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Treatment of atopic dermatitis in children

, medical expert
Last reviewed: 23.04.2024
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Treatment of atopic dermatitis in children should be complex and pathogenetic, including elimination activities, diet, hypoallergenic regimen, local and systemic pharmacotherapy, correction of concomitant pathology, patient education, rehabilitation. The tactics of treatment are determined by the severity of clinical manifestations.

Treatment should be aimed at the following goals:

  • reduction of clinical manifestations of the disease:
  • reducing the frequency of exacerbations;
  • improving the quality of life of patients;
  • prevention of infectious complications.

Indications for consultation of other specialists

  • Allergologist: to establish a diagnosis, carry out an allergological examination, prescribe an elimination diet, establish causal allergens, select and correct therapy, diagnose allergic diseases, teach the patient and prevent the development of respiratory allergies.
  • Dermatologist: for diagnosis, differential diagnosis with other skin diseases, selection and correction of local therapy, patient education.
  • Repeated consultation of a dermatologist and an allergist is also necessary in case of a poor response to treatment with local glucocorticoids (MHCs) or antihistamines, complications, severe or persistent disease, prolonged or frequent use of strong MHC. Extensive skin damage (20% of the body area or 10% involving the skin of the eyelids, the perineum, the presence of recurrent infections in the patient, erythroderma, or common exfoliative foci).
  • Nutritionist: to compose and correct individual diets.
  • Otorhinolaryngologist: revealing and sanitation of foci of chronic infection. Early detection of allergic rhinitis symptoms.
  • Psychoneurologist: with severe itching, behavioral disorders.
  • Medical psychologist: for psychotherapeutic treatment, training in relaxation techniques, stress relieving and behavior modification.

Medicinal treatment of atopic dermatitis in children

Local treatment of atopic dermatitis in children is an obligatory and important part of the complex treatment of atopic dermatitis. It should be done differentially, taking into account the pathological changes in the skin.

The goal of local treatment of atopic dermatitis is not only to stop inflammation and itching, but also to restore the water-lipid layer and barrier function of the skin, and to ensure proper and daily skin care.

Ointments and creams for atopic dermatitis in children based on glucocorticoids

Local glucocorticoids are the first line drugs for treating exacerbations of atopic dermatitis. As well as preparations for starting therapy for moderate and severe forms of the disease. At present, there is no precise data on the optimal frequency of applications, the duration of treatment, the amounts and concentration of the local glucocorticoids used to treat atopic dermatitis.

There is no clear evidence of the benefits of applying local glucocorticoids 2 times a day compared to a single application, on this basis, as a first stage of therapy, it is justified to administer single applications of local glucocorticoids for all patients with atopic dermatitis.

The appointment of short courses (3 days) of potent local glucocorticoids in children is just as effective as long-term use (7 days) of weak local glucocorticoids.

It is not recommended to dilute the officinal topical glucocorticoids with indifferent ointments in the local treatment of atopic dermatitis, since such dilution does not reduce the incidence of side effects, as evidenced by the data of randomized controlled trials, but accompanied by a significant decrease in the therapeutic efficacy of local local glucocorticoids.

With a significant decrease in the severity of clinical manifestations of the disease, local glucocorticoids can be used intermittently (usually 2 times a week) in combination with nutrients to maintain the remission of the disease, but only if long-term therapy with local glucocorticoids is justified by the undulating course of the disease. The use of local combined preparations of glucocorticoids and antibiotics does not have advantages over local glucocorticoids (in the absence of an infectious complication).

The risk of local side effects with local glucocorticoids (stria, skin atrophy, telangiectasia), especially on sensitive areas of the skin (face, neck, creases) limits the possibility of prolonged use of local glucocorticoids in atonic dermatitis. The minimal side effects are non-fluorinated MGCs with predominantly extragenomic mechanism of action (mometasone-Elokom) and non-halogenated MGCs (methylprednisolone aceponate-Advantan). Of these, mometasone has a proven advantage in effectiveness in comparison with methylprednisolone. '

Limited use of local glucocorticoids on sensitive areas of the skin.

Depending on the ability of local glucocorticoids to bind to cytosolic receptors, block the activity of phospholipase A 2 and reduce the formation of inflammatory mediators, taking into account the concentration of the active substance. MGC by force of action is usually divided into activity classes (in Europe, I-IV classes are allocated), united into 4 groups:

  • very strong (class IV)
  • strong (class III);
  • average (class II):
  • weak (class I).

Classification of MGC by degree of activity (Miller & Munro)

Class (degree of activity)

Name of the drug

IV (very strong)

Clobetasol (Dermovate) 0.05% cream, ointment

III (strong)

Fluticasone (Fliksotid) 0.005% ointment

Betamethasone (Celestoderm-B) 0.1% ointment, cream

Mometasone (Elokom) 0.1% ointment, cream, lotion

Methylprednisolone aceponate (Advantan) 0.1% oily ointment, ointment. Cream, emulsion

Triamcinolone (Triamcinolone) 0.1% ointment

II (medium strength)

Alclomethasone (Afloderm) 0.05% ointment, cream Fluticasone (Fliksotid) 0.05% cream Hydrocortisone (Lokoid) 0.1% ointment, cream

1 (weak)

Hydrocortisone (Hydrocortisone) 1%, 2.5% cream, ointment Prednisolone

General recommendations for children on the use of ointments and creams containing glucocorticosteroids

  • In case of severe exacerbations and localization of pathological skin lesions on the trunk and extremities, treatment begins with Class III MHC. To treat facial skin and other sensitive areas of the skin (neck folds), it is recommended to use calcineurin inhibitors.
  • For routine use in the localization of lesions on the trunk and extremities in children recommend MHC I or II classes.
  • Do not use Class IV Class IV in children under 14 years of age.

Creams and ointments containing glucocorticosteroids, antibacterial and antifungal agents

If there is or suspected of an infection complication, the appointment of glucocorticoids combined with antibiotics and antifungals (betamethasone + gentamycin + clotrimazole) is indicated.

It was found that with atopic dermatitis there is a violation of the barrier function of the skin. In recent studies have shown that the violation of the barrier function of the epidermis is noted not only with exacerbation of atopic dermatitis. But also in the period of remission, as well as in skin areas that are not involved in the pathological process. With an exacerbation of atopic dermatitis, as a rule, there is a violation of the integrity of the stratum corneum, which is often accompanied by clinical manifestations of secondary infection. Skin infections in atopic dermatitis (often severe, torpid in the conduct of etiotropic therapy, are prone to recurrence.The most common infectious complication of atopic dermatitis is pyoderma, which occurs in the form of impetigo, furuncles, folliculitis and ostiofolliculitis .In severe cases, even the development of abscesses is possible. To 90% of cases of bacterial skin infection caused when S. Aureus. applied external combined In the case of joining or enhance existing secondary infection lyukokortikosteroidy, which are composed of antibacterial and / or antifungal component.

As antibacterial in recent years in Russia began to use drugs containing a broad spectrum antibiotic. - fusidic acid (FC). FC has a bacteriostatic. But in very high doses and bactericidal activity, mainly against gram-positive bacteria. The greatest activity of FC is against S. Aureus and S. Epidermidis, including methicillin-resistant S. Aureus (MRSA). Atopic dermatitis, complicated by a secondary infection. FC is used both systemically and locally. Mainly as a part of combined topical preparations. Combined topical therapy of PK in combination with betamethasone (Fucicort) or PK in combination with hydrocortisone (Fucidine G) allows to achieve a quick and stable positive therapeutic effect in the treatment of complicated forms of atopic dermatitis, as well as to reduce colonization of S. Aureus skin in comparison with monotherapy with glucocorticosteroids.

trusted-source[1], [2], [3], [4]

Calcineurin Inhibitors

Topical inhibitors of calcineurin (local immunomodulators) include pimecrolimus (1% cream) and tacrolimus. Pimecrolimus is a non-steroid drug, a cell-selective inhibitor of the production of pro-inflammatory cytokines. Suppresses the synthesis of inflammatory cytokines by T-lymphocytes and mast cells (IL-2, IL-4, IL-10, IFN-IFN) by inhibiting the transcription of the genes of pro-inflammatory cytokines. Suppresses the release of inflammatory mediators of mast cells, which leads to the prevention of itching, redness and swelling. Provides long-term control over the disease when applied at the beginning of the exacerbation period. The efficacy of pimecrolimus in atopic dermatitis has been demonstrated. It is proved that the use of pimecrolimus is safe, effectively reduces the severity of atopic dermatitis symptoms in children with mild and moderate course of the disease. The drug prevents the progression of the disease, reduces the frequency and severity of exacerbations, reduces the need for the application of MHC. Pimecrolimus is characterized by low systemic absorption; it does not cause skin atrophy. Can be used in patients with 3 months in all parts of the body and especially in sensitive areas (face, neck, skin folds) without restrictions on the area of application.

Given the mechanism of action, the possibility of local immunosuppression can not be ruled out, but in patients using pimecrolimus, the risk of developing secondary skin infections is lower than in patients receiving MHC. Patients using topical inhibitors of calcineurin are recommended to minimize exposures to natural sunlight and artificial radiation sources, and on sunny days use sunscreens after applying the drug to the skin.

trusted-source[5], [6], [7], [8], [9], [10],

Preparations of tar

Used for the treatment of atopic dermatitis in children, in some cases they can serve as an alternative to MHC and calcineurin inhibitors. However, the slow development of their anti-inflammatory action and pronounced cosmetic defect limit the wide application. It should take into account the data on the possible risk of carcinogenic effect of tar derivatives, which is based on studies of occupational diseases in persons working with tar components.

Local remedies with antibacterial and antifungal properties

Topical antibacterial and antifungal agents are effective in patients with atopic dermatitis, complicated by bacterial or fungal skin infections. To avoid the spread of fungal infection against antibiotics, it is justified to use complex preparations containing both bacteriostatic and fungicidal components (eg, mometasone + gentamycin, betamethasone + gentamicin + clotrimazole).

Antiseptics are used in the complex therapy of atopic dermatitis. But evidence of their effectiveness, confirmed by randomized controlled trials, no.

Moisturizing (softening) remedies of medical cosmetics

Moisturizing and emollients are included in the modern standard of therapy for atopic dermatitis, as they restore the integrity of the water-lipid and horny layers of the epidermis, improve the barrier function of the skin (corneotherapy), have a GCS-saving effect and are used to achieve and maintain control over the symptoms of the disease. These drugs are applied to the skin regularly, daily, at least twice a day, including after each washing or bathing, as against the use of MHC and calcineurin inhibitors. And during the remission of atopic dermatitis, when there are no symptoms of the disease. These products nourish and moisturize the skin, reduce dryness and reduce itching.

Ointments and creams more effectively restore the damaged hydro-lipid layer of the epidermis than the lotions. The maximum duration of their action is 6 hours. Therefore, the application of nutrients and moisturizers should be frequent. Every 3-4 weeks, a change in nutritional and moisturizing agents is necessary to prevent the phenomena of tachyphylaxis.

Nutritious and moisturizing agents include traditional (indifferent) and modern means of therapeutic dermatological cosmetics.

Dermatological cosmetics for dry and atopic skin care

Program

Hygiene

Humidification

Food

Anti-sleeping

Atoderm program

(laboratory

Bioderma)

Mouss Atoderm,

Soap Atoderm

Cream Atoderm PP

Cream Hydrabio

Cream Atoderm

Cream Atoderm

PP

Atoderm

RO

Zinc cream

Program for dry and atopic skin (Uryazh laboratory)

Soap Cu-Zn

Cu-Zn Gel

Thermal water Uryazh (spray)

Hydrolipidic Cream

Emollient Cream Emollient Cream Extreme

Spray Cu-Zn

Cream Cu-Zn

Cream Prusied

Gel Prusied

Program A-Derma (Ducret's laboratory)

Soap with milk of oats Realba, Gel with milk of oats Realba

Milk of Exomega

Exomega Cream

Lotion Sitelium

Cream Elitelial

The Müstell program (Laboratory Expansciece)

Cleansing Cream Stel Atopy

 

Cream-Emulsion Stel Atopy

 

The Lipikar program (La Roche-Posay lab)

Soap Surgra Mousse Lipikar Sindat

Thermal water La Roche-Posay (spray), cream Hydronorm, cream Toleran

The emulsion of Lipikar,

Lipicar bath oil

CERALIP LIP CREAM

 

A series of Friederm shampoos

Friederm Zink

Friederm

PH balance

   

Friederm Zink

Program for dry and atopic skin on the thermal water Aven (laboratory Aven)

Soap with Cold-Cream. Gel with Cold Cream

Thermal Water Aven (Spray)

Cold-Emulsion Body Emulsion

Lotion for supersensitive skin without rinsing

Thicker Tricker Cream, softening bath

Cold-Body Cream Lip Balm with Cold-Cream

Lotion Sicalfate

Cream Sicalfate

Traditional means, especially on the basis of lanolin or vegetable oils, have a number of drawbacks: they create a waterproof film and often cause allergic reactions. Therefore, modern means of medical dermatological cosmetics are considered more promising. The most common are the programs of several specialized dermatological laboratories: Bioderma (Atoderm program), Uryazh lab program, Ducret (A-Derma program), Aven (atopic skin program).

These programs are based on the use of specific, balanced and carefully selected components.

Daily skin care for atopic dermatitis in children

The third important task of local treatment of atopic dermatitis in children is proper daily skin care (cleansing, moisturizing), which allows to reduce pathological changes in the epidermis, restore its functions and prevent exacerbations, which also increases the effectiveness of treatment and increases the duration of remission.

It is important to note that the old obsolete installation of dermatologists, which prohibits bathing of children with atopic dermatitis, and especially with exacerbation of the disease, is incorrect. On the contrary, daily bathing (the use of baths is preferable to the shower) actively hydrates and cleanses the skin, providing better access to the medicinal preparations and improving the functions of the epidermis.

To cleanse the skin, it is advisable to use daily short cool (32-35 ° C) baths lasting 10 minutes with a mild detergent base (pH 5.5) that does not contain alkali [for example, shampoo of the Friederm pH range, which can also be used as a gel for shower or foam for a bath (a 10-minute exposure is required)).

For the same purpose, it is recommended to use medicinal dermatological cosmetics - soaps, mousses, gels. They have a mild wash base without alkali, effectively clean and simultaneously soften, nourish and moisturize the skin without irritating it.

When cleaning the skin, do not rub it. After bathing, it is recommended to only wet the surface of the skin without wiping it dry.

Improve the skin condition, reduce irritation, restore the structure and function of damaged epithelium in atopic dermatitis can help D-Panthenol.

D-Panthenol can be used from the first days of a child's life in any area of the skin. D-Panthenol helps to preserve the natural protective layer of the skin and promotes rapid healing of damaged skin.

D-Panthenol saturates the skin with the necessary dexpanthenol for the activation of metabolism. A derivative of pantothenic acid (water-soluble vitamin B), which normalizes cellular metabolism, stimulates skin regeneration, increases the strength of collagen fibers.

Optimum molecular weight, hydrophilicity and low polarity make it possible to penetrate D-Panthenol into all layers of the skin.

Thus, D-Panthenol promotes normalization of cellular metabolism, providing skin cells with energy and nutrients. Has a regenerating, anti-inflammatory effect on the skin. Reduces irritation, nourishes and softens the skin, helps to eliminate dryness and peeling.

For external therapy of atopic dermatitis in children, daily skin care is more comfortable cream D-Panthenol. It has a light texture, quickly absorbed, leaving no traces.

To protect the delicate skin of the diaper zone in infants, as well as to treat already appeared diaper rash, D-Panthenol ointment, which creates a reliable barrier against moisture, is more suitable.

trusted-source[11], [12], [13], [14], [15]

Systemic treatment of atopic dermatitis in children

Antihistamines are the most commonly used group of drugs for treating atopic dermatitis all over the world. Modern recommendations for the purpose of this group of drugs are reduced to the following general provisions:

  • as sedatives. And non-sedative drugs (1 st and 2 nd generation) should be considered as a means of basic therapy of atopic dermatitis in children;
  • antihistamines should be used in atopic dermatitis as a means of combating itching (since itching in atopic dermatitis is one of the pathogenetic mechanisms that support inflammation);
  • antihistamines can be used both continuously during the day, and just before bedtime, which depends on the individual course of the disease in each patient.

Modern antihistamines

1st generation (sedative)

2nd generation (non-sedentary)

Inactive metabolites

Active metabolites

Dimetinden (Fenistil)

Loratadin (Claritin)

Desloratadine (Erius)

Sequifenadine (Fenkarol)

Ebastin (Kestin)

Levocetirizine (Xisal)

Clemastin (Tavegil)

 

Cetirizine (Zirtek)

Chloropyramine (Suprastin)

 

Fexofenadine (Telfast)

Cyproheptadine (Peritol)

   

Antihistamines of the 1st generation

Antihistamines of the 1st generation only block H1 receptors by only 30%. To achieve the desired antihistamine effect requires high concentrations of these drugs in the blood, which requires the appointment of them in large doses. It is important to note that these drugs have a pronounced sedative effect, because of their high lipophilicity, they easily penetrate the blood-brain barrier and cause blockade of H1 receptors and central m-cholinergic receptors of the central nervous system (CNS), which causes their undesirable sedative effect. The purpose of these drugs can increase lethargy and drowsiness of patients, worsen cognitive functions in children (concentration of attention, memory and learning ability). That is why they should not be used constantly and for a long time and can be used only with exacerbation of atopic dermatitis short courses at night to reduce itching. In addition, because m-holinoliticheskogo (atropinopodobnogo) action, these drugs are not recommended for children with a combination of atopic dermatitis with bronchial asthma or allergic rhinitis.

trusted-source[16], [17], [18], [19], [20]

Antihistamines of the 2nd generation

These drugs selectively act on H1-receptors, do not possess m-cholinolytic action. Their significant advantage is the absence of sedative effect and influence on cognitive functions. Therefore, they are the drugs of choice in the treatment of atopic dermatitis, including in children with respiratory allergies (bronchial asthma and allergic rhinitis). They can be used for a long time to eliminate not only the night, but also the day itching. A significant difference between antihistamines of the second generation is the presence of not only selective H1 blocking action, but also anti-inflammatory effect.

The efficacy of atopic dermatitis of ketotifen and oral forms of cromoglycic acid in randomized controlled trials has not been demonstrated.

trusted-source[21], [22]

Antibacterial treatment of atopic dermatitis in children

The skin of patients with atopic dermatitis in the foci of the pathological process and outside of it is often colonized by Staphylococcus aureus. Local and systemic use of antibacterial drugs temporarily reduces the degree of colonization. In the absence of clinical symptoms of infection, systemic use of antibacterial drugs has minimal effect on the course of atopic dermatitis. The systemic use of antibiotics can be justified in patients with confirmed severe bacterial skin infection, accompanied by fever, intoxication, disruption of the general condition and poor health of the patient. Prolonged use of antibiotics for other purposes (for example, for the treatment of resistant to standard therapy forms of the disease) is not recommended.

trusted-source[23], [24], [25], [26]

Immunosuppressive therapy

It is used for particularly severe atopic dermatitis and insufficient effectiveness of all other methods of treatment. The question of the appointment of immunosuppressive therapy is decided by an allergist-immunologist.

Cyclosporine and azathioprine

These drugs are effective for the treatment of severe forms of atopic dermatitis, but high toxicity and numerous side effects limit their use. Short courses of cyclosporine have a significantly lower cumulative effect compared with long-term therapy (taking the drug for 1 year). The initial dose of cyclosporine 2.5 mg / kg is divided into 2 divided doses per day and taken internally. In order to reduce the likelihood of side effects, the daily dose should not exceed 5 mg / kg per day.

trusted-source[27], [28], [29], [30],

Systemic glucocorticoids

Systemic glucocorticoids are used to relieve severe exacerbations of atopic dermatitis in short courses. However, side effects limit the use of this method of treatment in children, so the systemic use of glucocorticoids can not be recommended for routine use. Randomized controlled trials confirming the effectiveness of this method of treatment are not available, despite its long-term use.

Allergen-specific immunotherapy

Atopic dermatitis, this method of treatment is not used, but it can be effective with concomitant asthma, allergic rhinoconjunctivitis.

trusted-source[31], [32], [33], [34], [35], [36]

Alternative methods of treatment of atopic dermatitis

There are no data from randomized controlled trials confirming the effectiveness of homeopathy, reflexology, herbal medicine, biologically active additives, etc. In the treatment of atopic dermatitis.

trusted-source[37], [38], [39], [40], [41], [42]

Non-pharmacological treatment of atopic dermatitis in children

Diet in children with atopic dermatitis

The diet for children with atopic dermatitis plays a key role in the treatment and primary prevention of atopic dermatitis, especially in infants and young children. Exclusion from the diet of causally important food allergens can significantly improve the condition and quality of life of children, the prognosis and outcome of the disease.

The most common cause of atopic dermatitis in children of the first year of life is an allergy to cow's milk proteins (79-89%). Natural feeding provides optimal conditions for normal growth and development of the child, but even 10-15% of children who are breastfed have a "milk" allergy. Soy mixtures are used in such situations: Alsoy (Nestle, Switzerland), Nutrilak soya (Nutritek, Russia), Frisoosa (Frisland, Holland), and others.

With the development of allergies to soy proteins, as well as with severe forms of food allergy, hypoallergenic mixtures with a high degree of protein hydrolysis are recommended: Alfare (Nestle), Nutramigen and Pregestimil (Mead Johnson), etc.

If gluten allergy is a protein of cereal products (wheat, rye, oats) found in 20-25% of children with atopic dermatitis, it is recommended to use gluten-free hypoallergenic cereals of industrial production based on buckwheat, rice, corn (producers: Istra Nutricium, Remedia, Heinz, Humann and others).

It is not recommended to use in foods with atopic dermatitis in children (especially the first years of life) foods with high allergenic activity. The introduction of each new product should be done under the strict supervision of the pediatrician.

Exclude from the diet of sick children foods containing food colorings, preservatives, emulsifiers; sharp, salted and fried dishes, broths, mayonnaise; restrict products with high sensitizing activity.

NB! The exclusion of any product from the diet of children should be carried out with its proven intolerance. When determining the tolerability of foods and medicines, it is advisable to consider the likelihood of cross-allergy. Thus, in children with allergies to cow's milk proteins, an allergy to beef and some enzyme preparations prepared from the mucous membrane of the stomach, pancreas of cattle can be observed; when allergic to mold fungi, hypersensitivity to yeast-containing foods is often noted: kefir, baked goods, kvass, mold varieties of cheese (Roquefort, Bree, Dorblus, etc.), penicillin antibiotics, etc.

trusted-source[43], [44], [45], [46], [47], [48], [49], [50]

Phototherapy

UV irradiation is used in patients with 12 years of age with common skin manifestations that are resistant to standard treatment.

Bioresonance therapy

Randomized controlled trials of the efficacy of this method of exposure were not conducted.

trusted-source[51], [52], [53]

Psychotherapy

Treatment of atopic dermatitis in children can be performed using group psychotherapeutic influences, where training in relaxation techniques, stress removal and behavior modification is conducted.

Indications for hospitalization

  • Exacerbation of atopic dermatitis, accompanied by a violation of the general condition.
  • A common skin process, accompanied by a secondary infection.
  • Recurrent skin infections.

Patient education

The patient should be trained:

  • rules of skin care;
  • correct use of nutrients and moisturizers, local glucocorticosteroids and other drugs;
  • Limitation of contact with adverse environmental factors.

General recommendations for patients with atopic dermatitis:

  • Hypoallergenic regime, diet.
  • Maximum limit contacts with environmental factors that exacerbate the disease.
  • Ensure optimum air humidity in the room (50-60%).
  • Maintain a comfortable air temperature.
  • Use the air conditioner in a room in hot weather.
  • Exclude the use of synthetic fabrics, clothing made of wool, preference given to cotton fabrics, silk, linen.
  • Provide a quiet environment in school and at home.
  • Brush nails short.
  • During an exacerbation, sleep in cotton socks and gloves.
  • Do not prohibit bathing, do not use hot water for a shower and / or bath; Water procedures should be short-term (5-10 min) with the use of warm water.
  • Take a shower and apply moisturizer after swimming in the pool.
  • Use special skin care products for atopic dermatitis.
  • Use liquid, not powder detergents for washing.
  • Minimize contact with allergens that exacerbate the disease, as well as with irritants.
  • Use sunscreens that do not cause skin irritation in sunny weather.
  • Fully fulfill the appointment of the attending physician.

Patients should not:

  • use alcohol-containing hygiene products;
  • Use antimicrobial agents without the recommendation of a physician;
  • To participate in sports, as this causes intense sweating and is accompanied by a close contact of the skin with clothing;
  • too often take water procedures;
  • during washing, rub the skin intensively and use a harder device to wash the device than a terry cloth sponge.

Atopic dermatitis has a significant impact on the quality of life of children. By the degree of negative impact on the quality of life, atopic dermatitis is superior to psoriasis and comparable to such serious conditions as the debut of diabetes.

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