The Heterogeneity of Atopic Dermatitis

February 2022 | Volume 21 | Issue 2 | 6408 | Copyright © February 2022

Published online January 13, 2022

R. Chovatiya MD PhDa, J.I. Silverberg MD PhD MPHb

aFeinberg School of Medicine at Northwestern University, Chicago, IL
bThe George Washington University School of Medicine and Health Sciences, Washington, DC

Background: Recent advances were made in characterizing the clinical heterogeneity of atopic dermatitis (AD).
Objective: To review the clinical domains contributing to AD heterogeneity and describe their importance in clinical practice.
Methods: We conducted a focused review of the published literature, including retrospective, observational, and prospective studies, clinical trials, and consensus guidelines.
Results: AD is associated with heterogeneous skin manifestations, symptoms, lesional severity, lesional extent, longitudinal course, burden of signs and symptoms, and comorbidities. Each of these domains characterizes a different aspect of AD and should be used to guide overall severity assessment and clinical management. Primary focus on any one specific clinical domain of AD is insufficient to describe the full burden of disease.
Conclusion: Heterogeneity should be routinely considered during AD clinical encounters.

J Drugs Dermatol. 2022;21(2): doi:10.36849/JDD.6408


Atopic dermatitis (AD) is a chronic and burdensome inflammatory skin disease. Classically, AD is characterized as a relapsing, itchy, red, rash with a predilection for skin flexures, presenting mainly in childhood before “burning out” by adulthood. This narrow and overly simplified description overlooks the heterogeneity of AD. AD lesions have differing morphologies (eg, prurigo nodules, lichenoid papules, follicular eczema) and distributions (eg, extensor, head/neck, hand/foot).1 While itch is the most prevalent and burdensome symptom of AD,2,3 skin-pain is one of several other symptoms that contribute to disease-burden.4,5 The course of AD is not homogenous – incidence, chronicity, and persistence vary widely over time.6 This complex constellation of features poses physical, emotional, and psychosocial burden that contributes to reduced quality-of-life (QOL).7,8 Herein, we review clinical domains contributing to AD heterogeneity and discuss how balanced consideration of these aspects can improve AD management.

Skin Manifestations
The notion of a pathognomonic morphology and distribution of skin signs in AD, ie eczematous patches/plaques favoring flexural skin, has long been taught in dermatology. This view of AD is outdated, derived from older literature and anecdotal clinical experience of disease presentation in individuals of white race and Northern European ancestry, and ignores major differences in lesional morphology, distribution, and extent. Clinical presentation of AD varies widely across geographic regions, age,9-11 ethnicity,12 and underlying immunopathogenesis,13 suggesting genetics14 and environment15 contribute to disease heterogeneity.

A systematic review and meta-analysis of 101 observational studies published from 1984–2017 underscored many regional and age-related differences in skin manifestations of AD.1 Overall, lesions were distributed most commonly on flexural sites (58%), followed by extensor surface of upper extremities (51%), head, face, and neck (42%), hands and feet (36%), scalp (34%), and extensor surface of lower limbs (25%). Flexural involvement was more common in Australia, followed by Africa, Southeast Asia (SEA), East Asia (EA), and Europe, and less common in the Americas and Iran. Extensor lesions were most common in India, Iran, and EA. Head, face, and neck involvement was more common in Iran, Africa, and the Americas, and least common in SEA. Compared to European studies, truncal, extensor, scalp, and auricular involvement was more common in EA; head, face, and neck involvement was more common in Iran. Moreover, commonly reported morphological characteristics included perifollicular accentuation (follicular eczema; 34%), papular lichenoid (22%), nummular (13%), and prurigo lesions (7%). Papular lichenoid lesions, palmar hyperlinearity, orbital darkening, and ichthyosis were more prevalent in Africa. Dermatitis of eyelids, auricle, and ventral wrist, exudative eczema, and seborrheic dermatitis-like