1-ATOPIC DERMATITIS
Atopic dermatitis is the most common dermatological disease in early childhood. The incidence in these periods is 20%. Studies show that this rate is increasing in developed countries. The reason for this increase is related to the frequency of allergic diseases, skin barrier defects, and the increase in the use of cleaning products such as soap and detergent in childhood in the last three decades.
Atopic dermatitis usually occurs in children with dry skin in the first months of life. The causes that initiate atopic dermatitis are not fully known. Generally, an allergy occurs after atopic dermatitis lesions appear. Allergy is a result of atopic dermatitis.
Four important factors play a role in the formation of atopic dermatitis:
1-Skin barrier defects:
Numerous scientific studies emphasize the role of skin barrier defects in the etiology of atopic dermatitis. Environmental stimuli cause disruptions in the skin barrier. These barrier defects cause chronic inflammation in the skin. Atopic dermatitis is a multifactorial disease. Genetic mutations alone are not sufficient to explain the etiology of atopic dermatitis. Genetic mutations facilitate epidermal barrier dysfunction only in predisposed children. Recent studies have shown abnormalities that disrupt skin barrier function, such as excessive production of chemotryptic enzyme and non-functional flagrin protein in the stratum corneum. Ensuring skin barrier integrity is a complicated event. It is under the influence of some enzymes (protease, etc.). This barrier integrity is disrupted by hard water, washing the skin with soap and detergents, and exposure to house dust mites. Other factors that affect the deterioration of skin barrier integrity are home insulation and insulation systems that create a suitable environment for the reproduction of mites. All these factors directly disrupt the skin barrier function. It also doubles the risk of allergy. In the etiology of atopic dermatitis, it is still unknown whether the deterioration of skin integrity or inflammation occurs first. Two hypotheses are put forward here. In the first theory, inflammation that develops in response to irritants and allergens It is suggested that it disrupts skin integrity (inside-outside hypothesis). In the other theory, it is claimed that skin dryness and abnormalities in skin permeability initiate inflammation in atopic dermatitis.
Outside-inside theory, since skin dryness in infants begins before inflammation. It seems closer to reality. These defects in skin integrity facilitate the passage of allergens through the epidermis, which triggers the release of some cytokines from keratinocytes in the stratum corneum and stratum granulosum. The release of these cytokines also initiates inflammation.
The penetration barrier against irritants and allergens is localized in the lower layers of the stratum corneum. It is the corneocytes that provide the structural strength of the stratum corneum. Proteases regulate the desquamation of corneocytes. The proteases responsible for desquamation are stratum corneum chemotryptic enzyme and stratum corneum tryptic enzyme. Other proteases related to skin barrier defects are secreted by cells that initiate inflammatory reactions that cause deterioration in barrier functions. The more severe the reaction, the more the amount of these secreted proteases increases. External factors such as house dust mites cause separation of adhesion proteins that increase skin and lung permeability. These proteins, which cause immune system activation or skin irritation through direct proteolytic activity, elicit non-IgE-mediated immune or irritative reactions.
Staphylococcus aureus is not a member of the normal skin flora. It plays a role in the etiopathogenesis of atopic dermatitis through the release of superantigenic toxin. In addition to their immunological effects, these toxins have direct damaging effects on the skin barrier. Staphylococi cause damage to the skin barrier by causing proteinase production that causes damage to corneodesmosomes, with a mechanism similar to the effect of stratum corneum chemotrypsin proteases.
Flagrins are basic proteins in the skin barrier structure that contribute to the tightening of keratin filaments in the stratum corneum. In addition, these proteins also provide hydration of the skin. M that causes loss of function in the flagrin gene mutations can lead to ichthyosis. This gene is localized on chromosome 1q21. There are more than 30 genes on this chromosome. Mutations on these genes cause atopic dermatitis, asthma, allergic rhinitis, allergic sensitization and eczema.
Loricrin is the basic protein of cornified cells in the stratum corneum. It is one of the proteins that facilitates skin barrier formation and terminal differentiation of the epidermis. In electron microscopy, loricrin is found in the granular layer of the epidermis. In a study by Kim et al., it was shown that there is excessive production of Th2 cytokines in patients with atopic dermatitis, which reduces loricrin production.
Involucrin is synthesized in the suprabasal layers of stratified squamous epithelium and is a marker in keratinocyte terminal differentiation. Loricrine is synthesized in the granular layer of the epidermis. It is a protein consisting of 585 amino acids weighing 83 kilos. Flagrin, loricrin and involucrin are three essential proteins required for skin barrier integrity. Excessive production of Th2 cytokines in patients with atopic dermatitis causes a decrease not only in involucrin synthesis but also in loricrin synthesis.
2-Allergy:
Atopic dermatitis and IgE specific The connection between allergens is not fully explained and some points are still controversial. According to some, allergic reactions cause atopic dermatitis lesions. According to some claims, allergen penetrates through defective skin and causes chronic atopic dermatitis. Extensive studies have yielded important results regarding the relationship between atopic dermatitis and IgE-mediated hypersensitivity. Important findings obtained in these studies;
1-Patients with high IgE levels suffer from both atopic dermatitis and asthma.
2-In 80% of the patients, total IgE is high and total serum IgE is high. There is a correlation between the severity of atopic dermatitis and atopic dermatitis.
3-Positive skin prick test and positive specific IgE, especially against house dust mites and food allergens, were detected in a large proportion of patients.
4-Atopic. family history has been observed in the majority of patients.
5-Patients with atopic dermatitis Asthma and/or rhinoconjunctivitis were detected in 50-80% of them.
Scientific studies have also revealed that there is a greater increase in IgE levels in patients with severe atopic dermatitis than in moderate cases.
Against foods. Urticaria or angioedema are common as a result of IgE-mediated reactions. The relationship between atopic dermatitis and IgE-mediated immunological reactions is still controversial. However, controlled studies have shown a decrease in the incidence of atopic dermatitis in infants on a low-allergic food regimen. It has been observed that allergic foods such as eggs and cow's milk aggravate the condition, especially in patients with severe atopic dermatitis at a young age. In those with moderate atopic dermatitis at older ages, the relationship between atopic dermatitis and foods is less.
Allergy to house dust mites can be detected by skin prick test or the presence of serum specific IgE in children with severe atopic dermatitis. The role of house dust mites in the etiology of atopic dermatitis is controversial. However, in some of the studies, a relationship between house dust mite allergy and atopic dermatitis was clearly detected.
In the past, it was accepted that allergic reactions were related to the pathogenesis of atopic dermatitis. However, recently there have been scientific studies that bring different perspectives on the role of allergen in atopic dermatitis. It is clear that allergy sensitization and skin inflammation occur as a result of skin barrier defects. Loss-of-function mutations in the flagrin gene cause early-onset atopic dermatitis, eczema-related asthma and allergy sensitization. Since flagrin protein is not found in the lungs, allergen absorption through the skin leads to the production of specific IgE against food and inhaled allergens. It has also been reported in studies that flagrin gene mutations increase the severity of asthma in children and young adults.
In studies conducted on a large group of patients with atopic dermatitis, the presence of positive IgE against these foods was detected in the majority of foods. Consumption of these foods may cause reactions such as urticaria and angioedema. . As a result, foods can trigger urticaria and angioedema in patients with atopic dermatitis. However, it causes less flare-ups in atopic dermatitis lesions.
It has long been claimed that sensitization to foods is a result of oral intake of foods. Other food sensitization pathways have been revealed in numerous recent studies. Another study showed that more than 90% of sensitization to chicken eggs occurs through breast milk. It has also been determined that breast milk plays a role in sensitization to foods such as lactaalbumin, peanuts and ovalbumin. Other studies have shown that there is sensitivity to various allergens in prenatal sensitization as a result of active transport via the placenta. House dust mites have also been identified in amniotic fluid. Some authors claim that there is sensitization to allergens even through smell.
4-Autoimmunity
It has been determined that there are IgE antibodies against endothelial cells and keratinocyte proteins in the serum of patients with severe atopic dermatitis, and the presence of these antibodies correlates with the severity of the disease. As a result of the patient scratching the skin, these proteins are released from keratinocytes. In patients with positive early-onset autoantibodies, intense itching, bacterial skin infections and high serum IgE levels are observed more frequently. Studies on autoimmunity are limited in children. It has not been fully revealed whether there is a maternal role in the formation of these autoantibodies in infants.
5-Colonization of microbial agents
A)-Staphylococcus aureus
Stap in children with atopic dermatitis. aureus colonization has been known for a long time. The excess of this colonization occurs in atopic dermatitis patients due to immunosuppression of the skin through inflammation. S.aureus toxins (enterotoxin and TSST-1 etc.) play a role as superantigens and increase inflammation in atopic dermatitis. These superantigens can activate 20% of natural T lymphocytes. These enterotoxins interact with the Major histocompatibility class-II complex and bind to the beta chain of T cells, thus inhibiting T cells.
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