Epidermolysis bullosa (EB) is a rare genetic disease. The skin of patients is fragile and can break with a slight friction, forming blisters or blood blisters. In severe cases, blisters may even appear in the mucous membranes of the mouth, tongue, esophagus, stomach, etc., blocking eating, causing malnutrition, skin deformation, limb atrophy, and even skin cancer.
Epidermolysis bullosa (EB), also known as hemidesmosome epidermolysis bullosa and hereditary epidermolysis bullosa, is a large class of mechanical bullous skin diseases. The skin of patients is extremely fragile, and the slightest friction can cause the skin to break or form blisters. Symptoms usually appear at a very young age. Blisters are a typical sign of epidermolysis bullosa. Some forms of EB may gradually heal, but others will develop over time and have a serious impact on life. Because the skin of patients is particularly fragile, they are also called "butterfly babies". Epidemiology: All types and subtypes of hereditary epidermolysis bullosa are rare. In the United States, the total incidence is about 1/53,000, and the prevalence is about 1/125,000. Data from some European countries are similar. All races can be affected, with no gender difference. It is estimated that 1 in every 50,000 live births has some type of EB.
What are the clinical manifestations of hereditary epidermolysis bullosa (EB)?
The common feature of all types of hereditary epidermolysis bullosa is mechanically fragile skin, which can affect the eyes, mouth, digestive tract and urogenital tract, manifested as blisters, erosions, ulcers and scar formation. Slight friction or collision can cause separation of a certain ultrastructural part of the skin and cause madness. It is easy to occur on the extensor side of the limb joints. In severe cases, it can affect the whole body. All types of EB can form scars after healing. Repeated attacks of acral skin lesions can cause atrophy or absence of fingernails and toenails. Some patients can see miliary papules and atrophic hair on the scalp. The simple type has the mildest clinical symptoms, and blisters are often found in the friction area within 2 years of age. The junctional type has blisters at birth, with a poor prognosis, and most of them die within 2 years of age. The malnutrition type is more serious, with deeper blisters, which often appear at birth. Repeated blisters and scars on the extremities can cause skin adhesion between the fingers and toes, atrophy of the phalanges, and form claw-shaped hands. The mucosa can also be affected. Repeated ulceration and scabs of the oropharyngeal mucosa can cause patients to have difficulty opening their mouths and swallowing; the prognosis is poor. The incidence of skin tumors in patients with autosomal recessive malnutrition is increased.
Hereditary epidermolysis bullosa is mainly differentiated from the following diseases:
(1) Acquired epidermolysis bullosa This disease is an autoimmune skin disease, with the target antigen being type VII collagen. It is common in adults and manifests as blisters or bullae at the friction site, but there is no family history of this disease. Immunofluorescence can show IgG deposition in the basement membrane zone.
(2) Bullous pemphigoid It is common in the elderly and manifests as multiple tension bullae on the basis of erythema. Mucosal involvement is rare and it is accompanied by severe itching. Histopathological examination shows eosinophil infiltration, immunofluorescence shows band-like deposition of IgG and C3 in the basement membrane zone, and serum anti-BP180 antibody (+). (3) Porphyria Porphyria cutanea tarda is caused by a defect in the activity of uroporphyrinogen decarboxylase in the liver. The disease is divided into acquired and hereditary types. The latter is often autosomal dominant. Accumulation of uroporphyrin and other highly carboxylated porphyrins causes skin damage. The skin may develop blisters, erythema, scars, hirsutism, pigmentation or loss, and scleroderma-like changes. Laboratory examinations can reveal a significant increase in uroporphyrins, as well as increased levels of coproporphyrin and D-amino-C-ketovaleric acid, accompanied by increased serum iron and abnormal liver function. Congenital erythropoietic porphyria is an autosomal recessive 237 inheritance caused by a lack of uroporphyrinogen III polymerase. Most patients have photosensitivity of the skin from early childhood, manifested as erythema, blisters, blood blisters, etc. in the sun-exposed parts. The skin lesions are repeated, severe in summer and mild in winter, and eventually severe scars are formed, resulting in the destruction and deformity of the exposed parts.
Clinical manifestations:
The common feature of various types of epidermolysis bullosa is that blisters and blood blisters appear on the skin after slight friction or collision; the extensor side of the extremities and limb joints is particularly prone to occur. In severe cases, any part can be affected, and scars can form after healing. Repeated attacks of extremity skin lesions can cause atrophy of the fingernails and toenails, and miliary papules and atrophic baldness of the scalp can be seen. There are many types of EB, all of which are closely related to gene mutations. EB can be divided into three categories according to the location of skin separation: simple EB (blister located in the epidermis), junctional EB (blister located in the center of the transparent plate and basement membrane zone) and malnutrition EB (blister located under the dense plate).
(1) Simple EB is mostly chromosomal dominant inheritance and is the mildest type. Blisters occur in the basal cell layer of the epidermis and are relatively superficial. They are seen on the extensor side of the extremities and limb joints. Generally, no scars are left after healing. There is little damage to the mucosa and nails. Blisters are often found in the friction area within 2 years of age, and the Nikolsky sign is negative.
(2) Junctional EB
It is an autosomal recessive inheritance. There are extensive blisters, bullae, erosions and scabs after birth. Atrophic scars appear after healing, which can cause syndactyly, enamel hypoplasia, nail dystrophy or nail loss; the prognosis is poor, and most patients die within 2 years of age.
(3) Malnutrition-type EB is inherited in an autosomal dominant or autosomal recessive manner. The disease is usually severe. Blisters often appear at birth and are located deep. Obvious scars are left after healing. Blisters can occur anywhere on the body surface, but are often most serious on the extremities. Repeated blisters and scars on the extremities can cause skin adhesion between the fingers and toes, atrophy of the phalanges, and claw-shaped hands. Mucosa can also be involved. Repeated ulceration and scab formation of the oropharyngeal mucosa can cause patients to have difficulty opening their mouths and swallowing. The prognosis is poor. The incidence of skin tumors in patients with autosomal recessive malnutrition-type EB is increased.
Auxiliary examinations: including common histopathology of skin lesions, skin immunofluorescence pathology, and salt splitting tests. Depending on the subtype, skin histopathology shows intraepidermal or subepidermal blisters lacking inflammatory cell infiltration. Both direct and indirect immunofluorescence are negative. Skin salt splitting tests indicate that fluorescence is deposited on the dermis. Diagnostic basis: The best way to diagnose and classify hereditary epidermolysis bullosa is to inquire about the patient's personal and family history in detail, and further verify it through skin tissue pathology, immunofluorescence, transmission electron microscopy and genetic testing. Patients with severe clinical phenotypes can undergo prenatal diagnosis and genetic counseling.
How should patients with hereditary epidermolysis bullosa (EB) be cared for?
① Diet: EB patients should be given a high-protein diet (eggs, milk, fish, etc.); avoid eating hard foods to avoid no taboo food types, but because blisters lose a lot of white matter, causing oral mucosal damage and causing blister erosion; patients with gastrointestinal ulcers should not eat spicy and irritating foods.
② Activities: EB patients should try to avoid strenuous activities to avoid friction and injury to the skin causing blisters and erosion
③ Wear loose and soft clothes and shoes, and use pads, bandages, gloves, etc. to protect the parts that are susceptible to friction.
④ For eroded and ulcerated skin, clean and disinfect the wound in time, apply new dressings, sterile gauze wet compresses or broad-spectrum antibiotic ointment externally (if the wound is cleaned and disinfected properly and there is no sign of infection, it can be omitted) to avoid infection.
⑤) Non-adhesive sterile synthetic hydrogel dressings can be used for wound care. Finger separation bandage protection can be used to prevent its deformed fusion from causing dysfunction
Treatment progress
Birch triterpenes: Birch triterpenes are the first EMA-approved botanical drug for the hereditary skin disease bullous epidermolysis. The extract with betulin as the main ingredient can regulate inflammatory mediators and activate intracellular pathways involved in keratinocyte differentiation and migration, wound healing and closure. At present, the treatment of EB is mainly symptomatic, with slow wound healing, repeated infection, and increased pain when changing dressings. There is an unmet clinical need. Birch triterpenes are a drug that accelerates wound healing, improves clinical symptoms, and improves the quality of life of patients.
