The neglected twin: Nummular eczema is a variant of atopic dermatitis with codominant TH2/TH17 immune response

Böhner, Alexander; Jargosch, Manja; Müller, Nikola S.; Garzorz‐Stark, Natalie; Pilz, Anna Caroline; Lauffer, Felix; Wang, Rosi; Roenneberg, Sophie; Zink, Alexander; Theis, Fabian J.; Biedermann, Tilo; Eyerich, Stefanie; Eyerich, Kilian

doi:10.1016/j.jaci.2023.04.009

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…64,65 A codominant Th2/Th17 response has been shown for nummular eczema as well. 66 European patients with AD and PV present higher IL-17 serum concentrations 12 than patients with only AD or PV.…”

Section: From An Immunological Perspective Ad and Pv Might Have A Commonmentioning

confidence: 90%

“…In pediatric and Asian AD subtypes, the activation of IL‐17 plays even a more important role; histological examinations often show “psoriasiform dermatitis” or “eczematous psoriasis” 64,65 . A codominant Th2/Th17 response has been shown for nummular eczema as well 66 . European patients with AD and PV present higher IL‐17 serum concentrations 12 than patients with only AD or PV.On the contrary, AD and PV are characterized by disease‐specific discordant cytokine signatures (Th2/IL‐4/IL‐13 and Th‐1/17 dichotomy) that are even strictly separated in skin specimen of eczema and psoriatic plaques in the same patient 67 .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Müller,

Welchowski,

Schmid

et al. 2023

Allergy

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BackgroundAtopic dermatitis (AD) and psoriasis vulgaris (PV) are almost mutually exclusive diseases with different immune polarizations, mechanisms and therapeutic targets. Switches to the other disease (“Flip‐Flop” [FF] phenomenon) can occur with or without systemic treatment and are often referred to as paradoxical reactions under biological therapy.MethodsThe objective was to develop a diagnostic algorithm by combining clinical criteria of AD and PV to identify FF patients. The algorithm was prospectively validated in patients enrolled in the CK‐CARE registry in Bonn, Germany. Afterward, algorithm refinements were implemented based on machine learning.ResultsThree hundred adult Caucasian patients were included in the validation study (n = 238 with AD, n = 49 with PV, n = 13 with FF; mean age 41.2 years; n = 161 [53.7%] female). The total FF scores of the PV and AD groups differed significantly from the FF group in the validation data (p < .001). The predictive mean generalized Youden‐Index of the initial model was 78.9% [95% confidence interval 72.0%–85.6%] and the accuracy was 89.7%. Disease group‐specific sensitivity was 100% (FF), 95.0% (AD), and 61.2% (PV). The specificity was 89.2% (FF), 100% (AD), and 100% (PV), respectively.ConclusionThe FF algorithm represents the first validated tool to identify FF patients.

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Section: From An Immunological Perspective Ad and Pv Might Have A Commonmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Müller,

Welchowski,

Schmid

et al. 2023

Allergy

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“…Recently, it has been reported that NE has more mechanistic similarity to AD than psoriasis, though it has both type 2 and 3 immune signatures, and inhibition of type 2 immune response by treatment with dupilumab showed improvement of both type 2 and 3 immune signatures in patients with NE ( 40 ). This may support the similarity in increased LEKTI-1-mediated impairment of desquamation between NE and AD.…”

Section: Discussionmentioning

confidence: 99%

Higher Expression of Lympho-epithelial Kazal-type-Related Inhibitor-1 Fragments and Decreased Desquamation in the Lesional Skin of Nummular Eczema

Montenegro,

Oh,

Suh

et al. 2024

Acta Derm Venereol

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Nummular eczema, a chronic dermatitis characterized by coin-shaped lesions, was first documented in 1857. However, its pathophysiological characteristics are still not well known. To investigate differences in the regulation of the desquamation process in the stratum corneum of lesional and nonlesional skin of patients with nummular eczema and healthy control subjects, tape-stripped stratum corneum samples from patients with nummular eczema and healthy volunteers were analysed using immunofluorescence staining and western blot analysis. In the nummular eczema lesional skin, expression of desmoglein-1, desmocollin-1, and corneodesmosin exhibited a disorganized, dense or partially diffuse non-peripheral pattern with increased intensity, compared with the peripheral patterns observed in healthy or nonlesional skin, suggesting the impaired desquamation process in nummular eczema. Furthermore, although the expression of the desquamation-related serine proteases, kallikrein-related peptidase 7 and 5, was increased in nummular eczema lesional skin, the immunofluorescence staining of lympho-epithelial Kazal-type-related inhibitor-1, an endogenous inhibitor of various kallikrein-related peptidases, and its fragments were significantly increased in the nummular eczema lesional skin, suggesting its contribution to the inhibition of corneodesmosomal degradation. Therefore, the increased detection of corneodesmosomal proteins in nummular eczema lesions may be due to the increased amount of the fragments of lympho-epithelial Kazal-type-related inhibitor-1, which could contribute to delayed desquamation.

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“…In the spirit of further characterizing various subtypes of AD, some studies have considered nummular eczema to be a variant of AD. Recently, Böhner et al [36 ▪ ] showed that the transcriptome of lesional nummular eczema demonstrates an upregulation of Th2, attenuated relative to AD, and Th17 pathway, greater than AD. Principal component analyses showed that nummular eczema and AD overlapped more closely in a cluster separate from psoriasis, suggesting that nummular eczema should be considered a subvariant of AD with a codominant Th2/Th17 immune signature.…”

Section: Il-17 and Atopic Dermatitis: The Plot Thickensmentioning

confidence: 99%

The pathogenetic role of Th17 immune response in atopic dermatitis

David,

Czarnowicki

2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review As we continue to unravel the pathophysiology and immune mechanisms underlying atopic dermatitis (AD), the emergence of targeted treatments has provided new options for management. Although there are available therapies targeting various immune pathways in AD, the precise pathogenic role of interleukin (IL)-17 in AD pathogenesis remains unclear. The objective of this review is to examine the existing data pertaining to the role of IL-17 in AD and shed light on the potential of targeting this pathway as a therapeutic approach in AD treatment. Recent findings IL-17 has a dual role of pro-inflammatory and immune protective function, making it an important player in several autoimmune and inflammatory conditions. The extent of IL-17 axis involvement in AD pathogenesis is still debatable. Emerging data show that Th17-related cytokines/chemokines are elevated in skin and sera samples of AD patients, with some articles reporting correlations with disease severity. Particularly increased Th17 signature in specific AD patient subsets, such as Asian-origin or pediatric patients, suggests that certain patients’ disease presentations are more predominantly influenced by Th17, and, thus, they may benefit more from Th17 therapeutic targeting approaches. Lack of clinical efficacy with anti-Th17 biologics in AD patients, underscores the need to better elucidate the role of Th17 in AD pathogenesis, along with its utility in therapy. Summary The well established role of IL-17 in autoimmune disorders hints for its possible participation in AD disease pathogenesis. Subsequent investigations are needed to assess whether the targeting of specific IL-17 isoforms, homodimers, or heterodimers in specific subpopulations of AD can modify treatment outcomes.

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The neglected twin: Nummular eczema is a variant of atopic dermatitis with codominant TH2/TH17 immune response

Cited by 11 publications

References 36 publications

Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Development of a clinical algorithm to predict phenotypic switches between atopic dermatitis and psoriasis (the “Flip‐Flop” phenomenon)

Higher Expression of Lympho-epithelial Kazal-type-Related Inhibitor-1 Fragments and Decreased Desquamation in the Lesional Skin of Nummular Eczema

The pathogenetic role of Th17 immune response in atopic dermatitis

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