Epidermolysis bullosa dystrophica or dystrophic EB (DEB) is an

inherited disease A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders are ...

affecting the skin and other organs. "Butterfly child" is the colloquial name for children born with the disease, as their skin is seen to be as delicate and fragile as the wings of a butterfly.

Signs and symptoms

The deficiency in anchoring fibrils impairs the adherence between the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

and the underlying dermis. This deficiency occurs due to the genetic mutation(s) in the COL7A1 gene in

chromosome 3 Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 3 spans more than 201 million base pairs (the building material of DNA) and represents about 6.5 percent of the total DNA ...

. The COL7A1 gene in chromosome 3 is responsible for coding for type VII collagen, a protein that assists in helping anchor the

and

dermis The dermis or corium is a layer of skin between the epidermis (skin), epidermis (with which it makes up the cutis (anatomy), cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from s ...

. Thus, the skin of DEB patients is highly susceptible to mild to severe

blister A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...

ing, depending on the subtype. Collagen VII is also associated with the

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

of the esophageal lining, and DEB patients may have chronic scarring, webbing, and obstruction of the

esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...

. Affected individuals are often severely malnourished due to trauma to the oral and esophageal mucosa and require feeding tubes for nutrition. They also have iron-deficiency anemia of uncertain origin, which leads to chronic fatigue. Open wounds on the skin heal slowly or not at all, often scarring extensively, and are particularly susceptible to infection. Many individuals bathe in a bleach and water mixture to fight off these infections. The chronic inflammation leads to errors in the DNA of the affected skin cells, which in turn causes

squamous cell carcinoma Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

(SCC). The majority of these patients die before the age of 30, either of SCC or complications related to DEB. The chronic inflammatory state seen in recessive dystrophic epidermolysis bullosa (RDEB) may cause

small fiber peripheral neuropathy Small fiber peripheral neuropathy is a type of peripheral neuropathy that occurs from damage to the small unmyelinated and myelinated peripheral nerve fibers. These fibers, categorized as C fibers and small Aδ fibers, are present in skin, perip ...

(SFN). RDEB patients have reported the sensation of pain in line with neuropathic pain qualities.

Causes

DEB is caused by genetic defects (or

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s) within the human COL7A1 gene encoding the

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

type VII collagen (collagen VII). DEB-causing mutations can be either dominant or

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

. Most families with family members with this condition have distinct mutations. Collagen VII is a very large molecule (300

kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

) that dimerizes to form a semicircular looping structure: the anchoring fibril. Anchoring fibrils are thought to form a structural link between the epidermal

basement membrane The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tis ...

and the fibrillar

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

s in the upper

Pathophysiology

In the absence of mutations of the COL7A1 gene, an

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...

response against type VII collagen can result in an acquired form of

epidermolysis bullosa 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. Inherite ...

called epidermolysis bullosa acquisita. There exist other types of inherited

, junctional epidermolysis bullosa and epidermolysis bullosa simplex, which are not related to type VII collagen deficiency. These arise from mutations in the genes encoding other proteins of the

or the

at the junction between the epidermis and the

Diagnosis

Classification

Treatment

In May 2023, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved Vyjuvek for the treatment of wounds in people with dystrophic epidermolysis bullosa with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene.

Signs and symptoms

Causes

Pathophysiology

Diagnosis

Classification

Treatment

Birch triterpenes

References

Sources

External links