Epidermolysis Bullosa Dan Flashcards
what are the 4 major types of EB?
Simplex
Junctional
Dystrophic
Kindler syndrome
T/F EB types share 3 features; Genetic transmission Skin fragility Blister formation
T
T/F there are >15 distinct clinical phenotypes of EB and >30 different proteins may harbour the causative gene mutation
F
numbers are the other way around
there are several genes for some of the proteins so there are more genes than there are proteins
T/F
EB affects;
20 per million live births
8 per million of the population
T
T/F
EB simplex has a suprabasal split
T
T/F
Junctional EB split is sublamina densa
F
Junctional EB split is in lamina lucida of BMZ
Dystrophic EB split is sublamina densa
T/F
In kIndler syndrome the level of the split is variable within the BMZ
T
T/F
Most cases of EB Simplex (EBS) are autosomal recessive
F
most AD
but several AR types esp EBS-MD and several rare types
What are the major subgroups of EBS?
Basal and suprabasal
Can also be divided as common and rare
T/F
In Junctional EB (JEB) the lamina densa remains firmly attached to the dermis and forms the base of the blisters
T
What are the subgroups of JEB?
Generalized or localized
Can also be divided as common and rare
JEB is almost always AR
T
one reported kindred AD
T/F
JEB is due to mutations in laminin332, BP230 or α6β4-integrin
F
laminin332, BP180 (collagen 17) or α6β4-integrin
remember 17, 18 (180) are the same
T/F
All dystrophic EB (DEB) is due to mutations in gene for collagen 17
F
collagen 7
What are the subtypes of DEB?
Dominant or Recessive
Can also be divided as common and rare
T/F
there are 3 most common subtypes in each of the 3 major categories of EB
T
What are the most common types of EBS?
EBS-generalized severe. Formerly Dowling-Meara
EBS-localized. Formerly Weber-Cockayne
EBS-Generalized intermediate. Formerly Koebner
T/F
the 3 most common types of EBS are all AD due to mutations in keratin 5 or 14
T
The one more common recessive types is EBS with muscular dystrophy (EBS-MD) due to plectin mutations
What are the most common types of JEB?
JEB-generalized severe. Formerly Herlitz
JEB-generalized intermediate
JEB-localized
generalized intermediate type includes types previously known as; JEB-non-Herlitz, JEB-gen other and Generalized Btrophic Benign EB (GABEB)
NB JEB-PA with pyloric atresia used to be considered a major group but is actually rare
What are the most common types of DEB?
DDEB-generalized. Formerly known as Pasini or Cockayne-Touraine type
RDEB-generalised severe. Formerly Hallopeau-Siemens
RDEB-generalised Intermediete. Formerly RDEB-non-Halllopeau-Siemens or RDEB-gen other
T/F
Kindler syndrome is a rare AD form of EB due to mutations in the Kindlin 1 gene which can alos be classes as a Poikilodermatous genodermatosis
F
AR
all the rest true
gene code is KIND1 AKA FERMT1
T/F
In Kindler syndrome skin cleavage occurs in mixed planes – within and/or beneath BMZ
T
T/F
Kindler syndrome can look like other classical types of EB esp JEB-PA or RDEB types or like other poikilodermas
T
What are the features of KIndler syndrome?
Photosensitivity
Skin atrophy & poikiloderma
Trauma-induced blistering – lessens with age
May have nail dystrophy and pseudosyndactyly and PPK
Mucosal inflammation and stenosis (oesophageal, anal, urethral, vaginal) – colitis, oesophagitis, gingival hypertrophy, ectropion
Increased risk of SCC of skin and mucosae after age 30
Mx is symptomatic like other EB types + strict photoprotection
What is ‘EB with congenital absence of skin’ formerly Bart syndrome?
Any type of EB with aplasia cutis congenita
e.g JEB-PA
Unusual for aplasia cutis congenita as involves acral sites rather than scalp
T/F
The genes involved in EBS encode major scaffold proteins of basal keratinocytes
T
True for basal types
Suprabasal types affect higher keratinocyte layers, just beneath SC
T/F
EB kids often don’t crawl
T
bottom shuffle and reach then start walking
T/F
atrophic scarring occurs in most cases of EB
F
Only in 15% of EBS cases
More in subtypes with BMZ destruction or with generalized cutaneous and extracutaneous disease e.g. RDEB
Reticulated hyperpigmented macules are seen in which type of EB?
EBS with mottled hyperpigmentation (EBS-MP)
similar appearance may be seen in EBS-AR exophilin 5
T/F
Scalp and lower leg lesions are typical of all forms of dystrophic EB
F
typical of Junctional EB
T/F
dystrophic or absent nails are common in JEB
T
exuberant granulation tissue is typical of which form of EB?
JEB esp gen sev (Herlitz)
What are the types of superficial EBS?
Acral peeling skin syndrome (APSS)
EBS superficialis
Acantholytic EBS
Skin fragility syndromes (3 syndromes)
What are the genes and inheritence for superficial EBS?
Autosomal recessive (except EBS-superficialis; inheritance unknown) Mutations in plakophilin-1, plakoglobin or desmoplakin or Transglutaminase 5 (APSS)
What are the 3 major skin fragility syndromes?
Desmoplakin deficiency (EBS-desmoplakin; skin fragility-woolly hair syndrome) Plakoglobin deficiency (EBS-plakoglobin; skin fragility-plakoglobin deficiency) Plakophilin deficiency (EBS-plakophilin; skin fragility-ectodermal dysplasia syndrome)
Grouped herpetiform blisters in arcuate or polycyclic arrangement are characterisitic of what type of EB?
EBS generalized severe (EBS-gen sev; Dowling Meara)
widespread when younger - resembles Hailey-Hailey
When older, blisters occur in clusters esp around fingertips and in mouth
Which types of EB get EB naevi?
EBS generalized severe EBS generalized intermediate JEB generalized intermediate - most at risk RDEB generalized severe RDEB generalized intermediate
Albopapuloid lesions are typical of which type of EB?
DDEB generalized
T/F
Enamel hypoplasia and caries are most associated with dystrophic EB
F
Junctional EB
Which types of EB are at risk of skin cancers?
EBS generalized intermediate - melanoma; low risk
JEB-gen intermediate - high SCC risk (25% if >25yrs)
JEB-gen sev - low SCC risk
RDEB-gen sev - SCC risk if survive, Inc melanoma risk
RDEB-gen intermediate - significant SCC risk
RDEB or DDEB pretibial - small SCC risk
DDEB pruriginosa - small SCC risk
T/F
EBS-localised mainly affects the palms and soles
T
Blisters from trauma or spontaneously in hot/humid weather
may develop focal keratoderma by adulthood
25% get oral erosions
usually no other features
T/F
EBS generalized severe develop diffuse keratoderma
T
T/F
EBS generalized intermediate has widespread blistering at birth but educes with age – later hands and feet most problematic
T
may develop focal keratoderma
T/F
EBS with muscular dystrophy (EBS-MD) always develop muscular probelsm before skin problems
F
More often skin presents first
blisters either at birth or in early childhood
Muscular dystrophy may present in infancy or not until adulthood
T/F
EBS with muscular dystrophy (EBS-MD) have a reduced life span
T
often die before age 30
T/F
EBS w/ pyloric atresia (EBS-PA) is usually due mutation in α6β4-integrin genes
F
usually plectin gene but can be
α6β4-integrin genes (ITGA6 or ITGB4)
NB JEB-Pyloric atresia (JEB-PA) is due to mutation in α6β4-integrin genes
What are the rare typs of EBS and their genes?
Rare-basal;
EBS w/ pyloric atresia - plectin or α6β4-integrin
EBS w/ mottled pigmentation - Keratin 5
EBS, migratory circinate - Keratin 5
EBS-Ogna - plectin
EBS-Autosomal recessive Keratin 14
EBS-Autosomal recessive-BP230 deficiency
EBS-Autosomal recessive-exophilin 5 deficiency
Suprabasal - all rare;
Acral peeling skin syndrome - Transglutaminase 5
EBS superficialis - unknown
Acantholytic EBS - desmoplakin or plakoglobin
Skin fragility syndromes (3 syndromes);
EBS-desmoplakin; skin fragility-woolly hair syndrome
EBS-plakoglobin; skin fragility-plakoglobin deficiency
EBS-plakophilin; skin fragility-ectodermal dysplasia syndrome
T/F
Acral peeling skin syndrome is the same as Oudtshoorn disease
F
both are peeling skin syndromes
Oudtshoorn disease = Erythrokeratolysis hiemalis - AD but gene unknown; mainly palms and soles but extends elsewhere; S African kindreds
T/F
Neonatal teeth are seen in acantholytic EBS due to plakoglobin mutation
F
seen in acantholytic EBS due to desmoplakin mutation
also get oral erosions and cardiomyopathy
T/F
All 3 skin fragility syndromes present with generalized blistering at birth or in infancy + hypotrichosis + Woolly hair + focal keratoderma with fissuring (can be punctuate or striate in desmoplakin deficiency)
T
T/F The following are commonly seen in JEB types; Alopecia exuberant granulation tissue GU tract involvement
T
What are the affected proteins/genes in the common types of JEB?
JEB-generalized severe - Laminin 332 protein - genes; LAMA3, LAMB3, LAMC2
JEB-generalized intermediate - Laminin 332 or Collagen 17 protein (=BP180, BPAg2) – gene COL17A1
JEB-localized - Collagen 17 protein
T/F
about 50% of affected infants with JEB-generalized severe or intermediate dont survive beyond age 2
T
death due to laryngeal erosion, resp distress, uncorrectable failure to thrive, chronic wounds and sepsis
T/F
JEB-generalized severe has a higher SCC risk than JEB-gen intermediate
F
In JEB-gen intermediate up to 25% risk of SCC in pts surviving after age 25
SCC uncommon in JEB-generalized severe
T/F
JEB-localised mainly affects acral sites and oral and has amuch better prognosis than other common JEB types
T
What are the rare types of JEB?
Generalised;
JEB-PA - α6β4-integrin
JEB late onset - Collagen 17
Localised:
JEB with respiratory and renal involvement - integrinα3
Laryngo-onycho-cutaenous (LOC) syndrome - laminin 332
JEB inversa - laminin 332
T/F
JEB late onset get symptoms in late middle age
F
usually young adults but can be older
T/F
JEB late onset have rudimentary ears
F
JEB-PA have rudimentary ears
also
Can be pyloric, duodenal or anal atresia; Rare individuals lack the pyloric atresia
May be large areas of aplasia cutis
Severe urogenital tract involvement and malformations – congenital and acquired from disease
often fatal in infancy
T/F
JEB-PA always have GI tract atresia
F
Can be pyloric, duodenal or anal atresia
But rare individuals lack atresia
T/F
JEB-inversa affects intertriginous areas
T
also nail dystrophy
T/F
JEB-LOC (Laryngo-onycho-cutaneous syndrome) is more common in parts of Indian subcontinent
T
Punjab - composed of parts of India and Pakistan
T/F
DDEB-generalized is more severe than JEB-gen, sev
F
less severe
T/F
RDEB-generalised severe is the most severe form of EB
T
severe skin disease, atrophic scarring and contractures; develop pseudosyndactyly
T/F
DDEB-generalized is very itchy
F
RDEB-gen sev is very itchy
DDEB-pruriginosa is very itchy
What are the features of RDEB-gen sev?
formerly Hallopeau-Siemens always most severe skin disease, atrophic scarring and contractures; develop pseudosyndactyly recalcitrant pruritus and pain granulation tissue and EB naevi Corneal blisters, ulcers and scarring severe systemic disease affecting most systems (GU, GIT, ocular, oral) and anaemia and growth failure usually die early SCC risk if survive
T/F
RDEB-gen intermediate is mild with a good prognosis
F
Less severe than RDEB-gen sev but still severe skin disease widespread blistering and scarring with finger webbing but rarely pseudosyndactyly
EB naevi
Oral involvement and increased caries also GI involvement but usually spares other systems
Growth retardation
Significant risk of SCC and of early death
What are the rare types of DEB?
RDEB or DDEB localised RDEB or DDEB pretibial RDEB or DDEB-bullous dermolysis of the newborn (RBDN) DDEB pruriginosa DDEB localised nails only RDEB inversa RDEB centripetalis
Which types of EB get pseudosyndactyly?
JEB-gen sev
RDEB-gen sev
RDEB-gen intermediate
T/F
Atrophic or lichenoid papules or plaques esp on shins are typical of RDEB or DDEB -pretibial
T
But DDEB-pruriginosa may mimic due to effect of scratching++ on shins
Which types of EB get ectropion?
JEB-gen sev
Kindler
not Dystrophic but they get severe eye disease
T/F Microstomia and/or ankyloglossia (tongue tie) may be seen in; RDEB-gen sev(>50%) RDEB-gen intermediate JEB-gen sev
T
T/F
Tracheolaryngeal stenosis occurs most commonly in RDEB-gen intermediate
F
JEB-gen sev >50%
can be seen in JEB-gen intermediate
T/F
Oesophageal strictures occurs most commonly in JEB-gen sev
F
most commonly in RDEB-gen sev or RDEB-gen intermediate
can occur in JEB-gen sev or Kindler
T/F
RDEB-gen sev has 12% risk of death from renal failure before age 35
T
Get CRF due to glomerulonephritis, obstruction or renal amyloidosis
T/F
Dilated cardiomyopathy is seen in RDEB-gen sev
T
less than 50% of cases
thought that deficiency of selenium or carnitine may be a contributing factor
T/F
SCC is leading cause of death in EB patients from mid-adolesence onwards
T
Often die within 5 years of first SCC diagnosis
T/F
The risk of SCC in severe forms of EB goes up significantly after age 20
T
20 = 7.5%
35 = 68%
and continues to rise; 90% at age 55
T/F
RDEB-gen sev has a cumulative risk of melanoma of 5% by age 12
F
2.5%
T/F
EM alone can distinguish the subtypes of EB
F
Need to use EM combined with IF (Immunofluoresence antigenic mapping)
T/F
EM samples go in 10% gluteraldehyde
F
2.5%
T/F
EMLA should be avoided prior to EB biopsies
T
don’t use EMLA as it can induce changes that mimic epidermolysis bullosa simplex
When working up a case of EB what information is needed?
Good clinical Hx - usually from parent
e.g. age of onset, sites most affected
Systems rw - ?eyes, oral, GI, GU problems
aska bout anaemia and growth
Must ask about FHx and map family tree to help diagnose inheritance
Examine skin for blisters, milia, atrophic scarring, granulation tissue, pseudosyndactyly, keratoderma, secondary infection, skin cancers, EB naevi
Nails for dystrophy or loss
scalp for alopecia
eyes for ectropion, ulcers, scarring
mouth for erosions, hypoplasic enamel, tooth decay
Biopsy - H+E, IF, EM
Mutational gene analysis
What are the differentials for blistering in infants?
SSSS, herpes simplex, bullous impetigo sucking blisters bullous mastocytosis autoimmune bullous disease (e.g. neonatal pemphigoid) congenital erosive and vesicular dermatosis Incontinentia pigmenti Icthyosis bullosa of Siemens, BCIE, Congenital erythropoietic porphyria AEC syndrome Mendes da Costa syndrome
What is the ‘onion skin’ method of classification and diagnosis in EB?
Major EB type (e.g. JEB) Phenotype - severity + distribution (e.g. gen sev) Ultrastructural site of cleavage (e.g. lamina lucida) Protein involved (e.g. laminin 332 absent) Gene involved (e.g. LAMA3) Specific mutation (e.g. missense)
What are the principles of managing EB?
Need specialist clincis with dedicated specialist nurses and an MDT of Derm, nurse, physio, OT, speech pathologist etc
Education for family and patient
Prevent mechanical trauma
Strict photoprotection for Kindler and types at risk of skin cancer esp RDEB
Dressings for blisters
Prevent infection
Pain management
Monitor for and manage complications
Prenatal testing for known patients or carriers planning
Pt/family support groups are hugely beneficial families
Some pts/families need psychiatric care/ counselling etc
What skin measures are considerd in EB?
Strict photoprotection for Kindler and types at risk of skin cancer
Prevent infection - bleach or vinegar baths
- treat infection if present but avoid chronic topical antibiotics as risk of resistance and ACD
Avoid trauma
Treat hyperhidrosis if present – driclor, botox etc
Rw and examine regulalry as determined by severity
DEB pruriginosa has been treated with CsA or thalidomide to relieve symptoms
Systemic retinoids have been used in RDEB to reduce SCC formation
Dressing guidance;
Non-adherent
Foam backed e.g. mepilex/mepitel often used
Xeroform/jelonet etc useful for non-infected wounds
Exudative wounds – allevyn, mepilex
Silver dressings for short term use only (risk of silver absorption)
dress fingers/toes individually
Pseudosyndactly is treated with splinting
What systemic monitoring is needed for EB?
Depends on type - determines risk of complications
refer to appropriate specialist if concerns
Infants need close monitoring of height, weight, BMI and growth
Severe types need to periodically assess zinc, selenium, iron, vit D, carnitine etc – ideally have specialist paediatric dietician involved
RDEB pts need FSE every 3-6 months from age 10 and every 3 months minimum for age 16
RDEB need 6 monthly urinalysis
RDEB and JEB pts need regular DEXA and spine Xrays from age 5 + calcium and Vit D
What dressings are used for neonates with suspected EB?
Polymem first choice for wounds other than nappy area
- Polymeric membrane dressing; change when wet as determined by exudates level
Intrasite comfortable first choice for nappy area wounds
- Hydrogel impregnated gauze dressing; Change when dry
May need to use a contact layer underneath e.g. Mepitel silicone mesh
If very traumatized area or very exudative use a secondary dressing layer of silicone foam e.g. Mepilex or mepilex lite (not mepilex border as has adhesive border)
Can do dressings one limb at a time
Dress digits individually if any skin loss
Irrigate dressings off with warm saline if required
T/F
Plastic clingfilm/gladwrap should never be used on neonates with suspected EB
F
Plastic clingfilm/gladwrap should be used prior to receiving specialist dressings
T/F
You should Never lift an EB baby from underneath the arms
T
T/F
EB neonates should go in an incubator
F
Do not use incubator unless necessary
humid env increases blistering
T/F
EB neonates should be bathed daily from birth
F
Avoid bathing for first few weeks while birth trauma heals
T/F
It is fine for EB neonates to breast feed
T
use a Pigeon cleft palate bottle if not breast fed
T/F
EB neonates should be handled with aseptic technique
F
Use non-touch/clean technique when handling baby (aseptic technique not necessary)
What are tips for looking after EB neonates?
nurse the baby in a cot laying the child on a soft pad or neonatal incubator mattress
Use a ligature rather than a cord clamp – replace if cord already clamped
Do not attach hospital ID to baby – put on clothing
Dress babies in loose jumpsuits turned inside out
When handling baby use non-sterile gloves with fingertips wet with water or saline or dermeze
Never lift an EB baby from underneath the arms
Avoid adhesive dressings or tapes – use non-adherent silicone tape to secure lines etc (mepiform/mepifilm)
Avoid tourniquets and rubbing of skin
If sticking electrodes etc used, remove with Niltac silicone medical adhesive remover and do not peel off
Cleanse nappy area w/ dermeze – don’t use wipes
Line nappy with liner cut from polar fleece
Prescribe appropriate analgesia
Lance tense blisters w/ sterile hypodermic and express fluid with gauze compression
T/F
cornflour can be used on eosions in infants with EB
F
can apply cornflour to dry blisters out after lacing but don’t apply to open erosions
