Epidermolysis Bullosa: Causes, Symptoms, and Treatments

Introduction 

Epidermolysis bullosa is an inheritable disease which is characterized by the formation of blisters on the skin. Formation of blisters occurs in response to various stimuli like friction from rubbing, scratching, injury, mechanical trauma or heat. Though very rare, the blisters may also occur in the intestines and the mouth lining. It is important to note that most epidermolysis bullosa types begin to show at early childhood, but some people may not notice any signs of the disorder until later during their early adulthood. Unfortunately, there is no cure for epidermolysis bullosa. The treatment administered to patients with the disorder only focuses on reducing symptoms, minimizing pain and eliminating wounds. Epidermolysis bullosa (EB) is a disease may bring forth additional medical complications that may cause death. The following paper will discuss the types, symptoms, and treatment of epidermolysis bullosa. It will begin with a brief overview of the epidemiology of the disease followed by a description of how it is acquired. 

Objectives 

To determine the different types of Epidermolysis bullosa. 

To determine the symptoms associated with EB 

To determine the diagnosis process for EB. 

To identify the various treatment options for EB. 

To identify an experiment demonstrating hoe researchers cure the disease. 

About epidermolysis bullosa 

Epidemiology 

Much research and survey have been conducted to determine the prevalence and the incidence of epidermolysis bullosa among different populations worldwide. The most credible and reliable data on the prevalence of the disease is obtained from National Epidermolysis Bullosa Registry (Marinkovich, 2014). The registry collected longitudinal data on approximately 3300 EB patients in America from the year 1986 and the year 2002. Over this period, the prevalence of the disease was estimated as 11 per million live births and its incidence was estimated as 20 per million live births. The data collected during this period also reflects on the incidence rate of EB according to its subtypes. It was estimated that rate of incidence for EB simplex was 8 per million live births, junctional EB was 3 per million live births, dominant dystrophic EB was 2 per million live births and recessive dystrophic EB was 3 per million live births. NEBR estimates that the number of patients with hemidesmosomal EB does not exceed 1% of the total number of EB cases identified. The data collected was then used to estimate the carrier frequency of the disease within America. It is important to note that the data compiled by the NEBR is consistent and, therefore, can be generalized in other parts of the world apart from the United States. For example, it has been estimated that the incidence rate of EB in Norway is approximately 54 cases per million live births and Japan is about 7.8 per million live births. Of note, the data presented by the NEBR did not identify the prevalence of EB among the study population based on ethnicity and gender. Another study on the prevalence of EB was conducted by the Dystrophic Epidermolysis Bullosa Research Association of America (DebRA) between the year 2007 and the year 2011. The incidence rate for junctional EB was estimated to be 3.6 per million annually. 

Concerning mortality, research shows that severe EB increases the mortality risk especially during the infancy stage (Marinkovich, 2014). Individuals with Herlitz form of junctional EB are most vulnerable during the infancy stage. Their mortality rate of such individuals in their first twelve months of life is estimated at 87%. For those who survive their childhood with the disease, they may die later due to Metastatic Squamous Cell Carcinoma (SCC). This is a type of skin cancer that mostly affects individuals who have a recessively inherited EB. In contrast, EB types that are dominantly inherited may not have adverse effects on the life expectancy of the patient (Marinkovich, 2014). 

Occurrence and Inheritance of Epidermolysis bullosa 

The major types of epidermolysis bullosa occur as a result of a mutation in KRT5 or the KRT14 gene (Paller & Mancini, 2016). These are the genes that are responsible for providing instructions for the formation of the proteins keratin 14 and keratin 5. The fibrous proteins play a significant role in strengthening the epidermis and providing it with resiliency. According to Paller and Mancini (2016), mutation of the KRT5 or the KRT14 weakens the keratin proteins, causing damage to the epidermis cells. As the epidermis cells become more fragile, the skin becomes more prone to forming blisters as a result of minor trauma and frictions. Mutation in the PLEC gene is also associated with the Ogna type of EB. This is the gene responsible for providing instructions for the formation of the plectin protein that attaches the epidermis to the skin’s underlying layers. However, presently, scientists are conducting more research to determine how the mutation of PLEC gene is associated with EB. 

EB occurs as a result of inheritance of faulty genes which are inherited either from one or both parents (Paller & Mancini, 2016). This implies that a child is likely to inherit EB if one of the parents has the condition. However, there are some cases whereby the child has EB yet none of the parents has the disease. A situation like this one would happen when both parents are just carriers of the faulty genes that would cause the disease. It is important to note that EB may also occur as a result of autosomal recessive inheritance. This recessive inheritance, however, is very rare. 

Types and Symptoms of EB 

Researchers have identified common symptoms associated with the disease. Some of these common symptoms include fluid-filled blisters on hands and feet, loss of fingernails, internal blistering, scalp blistering, pimples, dental problems as well as difficulties in swallowing (Mayo Clinic Staff, 2014). It is important to note that the symptoms of EB vary depending on the type of the disorder. For instance, patient with epidermolysis bullosa simplex may experience some blisters on the epidermis (Stoelting, Hines & Marschall, 2008). This is a mild type of EB and, therefore, the blisters do not cause scars. Patients with this type of EB are likely to have inherited it from one of their patients. 

Children with junctional epidermolysis bullosa start developing a hoarse-sounding cry as a result of continual blistering as well as scarring of vocal cords (Stoelting, Hines & Marschall, 2008). The gene defect associated with this EB type results in the separation of the epidermis tissue and blistering in the skin’s inner layers. A child with junctional epidermis bullosa means that both the parents are carriers of one defective gene associated with EB. One major symptom associated with Kindler syndrome (another type of EB) is the patchy discoloring of the skin when the patient exposes himself or herself to the sun. In the case of dystrophic epidermolysis bullosa, the patient may experience mild to severe symptoms. One important thing to note about the symptoms of EB is that blisters on the skin, especially in children, may not be noticeable until the child starts walking or engaging in physical activities that would cause more friction on his or her feet (Stoelting, Hines & Marschall, 2008). 

Diagnosis 

Considerable progress has been made in explaining the underlying molecular pathology of the few forms of the hereditary skin diseases (Thappa, 2009). This progress has led to the advancement of the genetic counseling in the development of the DNA-based diagnosis. The most significant benefit is the development of DNA-based prenatal diagnosis in recurrence of EB during pregnancy. Prenatal tests have progressed from the middle trimester of the fetus skin biopsies to the first chorionic villus in a much wider range of the genodermatoses (Fine & Hinter, 2009). The fetal skin biopsy and chorionic villus sampling are unfortunately invasive and non-risky completely. They are available for the two most affected subtypes which are junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. A further molecular test with the use of chorionic villus sampling is done to know the specific genetic defect. Advances in both embryo manipulation technology and the vivo fertilization protocols have led to the viability of earlier diagnosis through the pre-implantation genetic diagnosis. The new diagnosis technique encompasses a single blastomere biopsy from about six to ten cell stage of the fertilized embryo and is them followed by single cell DNA mutational analysis. The embryo becomes disease free and is implanted into the uterus thereby avoiding terminations that are brought through conventional methods (Fine & Hinter, 2009). 

Treatment 

There have been frequent feelings of despair for patients with severe symptoms of EB. The current treatments are limited to painkilling, friction prevention, dressing wounds and using corticosteroid creams. However, there are some possible treatments for EB patients through different forms of gene therapy (Weiss & Prinz, 2013). These therapies include in vivo gene therapy, ex vivo gene therapy and fetal gene therapy. In vivo therapy has limitations in the long-term countenance of the transgene and requires direct contact with the patient. However, in this therapy, it is hard to control and monitor the incorporation of the genes and the extent of the introduction of a transgene. Ex vivo therapy allows an excellent control of any extent of the transgene and any negative effects that can be examined, limited and dealt with before corrected genes are applied to the patient. By using the patient’s cells to reduce the possibility of the immune system responding and using viral vectors, the long-term expression can be regulated using techniques in ex vivo (Weiss & Prinz, 2013). Fetal gene therapy has the potential to provide significant benefits in treating severe congenital diseases which include genodermatoses. The increased stem cells’ population and fetal tissues the fetal therapy increases the chances of transgenes. It would be particularly beneficial for the most congenital behavior whereby the therapeutic window for the expression of the transgene is treated immediately after birth. However, if it is treated at the appropriate developmental stage can help reduce the early onset of damaging the epidermis to improve the survival rate of patients (Thappa, 2009). 

Research for the cure of epidermolysis bullosa 

Epidermolysis Bullosa Medical Research Foundation (EBMRF) is a non-profit foundation that has dedicated resources to support the medical research on epidermolysis bullosa. The foundation was established by Gary and Lynn Anderson following a request by Dr. Eugene Bauer who was then, the chairman of the Dermatology department at the School of Medicine at Stanford University (Sheridan, 2010). The primary goal of establishing the foundation was to find a cure for EB. One of the biggest achievements of EBMRF is to help create the Epidermolysis Bullosa Clinical Research Consortium (EBCRC), a research group consisting of clinical researchers in epidermolysis bullosa. The research group was founded in the year 2010 by some pediatric dermatologists from North America. Its main mission is to improve care and enhance the health outcomes for EB patients. Its vision is to become a recognized research group conducting clinical research intended to not only improve the diagnosis of EB but also find its cure. 

EBMRF has helped Stanford Dermatology carry out research on EB in different ways. For example, it has helped in carrying research on the occurrence and treatment of recessive dystrophic epidermolysis bullosa (RDEB). From research, it is clear that patients with this type of EB present skin blisters caused by a lack of the essential protein, type VII collagen. It is the protein responsible for holding together the skin layers (Fine & Hintner, 2009).The main therapy of the RDEM is to restore the normal type VII collagen. Dermatologists at Stanford have made progressive efforts in achieving this goal. 

An effective approach to restoring the protein in the skin is by replacing the faulty type gene with the non-faulty one. To achieve this, researchers at Stanford’s Dermatology department have used a phase I clinical trial which is approved by the United States Food and Drug Administration. The main aim of the clinical trial is to study the transfer of the protein gene for RBEB. While in the lab, the scientists culture the skin cells of RDEM obtained from the patient biopsies and transferred or restore normal protein gene into the patient’s skin by using a retrovirus, a transfer tool for genes. After transferring the protein gene, the skin cells are then set into a sheet and then placed on the patient’s wounds and bandaged. As a follow-up, the researchers perform biopsies using an electron microscope to verify that the protein genes are properly localized in the fibrils (Thappa, 2009). 

Researchers in this field have also developed protein therapy as an alternative to gene therapy for EB as discussed above. The protein therapy for epidermolysis bullosa involves the injection of the protein gene (type VII collagen) into the RDEB skin. Since conventional needles are not efficient in injecting the protein into the desired position under the skin, researchers use bio-degradable micro-needles. The benefit of using these devices is that they can carry the desired amount of protein and that they can deposit it at the desired location. When placed under the skin, the needles are then dissolved by the human serum, and they release the protein. Scientists feel that injecting type VII collagen using micro-needles is the most effective method of treating patients with EB. They hope that protein therapy will have a wider applicability in the future. 

Conclusion 

Epidermolysis bullosa is a disorder that is acquired through inheritance of faulty genes. From this paper, it is clear that EB is characterized by the formation of blisters on the skin. These blisters form as a result of minor trauma, injury or friction. It is also clear that EB is more prevalent in children whose parents are carriers of faulty genes associated with the disorder. Researchers in the field of EB have conducted extensive research to determine approaches that could be effective in treating EB patients. Among the identified approaches include protein therapy, gene therapy, and stem cell therapy. The good thing about these methods is that they have become successful in treating EB. 

References 

Fine, J.-D., & Hintner, H. (2009). Life with epidermolysis bullosa (EB): Etiology, diagnosis, multidisciplinary care, and therapy. Wien: Springer. 

Marinkovich, P. (2014, January 8). Epidermolysis Bullosa. Retrieved from http://emedicine.medscape.com/article/1062939-overview#a6 

Mayo Clinic Staff. (2014, July 22). Diseases and Conditions: Epidermolysis bullosa. Retrieved from http://www.mayoclinic.org/diseases-conditions/epidermolysis- bullosa/basics/symptoms/con-20032497. 

Sheridan, M. (2010).   Unconditional Uncensored . Lulu.com. 

Stoelting, R. K., Hines, R. L., & Marschall, K. E. (2008).   Stoelting's anesthesia and co-existing disease . Philadelphia: Churchill Livingstone/Elsevier. 

Thappa, D. M. (2009).   Clinical pediatric dermatology . Noida, Uttar Pradesh, India: Elsevier. 

Weiss, H., & Prinz, F. (2013). Occupational therapy in epidermolysis bullosa: A holistic concept for intervention from infancy to adult . Wien: Springer.