epidermolysis bullosa

1. Dr. vivek ranjan
Mbbs,dch(pmch),dnb(pedia)
st.Stephen hospital,new delhi

2. definition
 Epidermolysis bullosa (EB) comprise a group of
generally determine skin disorder characterized by
blistering of skin and mucosa at birth or soon
afterwards, follows mild mechanical trauma (due to
increase fragility of skin)

3. incidence
 The overall incidence of hereditary epidermolysis
bullosa is placed 19.6live birth/1 million birth in US.
 Incidence 11 for EBS,2 for JES,5 for DEB.
 Estimated prevalence in US is 8.2/million,but the
figure represent only most severe case,as it did not
includes the
 Majority very mild disease going unreported.

4. Types
 EB simplex
 JEB
 DEB
 KLINDER SYNDROME
 The classification is on mode
of inheritance and
combination of
clinical,electromicroscopic,
immunohistochemical,
genotype features

5. Skin

6. introduction
 Intraepidermal blistering is the hallmark feature of EB
simplex, in contrast, JEB and DEB patients develop their
blisters within the lamina lucida and sub-lamina densa of
the skin basement membrane zone (Dermo-epidermal
junction), in Kindler syndrome, multiple skin cleavage
planes may be seen in same sample of skin.
 Previously kindler syndrome is known or consider a
POIKILODERMATOUS photosensitivity disease; and
inclusion of the Laryngo-onycho-cutaneous syndrome
(LOC; previous known as) Shabbir's syndrome, given its
shared molecular target with JEB.

7. Cont…
 Major EB type Level of Blister formation
 EB simplex Intrapidemal
 Junctional Intra-Lamina Lucide
 Arystrophic EB EB lamina dense
 Kindler syndrom Multiple level (Intra-
lamina lacide + sub lamine dense)

8. Cont..
 The hallmark cutaneous features of inherited EB, in
additional to mechanically fragile skin and easy
inducibility of blisters or erosions, includes.
 1. Milia
 2. nail dystrophy
 3.Scarring (usually atrophic)
 4. exuberant granulation tissue (periorificial; axillary
vaults; nape of the neck; lumbosacral spine;
periungual and proximal nail folds),

9. Cont…
 5. localized or confluent keratoderma of the palms and
soles
 6. dyspigmentation (postinflammatory hypo- or
hyperpigmentation)
 7. Decreased or absence of hair
 8. albopapuloid lesions (flesh-colored or
hypopigmented papules, usually arising on the lower
trunk)
 9. Hypo- or hyper hidrosis

10.  Several factors must be considered when attempting to use
cutaneous findings as surrogate diagnostic markers.
 The presence or absence of one or more findings mention
above may be age-dependent.
 So, not all of these skin findings are necessarily seen in
neonates or infants
 Exuberant granulation tissue is pathognomonic of EB,
exclusive in Herlitz subtype of generalized JEB
 Albopapuloid/Aplasia cutis is seen in more than one
subtype of EB, so, insufficient to be reliably used as
diagnostic tools.

11.  Skin fragility in EB is characteristically worsened in
warm weather or warm living environments; hence
the value of air-conditioning for families with affected
children.
 The exception is sub type of EBS-DM is temporary
reduce of blistering during periods of fever.
 Non-epithelial organs or tissues may also may also involved
in selected EB subtype.
 1. Enamel hypoplasia – Exclusively in JEB
 2. Muscular dystrophy (congenital or late)– a subtype of
EBS

12. E b simplex

13.  Onset – usually at or shortly after birth.
 -Blister arises from Basal layer of epidermis.
 Mostly distrubuted over hand,feet,elbow,knee,legs and scalp.
 -In localized EBS may not develop blister until late childhood or even
early adulthood.
 As rule EBS, for less-scarring, milia formation & nail dystrophy are seen
in EBS as compare to JEB and DEB.
 v Combination of all these three clinical finding, when used as a
diagnostic test to distinguish EBS form all other EB type to provide
sensitivity and specificity > 90%.
 – Mutation in gene coding for keratin 5 and 14 (major keratin of BMZ
& separation will be epidermal)
 – EBS – The most common subtype is localized EBS. Also known as
Weber-Cockayne disease.
 –The usual dismution of Blisters in the patient in Palms and soles.

14. The blistered foot of localized EBS

15.  EBS - Dowling – Meara (DM) is frequently associated
and marked morbiding and in minority of patients
may result in death during early infancy.

16. Circinate grouping of blisters arising on the skin
of a patient
with the Dowling-Meara variant of generalized
EBS.

17. JUNCTIONALEB
 There is only one clinical finding that is characteristic
of all subtypes of JEB the presence of enamel
hypoplasia, manifested as localized or more extensive
thimble-like pitting of some or all of the tooth
surfaces.
 This is cannot be diagnostic tool until after the
primary teeth have erupted.
 Blister characteristic spares hand and feet.

18. Enamel pitting in pt of JEB

19.  The mutation in laminin a-3 (LAM a-3), (LAM b-3),
(LAM g-2) as the laminin is part of basement
membrane so the separation will be dermo,
epidermal junction.
 JEB Herlitz
 Incidence 20% of all type of JEB.
 Present at birth and involve all skin surface.
 Pathognonic finding is Exuberant granulation
tissue, which is arises within 1st several month to 1-2
year of life.

20. Exuberant granulation tissue(JEB-H)

21.  This may involve not only skin but also upper air
ways.
 There may be finding of Microstomia or
Ankyloglossia. Moderate to severe intra oral blister is
invariably present with some eventual narrowing of
the opening of mouth (Microstomia) and reduced the
extension of tongue (Ankyloglossia)
 The growth retardation and severe
multifunctional Anemia normal in JEB-H

22.  The other organ involve is (1) Esophagus (Stricture)
(2) External eye (Corneal blister), erosion, scarring,
ecopion formation (3) upper air way Stricture and
occulusion (4) Genitourinary tract (5) Neonatal death
 Squamous cell carcinomas may also arise in a minority
of JEB-H patients (cumulative risk of 18% by age 25)

23. Non-Herlitz JEB (80%)
 A generalized disorder present with blistering atrophic
scarring, nail dystrophy or absent.
 It is usually clinically present at birth.
 The risk of upper air way occulation risk is lower than JEB-
H type
 Death is due to complication same as JEB H-type.

 A rare but clinically important JEB subtype, inverse
JEB, is associated with rather severe blistering and
erosions confined to intertriginous skin sites,
esophagus, and vagina.

24. Dystrophic EB
 Mutation in collegen VII-A1 gene as collegen VII
containing fibre join BM to dermal papilla, so
separation will be in the dermis.
 Dystrophic EB is separated in two type, based on the mode
of transmission (AD or AR).
 DDEB has generalized Blister at birth, with time is
associated with mila, atrophic and scarring and nail
dystrophy.
 Recurrent esophageal blistering and erosions, leads
to progressive dysphagia secondary to esophageal
stricture formation, is common among these patients.

25.  RDEB in contrast generalized RDEB and JEB-H,
However, failure to thrive, growth retardation, severe
anemia, early infant mortality, and risk of squamous
cell carcinoma are not characteristic features of
DDEB.(RDEB)
 The most severe subtype, severe generaliazed RDEB is
clearly one of the most Devastating multi organ
genetically transmitted diseases of mankind.

26.  Phenotypic finding
 — Generalised blister at birth.
 — Progressive and often time multilating.
 — Scarring of skin
 —corneal blisters or scarring
 —profound growth retardation
 —multifactorial anemia
 —failure to thrive
 —esophageal strictures
 —debilitating hand and foot deformities ("mitten
deformities"; pseudosyndactyly)

27. Complete mutilating deformities
(RDEB)

28. Kindler syndrome
 Cause of mutation of gene kindlin-1 component of
focal contact in basal keratocytes. Kindler
syndrome is characterized by generalized blistering at
birth and the later development of characteristic
poikilodermatous pigmentation and
photosensitivity. Skin findings may includes atrophic
scarring and nail dystrophy, at times closely. Teeth
are uninvolved but gingival hyperplasia may
develop. The Skin derived squamous cell carcinomas
have been reported in at least two of these patients.

29.  Diagnosis/diagnostic criteria/diagnostic methods
 Each major EB type is diagnosed by determination of
the ultrastructural level within which blisters develop
following minor traction to the skin.
 Subtypes are then defined on the basis of mode of
transmission, immunohistochemical and electron
microscopic findings, and clinical phenotype.

30.  Diagnostic methods
 Postnatal diagnosis
 Every patient suspected of having inherited EB should have
one or more skin specimens harvested
 and properly processed for diagnostic immunofluorescence
antigenic mapping (IAM) and transmission electron
microscopy (TEM). The best samples for IAM and TEM are
small punch biopsies and shave biopsies,
 respectively, harvested from nonblistered skin which has
been first subjected to mild rotary traction. The IAM study
may allow further subclassification of these patients, based
on the location, pattern, and relative
 intensity of staining by one or more of these antibodies.

31.  TEM also permits the direct semiquantification
 of specific ultrastructural structures (i.e., keratin filaments;
hemidesmosomes; anchoring fibrils;
 subbasal dense plates). routine histological processing of
skin is not recommended in the setting of EB,
 since it may be difficult or impossible to distinguish at the
light microscopy level between even lower intraepidermal
and subepidermal cleavage in some specimens.
 The precise distinction between intra-lamina lucida (i.e.,
JEB) and sub-lamina densa (i.e., DEB) cleavage can
 be ascertained only by IAM or TEM.

32.  The further reason for not pursuing routine histology,
most of the EB-relevant antibodies used in IAM
cannot be employed on conventional formalin-
preserved tissue samples, due to loss of antigenicity in
the latter tissues. Alternatively, attempts at using these
paraffin embedded tissue blocks for subsequent TEM
evaluation are also invariably suboptimal, due to
differences in the fixatives used for tissue preservation.

33. DNA mutational
 analysis for subclassification of EB is still primarily
reserved for prenatal diagnosis, or when
preimplantation
 therapy is being considered, given the considerable
problems that have been seen with genotype-
phenotype
 correlation within most of the EB subtypes.
 DNA testing is not routinely performed in the absence
of prior tissue confirmation of the major type of EB
which is present or when gene replacement therapy
becomes a reality.

34.  Prenatal diagnosis
 DNA mutational analysis has become the standard of care,
using specimens obtained from chorionic villi.
 Differential diagnosis
 In the most situations the diagnosis of inherited EB should
be obvious to a dermatologist; In the neonatal period,
however, in utero herpes simplex infection might need be
considered, especially if there is no family history of a
blistering disease. or if the clinical findings are very
atypical for EB.
 Genetic counseling
 In-depth recommendations on the counseling of EB
patients and their families have been recently published.

35. Management
 The basic underlying tenets of care for all EB patients
are avoidance of blistering (by meticulous protective
padding of the skin) and prevention of secondary
infection.
 Specific extracutaneous complications need careful
surveillance for their occurrence, and implementation
of appropriate interventions (medical; surgical; dental;
nutritional; psychological; other).
 -Prompt evaluation by an ophthalmologist so as to
prevent the development of permanent corneal
scarring and impaired vision.

36. Cont..
 - Symptomatic esophageal strictures need to be
dilated, oftentimes repeatedly, in order to maintain
 adequate intake of nutrients by mouth.
 Those children unable to take in sufficient nutrients by
mouth are instead given nutrient supplements via
gastrostomy.
 Hand deformities, if they cannot be prevented by
meticulous nightly wrapping of the digits, may be
temporarily improved by surgical degloving
procedures.

37. Cont…
 Squamous cell carcinomas, which may arise as early as
the second decade of life in patients with severe
generalized RDEB and JEB-H, are treated by
conventional wide excision, with careful follow-up to
monitor for local or regional recurrence.
 Patients with generalized forms of JEB and RDEB need
to be monitored by serial DEXA scans for
 possible osteoporosis or osteopenia.

38. Management of blister

40.  The presence of multiple wounds of varying duration
and ability to heal makes management of EB difficult
and complex.
 The blister of are not selft limiting and will expand
rapidly if left unchecked. The blister should be lanced
at their lowest point to limit tissue damage.
 A fresh hypodermic needle should be used or, if this is
not available, a sterilized sewing needle. A needle
should be passed through the blister roof, parallel to
the skin, to create an entry and exit hole through
which fluid can be expelled.

41.  De roofing should be discourage if possible.
 Most effective management is lancing the Blister.
 The patients who dislike dressing or find the exacerbate the
blister sites, commercial cornflour (corn starch) may be
used to dry up the blisters area and provide low friction
surface.
 Clinical experience also suggests that silver may help to
keep feet cool.
 Thin layer of equal part of white soft and liquid paraffin can
reduce friction and soft seam free – clothing offers
protection.

42.  Management of Junctional EB
 Use of very potent topical steroid ointments greatly
reduces over-granulation and may encourage healing.
 Management of dystrophyic EB
 1. Management of Critical colonization and infection.
 2. Avoidence of contractures
 3. Reduce prupitus
 4. Dressing

44.  MANAGEMENT OF KINDLER SYNDROME
 The lancing of blisters is important in infants and the rate
of blistering decreases with age. Application of high factor
sun protection is essential from an early age.

 Other Therapy (In trial)
 Ex. Vivo gene replacement
 Transplanation of allogenic fibroblast
 Transplanation of bone marrow derived stem cells.
 Infusion of recombinant protein
 Tropical application of small molecular weight protin
thymosin b4 to open wound.