Latent class analysis categorizes chronic hand eczema patients according to skin barrier impairment

Abstract

BackgroundChronic hand eczema (CHE) is the most common skin disorder affecting the hands. It causes major physical and psychological burden for patients. Classification of CHE remains challenging because of its aetiological and clinical heterogeneity.ObjectivesUsing latent class analysis (LCA) on a large categorical data set, our aim was to identify distinct phenotypes in a cohort of unselected CHE patients based upon clinical, genetic, molecular and physical parameters of the affected skin.MethodsWe performed two independent LCA on a cohort of 71 well‐characterized patients that initially integrated clinical severity, total immunoglobulin E plasma level, transepidermal water loss, hydration index, interleukin(IL)‐8 lesional skin level, Staphylococcus (aureus and epidermidis) colonization, FLG genotype and the expression (mRNA) of genes involved either in the filaggrin degradation and the natural moisturizing factor synthesis, the cornified envelope formation, the tight junctions’ structure and the desquamation process, or encoding antimicrobial peptides and chemokines.ResultsThe first LCA categorized patients into a group displaying high severity of CHE, high skin barrier impairment, high Staphylococcus colonization, high IL‐8 skin level and high frequency of mutation in the FLG gene and a second group with opposite characteristics. The second LCA identified two independent groups of patients categorized by their low or high level of skin barrier impairment and corresponding changes in the expression of the related genes.ConclusionsOur study suggests that the degree of skin barrier dysfunction is the most important parameter to discriminate CHE patients and probably plays a pivotal role in the pathogenesis of the disease whatever the aetiological factors. As far as we know, this is the first study to address this topic using a statistical categorization method without preconception.

Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges

“…15,21,24 Atopic hand eczema, like other atopic conditions, presents with a Th2/ Th22 immune profile, in conjunction with endogenous factors such as tight junction defects and an increase in transepidermal water loss (TEWL), thereby compromising the integrity of the epidermal barrier. 1,[25][26][27][28] Atopic hand eczema lesions are characterized by increased Th2 activation and production of IL-4, IL-13, IL-31, CCL17, CCL18, and CCL22, and T-cell activation that produces IL-22. IL-4/IL-13 also induce increased IgE synthesis, which characterizes many CHE cases.…”

Vesicular hand eczema transcriptome analysis provides insights into its pathophysiology

“…To identify chronic HE phenotypes, the mRNA expression of a set of genes involved in skin barrier function was recently studied using qPCR. 35 Genes involved in filaggrin degradation, natural moisturizing factor synthesis, and structural barrier genes were downregulated suggesting that skin barrier dysfunction is an important parameter to discriminate chronic HE patients. However, a comparison with our data is difficult, since Tauber et al .…”

The pan‐JAK inhibitor delgocitinib in a cream formulation demonstrates dose response in chronic hand eczema in a 16‐week randomized phase IIb trial*

“…irritants, allergens 5 ) and endogenous factors (e.g. skin barrier or immune dysfunction with associated dysregulated skin microbiome [6][7][8][9] ) drive the aetiopathogenesis. Risk factors associated with HE are female sex, prior/current atopic dermatitis, and occupations involving exposure to irritants and/or allergens, in particular wet-work occupations.…”