THE COMPREHENSIVE

MANAGEMENT OF ALLERGIC
DISEASES IN CHILDREN
Zakiudin Munasir

Allergy-Immunology Sub Division

CURRICULUM VITAE
Nama
Tempat/ tanggal lahir
Pekerjaan/jabatan

: Zakiudin Munasir, dr SpA(K)

: Mojokerto 14 Agustus 1953
: Kepala subbagian Alergi
Imunologi,Bagian ilmu kesehatan anak
FKUI/RSCM

Riwayat pendidikan formal

:
Dokter umum
: Fakultas kedokteran UI, lulus tahun 1976
Spesialis anak
: Fakultas kedokteran UI, lulus tahun 1986
Konsultan AlergiImunologi Anak
: Ikatan Dokter Anak Indonesia 1996
Riwayat pendidikan
tambahan
:
Pediatric Allergy Immunology (Groningen, Belanda 1989 1990 )
Principle Epidemiology and Epidemiology of AIDS ( Johns Hopkins University,
Baltimore USA 1994)
Rheumatology course ( Singapore 1993 )
European Pediatric Rheumatology course ( Geneva 2000 ).
Workshop Allergy and Environtment, Lausanne, Switzerland 2003
Riwayat Organisasi
: Anggota IDI/pengurus PP IDAI
Ketua Perhimpunan Alergi Imunologi Jakarta
Raya
Ketua UKK Alergi Imunologi PP IDAI
Ketua SATGAS HIV
Sekretaris Pokja Campak IDAI
Sekretaris Badan peneliti IDAI

Globally important
allergens

ALLERGIC INFLAMMATION

Intact allergen

T Cell

Antigen Presenting Cell

ALLERGIC INFLAMMATION

IMMUNE RESPONS BALANCE

Th1 IFN
IL-2
TNF

CELLULAR RESPONS

Th2

IL-4
IL-5
IL-10
IL-13

HUMORAL RESPONS

ALLERGIC INFLAMMATION
Th2
IL-5
IL-4

B-cell

Eosinophil

IL-3, IL-4
Mast-cell

SENSITATION

IgE
Plasma-cell

Mediator release from

degranulated mast cell
IgE

YY
IL-5
B cell

EOSIN

IL-4, 6
Histamine,
mediators, cytokines

ALLERGIC INFLAMMATION

Early Allergic Response

IL-5

Mast cell

Sneeze
Itch

Eosin
Histamine

Mucus

PGD2

Smooth
muscle

Tryptase
TNF

Congestion
ICAM-1

ALLERGIC INFLAMMATION

Late Allergic Response

Arachidonic Acid
5-LO

Oedema
Mucus

LT-A4

LT-B4
Chemotaxis

Chemotaxis
LT-C4

Sm muscle stim

LT-D4

BHR

LT-E4

Eosinophilia

ALLERGIC MARCH

ATOPY
GIT ALLERGIC DISEASES
ATOPIC DERMATITIS

ASTHMA
ALLERGIC RHINITIS

Step-wise management of
allergic diseases

Gloria 2000
Step 3

Step 2

Step I

Immunotherapy
Pharmacotherapy

Allergen Avoidance and Environmental

Control

Treatment

Antihistamine

Found 1930, clinical use 1940

Structure close to histamine block
histamine receptor histamine
effects inhibitor

Church MK, Journal WAO May/June 2004

Antihistamines
Block histamine receptor
Stabilise mast cell membrane
Reduce

Mediator release
ICAM-1 expression
Eosinophil recuitment

Church MK, Journal WAO May/June 2004

Antihistamine

Generation I (classic) : Chlorpheniramine

maleat,diphenhydramine
(sedative,anticholinergic effect)
Generation II: cetirizine,loratadine
Generation III: levo-cetirizine, desloratadine
(non sedative, no anti cholinergic,
antiinflammation effect)

Cetirizine
Potent and specific AH
Second generation H1 receptor
antagonist, active metabolite of
carboxylic acid of first generation
H1 antihistamine , hydroxyzine
Not metabolized through
cytochrome P450, excreted in large
amount in urine

Cetirizine

Antiinflammation effect, inhibits

eosinophil migration induction in the
skin of atopic patient.atopik (invivo )
Decreases ICAM-1 receptor in nasal
epithel.
Controls persistent minimal
inflammation

Roitt, Brostoff, Male : Immunology 2002

Roitt, Brostoff, Male : Immunology 2002

Roitt, Brostoff, Male : Immunology 2002

ATOPY
AN
TI

EARLY TREATMENT

BR
-IN
ON
FL
CH
AM
OD
MA
I LA
TI
TO
ON
R

ALLERGIC DISEASES

ALLERGIC MARCH

ATOPIC DERMATITIS
GEN

GRASS POLLEN
HOUSE DUST MITE
CAT DANDERS

BRONCHIAL ASTHMA
ALLERGIC RHINITIS

Corticosteroids

Mucus secretion
Vascular permeability/oedema
Mediator release
Cytokine production
Inflammatory infiltrate/activation
Langerhan cells in epithelium

Glucocorticoid inhibits
The production of the major RV receptor,
ICAM-1
Van de Stolpe et al. Am J Respir Cell Mol Biol 1995

The wise way to choose

corticosteroid

Correct indication and know the

contraindication
Choose the appropriate potency
Minimal side effects
Acceptability
Cost and benefit

Relative Potencies and Equivalent Doses

of Representative Corticosteroids
Compound

Antiinflamatory
potency

Na+ - Retaining
potency

Duration of action

Equivalent dose,
mg

20

Cortisone

0.8

0.8

25

Fludrocortisone

10

125

++

Prednisone

0.8

Prednisolone

0.8

6-methylprednisolone

0.5

Triamnicolone

Betamethasone

25

0.75

Dexamethasone

25

0.75

Cortisol

+ + This agent is not used for glucocorticoid effects

(Schimmer BP, Parker KL. Adrenocorticotropic hormone, adrenocortical steroids and their
synthetic analogs, inhibitor of the synthesis and actions of adrenocortical hormones;
Goodman & Gilmans the pharmacological basis of theurapeutics, 2001)

Macrolide antibiotics
inhibit
1.

The production of ICAM-1, the major

RV receptor.
Khair et al. Eur Respir J 1995

5.

The production of cytokine in the

airway epithelial cells.
Takizawa et al. Biochem Biophys Res Commun 1995

Symptomatic drugs
Bronchodilator :
2 agonists
Phosphodiesterase inhibitors

Intrinsic Efficacy of 2-agonists

100%

Epinephrine

FULL AGONISTS

Isoproterenol

80%
PARTIAL AGONISTS

60%
Fenoterol (42%)

40%

Strong

Procaterol
Pormoterol (30-40%)
Weak

20%
Salbutamol (5%)

0%

Salmeterol (<1/3 albuterol)

January B, et al. J Biol Chem 1997, 272:23871

January B, et al. Brit J Pharmacol 1998, 123:701

Hanania NA, et al. AJRCCM 2002, 165:1353

Bronchodilator & Vasoconstrictor

Adrenaline/ Nor epinephrine

HCL Ephedrine

Decongestant

Pseudoephedrine: stereoisomer of
ephedrine but less potent

Mast cell stabilizers

Ketotifen
Generation II AH
Sodium cromoglycate
2 agonist + phosphodiesterase
inhibitor combination

LEUKOTRIEN RECEPTOR
ANTAGONIST

Montelukast
Zafirlukast

Immunotherapy
Reduced allergen-specific IgE
Blocking IgG antibodies
Altered Th1 / Th2 response
reduced IL-4/IL-5 secretion
reduced eosinophil recruitment

Immunotherapy: The Future

Allergoids
Allergen peptides
immunogenic
analogues
Allergen-encoded DNA
vaccination
Anti-IgE antibodies

Thank you beybeh!