Anne W' Lucky, M'D'

1
Clinical Update on Epidermolysis Bullosa 2006

• Anne W. Lucky, M.D.
• Professor of Dermatology and Pediatrics
• The Cincinnati Childrens EB Center
• The Cincinnati Childrens Hospital
• Cincinnati, Ohio
• USA

2
Epidermolysis Bullosa

• Three major types
• Simplex (Epidermal)
• Mutations of keratin 5 / 14 and plectin
• Junctional (Basement Membrane)
• Mutations of basement membrane proteins
• Dystrophic (Dermal)
• Mutations of type VII collagen
• Some authors also include Hemidesmosomal
• Revised classification in 2000
• Fine, JD et al, J Am Acad Dermatol 42 1051-1066

3
EBS
BP180 BPAg2 type XVII col
JEB
Laminin 5 has a3/ß3/?2 chains
DEB
Fine, JD et al, JAAD 2000 43 135-137
4
EB Clinical-Molecular Correlations
From Pai, Am J Clin Derm 20023371-380
5
EB Simplex (EBS)

• Mutations in genes for
• keratins (intermediate filaments)
• plectin (hemidesmosome plaque)
• Most are autosomal dominant
• Subtypes of EBS
• Weber-Cockayne Keratin 5,14
• palms and soles
• childhood or adult onset
• Köbner Keratin 5,14
• generalized, at birth

6
EBS cont.

• Dowling-Meara Keratin 5,14
• generalized, at birth,
• herpetiform
• hyperkeratosis
• EBS Muscular Dystrophy Plectin
• Generalized EB
• MD later in life
• Some classify as EB HD

7
Junctional EB (JEB)

• Lamina lucida defects of
• anchoring filaments
• hemidesmosomes
• Most are autosomal recessive
• Types
• JEB-H (Herlitz) Laminin 5
• Anchoring filament protein
• Any of 3 chains (a3ß3?2)
• Severe, generalized, granulation tissue
• Lethal in lt 2 years

8
JEB cont.

• JEB-nH (Non-Herlitz) Laminin 5
• Variable severity Type XVII Col
• Alopecia (BP 180)
• Dental problems
• ? risk of squamous cell ca ?
• JEB-PA (pyloric atresia) ?6?4 Integrin
• Either of 2 chains
• Variable severity
• pyloric atresia
• Some classify as EBHD
• Bauer, JW, and Lanschuetzer, Clin Exp Derm 2003
  2853-60.

9
Dystrophic EB

• Dominant (DDEB) and Recessive (RDEB)
• Many (gt500) mutations identified in collagen VII
  gene (COL7A1) on 3p21
• Collagen VII is found in the
• anchoring fibril
• anchoring plaque

10
Dominant Dystrophic EB (DDEB)

• DDEB
• Wide spectrum of severity
• Generally mild
• May be generalized or severe at birth
• Improves with age

11
RDEB

• RDEB-nHS (non-Hallopeau-Siemens)
• Less severe, variable
• RDEB-HS (Hallopeau-Siemens)
• Severe with
• Esophageal strictures
• Pseudosyndactyly
• Anemia and failure to thrive
• Dental problems
• Risk for squamous cell carcinoma

12
RDEB Adolescence
19 Years Old Squamous Cell Carcinoma BK Amputation
20 Years Old Same patient Fatal Metastatic SCC
13
RDEB Variants
9 Year Old Boy Non-Hallepeau-Siemens Inverse
involvement Pigmentary Abnormality
14
DEB Compound HeterozygoteDDEB and RDEB Mutations

• Father with DDEB
• Mother Asymptomatic with RDEB Mutation
• Child with one Mutation on Each Collagen 7 Allele
• Also has Deafness

15
EB Diagnosis

• Skin Biopsies
• Routine histology
• Electron microscopy
• Immunofluorescence mapping of BM
• Immunofluoroescence for specific proteins
• Blood or skin
• Genetic identification of the mutation

16
Recent Reviews

• 1.Fine, JD et al, Revised classification system
  for inherited epidermolysis bullosa report of
  the Second International Consensus Meeting on
  diagnosis and classification of epidermolysis
  bullosa. J Am Acad Derm 2000421051-1066.
• 2.Fine,JD, McGrath,J, Eady, RA, Inherited
  epidermolysis bullosa comes into the new
  millennium. J Amer Acad Derm 2000 43135-137.
• 3. Pai,S, Marinkovich,MP, Epidermolysis bullosa
  new and emerging trends. Am J Clin Dermatol
  20023371-380.
• 4. Fine, JD et al, Assessment of mobility,
  activities and pain in different subtypes of
  epidermolysis bullosa, Clin Exp Dermatol 2004
  29 122-127

17
Recent Reviews cont.

• 5. Devries,DT et al, Relative extent of skin
  involvement in inherited epidermolysis bullosa
  (EB) Composite regional anatomic diagrams based
  on the findings of the National Registry, 1986 to
  2002, J Am Acad Dermatol 2004 50 572-581
• 6. Fine, JD, et al, Eye involvement in inherited
  epidermolysis bullosa experience with the
  National Epidermolysis Bullosa Registry. Am J
  Ophthalmol 2004138254-262.
• 7. Woodley, DT, Chen, M, Epidermolysis bullosa
  then and now. J Am Acad Dermatol 2004
  51Suppl1,S55-57.
• 8. Ingen-Housz-Oro, S et al, Vitamin and trace
  metal levels in recessive dystrophic
  epidermolysis bullosa. J Eur Acad Dermatol
  Venerol 200418649-53.
• 9. McAllister, JC, Marinkovitch, P, Advances in
  inherited epidermolysis bullosa. Adv, Dermatol
  200521303-34

18
Recent Reviews cont.

• 10. Uitto, J and Richard, G. Progress in
  Epidermolysis Bullosa from eponyms to molecular
  genetic classification. Clin Dermatolol
  20052333-40.
• 11. Pseudosyndactyly and musculoskeletal
  contractures in inherited epidermolysis bullosa
  experience of the National Epidermolysis Bullosa
  Registry,1986-2002. J Hand Surg (Br)
  20053014-22.
• 12. Fine, JD et al. Impact of inherited
  epidermolysis bullosa on parental interpersonal
  relationships, marital status and family size.
  Br. J Dermatol.20051521009-14
• 13. Fewtrell, MS et al, Bone mineralization in
  children with epidermolysis bullosa. Br J
  Dermatol 2006154959-62.
• 14. Azizkhan, RG et al, Esophageal strictures in
  children with recessive dystrophic epidermolysis
  bullosa an 11 year experience with
  fluoroscopically guided balloon dilatation. J
  Pediatr Surg 20064155-60