Atopic Dermatitis Host and Environment Model: Revisiting Therapeutic Options

Abstract

Atopic Dermatitis affects both children and adults and is a serious health concern in many countries. AD is a complex disease with host and environmental factors underlying its pathology. Its treatment is multidimensional reflecting the diverse nature of its triggers and includes emollients, topical steroids and calcineurin inhibitors among others. Immunological dysfunction can be addressed broadly with systemic immunosupressors and specifically with monoclonal antibodies. Dupilumab, which targets IL-4 and IL-13 was granted approval for treatment of moderate-to-severe AD. Biologics targeting IgE/Th2 pathways may have its role in patients with overlapping AD and asthma. Psychological distress can exacerbate symptoms and is associated with increased severity of AD. Environmental triggers, such as, allergens can be addressed in selected cases with allergic immunotherapy. In this paper, we discuss AD treatment and propose a new step-by-step approach aiming at maintaining disease control and improving quality of life. ty is associated with various inflammatory conditions, including asthma and allergic diseases. As such, a fundamental role for microorganisms in human health, whether indigenous or environmental, is becoming increasingly evident. Besides the importance of the environment in the development of allergic diseases, an increased familiar predisposition for the development of these conditions may exist. This observation led researchers to hypothesize that host genetic factors could be involved in the pathogenesis of AD. The description, back in 2006, that loss-of-function mutations in the filaggrin (FLG) gene were a strong genetic risk factor for AD, became a significant breakthrough regarding prognosis and treatment. FLG monomers aggregate keratin filaments into tight bundles, resulting in the collapse and flattening of corneocytes that maintain both skin barrier integrity and normal stratum corneum (SC) lipids. Therefore, mutations in the FLG gene may increase skin permeability, predisposing individuals to skin allergen penetration and subsequent infection. These mutations have also

Treatment Guidelines for Atopic Dermatitis Since the Approval of Dupilumab: A Systematic Review and Quality Appraisal Using AGREE-II

“…The only CPGs to obtain AGREE-II scores above 70% were Smith et al ( 38 ) and Wollenberg et al ( 40 ). The patients' point of view and preferences were only taken into account in the Wollenberg et al ( 40 ) and Lopes et al ( 36 ) CPGs.…”

“…The most widely adopted guidelines for AD management were published by the American Academy of Dermatology in 2014; however, these predate the approval of dupilumab, leaving a gap of evidence-based, practical recommendations for up-todate management of adult AD (8,9). A number of recent clinical practice guidelines (CPGs) and recommendations from various groups were developed internationally to incorporate dupilumab in treatment algorithms (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). To the best of our knowledge, the quality of these CPGs' methods and development processes…”

Atopic dermatitis in adolescents with acne vulgaris

“…This seems to be a positive finding, as emollients and other non-medical products may decrease the number of flares and the use of medication. Availability of these products increases long-term adherence [12]. Medical treatment ranged from 62 to 67%, which is a relatively low percentage.…”

MRGPRX2 signals its importance in cutaneous mast cell biology: Does MRGPRX2 connect mast cells and atopic dermatitis?

“…[53] In support of this, patients with extrinsic AD have more pronounced barrier defects than those with intrinsic AD. [54] There is also limited improvement of AD with IgEdirected strategies (Omalizumab), especially in patients with pure AD and the same applies to specific immunotherapy (reviewed in [55][56][57][58] ).…”

“…[ 53 ] In support of this, patients with extrinsic AD have more pronounced barrier defects than those with intrinsic AD. [ 54 ] There is also limited improvement of AD with IgE‐directed strategies (Omalizumab), especially in patients with pure AD and the same applies to specific immunotherapy (reviewed in [ 55‐58 ] ). In addition, AD occurrence in infancy can precede sensitization, and exacerbations of AD by food allergen ingestion have been reported but are not prevalent (especially in older children and adults).…”