Allergic rhinitis E&Dih dtiEuropean & Danish recommendations · Classic symptoms and signs of rhinitisClassic symptoms and signs of rhinitis Rhinorrhoea - sniffing Pruritus - nose

Allergic rhinitisE & D i h d tiEuropean & Danish recommendationsSusanne HalkenSusanne HalkenHans Christian Andersen Children’s HospitalOdense University HospitalOdense University HospitalDenmark

Hans Christian Andersen Children’s Hospital

Hvorfor beskæftige sig med allergisk rhinit?

Ofte en overset og undervurderet sygdom Hyppig sygdom Ofte svær at behandle sufficient Ofte dårlig kompliance

Betydelig indflydelse på indlæring og livskvalitet

S t f jlt lk ft t Symptomerne fejltolkes ofte som astma Betydning for behandling af astma


EAACI Task Force on Pediatric RhinitisEAACI Task Force on Pediatric Rhinitis

Pediatric rhinitis: position paper of the European Academy of Allergology andAcademy of Allergology and Clinical Immunology

G Roberts, M Xatzipsalti, L M Borrego, A Custovic, S Halken, P W Hellings, N G Papadopoulos, G Rotiroti, G Scadding F Timmermans EScadding, F Timmermans, E Valovirta


Dansk vejledning

Allergisk rhinokonjunktivitis hos børn

Dansk vejledning

Allergisk rhinokonjunktivitis hos børn

Susanne Halken, Arne Høst, Birgitte Frederiksen , , gVidebæk, Lars G Hansen og Ole D. Wolters

“Selvbestaltet” arbejdsgruppeManuskriptet DPS allergologi & pulmonologiudvalgEft f l d i i t f l tt tEfterfølgende revision næsten afsluttetSendes til Ufl mhp publikation som klaringsrapportLink på DPS’s hjemmesideLink på DPS s hjemmeside


All i hi itiAllergic rhinitis

Manifestations Differential diagnosis Differential diagnosis Comorbidities Cross reactions Diagnosisg Treatment


Prevalence of allergic rhinitisPrevalence of allergic rhinitis

15-20

161820

9,8101214

4,76,9 6,9

468

10

1,2

024

0-2 år 3-5 år 6-8 år 9-12 år 13-15 år adults

Ref :Danish Institute of Clinical Epidemiology 1997 Mygind N


Ref.:Danish Institute of Clinical Epidemiology 1997. Mygind N, Dahl R Pediatr Allergy Immunol 1996; 7 (suppl 9) : 57-62

Classic symptoms and signs of rhinitisClassic symptoms and signs of rhinitis

Rhinorrhoea sniffing Rhinorrhoea - sniffing Pruritus - nose rubbing, the “allergic salute”, “allergic

crease” paroxysmal sneeze ”crease , paroxysmal sneeze, Congestion - mouth breathing, snoring, sleep

apnoea, allergic shinersapnoea, allergic shiners Habitual open mouth breathing

May be misinterpreted as Tics and even Tics, and even Tourette’s syndrome



Potential atypical presentations of rhinitisPotential atypical presentations of rhinitis Cough Poorly controlled asthma Eustachian tube dysfunction

i h ear pain on pressure changes reduced hearing

chronic otitis media ith eff sion chronic otitis media with effusion Sleep problems - tired, poor school performance, irritability Rhinosinusitis catarrh headache facial pain halitosis Rhinosinusitis - catarrh, headache, facial pain, halitosis,

cough, hyposmia Prolonged and frequent respiratory tract infectionsg q p y Pollen-food syndrome


Co morbiditiesAR & asthma

Co-morbidities

A high degree of comorbidity !

A th

A high degree of comorbidity !

Many children with AR do Asthma Hayfevernot recognize that they

have asthma !

Reviewed in ARIA report


Bousquet, J. et al. JACI 2001;108(5 Suppl):S147-S334

Co morbiditiesCo-morbidities Conjunctivitis

red, itchy, watery eyes, eye rubbing Asthma Impaired hearing Impaired hearing Rhinosinusitis

nasal obstruction or discharge (purulent) with or without hyposmianasal obstruction or discharge (purulent) with or without hyposmia, headache, facial pain or cough.

Sleep problemsdisturbed sleep, snoring, apnoea, tiredness, irritability

Pollen-food syndromeoral pruritus with symptoms with (not cooked or frozen) foods suchoral pruritus with symptoms with (not cooked or frozen) foods such as apples


Impact of untreated rhinitis in childrenImpact of untreated rhinitis in children

Difficulties in concentrating Poor school performance Poor school performance Reduced quality of life


Allergens and allergic airway disease

Allergens associated with allergic airway disease depend on age, climatic, seasonal, p gsocial factor and housing conditions

Allergic asthma most often associated withAllergic asthma most often associated with indoor allergens

Allergic rhinitis most often are associated Allergic rhinitis most often are associated with outdoor allergens (pollen)


Rhinitis and allergy

Perennial symptoms: House dust mites House dust mites Pets

M ld Moulds Foods*

* Young children, especially in case of other allergic manifestations


Rhinitis and allergyRhinitis and allergy

Seasonal symptoms:Seasonal symptoms: Grasspollen Birchpollen Birchpollen Mugwort

M ld Moulds

Ob ll l t d ti ll f d dObs: pollen related cross reactions – pollen-food syndrome


Pollen related cross reactions – pollen-food syndromePollen related cross reactions pollen food syndrome

Different allergens with similar protein structures (epitopes) binds to the same antibodies(epitopes) binds to the same antibodies

Allergen components can be classified by protein families based on their function and structurefamilies based on their function and structure Stability to heat and digestion (e.g. LTP are stable,

PR-10 are heat-labile)PR 10 are heat labile) Severity of reactions

Most often related to a birch Bet v1 homologous in some fruits, vegetables, hazelnuts and peanuts

Most often only reactions to raw fruits / vegetables / nuts Symptoms often itching in mouth and throat


Pollen related cross reactions – pollen-food syndrome

Possible cross reacting allergens in SARPossible cross reacting allergens in SAR

Birch Grass Mugwort

FoodsApple, cherry, pear, hazelnut, potato, carrot celery kiwi

Potato, tomato, wheat, peanut

Celery, carrot, fennel, parsley, coriander mustardcarrot, celery, kiwi p coriander, mustard

Pollen Alder, elm, hazel, b h h

Rye, wheat, corn barley

Composites, chrysanthemuPollen beech, ash corn, barley,

oatchrysanthemu, camomile, dandelion

S l i ti i t il li i l l tSerologic cross reactions is not necessarily clinical relevant


DiagnosisDiagnosis

Often obviousOften obvious If doubt: consider differentialdiagnosis If asthma: allergic rhinitis? If other co-morbodities Allergic rhinitis? If other co-morbodities. Allergic rhinitis? If allergic rhinitis: consider asthma!

Allergy testing: if clinical consequences Allergy testing: if clinical consequences


Differential diagnosis of rhinitis in children

Diagnosis Suggestive features

Adenoidal hypertrophy Mouth breathing discoloured nasal secretions snoringAdenoidal hypertrophy Mouth breathing, discoloured nasal secretions, snoring

Septal deviation, choanal atresia or stenosis Obstruction

Foreign body Unilateral discoloured nasal secretions

Rhinosinusitis Discoloured nasal secretions, headache, facial pain, Rhinosinusitis , , p ,poor smell, halitosis, cough

CF Bilat. nasal polyps, chest symptoms, malabsorption, failure to thrivefailure to thrive

PCD Persisting mucopurulent discharge, bilat. stasis of mucus at nasal floor, symptoms from birth

Encephalocoele Unilateral nasal “polyp”

CSF leakage Colourless nasal discharge often a history of trauma


All i hi iti t l / tAllergic rhinitis – control / management

Environmental measures? Environmental measures? Pharmacologic treatment Antihistamines Topical corticosteroidsp Leucotriene receptor antagonists

SIT SIT Other options Conclusion


All i hi iti i f t lAllergic rhinitis - aims for control

Rhinitis symptoms Rhinitis symptoms Concomitant diseases conjunctivitis asthma OAS

QOLQOL Prevention of development of asthma


Allergen avoidance / reduction

the logical choise of treatment

but is it possible ? and

does it work ??does t o


Allergen avoidance

Seasonal allergense g treepollen grasspollen

No symptoms t ide.g. treepollen, grasspollen outside season

Indoor perennial allergense.g. Housedustmites & pets ?g & p


H d t it t l fHouse dust mite control measures for perennial allergic rhinitis: Cochrane review

Conclusion:

9 i l i l d d9 trials included

Trials to date too small and of too poor quality toTrials to date too small and of too poor quality to make any definitive recommendations

R lt t th t i t ti th t dResults suggests that interventions that reduce exposure to HDM may be of some benefit in

d i hi iti treducing rhinitis symptomsSheik A, Hurwitz B. 2010


Th ff ti f t h th i d i t iThe effectiveness of measures to change the indoor environment in the treatment of allergic rhinitis and asthma: an ARIA update

Effect on ClinicalPet allergen avoidance Effect on allergen level

Clinical effectiveness

Removing cat/dog from the home IIb IVg g IIb IV

Keeping the pet out of main living areas/bedrooms IIb IV

HEPA filter air cleaners Ib Ia - no in pet allergy

W hi tWashing a pet IIb IV

Replacing carpets with hard flooring IV IV

Vacuum cleaners with HEPA filter and double thickness bags IV IV


Custovic A et al. Allergy 2005

Allergen a oidance in allergic rhinitisAllergen avoidance in allergic rhinitis

N id f li i l ff t No evidence for clinical effect Small and few studies Neither is there any evidence for no effect

Hans Christian Andersen Children’s Hospital 26

H1 A tihi t iH1 Antihistamines Administered orally, intranasal or ocular Effective and safe 1.generation should be avoided due to sedative effect Also some 2. generation may have some sedative effect,

whereas others (desloratadine and phexophenadine) is regarded non-sedative

Topical (eye, nose) antihistamines acts faster and may b ff ti th l d i i t tibe more effective than oral administration

Juniper E. JACI 2005;115:S390-413Simons FE. JACI 2011;128(6):1139-50Church MK. Allergy 2010;65:459-466Ng KH. Pediatrics 2004;113:e116-121


g ;

Intranasal corticosteroids - effectsIntranasal corticosteroids effects Several well designed DBPC-studies demonstrated its

effectiveness in children from 2 years of ageeffectiveness in children from 2 years of age A recent Cochrane review failed to find evidence supporting

the effectiveness of intranasal corticosteroids, but it excluded all studies allowing rescue medication

The effect of momethasone furoate, fluticasone furoate and i l id ithi f dciclesonide commence within a few days

Intranasal momethasone furoate and fluticasone furoate may also improve co-existing conjunctivitis and asthmaalso improve co existing conjunctivitis and asthma

Brozek JL.ARIA. JACI 2010;126:466-76W d l GF A J Rhi l All 2012 24 32 36Wandalsen GF. Am J Rhinol Allergy 2012;24:e32-36Anolik R. Allergy Asthma Proc 2009;30:406-12Bielory L. Ann Allergy Asthma & Immunol 2008;100:272-279C P All 2007 62 310 6


Carmagos P. Allergy 2007;62:310-6

50

60ab

ility

44 % 44 %

50 %

40

Bio

avai

la

33 %

20

30

yste

mic

B

10

20

% S

0 5% <0 5% 0 5%

0

Fluticasonefuorate

Mometasonefuorate

Fluticasone proprionate

Budesonide FlunisolideBeclometasone diproprionate

Triamcinolone

0.5% <0.5% 0.5%

fuorate fuorate proprionate diproprionate

Nasonex, Rhinocort and Beconase Summaries of Product Characteristics 2011,Daley-Yates P et al Br J Clin PharmPharmacol 2001, Scadding GK Paediatric Drugs 2008


Kariyawasam H and Scadding GK J of Asthma and Allergy 2011

Intranasal corticosteroids adverse effectsIntranasal corticosteroids – adverse effects

In general intranasal corticosteroids are well toleratedg Some systemic effect (reduced growth velocity) of older

products Newer once daily products have been shown not to reduce

growth velocity, e.g. momethasone furoate, fluticasone furoate and ciclesonideand ciclesonide

Nasal septum perforation and epistaxis are described, but there are no systematically collected data in the literature

Vasar M. Allergy Asthma Proc 2008;29:313-21Daley-Yates PT European J Clin Pharmacol 2004;60:265-68Daley-Yates PT. European J Clin Pharmacol 2004;60:265-68Schenkel EJ. Pediatrics 2000;105:E22Allen DB. Allergy & Asthma Procedings 2002;23:407-413


Systemic corticosteroids for AR in children

Evidence is lacking especially in children Depot corticosteroids are not advised in childrenDepot corticosteroids are not advised in children Risk for systemic side effects with reduced bone

mineralisation and impaired growth Risk for subcutaneous and muscular atrophy & necrosis

Oral treatment with prednisoloneFew adult studies Few adult studies

If systemic corticosteroids treatment is necessary a short syste c co t coste o ds t eat e t s ecessa y a s o tcourse with 10-15 mg oral prednisolone once daily for 3-7 days may be sufficient though no evidence

Wolthers O. Acta Paediatr Scand 1993;82:635-40Mygind N. Allergy 2000;55:11-55


LeukotrienereceptorantagonistsLeukotrienereceptorantagonists

Effective in adults with AR in two systematic reviews and metaanalyses Wilson AM Am J of Medicine 2004;116:338-44 Wilson AM. Am J of Medicine 2004;116:338-44. Grainger J. Clin Otolaryngology 2006;31:360-367.

Have been shown effective in seasonal and perennial AR in two well designed but small pediatric studies Li Albert M Pediatr Pulmonol 2009;44:1085 92 Li Albert M. Pediatr Pulmonol 2009;44:1085-92 Razi C. Ann Allergy Asthma & Immunol 2006;97:767-774

Size of effect?


Topical cromones

Mast cell stabilizer Weaker effect than antihistaminesWeaker effect than antihistamines 1-4 weeks before onset of action Has to be administered at least 4 times a dayHas to be administered at least 4 times a day Safe

Kushnir NM Immunol Allergy Clin N Am 2011; 31:601-17Kushnir NM. Immunol Allergy Clin N Am 2011; 31:601-17


OthersOthersIntranasal cholinergics Effective for controlling watery nasal discharge (vasomotor rhinitis),

but not for itching, sneezing or obstruction.

Intranasal decongestants May be used for a few days for severe nasal obstruction Prolonged use may lead to rebound swelling of nasal mucosa

Hypertonic or normal saline

K h i NM I l All Cli N A 2011 31 601 17

Hypertonic or normal saline Effective additional therapy in children

Kushnir NM. Immunol Allergy Clin N Am 2011; 31:601-17Garavello W. Int archives of allergy and immunology 2005;137:310-14Li H. ORL;J for oto-rhino-laryngology & its related specialities 2009;71:50-55Jeffe JS Int J of Ped Otorhinolaryngology 2012;76:409 13


Jeffe JS. Int J of Ped Otorhinolaryngology 2012;76:409-13

Omalizumab

Effective in controlling asthma and rhinitis as add on therapytherapy

No evidence in children with allergic rhinitis

Vignola AM. Allergy 2004;59:709-717


Effect of pharmacologic treatment of AR

Symptoms Sneezing Runny nose

Stuffed nose Itching Eye sympt

AntihistaminesAntihistamines- systemic- nosespray

++++++

++++

+/-+

++++++

++0

- eyedrops 0 0 0 0 +++

Corticosteroids, topical +++ +++ +++ +++ ++

Cromones, eyedrops 0 0 0 0 ++

Decongestants0 0 0 0- nosespray

- nosedrops00

00

++++0

00

00

Anticholinergics, nosespray 0 ++ 0 0 0Anticholinergics, nosespray 0 0 0 0

LTR + + ++ 0? +?

Benninger M Ann Annals Asthma Immunol 2010;104:13 29


Benninger M. Ann Annals Asthma Immunol 2010;104:13-29Scadding GK Paediatric Drugs 2008

SIT SIT induces a shift from Th2 to Th1-like

b i i f

SIT

response by exposure to increasing amounts of allergens

S b t t (SCIT) Subcutaneous route (SCIT) Sublingual (SLIT)Drops or tablets +/- swallowing

SIT is the only treatment that influences the basis course of the allergic diseaseg


When to consider SIT - Preconditions for SIT

Correct diagnosis Documented IgE mediated diseaseg Sensitisation is relevant for the symptoms Symptoms of sufficient severity and duration Symptoms of sufficient severity and duration Availability of a standardised high-quality (best

t h i ll ibl ) ll t t f thas technically possible) allergen extract of the specific allergen intended to be used for SIT

Zuberbier T. GA2LEN/EAACI pocket guide for ASIT for allergic rhinitis and asthma. Allergy 2010;65:1525-1530


gy

SCITSCITfor seasonal allergic rhinitis (review)

51 d i d t ll d t di bli h d 1950 200651 randomized controlled studies published 1950 – 200610 studies included children

Allergen-specific immunotherapy: significantly reduces symptom scoressignificantly reduces symptom scores significantly reduces medication score Is a safe treatmentIs a safe treatment In the literature fatalities is reported, occurring

almost exclusively in patients with co-existing asthma, and most frequently in patients with poorly controlled asthma


Calderon MA. Cochrane 2008 (2006)

S b t i th i hildSubcutaneus immunotherapy in children: an updated review from 2006 onward

High quality evidence (GRADE):

Larenas-Linnemann DES. Ann Allergy Asthma Immunol 2011;107:407-416

g y ( ) Grass pollen SCIT causes a reduction in the combined symptom-

medication score & increases the threshold of CPT, BPT and SPT immediately and up to 7 years after end of SCIT

Alternaria SCIT improves medication scores, combined symptom-medication scores and QOL

House dust mite SCIT improves symptom and medication scores and reduces emergency department visits and skin reactivityand reduces emergency department visits and skin reactivity

Moderate evidence (GRADE): House dust mite SCIT improves pulmonary function tests House dust mite SCIT improves pulmonary function tests Pollen SCIT prevents development of asthma (low – moderate)


SLIT efficacy in allergic rhinitis in childrenPenagos M. Ann Allergy Asthma Immunol 2006. Review

SLIT - efficacy in allergic rhinitis in children

C l i

10 randomized controlled studies (n 577 children 3-18 years) published 1966 – 2006

Conclusion: Significant heterogeneity between studies SLIT significantly both reduces symptom scores & need for anti g y y p

allergic medication as compared with placebo significant effect of SLIT pollens no significant effect of SLIT with house dust mite allergensg g More effective in monosensitized children

SLIT is a safe treatment with only mild local side-effects Size of benefit? Size of benefit? Dose and duration of treatment?


SLITfor seasonal allergic rhinitis (review)49/60 randomized controlled studies published 1966 – 200915 studies included children23 grasspollen, 5 Paritaria, 2 ragweed, 9 trees (olive:2, cypress: 3,

birch:2 mixed trees: 3) 8 HDM & 1 cat

Allergen-specific immunotherapy:Si ifi t h t it

birch:2, mixed trees: 3), 8 HDM & 1 cat

Significant heterogeneity significantly reduces symptom scores, SMD -0.49 [-0.64 to -0.34]

Subgroup analysis children SMD -0 52 [-0 94 to -0 10]Subgroup analysis children, SMD 0.52 [ 0.94 to 0.10] significantly reduces medication score, SMD -0.32 [-0.43 to -0.21] Treatment effect for children appears to be similar to that seen in

adults Is a safe treatment

R d l i S C h 2010


Radulovic S. Cochrane 2010

SLIT grasspollen – in children with AR

Median improvement vs placebo - ITT population

SLIT grasspollen in children with AR

80%

90%

100% Placebo(n=132)300 IR80%

90%

100% Placebo(n=135)300 IR

60%

70%80% 300 IR

(n=129)

60%

70%

80% 300 IR(n=131)

30%40%

50%

30%

40%

50%39.3% 42.9%

0%

10%

20%

0%

10%

20%

RTSSRTSS

Pollen season Worst pollen period

RTSS Rhinoconjunctivitis Total symptom Score W h U t l JACI 2009 123 160 66


RTSS = Rhinoconjunctivitis Total symptom Score Wahn U et al JACI 2009; 123:160-66

Subcutaneus immunotherapy (SCIT) in children

D t d ff t f SCIT i h f d ild/ d t Documented effect of SCIT in hay fever and mild/moderate asthma with pollen, furry pets (especial cat) and HDM-allergen extractsallergen extracts

Long-term effect 5-7 (12) years after termination of SIT only documented after treatment for 3-5 yearsdocumented after treatment for 3 5 years Shown in SAR Asthma?

No consistent effect on OAS Possible preventive effect for:

Development of asthma/BHR in children with hay fever Development of new sensitizations in monosensitized


Sublingual immunotherapy (SLIT)

DBPC studier have demonstrated its effectiveness in DBPC-studier have demonstrated its effectiveness in Rhinitis (1a), only pollen (grass, birch) Asthma (1a), house dust mites, pollen?( ), , p NB: few studies including asthmatic children only

Well tolerated Lack of studies to clarify

Optimal dose and duration Effect in children Effect in children Magnitude of effect as compared with other treatments Long-term effect: only 1 open non-randomised study (self-selected

hild )children) Preventive effect


I di ti f SIT i hildIndications for SIT in children

Allergisk rhinitis and/orAllergisk rhinitis and/or

Allergic asthma in children > 5 years withmild moderate asthma FEV1 > 70% of predicted aftermild - moderate asthma. FEV1 > 70% of predicted after sufficient pharmacological treatment and:

Unsatisfactory symptom control after environmental control and pharmacological treatment

Coexisting rhinoconjunctivitis and asthma

Poor compliance to pharmacological treatment ? Poor compliance to pharmacological treatment ?

Side effects to pharmacological treatment


Treatment of allergic rhinitis – effect on lower airways ?

Eff t LEffect on Long term effect

Possible preventive effectrhinitis asthma

Pharmacotherapy antihistamines + -

??? topical corticosteroids

+ + -???

BHR & development of

SIT + + +

BHR & development of asthma in children with AR development of new sensitivities ??


Effective control of AR in children

Eff ti t l i b d i di id l l ti fEffective control is based on an individual evaluation of Which symptoms

St ff d Stuffed nose Itching Watery dischargeWatery discharge

Severity: Mild or moderate to severe Frequency & duration of symptoms: Intermittent orFrequency & duration of symptoms: Intermittent or

persistent Co-morbidities, e.g. asthma & conjunctivitis, g j


Different pharmacological approaches in AR -l ti ff tirelative effectiveness

Nasal corticosteroids more effective than either antihistamines or LTRA (Montelukast)

Nasal corticosteroids, antihistamines and LTRA (Montelukast) are all more effective than cromoglicateare all more effective than cromoglicate

Congestion is only effectively controlled by nasal corticosteroids Some studies indicate more effect, especially on itching, of

antihistamines than LTRA. Insufficient comparative data Antihistamine and LTRA may add further benefit as add-on with

nasal corticosteroid therapynasal corticosteroid therapy Time to relief: topical antihistamines < antihistamines / LTRA <

topical steroids

Benninger M. Ann Annals Asthma Immunol 2010;104:13-29Di LG. Clin Exp Allergy 2004:34:259-267Chen ST Pediatr Allergy Immunol 2006;17(1):49 54


Chen ST. Pediatr Allergy Immunol 2006;17(1):49-54

Approach to therapy for pediatric allergic rhinitisApproach to therapy for pediatric allergic rhinitis

y f ❸ Trial of addition of

s othe

rapy

ngy if

ed*

hera

py i

rolle

d

❸ Trial of addition of antihistamine ± LTRA to nasal corticosteroid

d tri

gger

s

fic im

uno

douc

hin

p th

erap

yco

ntro

lle

dow

n th

wel

l con

tr

❷ Nasal corticosteroid

❶ Antihistamine oral

Avoi

d

Spe

cif

Sal

ine

Ste

p up

poor

ly c

Ste

p w

❶ Antihistamine, oral or nasal

Draft by EAACI Task Force of Pediatric Rhinitis 2012

The choice of initial treatment depends on symptoms & severity


Draft by EAACI Task Force of Pediatric Rhinitis 2012

R iti & ff ti t t t f ll i hi itiRecognition & effective treatment of allergic rhinitis

Effective treatment of Effective treatment of allergic rhinitis may have important concequencesimportant concequencesin terms of

Q f f Quality of life Asthmacontrol Reducing the

prevalence of asthmap

June 200951


Documents

Allergic rhinitis E&Dih dtiEuropean & Danish recommendations · Classic symptoms and signs of rhinitisClassic symptoms and signs of rhinitis Rhinorrhoea - sniffing Pruritus - nose