Chapter 33 - Epidermolysis Bullosa Flashcards
What are the three main types of inherited epidermolysis bullosa (EB)?
Simplex, junctional, and dystrophic
True or false: any epithelial-lined organ is at risk of involvement in the severe forms of inherited EB.
True
How are most forms of EB simplex inherited?
Autosomal dominant inheritance
Which two molecules are most commonly involved in the various types of EB simplex?
Keratin 5 and 14
Mutations in either K5 or K14 are typically involved in EB simplex, however EB simplex with muscular dystrophy is an exception. Which protein is affected in this form of EB simplex?
Plectin
How is junctional EB inherited? What is the exception?
Autosomal recessive inheritance; there is no exception (they’re all AR)
What protein is mutated in the most severe form of junctional EB, Herlitz subtype?
Laminin 332
What are the two possible proteins that can be mutated in JEB-non-Herlitz type?
Laminin 332 and BP2
What are the three major eponymously named subtypes of EB simplex?
Weber-Cockayne EB simplex, Koebner EB simplex, and Dowling-Meara EB simplex
Where do blisters form in the simplex types of EB?
Within the basal keratinocyte layer
True or false: hemidesmosomes are absent in the Herlitz type of junctional EB.
True
True or false: hemidesmosomes are absent in the non-Herlitz type of junctional EB.
False; however they are reduced in number and rudimentary in appearance
True of false: anchoring fibrils appear rudimentary in dominant dystrophic EB.
False; they appear normal in size in structure (although they are, of course, functionally abnormal)
True or false: anchoring fibrils are completely absent in the Hallopeau-Siemens subtype of recessive dystrophic EB.
True
True or false: in the non-Hallopeau-Siemens subtypes of recessive dystrophic EB the anchoring fibrils are drastically reduced in number, and if present, appear rudimentary.
True
What two proteins could be mutated in JEB-non-Herlitz type EB?
Laminin 332 or BP2
True or false: BP2 and collagen VXII are the same molecule.
True
What protein is mutated in JEB with pyloric atresia?
Either of the genes that code for alpha6-beta4
True or false: dystrophic EB can be inherited in either an AR or AD way.
True
True or false: patients with recessive dystrophic EB have an increased risk of BCC.
False; they have an increased risk of SCC
How quickly do blisters typically form in patients with EB after mechanical trauma? Within minutes, hours, or days?
Within minutes
Which type of EB is characterized by exuberant granulation tissue of the periorificial skin?
Herlitz subtype of JEB
Other than the skin, which other body tissues can be affected by EB?
Any tissue with an epithelial lining, including the eye, oral cavity, GI tract (excluding the stomach), and GU tract
What dental feature is characteristic of all forms of JEB?
Enamel hypoplasia; if untreated, the teeth are lost during childhood
Which type of EB most commonly develops pseudosyndactyly (mitten deformities of the hands and feet)?
Primarily recessive dystrophic EB, especially the Hallopeau-Siemens subtype, although it may also occur in dominant dystrophic EB and junctional EB
What protein is mutated in JEB with pyloric atresia?
Alpha6-Beta4
In which type of EB is there a risk of acute airway obstruction due to blisters within the trachea?
JEB; tracheostomy is considered standard-of-care
True or false: light microscopy has no role in the diagnosis of inherited EB.
True
What is another term of congenital localized absence of skin (CLAS)?
Aplasia cutis congenita
What two features characterize Bart’s syndrome?
Aplasia cutis congenita in combination with any type of EB
What are the 3 major forms of inherited epidermolysis bullosa?
1) simplex, 2) junctional, 3) dystrophic
What are the 4 subtypes of EB simplex?
1) Weber Cockayne, 2) Koebner, 3) Dowling-Meara, 4) EBS generalized with muscular dystrophy. There are also 5 minor subtypes including (5) EBS superficialis, (6) EBS with mottled pigmentation, (7) EBS-Ogna, (8) EBS pyloric atresia, (9) EBS-autosomal recessive
What are the 3 subtypes of junctional EB?
1) JEB-Herlitz, 2) JEB-non-Herlitz, 3) JEB with pyloric atresia. There are also 2 minor subtypes: (1) JEB inversa, (2) JEB localized
What are the targeted proteins in JEB-Herlitz, non-Herlitz, and with pyloric atresia subtypes?
1) JEB-H laminin 332, 2) JEB-nH laminin 332/BPAG2/type XVII collagen, 3) JEB-PA alpha4beta4 integrin
What is the inheritance pattern for EBS?
Autosomal dominant (negative mutations for keratin 5 or 14), except for generalized EB simplex with muscular dystrophy, where it is autosomal recessive with mutation for plectin
What is the inheritance pattern for JEB?
Autosomal recessive
What is the targeted protein in DEB?
Type VII collagen
What are the 3 major subtypes of dystrophic EB?
1) Dominant DEB, 2) recessive DEB Hallopeau-Siemens, 3) recessive DEB non-Hallopeau-Siemens
Other than scarring, what other types of cutaneous findings can you find in patients with EB?
Nail dystrophy, nail absence, milia, scarring alopecia
Name the 6 minor subtypes of DEB.
1) DDEB pretibial, 2) DDEB pruriginosa, 3) RDEB inversa, 4) RDEB centripetalis, 5) DEB transient bullous dermolysis of the newborn, 6) DEB autosomal dominant/autosomal recessive heterozygote
What extracutaneous finding is characteristic of all forms of JEB?
mel hypoplasia (ie. pitting oof teeth, teeth loss if untreated)
What extracutaneous finding is characteristic of RDEB, especially of the HS subtype?
Psuedosyndactyly (mitten deformities of hands, feet)
What 2 diagnostic tests are routinely used in diagnosis of inherited EB?
Transmission electron microscopy, immunofluorescence antigenic mapping. Either may be used as the gold standard
What is the treatment for EB?
No specific treatment. Day-to-day symptomatic management including prevention of mechanical trauma and infection. Antibiotics (topical, PO) for infections, aluminum chloride hexahydrate for hyperhidrosis, artificial dressings for wounds, etc. Watch out for depression!
What are the three major features shared by all forms of EB?
- Genetic transmission
- Mechanical fragility of the skin
- Blister formation
What form of EBS does not involve k5 and k14?
Generalized EBS with muscular dystrophy
Plectin
What is the other name of JEB-non-Herlitz?
GABEB
Generalized atrophic benign EB
Where is the mutation in the different types of JEB?
JEB-Herlitz = laminin 5
JEB-non-Herlitz = laminin 5 and BPAg2
JEB with pyloric atresia = a6b4 integrin
What is the leading cause of death in EB?
SCC
What are the gold standard for the diagnosis of inherited EB?
- Transmission electron microscopy
2. Imuunohistochemisty (immunofluorescence antigenic mapping)
