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Juvenile acne (acne) is the most common skin disease in children and adolescents. The debut of the disease usually manifests itself in girls aged 12-14 years, in boys at 14-15 years old - due to late puberty. Currently, the myth that the development of acne depends on the nature of nutrition, hygiene, age, sex life, has been debunked. Acne is a disease of the sebaceous glands and hair follicles, the functioning of which is associated with the exchange of sex hormones. It is generally accepted that the skin is the main link in the metabolism of sex steroid hormones, and the main "targets" for them are the epidermis, hair follicles and sebaceous glands. Changes in the functional activity of the endocrine system in adolescents during different periods of puberty have their own characteristics. At each stage of development, there is a sequential inclusion and functioning of the endocrine glands, hormones and biologically active substances. They are in close interaction with the synthesis of testosterone (Te) and sex steroids that bind globulin (PSSH) secreted by hepatocytes. In addition, the mechanisms of central regulation of the hypothalamic-pituitary system change, which affects the secretion of sex steroid hormones. During puberty, acne disrupts the ratio between androgens and estrogens, and androgens are twice as much as in healthy individuals. So, in the development of acne, the leading role is given to Te and its metabolite - dihydrotestosterone (DTT), the biosynthesis of which is 20-30 times higher than in healthy people, and in boys this process proceeds more intensively than in girls. At the same time, the biosynthesis of some skin enzymes also increases: the activity of 3-hydroxydehydrogenase and 5-reductase is also significantly increased compared to normal. The latter translates free Te into DHT, which is the main hormone involved in the hypersecretion of the sebaceous gland.
Hypersecretion of sebum is a consequence of high levels of androgens and hypersensitivity to them of the sebaceous glands.
Decisive in this case are: the direct effect of the increased content of androgens in the blood on the hair follicles and sebaceous glands; increasing the sensitivity of target cells, sex steroid receptors to circulating androgens; a combination of these two factors.
The secretion of sebum and the size of the sebaceous glands are stimulated by free testosterone of testicular or ovarian origin, dehydroepiandrosterone and androstenedione of adrenal origin. Progesterone, a precursor of testosterone, estrogen and adrenocorticosteroids, has the same effect. Progesterone enhances the secretion of the sebaceous glands due to androgenic and antiestrogenic activity. This fact explains the increase in sebum secretion and the appearance of acne elements before menstruation in women.
An increase in the level of androgens in the blood can be temporary physiological in nature, for example, in the premenstrual period in women.
Sometimes high levels of free testosterone are due to a decrease in the level of sex hormone binding globulin (PSSH). This protein, which binds to 65% of the circulating Te in the blood, is synthesized in the liver. The other part of it combines with albumin, and only 2% of the circulating total testosterone remains in an active unbound form. Therefore, markers of latent hyperandrogenism in males are an increase in the free fraction of Te, rather than total testosterone, and a decrease in PSSH.
In women, an important pathogenetic link in hyperandrogenism is a violation of androgen binding by a specific sex-steroid-binding globulin (SSH), and its concentration is twice as high as in men. This sex difference is explained by the fact that estrogens stimulate, and androgens inhibit the production of SSH.
Genetic factors are the starting point in the development of acne, different expressiveness and allelic variations of genes that determine the development of the sebaceous glands and their functional ability, and the level of enzymes and hormones to a large extent determine the severity of clinical manifestations. In addition, there is a report of the presence of a nuclear R-factor that determines a genetic predisposition. These facts can probably explain the fact that some patients develop rapidly passing physiological acne, while others develop more severe forms. According to numerous studies, the probability of developing acne in adolescents, in the presence of the disease in the family or in relatives, ranges from 50-70%.
In addition to androgen stimulation, hypersecretion of sebum by the sebaceous glands, in most patients, the debut of acne is accompanied by hyperkeratinization of the base of the follicle, which leads to blockage of the follicular duct with scales and the formation of microcomedone or clinically visible - closed (white head); or open (black head). In the future, damage and rupture of the duct occur, followed by the development of perifocal inflammation. Retention hyperkeratosis of the follicle achromoron and hyperplasia of the follicular epithelium are decisive in the development of the disease.
Blockage of the duct of the sebaceous gland entails the cessation of air access, and the created anoxic conditions are optimal for the reproduction of P. acnes, so closed comedones are called a "time bomb". P. acnes are normally found in the sebaceous glands and follicles. On the skin there are also staphylococci (epidermal and golden), micrococci, fungi of the genus Candida and Pytirosporum ovale. At the same time, the number of colonies of microorganisms is proportional to the severity of acne elements: comedones - open and closed, papules, pustules. The outcome of inflammation, as well as the predominance of one of the pathogenetic factors, largely determine the variety of clinical forms of the disease.
An important aspect is the participation of P. acnes in the development of inflammation: they synthesize various chemoattractants that attract leukocytes to the focus of inflammation, lipases and a number of enzymes that lead to damage to the follicle wall. They are able to induce the production of anti-inflammatory cytokines by mononuclear cells: IL-8, IL-1, TNF, etc., synthesize antigens that stimulate the production of antibodies, the number of which is increased in acne patients compared to healthy people. P. acnes produce vasoactive amines, similar to histamine, which increase inflammation. If comedones and papular-pustular eruptions are characterized by high contamination of P. acnes, then with nodular cystic eruptions, the amount of P. acnes is minimal. The formation of conglobate acne is probably due not so much to the number of microorganisms as to the delayed-type hyperreaction (HRT) in the dermis, this can explain the high therapeutic effect isotretinoin.
The peculiarity of propions largely determines the features of the resolution of inflammatory acne elements. Unlike most streptoderma and staphyloderma, inflammatory acne elements resolve more slowly, despite intensive treatment. Torpid to therapy is due to the resistance of P. acnes to destruction by neutrophils and monocytes, persistence in phagocytic cells, where microorganisms remain viable for a long time, despite antibiothiotherapy. In addition, Hyperproduction of fat does not make it possible to create the necessary concentration of the antibiotic in the ducts of the sebaceous gland. This may explain the appointment of long courses of antibiotics in the treatment of acne.
Thus, genetic predisposition, androgen stimulation, increased sebum secretion and follicular hyperkeratosis lead to blockage of the duct of the sebaceous gland by comedones. As a result of the reproduction of P. acnes and the formation of inflammation around the follicle and sebaceous gland, non-inflammatory and inflammatory acne elements (papule, pustule, nodule) are formed. Depending on the nature of the inflammation and the spread of the pathological process in the dermis, the foci may be compacted, infiltrate or abscess with the formation of cysts, which is due to the variety of clinical manifestations of the disease. In the course of therapy or spontaneously when acne elements are resolved, spots, depigmented scars, hypertrophic or disfiguring keloid scars remain.
Often in adolescents, the onset of the disease is accompanied by the appearance of non-inflammatory and inflammatory acne elements, which are regarded as "physiological" acne. They accompany the pubertal hormonal crisis and, due to their insignificant manifestation (comedones, single papular-pustular acne elements), can spontaneously and without a trace disappear without treatment. "Clinical" acne occurs in 15% of patients and requires treatment lasting from several months to a year or more, or until spontaneous remission is achieved, usually occurring by the age of 25.
According to the modern classification, the following clinical varieties of juvenile acne are distinguished:
- Comedonal acne.
- Papular-pustular acne.
- Conglobate acne.
- Inverse acne.
- Fulminant eels.
- Mechanical acne.
The development and course of dermatosis depend on the following factors: familial (genetic) predisposition, clinical form of the disease, type and color of the skin. When conducting clinical diagnosis, it is necessary to take into account the following features of acne:
- type of rash (inflammatory or non-inflammatory);
- the number of rashes and their prevalence, magnitude and localization;
- severity of complications (pigmentation, excoriations, scars);
- assessment of psychosocial status (anxiety, depression, social maladaptation, etc.);
- if necessary, bacterial culture with the determination of sensitivity to antibiotics, studies of hormonal status, skin biopsy for differential diagnosis with other dermatoses;
- patients with severe and often recurrent forms of acne should be examined for the presence of concomitant pathology;
- measurement of the level and rate of sebum excretion (SES);
- creating a trusting relationship between the doctor and the patient.
In the pathogenesis of acne, primary and secondary factors leading to the development of the disease are distinguished.
Basic principles of treatment: it is necessary to reduce the secretion of the sebaceous gland, reduce inflammation, reduce the colonization of the skin by Propionbacterium acnes and other microorganisms, normalize the mitotic activity of keratinocytes and eliminate blockage of the duct of the sebaceous gland.
Treatment in many cases is a difficult task, and the use of various therapeutic methods and cosmetics leads only to clinical remission, less often to cure. The choice of therapy is determined not only by the severity of acne, but also by the general condition, psycho-emotional characteristics of the individual.
At present, recommendations and an algorithm for the pathogenetic treatment of various forms of acne have been developed (XX World Congress of Dermatology, Paris, 2002).
The main objectives in the treatment are:
- prevention of the formation of comedones (preventive measures and tips for caring for "problematic" skin);
- removal of comedones (acne toilet, comedo extraction, tretinoin, retinoic acid, adapalene, salicylic acid, resorcinol);
- decrease in sebum production (retinoids systemically and externally, hormonal drugs - antiandrogens, estrogens, etc.);
- prevention of the opening of comedones, pustules and the development of inflammation (systemic antibiotics and antibacterial drugs for external use);
- combination therapy (systemic antibiotics and external retinoids or sequential use of glucocorticoids, retinoids systemically, in severe forms of acne);
- prevention of scarring (early start of treatment, retinoids, exclusion of the possibility of mechanical injury to acne elements);
- improvement of the appearance of scars only after achieving stable clinical remission (peeling, resurfacing, insertion of implants, corticosteroids, laser therapy, etc.).
The choice of treatment method depends on the following factors: the clinical form of the disease, the nature of acne elements (non-inflammatory, inflammatory), severity (mild, moderate, severe), depth, localization and prevalence of the process.
For example, comedonal acne is best treated with topical retinoids, while mild inflammatory acne shows retinoids, topical antibiotics, VRO, etc. In addition to the severity of acne lesions, complications of dermatosis in the form of scarring, pigmentation, as well as psychosocial problems should be taken into account.
In practice, systemic and external retinoids are the drugs of first choice and were first used to treat acne about 30 years ago by Stuttgen and Baer. Retinoids of the first, second and third generation have a general and local effect and are able to cause a specific biological response as a result of binding and activation of retinoic acid receptors - RAR (retinoid acid receptor).
The mechanism of action of retinoids is to inhibit the processes of keratinization (keratinization), reduce sebum secretion, as well as the activity of P. acnes and increase the proliferation of epithelial cells of the skin and sebaceous glands, thus affecting all parts of the pathogenesis of the disease.
Indications for the appointment of external therapy are: mild non-inflammatory and inflammatory forms of acne, as well as non-inflammatory forms of moderate severity.
It is possible to be combined with systemic drugs for inflammatory acne of moderate severity and severe forms.
The group of synthetic retinoids of the new (third) generation includes adapalene (differin) - a derivative of naphthoic acid, which has not only the properties of retinoids, but also an anti-inflammatory effect.
The anticomedogenic-comedolytic effect of differin is based on selective interaction with nuclear γ receptors of epithelial cells (RAR-γ), as a result of which the processes of differentiation of keratinocytes in the funnel of the sebaceous gland are improved and the production of sebum is normalized (blockage of the duct is prevented), as well as the proliferation of corneocytes of the skin. Thus, differin prevents the formation of microcomedones and promotes the removal of the "keratin plug" (comedogenic and comedonolytic action).
The anti-inflammatory effect of differin has also been studied in vitro and in vivo. It has been established that the drug inhibits the release of cytokines (inflammatory markers) — IL-1, IL-8, IL-12 — through competitive binding to TLR2 receptors of monocytes. In addition, inhibition of lipoxygenase and arachidonic acid, which is involved in the regulation of lipid metabolism in the skin, is observed. The unique pharmacological properties of differin explain its advantages (anti-inflammatory effect, better tolerability) over trans-retinoic and retinoic acid.
One of the disadvantages of external retinoids is their mild effect on the hypersecretion of the sebaceous glands, which requires, in some cases, the appointment of systemic retinoids (isotretinoin) in adequate doses for severe forms of acne. Drugs are prescribed for a long time (up to three months or more), as well as for prophylactic purposes to prevent the appearance of new acne elements.
For the treatment of conglobate acne, the basic drug is isotretinoin-roaccutane at 0.5-1.0 mg / kg body weight per day until a total cumulative dose of 120 mg / kg is reached. In adolescence, the use of antibiotics should be limited with the appointment of short courses of no more than four to six weeks, so the emphasis is on the use of topical drugs of multidirectional action, especially with mild and moderate severity of juvenile acne.
With mechanical acne (pathomimia), psychological rehabilitation, the establishment of trusting relationships with adolescents and the appointment of sedatives in combination with topical pathogenetic drugs are necessary.
In severe fulminant and inverse acne, treatment begins with the appointment of glucocorticoids (prednisolone) in a daily dose of 20-30 mg with a gradual dose reduction of 0.05 mg every five days, until the drug is completely discontinued. Prednisolone is prescribed in combination with antibiotics (according to antibiotic sensitivity), and then switch to isotretinoin in adequate doses: 0.5-1.0 mg / kg body weight per day until a total cumulative dose of 120 mg / kg is reached.
Systemic therapy (oral antibiotics, isotretinoin), often in combination with topical drugs, is indicated for the treatment of patients with moderate or severe acne. Basic antibiotics are tetracyclines: tetracycline - a daily dose of 500 mg twice a day, tetracycline monohydrate - 0.1 mg twice a day, minocycline - 0.1 mg twice a day; macrolides: erythromycin 500 mg twice a day, josamycin: 500 mg twice daily. Alternative drugs for antibiotic intolerance are cotrimoxazole 480 mg twice or thimetoprim 100-200 mg from 14 to 21 days. If one antibiotic is ineffective, in some cases it can be replaced by another. However, long-term antibiotic therapy can cause resistance to P. acnes, as a result of which treatment becomes ineffective.
When treating with isotretinoin, it should be remembered that young men with trunk lesions respond worse to treatment with small doses, so they should be prescribed a starting dose of 1.0 mg / kg, and in older people and sensitive (white) skin - 0.5 mg / kg per day, with mandatory monthly biochemical control.
In the pharmaceutical market for topical (external) therapy, various commercial firms offer modern drugs with comedogenic, keratolytic, antibacterial, anti-inflammatory and antiandrogenic properties. One of their drawbacks is a mild effect on the hypersecretion of the sebaceous glands, which requires in some cases the use of systemic retinoids (isotretinoin) in adequate doses. Drugs are prescribed for a long time (up to three months or more), as well as for prophylactic purposes - to prevent the appearance of new acne elements.
The basic drugs for external treatment of acne, as well as for systemic acne, are retinoids, as well as antibacterial drugs - benzoyl peroxide (baziron AS), local forms of antibiotics (clindamycin, erythromycin, tetracycline, mupirocin, fusidic acid) and systemic antibiotics; alternative - azelaic acid, hyaluronic acid.
Azelaic acid - natural dicarboxylic acid (skinoren) has an antimicrobial and anti-inflammatory effect, normalizes keratinization processes, blocks 5-α-reductase and the conversion of testosterone to 5-dihydrotestosterone.
In cosmetology, β-hydroacids (salicylic acid) are used, as well as resorcinol in small concentrations (1-3%), α-hydroacids (AHA) - malic, tartaric, citrus, lactic and glycolic acids. It should be remembered that topical antibiotics are not recommended to be combined with systemic antibiotics.
The antibacterial drug baziron AS, containing benzoyl peroxide, does not develop resistance in microorganisms, so it can be used in long courses of treatment, as well as as maintenance therapy. In addition, the risk of developing resistance of microorganisms to antibiotics is reduced when they are combined with benzoyl peroxide. Water-based gel for external use Baziron AS in addition to antibacterial and anti-inflammatory, it also has a comedonolytic and moisturizing effect. The combined preparation Baziron AS contains a system of "acrylic copolymer - glycerin", which provides controlled absorption of sebum and moisturizing the skin: the gel is indicated for all skin types, including sensitive.
An important place in the rehabilitation of acne patients and the prevention of complications is given to compliance with the recommendations for facial skin care (acne toilet) using maintenance therapy with topical retinoids, cleansing lotions, gels that do not have comedogenic effects. Each of these drugs for topical and systemic action has its own advantages and side effects, so it is very important to follow the recommendations given by the doctor.
