Butterfly people: what is epidermolysis bullosa and what are modern approaches to therapy

November 3, 2023

For the first time, the term "orphan" in relation to diseases and medicines (from the English orphan — orphan) was used in the USA in 1983 in the legislative act "Orphan Drug Act" (Orphan Drug Act), highlighting about 1,600 diseases and syndromes known at that time and about 300 medicines classified as rare. One of these rare diseases is epidermolysis bullosa.

Epidermolysis bullosa is a disease associated with mutations in different genes. The severity and variety of clinical manifestations depends on which gene is affected, and covers a group of clinically and genetically heterogeneous diseases classified into four main types: simple BE (PBE), borderline BE (borderline BE), dystrophic BE (DBE) and Kindler BE syndrome. 

Until 1886, congenital epidermolysis bullosa was called hereditary pemphigus. For the first time, the clinical picture of this disease was described by the British doctor J. Hutchinson in 1875. 

For many years, the incidence of congenital epidermolysis bullosa was unknown, but after the creation of the National Register of VBE in the USA in 1986, researchers began to collect and systematize data on the prevalence of this hereditary pathology. Forms with a mild course occur with a frequency of 1:50,000 newborns, more severe – with a frequency of 1:500,000 annually. It is estimated that the population frequency of congenital epidermolysis bullosa in Russia is 1:50000-1:300000, and the projected annual number of patients with VBE is 14-34 cases per 1.7 million newborns.  In the Republic of Uzbekistan, 287 patients with epidermolysis bullosa were registered in 2021.   At the beginning of 2023, 112 patients with various forms of this disease were registered in Kazakhstan.

 The development of congenital epidermolysis bullosa (VBE) is caused mainly by mutations of genes encoding structural proteins of the skin that provide a link between the epidermis and the dermis.

The diagnosis of VBE in the Republic of Kazakhstan is mainly based on phenotypic data. In the presence of typical manifestations, verification of the type and subtype of VBE is a simple task. However, atypical manifestations, the absence of the disease in the family and the newborn period make it difficult to identify the disease. In these cases, dynamic observation makes it possible to identify additional clinical signs of VBE, and conducting laboratory and instrumental research methods - to establish the type and subtype of VBE.  For this purpose, DNA diagnostics, immunofluorescence antigenic mapping and electron microscopy are used.    

The main clinical sign of any form of epidermolysis bullosa is the appearance of blisters with minor mechanical injury, such as a cut, rubbing with clothes, abrasion, combing, etc. If these blisters are damaged, an open wound is formed into which infection can penetrate.

Other clinical signs include coarsening and keratinization of the surface of the palms and soles, as well as a violation of skin pigmentation: both bright spots and areas with loss of pigment (depigmentation) may appear on it. These disorders occur at the site of burst bubbles.

People who were born with this diagnosis are called "butterflies" because of the vulnerability of the skin, like a butterfly's wing. The name epidermolysis bullosa (BE) comes from the Latin word bulla ("bubble"). Since from a little friction, the patient has bubbles that turn into wounds. Skin problems are not limited to wounds on the skin, but also the gastrointestinal tract, kidneys, heart, organs of vision, musculoskeletal system suffer from this disease. A common complication is squamous cell skin cancer.  This requires a multidisciplinary approach to patients, i.e. observation by various specialists, such as pediatrician, dentist, surgeon, traumatologist, hematologist, gastroenterologist, etc.

In most cases, the first signs of congenital epidermolysis bullosa of the disease appear from birth, and such patients require a special approach to examination, treatment, care and social adaptation to the environment. 

Moderate and severe course is characterized by the presence of multiple complications and concomitant diseases that lead to disruption of vital activity and deterioration of the patient's quality of life.  The lack of an interdisciplinary approach to a comprehensive examination of VBE by doctors of related professions and timely treatment of cutaneous and extracutaneous lesions of VBE leads to disability of the patient.  

To date, VBE in the Republic of Kazakhstan remains a rare and incurable disease, and the need for specialized medical care from the state remains lifelong.

Etiopathogenetic treatment of congenital epidermolysis bullosa does not currently exist. All medical measures are palliative and are primarily aimed at preventing the occurrence of injuries and, as a consequence of them, blisters through the selection of optimal skin care and affected surfaces. The patient must undergo all age-appropriate tests, dispensary examination and immunization (vaccinations). All patients are registered at the dispensary with a dermatologist and a pediatrician, a therapist, they are issued a disability and disability-related benefits are provided.

Treatment is also aimed at eliminating itching, pain, fighting infectious complications of the disease, correcting the pathology of the gastrointestinal tract, teeth, bone and joint apparatus. Patients with congenital epidermolysis bullosa need active dynamic monitoring and treatment not only by dermatologists, but also by other specialists, such as surgeons, dentists, gastroenterologists, pediatricians, oncologists, ophthalmologists, hematologists, psychologists.

The nutrition of patients with EB should be mechanically, thermally and chemically gentle (mashed, semi-liquid, non-hot), enriched with basic macro- and microelements, vitamins with high caloric content due to impaired metabolism.  With numerous blisters and erosive surfaces, the patient needs to replenish the lost fluid. Younger children need antireflux mixtures

External treatment of patients with congenital epidermolysis bullosa should be comprehensive and carried out taking into account the clinical manifestations of the disease.  First aid, including the imposition of atraumatic specialized dressing material should be carried out before the establishment of clinical forms of VBE. Parents' training in proper child care should begin as soon as possible. The following measures should be taken to prevent the formation of new bubbles. Bandages for patients with EB should provide an appropriate level of skin hydration, since the necessary criterion for wound epithelization is healing  in a humid environment, do not stick and be atraumatic, promote healing of the wound surface, reduce pain, increase the rate of epithelization.  The choice of dressing material depends on  It depends on the type of EB, the localization of the lesion, the relative need for mechanical protection, the volume of exudate, the presence of bacterial colonization or infection. Primary, contact dressings should be atraumatic, ensuring non-adhesion to the wound, containing silicone, paraffin, vaseline, lipids, creams, beeswax. With abundant discharge, sorbing wound dressings consisting of polyurethane sponge, polysaccharides, collagen sponge are used. And for the treatment of infected erosions, bandages with the addition of antimicrobial agents are used. To fix primary bandages, secondary bandages are used, which include self-fixing, fixing, tubular fixing, elastic tubular bandages or underwear.      

To date, VBE in the Republic of Kazakhstan remains a rare and incurable disease, and the need for specialized medical care from the state remains lifelong.

EB is a rare disease, but it opens up opportunities for therapeutic developments aimed at wound healing. Other approaches use low-molecular-weight drugs to change the microenvironment of the skin and the course of the disease. Cell therapy and genetic engineering developments offer new methods of treating VBE.

Thus, in recent years, significant progress has been made in the development of methods for the treatment of RDBE, including approaches based on the use of allogeneic cells (the advantage of which is simplicity, rapid scaling of the production process, the possibility of repeated use if necessary, relatively low cost), and the use of autologous cells in combination with gene therapy based on viruses and programmable synthetic nucleases. The advantage of the latter approach is in personalized therapy and long—term (possibly life-long) clinical effect, however, this is a therapy that requires very high costs. To date, all available strategies are at different stages of study and require significant refinement before they are implemented into clinical practice. And perhaps it makes sense to develop all strategies that have proven safety and clinical effectiveness, since only the presence of several effective, accessible and inaccessible methods, and possibly their combination, will allow timely assistance to patients with such a severe, debilitating disease.

A. Taubayeva,
Dermatovenerologist, head of the RSE clinic at the Kazakh Scientific Center of Dermatology and Infectious Diseases of the Ministry of Health of the Republic of Kazakhstan

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