Epidermolysis bullosa (EB) is caused by mutations in genes that produce the proteins holding skin layers together. Without these proteins functioning correctly, the skin becomes so fragile that even minor friction, like rubbing from clothing or being picked up as an infant, can cause painful blisters and open wounds. EB affects roughly 41 out of every million live births, and the specific gene involved determines which type a person has and how severe their symptoms will be.
How Healthy Skin Stays Together
To understand what goes wrong in EB, it helps to know how skin is built. Your skin has two main layers: an outer layer (the epidermis) and a deeper layer (the dermis). Between them sits a thin structure called the basement membrane zone, which acts like glue binding everything together. Different proteins anchor each layer to the next, forming a chain of connections from the surface of the skin down into the tissue beneath it.
In EB, a mutation knocks out one link in that chain. Where the break occurs determines which type of EB a person develops, because the skin separates at the level where the faulty protein was supposed to be doing its job.
EB Simplex: Fragile Cells in the Outer Skin
EB simplex is the most common form, with an incidence of about 17.5 per million live births. It’s caused by mutations in the genes that produce keratin proteins inside the cells of the outermost skin layer. These keratins normally form a tough internal scaffold that gives skin cells their strength. When the mutations disrupt how keratin molecules pair together, the scaffold becomes unstable and the cells essentially fall apart under pressure. The blistering happens within the epidermis itself, so the deeper layers remain intact.
Most cases of EB simplex follow a dominant inheritance pattern, meaning only one copy of the mutated gene is enough to cause the condition. A parent with EB simplex has a 50% chance of passing it to each child. Some cases also arise from brand-new mutations in people with no family history at all. In rare instances, EB simplex can be recessive, requiring a child to inherit a defective copy from both parents.
Junctional EB: A Break at the Basement Membrane
Junctional EB occurs when mutations affect proteins in the lamina lucida, a specific zone within the basement membrane that attaches the epidermis to the dermis. The proteins involved here normally form molecular anchors that lock the outer skin layer in place. When those anchors are missing or defective, the skin peels apart right at the junction between its two main layers.
Junctional EB is always a recessive condition. Both parents must carry one copy of the mutated gene, and neither parent typically shows any symptoms. With each pregnancy, there is a 25% chance the child will have junctional EB, a 50% chance the child will be a silent carrier, and a 25% chance the child will inherit no mutations at all. Junctional EB is rarer than the simplex form, occurring in roughly 9.3 per million live births, but it tends to be more severe. Some subtypes can be life-threatening in infancy.
Dystrophic EB: Missing Collagen Anchors
Dystrophic EB is caused specifically by mutations in a single gene called COL7A1, which provides the blueprint for type VII collagen. This collagen is the main ingredient in anchoring fibrils, tiny fiber-like structures that stitch the basement membrane to the dermis below. When the gene is mutated, the collagen molecules come out misshapen or aren’t produced at all, so the anchoring fibrils can’t form properly. Without them, the skin separates beneath the basement membrane at the slightest friction.
Dystrophic EB comes in two forms. The dominant version requires only one mutated copy of the gene and tends to produce milder symptoms, often limited to blistering on the hands, feet, elbows, and knees. A parent with this form has a 50% chance of passing it on. The recessive version is more severe. A child must inherit a faulty copy from each carrier parent. In severe recessive dystrophic EB, the body produces little to no type VII collagen, leaving skin with almost no anchoring fibrils. This leads to widespread blistering, scarring that can fuse fingers and toes together over time, and chronic wounds that struggle to heal.
Kindler EB: A Rarer Fourth Type
A fourth type, Kindler EB, is the rarest form, affecting only about 0.5 per million live births. It involves a different protein that helps connect cells to the basement membrane. Unlike other forms where blistering is confined to one specific skin level, Kindler EB can cause separation at multiple levels. It follows a recessive inheritance pattern.
What Triggers Blisters Day to Day
EB is genetic, so nothing in the environment “causes” it. But everyday physical forces trigger the blistering that the genetic defect makes possible. For most people with EB, the main culprits are friction and pressure: shoes rubbing against feet, clothing seams against skin, or even the simple act of crawling for a baby. Heat and sweating can worsen blistering in EB simplex specifically. In more severe forms, blisters can appear inside the mouth, throat, and digestive tract, triggered by eating or swallowing.
Because the underlying fragility is always present, there is no way to fully prevent blisters. Management focuses on protecting the skin with soft bandaging, avoiding known friction points, and carefully treating wounds to prevent infection.
How EB Is Diagnosed
Because several types of EB look similar on the surface, a standard skin biopsy under a regular microscope often can’t distinguish between them. Doctors use a specialized technique called immunofluorescence mapping, which uses fluorescent-tagged antibodies to identify exactly which proteins are present or absent in a skin sample and pinpoint the precise level where the skin is splitting apart. Genetic testing then confirms which gene is mutated, which is critical for understanding the prognosis and inheritance risk for future children.
Long-Term Risks of Chronic Wounds
People with severe forms of EB, particularly recessive dystrophic and junctional types, face a significantly elevated risk of developing an aggressive form of skin cancer called squamous cell carcinoma. The constant cycle of tissue damage, inflammation, and healing creates conditions that can drive cells toward cancerous changes over years. These cancers tend to appear in areas of chronic wounding and scarring, often starting in early adulthood. They are more likely to spread than typical skin cancers and are a leading cause of reduced life expectancy in people with severe EB.
Gene Therapy for Dystrophic EB
In 2023, the FDA approved the first gene therapy for EB. The treatment is designed for people with dystrophic EB who carry mutations in the COL7A1 gene. It works by using a modified, non-replicating virus to deliver a working copy of the gene directly to wound cells. The therapy is mixed into a gel and applied to wounds once a week by a healthcare provider. By supplying skin cells with the correct genetic instructions, the treatment enables them to produce functional type VII collagen and rebuild the anchoring fibrils that the disease destroys. It is approved for patients six months of age and older.
This approach treats wounds rather than curing the underlying condition throughout the body. Skin that hasn’t been treated remains fragile. But for people living with chronic, non-healing wounds, it represents a meaningful change in what’s possible.