Clinically uninvolved but not healthy—The skin of patients with atopic dermatitis is primed for itch and inflammation

Moon, S.; Stasikowska‐Kanicka, O.; Wągrowska‐Danilewicz, M.; Hawro, M.; Metz, M.; Maurer, M.; Hawro, T.

doi:10.1111/jdv.19694

Cited by 4 publications

(3 citation statements)

References 78 publications

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“…Additionally, in line with our findings in the high IFNG AD group, Th1/type 1-associated cytokines were identified in the adult- compared to the pediatric-onset AD cohort, in chronic compared to acute AD, and in intrinsic compared to extrinsic AD [ 38 , 39 , 40 , 41 ]. Furthermore, the PCA of the low IFNG AD group revealed less separation between the lesional and non-lesional transcriptome in comparison to the high IFNG group, which might be explained by a strong alteration of healthy skin in extrinsic AD [ 42 , 43 , 44 ]. Moreover, in the low IFNG AD group, a significant reduction was observed in lipid production (glycerolipid metabolic process), a hallmark of the impaired barrier characteristic of extrinsic AD [ 41 , 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis

Wasserer,

Jargosch,

Mayer

et al. 2024

IJMS

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Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, with an increasing number of targeted therapies available. While biologics to treat AD exclusively target the key cytokines of type 2 immunity, Janus kinase inhibitors target a broad variety of cytokines, including IFN-γ. To better stratify patients for optimal treatment outcomes, the identification and characterization of subgroups, especially with regard to their IFNG expression, is of great relevance, as the role of IFNG in AD has not yet been fully clarified. This study aims to define AD subgroups based on their lesional IFNG expression and to characterize them based on their gene expression, T cell secretome and clinical attributes. RNA from the lesional and non-lesional biopsies of 48 AD patients was analyzed by RNA sequencing. Based on IFNG gene expression and the release of IFN-γ by lesional T cells, this cohort was categorized into three IFNG groups (high, medium, and low) using unsupervised clustering. The low IFNG group showed features of extrinsic AD with a higher prevalence of atopic comorbidities and impaired epidermal lipid synthesis. In contrast, patients in the high IFNG group had a higher average age and an activation of additional pro-inflammatory pathways. On the cellular level, higher amounts of M1 macrophages and natural killer cell signaling were detected in the high IFNG group compared to the low IFNG group by a deconvolution algorithm. However, both groups shared a common dupilumab response gene signature, indicating that type 2 immunity is the dominant immune shift in both subgroups. In summary, high and low IFNG subgroups correspond to intrinsic and extrinsic AD classifications and might be considered in the future for evaluating therapeutic efficacy or non-responders.

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Section: Discussionmentioning

confidence: 99%

Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis

Wasserer,

Jargosch,

Mayer

et al. 2024

IJMS

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“…Even though literature data are very limited, a proactive systemic treatment might modify disease progression, leading to pruritus alleviation, enhanced quality of life, less reliance on intensive topical treatments, improved psychological well-being, and secondary complications prevention. Besides, the chronic nature of AD and its association with atopic comorbidities, namely allergic rhinitis and asthma, further highlight the need to target the disease at its inception [ 6 ]. A recent meta-analysis regarding adolescent and adult AD under dupilumab demonstrated that the inhibition of IL-4/IL-13 hampered the development of new or the deterioration of established allergic conditions in a large AD clinical trial database in a highly atopic population [ 7 ].…”

Section: Key Summary Pointsmentioning

confidence: 99%

Insights into Early Systemic Treatment in Atopic Dermatitis: Scientific Facts and Practical Considerations

Vakirlis,

Gregoriou,

Bakirtzi

et al. 2024

Dermatol Ther (Heidelb)

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Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized clinically by pruritus, and pathophysiologically by immune dysregulation, and compromised skin barrier function. While topical therapies are currently the cornerstone of AD management, especially in mild disease, recent advancements in systemic treatments and a deeper understanding of similar skin diseases, such as psoriasis, have highlighted the importance of early intervention. In this commentary, we explore the potential benefits of early systemic intervention in AD, with pruritus determining such a decision. Building on this concept, we assume that, through the timely systemic treatment that targets the immune dysregulation present in AD, the progression of the disease could be modified, improving overall patient outcomes. Early systemic intervention may minimize systemic inflammation, halting the “atopic march” and disrupting the “itch–scratch” cycle. Managing pruritus at its root could prevent secondary complications and reduce the psychosocial burden of the disease. This paradigm shift fosters a collaborative healthcare approach that empowers patients with long-term disease control strategies. In conclusion, the safety and efficacy of novel systemic treatments offer a compelling scenario for early intervention in atopic dermatitis care.

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“…Plaque psoriasis is an autoimmune disorder that primarily affects the skin, causing hyperproliferation of keratinocytes, manifesting as well-defined erythematous plaques covered with silvery-white scales [5]. PsA, on the other hand, is a type of spondyloarthritis often preceded and accompanied by psoriasis [6].…”

Section: Introductionmentioning

confidence: 99%

Guselkumab, a Novel Monoclonal Antibody Inhibitor of the p19 Subunit of IL-23, for Psoriatic Arthritis and Plaque Psoriasis: A Review of Its Mechanism, Use, and Clinical Effectiveness

Kerut,

Wagner,

Daniel

et al. 2023

Cureus

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Psoriatic arthritis and plaque psoriasis are autoimmune conditions affecting multiple organs, including the skin. The pathophysiology and etiology of these conditions are not fully understood; however, numerous factors are believed to play a critical role, including genetics and environmental risk factors. Furthermore, research suggests the IL-23/IL-17 pathway partially mediates these diseases. Once the IL-23 receptor is bound and activated, two subunits, p19, and p40, act through different signaling pathways. Ultimately, inflammation is produced through the effector molecule, IL-17, other cytokines, and tumor necrosis factor (TNF). Traditionally, these chronic conditions have been treated with TNF-α inhibitors and methotrexate, a dihydrofolate reductase inhibitor. Although successful in inhibiting the immune system, these drugs can have many adverse effects due to their broad targets. In recent years, more targeted therapy has become popular. Guselkumab is a monoclonal antibody that inhibits the p19 subunit of IL-23. It has been FDA-approved to treat both plaque psoriasis and psoriatic arthritis. Clinical trials showing guselkumab’s efficacy have been promising, even showing improvement in symptoms of plaque psoriasis patients resistant to adalimumab, a TNF-α inhibitor. Guselkumab has also been shown to be well tolerated with a similar safety profile as other biologics inhibiting the immune system. In addition to its efficacy in treating plaque psoriasis and psoriatic arthritis, the mechanism of action offers a targeted approach that may minimize the broad immunosuppressive effects often associated with traditional therapies, providing a potential advantage in the long-term management of these autoimmune conditions.

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Clinically uninvolved but not healthy—The skin of patients with atopic dermatitis is primed for itch and inflammation

Cited by 4 publications

References 78 publications

Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis

Characterization of High and Low IFNG-Expressing Subgroups in Atopic Dermatitis

Insights into Early Systemic Treatment in Atopic Dermatitis: Scientific Facts and Practical Considerations

Guselkumab, a Novel Monoclonal Antibody Inhibitor of the p19 Subunit of IL-23, for Psoriatic Arthritis and Plaque Psoriasis: A Review of Its Mechanism, Use, and Clinical Effectiveness

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