The neglected twin: Nummular eczema is a variant of atopic dermatitis with codominant TH2/TH17 immune response - 03/08/23
, Manja Jargosch, PhD a, b, Nikola S. Müller, PhD e, Natalie Garzorz-Stark, PhD, MD a, c, Caroline Pilz, MD b, d, Felix Lauffer, PhD, MD a, Rosi Wang, MD a, Sophie Roenneberg, MD a, Alexander Zink, PhD, MD, MPH a, Jenny Thomas, PhD a, c, Fabian J. Theis, PhD e, f, Tilo Biedermann, MD a, Stefanie Eyerich, PhD b, Kilian Eyerich, PhD, MD c, dGraphical abstract |
Abstract |
Background |
Nummular eczema (NE) is a common chronic inflammatory skin disease characterized by multiple, pruritic, discoid-shaped lesions. Since the underlying immune mechanisms are not fully understood, it is unclear whether NE should be regarded as variant of atopic dermatitis (AD) or a distinct disease.
Objective |
We compared the clinical, histopathologic, and molecular signatures of NE with that of type 2 and type 3 skin diseases.
Methods |
We performed bulk RNA sequencing as well as histologic and clinical studies in lesional and nonlesional skin biopsy specimens from NE (n = 50), AD (n = 47), and psoriasis (n = 90) patients.
Results |
NE displayed typical hallmarks of AD, such as an impaired epidermal barrier, microbial colonization, spongiosis, and eosinophil infiltration, but also aspects of psoriasis, including increased epidermal thickness, number of Ki-67+ cells, and neutrophilic infiltration. At the gene expression level, neutrophil-attracting cytokines (IL19, CXCL8, CXCL5) were upregulated, whereas TH2-related cytokines (IL13, CCL17, CCL18, CCL26, CCL27) were similarly expressed in NE compared to AD. Principal component analysis of transcriptome data from lesional skin showed that AD and NE cluster together distinct of psoriasis. In line with this, an established molecular classifier identified NE as AD rather than psoriasis. Finally, we demonstrated clinical and molecular efficacy of dupilumab treatment in NE.
Conclusion |
NE shows overlapping type 2 and type 3 immune signatures, while type 2 immunity predominates and should be the primary target of specific therapeutic interventions. This supports the view of NE as a variant of AD.
Le texte complet de cet article est disponible en PDF.Key words : Inflammatory skin diseases, nummular eczema, atopic dermatitis, dupilumab
Abbreviations used : AD, DEG, DLQI, HPF, ncISD, NE, NET, PCA, SCORAD
Plan
| The first 2 authors contributed equally to this article, and both should be considered first author. |
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| This study was performed with samples from the Biobank Biederstein of the Technical University of Munich. This work was supported by the European Research Council (IMCIS 676858), German Research Foundation (EY97/3-1), and the Helmholtz Association (“Impuls- und Vernetzungsfonds”). |
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| Disclosure of potential conflict of interest: A.B., K.E., F.L., and T.B. report receipt of grants from Sanofi, including the realization of an investigator-initiated phase 2 study of dupilumab in nummular eczema (ClinicalTrials.gov NCT04600362). The rest of the authors declare that they have no relevant conflicts of interest. |
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| Data sets related to this article can be found at GEO (Gene Expression Omnibus, geo), an open-source online data respository hosted at the National Center for Biotechnology Information under accession number GSE154200. |
Vol 152 - N° 2
P. 408-419 - août 2023 Retour au numéro
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