60 - Inherited Epidermolysis Bullosa Flashcards
Blistering level categories in inherited EN
Simplex
(Hemidesmosomal)
Junctional
Dystrophic
Major constituent of anchoring fibrils
Collagen VII
Traditionally the diagnostic gold standard for grouping EB
Electron microscopy
Characterized by intraepidermal blistering and most often id associated with keratin gene mutations
EB simplex
Major EBS types
Generalized severe (Dowling-Meara) Generalized intermediate (Koebner) Localized (Weber-Cockayne)
Most severe form of the EBS subtypes
Generalized severe EBS (Dowling Meara)
Heat exacerbates the blistering in EBS subtypes except
Generalized severe EBS (Dowling Meara)
Generalized severe EB differs from the generalized intermediate variant in that the ______ is more often involved
Oral mucosa
Most common form of EB
Localized EBS (Weber-Cockayne)
Hyperhidrosis of the palms and soles is a common association with
Localized EBS (Weber-Cockayne)
Milia and scarring as a rule are absent
Localized EBS (Weber-Cockayne)
Blistering activity in localized EBS is most common on the _____ and least common on the _____
Hands and feet
Scalp
Seasonal blistering (summer) on the acral areas
Healing occurs without scarring
Characteristic onychogryphosis of the great toenails
EBS of Ogna
Generalized blistering of the skin at birth or shorty thereafter
Accompanied by progressive muscular dystrophy
EBS with muscular dystrophy
EBS with muscular dystrophy patients have been shown to harbor mutations in the gene coding for
HD1/plectin
Characterized by mottled hyperpigmentation of the trunk and proximal extremities with blistering in a generalized distress beginning at birth or early infancy
EBS with mottled pigmentation
Named after the subcorneal separation that produces the blisters in this disease
Erosions and crusts, rather than intact bullae m, are usually seen
EBS superficialis
Lethal disorder
Characterized by generalized erosions at birth with a very superficial level of separation, which has been described as sheetlike
Alopecia, neonatal teeth, oral erosions, and respiratory involvement distinguish this disorder from other superficial EBS subtypes
Acantholytic EBS
Suprabasilar epidermal separation characterized by generalized erosions and sometimes superficial blisters
Plakophilin deficiency or ectodermal dysplasia skin fragility syndrome
BP230 deficiency is caused by mutations of the
DST-e gene
Has beed described in a small collection of Kuwaiti and Iranian families
Localized, often affecting the feet
BP230 deficiency
Exophillin-5 deficiency is caused by mutations of the
EXPH5 gene
Trauma-induced crusting or fragile blisters and vesicles
Remission during childhood is characteristic of this disease
Exophillin-5 deficiency
Superficial and painless skin peeling most commonly on the hands and feet
Humidity, heat, and water exposure can exacerbate this condition
Acral peeling skin syndrome
Level of separation in acral peeling syndrome
Between the stratum granulosum and startum corneum
Most of the patients with EBS have been found to be associated with mutations of the genes coding for
Keratins 5 and 14
Majority of keratin gene mutations associated with EBS are _____ inherited
Domintantly
Ectodermal dysplasia skin fragility syndrome involves loss-of-function mutations in the _____ gene coding for _____
PKP1
Plakophilin 1
Plakophilin is expressed mainly in
Suprabasilar keratinocytes
Outer root sheath cells
Acral peeling skin syndrome is caused by mutations of _____, which produces alterations of _____ expression
TGM5
Transglutaminase
Blister formation within the lamina lucida of the BMZ
Junctional EB
Junction EB mode of unheritance
Autosomal recessive
Principal forms of junctional EB
Generalized severe JEB (previously termed Herlitz disease, JEB gravis, or lethal JEB) Generalized intermediate JEB (nonlethal JEB or JEB mitis) Localized JEB (minimus JEB)
Most common subtype of JEB
Generalized severe JEB
Results in lethality during infancy or early adulthood
Distinctive periorificial granulation manifests later during infancy
Involvement of the large airways including tracheolaryngeal stenosis or obstruction
Failure to thrive
Growth retardation
Sepsis
Generalized severe JEB
Lack of lethality in infancy
Lack of significant hoarseness is regarded as a favorable prognostic sign
Generalized intermediate JEB
Distinct subset of generalized intermediate JEB
Heal with a characteristic atrophic scarring
Progressive alopecia of the scalp and terminal hairs
Generalized atrophic benign EB
Characterized by nail dystrophy, cutaneous erosions, and extensive granulation tissue, especially localizing to the conjunctiva and larynx
Laryngo-onycho-cutaneous syndrome
Characterized by blisters that heal with scarring and milium formation from sublamina densa separation
Dystrophic EB
DEB mode of inheritance
Autosomal recessive or dominant
One of the most important reasons to distinguish between recessive or dominant DEB
Increased prevalence of invasive SCC associated with the recessive form
DEB is derived from defects of the
Anchoring fibril
Localized autosomal dominant DEB is also called
Cockayne-Touraine of DDEB
Generalized autosomal dominant DEB is also called
Pasini subtype of DDEB
Distinguished by the spontaneous appearance of distinctive scarlike, flesh-colored papules on the trunk (albopapuloid lesions)
Generalized autosomal dominant DEB
Self-remitting generalized DDEB
Biopsy often shows basal epidermal intracytoplasmic accumulations of collagen VII
Bullous dermolysis of the newborn
Localized recessive DEB is also known as
RDEB mitis
Severe recessive DEB is also known as
Hallopeau-Siemens
Congenital absence of the skin
Bart syndrome
DEB has been shown to be associated in all cases thus far with mutations of the gene coding for
collagen VII (COL7A1)
EB-like trauma-induced blistering at birth and during infancy, with atrophic changes during healing reminiscent of JEB or DEB
Kindler syndrome
Most consistent feature seen in Kindler syndrome
Reduplication of the basement membrane
Y/N: Routine histologic analysis can be used to diagnose EB
No - Routine histologic analysis cannot be used to diagnose EB but can be useful for excluding other causes of blistering
It is best to place the circular biopsy punch so that only _____% of the punch covers the visible blister with _____% covering intact skin
10
90
Clumping of keratin intermediate filaments in basal keratinocyte cytoplasm is a pathognomonic finding for
Severe generalized (Dowling-Meara) EBS
Rudimentary hemidesmosomes can be an important clue to the disgnosis of
JEB
Absent or altered anchoring fibrils often occur in
DEB, especially the recesive forms
EB variant most in need of surgical intervention
Severe recessive DEB (Hallopeau-Siemens)
Has been used for patients with RDEB for chemoprevention of SCC
Isotretinoin
Patients with EBS, particularly those with the _____ subtype, can experience recurrent inflammation of the eyelid, with bullous lesions in the conjunctivae
Dowling-Meara
Devastating and potentially fatal complication of severe DEB and JEB that is highly associated with chronic anemia
Dilated cardiomyopathy
Shown promise in reducing the fibrosis accompanying DEB wounding by reducing transforming growth factor-beta in the skin
Losartan
Often the most disabling complication found in recessive DEB and JEB of both the severe and intermediate generalized variants
Esophageal lesions
