EB disease, or epidermolysis bullosa, is a group of rare genetic skin disorders that cause the skin to blister and tear from minor friction or trauma. About 50 in every 1 million live births are affected. The underlying problem is a defect in the proteins that hold skin layers together, so even gentle contact like rubbing, scratching, or wearing shoes can cause painful wounds.
What Happens in the Skin
Healthy skin stays intact because proteins act like anchors between its layers. In EB, genetic mutations cause one or more of these anchoring proteins to be missing, defective, or produced in insufficient amounts. Without that structural glue, the layers separate under even light mechanical stress, forming fluid-filled blisters and open wounds.
In the most common form, EB simplex, the faulty proteins are keratin 5 and keratin 14. These normally pair together to form a scaffold inside skin cells. When they’re defective, they clump into abnormal aggregates, trigger inflammation, and leave the outer skin layer fragile enough to rupture from everyday activity like walking or being picked up.
The Four Main Types
EB is classified by where in the skin the blistering occurs. Each type involves different proteins and different skin layers, which is why severity varies so widely from one person to another.
EB Simplex
This is the most common form. Blisters form within the outermost skin layer (the epidermis). In mild cases, blistering is limited to the palms and soles. More severe subtypes cause blisters across the entire body. The skin on the hands and feet often thickens over time. Most people with EB simplex have a normal or near-normal life expectancy.
Junctional EB
Blisters form at the junction between the outer and deeper skin layers. This type is often severe. Open sores can develop on the face, trunk, and legs and may lead to serious infection or dangerous fluid loss. Blisters can also form inside the mouth, throat, digestive tract, and urinary system. Nails may be rough, thickened, or absent, and tooth enamel is often poorly formed. The most severe form of junctional EB carries a high rate of infant and early childhood mortality, with many children not surviving past age 2.
Dystrophic EB
Blisters form below the basement membrane, in the upper portion of the deeper skin layer (the dermis). Most people with dystrophic EB have the recessive subtype, which tends to be more severe. Blistering can cover large areas of the body, and repeated wound healing causes heavy scarring. Over time, that scarring can fuse fingers and toes together, a complication called pseudosyndactyly. Internal blistering in the mouth and esophagus makes eating painful and difficult. Small white bumps called milia are common on the skin.
Kindler Syndrome
This rarer form causes blistering across multiple skin layers simultaneously. It typically starts on the hands and feet but can spread, sometimes involving the esophagus and bladder. Over time the skin becomes thin and wrinkled, and it’s unusually sensitive to sun damage.
How EB Is Inherited
EB is caused by mutations in genes that code for structural skin proteins. It can be passed down in two ways. In autosomal dominant inheritance, a child needs only one copy of the mutated gene (from one parent) to develop the condition. Most cases of EB simplex follow this pattern. In autosomal recessive inheritance, both parents must carry a copy of the mutation, and the child must inherit both copies. Severe junctional EB and recessive dystrophic EB follow this pattern. In rare cases, EB results from a new spontaneous mutation with no family history.
How It’s Diagnosed
Doctors typically suspect EB based on visible blistering, especially if it appears in infancy after minor skin contact. Two tests confirm the diagnosis. The first is a skin biopsy examined under a special microscope that uses reflected light (immunofluorescence mapping). This shows exactly which skin layer is separating and whether the key structural proteins are present and functioning. The second is genetic testing through a blood sample, which identifies the specific gene mutation. Together, these tests pinpoint the exact EB subtype, which is critical for predicting severity and guiding care.
Serious Complications
Mild EB may cause little more than inconvenient blistering. Severe forms, however, can affect nearly every system in the body.
Chronic wounds create a constant risk of bacterial infection. Repeated scarring in dystrophic EB can fuse fingers together and lock joints into fixed positions, progressively limiting mobility. Blistering in the esophagus leads to narrowing and scarring that makes swallowing painful, contributing to poor nutrition and weight loss.
The most dangerous long-term complication is an aggressive form of skin cancer called squamous cell carcinoma. Chronic wounds and scarring dramatically raise the risk, particularly in junctional and dystrophic EB. In severe recessive dystrophic EB, the risk of dying from this cancer reaches nearly 79% by age 55, and median survival after initial diagnosis of the cancer is roughly 5 years. This cancer is the leading cause of death in adults with severe EB.
Anemia is another frequent problem, driven by chronic inflammation and low iron and zinc levels. When hemoglobin drops too low, wound healing slows because tissues don’t get enough oxygen. Eye complications, including corneal erosions and scarring, can also occur and usually require ongoing monitoring.
Daily Wound Care
There is no routine that eliminates blistering entirely, so daily wound management is central to living with EB. When blisters form, the standard approach is to puncture them at multiple points with a sterile needle to drain the fluid while leaving the overlying skin intact. That top layer of skin acts as a natural bandage, reducing pain and infection risk.
Dressing selection matters enormously. Anything that sticks to wounds can rip fragile skin when removed, so all dressings must be non-adherent. Common options include silicone-coated foam dressings, modified absorbent pads with a plastic film layer, and specialized mesh dressings impregnated with petroleum-based compounds that won’t bond to the wound surface. Caregivers often spend one to several hours each day changing dressings, depending on how much of the body is affected.
Nutrition and Growth
Children and adults with severe EB need significantly more calories and protein than average because their bodies are constantly healing wounds. Nutritional guidelines suggest children with EB may need 100% to 150% of the normal estimated energy requirement for their age, and 115% to 200% of normal protein intake. Many children with severe forms receive nutrition through a feeding tube placed directly into the stomach to ensure they get enough.
Iron and zinc deficiencies are common, especially in junctional and recessive dystrophic EB. Oral iron supplements are the first-line treatment for anemia, though they don’t work equally well for everyone. When hemoglobin stays persistently very low, blood transfusions may be needed. There are no EB-specific guidelines for micronutrient supplementation, so clinicians typically adjust doses based on blood test results.
Gene Therapy and Treatment Advances
For most of EB’s history, treatment has been limited to wound care and managing complications. That changed in 2023 when the FDA approved Vyjuvek, the first gene therapy for any form of EB. It’s approved for patients 6 months and older with dystrophic EB caused by mutations in the COL7A1 gene, which provides instructions for making a critical collagen protein.
Vyjuvek works by delivering a functional copy of that gene directly into wound cells using a modified herpes simplex virus as a carrier. A healthcare provider applies the gel in droplets to open wounds once a week. In clinical trials, 65% of wounds treated with Vyjuvek fully closed, compared to 26% of wounds treated with a placebo. The therapy does not cure EB or prevent new blisters from forming elsewhere, but it represents a meaningful step toward addressing the root genetic cause rather than just managing symptoms.
Life Expectancy Across Subtypes
Prognosis depends almost entirely on which subtype a person has. Milder forms of EB simplex have little to no impact on lifespan. People with these forms may deal with painful blistering throughout life but face no elevated mortality risk. Severe junctional EB sits at the other extreme, with most affected infants not surviving beyond their second year. Severe recessive dystrophic EB falls in between: many people live into their 30s, 40s, or 50s, but face increasing risk from squamous cell carcinoma and cumulative organ damage as they age. Kindler syndrome can lead to skin cancer in adulthood, typically at sites of chronic damage on the hands, feet, and mucous membranes.