Chronic hand eczema: patients share similar molecular signatures regardless of AD status

Tape-strips from patients with chronic hand eczema revealed shared immune and barrier dysregulations in patients both with and without atopic dermatitis (AD). Thus, a common therapeutic approach irrespective of atopic status might be effective.

Chronic hand eczema is a highly prevalent, heterogeneous inflammatory skin condition with a multifactorial aetiology. Approximately one-third of these patients have a history of AD, which is considered a major risk factor [1]. The indistinct pathogenesis of chronic hand eczema has hindered the development of effective, targeted therapies for this condition.

"Due to the lack of comprehensive transcriptomic studies on chronic hand eczema, our focus was to characterise the transcriptome and compare the inflammatory and barrier-related characteristics across chronic hand eczema endotypes, using a minimally invasive tape-strip approach,” explained Dr Jonathan Bar (Icahn School of Medicine at Mount Sinai, NY, USA) [2].

The research team obtained lesional and non-lesional skin samples from 95 patients with chronic hand eczema and compared them with normal skin samples from 20 healthy controls by using 20 tape-strips at each sampled site. Of the 95 participants, 45 had a history of AD (15 men and 30 women). RNA sequencing was conducted on these samples, analysing differentially expressed genes (DEG) across the entire chronic hand eczema cohort. The team then established correlations between these biomarkers and known clinical severity scores (e.g. the Hand Eczema Severity Index [HECSI] and the Dermatology Life Quality Index [DLQI]).

The number of DEGs identified in lesional versus non-lesional skin, non-lesional versus normal skin, and lesional versus normal skin was 8,902, 6,782, and 3,193, respectively. These included the upregulation of several immune pathways and genes associated with Th1, Th2, and Th17/Th22, as well as the downregulation of key epidermal barrier markers and lipid metabolism genes. Non-lesional skin demonstrated a hybrid phenotype between lesional eczema and normal skin.

Notably, the lesional hand eczema signature exhibited no significant differences between participants with and without AD. However, the non-lesional skin of participants with hand eczema and AD displayed a notably higher inflammatory tone than those without AD, suggesting a higher disease burden in the former group. Inflammatory and barrier biomarkers significantly correlated with clinical severity measures in all participants with chronic hand eczema.

"No transcriptomic differences were identified in the lesional skin of patients with chronic hand eczema, regardless of their AD status, suggesting that common therapeutic targeting may be effective for both categories,” Dr Bar concluded. Thus, Th2-targeting treatments may apply to all patients with chronic hand eczema, but some patients may need targeting of Th1 and JAK1. Moreover, tape-strips can be a useful approach to evaluating and monitoring chronic hand eczema in trials and real-life settings.

1. 
   
   1. Thyssen JP, et al. Contact Dermatitis 2010;62:75–87.
   2. Bar J, et al. Chronic hand eczema shares a common molecular signature regardless of atopic dermatitis status. D2T01.3A, EADV Congress 2023, 11–14 October, Berlin, Germany.

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Posted on 28 November, 202327 March, 2024