The term epidermolysis bullosa, butterfly skin, or butterfly disease is used to describe a very heterogeneous spectrum of genetic skin disorders associated with blistering due to skin fragility. Epidermolysis bullosa has an incidence of approximately 1:50000 to 1:100000, with both sexes equally affected.
What is epidermolysis bullosa?
Epidermolysis bullosa is the name given to a number of genetic or mutational dermatoses (skin diseases) in which minimal trauma results in blistering of the skin and/or mucous membranes. Depending on the underlying mutation, epidermolysis bullosa can manifest itself clinically in an extremely heterogeneous manner (from lethal courses with pronounced affection early in life, to mild forms with an acral pattern of affection, to minimal lesions that do not lead to blistering). Traditionally, three forms of epidermolysis bullosa are differentiated, each with distinct subtypes. In the so-called epidermolysis bullosa simplex (EBS), blistering is mainly seen on the hands and feet (Weber Cockayne) or generalized (Dowling-Meara, Koebner EBS). The generalized form of epidermolysis bullosa junctionalis (EBJ) usually involves the mucosa and gastrointestinal tract, while the localized form has acral blistering with nail dystrophies and enamel defects. The most severe form of epidermolysis bullosa dystrophica (Hallopeau-Siemens type) is associated with scarring, disability, and decreased life expectancy. Secondary clinical symptoms of epidermolysis bullosa include pseudosyndactyls, esophageal stenosis, muscular dystrophy, pyloric atresia, anemia, and protein and iron deficiency, developmental retardation, and psychosomatic impairment, depending on the form of the disease.
Causes
Epidermolysis bullosa is due to autosomal-dominant or autosomal-recessive inherited mutations in certain structural proteins of the basement membrane zone (BMZ) of the skin that cause fragility in each affected skin layer. The affected genes encode important structural components (hemidesmosomes, anchoring fibrils) that connect the epidermis to the dermis. As a result of the mutations, these structural elements exhibit a loss of function or are completely absent, so that the cohesion of the skin layers is no longer guaranteed and mild trauma induces blistering of the skin and mucosa. In epidermolysis bullosa simplex, mutations on the keratin or plectin genes (especially for keratins 5, 14) cause a breakdown of the keratin cytoskeleton as well as cytolysis (cell disintegration) of the keratinocytes in the basement membrane, while in epidermolysis bullosa junctionalis the hemidesmosomes anchoring the epidermis to the basement membrane are lost or completely absent, among other things as a result of mutations on the keratin gene. The hemidesmosomes anchoring the epidermis to the basement membrane show morphological and functional abnormalities, among other things, as a result of mutations on the laminin 5 gene. In so-called epidermolysis bullosa dystrophica, the cross-linking of the basement membrane with the underlying dermis is impaired as a result of defective anchoring fibrils.
Symptoms, complaints, and signs
Due to epidermolysis bullosa, affected individuals usually suffer from various skin complaints, which have a very negative impact on the quality of life of the affected individual and significantly reduce it. Severe blisters appear on the skin, which can cover the entire body of the affected person. The blisters can also appear inside the body. They are associated with pain and are usually also filled with a liquid. Furthermore, there are also wounds or scars if the blisters burst. There can also be various deformities on the body due to epidermolysis bullosa, so that, for example, toes become fused or the nails fall out. As a result, the patient’s aesthetic appearance is also significantly reduced and limited, so that many affected individuals suffer from a significantly lowered self-esteem or even inferiority complexes. In children, epidermolysis bullosa can lead to bullying or teasing. Furthermore, patients also suffer from short stature and not infrequently from hair loss. In many cases, there is also very heavy sweating, so that the affected person also has difficulty sleeping at night. As a rule, epidermolysis bullosa does not have a negative effect on the patient’s life expectancy.
Diagnosis and course
Epidermolysis bullosa is generally diagnosed on the basis of characteristic blistering. Molecular diagnostics allow accurate determination of the subtype already in the neonatal period, while skin biopsy and antigen mapping provide information on the localization of blistering as well as on the specifically affected structural proteins. Electron microscopy can assess conspicuous structures and typical features in the keratin filaments, hemidesmosomes, and anchoring fibrils. The course and prognosis of epidermolysis bullosa depend on the specific subtype present. While the course of the common mild EBS is usually very favorable, EBJ (especially Herlitz EBJ), for example, can be lethal.
Complications
Epidermolysis bullosa causes increased formation of blisters on the skin and also inside the body. These blisters reduce self-esteem in many people and can also lead to inferiority complexes, causing psychological distress and depression. It is not uncommon for scars and wounds to remain from the blisters. Likewise, the patient suffers from various deformities in different regions of the body and short stature. It is also not uncommon to experience hair loss and severe sweating and panic attacks. The patient’s quality of life is severely limited by epidermolysis bullosa. Blisters on the skin may also be affected by itching and lead to severe redness. Treatment primarily targets the symptoms and heals the blisters. These are usually broken open and disinfected. Inflammation and itching can be treated with the help of antibiotics, and the patient often has to change his diet. In many cases, epidermolysis bullosa can be treated well, resulting in a positive course of the disease. Life expectancy is usually not reduced.
When should you see a doctor?
If newborns show unusual changes in the appearance of the skin, they should be clarified by a doctor. If blisters form on the body, this is considered an unusual appearance. A doctor should initiate comprehensive examinations to determine a cause. If wounds appear or the affected person suffers from scarring, it is advisable to consult a doctor. In the case of open wounds, germs can penetrate the organism and trigger further illnesses. A visit to the doctor should therefore take place in good time. A visual abnormality of nail formation on the fingers or toes is considered to be a cause for concern. A doctor should be consulted so that treatment can be initiated. If the hair falls out for reasons that cannot be explained, it is necessary to consult a doctor. In case of heavy sweating, it is advisable to discuss the symptoms with a medical professional. If emotional or mental problems occur, the support of a doctor or therapist should be sought. If social withdrawal, behavioral problems or mood swings occur, it is helpful to consult a physician. If there is decreased self-confidence, depressed emotional state and persistent apathy, a doctor should be consulted. If discomfort occurs due to the scars, it is recommended to seek contact with a plastic surgeon.
Treatment and therapy
Therapeutic measures in epidermolysis bullosa are aimed at symptom relief and stabilization. As part of daily local therapy, the blisters are pricked, disinfected, and the wounds are treated with moisturizing lotions, although plasters and adhesive materials should be avoided in wound care. Self-adhesive bandages, tubular dressings, grease gauzes in combination with fleece compresses and silicone-coated mesh dressings have proved effective in this respect. In cases of itching and eczematization, steroids and topical antibiotics can be used in the short term for secondary infections. Systemic therapeutic approaches do not yet exist for epidermolysis bullosa, and systemically applied steroids and phenylhydantoin have not proven effective. In individual cases, therapies with antibiotics, retinoids or vitamin E have been successful. In addition, a change in diet is recommended, since the increased epithelial regeneration and wound secretion leads to an increased demand for calories, minerals (especially iron and zinc) and protein.Gene therapy treatment approaches, which are still being researched at the present time, may lay the foundations for a future causal therapy. Here, the respective affected gene should be replaced by healthy or synthetically “repaired” keratinocyte grafts or with the help of external gene vehicles (mainly liposomes) to induce the synthesis of normally functioning structural proteins and thus prevent the manifestation of epidermolysis bullosa.
Outlook and Prognosis
The outlook for epidermolysis bullosa varies. In one spectacular case, gene therapy saved the life of a terminally ill boy. The transplantation of genetically modified autologous skin was performed for the first time. In gene therapy, physicians see the best chances for complete recovery in severe cases of epidermolysis bullosa. In most cases, the prognosis depends on the structure of a specific protein. Epidermolysis bullosa can be mild, but it can also be associated with severe sequelae such as skin tumors. Because epidermolysis bullosa is hereditary, it is often detected early. In severe epidermolysis bullosa, affected children do not reach adulthood – except through gene therapy, which has not yet been approved. In mild forms of epidermolysis bullosa, symptoms may lessen somewhat with advancing age. The mild forms of epidermolysis bullosa are more common. As a result, the prognosis is better overall. The symptoms of this hereditary disease are usually recognizable at such an early stage that the type of disease can be quickly determined. However, it is problematic that, apart from gene therapy, there are no suitable treatment approaches to date. Epidermolysis bullosa can therefore only be treated sympthomatically. This means that mainly prophylactic and pain therapeutic measures as well as wound care are applied. If necessary, surgical measures can improve the quality of life somewhat.
Prevention
Because epidermolysis bullosa is genetic, it cannot be prevented. However, affected individuals should avoid trauma and heat and prevent symptoms of epidermolysis bullosa by consistent skin care and local treatment of blisters (secondary).
Aftercare
In most cases of epidermolysis bullosa, the options or measures of aftercare are very limited. Affected individuals are primarily dependent on early diagnosis and treatment of this disease to prevent further complications and discomfort to the skin. Only an early diagnosis can lead to a complete cure. For this reason, the main focus in epidermolysis bullosa is the rapid diagnosis of the disease. In most cases, the disease is treated with the help of antibiotics. The affected person is dependent on a correct and regular intake and should follow the instructions of the doctor. Furthermore, when taking antibiotics, alcohol should not be drunk, as this can significantly reduce their effect. Even after the symptoms of epidermolysis bullosa have subsided, the medication should still be taken for a few days according to the doctor’s instructions. It is not uncommon for the use of vitamin E preparations to have a positive effect on the course of epidermolysis bullosa. Affected individuals generally also rely on the support and help of their own family to prevent psychological upset or depression.
Here’s what you can do yourself
When dealing with epidermolysis bullosa, patients should use only dermatologically tested cosmetic items. In many cases, it is helpful if the use of cosmetics can be completely avoided. This relieves the skin and prevents additional skin irritations. Itching and rubbing of the affected regions should be completely refrained from. This increases the discomfort and pathogens can enter the organism through the open wounds. In order for the body to generate sufficient defenses in the fight against the disease, it is advisable to pay attention to a healthy lifestyle. A balanced diet rich in vitamins strengthens the immune system. In addition, regular exercise and the pursuit of sporting activities promote general well-being. To stabilize the psyche, it is helpful if the patient uses relaxation techniques.Stress can be reduced via methods such as yoga or meditation and an inner balance is established. Conversations and exchanges with other people are always felt to be beneficial in dealing with epidermolysis bullosa. In self-help groups, patients can share experiences with each other in a trusting atmosphere and give each other mutual support. In conversations with relatives or people in the social environment, concerns or fears can be discussed and reduced.
