How Do Classical Subtypes Correspond to Endotypes in Atopic Dermatitis?

Abstract

Since atopic dermatitis (AD) is a heterogeneous condition, the subtyping of AD is a crucial issue. The classical subtypes of AD are represented by extrinsic and intrinsic subtypes, European-American and Asian subtypes, and adult and pediatric subtypes. While the subtyping of AD was historically conducted based on the phenotype, recent findings on the mechanisms of AD have revealed the importance of the endotype, which can characterize individual patients more accurately. Considering the current development of AD therapies, AD endotyping is a prerequisite for a personalized therapeutic choice. Endotypes of AD can be stratified from different viewpoints, including cytokine expression patterns, allergen properties, epidermal barrier conditions, ceramide variation, the involvement of innate immunity, and serum biomarkers. Among them, the cytokine-based endotype seems to be the most useful one and is categorized into type 2 cytokine (IL-4, IL-13 and IL-31)-high, type 1 cytokine (IFN-γ)-high, and/or type 3 cytokine (IL-22 and IL-17)-high, or mixed subtypes. Recently proposed biomarker endotyping aims at individualized treatment options, although the daily clinical use of endotypes is a future issue. To better understand the endotypes for clinicians, attempts to adjust each of the classical subtypes to endotypes are required. This review will discuss the correspondence of the classical subtypes to the various endotypes that have recently been proposed.

Keywords: atopic dermatitis; endotype; extrinsic type; intrinsic type; phenotype; subtype.

Figure 1

Cytokine patterns in extrinsic/intrinsic AD and Asian AD. Clinical photographs showing representative patients. Extrinsic AD: a 31-year-old man with a serum IgE level of 15,231 kU/L. Intrinsic AD: a 22-year-old woman with a serum IgE level of 11 kU/L, showing a nickel- and cobalt-positive patch test. Asian type of AD: a 31-year-old Japanese man with a serum IgE level of 22,216 kU/L, showing well-demarcated eczematous lesions.

Figure 2

Type 2 cytokines and JAK/STAT signaling. Modified from References [7,54].

Figure 3

Type 1/Type 3 cytokines and JAK/STAT signaling. Modified Reference [50].