Introduction "epidermolysis bullosa" (EB) was first proposed by Koebner in the late 19th century to depict a blistering skin disease without scarring. It is then used to describe a group of polygenic hereditary skin diseases characterized by skin and mucous membrane susceptibility to mechanical damage and formation of bullae, a group of typical diseases that invade the basement membrane area of the skin. Internal organs can also be involved. Clinically, the condition shows great variability. At the same time, gene heterozygosity is also obvious, with autosomal dominant and recessive inheritance. Abnormal wound repair can lead to chronic damage and scarring, and metastatic cancer is also common. At present, significant progress has been made in the study of this disease. The main research method is to encode some key protein-based networks that maintain the integrity of the skin's hierarchical structure through molecular cloning. The disease also belongs to the category of "pemphigus" of Chinese medicine. Etiology (I) Causes of bullying Epidermolysis is classified into three categories according to the level of blister formation under transmission electron microscopy (see Table 1). Mutations in different genes encoding proteins in the dermal-epidermal junction provide a molecular basis for different clinically distinct subtypes. The level of epidermal release of simple bullous epidermolysis is in the basal cell layer and is the result of basal keratin protein KRT5 and KRT14 mutations. The tissue release of borderline bullous epidermolysis occurs at the level of the zona pellucida of the basal membrane of the dermis, and the ultrastructure shows an abnormality of the hemidesmosome anchor filament complex, which encodes the anchor fibroin-laminin-5 ( The genes of the three polypeptides α3, β3 and γ2 of 1aminin are specifically mutated. In addition, gene mutations encoding hemidesmosome components were found in subtypes of borderline bullous epidermolysis, including mutations encoding the α6β4 integrin β4 subunit gene and bullous pemphigoid antigen encoding 18OkDa. BPAG2, also known as a mutation in the type VII collagen gene. The tissue release of dystrophic bullous epidermolysis occurs at the level of anchor fibrils in the dense zone, and only the VII collagen gene (COL7A1) mutation has been found. (B) Molecular pathophysiology of pathogenesis diseases; the mutation site of keratin polypeptide is closely related to the severity of simple bullous epidermolysis. The DM-type keratin mutation is located at the amino (1A) or hydroxyl (2B) end of the central apron region of the polypeptide. The position of the K-type mutation is more likely to be in the central portion of the rod region, and the position of the wc-type mutation is often or in the non-helical junction of the rod region. (L12) zone, or the front end of bit K5. 1. Epidermolysis bullosa simplex (EBS) genetics based on the analysis of keratin K5 and K14 genes in patients with simple bullous epidermolysis, found three major subtypes of keratin mutation. Functional studies have shown that these mutations cause disease. The disease gene is located on chromosomes 12qll to q13 or 17q12 to q21, and keratin proteins K5 and K14 are located at two sites, respectively. Therefore, simple bullous epidermolysis is caused by a defect in the specific basic keratin gene. Point mutations in the coding region of the two keratin genes are present in most of the cases reported. However, genetic defects may also be located outside of the K5 and K14 genes. It has recently been found that simple bullous epidermolysis with muscle nutrition is associated with a prectin mutation. Because keratin genes and transcript lengths (1.8 to 2.1 kDa) are small, screening for keratin mutations in patients with simple bullous epidermolysis is mostly performed by DNA sequencing. Especially when skin biopsy, keratinocyte culture and mRNA extraction are available. If an antibody is used for diagnosis and analysis, the generation of a panel of antibodies directed against a critical region of the keratin polypeptide may be useful for future diagnosis. In addition, with the introduction of methods such as morphological-sensitive gel electrophoresis (CSGE), rapid detection of changes in single bases of DNA can be made. Screening for keratin gene mutations can also be made easier. This method is especially useful when screening a large number of patient specimens. It also eliminates the need for sequencing of the entire genomic or transcriptional gene. 2. Malnutrition The dystrophic genetic basis is based on normal skin. Type VII collagen forms a reverse dimer and is joined by overlapping carboxy termini. This linkage is reinforced by disulfide bonds within the chain. This stable type VII collagen molecule aggregates laterally to form anchor fibrils. Thus, after synthesis of collagen type VII, it is further assembled into anchor fibrils. Thus, mutations that affect the synthesis of collagen type VII at the transcriptional or translational level or interfere with the assembly of the supramolecular assembly into anchor fibrils can be manifested as dystrophic bullous epidermolysis. For HS-RDEB, it has been found that the mutated gene of the early stop codon (PTC) of the two alleles of type VII collagen has low level expression, but the translated protein is truncated at its carboxy terminus and cannot be assembled into anchor fibrils. . This is consistent with the complete lack of anchor fibrils in the HS-RIDEB ultrastructure, which also explains the nature of this type of skin is extremely fragile. In light RDEB, the allele can encode a full-length collagen type VII polypeptide, but often missense mutations alter the spatial conformation of the protein, thus affecting anchor fibril assembly. Mutations in which dominant hereditary bullous epidermolysis is currently detected are glycine residue substitutions that occur within the collagen molecule as a domain characterized by repeated Gly-XY amino acid sequences. Glycine replacement destabilizes the collagen tricyclic structure, interferes with its secretion, and makes it susceptible to extracellular degradation. Therefore, the role of glycine substitution is at the post-translational level. Since type VII collagen is a homodimer composed of three identical α1(VII) polypeptides, 1/8 of the tricyclic molecule is normal. Thus the mouth can form some normal anchor fibrils, which is consistent with the relatively mild clinical manifestations of fine anchor fibrils and DDEB observed in ultrastructure. In addition to the classic DDEB type, glycine substitution mutations were present in two clinical subtypes (pre- dystrophic bullous epidermolysis and Bart syndrome). 3. The genetic basis of the junctional bullous epidermolysis (JEB) is different from the homozygosity observed in the first two types of bullous epidermolysis. The borderline bullous epidermolysis is very high. The degree of genetic heterozygosity is currently thought to be related to at least six different genes. In borderline bullous epidermolysis (JEB), blisters occur in the basement membrane at the junction of the dermal epithelium, ie, the zona pellucida or overlapping hemidesmosome levels. Under the electron microscope, an abnormality was observed in the area of the semi-bridged anchor wire complex. A study of a large number of patients with lethal and non-sexual borderline bullous epidermolysis found that the three genes encoding the three constituent polypeptides α3, β3 and β2 of anchor fibroin-laminin 5 were specifically mutated. Recently, mutations in genes encoding other components of hemidesmosomes have been detected in some subtypes of borderline bullous epidermolysis. For example, a mutation in a subunit β4 encoding epidermal cell-specific integrin α6, β4 was detected in a patient with bullous epidermolysis and pyloric atresia. In borderline bullous epidermolysis, patients with milder systemic dystrophic benign bullous epidermolysis showed bullous pemphigoid antigen 2 (BPAG2, also known as 180kDa). Mutation of the XVII type collagen). A recent understanding of the molecular basis of borderline bullous epidermolysis has emphasized the complexity of the hemidesmosome-anchored filament complex and its role in pathogenesis. Herlitz type borderline bullous epidermolysis, mutation detection showed that each gene of laminin 5 has mutations (LAMA3, LAMB3 and LAMC3, three genes encoding α3, β3 and γ2 chains, respectively). Most of the mutations were found to occur in the LAMB3 gene, and there are two hotspots that cause mutations, namely R42x and R635x. At the same time, all mutations currently found lead to the early termination of codon production, thereby reducing the corresponding mRNA transcription to a very low level by antisense-mediated mRNA degradation mechanism. Non-Herlitz type borderline bullous epidermolysis also has a mutation in the laminin 5 gene. In some cases, mutations in one of the laminin 5 genes are early termination codes. However, other genetic mutations are missense mutations or exon skip mutations within the framework, and two regional gene mutations were found in these cases. These studies show that full-length polypeptides with intact carboxy termini can assemble into three-dimensional molecules. Three-dimensional structural molecules have a role in anchor filaments. In some patients, bullous plaques occur within the hemidesmosome and are similar and are classified as "false border type" according to the classification of the ultrastructure of the tissue and the severity of the clinical condition. The main components of hemidesmosome (HD) are mainly polypeptides named HD1 to HD5. These multiple abnormalities are likely to be the cause of these subtypes of borderline bullous epidermolysis. According to the ultrastructural changes, patients with bullous epidermolysis with blistering at the level of hemidesmosome can be classified into at least three categories. Its clinical manifestations are different from any of the classic bullous epidermolysis. They are systemic dystrophic benign bullous epidermolysis (GABEB), bullous epidermolysis with pyloric atresia (PA-JEB), and muscular dystrophy bullous epidermolysis (EB/ MD). In the special subtype of nonfatal bullous epidermolysis, systemic dystrophic benign bullous epidermolysis, the BPAG2 gene was found to be mutated. Another rare subtype of nonfatal borderline bullous epidermolysis is characterized by pyloric stenosis and skin blistering as its first symptom, which is the result of mutations in beta integrin. Symptoms 1. Simple bullous epidermolysis (EBS) is a group of hereditary skin diseases characterized by vesicles in the epidermis, mainly caused by keratin mutations, invading a quarter of the population. Further subtypes are divided according to clinical severity. The simple bullous epidermolysis family has a high penetrance rate, and its most severe subtype, the disease manifests itself at birth. There are at least 11 subtypes of simple bullous epidermolysis, of which 7 are autosomal dominant. The three most common subtypes are autosomal dominant, including generalized bullous epidermolysis (Koebnet), localized bullous epidermolysis (Weber Cockayne), and herpes-like bullous epidermium Dowling Meata (Table 2). The blister can be significantly reduced with age, and sometimes it can be blistered for a few months. It may be that as the patient grows older, the epidermis is fully stretched and the mechanical tension is naturally reduced. (1) Generalized bullous epidermolysis: starting from the newborn to the early stage of the baby, more common in the hands, feet and limbs. It can also be seen that the palmar hyperkeratosis and desquamation. Do not involve nails, teeth and oral mucosa. (2) Localized bullous epidermolysis: It is the most common type that begins in childhood or later. It can also appear in adults, which is characterized by thick blistering of the hands and feet after high-intensity exercise. Common hands and feet sweating. The blister on the foot is often infected. (3) herpes-like bullous epidermolysis: can be seen at birth, is the most serious type, vesicles spread throughout the body, can affect the oral mucosa. Significant inflammation and miliary rash can occur in infancy, and blistering is not scarred in early childhood. The trunk and the proximal extremities can be white hair or "herplike" blisters, because the blister fissures are located in the epidermis, leaving no scars. Finger nails may be lost, but are usually regenerable. Unlike the first two types, the blister does not become heavier after the heat. At the age of 6 or 7 years, there may be excessive keratosis. Although some patients have very serious blisters, they are rarely life-threatening. Because of the loss of localized skin barrier function, it is easy to secondary infection. Simple bullous epidermolysis with muscular dystrophy is the only non-keratin mutation in simple bullous epidermolysis, similar to the Koeber type, but with muscular dystrophy in adulthood. 2. Malnutrition Bullous epidermolysis is often accompanied by the formation of scars and miliary rash after blister formation. Subepidermal blisters due to mutation of collagen type VII collagen. It mainly includes four subtypes, namely Cockayne Touraine dominant hereditary type, Pasini white papular-like dominant hereditary type, localized recessive hereditary type and generalized recessive hereditary type. In addition, there are some rare subtypes. Such as Bart syndrome, neonatal temporary bullous epidermolysis and so on. Read more...