The presentation and primary symptoms of all subtypes of epidermolysis bullosa are similar. However the age at onset, dermal layer involved, severity and extent of blistering differ  .
The most severe forms of epidermolysis bullosa are associated with clinically significant complications that may lead to permanent disability or death . Complications include the following  :
DNA analysis for mutations is the definitive test for diagnosis of epidermolysis bullosa and the classification of subtype by identifying the underlying molecular defect   .
Biopsy of the lesions can further identify the subtype and level of dermal involvement  . Procedures for this evaluation include :
Patient history should include  :
A complete physical examination with inspection of all skin, conjunctival, oral, and genital mucosae should be done on any patient suspected of having epidermolysis bullosa  . This should include evaluation of the size, location, and character of blisters . The character of the lesions varies by subtype and the layer of dermal involvement :
Reliable prenatal diagnosis is now possible. Diagnostic tests for epidermolysis bullosa include prenatal testing based on a better understanding of the genes responsible for the disease   . DNA for prenatal diagnosis can be obtained as a chorionic villi sample as early as the ninth week of gestation. A Western blot analysis of amniotic fluid drawn after the eleventh week  .
There is currently no preventive or curative therapy for epidermolysis bullosa. Molecular therapies, protein and gene therapy are being researched and are at the preclinical stage   . The goal of gene therapy is to provide genes that will restore normal protein production and solutions to the skin fragility found in patients with epidermolysis bullosa  . Gene therapy for Epidermolysis bullosa has been used and shown to be effective in small clinical trials.
These new treatment modalities may provide engineered tissue grafts produced by recombinant methods containing the missing or defective proteins, especially type VII collagen, are applied directly to blistered skin [13 ].
Further clinical trials are currently underway. In one, bone marrow transplantation is used for the delivery of corrective skin cells. Patients undergo bone marrow ablation and immunosuppression before transplantation of healthy marrow  , therefore the procedure is not without risk.
Current treatment and management of epidermolysis bullosa is supportive . The goal of therapy is effective wound care to prevent infection, scarring, and sepsis  . Beyond this is the prevention, early identification, and repair of damage and dysfunction resulting from extensive blistering  .
Wound care and healing is complicated by many factors including traumatic injury, skin fragility, exposure to bacteria, nutritional status, tissue anoxia, and aging . Optimizing wound healing in patients with epidermolysis bullosa involves controlling all of these factors.
Blisters should be treated aggressively with wound and nutritional management . Regular whirlpool therapy can help with gentle cleansing and debridement of wounds . This should be followed by sterile dressings using semiocclusive non-stick materials . Never apply tape to the skin of patients with Epidermolysis bullosa  . Take great care to avoid trauma to the skin that will cause additional blistering .
Gastrointestinal blistering causes some of the most disabling complications of Epidermolysis bullosa. Pain, dysphagia, mal-absorption, and malnutrition can result from these complications. Management of the lesions may include the use of phenytoin and oral steroid solutions to reduce the symptoms  .
Oral mucosal involvement can accompany severe forms of epidermolysis bullosa. Good oral and dental hygiene is essential; gentle tooth brushing, routine dental care, avoidance of harsh mouthwashes, normal saline rinses, gently cleansing of mucosal surfaces  . Many patients with epidermolysis bullosa develop dental caries despite good care, because of enamel erosion .
Oral candidiasis often occurs and can be treated with an anticandidal medication .
Ocular complications, corneal abrasions, conjunctivitis, corneal scarring, are also common in patients with epidermolysis bullosa . Corneal erosions can be treated with antibiotic ointments and cycloplegic agents to reduce ciliary spasm and provide comfort. Ocular lubricants may also reduce irritation .
Chronic forms may be treated with short-term high doses of systemic corticosteroids and a other immunosuppressants to reduce the severity of blister formation . However long-term steroid therapy is contraindicated because it suppresses the body’s defense against infection. Some research has shown success with colchicine, dapsone, infliximab and immunoglobulin .
Surgery may be required to repair damage done by repeated blistering and scarring as a result of Epidermolysis bullosa. Surgical management can include the following  :
Considerations for nutritional management include the following  :
Epidermolysis bullosa is a genetic disease and there are no drugs to correct or cure the underlying molecular defects. No drugs improve the symptoms of epidermolysis bullosa significantly or consistently .
Antibiotics, topical, oral, and intravenous, are used routinely to treat and prevent infection. The specific medication is adjusted according to the causative bacterium.
Genetic counseling is beneficial for families and siblings of patients with inherited epidermolysis bullosa that are considering children. Education of patient and family members is essential. Prenatal testing along with appropriate counseling has become an integral part of clinical management .
Epidermolysis bullosa simple tends to have a good prognosis. However, the disease can occasionally be severe, especially during the neonatal period   .
Epidermolysis bullosa simplex, dystrophic epidermolysis bullosa and milder forms of junctional epidermolysis bullosa may not affect a patient's life expectancy  .
Infection is the leading cause of death at all ages . Neonates, in particular, with extensive skin involvement may die as a result of overwhelming sepsis  . Extensive areas of skin involvement cause the loss of this barrier to pathogens .
The milder forms of epidermolysis bullosa are lifelong diseases. Some subtypes improve with age .
Epidermolysis bullosa is a group of severe, inherited blistering disorders which often results in death during infancy . Over the last 25 years there have been major advances in prenatal testing for inherited skin disorders  . Since 2000 many advances have been made in the understanding of epidermolysis bullosa due to the identification of the genetic mutations responsible for its pathogenesis  .
Epidermolysis bullosa subtypes are classified according to skin morphology   . The 4 major categories include  :
Approximately 92% of cases are epidermolysis bullosa simplex, 5% dystrophic epidermolysis bullosa, 1% junctional epidermolysis bullosa, and 1% hemidesmosomal epidermolysis bullosa. The rest are unclassified .
Epidermolysis bullosa simplex is generally associated with little or no extracutaneous involvement, while the more severe junctional, dystrophic, and hemidesmosomal forms may produce significant multi-organ system involvement .
Junctional epidermolysis bullosa has the highest risk during infancy with an estimated mortality rate of 87% during the first year of life . The major cause of death is due to infection and subsequent sepsis  .
In patients with epidermolysis bullosa who survive childhood, the most common cause of death is metastatic squamous cell carcinoma .
The incidence of epidermolysis bullosa is reported to be 50 cases occur per 1 million live births  . However, mild cases of epidermolysis bullosa simplex may not be identified and reported. This affects the reported incidence of the disease .
Incidence has been reported to be much lower in some parts of the world; in Japan 7.8 cases per million live births, and in Croatia 9.6 cases per million live births .
The overall annual mortality rate is 0.103 deaths per 100, 000 population . The mortality rate is highest during infancy  .
The mortality rate is much higher among blacks (0.192 death per 100 000) than whites (0.025 per 100 000) .
The continuous renewal of human epidermis is mediated by stem cells contained in the epidermal basal layer and in hair follicles . The skin and mucus membranes have a complex basilar membrane made up of specialized keratin-containing intermediate filaments that connect one layer of the dermis to another . Many intracellular proteins, including plectin, laminin 5 and laminin 6, and type VII collagen  , bind these anchoring filaments to anchoring fibrils. Anchoring fibrils are critical for stable adherence of the epidermis to the underlying dermis  . Aberrations in this network, due to genetic abnormalities, result in fragility of the skin  .
Epidermolysis bullosa occurs due to keratin gene mutations that interfere with keratin filament production . Mutations of the genes coding for these essential proteins are the cause of the disease  . As many as 10 genes have been identified as responsible for epidermolysis bullosa  . These proteins are critical for epidermal-dermal adherence .
Mal-attachment of the dermal layers allows slippage of the skin layers that cause the blistering and fragility that characterize the disorder. The specific gene mutation and resulting protein deficiency determine the layer of dermis involved and variations in the symptoms of the subtypes .
The one variant in which the pathogenesis is different is epidermolysis bullosa acquisita (EBA) . This variant is acquired rather than inherited. Autoimmunity against type VII collagen protein is thought to be the cause .
The incidence of epidermolysis bullosa cannot currently be prevented. Research is aimed at the identification of therapeutic interventions, including gene therapy, recombinant protein infusions, intradermal injection of allogeneic fibroblasts, and stem cell transplantation  . New therapies may eventually lead to a cure for this disease  .
The development of prenatal testing can be of benefit to families at risk of having children with epidermolysis bullosa in the absence of a cure  .
Epidermolysis bullosa (EB) refers to a group of genetic disorders characterized by fragility and blistering of the skin in response to mechanical injury  . There are multiple variants of the disease with similar presentations and common, but not identical, pathogenesis  . Most forms are autosomal dominant inherited, however some variants have been identified as autosomal recessive and at least one as an acquired disorder  .
Classification of epidermolysis bullosa is based on symptoms, severity, and the level of tissue separation within the cutaneous basilar membrane zone . The most common subcategories include simplex, hemidesmosomal, junctional and dystrophic variants  .
The blistering of epidermolysis bullosa may be localized or generalized and may be associated with abnormal wound healing . In some instances there is involvement of the mucus membrane lining the internal organs .
The extensive blistering and superficial tissue loss in epidermolysis bullosa may result in infection, sepsis, and death. Neonates and early infants are at highest risk . Other complications of the disorder are scarring, and strictures, obstructions and deformities due to scarring .
What is epidermolysis bullosa?
Epidermolysis bullosa is a group of genetically inherited disorders. They are characterized by extremely fragility and blistering of the skin resulting from minimal trauma. It is divided into three sub-types according to severity of symptoms, presentation, and layer of dermis involved. The more severe forms present at birth or early infancy and are often fatal. Milder cases may not present until later and, though not curable, can be managed medically.
What are the symptoms?
The primary symptoms of epidermolysis bullosa are skin fragility and blistering. The characteristics of the blisters and area of involvement varies depending on the subtype of the disease.
Blistering and skin damage can occur on any skin surface and usually involves mucous membranes as well. Mucosal involvement can affect the mucous lining of the mouth, nose, throat, eyes, urinary tract, reproductive system gastrointestinal tract, or respiratory system. Damage can cause scarring, obstruction, strictures, and deformities of the involved structures.
What causes epidermolysis bullosa?
Epidermolysis bullosa is caused by an inherited mutation of a gene responsible for the production of one of several proteins. These proteins are necessary for the construction of filaments that connect one layer of the dermis to another. Without these filaments the layers slip resulting in damage to the tissue and blister formation.
Who gets epidermolysis bullosa?
Epidermolysis bullosa is usually a autosomal, dominant or recessive, disorder, which means that fetuses inherit the gene mutation from their parents. It is a very rare condition, occurring in only 5 infants for every 100,000 live births. A few cases of acquired Epidermolysis bullosa have been reported. These individuals do not present until much later in life.
How is it diagnosed?
Epidermolysis bullosa is diagnosed by DNA analysis and the presence of one of the specific gene mutations. The disease is suspected by the clinical symptoms. Biopsy and electron microscopic examination of the blisters help determine the specific subtype. The disease can be diagnosed prenatally by chorionic villi or amniotic fluid testing.
How is epidermolysis bullosa treated?
Epidermolysis bullosa is treated symptomatically to provide comfort and prevent complications such as infection, scarring, stricture, obstruction, and deformity. There are techniques currently being researched to correct the underlying gene mutations. These include recombinant DNA and stem cell techniques.
What are the complications?
The complications of epidermolysis bullosa include:
How can it be prevented?
The symptoms of epidermolysis bullosa are treated to prevent the complications of infection and deformity. Management should include: