Epidermolysis bullosa (EB) refers to a series of hereditary disorders characterized by fragility of the skin and mucous membranes and the tendency of the skin to blister in response to minor friction or trauma. Some patients experience blistering since birth, while others present clinical manifestations later in life.
The severity of presentation in a newborn does not indicate prognosis; thus, clinical classification based on morphology alone at this age should not be attempted.1 Even later in life, classification based only on clinical findings is difficult, as the same type of EB may range from very mild to severe clinical findings.2,3 The clinical picture depends not only on the level of split, but also on the type of mutation that a particular patient has; the same genetic abnormality can be associated with different clinical features.4
Classification of Epidermolysis Bullosa
The first attempt at classification of this condition was made by Pearson, who proposed three broad categories of presentation according to the location of the skin separation: epidermolytic, lamina lucidolytic and dermolytic.5
Three types of EB. In 1989, the first consensus meeting on the diagnosis and classification of EB took place.6 The meeting resulted in a classification that lasted for almost a decade, separating EB into:
1. simplex
2. junctional
3. dystrophic.
The different forms of the disease were further subclassified according to their clinical presentation and mode of transmission leading to 23 different clinical pictures.7
New findings explaining the molecular basis of many of these subtypes led to a revision of this categorization in 1999.7 The goal was to simplify the classification and eliminate eponyms and ambiguous terms.8
A new fourth type of EB. Recently, a fourth type, hemidesmosomal EB, has been described.9 Table 1 outlines the most recent classification, incorporating molecular changes in EB.10, 11
The Basement Membrane Zone (BMZ)
The basement membrane zone is the area of linkage between the epidermis and the dermis, and provides integrity of the two. Structures and proteins from the cytoplasm of the inferior pole of the basal keratinocytes to the papillary dermis make up the BMZ.8
Mutations in 10 different genes expressing proteins at the dermal-epidermal junction are the basis for the different types of EB.12
With the help of electron microscopy, polyclonal and monoclonal antibody technology and recent molecular biology studies, the structure and abnormalities of the BMZ have been studied.
A BMZ consists of lamina lucida and lamina densa and is held together by several attachment complexes that include the hemidesmosomes (HD). The lamina lucida is composed of several proteins: laminin 5, laminin 6 and uncein.8 The lamina densa is composed of type IV collagen, heparin sulfate proteoglycan and chondroitin 6-sulfate proteoglycan.8 The HDs are multiprotein complexes that extend from intracellular compartment of the basal keratinocytes to the lamina lucida in the upper portion of the dermal-epidermal basement membrane.10
The intracellular portion of the HDs connects with the keratin intermediate filament network.10 The extracellular portion interacts with anchoring filaments that are thread-like structures traversing the lamina lucida and concentrating below the HDs.10
At the lower portion of the dermal-epidermal attachment zone, fibrillar structures known as anchoring fibrils extend from the lamina densa to the papillary dermis, but also attach to themselves and to the anchoring plaque, a name given to collections of electron-dense condensations within the papillary dermis.8, 11
The HDs consist of four different proteins: the 230-kDa bullous pemphigoid antigen (BPA), the 180-kDa BPS, a transmembrane integrin a6b4 and plectin.13 The anchoring filaments consist of laminin 5 and the anchoring fibrils of type VII collagen.8 The hemidesmosome-mediated adhesion relies on the binding of a6b4 integrin to laminin 5; laminin 5 not only interacts with integrin a6b4 but also with type VII collagen, leading to integrity of the BMZ.14
In EB, abnormalities in the different structures of the BMZ determine the different classifications.
Epidermolysis Bullosa Simplex (EB-S)
All subtypes of EB-S are explained by mutations in keratins. Keratins are the major components in epithelial cells, and make up a family of about 50 different proteins.11 Keratins 5 and 14, which are encoded by KRT5 and KRT14, respectively, are affected in the different forms of EB-S.13 This leads to intraepidermal blistering with the separation occurring within the basal keratinocytes.
The type of mutation and its location along the affected polypeptide appear to determine the severity and mode of inheritance of the disease.11 This explains why within this group we find severe forms like the Dowling-Meara subtype grouped together with relatively mild, localized forms like the Weber-Cockayne syndrome.
Hemidesmosomal Epidermolysis Bullosa (H-EB)
The new proposed EB type, hemidesmosomal EB (H-EB), brings together subtypes of EB that had been previously classified as EB-S or Junctional-EB.
Subtypes of H-EB. The subtypes of EB that can be explained by abnormalities within the hemidesmosomes are: generalized atrophic benign EB, EB with pyloric atresia, EB with muscular dystrophy, and the previously called Ogna variant of EB.10,11 The level of the split resides in the hemidesmosomes, at the basal cell-lamina lucida interface.
Generalized atrophic benign EB (GABEB) was originally classified as a non-Herlitz J-EB.7 These patients usually present moderate blistering with normal lifespan. The blistering is found along with extracutaneous manifestations (dystrophy of fingernails, focal scarring alopecia, loss of eyelashes, dental anomalies and patchy hyperpigmentation).10 Abnormal immunofluorescence for 180-kDa BPAG and later identification of mutations in the corresponding gene (BPAG2/COL17A1) was recognized.13
Epidermolysis bullosa with pyloric atresia usually presents with blistering in neonates that is associated with either pyloric atresia or stenosis. Previously, it was also classified as a non-Herlitz J-EB.11 Analysis of the phenotype revealed a range of blistering from mild to moderate. The mutations causing this condition have been identified in the genes encoding the subunit polypeptides of the a6b4 integrin, ITGA6 and ITGB4, respectively.13 Phenotypic manifestations of mutations in these genes have suggested that a6b4 integrin plays an important role in the integrity of the skin as well as in the development of the gastrointestinal tract.10
Epidermolysis bullosa with muscular dystrophy is a condition that usually presents with blistering in the neonatal period and with late onset in the first or second decade of life of muscular dystrophy, added to characteristic nail and tooth abnormalities.10 Severe mucocutaneous involvement has also been described.15 Immunofluorescence in these patients revealed absence of plectin. Mutations in the corresponding gene, PLEC1, were later identified.13 Plectin is one of the major cross linking elements of the cytoskeleton and there is growing evidence of its essential role in epithelial tissues.16
Another mutation in the PLEC1 is responsible for the type of EB known as the Ogna variant.16 Previously this condition was included in the EB-S type, but the fragility in this condition is at the level of the hemidesmosomes.11 The clinical characteristic of this condition is the presence of hemorrhagic blisters.10
Junctional Epidermolysis Bullosa (J-EB)
Laminin 5 is the protein that is affected in J-EB. The level of skin separation is within the dermal-epidermal junction, at the level of the lamina lucida. Mutations in the three constitutive subunit polypeptides of laminin 5, LAMA3, LAMB3 and LAMC2, encoding the a3, b3, g2 chains, respectively, have been described in Herlitz J-EB.13 The milder non-Herlitz subtype is also explained by mutations in laminin 5, but the type of mutation and combination of mutations lead to a milder course.10
Of growing interest is the role of the mid-lamina lucida antigen, 19-DEJ-1, also known as uncein. It is still not clear what role it plays in J-EB, but this antigen is completely absent in all types of J-EB.17
Dystrophic Epidermolysis Bullosa (D-EB)
The anchoring fibrils, made up of collagen VII, can either be morphologically abnormal, reduced in number or completely absent in D-EB.10 Mutations in the gene COL7A1, encoding for collagen VII, explain D-EB,13 although other minor components of the anchoring fibrils may contribute to its structure, stability and size.17
The precise nature of the genetic lesion, its position along the type VII collagen gene and the consequences of the mutations at the mRNA and protein levels, together with the degree of trauma determine a patient’s phenotype.11
The level of blistering in D-EB is below the lamina densa, within the upper papillary dermis at the level of the anchoring fibrils. This is the same site affected by the acquired form of EB, EB acquisita, in which IgG autoantibodies to type VII collagen cause clinical manifestations.18
Future Therapies
The newer molecular advances in the diagnosis and phenotyping of the disease have had huge clinical implications. An early molecular diagnosis will enable physicians to paint a more accurate picture of what the future will hold for individual families.
In addition, discovering a particular mutation in a family will allow adequate genetic counseling and early prenatal or preimplantation diagnosis.
Identification of mutations is also a prerequisite for successful gene therapy. Gene modification of stem cells in combination with tissue engineering techniques could represent a treatment option for patients with EB.14 Also, direct application of DNA into the skin in an attempt to elicit genetic reversal of the underlying mutation could be attempted.17
Currently, there is no cure for EB and no effective, long lasting treatment to reduce the blistering or to improve skin fragility. However, newer advances in molecular diagnosis may shed light on a potential cure of a devastating disease.
Epidermolysis bullosa (EB) refers to a series of hereditary disorders characterized by fragility of the skin and mucous membranes and the tendency of the skin to blister in response to minor friction or trauma. Some patients experience blistering since birth, while others present clinical manifestations later in life.
The severity of presentation in a newborn does not indicate prognosis; thus, clinical classification based on morphology alone at this age should not be attempted.1 Even later in life, classification based only on clinical findings is difficult, as the same type of EB may range from very mild to severe clinical findings.2,3 The clinical picture depends not only on the level of split, but also on the type of mutation that a particular patient has; the same genetic abnormality can be associated with different clinical features.4
Classification of Epidermolysis Bullosa
The first attempt at classification of this condition was made by Pearson, who proposed three broad categories of presentation according to the location of the skin separation: epidermolytic, lamina lucidolytic and dermolytic.5
Three types of EB. In 1989, the first consensus meeting on the diagnosis and classification of EB took place.6 The meeting resulted in a classification that lasted for almost a decade, separating EB into:
1. simplex
2. junctional
3. dystrophic.
The different forms of the disease were further subclassified according to their clinical presentation and mode of transmission leading to 23 different clinical pictures.7
New findings explaining the molecular basis of many of these subtypes led to a revision of this categorization in 1999.7 The goal was to simplify the classification and eliminate eponyms and ambiguous terms.8
A new fourth type of EB. Recently, a fourth type, hemidesmosomal EB, has been described.9 Table 1 outlines the most recent classification, incorporating molecular changes in EB.10, 11
The Basement Membrane Zone (BMZ)
The basement membrane zone is the area of linkage between the epidermis and the dermis, and provides integrity of the two. Structures and proteins from the cytoplasm of the inferior pole of the basal keratinocytes to the papillary dermis make up the BMZ.8
Mutations in 10 different genes expressing proteins at the dermal-epidermal junction are the basis for the different types of EB.12
With the help of electron microscopy, polyclonal and monoclonal antibody technology and recent molecular biology studies, the structure and abnormalities of the BMZ have been studied.
A BMZ consists of lamina lucida and lamina densa and is held together by several attachment complexes that include the hemidesmosomes (HD). The lamina lucida is composed of several proteins: laminin 5, laminin 6 and uncein.8 The lamina densa is composed of type IV collagen, heparin sulfate proteoglycan and chondroitin 6-sulfate proteoglycan.8 The HDs are multiprotein complexes that extend from intracellular compartment of the basal keratinocytes to the lamina lucida in the upper portion of the dermal-epidermal basement membrane.10
The intracellular portion of the HDs connects with the keratin intermediate filament network.10 The extracellular portion interacts with anchoring filaments that are thread-like structures traversing the lamina lucida and concentrating below the HDs.10
At the lower portion of the dermal-epidermal attachment zone, fibrillar structures known as anchoring fibrils extend from the lamina densa to the papillary dermis, but also attach to themselves and to the anchoring plaque, a name given to collections of electron-dense condensations within the papillary dermis.8, 11
The HDs consist of four different proteins: the 230-kDa bullous pemphigoid antigen (BPA), the 180-kDa BPS, a transmembrane integrin a6b4 and plectin.13 The anchoring filaments consist of laminin 5 and the anchoring fibrils of type VII collagen.8 The hemidesmosome-mediated adhesion relies on the binding of a6b4 integrin to laminin 5; laminin 5 not only interacts with integrin a6b4 but also with type VII collagen, leading to integrity of the BMZ.14
In EB, abnormalities in the different structures of the BMZ determine the different classifications.
Epidermolysis Bullosa Simplex (EB-S)
All subtypes of EB-S are explained by mutations in keratins. Keratins are the major components in epithelial cells, and make up a family of about 50 different proteins.11 Keratins 5 and 14, which are encoded by KRT5 and KRT14, respectively, are affected in the different forms of EB-S.13 This leads to intraepidermal blistering with the separation occurring within the basal keratinocytes.
The type of mutation and its location along the affected polypeptide appear to determine the severity and mode of inheritance of the disease.11 This explains why within this group we find severe forms like the Dowling-Meara subtype grouped together with relatively mild, localized forms like the Weber-Cockayne syndrome.
Hemidesmosomal Epidermolysis Bullosa (H-EB)
The new proposed EB type, hemidesmosomal EB (H-EB), brings together subtypes of EB that had been previously classified as EB-S or Junctional-EB.
Subtypes of H-EB. The subtypes of EB that can be explained by abnormalities within the hemidesmosomes are: generalized atrophic benign EB, EB with pyloric atresia, EB with muscular dystrophy, and the previously called Ogna variant of EB.10,11 The level of the split resides in the hemidesmosomes, at the basal cell-lamina lucida interface.
Generalized atrophic benign EB (GABEB) was originally classified as a non-Herlitz J-EB.7 These patients usually present moderate blistering with normal lifespan. The blistering is found along with extracutaneous manifestations (dystrophy of fingernails, focal scarring alopecia, loss of eyelashes, dental anomalies and patchy hyperpigmentation).10 Abnormal immunofluorescence for 180-kDa BPAG and later identification of mutations in the corresponding gene (BPAG2/COL17A1) was recognized.13
Epidermolysis bullosa with pyloric atresia usually presents with blistering in neonates that is associated with either pyloric atresia or stenosis. Previously, it was also classified as a non-Herlitz J-EB.11 Analysis of the phenotype revealed a range of blistering from mild to moderate. The mutations causing this condition have been identified in the genes encoding the subunit polypeptides of the a6b4 integrin, ITGA6 and ITGB4, respectively.13 Phenotypic manifestations of mutations in these genes have suggested that a6b4 integrin plays an important role in the integrity of the skin as well as in the development of the gastrointestinal tract.10
Epidermolysis bullosa with muscular dystrophy is a condition that usually presents with blistering in the neonatal period and with late onset in the first or second decade of life of muscular dystrophy, added to characteristic nail and tooth abnormalities.10 Severe mucocutaneous involvement has also been described.15 Immunofluorescence in these patients revealed absence of plectin. Mutations in the corresponding gene, PLEC1, were later identified.13 Plectin is one of the major cross linking elements of the cytoskeleton and there is growing evidence of its essential role in epithelial tissues.16
Another mutation in the PLEC1 is responsible for the type of EB known as the Ogna variant.16 Previously this condition was included in the EB-S type, but the fragility in this condition is at the level of the hemidesmosomes.11 The clinical characteristic of this condition is the presence of hemorrhagic blisters.10
Junctional Epidermolysis Bullosa (J-EB)
Laminin 5 is the protein that is affected in J-EB. The level of skin separation is within the dermal-epidermal junction, at the level of the lamina lucida. Mutations in the three constitutive subunit polypeptides of laminin 5, LAMA3, LAMB3 and LAMC2, encoding the a3, b3, g2 chains, respectively, have been described in Herlitz J-EB.13 The milder non-Herlitz subtype is also explained by mutations in laminin 5, but the type of mutation and combination of mutations lead to a milder course.10
Of growing interest is the role of the mid-lamina lucida antigen, 19-DEJ-1, also known as uncein. It is still not clear what role it plays in J-EB, but this antigen is completely absent in all types of J-EB.17
Dystrophic Epidermolysis Bullosa (D-EB)
The anchoring fibrils, made up of collagen VII, can either be morphologically abnormal, reduced in number or completely absent in D-EB.10 Mutations in the gene COL7A1, encoding for collagen VII, explain D-EB,13 although other minor components of the anchoring fibrils may contribute to its structure, stability and size.17
The precise nature of the genetic lesion, its position along the type VII collagen gene and the consequences of the mutations at the mRNA and protein levels, together with the degree of trauma determine a patient’s phenotype.11
The level of blistering in D-EB is below the lamina densa, within the upper papillary dermis at the level of the anchoring fibrils. This is the same site affected by the acquired form of EB, EB acquisita, in which IgG autoantibodies to type VII collagen cause clinical manifestations.18
Future Therapies
The newer molecular advances in the diagnosis and phenotyping of the disease have had huge clinical implications. An early molecular diagnosis will enable physicians to paint a more accurate picture of what the future will hold for individual families.
In addition, discovering a particular mutation in a family will allow adequate genetic counseling and early prenatal or preimplantation diagnosis.
Identification of mutations is also a prerequisite for successful gene therapy. Gene modification of stem cells in combination with tissue engineering techniques could represent a treatment option for patients with EB.14 Also, direct application of DNA into the skin in an attempt to elicit genetic reversal of the underlying mutation could be attempted.17
Currently, there is no cure for EB and no effective, long lasting treatment to reduce the blistering or to improve skin fragility. However, newer advances in molecular diagnosis may shed light on a potential cure of a devastating disease.
Epidermolysis bullosa (EB) refers to a series of hereditary disorders characterized by fragility of the skin and mucous membranes and the tendency of the skin to blister in response to minor friction or trauma. Some patients experience blistering since birth, while others present clinical manifestations later in life.
The severity of presentation in a newborn does not indicate prognosis; thus, clinical classification based on morphology alone at this age should not be attempted.1 Even later in life, classification based only on clinical findings is difficult, as the same type of EB may range from very mild to severe clinical findings.2,3 The clinical picture depends not only on the level of split, but also on the type of mutation that a particular patient has; the same genetic abnormality can be associated with different clinical features.4
Classification of Epidermolysis Bullosa
The first attempt at classification of this condition was made by Pearson, who proposed three broad categories of presentation according to the location of the skin separation: epidermolytic, lamina lucidolytic and dermolytic.5
Three types of EB. In 1989, the first consensus meeting on the diagnosis and classification of EB took place.6 The meeting resulted in a classification that lasted for almost a decade, separating EB into:
1. simplex
2. junctional
3. dystrophic.
The different forms of the disease were further subclassified according to their clinical presentation and mode of transmission leading to 23 different clinical pictures.7
New findings explaining the molecular basis of many of these subtypes led to a revision of this categorization in 1999.7 The goal was to simplify the classification and eliminate eponyms and ambiguous terms.8
A new fourth type of EB. Recently, a fourth type, hemidesmosomal EB, has been described.9 Table 1 outlines the most recent classification, incorporating molecular changes in EB.10, 11
The Basement Membrane Zone (BMZ)
The basement membrane zone is the area of linkage between the epidermis and the dermis, and provides integrity of the two. Structures and proteins from the cytoplasm of the inferior pole of the basal keratinocytes to the papillary dermis make up the BMZ.8
Mutations in 10 different genes expressing proteins at the dermal-epidermal junction are the basis for the different types of EB.12
With the help of electron microscopy, polyclonal and monoclonal antibody technology and recent molecular biology studies, the structure and abnormalities of the BMZ have been studied.
A BMZ consists of lamina lucida and lamina densa and is held together by several attachment complexes that include the hemidesmosomes (HD). The lamina lucida is composed of several proteins: laminin 5, laminin 6 and uncein.8 The lamina densa is composed of type IV collagen, heparin sulfate proteoglycan and chondroitin 6-sulfate proteoglycan.8 The HDs are multiprotein complexes that extend from intracellular compartment of the basal keratinocytes to the lamina lucida in the upper portion of the dermal-epidermal basement membrane.10
The intracellular portion of the HDs connects with the keratin intermediate filament network.10 The extracellular portion interacts with anchoring filaments that are thread-like structures traversing the lamina lucida and concentrating below the HDs.10
At the lower portion of the dermal-epidermal attachment zone, fibrillar structures known as anchoring fibrils extend from the lamina densa to the papillary dermis, but also attach to themselves and to the anchoring plaque, a name given to collections of electron-dense condensations within the papillary dermis.8, 11
The HDs consist of four different proteins: the 230-kDa bullous pemphigoid antigen (BPA), the 180-kDa BPS, a transmembrane integrin a6b4 and plectin.13 The anchoring filaments consist of laminin 5 and the anchoring fibrils of type VII collagen.8 The hemidesmosome-mediated adhesion relies on the binding of a6b4 integrin to laminin 5; laminin 5 not only interacts with integrin a6b4 but also with type VII collagen, leading to integrity of the BMZ.14
In EB, abnormalities in the different structures of the BMZ determine the different classifications.
Epidermolysis Bullosa Simplex (EB-S)
All subtypes of EB-S are explained by mutations in keratins. Keratins are the major components in epithelial cells, and make up a family of about 50 different proteins.11 Keratins 5 and 14, which are encoded by KRT5 and KRT14, respectively, are affected in the different forms of EB-S.13 This leads to intraepidermal blistering with the separation occurring within the basal keratinocytes.
The type of mutation and its location along the affected polypeptide appear to determine the severity and mode of inheritance of the disease.11 This explains why within this group we find severe forms like the Dowling-Meara subtype grouped together with relatively mild, localized forms like the Weber-Cockayne syndrome.
Hemidesmosomal Epidermolysis Bullosa (H-EB)
The new proposed EB type, hemidesmosomal EB (H-EB), brings together subtypes of EB that had been previously classified as EB-S or Junctional-EB.
Subtypes of H-EB. The subtypes of EB that can be explained by abnormalities within the hemidesmosomes are: generalized atrophic benign EB, EB with pyloric atresia, EB with muscular dystrophy, and the previously called Ogna variant of EB.10,11 The level of the split resides in the hemidesmosomes, at the basal cell-lamina lucida interface.
Generalized atrophic benign EB (GABEB) was originally classified as a non-Herlitz J-EB.7 These patients usually present moderate blistering with normal lifespan. The blistering is found along with extracutaneous manifestations (dystrophy of fingernails, focal scarring alopecia, loss of eyelashes, dental anomalies and patchy hyperpigmentation).10 Abnormal immunofluorescence for 180-kDa BPAG and later identification of mutations in the corresponding gene (BPAG2/COL17A1) was recognized.13
Epidermolysis bullosa with pyloric atresia usually presents with blistering in neonates that is associated with either pyloric atresia or stenosis. Previously, it was also classified as a non-Herlitz J-EB.11 Analysis of the phenotype revealed a range of blistering from mild to moderate. The mutations causing this condition have been identified in the genes encoding the subunit polypeptides of the a6b4 integrin, ITGA6 and ITGB4, respectively.13 Phenotypic manifestations of mutations in these genes have suggested that a6b4 integrin plays an important role in the integrity of the skin as well as in the development of the gastrointestinal tract.10
Epidermolysis bullosa with muscular dystrophy is a condition that usually presents with blistering in the neonatal period and with late onset in the first or second decade of life of muscular dystrophy, added to characteristic nail and tooth abnormalities.10 Severe mucocutaneous involvement has also been described.15 Immunofluorescence in these patients revealed absence of plectin. Mutations in the corresponding gene, PLEC1, were later identified.13 Plectin is one of the major cross linking elements of the cytoskeleton and there is growing evidence of its essential role in epithelial tissues.16
Another mutation in the PLEC1 is responsible for the type of EB known as the Ogna variant.16 Previously this condition was included in the EB-S type, but the fragility in this condition is at the level of the hemidesmosomes.11 The clinical characteristic of this condition is the presence of hemorrhagic blisters.10
Junctional Epidermolysis Bullosa (J-EB)
Laminin 5 is the protein that is affected in J-EB. The level of skin separation is within the dermal-epidermal junction, at the level of the lamina lucida. Mutations in the three constitutive subunit polypeptides of laminin 5, LAMA3, LAMB3 and LAMC2, encoding the a3, b3, g2 chains, respectively, have been described in Herlitz J-EB.13 The milder non-Herlitz subtype is also explained by mutations in laminin 5, but the type of mutation and combination of mutations lead to a milder course.10
Of growing interest is the role of the mid-lamina lucida antigen, 19-DEJ-1, also known as uncein. It is still not clear what role it plays in J-EB, but this antigen is completely absent in all types of J-EB.17
Dystrophic Epidermolysis Bullosa (D-EB)
The anchoring fibrils, made up of collagen VII, can either be morphologically abnormal, reduced in number or completely absent in D-EB.10 Mutations in the gene COL7A1, encoding for collagen VII, explain D-EB,13 although other minor components of the anchoring fibrils may contribute to its structure, stability and size.17
The precise nature of the genetic lesion, its position along the type VII collagen gene and the consequences of the mutations at the mRNA and protein levels, together with the degree of trauma determine a patient’s phenotype.11
The level of blistering in D-EB is below the lamina densa, within the upper papillary dermis at the level of the anchoring fibrils. This is the same site affected by the acquired form of EB, EB acquisita, in which IgG autoantibodies to type VII collagen cause clinical manifestations.18
Future Therapies
The newer molecular advances in the diagnosis and phenotyping of the disease have had huge clinical implications. An early molecular diagnosis will enable physicians to paint a more accurate picture of what the future will hold for individual families.
In addition, discovering a particular mutation in a family will allow adequate genetic counseling and early prenatal or preimplantation diagnosis.
Identification of mutations is also a prerequisite for successful gene therapy. Gene modification of stem cells in combination with tissue engineering techniques could represent a treatment option for patients with EB.14 Also, direct application of DNA into the skin in an attempt to elicit genetic reversal of the underlying mutation could be attempted.17
Currently, there is no cure for EB and no effective, long lasting treatment to reduce the blistering or to improve skin fragility. However, newer advances in molecular diagnosis may shed light on a potential cure of a devastating disease.
