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Treating patients with
epidermolysis bullosa
Jemima Mellerio
Great Ormond Street Hospital and
St John’s Institute of Dermatology
London, UK
Treating patients with EB

EB and EB care in England and Wales

What are the problems and what can we do
about them?

Clinical trials in EB - what is there?

Why so few?

What could we do?

What is the way forward?
Epidermolysis bullosa (EB)

Group of inherited disorders

Skin +/- mucosal fragility
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Variable severity

Variable non-cutaneous features

Overall incidence of approx 1 per 20,000
births

Estimated 5,000 with EB in UK
Epidermolysis bullosa (EB)

Result from mutations in genes encoding
proteins at the dermal-epidermal junction

Latest classification: 13 different genes, many
more clinical subtypes
Fine J-D et al. J Am Acad Dermatol 2008; 58(6): 931-50
EB care in England and Wales

April 2002 NSCAG funding (National
Specialist Commissioning Advisory Group)
(now NCG)
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Specialist centres to develop expertise in rare
diseases

Funded by Department of Health

Reciprocal arrangements with Scotland and
N Ireland
EB care in England and Wales
Ninewells &
University of Dundee
Birmingham Children’s
Hospital
Great Ormond
Street Hospital
St Thomas’ Hospital
Heartlands Hospital
Robin Eady
National Diagnostic
EB Laboratory
Multidisciplinary EB care
Anaesthetist
Cardiologist
Clinical geneticist
Dentist
Oncologist
Ophthalmologist
Orthopaedic surgeon
OT/hand therapist
Dermatologist
Dietician
Endocrinologist
ENT surgeon
Gastroenterologist
General surgeon
Haematologist
Interventional radiologist
Microbiologist
Obstetrician
Paediatrician
Physiotherapist
Plastic surgeon
Play therapist
Podiatrist
Psychologist
Social worker
Specialist nurse
Symptom control team
Urologist
EB: what are the problems and
what can we do about them?
Wound healing
EB: what are the problems and
what can we do about them?
Infection
EB: what are the problems and
what can we do about them?
Hand contractures
EB: what are the problems and
what can we do about them?
Nutrition
EB: what are the problems and
what can we do about them?
Anaemia
EB: what are the problems and
what can we do about them?
Bone health
EB: what are the problems and
what can we do about them?
Airways
EB: what are the problems and
what can we do about them?
Eyes
EB: what are the problems and
what can we do about them?
Cancer
Pain
Itch
Constipation
GO reflux
Psychosocial
Delayed puberty
Cardiomyopathy
GU problems
So many problems…
So many interventions…
So little evidence…
Clinical trials in EB - what is
there?

Two double-blind placebo-controlled RCTs for
oral tetracyclines in EB simplex

Small numbers (n=12 and n=21)

No evidence of benefit
Clinical trials in EB - what is
there?

Two RCTs for topical interventions in EBS
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20% aluminium chloride hexahydrate (n=23)

5% bufexamac cream (n=8)
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No evidence for benefit from either
Clinical trials in EB - what is
there?

One RCT with phenytoin vs placebo in
recessive dystrophic EB

N=36

No benefit from phenytoin
Clinical trials in EB - what is
there?

Anecdotal reports and retrospective analyses

Small non-controlled trials with small numbers
e.g. acceptability and efficacy of Urgotul
dressings
e.g. parenteral iron and erythropoietin for
anaemia in EB

Tolerability of oral isotretinoin in patients with
recessive dystrophic EB
Clinical trials in EB - what is
there?

Pilot study of low dose trimethoprim in
children with junctional and dystrophic EB
Clinical trials in EB - what is
there?

Pilot study of low dose trimethoprim in
children with junctional and dystrophic EB

Topical thymosin beta4 for wound healing in
junctional and dystrophic EB
Clinical trials in EB - what is
there?

Pilot study of low dose trimethoprim in
children with junctional and dystrophic EB

Topical thymosin beta4 for wound healing in
junctional and dystrophic EB

Efficacy of 2 different devices for improving
microstomia in severe generalised recessive
dystrophic EB
Clinical trials in EB - what is
there?

Pilot study of low dose trimethoprim in
children with junctional and dystrophic EB

Topical thymosin beta4 for wound healing in
junctional and dystrophic EB

Efficacy of 2 different devices for improving
microstomia in severe generalised recessive
dystrophic EB
Clinical trials in EB - what is
there?

Topical opioids for wound pain in EB

Low dose amitriptyline for chronic pain in
children with EB
Clinical trials in EB - what is
there?

Ex vivo gene therapy for non-Herlitz junctional
and recessive dystrophic EB
Clinical trials - why so few?

EB is a rare disease especially if break down
into subtypes…hard to get decent numbers

Validity of comparing different subtypes of
EB?

Other variables e.g. temperature, infection,
anaemia, age
Clinical trials - why so few?

Hard to get objective measures e.g. blister
counts, wound healing
Clinical trials - why so few?

What would ‘normal’ healing rate be?
Clinical trials - why so few?

Could evaluate ‘before’ and ‘after’
Clinical trials - why so few?

More global measures e.g. pain diaries, QoL
measures may not be sufficiently sensitive to
detect real differences

Birmingham EB Severity Score

Sydney QoL EB index
Clinical trials - why so few?

May mean yet another intervention or
treatment for patient and carers

May be higher drop outs due to other factors
e.g. intercurrent illness

Extra visits for study may be unfeasible
Clinical trials - what to do?
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Anaemia in severe forms of EB
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Parenteral iron +/- erythropoietin
Clinical trials - what to do?
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Osteoporosis in severe forms of EB
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Effects of bisphosphonates on EB bone
turnover
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Potential benefits from low amplitude
vibrating platforms
Clinical trials - what to do?
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Cancer chemoprevention in recessive
dystrophic EB
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Trial of oral retinoids: tolerability and efficacy
Clinical trials - what to do?

Cancer management
Clinical trials - what to do?

Cancer management

Role of imiquimod for treatment of early in
situ tumours or palliation
Clinical trials - what to do?
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Cancer management

Role of Mohs micrographic surgery or
sentinnel lymph node biopsy?
Clinical trials - what to do?

Cancer management

Role of newer chemotherapeutic agents e.g.
EGFR inhibitors and tyrosine kinase inhibitors
Clinical trials - what to do?

Gene, cell and protein therapy
EB gene
Skin
biopsy
Clinical trials - what to do?

Gene, cell and protein therapy
Baseline
Allogeneic fibroblasts
What is the way forward?

UK in privileged position

Large clinical centres for adults and children
providing comprehensive multidisciplinary
care

Most patients with more severe forms seen
regularly at one of these centres

Links to excellent diagnostic services

Invaluable role of DebRA UK
What is the way forward?

UK multi-centre trials much needed
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International collaboration is the way forward
for more power and larger numbers

Already good communication and links
between EB centres in EU and beyond

Need to overcome administrative and
financial hurdles to enable clinical trials to be
undertaken