Epidermolysis bullosa (EB) refers to a group of genetic diseases characterized by blistering in response to minor trauma. It is divided into 3 major categories based on the depth of skin blistering: (1) EB simplex (intraepidermal skin separation), (2) junctional EB (skin separation within the lamina lucida), and (3) dystrophic EB (sublamina densa skin separation). A fourth major type that recently has been proposed encompasses Kindler syndrome, since that genodermatosis shares with the other 3 major EB types the presence of mechanically fragile skin and blisters that, in contrast to all other EB types, typically have cleavage planes within multiple levels of the basement membrane zone. Although, in general, individual EB subtypes vary in their overall clinical severity by mid-childhood or early adulthood, each may present with similar clinical features during the neonatal period. As such, accurate subclassification may not be possible until later in infancy or childhood, when characteristic phenotypic features become more apparent.

EB simplex is the most common form of EB. It is most often caused by mutations within the genes encoding for keratins-5 and -14, with the vast majority being autosomal dominantly transmitted. There are 2 major types of EB simplex, basilar and suprabasilar, based on the ultrastructural site within which blisters arise. Most subtypes are basilar. On the basis of collective clinical findings, in conjunction with ultrastructural and molecular data, basilar EB simplex is further divided into 3 main subtypes:

1. EBS, localized (EBS-loc; formerly known as EB simplex Weber-Cockayne), the mildest EB simplex subtype, is associated with blisters primarily limited to the palms and soles.
2. EBS, generalized severe (EBS-gen sev; formerly known as Dowling-Meara type) is a severe subtype characterized by widespread blistering, herpetiform or arcuate grouping of blisters, possible internal organ involvement (to rarely include the upper airway), and the potential for death in the neonatal period.
3. EBS, generalized intermediate (EBS-gen intermed; formerly known as Koebner type), is an EB simplex subtype having more widespread cutaneous involvement than EBS-loc but little or no extracutaneous disease activity.

EB simplex with mottled hyperpigmentation (EBS-MP) is a rare subtype characterized by nonscarring blisters on distal extremities during infancy and slow development of reticular hyperpigmentation later in life. EB simplex may also be associated with muscular dystrophy (EBS-MD).

In the mildest cases of EB simplex, first signs may not develop until the child begins to walk or crawl, whereas large bullae and erosions are usually present at birth or within the first days of life in infants having a generalized EB simplex subtype. All forms of EB simplex worsen in hot, humid environments, and most improve with age. Treatment is supportive.

There are some patients with a dominant mutation that promotes ubiquitination and excessive proteolysis of KRT14.

Related topic: epidermolysis bullosa acquisita