Congenital epidermolysis bullosa (hereditary pemphigus): causes, symptoms, diagnosis, treatment

Congenital bullous epidermolysis (hereditary pemphigus) is a large group of noninflammatory skin diseases characterized by a tendency of the skin and mucous membranes to develop blisters, mainly in places of minor mechanical trauma (friction, pressure, solid food intake). 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 identified: simple bullous epidermolysis (autosomal dominant), border bullous epidermolysis (recurrent), and dystrophic bullous epidermolysis (autosomal recessive).

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

When border forms of the disease, blistering occurs in the region of the light plate of the basal membrane as a result of hypoplasia or lack of hemidesmus. A mutation is possible in one of the three genes (LAMC 2, lq51, LAMB 3, lq32, LAMA 3, 18a 11, 2) encoding complement proteins of the fixing fibrils of lalimin 5.

In dystrophic forms, blisters are formed between the basal membrane and the dermis due to the lack or weak development of fibrils and, possibly, due to the lysis of the main substance and the fibers of the dermis. With these forms, mutations in the gene of type VII collagen (chromosome 3 r 21) have been determined.

In the pathogenesis of bullous epidermolysis lies the inherent deficiency of synergism of tissue enzymes and inhibitors.

Symptoms of congenital bullous epidermolysis (hereditary pemphigus). Simple, or benign, bullous epidermolysis begins with birth or in the first days of life. The disease is characterized by the appearance of blisters on the places of mechanical trauma - elbows, knees, brushes, feet, waist. But rashes may appear on other areas of the skin. Bubbles have different sizes, transparent, rarely - hemorrhagic contents. Erosions formed after the opening of the blisters quickly epithelize, leaving no traces. Mucous membranes are very rarely affected. In the pathological process, nail plates are usually not involved. Some dermatologists distinguish the herpetiform and summer (adult) types of simple bullous epidermolysis. In the herpetiform type, the blisters are arranged in groups, nail dystrophy, palmar-plantar keratoderma can be observed. The summer type is found in adults, the blisters appear in the summer, mainly on the feet. The keratodermia of the soles and the 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 occurs more often than the simple one, occurs in the form of bullous epidermolysis of Kokkein-Turen, the white-papilloid variant of Pazini, etc. Bubbles appear on the limbs, trunk, but more often in places undergoing pressure, mucous membranes, mainly the oral cavity. This form is characterized by the healing of blisters with the formation of scars, hyperpigmented atrophic sites, milium-like epidermal cysts. Nikolsky's symptom is positive, but it is difficult to call. Sometimes there is ulcerous decay, vegetation, warty hyperkeratosis. The development of mutation is described. Often the mucous membranes of the mouth, larynx, esophagus are involved in the process, which leads to dysphagia, hoarseness of the voice. Leukoplakias can remain on the site of the healed blisters. There are onychodystrophy up to aponchia, dystrophy of teeth, hair, lag in physical development.

Among the borderline form of bullous epidermolysis, lethal bullous congenital epidermolysis (epidermolysis bullosa hereditaria letalis Herlitz) is the most severe form characterized by an innate tendency to blistering. Bubbles with serous or hemorrhagic contents appear in the first days of life. There are extensive erosions, and sometimes deeper skin defects. After healing of erosion, atrophy or scars remain. Hypo- or hyperpigmentation spots and miliary cysts. With the formation of blisters on the mucous membranes of the mouth, pharynx, larynx, soreness, difficulty swallowing, hoarse voice are noted. Cicatricial healing leads to the development of microstoma, limiting the mobility of the tongue, strictures and obstruction of the esophagus. The symptom of Nikolsky is usually positive. Recurrence of the disease with the formation of blisters on the skin of the hands, feet, in the region of the knee, elbow, wrist joints leads to the formation of contractures, fusion of fingers. Nail plates can be thickened, thinned, exposed to onycholysis or torn. Dental caries, lag in physical development, anemia, etc. Are noted.

The disease occurs either during childbirth or in early childhood with a bubble eruption, erosion on the distal parts of the limbs. Characteristic of the presence of papules and nodes of purple, located linearly mainly on the lower legs, forearms, sometimes on the trunk. In adults, lesions are represented by lichenic plaques.

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

Histopathology. With a simple epidermolysis intraepidermal blisters are found, but at the same time the elasticity is not disturbed. In the dystrophic and borderline forms of epidermolysis, the bladder has subepidermalium, the elastic is destroyed. In the dermis, single eosinophils, fibrous changes and miliary cysts, bundles of connective tissue fibers can be observed, in the region of which elastic fibers disappear.

Differential diagnosis should be performed with vesicidal diseases observed during the newborn period: neonatal pemphigus, syphilitic pemphigus, hydroa vacciniformia, with an early phase of pigment incontinence, dermatophagia, toxic exanthems.

Treatment of congenital bullous epidermolysis (hereditary pemphigus). It is necessary to avoid injuries, overheating, as they can have a provocative effect. Assign fortifying treatment (vitamins, iron preparations, calcium, apilac, carnitine chloride, anabolic hormones, solcoseryl, etc.), recommend a protein-rich diet.

In the dystrophic variant, high doses of glucocorticosteroids are administered internally in combination with antibiotics and external antibacterial agents. Phenytoin or diphenin has been shown to exert a retarding effect on collagenosis, Aevit, zinc oxide, retinol palmitate, or neotigazone (0.3-0.5 mg / kg). External apply disinfectant, antibacterial, corticosteroid agents, etc.

[1], [2], [3]