УДК 61

Atopic dermatitis in young children in the practice of a pediatrician

Научный руководитель Ерёмичева Галина Георгиевна – кандидат медицинских наук, профессор Медицинского Университета Караганды, Республика Казахстан.

Агажанова Сабина Вагифовна – врач резидент кафедры педиатрии Медицинского Университета Караганды, Республика Казахстан.

Бакытжанова Зубайра Бакытжанкызы – врач резидент кафедры педиатрии Медицинского Университета Караганды, Республика Казахстан.

Жетписбаева Дарига Нуркасымовна – врач резидент кафедры педиатрии Медицинского Университета Караганды, Республика Казахстан.

Abstract: Atopic dermatitis is a genetically determined, chronic, recurrent skin disease that is clinically manifested by primary pruritus, inflammation, papulovesicular elements and lichenification. The pathogenesis of AD is based on altered body reactivity due to immunological and non-immunological mechanisms. The article presents current data on the epidemiology and dynamics of the prevalence of pathological symptoms, the basics of pathogenesis and key factors in the development of the disease and provides a modern classification of the disease. The purpose of this publication is to review and systematize the literature data on the development of modern concepts of atopic dermatitis in childhood. The high prevalence of atopic dermatitis in the children's population, the further growth of its severe forms, the tendency to chronic course, insufficiently studied medical, biological, and socio-hygienic development factors determine the relevance of this problem. The pathogenesis of AD is considered as two interconnected links: a defect in the skin barrier and the resulting immune inflammation, which determines the typical symptoms of AD: itching, swelling, redness and dryness of the skin. As a result of disruption of keratinization processes, increased transepidermal fluid loss, damage to structural proteins (filaggrin, involucrin, loricrin, claudins), and changes in the composition of lipids (ceramides), the protective properties of the skin are reduced. Foreign substances and bacteria penetrate the skin barrier, triggering a cascade of immunological reactions. There is dysregulation of the humoral immunity, activation of Th2 lymphocytes that synthesize IL-4, IL-13, IL-5, IL-31 and IL-10. P

Аннотация: Атопический дерматит — генетически детерминированное хроническое рецидивирующее заболевание кожи, клинически проявляющееся первичным зудом, воспалением, папуло-везикулярными элементами и лихенификацией. Патогенез АД основан на изменении реактивности организма за счет иммунологических и неиммунологических механизмов. В статье представлены современные данные об эпидемиологии и динамике распространенности патологических симптомов, основах патогенеза и ключевых факторах развития заболевания, а также дана современная классификация заболевания. Цель настоящей публикации – обзор и систематизация данных литературы о развитии современных представлений об атопическом дерматите в детском возрасте. Высокая распространенность атопического дерматита среди детского населения, дальнейший рост его тяжелых форм, склонность к хроническому течению, недостаточно изученные медико-биологические и социально-гигиенические факторы развития определяют актуальность данной проблемы. Патогенез АД рассматривают как два взаимосвязанных звена: дефект кожного барьера и возникающее в результате этого иммунное воспаление, определяющее типичные симптомы АД: зуд, отек, покраснение и сухость кожи. В результате нарушения процессов ороговения, увеличения трансэпидермальной потери жидкости, повреждения структурных белков (филаггрин, инволюкрин, лорикрин, клаудины), изменения состава липидов (церамидов) защитные свойства кожи снижаются. Инородные вещества и бактерии проникают через кожный барьер, запуская каскад иммунологических реакций. Происходит нарушение регуляции гуморального иммунитета, активация Th2-лимфоцитов, синтезирующих IL-4, IL-13, IL-5, IL-31 и IL-10.

Keywords: Atopic dermatitis, children, diagnostic criteria, local and general therapy, local glucocorticosteroids, topical calcineurin inhibitors.

Ключевые слова: атопический дерматит, дети, критерии диагностики, местная и общая терапия, местные глюкокортикостероиды, топические ингибиторы кальциневрина.

Introduction

The problem of allergic skin lesions in children is currently one of the most urgent in the practice of a pediatrician. Among allergic skin diseases in children, one of the leading places is occupied by atopic dermatitis, the prevalence of which, according to epidemiological studies, ranges from 17 to 25%. АтДAD occurs in all countries, in both sexes, and in different age groups. To date, the prevalence АтДof AD in the US child population has reached 17.2%, in children in Europe — 15.6%, in Japan — 24%, which reflects a steady increase in the frequency of AD detection over the past three decades. The frequency of AD is significantly higher among residents of economically developed countries, and the incidence АтДof AD is significantly increased among migrants from disadvantaged territories. (2)

The pathogenesis of AD is based on immune-dependent inflammation of the skin against the background of Th2-cell activation, which is accompanied by an increase in its sensitivity to external and internal stimuli. When the process is chronicled, Th1, Th17, and Th22 cells are included in the inflammatory process in addition to the remaining activity of Th2 cells. Violations of the epidermal barrier, increased dryness and transepidermal water loss in AD create conditions for transdermal entry of allergens involving mechanisms that lead to skin damage and contribute to early sensitization of the body and the initiation of inflammation. Genetic studies conducted in the United States have shown that mostly in the first year of a child's life, AD develops in 82% of children if both parents are allergic, in 59% - if one parent has AD and the other has an allergic pathology of the respiratory tract, in 56% - if only one parent is allergic, in 42% — if first-line relatives have symptoms of AD. (5)

Infantile stage of AD. The exudative form of AD is manifested in children from the newborn period to 2 years, which is characterized by acute inflammation of the skin with rashes of papules and microvesicles with pronounced exudation and wetness. Localization of rashes-more often on the face, less often on the lower leg and thighs. At the same time, against the background of hyperemia and exudation, infiltration, and edema of certain skin areas, microvesicles with serous contents, a sluggish tire are detected, which quickly open with the formation of"eczematous wells". Eczematous papules and microvesicles-manifestations of an acute inflammatory process-are asexual limited formations in the form of small nodules (up to 1 mm), slightly rising above the skin level, rounded configuration, soft consistency, mainly focal, sometimes grouped and rapidly evolving. There is also a pronounced itching and burning of the skin, soreness, and a feeling of tension. The child combs the skin, because of which the foci are covered with serous-bloody, and with the addition of a secondary infection — serous-bloody-purulent crusts. The location of skin lesions is symmetrical. Histological changes of the skin in atopic dermatitis in young children are characterized by edema, reticular dystrophy of the epidermis and the formation of perivascular infiltrates in the upper layers of the dermis. (4)

Most patients have a history of perinatal diseases: toxic erythema, persistent diaper rash (18.3%), natal spinal cord injury (28.3%), asphyxia (5.0%), intrauterine growth retardation syndrome (6.7%), neonatal pneumonia (8.3%).

In 73.3% of patients, clinical and laboratory signs of intestinal biocenosis disorders are detected, in 30% - parasitic diseases (giardiasis, enterobiosis), in 20.0% -phagocytic immunity dysfunction, in 13.3% -imbalance of metabolic processes-oxalate-calcium crystalluria, urate nephropathy. During neurological examination, hyperexcitability, myatonic and hypertensive syndromes attract attention. (7)

One-third of patients have respiratory problems in the early stages of the disease; they are re-hospitalized with laryngotracheitis (16.6%) or bronchial asthma (13.3%). Exacerbations of atopic dermatitis are associated by parents with nutritional disorders of a nursing woman (26.7%), excessive introduction of cow's milk and products based on it into the diet (20.0%), introduction of complementary foods (23.3%), acute respiratory viral diseases (3.3%), vaccination (3.3%), taking medications (33.3%). Food sensitisation is predominant in most children. The spectrum of food allergens indicates the predominant value of sensitization to everyday food products: for example, an allergy to cow's milk is observed in 88.2% of cases, to chicken egg in 83%. In second place among children under one year of age are cereals - most often wheat, corn, barley (33.5%), less often rice (18.6%) and buckwheat groats (6.4%). Several children under one year of age are allergic to meat, almost one - third (27.8%)- to pork, and 16.6% - to beef. Young children are also characterized by the development of candidiasis of the skin and mucous membranes outside the foci of allergic inflammation.(9)

Intertriginal candidiasis of the inguinal, interjagodic, axillary, cervical, behind-the-ear, and umbilical folds is most common. In the latter, sharply delineated hyperemia appears, against which exudative elements are formed-vesicles and pustules, which quickly open with the formation of erosions, merge with each other and form a cherry-red surface, moderately moist, with a whitish coating. Marked itching is noted. Around the focus, there may be "dropouts" in the form of vesicles, pustules, and small erosions. Making a diagnosis of atopic dermatitis in typical cases does not present significant difficulties. Due to the lack of pathognomonic tests and criteria for atopic dermatitis, this diagnosis in most cases is made based on basic and additional diagnostic criteria proposed by J. M. Hanifin, G. Rajka, K. D. Cooper in 1986. The main diagnostic criteria for atopic dermatitis include pruritus of the skin, typical morphology and location of the rash, tendency to chronic recurrent course, personal and family history of atopic disease, white dermography. (1)

SCORAD scale In Russia, the most widely used scale is the SCORAD scale (Fig. 1), which is used by specialists to assess the effectiveness of treatment and the dynamics of clinical manifestations of AD. Parameter A. The prevalence of the skin process is the area of affected skin (%), which is calculated using the rule of nine (see Fig. 1). For assessment, you can also use the “palm” rule (the area of the palmar surface of the hand is taken equal to 1% of the total skin surface). Parameter B. To determine the intensity of clinical manifestations, the severity of 6 signs is calculated (erythema, edema/papules, crusts/wetting, excoriation, lichenification, dry skin). Each sign is scored from 0 to 3 points, where 0 is absent, 1 is mildly expressed, 2 is moderately expressed, 3 is severely expressed (fractional values are not allowed). Symptoms are assessed on the area of skin where they are most pronounced. The total score can range from 0 (no skin lesions) to 18 (maximum intensity of all 6 symptoms). The same area of affected skin can be used to assess the severity of any number of symptoms. Subjective symptoms—itching of the skin and sleep disturbances—are assessed only in children over 7 years of age. The patient or his parents are asked to indicate a point within a 10-centimeter ruler that corresponds, in their opinion, to the severity of itching and sleep disturbances, averaged over the last 3 days. The total score of subjective symptoms can range from 0 to 20. How to calculate the SCORAD index The overall score is calculated using the formula: A/5 + 7B/2 + C. The total score on the SCORAD scale can range from 0 (no clinical manifestations of skin lesions) to 103 (the most pronounced manifestations of atopic dermatitis). When the SCORAD index is up to 20 points, the course of AD is defined as mild, from 20 to 40 points - as moderate, above 40 points - as severe. How to assess the severity of clinical manifestations in children under 7 years of age To determine the intensity of clinical manifestations, the modified SCORAD index - TIS (Three Item Severity Score, Three elements of severity assessment) can be used, which is determined by similar SCORAD parameters A and B and is calculated by formula: (3)

А/5 + 7B/2

Table 1. Assessment of the severity of atopic dermatitis according to the severity of clinical manifestations.

Mild course	Middle current	Severe course
Limited areas of skin lesions, mild erythema or lichenification, mild itching of the skin, rare exacerbations - 1-2 times a year	Widespread nature of skin lesions with moderate exudation, hyperemia and/or lichenification, moderate itching, more frequent exacerbations (3-4 times a year) with short remissions	Diffuse nature of skin lesions with severe exudation, hyperemia and/or lichenification, constant severe itching and an almost continuous recurrent course

Рисунок7

Methods

The author of this article conducted a search in the PubMed and EmBASEdatabases. The search results were articles published in January 2022 and May 2023. The search terms used were "аtopical dermatitis", "children", "diagnostic criteria", "local glucocorticosteroids", " topical calcineurin inhibitors", etc.

The authors initially found 78324 articles. To select articles, authors read the headings first and then the abstract to reduce the number of papers reviewed. To avoid exclusions from studies, it is not necessary to apply restrictive exclusion criteria. A total of 10 references were included in the study. Studies concerning atopic dermatitiswere limited, and therefore restrictive exclusion criteria were applied for them.

Results and discussion

Important in the treatment of patients with AD is the elimination of trigger factors (psychoemotional loads, house dust mites, mold, climate change, environmental problems, violation of the dietary regime, violation of the rules and skin care regime, irrational use of synthetic detergents, as well as shampoos, soaps, lotions with a high pH value, tobacco smoke etc.).

All patients with AD, regardless of the severity, prevalence, severity of the skin process, the presence or absence of complications, are prescribed basic skin care products.

With limited skin damage, with mild and moderate course of AD, with exacerbations of the disease, external therapy is mainly prescribed: glucocorticosteroid drugs for external use of a strong or moderate degree of activity and / or topical calcineurin blockers, not excluding basic therapy.

Treatment of patients with severe AD includes, in addition to external remedies, systemic drug therapy or phototherapy. Cyclosporine and/or short-course systemic corticosteroid medications may be prescribed as systemic treatment.(8)

Patients with AD require dynamic monitoring with regular assessment of the severity, severity, and prevalence of the skin process during each visit to the doctor. Therapy can change both with an increase (transition to a higher level of treatment) when the clinical manifestations become more severe, and with the use of more sparing methods of therapy (lowering the level of treatment) in the case of positive dynamics of the disease.

In the treatment of children with AD, onlythose means and methods of therapy that are allowed for use in children's practice in accordance with the age of the child should be used. Dosage forms in the form of a cream and monocomponent external agents are preferred: topical corticosteroids, calcineurininhibitors. (10)

Externaltherapyis a mandatory and important part of complex treatment of AD. It should be carried out differentially, considering the pathological changes in the skin. The goal of external AD therapy is not only to stop inflammation and itching, but also to restore the water-lipid layer and barrier function of the skin, as well as to ensure proper and daily skin care. Local glucocorticosteroids (mGCS) are first — line agents for the treatment of exacerbations of atopic dermatitis2, as well as initial therapy drugs for moderate and severe forms of the disease. Currently, there are no exact data on the optimal frequency of applications, duration of treatment, the amount and concentration of mGCS used for the treatment of atopic dermatitis D — they are determined by the characteristics of the active substance used in a particular drug. • There is no clear evidence of the benefits of applying mGCS twice a day compared to a single application. The frequency of application of mGCS is determined by the characteristics of the pharmacokinetics of the steroid: for example, methylprednisolone aceponate and mometasone furoate should be used 1 time per day, fluticasone-1-2 times a day, betamethasone, prednisone, and hydrocortisone 17-butyrate-1-3 times a day, hydrocortisone-2-3 times a day.

Topical calcineurin inhibitors (local immunomodulators) include pimecrolimus (ATX code: D11AH02) in the form of 1% cream and tacrolimus (ATX code: D11AH01) in the form of 0.03% and 0.1% ointment. Pimecrolimus is used in external therapy of mild and moderate AD in children over 3 months of age. Tacrolimus is used as a 0.03% ointment in children over 2 years of age and as a 0.1% ointment (or 0.03% ointment) in children over 16 years of age. The anti-inflammatory activity of tacrolimus corresponds to that of mGCS class III, and pimecrolimus-mGCS class I, and therefore pimecrolimus is indicated for the treatment of mild and moderate forms АтДof AD, and tacrolimus-moderate and severe forms.

Allergen-specific immunotherapy (ASIT) is the only treatment method that affects all pathogenetically significant parts of the allergic process and has a long-term preventive effect after the completion of treatment courses. There is no single expert opinion on the effectiveness of ASIT in administrative divisions. According to the results of placebo-controlled studies evaluating the effectiveness of ASIT in children with AD, therewas a statistically significant improvement in clinical signs in patients who received a subcutaneous course of ASIT.

Physiotherapy is an important step in the system of staged therapy for atopic dermatitis. In complex treatment, physiotherapeutic procedures are used that have local and systemic effects: alternating magnetic field, ultrasound treatment, electrosleep, polarized light, laser therapy, acupuncture. These factors are used strictly individually, taking into account the form and period of the disease, the severity of the disease and the presence of concomitant diseases. Prevention of atopic dermatitis should be carried out even before the birth of the child. Pregnant women and nursing mothers are prescribed a hypoallergenic diet, especially those who suffer from allergic diseases. For children at risk for developing allergic diseases, breastfeeding is recommended for as long as possible.

Conclusion

Thus, the first symptoms of AD usually appear at an early age, and in 50% of cases, the diagnosis is established by the first year of life. Atopic dermatitis has a wave-like recurrent course: in 60% of children, symptoms disappear completely over time, and in others, they persist or recur throughout life. Presumably, children who develop AD in the first year of life have a better prognosis for the disease. However, in general, the earlier the disease starts and the more severe it is, the higher the chance of its persistent course, especially in combined cases with other allergic pathology. There is a pathophysiological link between severe atopic dermatitis, bronchial asthma and allergic rhinitis, and AD is considered as the main predictor of asthma development in children. The negative impact of AD on the quality of life of children is comparable to such severe chronic diseases as psoriasis, diabetes mellitus, and others. Treatment of AD in children aimed at blocking the development of allergic inflammation should be strictly individual and based on identifying the features of pathogenesis in a particular child. Presumably, children who developed AD on their first year of life, have a better prognosis for the disease. Them However, in general, the earlier the disease debuts and the more severe the disease, the higher the chance of its persistent course, especially in combined cases with other allergic pathologies. Proven presence pathophysiological relationship between severe atopic dermatitis, bronchial asthma and allergic rhinitis, with AD considered as the main predictor of asthma development in children. (6)

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