Dr. Mark Koh Jean Aan and Dr. Ritu Jain

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DEBRA International Congress 2018 Zermatt:

EPIDERMOLYSIS BULLOSA IN SINGAPORE

AND THE SOUTH EAST ASIAN REGION

Agenda

1. Epidermolysis bullosa in Singapore

2. Epidermolysis bullosa in other South-East Asian

countries

3. DEBRA SG

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SINGAPORE

Population: 5.6 Mil

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SOUTH-EASTASIA

Population: 655.6 Mil

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INDONESIA

PHILIPPINES

Pop: 261.1 million

Pop: 103.3 million

VietnamPop: 92.7 million

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ThailandPop: 68.8 million

MALAYSIAPop: 31.2 million

MYANMARPop: 52.9 million

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CAMBODIA

LAOS

Pop: 15.7 million

Pop: 6.8 million

BRUNEIPop: 0.42 million

EB in Singapore

• 30-50 families with EB in Singapore

• Majority are EBS (80-85%)

• 15-20% JEB or DEB (mostly DDEB)

• Diagnosis and management:

– Hospitals: KKH, NSC, NUH

– A*STAR / IMB / SRIS

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KK Women’s & Children’s Hospital

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National Skin Centre

National University Hospital

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A*STAR . Skin Research Institute Singapore (SRIS)

EB in SG: Diagnosis

• Sources of Referrals:

– Intra and inter-hospital:

• KK Women’s & Children’s Hospital

• Singapore General Hospital, National University Hospital

• Private hospitals (MEH, RH, PEH etc)

– Dermatology clinics:

• National Skin Centre, Changi General Hospital

• Private dermatology clinics

– Overseas:

• South-East Asia

• South Asia e.g. Bangladesh

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EB in SG: Diagnosis

• KKH Genodermatoses Clinic:

– Clinical and molecular diagnosis

– Genetic counselling

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GeneticsService

DermatologyService

EB in SG: Diagnosis

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EB in SG: Diagnosis

Histology & Immuno-mapping:

• 3-4 mm punch biopsy from blister /

rubbed skin

• Transported in Michel’s medium

• Washed with Michel’s buffer

• Snap frozen in liquid nitrogen

• Cryo-sectioned and stained using

standard procedures:

– Hematoxylin and eosin staining

– Immuno-mapping with extended panel

of antibodies

Protein Clone

Keratin 5 XM26

Keratin 14 LL001RCK107

Plectin 31/plectin

Integrin alpha 6 NKI-GOH

Integrin beta 4 439-9B

Collagen XVII NC16A-3

Laminin 332 P3E4

Collagen IV CIV 22

Collagen VII LH 7.2

EB in SG: Diagnosis

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22 patients2011 - 2018

8Both biopsy and blood

14Only blood Samples

7 Samples from family

EB in SG: IMMUNOFLUORESCENCE MAPPING (8 CASES)

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Intra-epidermal2

Sub-Lamina densa1

Inconclusive2

CollXVII1

ITGB42

Lamina-lucida3

EB in SG: MUTATION ANALYSIS (22 cases)

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EB in SG: EB Simplex

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EB with Mottled Pigmentation

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K14c.373C>T,p.R125CMissense

EBS-MP - Novel

KRT5

KRT14

EB in SG: Junctional EB

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EB with Pyloria Atresia

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EB with Pyloria Atresia

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Compound heterozygousITGB4p.S26fsITGB4p.C536C

EB in SG: Dystrophic EB

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EB in SG: EB Pruriginosa

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COL7A1p.G2623DFrameshift

Dominant Dystrophic

EB in SG: Management

• Coordinated by KKH Dermatology:

– Dermatologists and dermatology nurses

– Genetics Service

– Dietitian

– Dental

– Orthopaedics

– Gastroenterology

– PT / OT / SLT

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EB in SG: Management

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EB in SG: Management

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EB in SG: Management

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EB Research in SG

• Collaborative Site for International Trials on EB:

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EB Research in SG

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EB Research in SG

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SOUTH-EASTASIA

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Hospital Kuala Lumpur (HKL)KUALA LUMPUR, MALAYSIA

EB in SE Asia: Malaysia

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Total Population: 31.2 mil

EB in SE Asia: Malaysia

Results of Laboratory Diagnoses (44 cases)

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Teaching Hospital Universitas PadjadjaranBANDUNG, INDONESIA

EB in SE Asia: Indonesia (Bandung)

Results of Genetic Testing (11 cases)

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JEB 1

DEB 8 EBS 2

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Preah Kossamak HospitalPHNOM PENH, CAMBODIA

EB in SE Asia: Cambodia

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EB in SE Asia: Cambodia

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EB in South East Asia

• Issues:

– Many undiagnosed cases

– Low socio-economic / rural areas

– Poor access to healthcare

– No diagnostic tools for EB

– Minimal treatment options

– No genetic counselling, prenatal testing

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EB in South East Asia

• Possible solutions:

– Improve access to healthcare for patients, especially

from rural settings

– Provide diagnostic services for EB (immunomapping,

genetic testing)

– Teach healthcare workers (dermatologists and other

doctors, nurses) on the importance of multi-

disciplinary management of EB patients

– Provide better access to better dressings

– Enrol in research?

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Conclusion

• Prevalence of EB in Singapore is low

• Most cases are mild (e.g. EB simplex) with handful of

moderate to severe cases

• Many cases in SE Asia - underdiagnosed

• Diagnostic services available but on research basis

• Multi-disciplinary management can be developed further

• Need to develop better expertise in diagnosis and

treatment in SE Asia

• Singapore can be the hub for multi-centre international

research in SE Asia

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DEBRA Singapore Established: May 2015

Government support/subsidy for EB

• MediShield Life (national insurance Policy) - subsidiseshospitalization bills .

• Medisave – compulsory, self-funded medical savings account for certain outpatient expenses for chronic conditions such as Diabetes, Hypertension, Epilepsy, osteoporosis, psoriasis, rheumatoid arthritis, etc. EB is not included.

• Most EB patients who seek outpatient treatment, wound care products/dressings get no support. DEBRA Singapore addresses this gap

DEBRA Singapore Organisation Structure

PresidentDr. Ritu Jain

Board

Vice PresidentDr. Sebastien Teissier

Board

TreasurerMrs Nurzeehan Halim

Admin Support:Sophie Loo Yan Ni

Medical AdvisorDr. Mark Koh

Board

BOARD OF GOVERNANCE

EXECUTIVE COMMITTEE

A/Prof. Steven TngBoard Member

Prof. Maurice van Steensel

Board Member

Board ChairProf. Birgit Lane

What we offer/do:

1. Raise funds/resources to support EB families through subsidised dressings, emollients, services (hospital, transport, etc.)

2. Make contact with all patient-families with EB and extend socio-emotional and material support (wound-care products, genetic tests, reimbursement for doctor consultations, support to families with new-borns, patient meetings, etc.)

3. Create awareness of Epidermolysis bullosa disorders through news and social media

4. Negotiate with companies for price reductions and/or help source for affordable dressings

5. Facilitate clinical trials (e.g.Amicus, Amryt), organize clinical meetings, seminars, conventions and similar gatherings.

6. Support the establishment of new Debra groups in Asia Pacific and of patients through sharing information and - where possible – supplies. Connect with research labs for help with genetic testing.

Accomplishments:

• Representation on international groups

➢ International Congress London 2015, Zagreb 2016, NZ 2017

➢ council of RDI, IRDiRC

➢ Board of Debra International, within EBWB

• Media coverage & public awareness

• Global Butterfly Run, Oct 2017

• Butterfly Children: documentary first screened on Channel NewsAsia

Cambodia

Abandoned purple baby SreYa

Small Debra, large heart

INDIA

Regional initiatives

EBWB supported first national EB Meeting, Bangalore 13-14th January 2018

Organized by: Prof Celia Moss (UK), Dr Ravi Hiremagalore (India), Ms LalithaPhadkar, Debra India and Dr Ritu Jain, Singapore.Invited speakers: Prof Birgit Lane (Singapore), Dr Francis Palisson (Chile), Prof Celia Moss (UK) and 11 members of the UK multidisciplinary EB team, doctors and residents from across India.

RSMPD Singapore: 26-29 April 2018

Pakistan: teaming up

DS’s long-distance assistance

Indonesia: May 1-3, 2018

Our partners

KK Hospital

IMB A*Star Lab

Thank you!

https://www.dropbox.com/s/56kv3j4v1cifg93/Butterfly%20Children%204.1%20min.mp4?dl=0

Acknowledgements

KKH:

Dermatology

Genetics Service

Dental Service

NSC:

Paediatric Dermatology

NUH:

Paediatric Dermatology

SGH:

Burns Unit / Burns Lab

Dermatology

Yann Barrandon

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DEBRA Singapore

A*STAR

Institute of Molecular Biology

Skin Research Institute, SG

Overseas Collaborators

Malaysia

Indonesia

Cambodia

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