Background
Topical therapies
Skin care: moisturizers and cleansers
Hygiene: detergents
Moisturizers - emollients
Product | Action | |
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1st-generation emollients | Vaseline, paraffin oil, fatty alcohols, hydrophilic polymers (collagen, ac. hyaluronic acid, chitosan, polysaccharides gelling) | Hygroscopic and occlusive |
2nd-generation emollients | Glycerol, sorbitol, substitutes NMF (Natural Moisturizing Factor) derivatives of pyrrolidone carboxylic acid, urea (5–10 %), lactic acid, ammonium lactate | Restoring hydration and barrier function |
3rd-generation emollients | Physiological lipids: ceramides, cholesterol, polyunsaturated fatty acids | Barrier repair therapy |
Population | Treatment | Frequency and duration of application | Efficacy | Safety |
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Infants (age <12 months) with moderate to severe AD (n = 173). Grimalt et al. 2007 [21] | Emollient containing oat extract (Exomega, Laboratories Pierre Fabre, France) | Twice/day for 6 weeks | Significant reduction in the use of high potency topical CS and improvement of SCORAD and QoL | Two severe reactions. |
Good tolerability in 94 % of patients. | ||||
Infants and young children (aged 2 months-6 years) with mild to moderate AD (n = 25) Nebus et al. 2008 [30] | Occlusive cream containing colloidal oatmeal and detergent with colloidal oatmeal and glycerin (Aveeno, Johnson & Johnson Consumer Companies, Inc., Skillman, USA) | Cream: twice/day for 4 weeks | Significant improvement of IGA, dryness and itching at 2 and 4 weeks; QoL significantly improved at 4 weeks | Well tolerated; no severe reactions related to treatment |
Cleansing: every wash | ||||
Children (aged 3 months-16 years) with mild to moderate AD (n = 65) Kircik et al. 2011 [31] | Emulsion containing ceramides (EpiCeram) | Twice/day for 3 weeks | Improvement of IGA, patient satisfaction and QoL | No severe reactions to the treatment |
Children with AD (aged 6 months-12 years) (n = 76) Giordano-Labadie et al. J 2006 [32] | Moisturizing milk (Exomega) compared to control | Twice/day for 2 months | Significant improvement of dryness, itching and QoL | Satisfactory or excellent level of tolerance in 97 % of patients |
Children (aged 6 months-12 years) with mild to moderate AD (n = 142) Breternitz et al. 2008 [17] | Glycyrrhetinic acid based cream (Atopiclair) compared to vehicle | Three times/day for 43 days | Significant improvement of IGA, reduced use of topical corticosteroids | No severe reactions related to the treatment |
Children and adolescents (aged 6 months-18 years) with mild to moderate AD (n = 121) Sugarman et al. 2009 [29] | Emulsion-containing ceramides (EpiCeram) compared to topical fluticasone (Cutivate, Pharmaderm, Melville, NY, USA) | Twice/day for 28 days | Significant improvement in SCORAD index. Comparable effectiveness between the two treatments | No severe reactions related to treatment |
Children (aged 1.5–12 years) with resistant treatments/recalcitrant AD (n = 24) Chamlin et al. 2002 [27] | Emulsion containing ceramides (Triceram, Osmotics Corp., Denver, CO, USA) instead of the previous moisturizer, continuing topical tacrolimus or topical corticosteroids | Twice/day for 12 weeks, then once/day for 9 weeks | Significant improvement of SCORAD in 92 % of patients within 3 weeks, in 100 % within 21 weeks; decrease of trans-epidermal water loss; hydration and integrity of the stratum corneum improved | No severe reactions related to treatment |
Children and adolescents (aged 2–17 years) with mild to moderate AD (n = 39) Miller et al. 2011 [33] | Glycyrrhetinic acid based cream (Atopiclair) vs. ceramide- based emulsion (EpiCeram) vs. petrolatum-based ointment (Aquaphor Healing Ointment, Beiersdorf Inc., Wilton, CT, USA) | Three times/day for 3 weeks | Improvement in the 3 treatment arms with no difference; Ointment-based petrolatum showed the best improvement measured through clinical evaluation | No severe reactions related to treatment |
Children and adults (aged 2–70 years) with mild to moderate AD (Study 1, n = 66; Study 2, n = 127) Simpson et al. 2011 [34] | Cetaphil Restoraderm moisturizing (Galderma Laboratories, Fort Worth, TX, USA) | Study 1: twice/day for 4 weeks; Study 2: twice/day for 4 weeks in addition to topical corticosteroid. | Study 1: significant decrease in pruritus and improvement of hydration and QoL. Study 2: only compared to steroid: significant improvement of hydration, decrease in EASI score and more rapid action | No severe reactions related to treatment |
Summary box
Cleansing
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Bathe for short amounts of time in warm water with gentle cleansers relatively free or free of preservatives and perfumes.
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Dry skin gently with smooth cloths
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In case of bacterial superinfection, use wash containing dilute sodium hypochlorite.
Hydration
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Emollients are the backbone of AD therapy.
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The most appropriate formulation should be chosen and applied at least daily to the entire surface of the skin in sufficient quantity to minimize xerosis, which may be affected by weather conditions and sports/activities.
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The constant use of emollients, even during remission, prevents flares and decreases the use of topical steroids.
Topical corticosteroids
Group I | Group II | Group III | Group IV |
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Low power | Moderately powerful | Powerful | High power |
• Hydrocortisone • Hydrocortisone Acetate | • Aclometasone dipropionate • Clobetasol butyrate • Dexamethasone sodium phosphate • Dexamethasone valerate • Desonide • Fluocortinbutilestere • Hydrocortisone butyrate | • Beclomethasone dipropionate • Betamethasone benzoate, dipropionate and budesonide valerate • Budesonide • Desossimetazone • Diflucortolone valerate • Diflucortolone valerianate • Fluocinolone acetonide • Fluocinonide • Fluocortolone • Fluocortolone caproate • Fluticasone propionate • Methylprednisolone aceponate • Mometasone furoate • Prednicarbate | • Halcinonide • Clobetasol propionate |
Phase of eczema | Formulation of CTS |
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Dry erythema | Cream/Milk |
Erythema with lichenification | Ointment |
Erythema with exudation | Lotion/Cream |
Hairy areas | Lotion/foam/gel |
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TCS are indicated for the treatment of eczema and not of xerosis and/or lichenification; these manifestations should be treated with moisturizers after resolution of the acute phase;
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Ointments can cause folliculitis;
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Topical agents should be applied in a thin layer until absorbed, as excess material can cause irritation;
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The selected formulation should be cosmetically acceptable to the patient in order to encourage good compliance.
Summary box
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TCSs represent the cornerstone therapy for eczema, especially for the moderate/severe forms: they should be applied on damaged, erythematous and/or exudative skin.
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TCS potency and vehicle (ointments, creams, lotions, milks or foams) should be chosen depending on the age of the patient, sites and types of eczema.
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Once daily application in the evening and continued use until complete resolution of lesions is a preferred method
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In cases of relapsing AD, “proactive” therapy should be encouraged, with the application of TCS twice a week (in the evening) on areas of frequent relapses.
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The safe monthly dose of medium to high potency TCSs is 15 g in infants, 30 g in children, 60–90 g in adolescents-adults.
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Newer generation TCS have a good safety profile, especially if used properly.
Topical antimicrobials
Summary box
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Topical antibiotics fusidic acid and mupirocin are indicated for the treatment of a monofocal bacterial superinfection (2–3 applications/day for 7-10 days).
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When S. aureus infection recurs, nasal colonization should be suspected and nasal swabbing should be performed. If positive, treat with nasal mupirocin for 3-18 months (2 applications/day for 5 days per month).
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For strains resistant to conventional treatments, retapamulin ointment is indicated as second-line treatment.
Topical immunomodulators
Summary box
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TIMs are a second-line therapy for AD.
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Tacrolimus ointment is used for moderate/severe forms:
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0.03 % formulation for patients aged 2–15 years;
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0.1 % formulation for patients ≥ 16 years.
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Pimecrolimus 1 % cream is indicated for mild/moderate AD in patients ≥ 2 years.
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Contraindications to the use of TIMs:
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<2 years old;
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congenital or acquired immunosuppression;
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known or suspected infection;
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eroded and/or exuding lesions
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significant sun exposure.
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Wet-wrap dressing
Summary box
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Wet dressing consists of a double layer of gauze or tubular dressings, the first of which is moistened, while the second layer remains dry.
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Wet wrap therapy is a short-term second-line therapy indicated for AD that is severe or resistant to topical treatments in patients older than 6 months of age.
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Topical steroids are used diluted with emollients to 10 % for the body and 5 % for the face.
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The most dangerous side effect is systemic absorption of steroid.
Systemic therapies
Systemic corticosteroids
Summary box
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The few available studies support a limited role for systemic corticosteroids in the management of severe AD in children.
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Exacerbation of symptoms often occurs after discontinuation of systemic steroids.
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Long-term use of systemic steroids may cause significant side effects.
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Short courses of therapy may be indicated in special situations.
Systemic antimicrobials
Bacterial infections
Viral infections
Fungal infections
Summary box
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Treatment with systemic antibiotics should be reserved exclusively for clear signs and symptoms of bacterial infection, not simple bacterial colonization.
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The first-choice antibiotic is a beta-lactam: flucloxacillin, amoxicillin and clavulanic acid or cephalosporins active on S. aureus, such as cefuroxime and cefixime.
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Additional treatment with intranasal mupirocin or baths with an antiseptic such as sodium hypochlorite can be useful to prevent or limit recurrence.
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Children with eczema herpeticum due to HSV require systemic therapy with acyclovir as soon as possible.
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In teenagers or others with AD localized to the head and neck that does not respond to therapy, the presence of Malassezia should be considered and an oral antifungal such as itraconazole may be administered.
Systemic immunosuppressant agents
Cyclosporine
Azathioprine
Methotrexate
Summary box
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Use of immunosuppressant agents in AD should be restricted to specialized centers.
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CsA is an immunosuppressive drug recommended as first-choice therapy for severe AD refractory to first- and second-line topical treatments.
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CsA is effective in reducing clinical scores and improving children’s quality of life, but frequent relapse of AD after the end of treatment has been reported.
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Blood pressure and renal function must be carefully monitored during CsA therapy
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AZA and MTX may represent therapeutic options for severe and refractory AD, but controlled studies defining the optimal dosage and duration of therapy are still lacking.
Antihistamines
First-generation H1 antihistamines | Second-generation H1 antihistamines | Active metabolites of second-generation H1 antihistamines (third- generation H1 antihistamines) |
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Alkilamines: Chlorpheniramine | Cetirizine | Levocetirizine |
Dimethindene | Loratadine | Decarboetoxiloratadine or Desloratadine |
Ethanolamines: Diphenhydramine | Ebastine | Norastemizole |
Ethylenediamines: Thonzylamine | Acrivastine | Fexofenadine |
Phenothiazines: Promethazine | Astemizole | |
Piperazines: Hydroxyzine | Terfenadine | |
Piperidines: Ciproeptadina | Azelastine | |
Oxatomide | Mizolastine | |
Intermediate degree of lipophilicity
| Bilastine | |
Ketotifen | Rupatadine | |
Levocabastine |
Summary box
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There is no evidence to support widespread use of antihistamines in AD.
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Short-term and intermittent courses of sedating (first-generation) antihistamines can be used in children if itch strongly affects quality of sleep.
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Topical use of antihistamines is not recommended due to risk of absorption and contact allergy.
Phototherapy
Summary box
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Phototherapy is a second-line treatment to be used when the AD is not controlled by other therapies.
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Narrow-band UVB (UVBTL01) is most commonly used and is indicated for children six years of age and older.
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Psoriasis treatment regimens are followed, with 2–3 sessions per week for a duration of a few months, depending on clinical response.
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Long-term carcinogenic effects have not been reported.
Allergen immunotherapy
Study | Study design | Patients n (age, yrs) | Allergen | Route | Duration (months) | Outcome | Adverse reactions % AIT compared to control group | Efficacy |
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Kaufman et al. 1974 [271] | qRCT DBPC | 52 (2–47) | Danders | SCIT | 24 | Success of the treatment (Physician) | Systemic: NA | Positive in 81 % of treatment group vs. 40 % of controls |
HDM | ||||||||
Moulds | Locals: 50 vs 40 | |||||||
Pollens | ||||||||
Warner et al. 1978 [272] | RCT DBPC | 20 (5–14) | HDM | SCIT | 12 | Success of the treatment (Patient) | Systemic: NA | Positive |
Locals: NA | ||||||||
De Prisco de Fuenmayor et al. 1979 [273] | Obs. | 15 (6–14) | Airborne allergens | SCIT | - | Clinical assessment | Occasional exacerbation of AD | Positive in 60 % of patients |
Ring 1982 [274] | PC | 2 twins (10) | Pollens (grasses) | SCIT | 24 | Clinical assessment sIgE (grasses) Total IgE | Occasional exacerbations of eczema in SCIT patients | Positive |
Seidenari et al. 1986 [275] | Open | 63 (4–45) | SCIT | 6–24 | Clinical assessment | Occasional mild exacerbation | Positive in 65 % of patients | |
Glover et al. 1992 [276] | RCT DBPC | 24 (5–16) | HDM | SCIT | 8 (phase I) | Success of the treatment | Systemic: 0 vs 8 | Uncertain with a possible positive effect of prolonged treatment (phase II) |
6 (phase II) | (Patient) | Locals: NA | ||||||
Heijer et al. 1993 [277] | Obs. | 93 (6–66) | Airborne allergens | SCIT | 39 | Clinical assessment | Asthma, RC, fever, fatigue, itching, dizziness | Positive |
Total IgE | ||||||||
Galli et al. 1994 [278] | RCT PC | 34 (0.5–12) | HDM | SLIT | 36 | Success of the treatment (Physician) | Systemic:0 | Negative |
Locals: 6.3 vs 5.6 | ||||||||
Trofimowicz et al. 1995 [279] | Obs. | 22 | HDM | SCIT | 36 | Clinical assessment | - | Positive in 75 % of patients treated with AIT for HDM and up to 80 % of patients treated with AIT for pollens |
Pollens | ||||||||
Zwacka et al. 1996 [280] | Controlled | 212 (6–15) | Airborne allergens | SCIT vs SLIT | 24 | Clinical assessment | - | Positive (both SLIT and SCIT) |
Total IgE | ||||||||
Czarnecka-Operacz et al. 2006 [281] | RCT DBPC | 66 (5–44) | HDM | SCIT | 48 | Success of the treatment (Physician) | - | Positive |
- 37 AIT | Pollens | |||||||
-29 Controls | ||||||||
Pajno et al. 2007 [282] | RCT DBPC | 56 (5–16) | HDM | SLIT | 18 | SCORAD (Physician) | - Local reactions in 7 SLIT patients | Positive only in patients with mild to moderate AD, not in those with severe |
- Itching and erythema in 2 SLIT patients | ||||||||
-28 AIT | Pharmacotherapy | |||||||
-28 Controls | ||||||||
Cadario et al. 2007 [283] | Obs. | 86 (3–60) | HDM | SLIT | 12 (at least) | SCORAD | No severe reactions | Positive |
Total IgE and sIgE | ||||||||
Bussmann et al. 2007 [284] | Obs. | 25 (5–65) | HDM (allergoid) | SCIT | 7 | SCORAD | - | Positive |
sIgE; sIgG4 | ||||||||
IL/mediators | ||||||||
Nahm et al. 2008 [285] | Obs. | 20 (7–58) | HDM | SCIT | 12 | Clinical assessment | None relevant | Positive |
SCORAD | ||||||||
Kwon et al. 2010 [286] | Obs. | 20 (6–33) | HDM | SCIT | 12–60 | Clinical assessment | No exacerbations | Positive |
sIgE (DP) | ||||||||
Total IgE | ||||||||
Chemokines |
Summary box
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Although its safety profile is favorable, AIT is not an appropriate therapeutic option for all patients suffering from AD.
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Its indication in clinical practice is limited by the small number of controlled randomized clinical trials and the high heterogeneity of the published works.
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AIT is most strongly indicated in a sub-group of patients with the following characteristics: sensitization to dust mites, clear correlation between allergen exposure and clinical manifestations, and severe AD.
Non-pharmacological interventions
The role of foods
Summary box
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AD is a multigenic and multifactorial disease often associated with increased production of total and/or specific IgE. This may be associated with sensitization to foods, inhalant allergens, or both.
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Allergic sensitization may occur through the gastrointestinal (breast milk) or the transcutaneous route.
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Allergic inflammation can alter the skin barrier by reducing the production of FLG.
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If a child with AD is suspected of having a FA, assess whether there is a food sensitization and whether symptoms (shock, urticaria, persistent diarrhea, asthma) require an elimination diet. Generally, it is preferable not to eliminate foods in sensitized patients without relevant immediate reactions.
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In subjects with moderate-severe AD, skin testing, particularly for the egg, may be justified. If positive, egg should be introduced in a protected environment, for the risk of immediate allergic reactions.
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In the event that appropriate therapy with emollients, topical corticosteroids and/or systemic treatments is ineffective and there is suspicion for a food a trigger, a short elimination diet and subsequent food challenge may be attempted.
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However, some advise against attempting elimination/reintroduction diets due to the possibility that reintroduction of the suspect food could cause a severe allergic reaction.
Role of the environmental triggers
House dust mites
Pets
Environmental pollutants
Climatic influences
Summary box
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Avoid mechanical and chemical irritants (eg. wool, irritant soaps, toiletries containing alcohol or perfumes).
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Anti-mite prophylactic measures should be recommended for AD patients sensitized to mites and insufficiently controlled by topical therapy.
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There is no conclusive evidence to recommend keeping or removing household pets for the sake of preventing sensitization.
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Emollient therapy should be adapted to climactic characteristics (relative humidity, solar exposure, temperature).
Textiles
Summary box
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Avoiding contact with irritating fabrics is essential AD patients.
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The use of textile products with antibacterial action must be confirmed by further studies.
Balneotherapy
Summary box
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Balneotherapy is possible adjuvant therapy in the long-term management of the AD.
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Further randomized controlled studies are needed to assess its effectiveness.
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The effects of hydrotherapy are probably enhanced by other factors such as the relaxing spa environment, the warm climate, increased sun exposure and therapeutic education program.
Educational interventions
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questions about the onset, history and evolution of the disease, as well as challenges in adhering to treatment
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evaluation of symptoms, such itching and sleep disturbance, by quantitative tools, such as the Patient Oriented SCORAD (PO-SCORAD) [265] and a Visual Analogue Scale of Pruritus;
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strategies for coping with itching and sleep disturbances [266]
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teaching the recognition of skin lesions and the application of topical medications, overcoming corticophobia, preventing flare-ups
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demonstration by nurses of techniques for bathing, applying topical medications while performing baby massage, and bandaging. The aim is for bathing, moisturizing, and dressing to be positive occasions of play.
Summary box
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The complexity of care for AD can be summarized in the following three levels: 1) bio-pharmacological; 2) educational, pedagogical and instructive; 3) psychological/psychotherapeutical
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Therapeutic education allows us to provide not only technical information about the disease and corresponding treatments, but also a customized treatment plan developed in partnership with the people involved in the case.
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The Intervention model requires a multidisciplinary team composed of the specialist physician (pediatrician, allergist, dermatologist), psychologist/psychotherapist, and other professionals including nurses, oriented toward improving not only the disease but also the quality of life of children and their families.