EB simplex (EBS) is the most common type of EB. It also is known as intraepidermal or epidermolytic EB. According to National EB Registry data, more than half of people with epidermolysis bullosa have EB simplex. EBS can be further classified based on the clinical presentation, with variations such as EB-Weber-Cockayne, EB-Koebner, EB-Dowling-Meara, EB with muscular dystrophy and EB with pyloric atresia.
EB simplex usually is caused by a mutation in the gene for keratin 5 or keratin 14. These genes encode keratin proteins, which form one of the major structural components of the superficial layer of the skin, the intermediate filaments. The presence of abnormal keratins results in weakness or fragility of the epidermis. With trauma and friction, the epidermis easily shears, and superficial blisters form. As these blisters are relatively superficial, they burst or rupture easily, leaving behind shallow erosions.
Rarely, people with EBS may have a mutation in another gene, either plectin (associated with EBS with muscular dystrophy, EBS with pyloric atresia and EBS Ogna), a6b4 integrin (associated with EBS with pyloric atresia), plakophilin-1 (associated with plakophilin deficiency) or desmoplakin (associated with lethal acantholytic EB).
Typically, EBS blisters heal without the development of a scar. When scars are seen in the setting of EB simplex, they generally are the result of infection. Post-inflammatory hypopigmentation (lighter areas of skin) or hyperpigmentation (darker areas of skin) occurs commonly with EBS. As blisters heal, the newly formed skin appears lighter or darker than unaffected skin. This change in skin color usually is temporary, although it may take months before the skin color returns to normal.
EB simplex usually is inherited as a dominant condition. In such cases, only one parent has EBS. The affected parent has one abnormal copy of the involved keratin gene and one normal copy of the keratin gene (humans have two copies of most genes). With each pregnancy, there is a 50-50 chance that the abnormal gene will be passed along, resulting in a child with EB simplex. Likewise, there is a 50 percent chance that the normal gene will be passed to the child, resulting in a child who does not have EB. (Figure 2) Rarely, a child affected with EBS may not have an affected parent; this is known as a de novo mutation, which means that the mutation occurred in the egg or the sperm before fertilization and is not carried by either parent. Very rarely, EBS may be transmitted in an autosomal recessive form, in which both parents are normal without any manifestations of EBS; however, they each carry an abnormal copy of the keratin gene. In this instance, there is a 25% chance that the child will inherit both abnormal keratin genes, in which case he or she will be affected.