Epidermolysis bullosa (EB) is a complex group of mechanobullous disorders characterized by painful blister formation as a result of minor trauma to the skin. With the exception of the acquisita type, EB is an inherited disorder. The classification system for hereditary EB was revised in 2007 and now includes four major types according to the level of blister formation: simplex or intraepidermal (’epidermolytic’), junctional or intralamina lucida (‘lamina lucidolytic’), dystrophic or sublamina densa (‘dermolytic’), and Kindler syndrome or mixed. The disease can involve the skin, mucosae, and internal organs. The severity of EB ranges from mild to severe, and skin involvement can be localized or generalized.
In addition to the four major types of EB, there are several dozen subtypes, resulting from more than 1000 documented mutations on at least 14 structural genes. The genetic variability of EB results in a wide variety of clinical presentations, extra-cutaneous manifestations, degree of morbidity, and risk for early mortality.
The management of inherited EB has classically been supportive: avoidance of trauma, blister management, wound management, treatment of infections, and nutritional support. More recent efforts have been directed at identifying and treating the underlying cause of disease with the goal of improving wound healing and preventing new wound formation.
Avoidance of trauma to intact skin is important but difficult. Sewing foam pads into the lining of clothing is helpful, especially over the elbows, knees, and other pressure points. Blister management involves puncturing new blisters with a sterile needle to avoid extension of the blister. The punctured area should be covered with a topical antibiotic and a non-adherent dressing.
Wound management comprises assessing the location and characteristics of wound; cleansing with low toxicity solutions (e.g., saline, water); gentle debridement of eschar/slough if present; and covering the wound with an appropriate non-adherent dressing. Wounds need to be evaluated and treated on a daily basis. In general, it is beneficial to soak wounds in a bath tub for 5 to 10 minutes. This facilitates cleansing and non-traumatic removal of dressings. Use of low concentration acetic acid or bleach in the bath water may also help control bacterial load in wounds.
Minimizing trauma to wounds is vital. Mepilex is a non-adherent, absorbent polyurethane foam pad that can be applied, removed, and reapplied to wounds with little discomfort, no trauma to the wound bed or surrounding skin, and no disruption of wound healing. Other non-adherent dressings, such as white petrolatum-impregnated gauzes, hydrogels, and foams, can be used and held in place with soft, roller gauze bandages or elastic tube dressings.
A variety of skin grafts have been used to treat the wounds of EB, including split-thickness skin grafts, allogeneic and autogeneic cultured keratinocytes, and cryopreserved acellular human dermis. A study using intradermal injections of allogeneic fibroblasts demonstrated therapeutic potential in patients with recessive dystrophic epidermolysis bullosa (RDEB). Several trials have reported impressive results with Apligraf, a bilayered, tissue-engineered skin derived from neonatal foreskin that contains living keratinocytes and fibroblasts. An allogeneic composite cultured skin (OrCel) has been approved by the US Food and Drug Administration to treat hands and donor sites in patients with RDEB. More recently, amniotic membranes have been used to treat patients with EB with chronic, non-healing wounds.
Avoidance of wound infection is also critical to promote more rapid healing and to avoid overwhelming infections and sepsis, which are associated with an increased mortality rate. Topical antibiotics are routinely used, but should be rotated monthly to avoid the development of resistant organisms. Cutaneous infections unresponsive to topical measures need to be treated with systemic antibiotics, but the chronic use of systemic antibiotics is not recommended as a preventive measure.
Common nutritional problems in patients with EB include chewing and swallowing difficulties, malnutrition, constipation, and vitamin and mineral deficiencies. Avoidance of malnutrition depends on active and continuous nutritional support. Early nutritional supplementation can promote better childhood growth rates and promote healing of skin lesions. In patients who develop esophageal strictures, balloon dilatation, surgery is sometimes needed. Daily multivitamin trace elements and zinc supplementation is recommended. Anemia may be profound in EB, and oral iron replacement is mandatory for patients with iron deficiency. Erythropoietin has been recommended if the iron level is <500 mU/mL. Some have recommended intravenous iron therapy for patients resistant to oral replacement. Albumin should be monitored to assess the patient’s nutritional status. If necessary, protein supplements can be added to the diet. Severe malnutrition can be treated with enteral feeding via gastrostomy tube if necessary.
Systemic therapies, such as psoralens in combination with UVA irradiation, corticosteroids, vitamin E, cyclosporine, antimalarials, retinoids, phenytoin, tetracycline, trimethoprim–sulfamethoxazole, and cyproheptadine, have been used to treat EB, but their efficacy is unproven.
Current therapies are focused on gene-, protein-, and cell-based techniques. There have been improvements in genetic manipulation of keratinocytes ex vivo and of graft techniques in vivo. Gene transfer of epidermal stem cells in combination with tissue engineering procedures is promising.