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      Nomenclature and clinical phenotypes of atopic dermatitis

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          Abstract

          Atopic dermatitis is a heterogeneous disease and resists classification. In this review, we discuss atopic dermatitis nomenclature and identify morphologic phenotypes, which will facilitate correct diagnoses and development of treatment strategies. We support using the term ‘atopic dermatitis’ rather than eczema, because it describes the allergic background and inflammation (‘itis’) as drivers of the disease. Atopic dermatitis has many morphologic manifestations that vary by topographic area affected, age, or race and require consideration in differential diagnosis. Different phenotypes based on morphology and topographic location, ethnicity, and age are discussed. A better-defined phenotype identification for atopic dermatitis will facilitate earlier and correct diagnosis of this complex condition and inform selection of the most appropriate treatment choice in an era in which targeted therapies may generate more individualized patient care.

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          Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

          Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. Methods In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. Results We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. Conclusions In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).
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            Atopic dermatitis.

            Atopic dermatitis (also known as atopic eczema) is a chronic inflammatory skin disease that is characterised by intense itching and recurrent eczematous lesions. Although it most often starts in infancy and affects two of ten children, it is also highly prevalent in adults. It is the leading non-fatal health burden attributable to skin diseases, inflicts a substantial psychosocial burden on patients and their relatives, and increases the risk of food allergy, asthma, allergic rhinitis, other immune-mediated inflammatory diseases, and mental health disorders. Originally regarded as a childhood disorder mediated by an imbalance towards a T-helper-2 response and exaggerated IgE responses to allergens, it is now recognised as a lifelong disposition with variable clinical manifestations and expressivity, in which defects of the epidermal barrier are central. Present prevention and treatment focus on restoration of epidermal barrier function, which is best achieved through the use of emollients. Topical corticosteroids are still the first-line therapy for acute flares, but they are also used proactively along with topical calcineurin inhibitors to maintain remission. Non-specific immunosuppressive drugs are used in severe refractory cases, but targeted disease-modifying drugs are being developed. We need to improve understanding of the heterogeneity of the disease and its subtypes, the role of atopy and autoimmunity, the mechanisms behind disease-associated itch, and the comparative effectiveness and safety of therapies.
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              Atopic Dermatitis: Global Epidemiology and Risk Factors

              Atopic dermatitis (AD) is a chronic inflammatory skin disease posing a significant burden on health-care resources and patients' quality of life. It is a complex disease with a wide spectrum of clinical presentations and combinations of symptoms. AD affects up to 20% of children and up to 3% of adults; recent data show that its prevalence is still increasing, especially in low-income countries. First manifestations of AD usually appear early in life and often precede other allergic diseases such as asthma or allergic rhinitis. Individuals affected by AD usually have genetically determined risk factors affecting the skin barrier function or the immune system. However, genetic mutations alone might not be enough to cause clinical manifestations of AD, and it is merely the interaction of a dysfunctional epidermal barrier in genetically predisposed individuals with harmful effects of environmental agents which leads to the development of the disease. AD has been described as an allergic skin disease, but today, the contribution of allergic reactions to the initiation of AD is challenged, and it is proposed that allergy is rather a consequence of AD in subjects with a concomitant underlying atopic constitution. Treatment at best achieves symptom control rather than cure; there is thus a strong need to identify alternatives for disease prevention.
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                Author and article information

                Contributors
                Journal
                Ther Adv Chronic Dis
                Ther Adv Chronic Dis
                TAJ
                sptaj
                Therapeutic Advances in Chronic Disease
                SAGE Publications (Sage UK: London, England )
                2040-6223
                2040-6231
                26 March 2021
                2021
                : 12
                : 20406223211002979
                Affiliations
                [1-20406223211002979]Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, Verona, 37126, Italy
                [2-20406223211002979]National Expertise Center of Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center, Utrecht, Netherlands
                [3-20406223211002979]Department of Dermatology, University of São Paulo School of Medicine, São Paulo, Brazil
                [4-20406223211002979]Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
                [5-20406223211002979]Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
                [6-20406223211002979]Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
                [7-20406223211002979]Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA
                [8-20406223211002979]Sanofi Genzyme, Cambridge, MA, USA
                Author notes
                Author information
                https://orcid.org/0000-0001-8548-0493
                Article
                10.1177_20406223211002979
                10.1177/20406223211002979
                8010850
                33854747
                914f492d-6a32-433c-a59f-d5699c29aaf1
                © The Author(s), 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 5 February 2021
                : 25 February 2021
                Funding
                Funded by: Sanofi, FundRef https://doi.org/10.13039/100004339;
                Award ID: Not applicable
                Funded by: Regeneron Pharmaceuticals, FundRef https://doi.org/10.13039/100009857;
                Award ID: Not applicable
                Categories
                Atopic Dermatitis
                Review
                Custom metadata
                January-December 2021
                ts1

                atopic,dermatitis,eczema,nomenclature,phenotype,treatment
                atopic, dermatitis, eczema, nomenclature, phenotype, treatment

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