Congenital bullous epidermolysis (hereditary vesiculitis): causes, symptoms, diagnosis, treatment

Congenital bullous epidermolysis (hereditary pemphigus) is a large group of non-inflammatory skin diseases characterized by a tendency of the skin and mucous membranes to develop blisters, mainly at the sites of minor mechanical trauma (friction, pressure, ingestion of solid food). This disease was first described by Hutchinson in 1875. Hallopean in 1896 identified two forms of the disease: simple and dystrophic. Currently, three forms of the disease are clinically distinguished: simple bullous epidermolysis (autosomal dominant), borderline bullous epidermolysis (recessive) and dystrophic bullous epidermolysis (autosomal recessive).

Causes and pathogenesis of congenital bullous epidermolysis (hereditary pemphigus). In simple bullous epidermolysis, blisters are formed at the level of keratinocytes of the basal layer, since lysis of keratinocytes occurs as a result of activation of cytolytic enzymes under the influence of trauma. A mutation of the genes encoding the expression of keratins 5 (12 q 11-13) and 14 (17q 12-q21) has been established.

In borderline forms of the disease, blisters form in the lamina lucidum zone of the basement membrane as a result of hypoplasia or absence of hemidesmasoms. A mutation is possible in one of three genes (LAMC 2, lq51; LAMB 3, lq32, LAMA 3, 18a 11, 2) encoding complements of the protein of anchoring fibrils lalimin 5.

In dystrophic forms, blisters form between the basement membrane and the dermis due to the absence or poor development of fibrils and, possibly, due to lysis of the ground substance and fibers of the dermis. In these forms, mutations have been identified in the gene for type VII collagen (chromosome 3 p 21).

The pathogenesis of epidermolysis bullosa is based on a congenital deficiency of synergism of tissue enzymes and inhibitors.

Symptoms of congenital bullous epidermolysis (hereditary pemphigus). Simple, or benign, bullous epidermolysis begins at birth or in the first days of life. The disease is characterized by the appearance of blisters at the sites of mechanical trauma - elbows, knees, hands, feet, lower back. But rashes can also appear on other areas of the skin. Blisters are of different sizes, transparent, rarely - hemorrhagic contents. Erosions formed after opening of blisters quickly epithelialize, leaving no traces. Mucous membranes are affected very rarely. Nail plates are usually not involved in the pathological process. Some dermatologists distinguish herpetiform and summer (adult) types of simple bullous epidermolysis. With the herpetiform type, blisters are located in groups, dystrophy of nails, palmoplantar keratoderma can be observed. The summer type occurs in adults, blisters appear in the summer, mainly on the legs. Keratoderma of the soles and hyperhidrosis of the palms and soles are observed. The general condition of patients does not suffer.

Dystrophic bullous epidermolysis exists from birth or begins in childhood, the disease lasts for many years. The dystrophic form is more common than the simple one, it occurs as bullous epidermolysis of Cockayne-Touraine, white papuloid variant of Pasini, etc. Blisters appear on the extremities, trunk, but more often in places subject to pressure, mucous membranes, mainly the oral cavity. This form is characterized by healing of blisters with the formation of scars, hyperpigmented atrophic areas, milium-like epidermal cysts. Nikolsky's symptom is positive, but is difficult to evoke. Ulcerative decay, vegetation, warty hyperkeratoses are sometimes observed. The development of mutulation has been described. The mucous membranes of the mouth, larynx, esophagus are often involved in the process, which leads to dysphagia, hoarseness. Leukoplakia may remain at the site of healed blisters. Onychodystrophy up to aponychia, dystrophy of teeth and hair, and delayed physical development are observed.

Among the borderline forms of bullous epidermolysis, lethal congenital bullous epidermolysis (epidermolysis bullosa hereditaria letalis Herlitz) is the most severe form, characterized by a congenital tendency to form blisters. Blisters with serous or hemorrhagic contents appear in the first days of life. Extensive erosions and sometimes deeper skin defects are formed. After the erosion heals, atrophy or scars remain. Hypo- or hyperpigmented spots and miliary cysts. With the formation of blisters on the mucous membranes of the oral cavity, pharynx, larynx, pain, difficulty swallowing, hoarse voice are noted. Cicatricial healing leads to the development of microstoma, limited mobility of the tongue, strictures and obstruction of the esophagus. Nikolsky's symptom is usually positive. Recurrence of the disease with the formation of blisters on the skin of the hands, feet, in the area of the knee, elbow, wrist joints leads to the formation of contractures, fusion of the fingers. The nail plates can be thickened, thinned, subject to onycholysis or rejected. Dental caries, delayed physical development, anemia, etc. are noted.

The disease occurs either during childbirth or in early childhood with vesicular rashes, erosions on the distal parts of the extremities. The presence of purple papules and nodes, located linearly mainly on the shins, forearms, and sometimes on the trunk, is characteristic. In adults, the lesions are represented by lichenified plaques.

The prognosis depends on the form of dermatosis. In simple bullous epidermolysis, a favorable outcome is noted, and in dystrophic and borderline forms - an unfavorable outcome, up to a lethal outcome. In dystrophic and borderline forms, patients die from various diseases (septic processes, pneumonia, tuberculosis, carcinoma, nephritis, cachexia, amyloidosis, etc.). Skin cancer can develop on the surface of long-existing lesions.

Histopathology. In simple epidermolysis, intraepidermal blisters are found, but the elastic is not damaged. In dystrophic and borderline forms of epidermolysis, blisters are located subepidermally, the elastic is destroyed. In the dermis, single eosinophils, fibrous changes and miliary cysts, bundles of connective tissue fibers, in the area of which elastic fibers disappear, can be observed.

Differential diagnosis should be made with blistering diseases observed in the neonatal period: neonatal pemphigus, syphilitic pemphigus, hydroa vacciniformia, with early phase of pigment incontinence, cutaneous gurphyria, toxic exanthema.

Treatment of congenital bullous epidermolysis (hereditary pemphigus). It is necessary to avoid injuries and overheating, as they can have a provoking effect. General strengthening treatment is prescribed (vitamins, iron preparations, calcium, apilak, carnitine chloride, anabolic hormones, solcoseryl, etc.), a protein-rich diet is recommended.

In the dystrophic variant, high doses of glucocorticosteroids are prescribed orally in combination with antibiotics and external antibacterial agents. Phenytoin or diphenin, which have an inhibitory effect on collagenosis, aevit, zinc oxide, retinol palmitate or neotigazone (0.3-0.5 mg/kg), are indicated. Disinfectants, antibacterial, corticosteroid agents, etc. are used externally.