Epidermolysis bullosa (EB) causes death through several different pathways depending on the type and severity of the disease. The most common causes are overwhelming infection (sepsis), aggressive skin cancer, heart failure, kidney failure, and airway obstruction. Which of these poses the greatest threat depends largely on which form of EB a person has and their age.
EB is a group of genetic conditions that cause the skin to blister and tear from minimal friction. In severe forms, blistering also affects internal tissues, including the lining of the mouth, throat, and digestive tract. The constant cycle of wounding and scarring drives most of the life-threatening complications.
Why the Type of EB Matters
There are four major types of EB, and they carry very different risks. The simplex form (EBS) is the mildest and rarely fatal, though it can occasionally cause death from sepsis in early childhood. Junctional EB (JEB), particularly the severe Herlitz subtype, carries the highest risk in infancy and early childhood. Most children with Herlitz JEB who die do so before age six, primarily from sepsis, failure to thrive, and respiratory failure.
Recessive dystrophic EB (RDEB), especially the severe generalized form, is the type most associated with death in adolescence and adulthood. These patients face a compounding series of threats as they age: skin cancer, heart failure, kidney failure, and chronic infection. The disease essentially wears down multiple organ systems over time.
Sepsis From Chronic Open Wounds
The most immediate threat across all severe EB types is sepsis, a life-threatening response to infection that spreads through the bloodstream. Because EB patients live with large areas of open, slow-healing skin, bacteria have a constant entry point into the body. The two most common culprits are Pseudomonas aeruginosa and Staphylococcus aureus, both of which frequently show resistance to standard antibiotics.
In children with severe RDEB, a history of bloodstream infection is associated with a sixfold increase in the odds of dying. For infants with junctional EB, sepsis is the single leading cause of death. The risk is highest in the first two years of life, when blistering is widespread and the immune system is still developing. Even with aggressive wound care and infection monitoring, the sheer volume of vulnerable skin makes prevention extraordinarily difficult.
Skin Cancer in Dystrophic EB
For people with severe RDEB who survive childhood, squamous cell carcinoma becomes the dominant threat. This is not the relatively slow-growing skin cancer most people think of. In EB, squamous cell carcinomas arise in areas of chronic scarring, tend to be highly aggressive, and metastasize at alarming rates. In one 28-year study, 52% of severe RDEB patients who developed this cancer had metastatic disease.
The numbers are stark. The cumulative risk of developing at least one squamous cell carcinoma reaches roughly 68% by age 35 and 90% by age 55 in severe RDEB. The median age at first diagnosis is just 29.5 years. The cumulative risk of dying from this cancer reaches about 39% by age 35 and 79% by age 55. These cancers often appear in wounds that have been cycling through breakdown and scarring for years or decades, and they can be difficult to distinguish from the surrounding damaged skin until they are advanced.
Heart Failure From Chronic Strain
Dilated cardiomyopathy, a condition where the heart muscle weakens and the heart enlarges, is a significant and sometimes sudden cause of death in severe RDEB. About 30% of patients with the most severe form of RDEB who developed this complication died from it, some as young as three years old. In one study tracking 61 children with RDEB, nearly 10% developed confirmed cardiomyopathy, with an average age of diagnosis around nine years. Three of those six children died within months.
The causes appear to be layered. Severe chronic anemia, which is nearly universal in serious EB due to ongoing blood loss from wounds and poor nutrition, forces the heart to work harder over years. Deficiencies in key nutrients like carnitine and selenium, both difficult to maintain when eating is painful and the body is constantly repairing tissue, may further damage heart muscle. Early cases were attributed to iron overload from repeated blood transfusions, but the picture is now understood to be more complex.
Kidney Failure
Renal failure is the second leading cause of death in adults with severe RDEB, surpassed only by metastatic squamous cell carcinoma. It can develop through several mechanisms. Chronic inflammation from years of wound healing can trigger a condition called secondary amyloidosis, where abnormal proteins accumulate in the kidneys and gradually destroy their function. Repeated streptococcal skin infections can cause a form of kidney inflammation. In some cases, scarring in the urinary tract physically obstructs urine flow.
Kidney disease in EB tends to develop silently over years. By the time symptoms appear, significant damage has often already occurred. It can also occur in junctional EB and milder forms of dystrophic EB, though much less commonly.
Airway Obstruction
In junctional EB, blistering can occur inside the airway, particularly around the voice box (larynx). Active blisters in the tissue above and around the vocal cords can swell and block airflow acutely. When those blisters heal, the resulting scar tissue thickens the surrounding cartilage and narrows the airway permanently. Scarring between the structures that control vocal cord movement can freeze the cords in place, further restricting breathing.
This complication can be fatal. One documented case involved a 22-month-old who died from acute airway obstruction. A postmortem examination revealed that granulation tissue had replaced the normal lining of the larynx, leaving a critically narrow passage. Some children require a permanent tracheostomy, a surgically created opening in the neck to bypass the damaged airway. Even with that intervention, the underlying disease continues to cause scarring in surrounding tissues.
Failure to Thrive in Infants
For babies with severe junctional EB, the simple act of feeding can be devastating. Blistering inside the mouth and esophagus makes eating painful, and the body’s massive energy demands for constant wound healing outpace what many infants can take in. This combination of reduced intake and increased need leads to severe malnutrition and failure to thrive, which is the second leading cause of death in children with JEB after sepsis. Malnutrition also weakens the immune system, making sepsis more likely, creating a cycle that becomes increasingly difficult to break.
In older children and adults with RDEB, esophageal scarring can progressively narrow the swallowing passage, compounding nutritional problems over time and contributing to the anemia and micronutrient deficiencies that drive heart and kidney complications.