Epidermolysis bullosa (EB) is a group of rare inherited diseases affecting the connective tissue and is responsible for the resulting blisters that appear on the skin. These blisters are a consequence of a defective anchoring mechanism between the dermis and epidermis. They come about in response to friction, minor trauma, or heat and are not limited to the cutaneous areas and, in severe cases, may occur in the mouth or intestines.
EB typically manifests in either infancy or early childhood; however, there are those who do not develop any signs or symptoms until well into early adulthood. Children born with the disorder have skin so fragile that they are called ‘butterfly children’, because their skin is as delicate as the wings of a butterfly. EB can range from mild to severe. It may be inherited either as a recessive (25% chance of acquiring it from both parents carrying the gene without showing any symptoms themselves) or dominant (50% chance of acquiring from one parent who has symptoms) form.
In addition to genetic linkage, EB may develop through spontaneous mutations in the gametes (sperm or egg cells) before the conception of the child in cases where neither parent is a carrier of the disorder. Furthermore, EB, in rare instances, may also be acquired as a result of an autoimmune disease where the body produces antibodies that target and destroy its own tissue proteins. There are four main types of EB that are classified based on the layer of the skin affected. These are dystrophic epidermolysis bullosa (DEB), epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), and Kindler syndrome (KS).
Dystrophic Epidermolysis Bullosa
DEB can be inherited either in an autosomal dominant (DDEB) or autosomal recessive (RDEB) pattern and accounts for 25% of EB cases. The three main common subtypes of DEB are DDEB generalized (DDEB-G), RDEB generalized severe (RDEB-GS), and RDEB generalized intermediate (RDEB-GI). DDEB-G has a good prognosis and manifests due to reduced collagen type VII expression. Blistering in DDEB-G is typically mild and limited to areas more prone to trauma such as the hands, elbows, knees, and feet. There is typically some scarring involved, but mucosal involvement is rare and the disease activity is reduced with increasing age.
RDEB-GS, previously called Hallopeau-Siemens type, has near complete absence or significantly reduced collagen type VII expression and as a result is the most severe of all DEB subtypes. The blisters may be present from birth and cause extensive scarring with pseudosyndactyly and hypo or hyperpigmentation and unlike DDEB-G, there is mucosal involvement of the eyes, mouth, and esophagus. RDEB-GS is associated with several complications as a result of its severity. These include alopecia (hair loss), failure to thrive, osteoporosis, and delayed puberty. In addition to these, children with RDEB-GS are at an increased risk for other conditions such as cardiomyopathy, glomerulonephritis, and aggressive squamous cell carcinoma and due to these severe complications, patients rarely survive past their 30th birthday.
RDEB-GI, previously called non-Hallopeau-Siemens type, has similar clinical manifestations like those of RDEB-GS. However, the blistering is much less severe, because there is more collagen type VII expression present, albeit reduced in comparison to physiological expression. Patients with RDEB-GI generally have a better prognosis than that of RDEB-GS and survive longer, although they are still at risk of some of the complications including squamous cell carcinoma and thus need to be followed up regularly.
Epidermolysis Bullosa Simplex
Four major types of EBS have been identified that differ in severity, but have many overlapping features, due to their mutations in the same genes. Moreover, EBS accounts for 75% of all EB cases. The form with the least severity is called the Weber-Cockayne type that manifests during childhood and up to adulthood with skin blistering that is typically limited to the hands and feet. Involvement of these areas may cause the skin there to thicken and harden, which is called hyperkeratosis.
The most severe form of EBS is known as the Dowling-Meara type and is associated with severe blistering that may present anywhere on the body, including the oral mucosa. Dowling-Meara type, like the Weber-Cockayne type, can cause hyperkeratosis on the palms and soles. The blistering usually is present from birth; however, it improves with age. Another form of EBS is called the generalized type, previously called Koebner type, which has widespread blistering from birth that is usually less severe than Dowling-Meara. Patchy areas of darker skin that fade by adulthood characterize the last of the four major types, the mottled type.
Junctional Epidermolysis Bullosa and Kindler Syndrome
JEB accounts for 5% of EB cases and has two main types: Herlitz JEB, the more severe of the two, and non-Herlitz JEB. Patients present with blistering over large areas of the body, including the mucosal areas, from birth or early in their infancy. Herlitz JEB-associated complications are similar to those seen in RDEB-GS and children may have a hoarse cry with difficulty breathing due to pathological changes in the airway. Unfortunately, many infants with the severe type do not survive past their first birthday. Non-Herlitz JEB blistering is limited to the same areas as DDEB-G with similar associated complications. KS can simulate the other three forms of EB and is characterized by fusion of the fingers and/or toes, acral blistering and generalized poikiloderma (skin areas of hypopigmentation and hyperpigmentation and atrophy).
Further Reading