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Hodjaeva Sabri Maxmudovna, PhD., assistant of the Dermatovenereology, children dermatovenereology and AIDS department Tashkent Pediatric Medical Institute
Bababekova Nigora Bahtiyarovna, PhD., assistant of the Dermatovenereology, children dermatovenereology and AIDS department Tashkent Pediatric Medical Institute Mun Andrey Vitalevich, assistant of the Dermatovenereology, children dermatovenereology and AIDS department Tashkent Pediatric Medical Institute E-mail: [email protected]
THE PROBLEM OF EPIDERMOLYSIS BULLOSA IN CHILDREN DERMATOLOGY
Abstract: The article describes a clinical case of rare dermatosis - congenital dystrophic epidermolysis bullosa in a child 8 years of age. The clinical features, course and therapy have been described. The data indicate that, despite intensive treatment, the prognosis for this form of epidermolysis bullosa remains poor, and optimization of therapies requires further studies.
Keywords: epidermolysis bullosa, children, prognosis.
Congenital epidermolysis bullosa refers to rare heredi- feet, back). Blisters have various sizes, containing transparent, tary diseases groups, enabling them to about 30 forms, from rarely hemorrhagic fluid. Erosion resulting from the rupture mild to extremely severe - incapacitating or even fatal, char- of blisters, quickly epithelialized, leaving no scars. Mucous
acterized by impaired intercellular contact in the epidermis or dermis, with the formation of blisters that appear on the skin spontaneously or after friction, pressure or injury [1; 2; 6].
Based on the revised clinical classification in 2008 including the nature of inheritance, the biochemical and histological changes there are four main groups of epidermolysis bullosa: epidermolysis bullosa simple, border (junctional) epidermolysis bullosa, dystrophic epidermolysis bullosa and Kindler syndrome [3; 6; 7].
In the simple form of epidermolysis bullosa, the cause of the occurrence of intraepidermal blisters is the mutation of the genes encoding the synthesis of keratin 5, 14 types and plectin. It leads to destabilization of the network of tonofila-ments and cytolysis of keratinocytes of the basal layer, as a result of which the basal layer flakes off, with the intact basal membrane located at the base of the blister [4; 5]. Inherited are most often of autosomal dominant type [4].
Simple epidermolysis bullous has an autosomal dominant mode of inheritance, manifested from birth or in the first days of life. The cause is a mutation of genes encoding keratin 5 and 14 types, which leads to disruption of the structure of the filaments and the destruction of keratinocytes on the basal layer of the epidermis, resulting in its detachment. The disease is characterized by the appearance of blisters in the field of mechanical trauma (elbows joints, knees joints, hands,
membranes are affected very rarely. The nail plate is usually not involved in the pathological process. The most common forms of simple epidermolysis bullosa are the localized form of Weber - Cockayne, generalized, Koebner type and Dowl-ing-Meara type [12].
In the junctional form of epidermolysis bullosa blisters are formed as a result of splitting at the level of the lamina lucida of the basement membrane at the border of the epidermis and dermis. Genetic defect - mutations ofgenes, LAMA 3, LAMB3, LAMC2 break encoding a protein of the basement membrane in bullous pemphigoid E (hemidesmosomes) and laminin 332 (in anchor filaments). The plate of the basal membrane is located at the base of the blister. The type of inheritance is autosomal recessive. It is distinguished 2 types ofjunctional epidermolysis bullosa - lethal form - type Herlitz and non-Herlitz type, with favorable course of the disease [5; 6; 10].
Typical symptoms of this form include forming a plurality of blisters, skin erosions and atrophic scars, onychodystrophy, leading to total loss of the nail plate, the heavy loss of soft tissue in the oral cavity, enamel hypoplasia and heavy caries. Pathognomonic symptom is formation granulation tissue, which is symmetrically formed around the mouth, in the region of the middle part of the face and around the nose, in the upper back, armpits and nail ridges. Possible systemic complications are severe polyetiological anemia, growth retardation,
THE PROBLEM OF EPIDERMOLYSIS BULLOSA IN CHILDREN DERMATOLOGY
erosion and strictures of the gastrointestinal tract, damage to the mucous membranes of the upper respiratory tract and urinary tract, damage to the kidneys, outer membranes of the eye. Often, the mucous membrane of the larynx and bronchi is affected, which is manifested by a weak or hoarse cry, and further obstruction develops, which can be fatal. In the lethal form of the Herlitz, the infant mortality rate in the first year of life is 40%. Non-lethal juvenile bullosa epidermolysis occurs with moderate and severe manifestations, and with age, the skin condition improves. The main symptom of the disease is non-healing erosion around orifice [1; 5].
In dystrophic epidermolysis bullosa, blisters form deep under the basement membrane, therefore, after healing, scars remain. The development of this form is due to gene mutation COL 7 A [3, P. 21.1] encoding type VII collagen - component anchor fastening fibrils. Because of this violation, the attached fibrils are rudimentary or absent [2; 5; 9].
Both autosomal recessive and autosomal dominant variants of inheritance of dystrophic epidermolysis bullosa have been described [4].
Dominant hyperplastic dystrophic congenital epidermolysis bullosa subtype Cockayne - Touraine appears from birth, at an early age the process is generalized, then the blisters are localized on the extensor surface and the back of the hands. After blistering, hypertrophic and keloid scars are formed, appear pseudomilia. The prognosis for life is favorable [7; 11].
Dominant dystrophic albopapuloid epidermolysis bullosa (subtype Passini) begins after birth or the first days of life. In the first months, the skin lesion is generalized, and later, blisters usually occur on the same often injured areas: hands, feet, knees, elbows, neck. Healing occurs with the formation of an atrophic scar. The nail plates are affected in all patients, and only in rare cases are the nails missing, more often they are dystrophic. The growth and development of children are not impaired. With age, blisters appear less and less, and in adults only dystrophic changes in the nails and barely noticeable scars on the elbows, knees and ankles may resemble the presence of the disease [3; 5].
Recessive dystrophic epidermolysis bullosa is severe, often leading to death at an early age. The disease always occurs from birth or the first hours of life. Already at birth, the skin of the limbs is often eroded [8].
In the first days of life, rash spreads. Healing occurs with the formation of atrophic scars, contractures and syndactyly gradually develop on the hands and feet. The nail plates are absent from birth or are gradually lost as a result of the formation of subungual blisters. Multiple blisters also appear on the mucous membrane of the mouth, esophagus, and rectum. The process of scarring in the mouth leads to a restriction of the mobility of the tongue, atrophy of its papillae, overgrowth of the vestibu-
lar folds and microstomy, in the esophagus - to its narrowing, disruption of food permeability, in the rectum - to chronic constipation, sharp pain during defecation. The teeth are affected in all patients, caries, defects of tooth enamel prevail [6; 12].
Kindler syndrome is a rare autosomal recessive disorder that is associated with increased photosensitivity, poikiloderma, and blistering when injured. The development of the disease is associated with a mutation in the FERMT 1 gene, leading to a defect in the synthesis of the Kindlin-1 protein, which links the cytoskeleton with the extracellular matrix. The clinical picture is characterized by the appearance ofblisters on the skin of the extremities; increased photosensitization develop with age, progressive poikiloderma and atrophy of the skin are appear.
Etiotropic treatment for epidermolysis bullosa does not currently exist. In this regard, the treatment of patients is symptomatic. The choice of symptomatic methods depends on the severity and extent of the lesion. The formation of blisters can be minimized by limiting the traumatic effects and the use of soft, well-chosen shoes and clothing.In the presence of a secondary infection, systemic antibiotic therapy is necessary. External therapy includes topical antibiotics and epithelial agents, use protective films, atraumatic dressings. In case of dystrophic forms of congenital epidermolysis bullosa, collagenase inhibitors (difenin, retinoids, vitamin E) are prescribed. Treatment of syndactyly and joint contracture requires surgery [4; 13; 14].
Description of the clinical case. Patient H., 8 years old, was admitted to the Tashkent Pediatric Medical Institute clinic where the diagnosis of "Epidermolysis bullosa, recessive dystrophic polydysplastic type" was made.
A child from the first pregnancy, maternal age at birth was 23, the father's 32, the marriage is not related. Pregnancy proceeded on the background of toxicosis: vomiting and nausea accompanied during all period of pregnancy. TORCH - HSV positive. She got registered at 12 weeks, on the 19-20th weeks suffered influenza. During the screening, turbid amniotic fluid was detected, inpatient treatment was given. The second half of the pregnancy was uneventful. Childbirth at 37 weeks by caesarean section (mother has myopia). Amniotic fluid contained blood. Body weight at birth was 3 kg 68 g, height 48 cm. Apgar scale assessment 6/7 points which is evaluated as moderately serious condition.
Since birth, the condition is severe due to skin lesions. During the first 2 weeks of life the process has spread almost the entire surface of the skin: the skin on the torso, upper and lower limbs were multiple blisters with serous-hemorrhagic content, prone to peripheral growth and mergers no tendency to epithelial isolation. In place of opened blisters, extensive erosion was formed, with a juicy bright red bottom. On the hands and feet observed a deformation and detachment of the
nail plate. The administration of prednisone (25 mg/day i.v.), provided marked stabilization of the skin process.
Local status: a pathological process of the skin but has general, symmetrical character with localization on the skin of the lateral surface of the body on the right, shoulders, scalp, lower and upper extremities. The lesions represented as bul-lous elements with a diameter of up to 2 cm of irregular shape, with a flaccid surface and serous-hemorrhagic fluid, as well as erosions of brightpink color of the same size.
Nikolsky's sign was weakly positive. Nails on the feet and hands are absent. In the area of the hands and feet the false syndactyly, mutilation of the terminal phalanges of the toes has observed. On the mucous membrane of the oral cavity in the area of the hard palate and gums - the bleeding erosion were investigated.
Hemogram: red blood cells - 4.1x 1012/l, hemoglobin -140g/l, leukocytes - 11.8 x 109/l, stab neutrophils - 2%, segmented neutrophils-25% lymphocytes-66%, monocytes-4%, platelets - 221 x 109/l.
Urinalysis - without features. Blood culture is sterile; urine culture - sterile; seeding of cystic fluid is sterile.
Chest X- ray: moderate thymomegaly, pneumatosis of the intestine.
Geneticist consultation: autosomal recessive type of inheritance.
Treatment. Infusion of erythrocyte mass diffusion system, blood plasma, glucose, albumin, Ringer's solution, calcium gluconatis, potassium chloride, cytoflavin, vitamins A, B, E and C. Antibacterial therapy included: cefotaxim, amikacin, metronidazole, fluconazole. Local treatment consisted of applying aniline dye solutions with lidocaine and reparation gels.
The child is transferred to the orphanage with recommendations.
Conclusion: The above clinical observation is interesting in connection with a rare occurrence of this dermatosis, diagnostic difficulties and the lack of effective treatment. Unfortunately, epidermolysis bullosa is an incurable disease, but this does not mean that such patients cannot be helped. The main aim of the treatment is the proper skin care, which minimizes complications and adapts such people in society. It should be noted that clinical supervision of patients with this disease should be carried out throughout life.
References:
1.
Albanova V I., Golchenko V A. Hereditary bullous epidermolysis: modern representation about etiology and pathogenesis // Russian Journal of Skin and Venereal Diseases. 2013.- No. 2.- P. 15-19. (Russian).
Wolf K., Johnson R., Surmond D. Dermatology: Atlas Guideline.- M.: Praktika, 2007.- P. 138-153. (Russian). Rodionov V. G., Provision L. N. Epidemolysis bullosa dystrophic type (clinical case) // Prospects for Medicine and Biology. 2012.- No. 4 (1).- P. 91-94. (Russian).
Kay Shu-Mei Kane, Peter A. Lio. Pediatric Dermatology: Color Atlas and Reference.- M.: Binom, 2011.- P. 94-104. (Russian). Makhneva N. V., Andreeva T. E. A case of severe generalized recessive-dystrophic congenital bullous epidermolysis // Russian Journal of Skin and Venereal Diseases.2012.- No. 3.- P. 12-15. (Russian).
Gorlanov I. A. Pediatric dermatovenereology: textbook / ed. I. A. Gorlanov.- M.GEOTAR-Media, 2017.- P. 258-266. (Russian).
Fine J. D., Eady R. A., Bauer E. A., et al. The classification of inherited epidermolysis bullosa (EB): report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J. Am. Acad. Dermatol.- 58, 2008. - P. 931-950. Kaneko K., Kakuta M., Ohtomo Y., et al. Renal amyloidosis in recessive dystrophic epidermolysis bullosa. Dermatology. 2000; 200: 209-212.
Koshida S., Tsukamura A., Yanagi T., et al. Hallopeau-Siemens dystrophic epidermolysis bullosa due to homozygous 5818delC mutation in the COL7A gene. Pediatr Int. 2013; 55 (2): 234-237.
10. Mallipeddi R., Keane F. M., McGrath J. A. et al. Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa. J Eur Acad Dermatol Venereol, 2004a; 18: 521-6.
11. Csikos M., Orosz Z., Bottlik G., et al. Dystrophic epidermolysis bullosa complicated by cutaneous squamous cell carcinoma and pulmonary and renal amyloidosis. Clin Exp Dermatol. 2003; 28(2):163-166.
12. Fine J. D., Johnson L. B., Weiner M. et al. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience. J Am Acad Dermatol 2009; 60: 203-11.
13. Wong T., Gammon L., Liu L. et al. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol 128: 2008; 2179-89.
14. Fine J.-D., Hintner H. Life with Epidermolysis Bullosa (EB): etiology, diagnosis, multidisciplinary care and therapy. Wein: Springer-Verlag; 2009: 210-26.
9.
