Epidermolysis bullosa (EB) primarily affects the skin, but it can also damage the mouth, esophagus, eyes, hands, feet, and urinary tract. While most people associate EB with skin blistering, the more severe forms reach well beyond the surface, affecting nearly any tissue lined with delicate membranes.
How EB Affects the Skin
The skin has two main layers: an outer layer (the epidermis) and an underlying layer (the dermis). Between them sits a thin zone called the basement membrane, which acts like glue holding the two together. In EB, the proteins that anchor these layers are defective or missing, so the skin tears apart with minimal friction.
Where that separation happens depends on the type of EB. In epidermolysis bullosa simplex, the most common form, blisters form within the epidermis itself. The structural proteins in that outer layer, keratin 5 and keratin 14, fail to assemble into the strong networks that normally keep skin cells resilient. In junctional EB, the split occurs right at the basement membrane. In dystrophic EB, the separation is deeper, in or just below the basement membrane, where a protein called collagen VII normally anchors the skin layers together. Kindler syndrome, a rarer type, can cause blisters across multiple layers at once, which is why it looks different from person to person.
Blisters can appear anywhere on the body, but friction points like the hands, feet, knees, and elbows are hit hardest. Even putting on shoes, crawling as an infant, or being picked up can tear the skin open.
Mouth, Throat, and Esophagus
The same fragile tissue that blisters on the outside also lines the inside of the mouth and the esophagus. In severe forms, particularly recessive dystrophic EB, eating becomes painfully difficult. Chewing and swallowing create the same kind of friction that damages the skin, so blisters and open sores develop on the tongue, gums, inner cheeks, throat, and the tube connecting the throat to the stomach.
Over time, repeated blistering and healing inside the esophagus produces scar tissue that narrows the passageway. This narrowing, called esophageal stricture, occurs in more than 50% of people with dystrophic EB. In mild cases, solid food becomes hard to swallow. In severe cases, a person may only tolerate liquids or nothing at all. Chronic difficulty eating leads to malnutrition and low body weight, which is one of the most serious ongoing challenges for people living with severe EB.
Hands and Feet
In dystrophic EB, the hands and feet undergo a particularly devastating process. Repeated blistering and scarring on the fingers and toes causes the skin between them to fuse together over time. The digits gradually curl inward as scar tissue tightens around the joints, eventually forming what doctors call “mitten deformities,” where the hand loses its individual fingers and becomes encased in a pouch of scar tissue. This fusion also affects the feet, limiting mobility significantly. Surgery can temporarily separate the fingers, but the scarring tends to recur.
Eyes and Vision
The surface of the eye is covered by a thin, delicate membrane that is vulnerable to the same blistering process. The most common eye problems in EB are recurring corneal erosions and abrasions, where the clear front surface of the eye blisters or scrapes off. Over time, repeated damage leads to corneal scarring, which clouds vision.
The eyelids can also blister and scar, pulling them out of their normal position. When an eyelid turns inward, the eyelashes rub against the cornea with every blink, creating a cycle of further damage. Because these problems can begin in infancy, early screening is important to catch sight-threatening complications before they progress.
Teeth and Gums
EB frequently affects dental health. The same proteins missing from the skin play roles in tooth development, and many people with junctional and dystrophic EB have teeth with weak, poorly formed enamel. This makes teeth unusually prone to cavities and breakage. Combined with the mouth blistering that makes brushing painful, dental decay becomes a persistent problem that often requires extensive care from an early age.
Urinary Tract
A less well-known consequence of EB is damage to the urinary system. The lining of the urethra and bladder is a mucosal membrane, the same type of tissue that blisters elsewhere in the body. In the most severe subtypes of junctional and recessive dystrophic EB, scarring can narrow the urethral opening. This was the most common urinary complication found in a large registry study, affecting roughly 8 to 12% of patients with the most severe forms. Urinary retention, bladder thickening, and kidney complications from backed-up urine also occur, though less frequently. Bladder infections are more common in certain subtypes as well.
Gastrointestinal Tract Beyond the Esophagus
Blistering can extend further down the digestive system. The lining of the stomach and intestines may be affected, and chronic constipation is a common complaint, particularly in dystrophic EB. Scarring around the anal canal can make bowel movements painful and difficult, creating a cycle of avoidance that worsens the problem. Combined with the nutritional challenges from esophageal involvement, gastrointestinal complications are a major source of day-to-day difficulty for people with severe EB.
Lungs and Airway
The respiratory tract is lined with mucous membranes that can blister in severe forms of EB. Blisters or sores in the throat and upper airway can cause hoarseness, a weak cry in infants, or breathing difficulties. In junctional EB, airway involvement is a serious concern, as scarring can progressively narrow the passages that carry air to the lungs.
Why So Many Body Parts Are Affected
The reason EB reaches so far beyond the skin comes down to biology. The proteins that hold skin layers together, collagen VII, laminin, keratin, and others, are also present in the mucosal membranes lining the mouth, eyes, digestive tract, airway, and urinary system. When the gene responsible for one of these proteins is defective, every tissue that relies on it becomes fragile. The skin takes the most visible damage because it faces the most friction, but internally, the simple act of swallowing food, blinking, or passing urine creates enough mechanical stress to injure these vulnerable tissues.
Not everyone with EB experiences all of these complications. The mildest forms, like localized epidermolysis bullosa simplex, may only cause blistering on the palms and soles. The most severe forms, particularly generalized junctional EB and recessive dystrophic EB, can affect virtually every mucosal surface in the body. The specific gene mutation and the protein it disrupts determine which tissues are at risk and how severely they are affected.