Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we go?

Abstract

Atopic dermatitis (AD) is a paradigmatic chronic inflammatory skin disease characterized by a complex pathophysiology and a wide spectrum of the clinical phenotype. Despite this high degree of heterogeneity, AD is still considered a single disease and usually treated according to the "one-size-fits-all" approach. Thus more tailored prevention and therapeutic strategies are still lacking. As for other disciplines, such as oncology or rheumatology, we have to approach AD in a more differentiated way (ie, to dissect and stratify the complex clinical phenotype into more homogeneous subgroups based on the endophenotype [panel of biomarkers]) with the aim to refine the management of this condition. Because we are now entering the era of personalized medicine, a systems biology approach merging the numerous clinical phenotypes with robust (ie, relevant and validated) biomarkers will be needed to best exploit their potential significance for the future molecular taxonomy of AD. This approach will not only allow an optimized prevention and treatment with the available drugs but also hopefully help assign newly developed medicinal products to those patients who will have the best benefit/risk ratio.

Atopic dermatitis in adults: An Australian management consensus

“…The validated diagnostic criteria suggested by Hanifin & Rakja were reviewed alongside systematic reviews and international AD guidelines (III C level evidence), and a diagnostic framework was agreed. There was majority consensus that there are no specific biomarkers that can be recommended for diagnosis and/or assessment of eczema severity, but this is an area of active research . Food elimination diets and allergy tests are of limited benefit unless there is a personal history of IgE‐mediated food allergy …”

Verbascoside Alleviates Atopic Dermatitis-Like Symptoms in Mice via Its Potent Anti-Inflammatory Effect

“…It is driven by both terminal keratinocyte differentiation defects and a strong type 2 immune response. AD pathology is characterized with skin barrier abnormalities and immune dysregulation, at local and systemic levels and with high heterogeneity [1,2,4]. It imposes considerable burdens upon the quality of life, health outcomes, and work productivity of sufferers, given that the standard steroid treatment has intrinsic side effects and that AD is often associated with microbial organism infection [10,15].…”

“…It affects 11-30% of children and 2-10% of adults, depending on the population studied [1,3]. It is often manifested as erythematous, thickened, epidermal lesions that vary in their intensity and the body surface area that is affected [2,4]. It is a major skin disorder that imposes a considerable burden on patients' quality of life, health outcomes, and work productivity [5].…”

Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

“…Biomarkers may help clarify AD diagnosis by defining endotypes, subsets of patients with common underlying mechanisms of disease . Biomarkers could be useful for screening those at high risk of AD before clinical disease appears and might aid in the early diagnosis of AD . Beyond its diagnostic potential, the development of biomarkers in AD will allow more accurate assessment of disease severity than current methods, which require subjective inputs and for which there are currently many different composite indices.…”