Allergic rhinitis

Prof DR Dr Ariyanto Harsono SpA(K)

Definition: Impaired function of the nose after allergen exposure through IgE-mediated allergic inflammation

Prevalence: 10-25%

Impacts Social Quality of life Performance Schools Cost

2Prof DR Dr Ariyanto Harsono SpAK

1. Allergen

2.Aspirin

3.Polution


1. Allergen:-Inhalant House dust

Polen

Bulu hewan

Tungau

-Foods


Arachidonic Acid

Phospholiphase A

Cyccloxygenase Lipoxygenase

Prostaglandine

TXA

Prostacyclin

Leukotriene A

Leukotriene B

Leukotriene C

Aspirin

2. Aspirin

HETE,5-HETE, PAF5Prof DR Dr Ariyanto Harsono SpAK

P

Bacterial/ viral infectionCytokinesStress

P

P

P

C

C

N

C

C

C

NN

I-B

p50

ATP ADP

I-B kinase

PhosphoryIation of I-B kinase

NF-B

Degradation of I-Bin proteosome

Ubiquitination of I-B

Nucleus

NF-B - responsive gene

(Ub) n (Ub) n

Polution

3. Polution

Sel EpitelMakrofagSel TSel B Sel MastEosinofil

Gejala

Sitokin/Kemokin IL-4, IL-5, IL-13, IL-10, IL-3GM-CSF,EotaxinRANTES,TGF-TGF-

Mediator

Histamin,ProstaglandinLeukotrien

Bersin,Buntu,RinoreaGatal

Infiltrasi Sel Eosinofil

Inflamasi AlergiKo-morbid


Mast CellPreformed Mediator: Histamin, TNF- Protease,Kinin, ECFNew Generated Mediator: PGD, Leukotriene 12

Prof DR Dr Ariyanto Harsono SpAK

Mast Cells Mediate Allergic and Inflammatory Reactions

IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10,

IL-13, TNF, MIPs, IFN,

GM-CSF, TGF, bFGF,

VPF/VEGF, PGD2, LTB4, LTC4, PAF,

Serotonin,Heparin,

Chondroitin-sulfate,

Chymase, Tryptase,

Cathepsin G

Recruitment

Extravasation

Vasodilation

Activation

MC

Graphics courtesy of Prof. M. Maurer.13

Prof DR Dr Ariyanto Harsono SpAK

Granule contents:Histamine,TNF-Proteases, Heparin Lipid mediators:

ProstaglandinsLeukotrienes

Cytokine production:Specifically IL-4, IL-13


EosinofilMediator: MBP,ECP,EDN, Protease, PeroksidaseSitokin: TGF- TGF- 15Prof DR Dr Ariyanto Harsono SpAK

Eosinophil activated and prolonged life-span by IL-5


Keluhan Utama:-Rhinorrea -Itchy nose -Sneezing -Congestion

Gejala minor: Rabbit Nose Allergic Salute Nasal crease Allergic Shiner Toothy mouth (Adenoid Face)


LeukotrieN C4

Prostaglandin D2

Tryptase

HISTAMIN

CYTOKINEIL-1IL-3IL-4IL-5IL-6IL-13TNF-

KemokinIL-8EotaxinRANTES

Adhesion MoleculesP-selectinICAM

Early phaseResponse

• Sneezing• Itchy, watery eyes• Runny nose• Congestion• Itchy nose

Rapid phase Inflammatory Response

Overview: Symptoms of Allergic Rhinitis

Early phase Mediator


IncreaseVaskularPermebility /secretion Vascular obstruction

Mucosal Inflammation

Nasal obstruction

Rapid phase Mediators Vasodilatation

Mediators of allergic inflammation

Etiologic Factors of Congestion


Allergic Rhinitis and co-morbid conditions

Allergic rhinitis

Nasal polyps

Sleep disturbance, including sleep-disordered breathing

Rhinosinusitis (acute and chronic)

Asthma with AR

CongestionInflammation

CongestionInflammation

Common cold


•anamnesis•physical examination•Total IgE / Specific•Nasal mucosa smear eosinophils•Skin test•Nasal mucosa provocation test


•avoidance of allergens•education•pharmacotherapy•immunotherapy


ARIA = Allergic Rhinitis and its Impact on Asthma.Bousquet et al. J Allergy Clin Immunol. 2001;108 (5 suppl):S147.

ARIA Guidelines: Recommendations for Management

of Allergic Rhinitis

Mildintermittent

Moderatesevere

intermittent

Mildpersistent

Moderatesevere

persistent

Immunotherapy

Allergen and irritant avoidance

Intranasal decongestant (<10 days) or oral decongestant

Second-generation nonsedating H1 antihistamine

Leukotriene receptor antagonists

Local cromone

Intra-nasal steroid


Jenis obatbersin rinorea Buntu Gatal

hidungKeluhan mata

Antihistamin H1OralIntranasalIntraokuler

++++0

++++0

++0

+++++0

++0

+++

Kortikosteroid intranasal +++ +++ +++ ++ ++

KromolinIntranasalIntraokuler

+0

+0

+0

+0

0

++

DekongestanIntranasalOral

00

00

+++

+

00

00

Antikolinergik 0 ++ 0 0 0

Antilekotrien 0 + ++ 0 ++

Gejala



hidungKeluhan mata


++++0

++++0

++0

+++++0

++0

+++



+0

+0

+0

+0

0

++


00

00

+++

+

00

00



Gejala


Drugs Choice for nasal congestion

• Antagonist reseptor H1

• Dekongestan oral & topical

– pseudoefedrin

– fenilefrin

• Topical nasal Cortikosteroid

Nayak AS et al. Allergy. 2001;56:1077-80. 49Prof DR Dr Ariyanto Harsono SpAK

Desloratadin reduces nasal congestion Score

*P = 0.005†P = 0.01‡P = 0.001 dibanding plasebo

15

Waktu Terpapar Alergen (menit)

0

0.6

1.2

1.6

2.0

1.8

1.4

1

0.8

0.4

0.2

45 75 105 135 165 195 225 255 285 315 345

†

*

* † * † ††

†

* ††

*

†

*

† *

‡

‡‡ ‡ ‡

‡

SumbatanReduced

DesloratadinPlaseboR

erat

a pe

ruba

han

Skor

Su

mba

tan

Hid

ung

Horak F et al. J Allergy Clin Immunol. 2002;109:956-61.50Prof DR Dr Ariyanto Harsono SpAK

Treatment with desloratadine:

• Inhibition of allergic inflammatory mediators

• Reduces symptoms of nasal obstruction in the well-designed studies

• Improve nasal airflow, an objective measurement of the nasal obstruction


0

10

20

30

40

50

60

70

IL-6 IL-8 IL-3 GM-CSF

AERIUS

Cetirizine

Lippert U, et al. Exp Dermatol. 2000;9:118-124.

Per

cen

t in

hib

itio

nDesloratadine: Inhibition of Allergic

Inflammation

TNF-

Greater inhibition than Cetirizine

Inhibition of Mast Cell Cytokine Release


Food Does Not Alter the Oral Bioavailability of Desloratadine

Desloratadine 7.5 mg* after high-fat, high-calorie meal

Desloratadine 7.5 mg* after 10-hour fast

Mea

n D

eslo

rata

din

e P

lasm

a C

on

cen

trat

ion

(µ

g/L

)

0 4 8 12 16 20 240

1

2

3

4

Hour

Randomised, open-label, single-dose, 2-way crossover study (n = 18)

*The recommended daily dose for desloratadine is 5 mg.Gupta S et al. Clin Pharmacokinet. 2002;41(Suppl 1):7-12. 53Prof DR Dr Ariyanto Harsono SpAK

0 6 12 18 240

50

100

150

200

0

1

2

3

4

0 6 12 18 24

(µg

/L P

las

ma

)

Hours

FexofenadineDesloratadine

(ng

/mL

Pla

sm

a)

Banfield C et al. Clin Pharmacokinet. 2002:41:311-8.

Effect of Grapefruit Juice of Desloratadine and Fexofenadine

Hours

With Grapefruit Juice

Without Grapefruit Juice


0 4 8 12 16 20 240

1

2

3

4

5

6

Hour

DL 7.5 mg/d* + placebo

DL 7.5 mg/d* + erythromycin 500 mg TDS7

8

Mea

n D

eslo

rata

din

e P

lasm

a C

on

cen

trat

ion

(µ

g/L

) o

n D

ay 1

0

DL, desloratadine; TDS, three times daily.

*The recommended daily dose for desloratadine is 5 mg.Banfield C et al. Clin Pharmacokinet. 2002;41:29-35.

• Changes in AUC not clinically significant

• Steady-state levels of DL achieved by day 10 after both treatments

Desloratadine/ErythromycinDrug-Coadministration


ECG Pharmacodynamic Effects of Desloratadine

• Desloratadine 45 mg* single daily doses for 10 days; placebo crossover design

– No statistically significant differences in QTc observed

• No clinically relevant adverse events reported

*Nine times the recommended daily dose.ECG, electrocardiogram.Bousquet J, et al.Allergy 2004;59 (suppl.77):4-16 56Prof DR Dr Ariyanto Harsono SpAK

Desloratadine and EAACI/ARIA Criteria for Antihistamines

in Allergic Rhinitis

• AERIUS meets all EAACI-ARIA criteria for antihistamines required for the treatment of allergic rhinitis– Efficacy

• Effective in the treatment of intermittent and persistent rhinitis

• Effective for all nasal symptoms including nasal obstruction

• Improvement of eye symptoms

• Improvement in asthma symptoms

• Efficacy in pediatric and elderly patients


Desloratadine and EAACI/ARIA Criteria for Antihistamines

in Allergic Rhinitis

- Safety and tolerability/side effects• No sedation or cognitive or psychomotor impairment

• No anti-cholinergic effects

• No weight gain

• No cardiac side effects

• Studies should be carried out in young children and elderly patients to assess safety

• Prospective postmarketing safety analysis should be conducted



hidungKeluhan mata


++++0

++++0

++0

+++++0

++0

+++



+0

+0

+0

+0

0

++


00

00

+++

+

00

00



Gejala


Efficacy NASONEX in Pediatric Patients with Perennial Allergic Rhinitis

• 4-week, double-blind study (double blind)• With the extension of the 26-week, open-

label• Children 3-11 years• MFNS 100 mcg qd or placebo


Results Clinical Experience NASONEX in Children

• Mometasone furoate nasal spray (MFNS) 100 mcg qd is the optimal dose in children over 2 years

• Low potential for systemic effects• There is no short-term growth disorders• There is no evidence of HPA axis suppression• Well tolerated• Incidence of adverse events similar placebo


Efek Jangka Panjang Nasonex thd Mukosa Hidung

AA BB

Before MFNS TreatmentBefore MFNS Treatment After 12 Months of TreatmentAfter 12 Months of TreatmentWith MFNSWith MFNS

Minshall E, et al. Minshall E, et al. Otolaryngol Head Neck Surg. Otolaryngol Head Neck Surg. 1998;118(5):6481998;118(5):648


Allergic rhinitis

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