Overview Hereditary epidermolysis bullosa (epidermolysis bullosa ahereditaria) is a group of relatively common hereditary disorders characterized by blistering after minor trauma to the skin and mucous membranes. Since 1991, Fine et al. have divided it into three major categories based on the location of blister or fissure formation under electron microscopy, and into several subtypes due to the characteristic clinical manifestations. with the progress of molecular genetics research, it is now clear that all three types of epidermolysis bullosa are autosomal recessive or dominant. Epidemiology: With the development of the economy and the improvement of people’s health care, some infectious diseases that seriously endanger human health have been gradually controlled and some have been eliminated. Among the various types of diseases that endanger human health or life, the proportion of infectious diseases is gradually decreasing, while some genetic diseases and chronic diseases related to genetics are becoming more and more prominent to humans. According to statistics, the number of single gene genetic diseases has reached more than 6,500, and the number is increasing by more than 100 every year. There are about 500 human chromosome number abnormalities or structural aberrations. Although the number of polygenic genetic diseases, but more common diseases, high incidence, China has 3% to 5% of the people affected by single-gene diseases; 15% to 20% of the people affected by polygenic genetic diseases; and chromosomal diseases about 100 species, nearly 10 million patients. In addition environmental pollution has led to an increase in base mutations and is also generating a number of new health-seeking genetic diseases. Therefore, there is a trend towards an increased burden of disease caused by genetic factors in the population Genetic epidemiology will play an increasingly important role, and is no exception in dermatological diseases. Etiology The disorder is autosomal recessive (AD) or dominant (AR). The causative genes are the keratin K5 and K14 genes, but do not include rare variants and subtypes can be due to new causative genes are still under investigation. Pathogenesis: Because dyskeratosis can form, the disease is considered a variant of follicular keratosis, and spicule relaxation and dyskeratosis can occur in both diseases, and both diseases may occur in the same patient. Electron microscopic findings of altered tension microfilaments and bridging granule complexes or impaired formation of intercellular material, this underlying genetic defect combined with external stimuli such as friction, heat, injury, cold and bacterial and fungal, especially Candida infections, can trigger the disease. Clinical manifestations Hereditary epidermolysis bullosa is divided into three types and many subtypes but has common clinical features, mostly after birth or within 2 years of age, rubbing areas such as hands, feet, knees, elbows, ankles, buttocks rubbing that appear blisters of varying size and health search (Figure 1), vesicles, crusting pigmentation. May be seen cornea, atrophy, scarring, nail dystrophy, baldness and secondary infection. Post-scarring of the fingers and toes affects function and even causes disability. The clinical manifestations of the three types are shown. The three types and subtypes are briefly described as follows: 1) Epidermolysis Bullosa Simplex (epidermolysis bullosasimplex, EBS) (1) limited (localized): ①Epidermolysis Bullosa Simplex of hands and feet (EBSofhandsandfeet): also known as Weber-Cockayne type, is the most common EBS subtype health search. Blistering occurs mainly on the plantar aspect of the feet followed by the palms of the hands, and when mechanical friction is severe, blistering can occur on any part of the body in neonatal or infantile onset, with a few delayed until adolescence or adulthood. Light in winter and heavy in summer, prolonged walking and mechanical friction can aggravate the condition, often forming a limited or extensive callus with age some patients have remission, a few patients have nail dystrophy cornea and scar formation, no extracutaneous lesions. ②Epidermolysis bullosa simplex withanodontia/hypodontia: also known as Kallin syndrome. This type is rarely associated with brittle hair, partial baldness and dental hypoplasia in addition to limited blistering. (2) Generalized: ①Koebner type epidermolysis bullosa simplex (EBS, Koebnervariant): the second most common subtype of EBS health search. It often develops at birth or shortly after birth with generalized blistering and pressure areas may be marked by nail dystrophy cornea and/or scarring. However, the scarring is superficial and limited. In addition to some patients in the early infant oral cavity will appear mild and limited blisters without extradermal lesions ② herpes-like simplex epidermolysis bullosa (EBSherpetiformis): also known as Dowling-Meara type, the third common subtype of EBS health search. It develops at birth with extensive skin exfoliation, often leading to death in the first year of life. Most patients have lesions similar to Koebner’s type Health Search, and the onset of nail dystrophy, milia, and/or scarring is similar to Koebner’s type. Extensive or fused palmoplantar keratosis develops in most patients by prepubescence. EBS withmottledpigmentationwith/withoutkeratoderma: In this type, irregular hyperpigmented patches of skin are rarely seen in certain areas, most of which do not occur at the site of previous blistering. Some cases may diminish with age. The palmoplantar keratosis is similar to the Weber-Cockayne type without extracutaneous lesions. Superficial epidermolysis bullosa simplex (EBSsuperficialis): blisters or fissures occur only in healthy search under the stratum corneum, similar to the desquamation syndrome. Because the lesions are very superficial, vesicles and post-inflammatory hyperpigmented or hypopigmented spots are more common than intact blisters. It is distinguished from desquamation syndrome by the absence of spontaneous desquamation and the absence of extracutaneous lesions. ⑤ Ogna-type herpetic epidermolysis bullosa simplex (EBS, Ognavariant): this type is rare and unique and has not been reported in China. The lesions are characterized by localized intra-dermal hemorrhagic health search, resembling contusion-like color and hooked nails. (6) Epidermolysis bullosa simplex with or withoutassociated neuromuscular disease (EBSwithorwithoutassociatedneuromusculardisease): this type is rare and severe. It is often associated with myotonic dystrophy or congenital myasthenia gravis. Some cases show atrophic scar pigmentation and nail dystrophy, which is clinically difficult to differentiate from JEB. There is often multi-organ involvement, such as severe anemia due to bone marrow abnormalities and moderate to severe growth retardation due to small intestine abnormalities (7) MendesdaCosta type epidermolysis bullosa simplex (EBS, MendesdaCostavariant): it is the rarest type of systemic EBS. All JEBs are autosomal recessive and are further divided into 6 subtypes based on the extent of lesion involvement and other clinical and laboratory features (1) localized: ① inverse junctional epidermolysis bullosa (JEB, inverse): blisters Vesicles and atrophic scarring occur only in the skin folds, such as the axillae, groin, and neck. There are no extradermal lesions except for blisters and scarring in the oral cavity and esophagus that are as severe as in the Herlitz type ② Junctional epidermolysis bullosa (JEB, acral): also known as minimal JEB (JEB, minimus). The lesion is confined to the limb area. (iii) Progressive junctional epidermolysis bullosa (JEBprogressive): also known as pro-neurotropica (JEB). Characteristically, it does not develop until mid-childhood or later. (2) Generalized: ① Heavy junctional epidermolysis bullosa (JEB, gravis): also known as Herlitz type, also known as lethal JEB (EBlethalis) because of the high mortality rate in infancy. Clinical features include generalized blistering, erosions and atrophic scarring. Symmetrical, highly proliferative granulation tissue may form around the mouth and nose, and when the nostrils are involved, they may become narrowed or even occluded. The granulation tissue may also involve the posterior neck, upper middle back, axillae, and perineural folds. This type of skin is extremely brittle and nail dystrophy is common, which can eventually lead to nail loss and the nail bed being covered by scar tissue. Contractures can occur due to axillary scar formation. Extracutaneous involvement is widespread and severe, including oral lesions resulting in microstomia and tongue tie shortening, esophageal strictures, small intestinal involvement resulting in growth disturbances, and other involvement of the eye and genitourinary tract. Iron malabsorption due to small intestinal damage and blood loss due to chronic extensive skin lesions often result in multifactorial anemia. A few patients may develop severe tracheal and laryngeal lesions to the point of occlusion. Tracheal laryngeal lesions are seen in at least 30% of patients with NE-BR, and tracheotomy can save the lives of these patients, but ultimately they often die in early infancy. Although the cause of death is unknown in most cases, some may be due to sepsis secondary to infection or arrhythmias due to electrolyte disturbances. Pyloric atresia is present in 15% of patients with this type of disease and accounts for only 3% of cases of NEBR. ② mild junctional herpetic epidermolysis bullosa (JEB, mitis): also known as non-Herlitz type or generalized atrophicbenign EB (generalizedatrophicbenignEB). Although blistering, vesicular atrophic scarring, and post-inflammatory hypopigmentation or deepening can occur, proliferative granulation is lacking. Also, extracutaneous lesions are lacking except for tracheal and laryngeal lesions, and nail and scalp lesions are similar to the Herlitz type but with normal lifespan. In many ways this type is similar to systemic DDEB except for enamel dysplasia. ③ scarring junctional maculopapular epidermolysis bullosa (cicatricialJEB): is a rare systemic JEB, characterized by pseudo-parallel finger (toe) deformity, clinically difficult to distinguish from Hallopeau-Siemens type. 3, nutritional health search poorly Dystrophic Epidermolysis Bullosa (DystrophicEB, DEB) The common features of this type are blistering, erosion, crusting, atrophic scarring, milia and nail dystrophy or nail deficiency, which are divided into 9 subtypes according to the distribution range of lesions and different genetic patterns. (1) Limited (localized): ①Dystrophic herpetic epidermolysis bullosa (DEB, inverse): It is a rare type. The lesions are confined to the neck, axillae, groin and lumbosacral region, with extracutaneous lesions involving the oral cavity and esophagus, sometimes with more severe esophageal lesions than cutaneous lesions. ②Dystrophic epidermolysis bullosa (DEB, acral): also known as minimal DEB (minimus). Pretibial dystrophic epidermolysis bullosa (DEB, pretibial): a special limited type, the lesions are confined to the pretibial area, with recurrent small blisters and papular scars, sometimes with purplish red papules, similar to lichen planus, without extracutaneous lesions except for nail dystrophy. (4) Centripetal dystrophic maculopapular epidermolysis bullosa (DEB, centripetal). (2) Generalized: ①Autosomal dominant forms of dystrophic epidermolysis bullosa (DEB, autosomaldominantforms): dominantly inherited white papular dystrophic epidermolysis bullosa (DDEB, albopapuloidea) and dominantly inherited hyperplastic dystrophic epidermolysis bullosa Dystrophic Epidermolysis Bullosa (DDEB, hyperplasique), also known as Pasini type and Cockayne-Touraine type. These two types of lesions are similar, but differ only in the presence of a white fibrotic papule in the former. The papules are confined scarring, which is sometimes difficult to distinguish clinically and requires genetic diagnosis of extracutaneous lesions that may present with mild oral erosions and scarring, sometimes with severe esophageal involvement Very few patients may develop squamous cell carcinoma but it has little impact on life expectancy. Transientbullousdermolysisofthenewborn often develops at birth or shortly after birth and resolves spontaneously by 6 to 9 months of age, leaving a slight atrophic scar and limited nail dystrophy. (2) Autosomal recessive dystrophic epidermolysis bullosa (DEB, autosomalrecessiveforms): recessive severe dystrophic epidermolysis bullosa (RDEB, gravis), also known as Hallopeau-Siemens type, is one of the severe types of hereditary EB. It develops at birth, with progressive involvement of lesions throughout the body and high early infant mortality. Surviving children often develop invasive squamous cell carcinoma on the surface of recurrent blisters and scarring. Most squamous carcinomas develop limited type or systemic metastases, leading to death. Severe multi-organ involvement is common, most commonly oral involvement resulting in microstomia and tongue tie shortening extensive dental caries leading to early tooth loss and further nutritional incorporation difficulties, in addition to esophageal stricture, growth retardation, and severe multifactorial anemia. Rarely, there is extensive genitourinary and lower gastrointestinal tract involvement with corneal and conjunctival blistering and crusting. Many patients develop pseudophalangeal syndactyly in early childhood, resembling a claw pattern, leading to muscle atrophy and partial resorption of the finger (toe) bones and eventually to severe dysfunction. Repeated health search secondary infections can also lead to septicemia. In recessive mild dystrophic epidermolysis bullosa (RDEB, mitis), patients with this type are clinically similar to Cockayne-Touraine type, and extracutaneous involvement is rare. On light microscopy all EBS except superficial EBS have a healthy search for blisters or fissures within the subepidermis near the lowermost part of the epidermis. The blisters or fissures of both JEB and DEB were located in the subepidermis, so the two could not be distinguished under light microscopy. Transmission electron microscopy showed that the fissures of superficial EBS occurred in the granular layer, whereas all other EBS had fissures within or on the basal layer; the blisters of JEB occurred in the middle layer of the hyaline plate, and the fissures of DEB were located at the dense plate below the dermal-epidermal junction. Anchor progenitor fibers are usually absent in severe RDEB, reduced in most RDEB, and reduced or normal in DDEB. Recent studies have found that the severity of DEB is negatively correlated with the mean diameter of the anchorigenic fibers in cross-section, i.e., the diameter becomes progressively smaller from the limited form of DDEB to the generalized form and finally to RDEB. In case of anemia, the peripheral blood picture shows a decrease in red blood cell count and hemoglobin amount; in case of complicated infection, the peripheral blood picture shows a significant increase in white blood cell count and neutrophil count; in case of severe infection with water-electrolyte disorders, blood sodium, potassium, chloride, pH and liver and kidney function should be examined. Immunofluorescence antigen localization showed that in EBS, herpes pemphigoid serum, type IV collagen antibody and laminin antibody were on the dermal side; in JEB, herpes pemphigoid serum was on the epidermal side and type IV collagen antibody and laminin antibody were on the dermal side; in DEB, herpes pemphigoid serum, type IV collagen antibody and laminin antibody were on the epidermal side. In addition electron microscopy showed varying amounts of collagen lysis health search in the upper dermis of most DEB. In neonatal transient maculopapular dermatolysis, amorphous stellate vesicles are seen in the perinuclear area of the basal cells. Other ancillary tests Chest X-ray electrocardiogram and ultrasound should be done in severe cases. Related tests: >Arterial blood pH >White blood cell count >Red blood cell count >Glucose >Hemoglobin Complications Scar formation affects function and even causes disability, resulting in microstomia and shortened tongue tie, esophageal stricture, small intestine involvement, tracheal and laryngeal lesions with myotonic dystrophy or congenital myasthenia gravis. Severe anemia and small bowel abnormalities often occur with multi-organ involvement and may result in growth retardation. Septic sepsis or electrolyte disturbances secondary to infection can lead to cardiac arrhythmias, etc. Diagnosis A preliminary diagnosis can be made based on the clinical manifestations of onset before 2 years of age, the characteristic clinical manifestations of blistering at the rubbing site combined with the medical history, and a definitive diagnosis can be confirmed by combining immunofluorescent antigen localization and projection electron microscopy with subtype and variant diagnosis. Differential diagnosis In the neonatal period, it is sometimes necessary to differentiate from herpes simplex, congenital porphyria pigmentosa, herpetic mast cell hyperplasia, Staphylococcus aureus scalded skin syndrome and epidermolysis bullosa hyperkeratosis ichthyosis, etc. Treatment There is no specific treatment for all types of genetic EB. Vitamin E and micronutrients such as zinc and iron supplementation. For extensive and severe lesions, oral corticosteroids can be given as appropriate, 0.5~1.0mg/(kg・d) for children, and the dosage should be gradually reduced after the onset of effect, and should not be applied for a long time to prevent adverse reactions. 3, local treatment (1) Protect the skin: pay attention to skin protection, reduce friction to prevent blistering. (2) Pick the blisters: When blisters appear, pick the blisters to prevent further expansion. (3) Prevention and treatment of secondary infections: Keep the trauma clean, clean the trauma daily or every other day if necessary, and apply topical anti-inflammatory creams. For chronic infections, topical mupirocin trade name Bactrim is used on the trauma. 4.Surgical treatment A few children with JEB and DEB who develop esophageal stricture can undergo stenosis dilatation and urethral release. The pseudo-webbing between the fingers (toes) of the hands and feet can be loosened. In the case of long-standing erosions, skin grafts or homologous or autologous keratinocyte culture grafts should be used to cover the occurrence of squamous carcinoma, and the lesion should be completely excised. In some patients with JEB, tracheotomy is performed if necessary to maintain spontaneous breathing and avoid death from airway obstruction. Early restorative dentistry is performed in patients with enamel hypoplasia.