Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited EB is a rare disease with a prevalence in the United States of 8.2 per million live births. Those with mild cases may not develop symptoms until they start to crawl or walk. Complications may include esophageal narrowing, squamous cell skin cancer, and the need for amputations.
Keratin 14 is a member of the type I keratin family of intermediate filament proteins. Keratin 14 was the first type I keratin sequence determined. Keratin 14 is also known as cytokeratin-14 (CK-14) or keratin-14 (KRT14). In humans it is encoded by the KRT14 gene.
Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach to adjacent cells. Hemidesmosomes are also comparable to focal adhesions, as they both attach cells to the extracellular matrix. Instead of desmogleins and desmocollins in the extracellular space, hemidesmosomes utilize integrins. Hemidesmosomes are found in epithelial cells connecting the basal epithelial cells to the lamina lucida, which is part of the basal lamina. Hemidesmosomes are also involved in signaling pathways, such as keratinocyte migration or carcinoma cell intrusion.
Epidermolysis bullosa simplex (EBS) is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14.
Kindler syndrome is a rare congenital disease of the skin caused by a mutation in the KIND1 gene.
Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the KRT5 gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.
Collagen XVII, previously called BP180, is a transmembrane protein which plays a critical role in maintaining the linkage between the intracellular and the extracellular structural elements involved in epidermal adhesion, identified by Diaz and colleagues in 1990.
The lamina densa is a component of the basement membrane zone between the epidermis and dermis of the skin, and is an electron-dense zone between the lamina lucida and dermis, synthesized by the basal cells of the epidermis, and composed of (1) type IV collagen, (2) anchoring fibrils made of type VII collagen, and (3) dermal microfibrils.
Genodermatosis is a hereditary skin disease with three inherited modes including single gene inheritance, multiple gene inheritance and chromosome inheritance. There are many different types of genodermatosis, the prevalence of genodermatosis ranges from 1 per 6000 people to 1 per 500,000 people. Genodermatosis has influence on the texture, color and structure of skin cuticle and connective tissue, specific lesion site and clinical manifestations on the body vary depending on the type. In the spite of the variety and complexity of genodermatosis, there are still some common methods that can help people diagnose. After diagnosis, different types of genodermatosis require different levels of therapy including interventions, nursing interventions and treatments. Among that, research of therapy for some new, complex and rare types are still in the developing stage. The impact of genodermatosis not only can be seen in body but also can be seen in all aspects of patients' life, including but not limited to psychological, family life, economic conditions and social activities. Accordingly, the patients need treatment, support and help in these areas.
Collagen alpha-1(VII) chain is a protein that in humans is encoded by the COL7A1 gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epidermal junction in the basement membrane. Mutations in COL7A1 cause all types of dystrophic epidermolysis bullosa, and the exact mutations vary based on the specific type or subtype. It has been shown that interactions between the NC-1 domain of collagen VII and several other proteins, including laminin-5 and collagen IV, contribute greatly to the overall stability of the basement membrane.
Laminin subunit beta-3 is a protein that in humans is encoded by the LAMB3 gene.
Anchoring fibrils extend from the basal lamina of epithelial cells and attach to the lamina reticularis by wrapping around the reticular fiber bundles. The basal lamina and lamina reticularis together make up the basement membrane. Anchoring fibrils are essential to the functional integrity of the dermoepidermal junction.
Epidermolysis bullosa acquisita, also known as acquired epidermolysis bullosa, is a longterm autoimmune blistering skin disease. It generally presents with fragile skin that blisters and becomes red with or without trauma. Marked scarring is left with thin skin, milia and nail changes. It typically begins around age 50.
Bart syndrome, also known as aplasia cutis congenita type VI, is a rare genetic disorder characterized by the association of congenital localized absence of skin, mucocutaneous blistering and absent and dystrophic nails.
Junctional epidermolysis bullosa is a skin condition characterized by blister formation within the lamina lucida of the basement membrane zone.
Transient bullous dermolysis of the newborn (TBDN) is a skin condition that presents in newborns. It is characterized by blister formation secondary to even mild trauma.
A coma blister, or coma bullae, is a skin lesion or blister that typically arises due to pressure in an individual with impaired consciousness. They vary in size, ranging from 4 to 5 centimeters in diameter, and may appear hemorrhagic or blood filled. Coma blisters are usually found in the extremities and trunk. These types of blisters have been associated with the overdose of central nervous system (CNS) depressants especially barbiturates, but also tricyclic antidepressants, hypnotics, benzodiazepines, opiates, antipsychotics, and alcohol. However, studies have found that coma blisters are not caused by the toxicity of these drugs, but due to hypoxia and external pressure on the comatose individual's skin from being immobilized. Coma blisters have been frequently found on individuals who have overdosed on drugs, but have also been found on individuals with chronic kidney failure, hypercalcemia, diabetic ketoacidosis, and a variety of neurologic conditions. Coma blisters are more frequent in adults and less common among children as demonstrated by the few cases published in literature.
The dermoepidermal junction or dermal-epidermal junction (DEJ) is the interface between the epidermal and the dermal layers of the skin. The basal cells of the epidermis connect to the basement membrane by the anchoring filaments of hemidesmosomes; the cells of the papillary layer of the dermis are attached to the basement membrane by anchoring fibrils, which consist of type VII collagen.
Scioderm, acquired by Amicus Therapeutics in 2015, was a rare disease company focused on developing a treatment for Epidermolysis Bullosa (EB), a rare genetic disease characterized by extremely fragile skin and recurrent blister formation. There are currently no approved therapies for EB. Scioderm was developing a topical treatment known as SD-101, or Zorblisa, aimed at triggering wound reduction and closure, and a reduction in body surface area coverage of blisters and lesions.
Beremagene geperpavec, sold under the brand name Vyjuvek, is a gene therapy for the treatment of wounds. Beremagene geperpavec is the first approved gene therapy to use herpes-simplex virus type 1 as a vector. Beremagene geperpavec is a genetically modified herpes-simplex virus used to deliver normal copies of the COL7A1 gene to the wounds.
