Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology*

background: Atopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis. objectives: The aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis. Methods: Eighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel. results/conclusion: The experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

# Introduction
Atopic dermatitis (AD) is a chronic inflammatory skin disease, with lesions showing typical morphology and distribution, and whose hallmark is intense pruritus. AD presents in patients with a personal or family history of atopic diseases such as asthma, rhinitis, or AD itself. It is one of the most frequent diseases of childhood, and its prevalence reaches up to 20% in infants and 2.1 to 4.9% in adults in Europe, North America, and Japan. [bib_ref] Atopic dermatitis: epidemiology and pathogenesis update, Eichenfield [/bib_ref] [bib_ref] Atopic dermatitis, Watson [/bib_ref] [bib_ref] Epidemiology of atopic dermatitis in adults: Results from an international survey, Barbarot [/bib_ref] Annual incidence of new cases of AD in patients below the age of 17 in the US is 11%; 85% of AD patients first manifest the disease before the age of 5, but 20-40% of children with AD persist with the skin disease in adulthood. [bib_ref] Atopic dermatitis and the atopic march, Spergel [/bib_ref] [bib_ref] Adult-onset atopic dermatitis, Ozkaya [/bib_ref] In the Brazilian population, prevalence of AD symptoms according to in children and 5.0% in adolescents. [bib_ref] Prevalence of atopic eczema and related symptoms in Brazilian schoolchildren: results from..., Sole [/bib_ref] Due to the complex pathogenesis of AD, which involves skin barrier defects, immune dysfunction, and microbiome alterations mediated by genetic, environmental, and psychological triggers, a single therapeutic approach is hardly capable of achieving disease control. [bib_ref] Profile of skin barrier proteins and cytokines in adults with atopic dermatitis, Orfali [/bib_ref] Increased transepidermal water loss (TEWL), decreased stratum corneum water content, and reduced expression of skin barrier proteins such as filaggrin and claudin 1 are the main alterations of the skin barrier in individuals with AD. [bib_ref] Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17..., Batista [/bib_ref] [bib_ref] Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms, Elias [/bib_ref] [bib_ref] Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and..., Gittler [/bib_ref] Of note is the cytokine dysregulation, leading to Th2, Th1, Th17, and Th22 polarization, which varies according to age, ethnicity, and AD phase. [bib_ref] Severe atopic dermatitis is characterized by selective expansion of circulating TH2/ TC2..., Czarnowicki [/bib_ref] [bib_ref] New insights into atopic dermatitis: role of skin barrier and immune dysregulation, Leung [/bib_ref] [bib_ref] The skin microbiome is different in pediatric versus adult atopic dermatitis, Shi [/bib_ref] Skin microbiome plays a crucial role in AD; about 90% of the skin of atopic individuals is colonized by Staphylococcus aureus (S. aureus). [bib_ref] Bacterial and Viral Infections in Atopic Dermatitis: a Comprehensive Review, Ong [/bib_ref] The diversity of skin microbiome of AD patients shows temporal shifts, with a predominance of S. aureus during flares and Streptococcus, Propionibacterium, and Corynebacterium after treatment. [bib_ref] Temporal shifts in the skin microbiome associated with disease flares and treatment..., Kong [/bib_ref] AD remains a challenging disease. Ideal treatment is targeted to long-term disease control with reduction of flares and maintenance of good quality of life. Moreover, treatment approaches depend on geographic, economic, and genotypic/phenotypic variations. This paper aims to communicate the experience, opinions, and recommendations of Brazilian dermatology experts on atopic dermatitis treatment.

# Methods
Eighteen faculty members from 10 university hospitals with expertise in AD were appointed by the Brazilian Society of Dermatology. The first step was the application of an online questionnaire with 14 questions regarding the management of AD patients by the experts at university hospitals. [fig_ref] Table 1: shows the data obtained from the applied questionnaire [/fig_ref] shows the compiled answers.
The second step was the analysis of recent international guidelines (American Academy of Dermatology, published in 2014, and the European Academy of Dermatology and Venereology, published in 2018). [bib_ref] Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis..., Eichenfield [/bib_ref] [bib_ref] Guidelines of care for the management of atopic dermatitis: section 2. Management..., Eichenfield [/bib_ref] [bib_ref] Guidelines of care for the management of atopic dermatitis: section 3. Management..., Sidbury [/bib_ref] [bib_ref] Guidelines of care for the management of atopic dermatitis: Section 4. Prevention..., Sidbury [/bib_ref] [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] All sections and recommendations regarding AD treatment were discussed with the 18 experts, and consensus was defined as approval by at least 70% of the panel. This paper expresses their opinions regarding international guidelines for AD treatment and provides practical guidance for dermatologists in Brazil. Daily bathing is possible for regular skin hydration, and emollients should be applied on slightly wet skin, immediately after drying; application twice daily is usually sufficient. [bib_ref] The Association Between Bathing Habits and Severity of Atopic Dermatitis in Children, Koutroulis [/bib_ref] Some emollients have additional ingredients such as urea and propylene glycol, which may lead to skin irritation, and there is still inconclusive evidence about superiority of emollients enhanced with components of the skin barrier such as ceramides. [bib_ref] The Association Between Bathing Habits and Severity of Atopic Dermatitis in Children, Koutroulis [/bib_ref] [bib_ref] Recommendations from a European Roundtable Meeting on Best Practice Healthy Infant Skin..., Blume-Peytavi [/bib_ref] Recent concepts regarding the microbiome and the skin highlight that the cutaneous microbiome in AD is not as heterogeneous as in healthy individuals, with the predominance of Staphylococcus aureus (S. aureus). [bib_ref] Temporal shifts in the skin microbiome associated with disease flares and treatment..., Kong [/bib_ref] [bib_ref] Topographical and temporal diversity of the human skin microbiome, Grice [/bib_ref] Recovery of the skin barrier by adjusting the inflammatory response reestablishes the skin microbiome in AD patients. [bib_ref] Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis..., Simpson [/bib_ref] [bib_ref] Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management, Mohan [/bib_ref] Bacterial lysates or topical application of commensal bacteria are promising, but skin hydration itself is able to recover the skin microbiome. [bib_ref] Temporal shifts in the skin microbiome associated with disease flares and treatment..., Kong [/bib_ref] [bib_ref] First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis, Myles [/bib_ref] There is evidence for early use of emollients in atopic dermatitis-prone children (three months of age and older) in the prevention of AD. [bib_ref] Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis..., Simpson [/bib_ref] [bib_ref] Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management, Mohan [/bib_ref] Recommendations by the dermatology experts for baseline therapy:

# Results/discussion
Daily cleansing for up to 5 minutes with mild agents with adequate pH Emollient application twice daily on slightly wet skin is the main component of baseline therapy

## Aeroallergens
Aeroallergens are relevant triggering factors of AD flares. [bib_ref] Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge..., Werfel [/bib_ref] [bib_ref] House dust mite reduction in the management of atopic dermatitis. A critically..., Garritsen [/bib_ref] [bib_ref] Atopy patch test with Aleuroglyphus ovatus antigen in patients with atopic dermatitis, Lorenzini [/bib_ref] Exacerbation of an eczematous lesion after skin contact or inhalation has been reported, but studies are still inconclusive. [bib_ref] House dust mite reduction in the management of atopic dermatitis. A critically..., Garritsen [/bib_ref] The skin prick test and specific IgE are routinely utilized but have a low positive predictive value. [bib_ref] House dust mite reduction in the management of atopic dermatitis. A critically..., Garritsen [/bib_ref] In the present panel of dermatology experts, 89% do not perform the skin prick test or RAST as part of routine practice.

## Food allergy
One-third of the children with moderate/severe AD have associated food allergy; however, food allergy is not the cause of AD. [bib_ref] Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions for improving established atopic..., Eigenmann [/bib_ref] Restrictive diets should only be prescribed for children with proven food allergy. [bib_ref] Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions for improving established atopic..., Eigenmann [/bib_ref] The published guidelines recommend restrictive diets only for those patients with a positive oral challenge test, the gold standard assay for food allergy. [bib_ref] Guidelines of care for the management of atopic dermatitis: Section 4. Prevention..., Sidbury [/bib_ref] [bib_ref] Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions for improving established atopic..., Eigenmann [/bib_ref] [bib_ref] Patterns of care and referral in children with atopic dermatitis and concern..., Thompson [/bib_ref] The detection of specific IgE to food through prick or serological tests does not prove food allergy, and their positive predictive value is low. [bib_ref] Specific IgE and skin prick tests to diagnose allergy to fresh and..., Cuomo [/bib_ref] The present panel of dermatology experts does not recommend restrictive diets, but considers that food allergy may be investigated in children with severe, treatment-resistant AD and in those with a history of flares following ingestion of specific foods.

## Contact dermatitis
Contact dermatitis is present in 40-65% of AD patients, usually exacerbating the existing eczema. [bib_ref] Frequency of contact allergens in pediatric patients with atopic dermatitis, Herro [/bib_ref] The patch test is recommended for refractory AD with atypical skin lesions. [bib_ref] Management of difficult-to-treat atopic dermatitis, Arkwright [/bib_ref] Patients should be tested for fragrances, preservatives, topical corticosteroids, and other topical components. [bib_ref] Frequency of contact allergens in pediatric patients with atopic dermatitis, Herro [/bib_ref] Patients are more prone to develop occupational dermatoses, since AD exacerbates the irritant effect of allergens in certain professions such as hairdressers, mechanics, metalworkers, janitorial workers, and nurses, in whom hand eczema is commonly reported. [bib_ref] Contact Dermatitis in Atopic Dermatitis Children-Past, Present, and Future, Borok [/bib_ref] Preventive measures should be taken in order to reduce the incidence of AD in such patients.
Fifty percent of the expert group recommend patch tests.
The main problem is the difficulty in performing the test, since ideal sites are usually limited in AD patients.

## Topical anti-inflammatory therapy
Topical anti-inflammatory therapy is the mainstay of AD treatment. Anti-inflammatory agents must have sufficient potency and should be applied on the skin lesions according to the recommendations and not exceeding the allowed amount per day. 41

## Topical corticosteroids (tc)
TC are the first line treatment for AD, with strong evidence of their superiority over placebo. [bib_ref] The management of moderate to severe atopic dermatitis in adults with topical..., Van Der Meer [/bib_ref] They are classified according to their potency based on vasoconstrictive effects, and every clinician should be aware of their potential local and systemic adverse effects, such as cutaneous atrophy and adrenal suppression. [bib_ref] Balancing efficacy and safety in the management of atopic dermatitis: the role..., Luger [/bib_ref] [bib_ref] Hypothalamus-pituitary-adrenal axis suppression by superpotent topical steroids, Walsh [/bib_ref] Strategies defining the use of TC vary according to their potency, but the suggested applied amounts of topical corticosteroids follow the fingertip unit rule. [bib_ref] Guidelines of care for the management of atopic dermatitis: Section 4. Prevention..., Sidbury [/bib_ref] [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] In the European guidelines, the approximate total amount of TC per month is 15g in infants, 30g in children, and 60-90g in adolescents and adults. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] The choice of corticosteroid and its vehicle depend on the affected site, the patients' age and the severity and clinical phase of AD. Wet-wrap dressings may improve AD flares, and ultrahigh potent topical corticosteroids should be applied for up to two weeks. [bib_ref] Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management, Mohan [/bib_ref] [bib_ref] Pathways to managing atopic dermatitis: consensus from the experts, Lebwohl [/bib_ref] TC use depends on the vehicle; as a cream, they should be applied 15 minutes before the moisturizer, and as an ointment, applied 15 minutes prior to the moisturizer. [bib_ref] Guidelines for treatment of atopic eczema (atopic dermatitis) part I, Ring [/bib_ref] Corticosteroid phobia is a relevant matter that should be addressed, especially due to its influence on adherence to treatment; it varies according to the country and culture. [bib_ref] Topical corticosteroid phobia in atopic dermatitis: International feasibility study of the TOPICOP..., Stalder [/bib_ref] Topical corticosteroids are the first-line topical treatment for AD, according to the experts.

## Calcineurin inhibitors (topical immunomodulators or tim)
Tacrolimus and pimecrolimus are second-line non-corticosteroid, anti-inflammatory therapies for AD with proven efficacy. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] [bib_ref] The role of topical calcineurin inhibitors in atopic dermatitis, Alomar [/bib_ref] The most widely reported adverse effect is burning sensation during the initial days of use (especially with tacrolimus); they do not induce skin atrophy, which makes them useful for application on eyelids, perioral lesions, axillae, and genitals. [bib_ref] Tacrolimus ointment does not affect collagen synthesis: results of a single-center randomized..., Reitamo [/bib_ref] Despite a black box warning in the package insert, studies have not reported an increased risk of lymphoma with the topical use of TIM at therapeutic doses. [bib_ref] Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in..., Arellano [/bib_ref] Intermittent use of TIM is recommended above two years of age. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] Eighty percent of the Brazilian experts use TIM as a second-line therapy for AD.

## Proactive treatment
Proactive treatment has been proposed in published guidelines. It consists of long-term use of topical anti-inflammatory agents, either TC or TIM (tacrolimus), twice a week in previously affected areas, combined with moisturizers. [bib_ref] Comparison of Dermatology and Allergy Guidelines for Atopic Dermatitis Management, Mohan [/bib_ref] [bib_ref] Pathways to managing atopic dermatitis: consensus from the experts, Lebwohl [/bib_ref] [bib_ref] Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis:..., Thaci [/bib_ref] [bib_ref] Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment, Wollenberg [/bib_ref] The rationale for proactive treatment is based on its efficacy and long-term safety (up to one year), reducing the number of flares and improving the quality of life of atopic patients. [bib_ref] Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis:..., Thaci [/bib_ref] [bib_ref] Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment, Wollenberg [/bib_ref] The Brazilian experts recommend proactive treatment with TC or TIM in AD patients.

## Topical antimicrobial therapy
Colonization by S. aureus is frequent on the skin of AD patients and is much higher than in non-atopic individuals (100% vs. Proactive therapy with either TC or TIM is safe, reduces flares and AD severity, and is indicated as long-term maintenance therapy.
The use of topical antibiotics and antiseptics is still variable. Topical antibiotics can be used for short periods, and bleachers (0.005% sodium hypochlorite may be useful for pediatric AD).
Wet-wrap bandages or occlusive treatment during hospitalization are helpful measures for improving flares.
In patients that fail to respond to topical treatment, the following should be considered:
-differential diagnoses of AD The aim of systemic antihistamines in AD is to allow better quality of sleep, since their role as anti-inflammatory agents in AD is controversial. There is no evidence of improvement of severity scores in randomized studies, and first-generation drugs are prescribed due to their sedative effect and to the relief of other conditions related to AD, such as asthma, rhinoconjunctivitis, dermographism, and urticaria. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] [bib_ref] Early Treatment of the Atopic Child Study Group. Long-term treatment with cetirizine..., Diepgen [/bib_ref] However, our group stresses that the quality of sleep induced by anti-H1R drugs is not ideal, since they do not alter the REM phase. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] [bib_ref] Early Treatment of the Atopic Child Study Group. Long-term treatment with cetirizine..., Diepgen [/bib_ref] Our group recommends the use of first-generation antihistamines (hydroxyzine and chlorpheniramine) based only on their sedative effect. flares. [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] Pregnancy is not a contraindication to CyA use. [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] Although CyA leads to prompt improvement in severity scores after 2 weeks from the initial dose, reactivation of AD after the drug's suspension is equally rapid, occurring in 2 weeks. 63

## Anti-inflammatory agents

## Methotrexate (mtx)
MTX can be indicated as initial treatment for moderate/severe AD, recalcitrant to topical treatment with corticosteroids. The drug has a good safety profile and is indicated for long-term maintenance;
clinical efficacy is reached after 8-12 weeks of administration. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] The therapeutic dose varies from 15 to 25mg/week for adults and 10-15mg/m 2 /week for children (oral, intravenous, or subcutaneous), and folate should be added to the treatment, usually 1-2 days after MTX. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] Average length of treatment ranges from 6 to 12 months, and clinical improvement is seen at 8-12 weeks from the initial dose. Side effects include hematological disorders, liver enzyme alterations, and gastrointestinal discomfort. Its use is recommended for up to 2 years, with constant monitoring of bone marrow and liver function. [bib_ref] Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults..., Wollenberg [/bib_ref] [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] [bib_ref] Atopic dermatitis: a practice parameter update 2012, Schneider [/bib_ref] Contraception is mandatory, since the drug is considered category X. [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] Azathioprine (AZA) AZA can be indicated as systemic treatment for refractory AD. Peak efficacy of AZA is reached after 8-12 weeks of use. [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] The initial dose is usually 50 mg/day for 1-2 weeks, increased thereafter to 2-3 mg/kg/day. [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] [bib_ref] Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind,..., Meggitt [/bib_ref] It can increase the risk of non-melanoma skin cancer and lymphoma. [bib_ref] Risk of lymphoma in patients with ulcerative colitis treated with thiopurines: a..., Khan [/bib_ref] [bib_ref] Waxweiler WT, Agans R, Morrell DS. Systemic treatment of pediatric atopic dermatitis..., Peyrin-Biroulet [/bib_ref] Thiopurine methyltransferase enzyme (TPMT) levels should be measured whenever possible, since TPMT deficiency while in use of AZA can lead to bone marrow aplasia. [bib_ref] Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind,..., Meggitt [/bib_ref] It can be prescribed for children (off label for AD) and is subject to restricted indication during pregnancy. [bib_ref] ETFAD/ EADV Eczema task force 2015 position paper on diagnosis and treatment..., Wollenberg [/bib_ref] suicidal ideation may be present. [bib_ref] Guidelines for treatment of atopic eczema (atopic dermatitis) Part II, Ring [/bib_ref] [bib_ref] Counseling of parents with children with atopic dermatitis, Gieler [/bib_ref] Low treatment adherence is common in AD, and educational programs are needed to reinforce the patient's understanding of the disease complexity and therapeutic approaches. [bib_ref] Evaluation of a parental training program for the management of childhood atopic..., Staab [/bib_ref] Various models focusing on AD education and with multidisciplinary approaches have shown subjective and objective improvement of AD worldwide. [bib_ref] Evaluation of a parental training program for the management of childhood atopic..., Staab [/bib_ref] [bib_ref] Improving the patientclinician and parent-clinician partnership in atopic dermatitis management, Mancini [/bib_ref] [bib_ref] Structured education program improves the coping with atopic dermatitis in children and..., Kupfer [/bib_ref] [bib_ref] Education of Patients with Atopic Dermatitis and Their Caregivers, Takaoka [/bib_ref] [bib_ref] Assessment of the quality of life of pediatric patients at a center..., Weber [/bib_ref] Future perspectives Immunobiologicals and small molecules are targeted therapies that have been developed for many inflammatory, autoimmune, and oncologic diseases.
Crisaborole ointment is a topical phosphodiesterase 4 (PDE4) inhibitor that was approved in the USA in 2017 for patients above the age of 2 years with mild/moderate AD. [bib_ref] Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4)..., Paller [/bib_ref] Dupilumab is a human monoclonal antibody for AD that blocks the alfa-chain receptor for IL-4 and IL-13 (dupilumab) and is approved for adults with moderate/severe AD. [bib_ref] Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase..., Simpson [/bib_ref] Its efficacy after 16 weeks as monotherapy (initial dose: 600 mg, followed by 300 mg every 2 weeks, SC), measured by the reduction of eczema severity scores (EASI) was 82.5% (EASI 50), 60.3% (EASI 75), and 36.5% (EASI 90). 81-83 Improvement of skin lesions and reduction of pruritus improved 2 weeks after initiating treatment. [bib_ref] Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase..., Simpson [/bib_ref] [bib_ref] Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately..., Thaci [/bib_ref] [bib_ref] Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis, Simpson [/bib_ref] The studies show sustained long-term efficacy (one year) with dupilumab combined with TC in AD patients. [bib_ref] The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted..., Brunner [/bib_ref] [bib_ref] Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids..., Blauvelt [/bib_ref] The main adverse event reported with dupilumab was conjunctivitis, detected in 25-50% of AD patients. [bib_ref] Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids..., Blauvelt [/bib_ref] [bib_ref] Conjunctivitis occurring in atopic dermatitis patients treated with dupilumabclinical characteristics and treatment, Wollenberg [/bib_ref] There are ongoing studies (phases 2-3) with novel immunobiologicals and small molecules for AD treatment. See Chart 1. [bib_ref] Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update, Wang [/bib_ref] [bib_ref] New and emerging targeted systemic therapies: a new era for atopic dermatitis, Lee [/bib_ref] Chart 1: New systemic drugs for AD treatment. [bib_ref] Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update, Wang [/bib_ref] [bib_ref] New and emerging targeted systemic therapies: a new era for atopic dermatitis, Lee [/bib_ref] 

# Conclusions
Despite the cultural and economic differences between Brazil, USA, and Europe, including in access to immunobiological therapies, the ideal management of AD is based on a better understanding of disease pathogenesis and knowledge of treatment strategies.
Basic treatment for AD includes skin hydration, topical anti-inflammatory therapy, avoidance of aggravating factors, and educational programs with a multidisciplinary approach. Systemic therapy should be only indicated for refractory or severe disease after attempts with topical therapy. Secondary infections must be diagnosed early and treated promptly, and hospitalization may be necessary to control flares [fig_ref] FIgure 1: Consensus-based recommendations of topical and systemic treatments for patients with atopic dermatitis [/fig_ref].
Novel target-oriented drugs are invaluable tools for AD treatment. q

## Basic therapy

## Systemic therapy
[fig] , 68 Mycophenolate: mofetil (MMF)Clinical efficacy of MMF is reached after 8-12 weeks of use (off label in AD), and the drug has a good safety profile.21,63 The recommended doses in adults are 1-2g/day (starting dose) and 2-3g/ day (maintenance); the pediatric doses are 20-50mg/kg/day (starting dose) and 30-50mg/kg/day (maintenance).21,68 Gastrointestinal and hematological side effects have been reported.21,63 Systemic corticosteroids (SC) There are few randomized controlled studies regarding the use of systemic corticosteroids in AD. In the 2018 European consensus, SC are used in exceptional cases of AD, but only for one week.21 There is a rapid clear up of skin lesions , but severe rebound tends to occur in 2 weeks.21 One controlled trial indicates lower efficacy of systemic prednisolone in comparison to CyA in severe AD.21,69 Position/recommendations for the use of systemic anti-inflammatory drugs in AD:CyA and MTX are the most widely used systemic drugs for severe refractory AD.CyA leads to fast improvement of AD severity scores after 2 weeks of initial treatment, but reactivation of AD after drug suspension is equally fast, occurring in 2 weeks.MTX can be used as the initial systemic medication for refractory moderate/severe AD and is indicated for long-term maintenance. Clinical efficacy is reached after 8-12 weeks of administration.Oral corticosteroids are used in exceptional cases for short periods (up to 1 week). [/fig]
[fig] FIgure 1: Consensus-based recommendations of topical and systemic treatments for patients with atopic dermatitis (AD) [/fig]
[table] Table 1: shows the data obtained from the applied questionnaire. The majority of experts (17/18) who answered the questionnaire work in public and private institutions. About 50% of the specialists see more than 50 AD patients/month, mostly at public hospitals. Twelve out of 18 of the dermatologists follow published consensuses, with emphasis on the American and European guidelines. The most widely used topical treatments are corticosteroids, followed by calcineurin inhibitors. The first choice for systemic therapy was cyclosporin, followed by methotrexate and azathioprine. [/table]