Epidermolysis bullosa
Encyclopedia
Epidermolysis bullosa is an inherited connective tissue disease
causing blisters in the skin
and mucosal membranes, with an incidence of 1/50,000. Its severity ranges from mild to lethal. It is caused by a mutation in the keratin
or collagen
gene.
As a result, the skin is extremely fragile. Minor mechanical friction or trauma will separate the layers of the skin and form blisters. People with this condition have an increased risk of cancers of the skin, and many will eventually be diagnosed with it as a complication of the chronic damage done to the skin.
The skin has two layers; the outer layer is called the epidermis and the inner layer the dermis
. In individuals with healthy skin, there are protein anchors, made of collagen, between the two layers that prevent them from moving independently from one another (shearing). In people born with EB, the two skin layers lack the protein anchors that hold them together, and any action that creates friction between the layers (like rubbing or pressure) will create blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns.
The condition was brought to public attention in the UK
through the Channel 4
documentary The Boy Whose Skin Fell Off, chronicling the life and death of Jonny Kennedy
, an English man with EB.
"Butterfly Children" is a term often used to describe younger patients because the skin is said to be as fragile as a butterfly’s wings.
Children with the condition have also been described as "Cotton Wool Babies," and in South America, "Crystal Skin Children" is the term used.
The disorder occurs in every racial and ethnic group throughout the world and affects both sexes.
Current clinical research at the University of Minnesota has included a bone marrow transplant to a 2-year-old child who is one of 2 brothers with EB. The procedure was successful, strongly suggesting that a cure may have been found. A second transplant has also been performed on the child's older brother, and a third transplant is scheduled for a California baby. The clinical trial will ultimately include transplants to 30 subjects. However, the severe immunosuppression that bone marrow transplantation requires causes a significant risk of serious infections in patients with large scale blisters and erosions. Indeed, at least two patients have died in the course of either preparation for or institution of bone marrow transplantation for epidermolysis bullosa, out of a small group of patients treated so far.
s produced in the skin. There are 54 known keratin genes, 28 type I intermediate filament
genes and 26 type II, which work as heterodimers. Many share substantial structural and functional similarity, but are specialized for different cell types or conditions under which they are normally produced. If a drug can shift the balance of production toward an intact keratin gene, symptoms can be reduced. For example, sulforaphane
, a compound found in broccoli
, was found to reduce blistering in a mouse model to the point where affected pups could not be identified visually, when injected into pregnant mice (5 µmol/day = 0.9 mg) and applied topically to newborns (1 µmol/day = 0.2 mg in jojoba oil
).
Connective tissue disease
A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...
causing blisters in the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
and mucosal membranes, with an incidence of 1/50,000. Its severity ranges from mild to lethal. It is caused by a mutation in the keratin
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...
or collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
gene.
As a result, the skin is extremely fragile. Minor mechanical friction or trauma will separate the layers of the skin and form blisters. People with this condition have an increased risk of cancers of the skin, and many will eventually be diagnosed with it as a complication of the chronic damage done to the skin.
The skin has two layers; the outer layer is called the epidermis and the inner layer the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
. In individuals with healthy skin, there are protein anchors, made of collagen, between the two layers that prevent them from moving independently from one another (shearing). In people born with EB, the two skin layers lack the protein anchors that hold them together, and any action that creates friction between the layers (like rubbing or pressure) will create blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns.
The condition was brought to public attention in the UK
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
through the Channel 4
Channel 4
Channel 4 is a British public-service television broadcaster which began working on 2 November 1982. Although largely commercially self-funded, it is ultimately publicly owned; originally a subsidiary of the Independent Broadcasting Authority , the station is now owned and operated by the Channel...
documentary The Boy Whose Skin Fell Off, chronicling the life and death of Jonny Kennedy
Jonny Kennedy
Jonny Kennedy was the subject of the documentary The Boy Whose Skin Fell Off, which documented the final months of his life as he suffered from the rare inherited condition known as dystrophic epidermolysis bullosa . He was born with no skin on his left leg...
, an English man with EB.
"Butterfly Children" is a term often used to describe younger patients because the skin is said to be as fragile as a butterfly’s wings.
Children with the condition have also been described as "Cotton Wool Babies," and in South America, "Crystal Skin Children" is the term used.
Epidemiology
An estimated 50 in 1 million live births are diagnosed with EB, and 9 in 1 million are in population. Of these cases, approximately 92% are EBS, 5% are DEB, 1% are JEB, and 2% are unclassified. Carrier frequency ranges from 1 in 333 for Junctional, to 1 in 450 for Dystrophic. Carrier frequency for Simplex is not indicated in this article, but is presumed to be much higher than JEB or DEB.The disorder occurs in every racial and ethnic group throughout the world and affects both sexes.
Current clinical research at the University of Minnesota has included a bone marrow transplant to a 2-year-old child who is one of 2 brothers with EB. The procedure was successful, strongly suggesting that a cure may have been found. A second transplant has also been performed on the child's older brother, and a third transplant is scheduled for a California baby. The clinical trial will ultimately include transplants to 30 subjects. However, the severe immunosuppression that bone marrow transplantation requires causes a significant risk of serious infections in patients with large scale blisters and erosions. Indeed, at least two patients have died in the course of either preparation for or institution of bone marrow transplantation for epidermolysis bullosa, out of a small group of patients treated so far.
Classification
Epidermolysis bullosa refers to a group of inherited disorders that involve the formation of blisters following trivial trauma, and which may be divided into the following types:Epidermolysis bullosa simplex
- Epidermolysis bullosa simplexEpidermolysis bullosa simplexEpidermolysis bullosa simplex is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14.Blister formation of EBS occurs at the dermoepidermal junction. Sometimes EBS is called epidermolytic.-Subtypes:...
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- Generalized epidermolysis bullosa simplexGeneralized epidermolysis bullosa simplexGeneralized epidermolysis bullosa simplex is a skin condition that presents at birth to early infancy with a predilection for the hands, feet, and extremities, and palmar-plantar hyperkeratosis and erosions may be present....
(Koebner variant of generalized epidermolysis bullosa simplex) - Localized epidermolysis bullosa simplexLocalized epidermolysis bullosa simplexLocalized epidermolysis bullosa simplex is a skin condition characterized by onset in childhood or later in life, and is the most common variant of epidermolysis bullosa simplex.- References :...
(Weber-Cockayne variant of generalized epidermolysis bullosa simplex) - Epidermolysis bullosa herpetiformisEpidermolysis bullosa herpetiformisEpidermolysis bullosa herpetiformis is a skin condition that presents at birth with a generalized distribution, often with oral mucosa involvement and variable lesions in infancy....
(Dowling-Meara epidermolysis bullosa simplex) - Epidermolysis bullosa simplex of OgnaEpidermolysis bullosa simplex of OgnaEpidermolysis bullosa simplex of Ogna is a skin condition with onset in infancy, presenting with seasonal blistering on acral areas during summer months....
- Epidermolysis bullosa simplex with muscular dystrophyEpidermolysis bullosa simplex with muscular dystrophyEpidermolysis bullosa simplex with muscular dystrophy is a rare clinical entity, and is the first and only epidermolytic epidermolysis bullosa described that is not caused by a keratin mutation, presenting as a generalized intraepidermal blistering similar to the Koebner variant of generalized...
- Epidermolysis bullosa simplex with mottled pigmentationEpidermolysis bullosa simplex with mottled pigmentationEpidermolysis bullosa simplex with mottled pigmentation is a skin condition resulting from a recurrent mutation in KRT14....
- Generalized epidermolysis bullosa simplex
-
Junctional epidermolysis bullosa
- Junctional epidermolysis bullosaJunctional epidermolysis bullosa (medicine)Junctional epidermolysis bullosa is a skin condition characterized by blister formation within the lamina lucida of the basement membrane zone.Types include:Another form, cicatricial junctional epidermolysis bullosa, is not included in OMIM....
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- Junctional epidermolysis bullosa gravisJunctional epidermolysis bullosa gravisJunctional epidermolysis bullosa gravis is the most lethal type of epidermolysis bullosa, a skin condition in which most patients do not survive infancy, characterized by blistering at birth with severe and clinically...
(Epidermolysis bullosa lethalis, Herlitz disease, Herlitz epidermolysis bullosa, Lethal junctional epidermolysis bullosa) - Mitis junctional epidermolysis bullosaMitis junctional epidermolysis bullosaMitis junctional epidermolysis bullosa is a skin condition characterized by scalp and nail lesions, also associated with periorificial nonhealing erosions. Mitis junctional epidermolysis bullosa is most commonly seem in children between the ages of 4 and 10 years old....
- Generalized atrophic benign epidermolysis bullosaGeneralized atrophic benign epidermolysis bullosaGeneralized atrophic benign epidermolysis bullosa is a skin condition that is characterized by onset at birth, generalized blisters and atrophy, mucosal involvement, and thickened, dystrophic, or absent nails....
- Cicatricial junctional epidermolysis bullosaCicatricial junctional epidermolysis bullosaCicatricial junctional epidermolysis bullosa is a skin condition characterized by blisters that heal with scarring.It was characterized in 1985.It is not included in OMIM....
- Junctional epidermolysis bullosa with pyloric atresiaJunctional epidermolysis bullosa with pyloric atresiaJunctional epidermolysis bullosa with pyloric atresia is a rare autosomal recessive form of junctional epidermolysis bullosa that presents at birth with severe mucocutaneous fragility and gastric outlet obstruction....
- Junctional epidermolysis bullosa gravis
-
Dystrophic epidermolysis bullosa
- Dystrophic epidermolysis bullosa
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- Dominant dystrophic epidermolysis bullosaDominant dystrophic epidermolysis bullosaDominant dystrophic epidermolysis bullosa is a skin condition characterized by vesicles and bullae on the extensor surfaces of the extremities....
(Cockayne-Touraine disease) - Recessive dystrophic epidermolysis bullosaRecessive dystrophic epidermolysis bullosaRecessive dystrophic epidermolysis bullosa is a skin condition resulting from mutations in the gene encoding type VII collagen, COL7A1, characterized by debilitating oral lesions that produce pain, scarring, and microstomia.It is named for François Henri Hallopeau and Hermann Werner...
(Hallopeau-Siemens variant of epidermolysis bullosa)
- Dominant dystrophic epidermolysis bullosa
-
Other genetic
| OMIM | Name | Locus | Gene |
|---|---|---|---|
Treatment
Recent research has focused on changing the mixture of keratinKeratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...
s produced in the skin. There are 54 known keratin genes, 28 type I intermediate filament
Intermediate filament
Intermediate filaments are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin , and that of 25 nm microtubules, although they were initially designated...
genes and 26 type II, which work as heterodimers. Many share substantial structural and functional similarity, but are specialized for different cell types or conditions under which they are normally produced. If a drug can shift the balance of production toward an intact keratin gene, symptoms can be reduced. For example, sulforaphane
Sulforaphane
Sulforaphane is an organosulfur compound that exhibits anticancer, antidiabetic, and antimicrobial properties in experimental models. It is obtained from cruciferous vegetables such as broccoli, Brussels sprouts or cabbages. The enzyme myrosinase transforms glucoraphanin, a glucosinolate, into...
, a compound found in broccoli
Broccoli
Broccoli is a plant in the cabbage family, whose large flower head is used as a vegetable.-General:The word broccoli, from the Italian plural of , refers to "the flowering top of a cabbage"....
, was found to reduce blistering in a mouse model to the point where affected pups could not be identified visually, when injected into pregnant mice (5 µmol/day = 0.9 mg) and applied topically to newborns (1 µmol/day = 0.2 mg in jojoba oil
Jojoba oil
Jojoba oil is the liquid wax produced in the seed of the jojoba plant, a shrub native to southern Arizona, southern California, and northwestern Mexico. The oil makes up approximately 50% of the jojoba seed by weight....
).