Dystrophic Epidermolysis Bullosa: Life Expectancy, Pictures, Treatment: The term epidermolysis bullosa, butterfly skin or butterfly disease is a very heterogeneous spectrum of genetic skin diseases that are associated with blistering due to skin fragility summarized. Epidermolysis bullosa has an incidence of about 1: 50,000 to 1: 100,000, with both sexes, equally affected.
What is Epidermolysis B
Epidermolysis bullosa is a series of genetically or putatively related dermatoses (skin diseases) in which minimal trauma leads to blistering of the skin and/or mucous membranes. Clinically, depending on the underlying mutation, epidermolysis bullosa may be extremely heterogeneous (from lethal progression with a pronounced infestation in early age to mild forms with acral infestation pattern to minimal lesions that do not cause blistering).
Traditionally, a distinction is made between three forms of epidermolysis bullosa, each of which has different subtypes. In the so-called epidermolysis bullosa simplex (EBS), blistering is mainly observed on the hands and feet (Weber Cockayne) or generalized (Dowling-Meara, Koebner-EBS). The generalized form of junctional epidermolysis bullosa (EBJ) involves mostly the mucosa and the gastrointestinal tract, whereas the localized form has acral blistering with nail dystrophies and enamel defects.
The most severe form of epidermolysis bullosa dystrophic (Hallopeau-Siemens type) is associated with scarring, disability and decreased life expectancy. Secondary clinical symptoms of epidermolysis bullosa include pseudo-syndactylia, oesophageal stenosis, muscular dystrophy, pylorus atresia, anemia, protein and iron deficiency, developmental retardation, and psychosomatic impairment, depending on the disease type.
CLASSIFICATION of Epidermolysis Bullosa
Depending on the depth of the lesion, there are three main forms of the disease and more than 30 pathology subtypes, differing in genotype, phenotype and inheritance.
- Simple form (PBE). Only the upper layers of the epidermis are affected. It has 12 subtypes, the most common ones are Weber-Cockayne syndrome (localized), Koebner (generalized), Dowling-Meara (herpetiform), more rare – OPS PBE, PBE with muscular dystrophy, PBE with spotty pigmentation.
- Border form (PgBE). The bottom of the bladder is located at the level of the bright plate – the surface layer of the basement membrane. It has 2 subtypes. One of them is represented by 6 clinical forms. The most severe type, which is characterized by high mortality – Herlitz subtype.
- Dystrophic form (DBE) – the upper part of the papillary dermis, which is located deeper than the luminous plate, suffers. It also has two subtypes that differ according to the mechanism of inheritance – dominant and recessive. The latter type is represented by several clinical forms, the most severe of which is the subtype of Allopo-Siemens.
- Kindler syndrome (mixed bullous epidermolysis) . Bubbles can simultaneously affect different skin levels. The rarest and least studied form of the disease.
Currently, this classification is considered conditional, since in practice there are a lot of clinical forms, which often cause difficulties with diagnosis. Experts are trying to develop a more structured and acceptable classification of the disease, but so far unsuccessfully.
Causes of Epidermolysis bullosa
The disease develops as a result of mutations in more than ten genes that encode proteins that make up the skin structure. In most cases, it is inherited, less commonly it is acquired when changes in the genes occur spontaneously.
The child may inherit the pathology from one of the parents. And even if they do not suffer from epidermolysis bullosa, adults can be hidden carriers of mutated genes.
Conventionally, all causes are divided into two groups – genetic and intrauterine. The main pathogenesis is a failure in the enzyme system, with the result that some proteins become targets for enzyme attack.
Genetic disorders are very diverse:
- mutations in the PLEC, KRT5 and KRT14 genes cause a simple form of the disease, the basement membrane proteins (alpha6-beta4-integrin) and desmosomal proteins of the basal layer of the epidermis – desmoplakin, plakofillin-1 are attacked;
- mutations in the LAMB3, LAMA3, LAMC2 genes provoke the development of a borderline form of pathology, type 17 collagen and laminin-332 become the target;
- mutations in the COL7A1 gene are the cause of the dystrophic form, they cause damage to type 7 collagen, which is responsible for the stability of the structure of other connective tissue fibers of the skin;
- Kindler protein is a target in Kindler syndrome.
The formation of bubbles occurs as a result of the destruction of key structural proteins and disruption of communication between cells with the slightest mechanical effect.
Fetal causes that can lead to gene mutations are the most commonplace – smoking, alcohol consumption, medication and other factors with a teratogenic effect.
Epidermolysis Bullosa Symptoms And Forms
Patient skin does not tolerate any mechanical or physical impact. Otherwise, in response, the epidermis and dermis quickly reject. At first, bubbles form, after opening, erosion appears in their place. In some cases, a secondary infection can join the rash.People with a diagnosis of epidermolysis bullosa are at risk for developing malignant tumors.
Congenital epidermolysis bullosa can manifest itself at birth. In some cases, the skin of the child is injured even when passing through the birth canal of the mother.Babies born with this pathology are called “butterfly children.”
However, the first symptoms may appear much later – there are no exact terms. This may be the period of newborn, infancy or early childhood. The disease is least likely to occur in adolescence, but such cases are also reported.
Acquired epidermolysis bullosa, as mentioned above, results from spontaneous mutations. Therefore, most often the first signs appear in adults.Bubbles and erosions on the skin of patients suffering from epidermolysis bullosa resemble grade 3 burns.
The clinical picture is in many ways similar to the symptoms of this disease in children and depends solely on the genes in which changes occurred.
Simple Epidermolysis Bullosa
- PBE subtype Dowling-Meara (herpetiform). The most severe form of pathology. The first signs are already visible at birth. Rashes are generalized, sometimes form large erosion. Most often affects the oral mucosa. Pathology is accompanied by herpetiform eruptions on the body and extremities. In this subtype may suffer nails. They are rejected. Subsequently, deformed nail plates or long nails with hyperkeratosis grow. Its manifestations also occur on the palms and soles, later they turn into keratoderma.Simple Herpetiformitis BE (Dowling-Meara)
- PBE Kebner (generalized subtype). Extensive rashes appear at birth. Their favorite localization is the hands and feet. After healing of erosion, depigmentation sites remain. Sometimes there is palmar and plantar hyperkeratosis.PBE heavy generalized (Kebner)
- PBE subtype Weber-Cockayne (localized). The easiest form. For the first time the disease manifests itself in infancy, at least – in childhood or adolescence. The favorite localization of the bubbles of this subtype is the palms and the feet, less often the scalp. Minor erosion occurs in the oral cavity. Often with pathology appears hyperhidrosis of the palms and soles. After healing of erosions, pigmentation remains.PBE localized (Weber-Cockayne)
- PBE Ogna. Characterized by seasonal bubble formation. Rashes appear in the summer, mainly on the limbs. They are accompanied by onychogriposis (curvature of the nail in the form of a claw) on the big toes.
- PBE with muscular dystrophy. The appearance of generalized bubbles at birth. Accompanied by progressive muscular dystrophy.
- PBE with spotted pigmentation . Extensive areas with hyperpigmentation on the body, hands and feet. At the same time little bubbles are formed, but as they regress, pigmentation may increase. An additional symptom of this subtype is verrucous papules – warty growths on the skin. Oral mucosa suffers slightly.
Border epidermolysis bullosa
- PgBE Gertlitsa. The most severe form of epidermolysis bullosa. It is fatal in infancy or in early childhood. The first manifestations are the extensive bubbles that occur at the birth of a child. Later, areas of hypertrophy of granulation tissue appear, mainly in the area of the mouth, eyes, nostrils, scalp and ears. An additional symptom of this subtype is the loss of nail plates and the formation of hypertrophic granulation tissue on the terminal phalanges. The oral cavity suffers – the fossa in the tooth enamel, extensive erosions on the mucosa of the oropharynx. Possible damage to the epithelium of the nasal cavity, conjunctival mucosa, esophagus, trachea, larynx, rectum and urethra. In severe cases, numerous systemic disorders develop. The disease occurs on the background of anemia, there is a delay in growth and physical development.Frontier generalized severe vbe (fatal herlitz)
- PgBE non-gertlitsa. Rash in the mouth and airway damage is not as severe as in the previous subtype. However, there are severe anomalies of epithelial adhesion (“gluing”), which requires a tracheotomy followed by the installation of a tracheostomy. The most common symptoms are rash patches on the scalp and dystrophy of the nail plates, as well as periorifistic (located around the body’s natural openings, most often around the anus) erosion.PogreBE generalized moderate (not Herlitz)
- Localized PgBE (minimal). The course of the disease is quite easy. The rash is localized on the hands, feet and front surface of the tibia. Less frequently, dystrophy of the nails develops, and small depressions appear on the tooth enamel. On the mucous membrane of the mouth and nose are formed small erosion. The prognosis is favorable.
- PgBE with atresia (absence or overgrowth) of the gatekeeper. Another severe form of the disease. Patients suffer from the incredible fragility of the skin and mucous membranes. They often have abnormal development of the urinary organs, for example, hydronephrosis or nephritis. Distinctive feature – rudimentary auricles.
Dystrophic epidermolysis bullosa
- Localized dominant TED (DDEB,
subtypeof Cockayn-Touraine ). Bubbles form in areas that are most often subject to friction — the knees, the sacrum area, and the acral surfaces. Subsequently, at the site of a rash, the skin undergoes dystrophic processes, scarring with the formation of milia. The nails suffer, up to the complete rejection and atrophic scarring of the last phalanges of the fingers.
- Generalized dominant TED (BDE, Pasini subtype). The pathology is more severe than the localized form. Bubbles are replaced by erosion. After their healing, cicatricial plaques and milia form. An additional symptom is the spontaneous appearance of colorless dense papules on the body. As the patient grows older, generalized foci regress to localized, with a predominant lesion of the skin of the extremities. The disease is accompanied by a dystrophic change in the nails, often leading to the loss of the nail plate, and the formation of small erosions on the oral mucosa.
- Recessive RHEED. The localized form is characterized by a moderate degree of severity and is similar in symptoms to the Cockayne – Touraine DDD. Subtype Allopo-Siemens – RDEB with a heavy current. At birth, there are extensive generalized rash. Sometimes a child develops large-scale skin detachment (Bart’s syndrome). The alternation of exacerbations and periods of unstable remission leads to widespread scarring, as a result of which flexion contractures are often formed. The disease is accompanied by the manifestation of
pseudosindactyly– the child’s fingers are in a kind of “mitten”, which can lead to their fusion. There is no peririfiedlesion, lesions are localized on the head and neck. The scalp is particularly affected, where alopecia is rapidly progressing. One of the most serious manifestations is an extensive lesion of the oropharyngeal mucosa. After erosion, scars are formed which limit the movement of the tongue and prevent the mouth from opening normally. Dental seals appear on the tooth enamel, often leading to caries and even complete loss of teeth. The foci of pathology on the mucous membrane of the upper respiratory tract provoke stenosis, which is why the patient often has to undergo tracheostomy. Erosions in the esophagus cause the formation of strictures. The combination of all these manifestations leads to malnutrition and as a result – growth retardation. Such children often develop anemia. The combination of all these manifestations leads to malnutrition and as a result – growth retardation. Such children often develop anemia. The combination of all these manifestations leads to malnutrition and as a result – growth retardation. Such children often develop anemia.Recessive dystrophic severe generalized BE (Allopo-Siemens)
Most often in patients with RDE, who have reached puberty, a severe complication develops – squamous cell carcinoma. This pathology is characterized by an aggressive course, a tendency to invasion and rapid metastasis.
What is Kindler’s syndrome?
The first signs are already visible at birth. Since the rash simultaneously affects various ultrastructural levels, the clinical manifestations may resemble both the dystrophic and borderline forms of epidermolysis bullosa. In the process of healing erosions atrophic changes occur on the skin.
As they grow older, the bullous eruptions pass, but poikiloderma develops. These are manifestations of atrophy, hyperkeratosis, vascular and pigment disorders on the skin of open areas of the body, that is, those that are subject to insolation. And most often they occur in patients with photosensitivity. In addition, pathology affects the nails and can lead to syndactyly of the fingers and toes.
Over time, the course of the disease is complicated by disorders of the internal organs. There are inflammatory processes in the oral mucosa and stricture in the esophagus and urethra.
Epidermolysis Bullosa Diagnosis
Anamnesis and clinical picture allow only a preliminary diagnosis. Final confirmation of the epidermolysis bullosa can only laboratory diagnostic methods. To do this, conduct a biopsy and skin samples are subjected to a number of specific tests.
- Transmission electron microscopy It helps to see and evaluate certain elements of the skin, as well as to detect ultrastructural changes in it.
- Immunofluorescent antigen mapping (IAA). Determines the level of formation of the bubble. Allows you to estimate the amount of structural proteins and determine which of them has become a target, as well as to clarify the enzymatic activity of the tissue. A decrease in the level of the key protein may indicate its low synthesis or mass destruction.
- Genetic analysis (molecular or DNA diagnostics). The final analysis. Direct sequencing (determining the sequence of a nucleotide or amino acid compound in a DNA or RNA chain) makes it possible to accurately determine the form of epidermolysis bullosa and its type of inheritance.
If there are relatives in the family who suffer from epidermolysis bullosa, it is advisable to undergo genetic counseling at the planning stage of pregnancy, as well as prenatal diagnosis, which will reveal the pathology at an early stage of fetal development.
Epidermolysis Bullosa Treatment
Epidermolysis bullosis is a systemic pathology, so a multidisciplinary team of doctors is engaged in treatment.
TreatmentThe disease cannot be completely cured, since specific drugs to combat it have not yet been found.
However, modern methods of symptomatic therapy, proper care of wounds, as well as preventive measures greatly facilitate the condition of patients and give them the opportunity to live for quite some time.
The goal of all therapeutic measures:
- prevention of the proliferation and opening of bubbles;
- rapid healing of erosions and epithelization of the skin;
- prevention of complications.
The following groups of drugs can be prescribed as symptomatic therapy:
- analgesics eliminate pain;
- antihistamines will relieve itching and burning;
- antibiotics will help with the secondary infection of erosion;
- glucocorticoids will relieve inflammation and discomfort on the skin;
- multivitamins will have a tonic effect.
External treatment and skin care consist in treating blisters with antiseptics, applying dressings based on non-adherent materials and several layers of bandages. In addition, ultraviolet irradiation is carried out – preventive irradiation of the skin with ultraviolet rays to prevent infection of erosion.
Epidermolysis Bullosa Life Expectancy and Prognosis
The prognosis and life expectancy of a patient with epidermolysis bullosa depends on many factors – the form of the pathology and its subtype, the quality of care, the presence of complications and the general condition of the patient.Previously, death occurred in infancy, less often the children lived to three years.
Simple epidermolysis bullosa and some localized forms of other types have the most favorable prognosis. Sometimes manifestations of the disease regress, and patients live a normal life. Achieving a stable remission, they never forget about preventive measures and follow all the recommendations of doctors.
The most unfavorable prognosis for the dystrophic form of the disease. Multiple complications often lead to death in childhood.