What Is Epidermolysis Bullosa (EB)?
“Butterfly children” is a term commonly used by the public to describe children living with Epidermolysis Bullosa (EB) (Figure 1). Although not a medical term, it powerfully captures the essence of the disease: skin as fragile as a butterfly’s wings, unable to withstand even the minor friction of everyday life—friction that would normally go unnoticed.
Figure 1. Butterfly Children
From a medical perspective, Epidermolysis Bullosa (EB) is not a single disease, but a group of rare inherited disorders caused by defects in structural proteins of the skin. Based on the specific level at which skin separation occurs, EB is mainly classified into Epidermolysis Bullosa Simplex, Junctional Epidermolysis Bullosa, Dystrophic Epidermolysis Bullosa, and Kindler syndrome. These subtypes differ markedly in severity, involvement of mucosal tissues, risk of complications, and long-term prognosis.
It is important to emphasize that EB is not contagious. It is a congenital, lifelong structural condition, and individuals living with EB often require long-term, continuous medical care as well as sustained social support.
How Does Epidermolysis Bullosa Begin?
Normal skin is not a single thin layer, but a complex structure composed of multiple layers, including the epidermis, basement membrane zone, and dermis. These layers are firmly connected by various structural proteins—such as keratins, laminin, and type VII collagen—which allow the skin to remain flexible while maintaining sufficient mechanical strength.
In individuals with Epidermolysis Bullosa, mutations occur in the genes that encode these critical structural proteins. These mutations do not make the skin “thinner.” Instead, they disrupt the anchoring system that holds the skin layers together. When external force is applied to the skin surface, the stress cannot be evenly distributed. Instead, it concentrates at the weakest points of attachment, ultimately causing separation between skin layers and resulting in blister formation or open wounds (Figure 2).
Figure 2. Blisters or open wounds
This structural defect is already present during embryonic development and cannot be repaired through growth, which is the fundamental reason why Epidermolysis Bullosa is a lifelong condition.
How Is Epidermolysis Bullosa Treated?
At present, there is no definitive cure for Epidermolysis Bullosa. Current management focuses primarily on minimizing friction and pressure on the skin in daily life and the environment, while carefully caring for existing wounds to reduce secondary tearing and infection. Meanwhile, gene therapy, protein replacement, and regenerative medicine are actively under investigation.
The most clinically advanced breakthroughs to date are centered on genetic reconstruction of the skin. Ex vivo gene therapy has achieved landmark success. In this approach, a small biopsy of relatively healthy skin is taken from the patient, and keratinocyte stem cells are isolated. In the laboratory, a functional copy of the defective gene—such as COL7A1—is introduced into these cells using safely engineered retroviral or lentiviral vectors. The corrected cells are then expanded to generate sheets of genetically repaired epidermis, which are surgically transplanted back onto the patient’s chronic wounds.
Research teams in Italy and Germany have successfully treated multiple patients with dystrophic EB using this method. Follow-up over several years has shown that the transplanted skin remains durable, does not blister, and stably expresses type VII collagen. Current efforts are focused on optimizing this technique to treat larger body surface areas.
Another promising strategy involves direct in vivo delivery of gene therapy tools to target cells within the patient’s skin. Ongoing research is exploring both local injection and systemic administration, using novel viral vectors—such as modified adeno-associated viruses (AAVs)—or non-viral platforms, including lipid nanoparticles, to deliver therapeutic gene sequences to affected skin cells.
In parallel, symptom-modifying therapies and regenerative approaches are also advancing. One example is antisense oligonucleotide therapy, which aims to reduce blister formation by silencing mutations that introduce premature stop codons, allowing cells to produce partially functional proteins. This approach has now entered clinical trials.