cytosolic phospholipase A2
leukotriene C4 arachidonic nucleus acid + 5-lipoxygenase activating protein 5-lipoxygenase leukotriene A4

leukotriene C4

leukotriene D4 leukotriene E4

leukotriene C4 synthase

mast cells basophils eosinophils macrophages

Efficacy of a CysLT1 Receptor Antagonist in Allergic Rhinitis with Seasonal Symptoms

Daytime Nasal Symptoms Score (0-3 point scale)
0 -0.2

Change from baseline (mean, 95% CI)

-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 H1 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 inflammation

reduction of mucosal mast cells

suppression of

reduction of late phase reactions priming nasal hyperresponsiveness

reduction of acute allergic reactions

glandular activity and vascular leakage induction of vasoconstriction

reduction of symptoms and exacerbations

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

Adjusted Geometric Mean 0.6 of the Change from Baseline 0.4

0.2

0.98
SE=1.14 N=31

0.94
SE=1.15 N=29

Fluticasone Proprionate Nasal Spray 200 g daily

Placebo

Adapted from Galant, S. P. et al. Pediatrics 2003;112:96

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 60C 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

Thank you for staying awake!

Or, you may now wake up and ask questions!