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Epidermolysis bullosa Flashcards

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Dermatology Board Prep flashcards
1
Q

Major types of EB

A
  1. EB simplex - intra-epidermal
  2. Junctional EB- intra-lamina lucida
  3. Dystrophic EB - sublamina densa
  4. Kindler syndrome - mixed
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2
Q

Which is the most common EB

A

EBS

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3
Q

Major target protein in EBS

A

KRT 5 and KRT 14

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4
Q

Major target protein in DEB

A

Type VII collagen

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5
Q

Major target protein in JEB

A

Laminin 322

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6
Q

What are the different distributions of EB

A
  • Inversa subtypes of JEB and RDEB: intertriginous
  • Localized JEB: acral
  • Pretibial DEB: exclusively to shins
  • RDEB centripetalis: rare, features acral blistering followed by slow progression of disease activity toward the trunk over the years
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7
Q

Risk of skin cancers in EB?

A
  • Risk of SCC: well diff in sites of chronic wounds, very difficult to treat and often recur locally, frequently metastasize –> leading cause of death after mid-adolescence
    • Primarily in RDEB
  • Risk of melanoma:
    • cumulative risk of 2.5% by age of 12 years
    • EB naevi: large, irregularly shaped, darkly pigmented melanocytic naevi –> look like melanoma but histologically fine, large sign from onset a good clue
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8
Q

EBS localized - which areas

A

Palmoplantar

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9
Q

What subtypes can have inversa

A

JEB and DEB

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10
Q

Which subtype has reticulated hyperpigmentation

A

EBS with mottle hyperpigmenration

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11
Q

Which organs are involved for extracutaneous manifestation

A 
Ocular
Oral
GIT
GU
Respiratory
Cardiac
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12
Q

Clinical of localized EBS

A

Infancy and third decade of life with trauma or friction induced blistering - palms and soles. Associated palmoplantar hyperhidrosis. Infants can get blistering or ulceration from trauma which resolves with age.
EB Naevi common, variable pigmentation and irregular borders (activation of melanocytes due to tissue damage)
No scarring

Can have localized with nephropathy

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13
Q

EBS localized with nephropathy target protein

A

CD151

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14
Q

EBS intermediate clinical and subtypes

A 
Blistering starts at birth
Mild hands, feet and extremities
Worse in heat
Plantar keratoderma
EB naevi common
Hyperpigmentation, atrophy and milia
Thick or dystrophic nails

Can get with cardiomyopathy, and muscular dystrophy

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15
Q

EBS cardiomyopathy target protein

A

Kelch like member 24

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16
Q

EBS muscular dystrophy target protein

A

Plectin

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17
Q

EBS severe clinical

A 
Generalized, common on hands and feet
Herpetiform pattern of blisters
PPK --> confluent
EB naevi
Atrophic scarring, milia
Nails thick and dystrophic
Hair not affected
Mouth involved
Risk in first year: infection, malnutrition, resp failure
GORD
Growth retardation

Can get with pyloric atresia –> really severe

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18
Q

EBS with mottled pigmentation clinical

A

Generalized skin blistering of intermediate severity
Development of mottled/reticulate pigmentation not related to sites of blistering
Focal keratoses of palms and soles
Dystrophic, thickened nails

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19
Q

Junctional EB intermediate genes

A

LAMA3, LAMB3, LAMC2 etc

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20
Q

Junctional EB intermediate clinical

A 
Generalized blistering from birth, no chronic granulation tissue
Ulcerated skin may be present at birth
Risk of SCC in adulthood
EB naevi
Atrophic scarring, milia formation, dyspigmentation
Oral involvement
Nails dystrophic or lost
Scarring or nonscarring alopecia
Extra-c:
Eyes: corneal blistering, erosions, pannus, scarring
GIT and GU involvement
Anaemia
Growth retardation
Protein-losing enteropathy
Diarrhoea
Dental enamel defects
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21
Q

Severe junctional EB clinical

A

Blistering from birth, may initially be mild then become generalized. Almost all of body surface
Blisters rupture with extensive erosions
Chronic wounds with bed of friable granulation tissue - perioroficial, face, ears, distal digits, gluteal
Areas of ulcerated skin may be present at birth
Atrophic scarring, dyspigmentation
Onychodystrophy
Friable granulation tissue and soft tissue swelling of distal digits
Alopecia
Oral and laryngeal involvement: airway obstruction, etc
Ocular: scarring, etc
GIT: protein losing enteropathy, failure to thrive, anaemia
Dental enamel defects
Death in first 24 months due to FTT, sepsis or airway involvement
Osteoporosis

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22
Q

JEB with pyloric atresia target protein

A

Integrin alpha 6 beta 4

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23
Q

JEB with pyloric atresia linical

A

Gestational hydramnios
Full thickness skin loss
Pyloric atresia
Lethal within first few weeks

24
Q

JEB inversa clinical

A

Flexural blistering
Atrophic scarring, milia, dyspigmentation
Nail involvement
Dental abnormalities

25
Q

JEB with ILD and nephrotic syndrome target protein

A

Integrin alpha 3
ILD - soon after birth
Nephrotic syndrome: early death

26
Q

Target protein for DEB

A

Type 7 collagen

27
Q

Localized DDEB clinical

A

Acral and pretibial skin fragility
Increased risk SCC
EB naevi
Progressive nail dystrophy

28
Q

DDEB mutation

A

COLD7A1

29
Q

Intermediate DDEB clinical

A 
Generalized scar fragility, scarring and milia from birth or early childhood
Bony prominences: elbows,knees, ankles
Risk of SCC
May have EB naevi
Mucosal involvement
Nail dystrophy and loss due to trauma

Mucosal: oeosphageal, blistering and fissuring around anal margin
Ocular: conjunctival involvement and corneal scarring
Nutritional impairment from oesophageal involvement + metabolic demand from wounds
Constipation

30
Q

Intermediate RDEB

A 
Again bony prominences
Mutilating deformities
Keratoderma striate pattern
SCC
EB naevi

Mucosal: oeosphageal, blistering and fissuring around anal margin
Ocular: conjunctival involvement and corneal scarring
Nutritional impairment from oesophageal involvement + metabolic demand from wounds
Constipation

31
Q

Severe RDEB clinical

A 
Widespread, bony prominences
Congenital skin ulcerations
High risk of SCC
EB naevi
Extensive scarring and flexion contractures of large joints --> mitten deformities
Distal resorption of digits
Oral mucosa: microstomia, dental overcrowding
Nail dystrophy and loss
Scarring alopecia

Oesophgeal: strictures, protein losing enteropathy, anal involvement, corneal, urethral
Nutritional impairment
Anaemia
Osteopenia
Renal impairment: 10% risk of death by age 35 –> from outflow obstruction, FN, systemic amyloidosis, IgA nephropathy
Cardiomyopathy

32
Q

DDEB, pruriginosa clinical

A

tarts like localized or intermediate but becomes intensely pruritic - excoirated violaceous papules or linear plaques
Milia common
Nail dystrophy

33
Q

JEB generalized intermediate target antigen

A

Type XVII collagen

34
Q

Kindler syndrome target antigen

A

Kindlin-1

35
Q

What is the recommended diagnosis for EB now

A

genetic testing + IFM

36
Q

What are the methods for genetic testing

A
  • NGS - Next generation sequence targeting
    • Relatively rapid and effective
    • Allows for prenatal diagnosis
    • Can provide incidental information which may not be wanted
  • WES - Whole exome sequencing
    • May identify new variants of EB
    • Can cause incidental findings
  • SS - Sanger sequencing
    • Straightfoward approach if candidate genes are obvious or have been identified by IFM or TEM
    • Will miss variations in other EB genes
    • May be more time consuming
    • Requires pre-selction
37
Q

What is IFM?

A

Immunofluourescence antigen mapping

  • recommended to obtain a rapid diagnosis and prognosis, and to prioritize genetic testing
    • High specificity and sensitivity can be reached at relatively low costs
    • 4-6 mm punch or shave from an area not exposed to the sun (may create nonspecific background fluorescent, interfering with interpretation). Should include peri-lesional skin as well as a small part of a fresh blister
      • Can induce a blister before taking the biopsy or after with a suction syringe
      • Often a blister is created from the trauma alone
    • Put in Michels medium or liquid nitrogen, and ship ASAP as cell cytolysis can occur after just 48 hours
    • Then compared to normal human skin
    • Recommend doing with at least one antibody for each main type of EB, as well as for antibody type 4 collagen
    • Staining of the type 4 collagen to the floor of the blister is indicative of junctional or intraepidermal blister, whereas staining to the roof defined a dermal blister
    • If lack of blistering –> do a TEM
    • If genetic testing indicates something but no blistering –> keratinocytes/fibroblasts for expression and functional studies
    • Pros: easy, rapid, may indicate protein, prognostic helpful, but may be uninformative, doesn’t give a genetic test
38
Q

What is TEM?

A

Transmission electron microscopy

  • then cut into small pieces 0.5-1 mm thick, then further processing
  • Ligh microscopy examination of sections
  • Allows definition of blister level
  • Requires someone who knows a lot about it
  • Can also see clumping of tonofilaments etc which may be seen in EBS
  • Pros: identified ultrastructural stuff
  • Cons: uninformative can occur, time consuming, no genetic defect
39
Q

DDx for EB

A
  • pretty minimal ddx for chronic mechanobullous diseases
  • Acrodermatitis enteropathica
  • IP stage 1
  • Pachyonychia congenita
  • Early lipoid proteinosis
  • Acute blistering
  • Bart syndrome: EB and congenital locazlied absence of skin
  • Genoderms:
    • EBS skin fragility syndromes such as Woolly hair
    • Acantholytic EBS
    • Acral peeling skin syndrome (transglutaminase 5)
    • EBS superficialist
    • Superficial epidermolytic icthysosi
    • Epidermolytic ichthyosis
    • Gunther
    • Mendes da Costa
    • AEC
40
Q

EB management principles

A
  1. Prevention of mechanical trauma
  2. Wound care
    1. Soft silicone dressings are wildly used
    2. Silver-impregnated dressing good –> but don’t use long term due to silver absorption
  3. Infection avoidance
    1. Bathing or soaking with 0.005% sodium hypochlorite in a full standard or 0.25% acetic acid
    2. Antibiotics - only use when needed
    3. Hyperhidrosis treatment: aluminium chloride hexahydrate, botox
41
Q

EB dressing recommendations

A

Soft silicone: mepilex, mepitel, for primary or secondary
Non-adherent lipido-colloid dressings
Hydrogel dressings - provide moisture to drier wounds
Foam dressings - absorb moderate amounts of wounds - Mepilex, Allevyn
Absorptive dressings - for heavy exudate
Silver containing dressings - for colonized or infected - Mepilex

42
Q

Systemic agents for EB management

A
  • Phenytoin: for JEB and RDEB, not effective in RCTR
  • Tetracyclines or erythromycin for EBS
  • Thalidomide and cyclosporin in DEB pruriginosa
  • Systemic retinoids: jury is out as to whether prevents SCCs in this group
43
Q

Excessive caries management

A

Oral hygiene
Antiseptic and fluoride
Dentist

44
Q

Microstomia management

A

Physical therapy

Mouth expanding devices

45
Q

Oral ulceration management

A

Topical antiseptics
NSAIDs
barriers

46
Q

GIT management

A

Dietary modification
PPI
H2 blocker
Gastro

47
Q

Nutritional management

A

Check growth and vitamins and minerals

Refer to dietician

48
Q

Anaemia management

A 
Monitor
Iron 
EPO
Transfusion
gen paeds
49
Q

Urinary outflow obstruction

A

Annual USS of UT

urology

50
Q

Renal disease mgmt

A

Monitor every 6 months - U/A, UEC, BP

51
Q

Osteopaenia management

A

Annual DEXA scan at age 5 on for RDEB and JEB, calcium and vitamin D
Consider bisphosphonate

52
Q

Pseudosyndactyly of hands/feet management

A

Splints
Wrapping of fingers in RDEB
Surgeons

53
Q

SCC monitoring

A

Skin exams for RDEB every 3-6 months starting from age 10, and every 3 months after 16 years
Serial photos

54
Q

Ocular management

A

Ophthal –> can do amniotic membrane transplantation

55
Q

When to monitor for cardiac

A

Annual TTE in late childhood for RDEB

56
Q

Pathogenesis of Kindler syndrome

A
  • Basement membrane reduplication and mixed planes of cleavage: can be in stratum basale, lamina lucida, lamina densa
  • FERMT1 mutation: involved in actin filaments in basal keratinocytes to underlying ECM
  • Kindlin-1: affects keratinocyte normality, and also regulates stem cell homeostasis –> increased risk of skin cancer if gone
57
Q

Kindler clinical

A
  • At birth - forearms, shins
  • Blistering - hands and feet
  • Skin fragility - decreases with age
  • Photosensitivity - increased burning, reticulated hyperpigmentation, telangiectasias in sun exposed sites –> moves to sun protected sites
  • Poikiloderma: persists throughout life
  • Mild webbing
  • Palmoplantar hyperkeratosis
  • Eczema –> resolves by early childhood
  • Extracutaneous:
    • Erosive gingivitis and poor dentition
    • Intraoral and corneal scarring, ectropian, colitis
    • Strictures of oesophagus, urethra, vagina, anus
  • Increased risk of SCC

Derm (57 decks)

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