UPDATE ON ALLERGIC RHINITIS

MANAGEMENT IN CHILDREN
R. A. MYRNA A LIA
DIVISI ALERGI IMUNOLOGI ANAK
FK UNSRI- RS MOHAMMAD HOESIN
PALEMBANG

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Outline

1 INTRODUCTION 4 MANAGEMENT

2:30
2 H I S T O RY & C L I N I C A L A N A L I S YS
PM
FINDINGS In facete putant oportere sit, eu ius nibh graeco,
ad pri clita dicunt.

3:00
3 DIAGNOSTIC APPROACH C O N TA C T U S
PM
Ea mea quodsi aliquid sadipscing. Sint nihil sit
cu, eam ad modus inermis.

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INTRODUCTION
 INTRODUCTION

ALLERGIC RHINITIS
symptomatic disorder of the nose induced
DEFINITION after allergen exposure due to an IgE-
mediated inflammation of the membranes
lining the nose.

C A R D I N A L S YM P T O M S
Sneezing, PHYSICAL, SOCIAL &
Nasal Obstruction S YM P T O M S WELL BEING
Mucous Discharge
I M PA C T Sleep disturbance, fatigue
School performance
Family financial burden

Bousquet et al. ARIA (Allergic Rinitis and its Impact onf Asthma) 2008 Update in Collaboration with the World Health Organization, GA2LEn and AllerGen
Roberts G, et al. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy 2013; 68: 1102–1116..
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 EPIDEMIOLOGY
ISAAC Phase 3 Study, 2002-2003
Prevalence of Allergic Rhinoconjunctivitis

3,6 4,8

Asher et al, Lancet 2006; 368: 733–43 5

PATHOGENESIS
Immediate hypersensitivity reactions

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 COMORBIDITIES

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Pawankar R et al. WAO Whitebook on Allergy: Update 2013. WAO
 COMORBIDITIES

Environment and Childhood Asthma Study (ECA) started 1992 in Oslo

Norway
1019 subjects participated at 10 year follow up
1015 subject had information of current rhinitis
254/1015 had symptoms of current rinitis

87.4% had at least one comorbidities:

conjunctivitis, current asthma, current atopic eczema, otitis
media, and anaphylaxis

Bertelsen RJ et al. Pediatr Allergy Immunol 2010;21:612-622

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HISTORY &
CLINICAL
FINDINGS
CLINICAL PRESENTATION & COMPLICATIONS
Preschool School Adolescent

Classic Rhinorrhoea- clear discoloured discharge, sniffing

Pruritus- nose rubbing, the “allergic salute”, “ allergic crease, “sneeze”, may be associated with complaints of an
symptoms
itchy mouth or throat in older children
and signs Congestion - mouth breathing, snoring, sleep apnoea, allergic shiners
of rhinitis

Eustachian tube dysfunction - ear pain

on pressure changes (eg flying), reduced
hearing, chronic otitis media with effusion

Potential Cough – often mislabelled as asthma

atypical Poorly controlled asthma – may co-exist with asthma
presentations Sleep problems - tired, poor school performance, irritability
Prolonged and frequent respiratory tract infections
Rhinosinusitis - catarrh, headache, facial
pain, halitosis, cough, hyposmia

Pollen-food syndrome, particularly with

pollen driven allergic rhinitis
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Roberts G, et al. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy 2013; 68: 1102–1116.
 HISTORY
Essential for accurate diagnosis

Symp toms s ugg es tive AR

Waterry rhinorrhea, sneezing, nasal
obstruction, nasal pruritus, ± conjunctivitis
for > 1 hour on most days

Usually no t asso ciat ed with AR

Unilateral symptoms, nasal obstruction without
other symptoms, mucopurulent rhinorrhea, post
nasal drip with thick mucous, and/or no anterior
rhinorrhea,pain, recurrent epistaxis, anosmia
Timing
The frequency, severity, duration,
persistence or intermittence
and seasonality of symptoms

Bousquet et al. ARIA (Allergic Rinitis and its Impact onf Asthma) 2008 Update in Collaboration with the World Health Organization, GA2LEn and AllerGen
Bousquet et al. J Allergy Clin Immunol 2001;108:S147-336.
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 Sneezers vs Blockers

Sneezers and Runners Blockers

Sneezing Especially paroxysmal Little or none
Rhinorrhea Watery anterior and posterior Thick mucus posterior
Nasal Itching Yes No
Nasal blockage Variable Often severe
Diurnal rhythm Worse during day, improving at night Constant, day & night, may be worse at night
Conjunctivitis Often present

Varshney J & Varshney H. Allergic Rinitis: An Overview.Indian J Otolaryngol Head Neck Surg (Apr–Jun 2015) 67(2):143–149
HISTORY
Essential for accurate diagnosis

Qu ality o f life
impairment of school/work
performance, interference with leisure
activities and any sleep disturbances.

Como rbidities
Asthma: history of cough, shortness of breath, wheezing
Conjunctivitis:red, itchy, waterry eyes, eye rubbing
Impaired hearing: speech/language delay, increase
volume of TV, poor concentration, failing at school
Rhinosinusitis: nasal obstruction or discharge, facial pain, Treat ment
headache or cough Effect of previous avoidance or
pharmacological treatment

Bousquet et al. ARIA (Allergic Rinitis and its Impact onf Asthma) 2008 Update in Collaboration with the World Health Organization, GA2LEn and AllerGen
Bousquet et al. J Allergy Clin Immunol 2001;108:S147-336.
Roberts G, et al. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy 2013; 68: 1102–1116. 13
 HISTORY
Essential for accurate diagnosis

F amily His tory

Family history of atopy: asthma, atopic
dermatitis, allergic rhinitis

Po ten tia l trig ger

Exposure in the home, workplace and
school.
Any hobbies which may provoke symptoms
Patients with inhalant allergies
may exhibit cross-reactivity with certain foods

Bousquet et al. ARIA (Allergic Rinitis and its Impact onf Asthma) 2008 Update in Collaboration with the World Health Organization, GA2LEn and AllerGen 14
Bousquet et al. J Allergy Clin Immunol 2001;108:S147-336.
Mouth breather Dentalmaxilofacial Dennie Morgan Eczema
alteration Lines

PHYSICAL FINDINGS
Halitosis, post nasal discharge, middle ear effusion, tympani membrane retraction, wheezing, dermographism, clear nasal discharge

Pale oedematous
Nasal crease
turbinate

Allergic shiner Allergic salute Geographic tongue

DIAGNOSTIC
APPROACH
 Diagnostic approach
ARIA, 2008

B Lipworth et al. Allergic rhinitis treatment algorithm: expert consensus. npj Primary Care Respiratory Medicine 17
(2017) 27:3 ; doi:10.1038/s41533-016-0001-y
 C L A S S I F I C AT I O N

ARI A CLAS SIFICATION OF AL LERG IC RH INITI S

Previously subdivided into Seasonal Allergic Rinitis (SAR) and Perennial Allergic Rinitis (PAR) not satisfactory

MinYG. The Pathophysiology, Diagnosis and Treatment of Allergic Rinitis.Allergy Asthma Immunol Res. 2010 April;2(2):65-76.
doi: 10.4168/aair.2010.2.2.65
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MANAGEMENT
 Management of allergic rhinitis
(ARIA)
moderate
severe
moderate mild
persistent
severe persistent
mild intermittent
intermittent intra-nasal corticosteroid
local chromone
oral or local non-sedative H1-blocker
intra-nasal decongestant (short time) or oral decongestant

allergen and irritant avoidance

immunotherapy
Bousquet J, et al. Allergy 2008; 63(S86):8-160.
 Treatment
Algorithm
ARIA, 2008

MinYG. The Pathophysiology, Diagnosis and Treatment of Allergic Rinitis.Allergy Asthma Immunol Res. 2010 April;2(2):65-76.
doi: 10.4168/aair.2010.2.2.65 21
 Next Generation ARIA Guideline for Allergic
Rhinitis

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Bousquet J, et al. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rinitis based on Grading of Recommendations
Assessment, Development and Evaluation (GRADE) and real-world evidence. J Allergy Clin Immunol 2020;145:70-80.
 Next Generation ARIA Guideline for Allergic
Rhinitis

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Bousquet J, et al. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rinitis based on Grading of Recommendations
Assessment, Development and Evaluation (GRADE) and real-world evidence. J Allergy Clin Immunol 2020;145:70-80.
 Next Generation ARIA Guideline for Allergic
Rhinitis

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Bousquet J, et al. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rinitis based on Grading of Recommendations
Assessment, Development and Evaluation (GRADE) and real-world evidence. J Allergy Clin Immunol 2020;145:70-80.
Effect on drugs on symptoms of AR
Antihistamines
First generation H1 anti Second generation H1
histamines antihistamines
some side effects such as sedation, memory Less penetration to BBB

impairment and psychomotor dysfunction Lesser side effects

The sedative effects of some non-sedating and lowsedating

Antihistamines.
Compared with loratadine (odds ratio = 1), the age- and sex-adjusted odds
ratios for the incidence of sedation were 0.63 (95% CI:
0.36–1.11; P = 0.1) for fexofenadine; 2.79 (95% CI:
1.69–4.58; P < 0.0001) for acrivastine, and 3.53 (95% CI:
2.07–5.42; P < 0.0001) for cetirizine

Blaiss MSS. Curr Med Res Opin 2004; 20(12)

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Antihistamines
Relative comparison of antihistamines on anticholinergic effects, drowsiness, and impairment

Blaiss MSS. Curr Med Res Opin 2004; 20(12)

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Antihistamines
fexofenadine decreases classroom time missed

Blaiss MSS. Curr Med Res Opin 2004; 20(12)

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Intranasal Corticosteroids
• Act locally on the nasal mucosa
• Useful for moderate to severe and/or persistent symptoms of A
• The therapeutic effect reached 7 hours after administration& reaches the maximal level
after 2 weeks.
• Mometasone has the highest binding affinity for nasal steroid receptors, followed by
fluticasone,beclomethasone, budesonide, triamcinolone, and flunisolide
• Both mometasone and fluticasone have lower systemic bioavailabilities very poor gut
absorption.
• FDA approval:
• Mometasone in children ages ≥ 2 years ,
• fluticasone in ages ≥ 4 years
• beclomethasone, budesonide, triamcinolone, and flunisolide in ages ≥ 6 years
Blaiss MSS. Curr Med Res Opin 2004; 20(12)

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Intranasal Corticosteroids

Gentile D, et al. J Allergy Clin Immunol: In Practice 2013;1:214-26)

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Bioavailability of ICS

Bioavailability of currently used INS

Bryson HM, Faulds D. Drugs 1992;43:760–75.; Daley-Yates PT, Baker RC. Br J Clin Pharmacol 2001;51:103–5.; Daley-Yates PT et al. Eur J Clin Pharmacol 2004;60:265–8.; Allen A et al. Clin Ther 2007;29:1415–20.
 FFNS improves nasal symptoms
In children with SAR

Mean change from baseline in mean daily rTNSS over 2-weeks in patients aged 6–11 yr
Global Paediatric PAR
US Paediatric SAR
Treatment Day
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 EP US Paediatric SAR

0 FFNS 110 µg FFNS 55 µg Placebo

Mean change from baseline

-0.5
Baseline mean
-1 daily rTNSS
8.5 8.6 8.4
-1.5
-2
-2.5 LS mean change
-3 from baseline over
2-week treatment –3.16 –2.71 –2.54
-3.5 period (* (*P=0.025) (*P=0.553)
-4 difference FFNS
-4.5 vs placebo)

-5
-5.5 Patient (n) 146 152 150
FFNS 110 µg FFNS 55 µg Placebo

Consistent improvement of nasal symptoms

Meltzer EO et al. Pediatr Allergy Immunol 2009;20:279-86
 FFNS improves nasal symptoms
In children with PAR
Treatment Day
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 E
Mean change from baseline

-0.5

-1

-1.5
FFNS 110 µg FFNS 55 µg Placebo
-2

-2.5

-3

-3.5 Global Paediatric PAR

-4 FFNS 110 µg FFNS 55 µg Placebo

-4.5 Baseline mean daily

8.6 8.5 8.5
rTNSS
-5

-5.5 LS mean change from

baseline over 4-week –3.6 –3.8 –3.0
treatment period
(* difference FFNS vs (*P=0.073) (*P=0.003)
placebo)

Patient (n) 185 185 188

Consistent improvement of nasal symptoms

Masperó J et al. Otolaryngol Head Neck Surg 2008;138:30–7
 Side effects of Intranasal steroids
The most common local AEs associated with INSs are:
 Epistaxis
 Throat irritation and nasal dryness
 Burning
 Stinging

Sastre. J Investig Allergol Clin Immunol 2012; 22: 1-12

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Paediatric safety
FFNS has a favorable safety and tolerability profile in patients aged 6–11 years with PAR or SAR

Placebo (n=330) FFNS 55µg (n=295) FFNS 110µg (n=321)

Most common (occurring ≥ 3%)

Headache 27 (8) 25 (8) 28 (9)
Nasopharyngitis 17 (5) 15 (5) 18 (6)
Pharyngolaryngeal pain 12 (4) 15 (5) 10 (3)

Epistaxis 14 (4) 13 (4) 12 (4)

Pyrexia 5 (2) 8 (3) 10 (3)

Pooled analysis of adverse events with an incidence of ≥3% and more common than placebo (6–11
year age group) (3 studies)

FFNS 55mcg: 2-week SAR study and 6 week PAR study; FFNS 110mcg:2-week SAR study,12-week and 6-week PAR study

Meltzer et al. Clin Invest 2009;29:79-86

 1 year growth study in paediatrics
Growth velocity (cm/year) measured by stadiometry

Subgroup FFNS Placebo

(N=217) (N=218)
Female, n 68 67
Baseline mean (SD) 6.08 (1.22) 6.16 (1.22)
Treatment mean (SD) 5.54 (1.44) 5.88 (1.19)

Change (SD) -0.54 (1.61) -0.28 (1.73)

Male, n 149 151
Baseline mean (SD) 5.87 (1.26) 5.89 (1.21)
Treatment mean (SD) 5.34 (1.05) 5.60 (1.24)

Change (SD) -0.53 (1.51) -0.29 (1.49)

FFNS over 52 weeks in pre-pubescent children resulted in a 0.27cm reduction in growth velocity
compared with placebo
Lee et al. J Allergy Clin Immunol Pract. 2014;2(4):421-7
Environmental
control

Blaiss MSS. Curr Med Res Opin 2004; 20(12)

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THANK YOU!