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CURRICULUM VITAE

Nama
: Sumadiono, dr SpA(K)
Tempat/ tanggal lahir
: Nganjuk, 9-10-1956
Pekerjaan/jabatan : Staf Bagian Ilmu Kesehatan Anak FKUGM
Riwayat pendidikan formal:
Dokter umum
: Fakultas kedokteran Unair, lulus tahun 1982
Spesialis anak
: Fakultas kedokteran UGM, lulus tahun 1994
Konsultan Alergi Imunologi Anak: Ikatan Dokter Anak Indonesia 2002
Riwayat pendidikantambahan:
Molecular Biology (ICMR Kobe, Japan, 1996)
Basic Immunology (VU Amsterdam, The Netherland, 1997)
Pediatric clinic/treatment (VU Amsterdam, The Netherlands, 1998 & 1999)
Pediatric Allergy Immunology (Saskatoon, Canada, 2003)
Medical Education: PBL (UM Mastrich, The Netherlands, 2004)
Trends in Medical Education (NUS, Singapore, 2004)
Workshop: Intraarticular Injection (IRA, 2005)
Riwayat Organisasi:
Kepala Sub Bag Alergi-Imunologi Bag. IKA FK UGM
Wakil Ketua Team Herbal RSUP Dr. Sarjito
Ketua Sub Komisi Evaluasi Proses Kolegium IDAI
Ketua Peralmuni Cab. DIY
Ketua UKK Alergi Imunologi IDAI

New Mechanisms in
Atopic Dermatitis
The Role of Emollients in its
Management.
Hugo Van Bever
Department of Pediatrics
Khoo Teck Puat CMI
NUHS - Singapore

March May 2014

ITCH

- Looks
- Sleep
- Study activities

Prevalence of potentially allergic


diseases in infants (PAI, 2005, 16, 151)

Atopic dermatitis in infantile

Atopic Dermatitis in Childhood phase (3-10 years)

Atopic Dermatitis in Childhood phase (3-10 yrs)

Siti Aisah_D. Atopik PIT 2012

Atopic Dermatitis in Adulthood phase (>13 years)

Siti Aisah_D. Atopik PIT 2012

Foot and hand atopic dermatitis in adults

Other symptoms

White Dermatographism

Catarak subcapsular
anterior

Xerosis/ichtyosis/
hyperlinear palm

Periauricular fissures

Cheilitis
Kepekaan infeksi kulit (Herpes/Strep/S aureus)

Pompholix

SCORing
Atopic
Dermatitis
(SCORAD)
index

Oranje AP et al, British Journal of

Hi Suma,
For research it is better to use a more extensive
score, such as SCORAD.
However, for myself in my daily clinic I use:
- MILD (dry skin, few patches, but <5)

- MODERATE (Fold eczema)


-SEVERE (FOLD + trunk eczema)
Hugo

A LOT OF NEW FINDINGS !

AD is not just a simple


allergic
reaction of the skin

Atopic dermatitis
Genetic constitution

Environmental factors

(role of epigenetics)

atopy
skin barrier defects

allergens
- food
- inhalant
microorganisms
pollution
irritants

X2

Chronic skin
inflammation

Atopic dermatitis the 4 player


model
= a complex and dynamic interplay of 4
(or more) causal factors.

1. Skin barrier defects (role of FLG others)

2. Allergy abnormal immune responses


3. Auto-immunity (? controversial)
4. Microbial colonization of the skin

Q: primary or second

4 Types of Skin Barrier Defects


in AD
- Mechanical (FLG)
- dry skin
- increased bacterial skin infections
- increased risk for food allergy
asthma
- Immunological / Chemical /
Microbiome
- increased bacterial infections
( infectious eczema)
- no dry skin

Skin Barrier Abnormalities


1. CONGENITAL (cause of AD)
2. ACQUIRED (consequence
of AD)

AD = a syndrome (subty

Defective skin barrier


function
Eczema is an
inflammatory
condition of the skin
In eczema, the lipid
layer is defective
causing:
Water loss
Cracks in the outer
layer of skin (stratum
corneum)
Penetration of
allergens and irritants
Cork MJ. (1997) The importance of skin barrier function. J of Dermatological Treatment (1997) 8, S7-13

Profilaggrin

(keratohyalin F granules)

Filaggrin

Hydrophilic amino acids

Natural moisturizing factor


Hydration of SC
Barrier permeability
Antimicrobial defense

Influencing factors on Atopic Dermatitis

Skin Barrier Function: Stratum corneum role


Filaggrin:
Protein incorporated in cornified cell
Not found on 2 deepest layer of stratum corneum
Lipid barrier alteration (intercellular lipid):
Ceramides (50%), Cholesterol (25%), Essential fatty acids (10-20

Filaggrin gene mutations presents in 26.7% patients with severe AD

Natural Moisturizing Factors:


Derived by hydrolysis of fillagrin in corneocytes
Complex mixture of low molecular weight, water soluble and hygroscopic compounds
Pretention of water within corneocytes prevent skin hydration

*Morar N, et al. J Invest Dermatol 2007; 127:1667-72; Cai S, et al. Br J Dermatol 2012; 166: 200-3

Singapore studies on FLG


FLG null-mutations are associated with:
1. early onset disease
2. increased disease severity
3. increased bacterial flares

REFERENCES:
- CAI S.C., CHEN H., KOH W.P., COMMON J.E., VAN BEVER H.P., McLEAN W.H., LANE E.B., GIAM, Y.C., TANG M. B.
Filaggrin Mutations are Associated with Recurrent Skin Infection in Singaporean Chinese Patients with Atopic
Dermatitis. Br J Dermatol 2011, 1111, 1365.

- CHEN H., COMMON J. E., BALAKRISHNAN A., BROWN S.J., GOH C.S., CORDELL H.J., SANDILANDS A,, CAMPBELL
L.E., KROBOTH K., IRVINE A.D., GOH D.L., TANG M.B., VAN BEVER H.P., GIAM Y.C., McLEAN W.H., LANE E.B. Wide
spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese
and European populations. Br J Dermatol. 2011, 165, 106 - 114.

Loss-of-function variants
in the filaggrin gene are a
significant risk factor for
peanut allergy.
Brown SJ, et al.
JACI 2011, 127, 661 7.

Sensitization to food

- Prenatally
- Through breast milk
- Eating drinking
- Transcutaneous
(eczema)
- Inhaling - smelling

Role of allergy in AD
1. not always involved in AD
2. allergy in severe eczema
3. allergic sensitization can occur through the
skin
4. allergic sensitization can be a

consequence of skin barrier defects

5. allergens contacts are unavoidable!

HDM-allergy in AD
- skin inflammation (IgE-mediated)
- skin barrier disruption (HDM-proteases)
- increased cytokine production by
keratinocytes

Nakamura T, et al. Reduction of skin barrier function by proteolytic activity of a


recombinant house dust mite major allergen Der f 1. J Invest Dermatol 2006, 126, 2719
23.
Oshio T, et al. Dermatophagoides farinae extract induces severe atopic dermatitis in
NC/Nga mice, which is effectively suppressed by the administration of tacrolimus
ointment. Int Immunopharm 2009, 9, 40311.
Arlian LG, et al. House dust and storage mite extracts influence skin keratinocyte and
fibroblast function. Int Arch Allergy Immunol 2008, 145, 3342.

Hypothetical Model of AD

1.
2.
3.
4.

Skin barrier defects


Allergy
Auto-immunity
Chronic Staph. colonization

HYPOTHETIC MODEL OF AD
early infancy

PHASE 1: Non-allergic inflammation


(commensals)
- ichtyosis pruritus
- auto-immunity ?
- Other (viruses) ?
early childhood
PHASE 2: Allergic inflammation
- food ( through urticaria)
- inhalants
late childhood
adulthood

PHASE 3: Infectious inflammation


- Staph colonization
- Viral colonization

HYPOTHETIC MODEL OF AD
early infancy

PHASE 1: Non-allergic inflammation


(commensals)
moisturizing
- ichtyosis pruritus
- auto-immunity ?
- Other (viruses) ?
early childhood
PHASE 2: Allergic inflammation
- foodallergen
( through avoidance
urticaria)
- inhalants
late childhood
adulthood

PHASE 3: Infectious inflammation


- Staph
colonization> antibiotics
antiseptics
- Viral colonization

Management of atopic
dermatitis

= A PACKAGE
(involving life style)

Cornerstones of treatment
of AD
1. Moisturizers
2. Topical
corticosteroids
3. Antiseptics

European & US Guidelines


EAACI and AAAAI PRACTALL
Consensus Report
Recalcitrant to severe
AD

se

as
e

Step 4

Step 3

Mid High Potency topical


corticosteroid and/or TCIs

Dry Skin
Only

In
t

Mild to
moderate AD

en
s

it y

of

Di

Moderate to
severe AD

Systematic therapy
e.g. CyA/ UV therapy

Step 1

Step 2

Low mid potency topical


corticosteroid and/ or TCIs

Basic Treatment:
Skin hydration, emollient, avoidance of
irritants, identification and addressing specific
trigger factors
41

Akdis CA, et al. Allergy 2006;61:969987.

Kelas Potensi Kortikosteroid


Topikal
(Alan B. Fleischer, Clinical Pediatrics, 2008)

Restoring the skin barrier

Prevention of food allergy?

Moisturizers
A lot of mositurizers on the market
Most were not the subject of clinical
studies
Doctors confused!

go for scientific evidenc

MAS036P
MAS036P:
A unique, clinically proven (!), nonsteroidal flare remission treatment for
Atopic Dermatitis
Repairs
Protects
Calms (mild anti-inflammatory effect)
46

Glycyrrhetinic acid

Glycyrrhetinic acid

chemical structure is related to cortisone


has anti-inflammatory activity via inhibiting
11--hydroxysteroid dehydrogenase and by
inhibiting the classical complement pathway
at the C2 level
reduced scratching behavior induced by
substance P and PAR-2 agonist peptide, which are
mediators of itch in chronic dermatoses
has anti-allergic and anti-oxidative
properties
48

3 Key Studies on MAS063P


(7 DBPC studies)

MAS063P - Key
conclusions
- Replenish skin moisture up to
72 hours
(Zhai, 2003)

- Itch relief in less than 3 minutes


(Boguniewicz, 2008)

- Safe for infants and children


above 1 months
(Abramovitz, 2008 / Cimaz, 2005)

Patrizi A, et al, PAI, 2008, 1

General conclusion
1. AD is complex, involving many players
2. FLG best gene we have (more to
come)
3. Food allergy: new insights (role of the
skin)
4. Treatment: new approaches, including
preventing transcutaneous sensitization

Information, registration and


programme details are
available at

Website:
www.apapari2014.com
Email:
admin@apapari2014.com

Contact person:
Asri Parantri, MD
+62-822 2623 8826

Secretariat:
Departement of Child Health
Faculty Of Medicine Gadjah Mada
University/Dr. Sardjito General
Hospital
phone-fax: +62 274
581088/5550045

Registration & Programme


Information
It will be available soon at our website
www.nuhkids.com (under Events)

Key contact person


For Wong Hock Boon Paediatric
Masterclass:
Ms Jean Sia
Email: jean_sia@nuhs.edu.sg
For Pre-Masterclass Courses:
Ms Faridah / Magase
Email: paev15@nus.edu.sg