Epidermolysis Bullosa
Original Editors - Cody Mumaw and Rachel Kirchgessner from Bellarmine University's Pathophysiology of Complex Patient Problems project.
Top Contributors - Rachel Kirchgessner, Cody Mumaw, Elaine Lonnemann, 127.0.0.1, WikiSysop, Lucinda hampton, Evan Thomas and Kim Jackson
Definition/Description[edit | edit source]
Epidermolysis bullosa (EB) consists of a rare group of genetically determined skin fragility disorders, categorized by blistering skin and mucosa in response to little or no apparent trauma, with some forms leading to substantial morbidity and increased mortalityCite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. The fragility of skin and mucosa within this disease is due to defects in structural proteins within the epidermis, specifically at the epidermal-dermal junction, that cause a deficiency of cellular structures that normally stabilize the adhesion of the epidermis. These, in turn, result from abnormalities in the genes encoding various proteins that define EB into specific categoriesCite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. Accordingly, EB has been classified into three major different subtypes based on mode of inheritance, location of lesions, and clinical features which include the following three major forms: EB simplex (EBS), junctional EB (JEB), and dystrophic EB (DEB)Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. These three different subtypes are based on the level of blistering of the skin, although the classification of EB continues to evolve with recognition of up to 30 clinical subtypesCite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title.
Prevalence[edit | edit source]
All types and subtypes of EB are rare. Estimates of prevalence and incidence of EB have been endeavored by many different sampling techniques in numerous populations worldwide, but the most accurate and up to date epidemiological data is derived from the National EB registry (NEBR) from the USA. This registry is a cross-sectional and longitudinal epidemiological study of patients diagnosed with EB across the entire U.S. Over 16 years (1986-2002), 3,300 patients were identified, enrolled, classified, characterized, and followed for outcomesCite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. Among this study, the overall incidence and prevalence of inherited EB, according to the National EB registry within the United States, is approximately 19.60 per one million live births and 8.22 per one million population, respectively. With EB simplex, the incidence and prevalence rates are 10.75 and 4.65, with junctional EB are 2.04 and 0.44, dystrophic EB recessive type are 2.04 and 0.92, and dystrophic EB dominant type are 2.86 and 0.99Cite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title.
Characteristics/Clinical Presentation[edit | edit source]
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Associated Co-morbidities[edit | edit source]
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Medications[edit | edit source]
Currently no drugs are known to correct the primary molecular effects in EB. Recently, the use of topical opiates for pain management has been proven to reduce the need for powerful systemic analgesia. Amitriptyline, as well, has also been found to be useful in both children and adults in reducing pain. As far as systemic treatment, no agents thus so far have proven to be effective in controlling blisters in patients diagnosed with EB. Along with this, prolonged use of corticosteroids is contraindicated because of the high risk of complications associated with this drug. No other medication, including phenytoin and tetracycline, have improved the blistering or epithelial disadhesion in EB. Thus, there is no current reliable clinical trial evidence for any type of treatment with medicationCite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title.
Diagnostic Tests/Lab Tests/Lab Values[edit | edit source]
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Etiology/Causes[edit | edit source]
With epidermolysis bullosa, the fragility of skin and mucosa in which erosions occur because of slight mechanical trauma are inadvertently the result of defects in structural proteins within the epidermis. These, in turn, occur because of abnormalities in the genes encoding these various proteinsCite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. Subsequently, EB has been classified into three major subtypes that include their own genetic abnormalities:
EB simplex
- In EB simplex, the gene that helps make keratin, a fibrous protein in the top layer of skin, is faulty. Though it does not cause scarring, this subtype causes blister cleavage to occur within the epidermis Cite error: Invalid
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Junctional EB
- In junctional EB, defects in the basement membrane, specifically laminins, cause blister cleavage below the epidermis but above the basal lamina. This in turn, causes tissue separation and blistering in this deep layer of skinCite error: Invalid
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Dystrophic EB
- In dystrophic EB, collagen VII mutations affect the anchoring fibrils and cause dermal blisters below the basal lamina within the papillary dermis. Because of this mutation layers of the skin don’t join properly. This type can be either dominant or recessiveCite error: Invalid
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Systemic Involvement[edit | edit source]
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Medical Management (current best evidence)[edit | edit source]
Currently there is no effective therapy or cure for EBCite error: Invalid <ref> tag; name cannot be a simple integer. Use a descriptive title. Listed below is medical management that was proven to be the most effective in managing EB.
Preventing blisters
- Avoidance of aggravating factors for blistering remains the backbone of management. Measures to reduce these factors by using heat and humidity to lower the threshold for blistering are importantCite error: Invalid
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Nursing Care
- Also deemed important is successful management through nursing care. Mother should be educated to nurse their children on thick foam pads to prevent them from inducing blisters from unnecessary trauma. As for older children, they should be educated upon certain precautions of using adhesive tapes, sphygmomanometer cuffs, tourniquets, and other instruments that may shear their skin or mucous membranes. The adhesions should be cleaned sterile saline and afterwards covered with nonadherant dressings. Because there is a risk of development of antibiotic resistant bacteria, topical antibiotics are usually avoided. Constipation needs to managed with a sufficient amount of fiber as well as stimulant laxatives. Balloon dilation is also required for esophageal stricturesCite error: Invalid
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Dental Care
- Good dental hygiene is vital for patients with EB, as regular visits to the dentist are recommended. This should be initiated as quickly as tooth eruption and oral mucosal involvement begins. In order to maintain function good oral hygiene, crown placements, and tooth implants should be maintained to preserve functionCite error: Invalid
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Dietary Care
- Lack of vitamins and trace metals are common with patients who receive gastrostomy feeding. It is important to do regular nutritional evaluations with patients who have EB as well as give provide them with dietary advice and appropriate supplementationCite error: Invalid
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Molecular Therapy
- Gene therapy is probable to become a reality sometime in the future. With gene therapy, there are two broad principles-ex vivo and in vivo. Ex vivo is a specific type of gene therapy uses cultured cells such as keratinocytes, specifically from the affected individuals, which are propagated and transduced in culture to re-express the gene that is malfunctioning in the patients. Contrarily, in vivo gene introduces the transgene directly into the target tissue by either direct injection of the genetic material into the skin or mucous membranes or by topical application. The objective of molecular therapy is to replace one of the two mutant alleles in recessive forms of EB by introducing one normal allele into somatic cells. The first successful gene therapy for EB was reported by Michele De Luca. With this, areas of skin on the anterior thighs of an adult male patient with junctional EB were “cured” by transplanting genetically modified epidermal sheets grown in culture with a total of 500cm2 on both legs. “These epidermal sheets taken from palm biopsies and transfected ex vivo with a retroviral expressing normal lamina 5-3 which were grown from the patient’s own laminin 5-3-chain-deficient epidermal stem cells. De Luca’s team is now planning the replacement of big proportion of the patient’s skin surface with this genetically modified skin. These current advances in molecular genetics has allowed prenatal and preimplantation genetic diagnosis to be possible, broadening many options with patients in management of EBCite error: Invalid
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Physical Therapy Management (current best evidence)[edit | edit source]
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Differential Diagnosis[edit | edit source]
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Case Reports/ Case Studies[edit | edit source]
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Resources
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Recent Related Research (from Pubmed)[edit | edit source]
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References[edit | edit source]
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