Adapted from:

ALLERGIC RHINITIS AND ITS IMPACT IN ASTHMA

ARIA 2007 & 2008 & 2010 Revision
Presented at Seminar Sehari , Mengelola Asma dan Rinitis Alergi Lebih Baik
Sumedang Hospital April 9th , 2011
 Allergic Rhinitis
Definition
• Allergic rhinitis is clinically defined as symptomatic disorder of
the nose induced after allergen exposure by an IgE-mediated
inflammation

• 3 Cardinal Characterized nasal reaction occuring in allergy :

 Mucous Discharge
 Sneezing
 Nasal Obstruction

.ARIA 2008 Update (in collaboration with the World Health Organization, GA2LEN* and AllerGen
2
 Recommendation ( WHO-Initiative ARIA)
AR is a major chronic Respiratory disease due to:
• Its prevalence (10-25%)
• Its impact on QOL
• Its impact on work / school performance and productivity
• Its economic burden
• And its links to asthma

AR is associated with sinusitis, conjunctivitis

AR is a risk factor for Asthma along with other known risk factors
Allergic inflammation is a systemic disease and shows
co-morbidities several organs

• Asthma
• Allergic Conjunctivitis
• Middle Ear Allergy
• Vestibular Disturbances
• Sinusitis
• Chronic Hypertrophic Adenoid
• Laryngitis
• Attopic Dermatitis
• Bronchial Hyperresponsiveness
Links between Rhinitis and Asthma Severity

.ARIA 2008 Update (in collaboration with the World Health Organization, GA2LEN* and AllerGen
 Allergic Rhinitis Problems

Risk factors for allergic rhinitis

 Major outdoor allergens (pollens and molds).
 Major indoor allergens (mites, animal danders, insects, molds)

Diagnosis : easy but often under diagnosed

These factors are the causes why prevention and treatment of

allergic symptoms is difficult

ARIA WORKSHOP
 Classify AR

• Based On The 2007 ARIA Workshop, Report And The Ipag Handbook. In Collaboration with
WHO, Galen, AllerGen and Wonca
 Trigger of Allergic Rhinitis
Allergens
Aeroallergens
mites, pollens, animal
danders, insects, plant origin,
moulds
Food allergens
Occupational rhinitis
Latex allergy

Pollutants
Indoor air pollution
domestic allergens,
indoor gas pollutants
(tobacco smoke)
Outdoors air pollution
Automobile pollution
 The complexity of pathophysiology of allergic inflammation

Allergen
Mastosit
A
C
U IgE
IgE
T
E
Rhinorea
Histamine
S
Tryptase IgE
Sneezing Y
PGD2 LTs
M Antibody
P Cytokines
Congestion T
O
M
S
CD4+
IgE

Allergen
CD25+
Th2 EOS C
Class II MHC H
T cell r R
O I
Basic proteins N
N
LTs Cytokines
I F Rhinorea
IF C L
Fragment A
S M Sneezing
Y A
Histamine M T
IL-1 CD4+ LTs P I Congestion
ANTIGEN Th1 Cytokines T O
O N
M

PRESENTING
S
Baso
CELLS
Early- and late-phase allergic reactions
(APC)
Sumarman. The rational manag of AR & its impact on asthma. WHO-ARIA 2001 12
 The Update Theory on Allergic Inflammation
Allergen APC CD
4+
Stimmulation IL-2c ce nT
et ll
r
n n
ge atio
e l
All mu
Th0 Th0 Sti
m
Activate M/DC
Inducing CMI:
IFN-γ, IL-2, TNF-β, ect M cell
(- )
as APC Humoral immunity
(+)
Allergic diseases:
Th 1 IL-4, IL-13, IL-5, dll
(CD4 + T)
Th 2
(+)
(-) (+)(-)
(CD4 + T)
(+)
(-) (+) T Reg (-) Eos &
IL10/ (-) (-) Baso
B cells TGFβ Accumu-
IgG4 & IgA pro- ASIT B cells
lation
duction IgE produc-
Adapted from Creticos 1998 & Akdis et al
tion
2005) (Modified by Sumarman, 2009).6
 DIAGNOSTIC OF ALLERGIC DISEASES

Subjective test
Symptoms and its severity
Family allergic history

Objective tests
for the diagnosis of IgE-mediated allergy
 Diagnosis
History Taking
General ENT Examination
– Anterior Rhinoscopy
– Nasal Endoskopi
Objective Test
Imaging
Alergic Test
Invitro
Invivo
• Typical Symptoms
– Rhinorrhoea History Taking
– Sneezing
– Nasal Obstruction
– Pruritus

Symptoms from other organs:

Eye itchy, Palatal Itchy, Urtica,
Derm. Atopic, Asthma

The quality of lifedisturbances

(Work / Education)

History for Co Morbidities

Occular Symptoms, Asthma
Chronic Sinusitis
Physical Examination

Nasal Crease /
Linea nasalis

Allergic Sallute

Allergic Shiners/
Dennies line
 Allergy Testing
• The Goals of allergy testing are to:
– Confirm the suspicion of allergy
– Identify the offending allergens
– Know how sensitivity the patient is

• Major indications for allergy testing: rhinitis, asthma, suspected

food allergy, suspected drug allergy

• Randomly allergy testing without clear clinical reason for the

testing  NOT RECOMMENDED

• Invivo And Invitro Testing

Volcheck, G. Clinical Allergy: Diagnosis and Management, Humana Press, 2009

 DIAGNOSTIC OF ALLERGIC DISEASES
Objective tests for the diagnosis of IgE-mediated allergy :

Skin Test
 Skin prick test (SPT)
 Scratch Test
 Intradermal Skin Test
 Atopy patch Test
 Prick – Prick Test

Serum-specific IgE
– Radioallergen Test (RAST)
– Enzyme-linked Immunosorbent Assay (ELISA)
– ImmunoCAP

Other working test (mucosa)

Nasal function test
Specific nasal challenge test
Specific bronchial challenge test
Specific food challenge test
Updated ARIA Recomendation 2008
 Objective Test for Diagnostic of IgE-mediated Allergy
Skin
Skin Test / Prick Test
The preferred methode
Mast cells

Blood vessel Measurement

of serum-specific IgE

Basophil cells Histamine release

Basophil
activation

Nasal challenge
Mast cells Bronchial challenge
Oral challenge
Conjunctival challenge

Mucosa
Updated ARIA Recomendation 2008
21
 Treatment Allergic Rhinitis

Treatment goals 
• Unimpaired sleep
• Ability to undertake normal daily activities
• No troublesome symptoms
• No or minimal side effects of rhinitis treatment

• Based On The 2007 ARIA Workshop, Report And The Ipag Handbook. In Collaboration with
WHO, Galen, AllerGen and Wonca
 Treatment Allergic Rhinitis

Recommendations of the ARIA workshop (2008)

The combine treatment strategy of AR :

 Education (include physical fitness)
 Allergen avoidance (when possible)
 Pharmacotherapy
 Allergen specific immunotherapy
 Diagnosis of allergic rhinitis Check for asthma
espescially in patients
with moderate-severe
Intermittent symptoms and/or persistent
Persistent symptoms
rhinitis

Mild Moderate-severe Mild Moderate-severe

Not in preferred order Not in preferred order In preferred order

• Oral H-1 antihistamine • Oral H-1 antihistamine •Intranasal CS
• Intranasal- H-1 antihistamine • Intranasal- H-1 antihistamine •Oral H-1 antihistamine or LTRA
• and/or decongestant or • and/or decongestant or
•LTRA • Intranasal CS review the patient after 2-4 weeks
• LTRA or
• (Chromone)
Improved Failure
Treatment In persistent rhinitis review the
patient after 2-4 weeks
Step-down and Review diagnosis

strategy:1
continue treatment Review compliance
for 1 month Query infections
If failure: step-up or other causes
1. Adapted from: Allergic If improved: continue for 1 month
Rhinitis and its Impact
on Asthma (ARIA) 2008 Increase Itch sneeze: Rhinorrhea: Blockage: add
Update. Allergy. intranasal add H-1 add ipratropium decongestant, or oral
European JACI. Supl CS dose antihistamine CS (short term)
86.Vol 63.2008
Failure:
Surgical refferal

Allergen and irritant avoidance may be appropriate

If + Conjunctivitis add:
• Oral H-1-blocker or Intraocular H1-blocker or Intraocular Chromone (or saline)

Consider Specific Immunotherapy

 Surgery
Indication for surgical intervention :

• Drug-resistant inferior turbinate hypertrophy

• Anatomical variation of the septum with functional relevance

• Anatomical variation of bony pyramid with functional/aesthetic

relevance

• Secondary or independently developing chronic sinusitis

• Different forms of nasal unilateral polyposis

• Fungal sinus diseases

 Therapeutic Options for Allergic Rhinitis
Effects on symptoms

Itch/ Nasal Nasal Sense Ocular

Drug
sneeze discharge congestion of smell symptoms

INS +++ +++ ++ + ++

Oral
+++ ++ ± – +++
antihistamine

Topical – – –
+++ +
decongestant

Chromone + + ± – ++a
Anticholinergic – +++ – – –
Oral
+++ +++ +++ ++ ±
corticosteroid
Alleviates ocular symptoms only when administered as eye drops
a
1. Bousquet J et al. J Allergy Clin Immunol 2001;108:S147–S334
2. Scadding G. J Allergy Clin Immunol 2001;108:S59
 History of Antihistamines

Second generation AH
First generation AH
desloratadine
Staub terfenadine fexofenadine
Bovet cetirizine
phenbenzamine loratadine
chlorphenyramine astemizole

1937 1942 1979 1988 1996 2001

Anti-histaminic effect

Anti-cholinergic effect

Sedative effect

Sumarman, Allergic Rhinits and Sinusitis , Update Management Presented at Scientific Sesion DUSTIRA HOSPITAL Bandung
November 3th 2010
 Decongestan

• Symphatomimetic drug
• Relieve Nasal Blockage
• Topical  Act more rapidly and effectively 
Rebound effect  Limit duration
• Oral decongestant  Very effective (especially for
nasal congestion)  Side Effect
• Combined with antihistamine more effective than alone
 Decongestan
Systemic side effects of these oral decongestants
are not rare, include 

 irritability
 dizziness
 headache
 tremor
 insomnia
 tachycardia and
 hypertension.

Sumarman, Allergic Rhinits and Sinusitis , Update Management Presented at Scientific Sesion DUSTIRA HOSPITAL Bandung
November 3th 2010
 Decongestan
Jenis Dan Sediaan
Name of Drug

Pseudoefedrin Oral

Phenilpropanolamin Oral

Phenileperin Oral / topical

Efedrin Oral / topical

Oxymetazolin Topical

Tetrahidrazolin Topical

Naphazolin Topical

Xylometazolin Topical

Epinefrin Systemic /Topical

Krouse : Pharmacoteraphy of Otolarnungologic. In: Krouse dkk. Allergy and Immunology an otolarygologic approach
 Allergen Specific Immunotherapy
Has a place in selected patient with demonstrable IgE-
mediated diseases 
• who either have a long duration of symptoms, or
• in whom insufficiently controlled by conventional
pharmacotherapy, or
• in whom pharmacotherapy produce undisirable side effect, or
• in patients who do not wish to be on pharmacotherapy, or
• in patients who do not want to receive long-term pharmacological
treatment

24
IL-4 / IFN-γ Ratio

The hypothesis of immunotherapy mechanism

TH1 response changes which occurred either as a consequently of decreasing of
regulation TH2 response (anergy), or immune deviation be influenced by IL-12.
(Adapted from Durham and Till, 1998) 25
IgE Eos
st Cell
Ma

FcεRI expression
and
Eosinophil survival
IgE-dependent and activation
mast cell activation
(-) (-)

ll
B ce
IL-10 T re g
4
IgG

IgE-dependent antigen
presentation
(-) (-) (-)
IL-10
Th2 produced by T Reg
IL-10 is another effective
inhibitive indicator of allergic
Cytokines and
inflammation proliferation

The potential anti allergic properties of IL-10 (produced by Treg) on different limbs of the allergic
immune response. (Till et al. J Allergy Clin Immunol 2004;113:1025-34) (
EOS = Eosinophil; T reg = T regulatory cell.
T REGULATORY CELLS (Treg)

Controlling Treg to imune

respone by 

1. Suppresor APC Activity

2. TH1 dan TH2 cell suppressor
3. Cell B regulation  IgG4,
IgA  inhibitor IgE
Spesific.
4. Mast cell, basophil dan
eosinophil suppresor
5. Residen tissue cell
Interaction and proses
remodelling

Akdis et all. JACI, 2005:116 6

 Intranasal Steroid

• Decrease AR clinical symptoms

• Decrease Eosinophilia (EG2+) (nasal epithelium and
submucous) through product inhibition of IL-5 by T
cells CD3+
• Decrease IL-5 and GM-CSF mRNA expression T
cells
• Inhibition of IL-5 secretion from blood peripher T
cells
 Limitations of Current Intranasal Steroid

• INS have shown inconsistent relief of ocular

symptoms
• INS sensory limitations: scent, taste/aftertaste,
run out of nostrils, feel in nose and throat
• Sensory perceptions have significant
associations with patients’ compliance
• Current devices are not easy to use

Weiner JM et al. BMJ 1998;317:1624–9. 2. Mahadevia P et al. Ann Allergy Asthma Immunol 2004;93:345–
50. 3. Southall J, Ellis C. Innov Pharma Tech 2000;110–5. 4. Berger W. Paediatr Drugs 2004;6:233–50.
Berger WE et al. Expert Opin Drug Deliv 2007;4:689–701.
 Stepwise Treatment Proposed
Mild intermitten AR : oral H1-antihistamines

Moderate severe Intermittent AR :

intra nasal topical steroid (high dose) +
if needed: oral H-1 antihistamine and/or oral steroid
(short term course)
Mild persistent AR :
oral H-1 Antihistamine, or
low dose intra nasal topical steroid

Moderate-severe persistent AR :
High dose intra nasal topical steroid
If symptoms are severe : add oral H-1
Antihistamine,
and or short course of oral corticosteroid at
beginning of the treatment
28
 Rational Treatment of allergic rhinitis
(ARIA WHO-2001; Allergic Rhinitis and its Impact on Asthma)

moderate
moderate mild severe
severe persistent persistent
intermittent
mild
intermittent intra-nasal steroid
local cromone

oral or local non-sedative H1-blocker

intra-nasal decongestant (<10 days) or oral decongestant
allergen and irritant avoidance

immunotherapy
27