Fact checked byKristen Dowd

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October 18, 2023
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Atopic dermatitis status does not impact molecular signature of chronic hand eczema

Fact checked byKristen Dowd
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Key takeaways:

  • 40% to 50% of patients with chronic hand eczema have concomitant atopic dermatitis.
  • Differentially expressed genes included upregulation of several immune pathways and genes.

Tape strips that capture the molecular fingerprint of chronic hand eczema indicated broadly shared immune and barrier dysregulations among patients who have and who do not have atopic dermatitis, according to a study abstract.

Based on these results — presented at the European Academy of Dermatology and Venerology Congress in Berlin — common therapeutic targeting may be effective in chronic hand eczema (CHE) despite atopic status, according to Jonathan Bar, MD, dermatologist and postdoctoral fellow in the Kimberly and Eric J. Waldman Department of Dermatology at Icahn School of Medicine at Mount Sinai, and colleagues.

Atopic dermatitis on hands
The elusive nature of the pathogenesis of chronic hand eczema precludes the development of effective, specific therapies. Image: Stock Photo

“Chronic hand eczema is a highly prevalent inflammatory skin condition, affecting approximately 10% of the population,” Bar told Healio.

Calling it a debilitating condition, Bar said there is a staggering unmet need for effective long-term treatments and that its relationship with atopic dermatitis is not fully understood, although some researchers consider AD a de facto cause of CHE.

Jonathan Bar

Bar and his colleagues also characterized CHE as a common heterogenous inflammatory skin condition with multiple morphologic and etiologic subtypes, including 40% to 50% of patients with concomitant AD.

However, the researchers continued, the elusive pathogenesis of CHE precludes the development of targeted therapies that are efficacious.

“Our goal was to characterize the molecular changes in chronic hand eczema, particularly in those with and without atopic dermatitis, to see if there are any type-specific molecular changes or whether hand eczema is a similar common endpoint of several causes,” Bar said.

Study design, results

The study enrolled 95 patients with CHE, including 45 who also had AD, and 20 matched healthy controls. Using tape strips, the researchers collected lesional (LS), nonlesional (NL) and normal (N) skin samples and analyzed them with RNA sequencing.

Also, the researchers evaluated differentially expressed genes (DEGs), defined as fold change (FCH) greater than 1.5 with a false discovery rate (FDR) less than 0.05, across the full CHE cohort.

Analysis of the global CHE transcriptome revealed 5,466 up and 3,436 down DEGs in LS vs. N skin, 1,574 up and 1,619 down DEGs in LS vs. NL skin, and 4,043 up and 2,739 down DEGs in NL vs. N skin.

Several immune pathways and genes were upregulated in these DEGs, including Th1 (OASL, IL12B, STAT1), Th2 (IL7R, CCL22, CCL24, OX40) and Th17/Th22 (CXCL3, IL23A).

There also were downregulations in negative regulators (IL34), epidermal terminal differentiation (FLG, LOR) and lipid metabolism (FA2H, GAL) genes.

The researchers additionally did not find any significant differences in the lesional CHE signature between the patients who did and did not have AD.

However, the researchers continued, the NL skin of the patients with CHE and AD had significantly higher inflammatory tone than the NL skin of the patients with CHE but no AD across the Th2 (OX40), and Th17/Th22 (IL23A) axes, with greater barrier dysregulation (LOR, FLG) in parallel.

Further, the researchers called correlations between CHE clinical severity measures such as the Hand Eczema Severity Index and Th1/Th2/Th12 immune markers including CCR4, STAT3, IL2RB and PDE4B in patients with CHE without AD significant and positive.

These CHE clinical severity measures also had significant negative correlations with barrier and negative regulator markers such as ELOVL3, LOR, FLG and IL34. CHE with AD had a positive correlation with CCL12 and a negative correlation with IL34 as well.

Conclusions, next steps

Based on these findings, the researchers said that common therapeutic targeting may be effective in treating CHE regardless of the patient’s atopic status and that the higher inflammation in the NL skin of those patients with both CHE and AD may suggest a greater systemic disease burden similar to classic AD.

“There is a broad inflammatory activation in chronic hand eczema, and it seems that the overall inflammatory signature is similar among patients with an atopic dermatitis background compared to those without,” Bar said.

“This might imply that a single therapeutic strategy might benefit all patients, and physicians won’t need to have different treatments for those with atopic dermatitis and those without atopic dermatitis,” he continued.

Bar said that clinical trials with medications targeting selected biomarkers found to be overexpressed in patients both with and without an AD background would be beneficial, in addition to investigations of other subtypes of CHE such as those caused by allergy to foreign materials.