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Highly effective targeted therapies are available to treat noncommunicable chronic inflammatory skin diseases. In contrast, the exact diagnosis of noncommunicable chronic inflammatory skin diseases is complicated by its complex pathogenesis and clinical and histological overlap. Particularly, the differential diagnosis of psoriasis and eczema can be challenging in some cases, and molecular diagnostic tools need to be developed to support a gold standard diagnosis. The aim of this work was to develop a real-time PCR-based molecular classifier to distinguish psoriasis from eczema in formalin-fixed and paraffin-embedded-fixed skin samples and to evaluate the use of minimally invasive microbiopsies and tape strips for molecular diagnosis. In this study, we present a formalin-fixed and paraffin-embedded-based molecular classifier that determines the probability for psoriasis with a sensitivity/specificity of 92%/100%, respectively, and an area under the curve of 0.97, delivering comparable results to our previous published RNAprotect-based molecular classifier. The psoriasis probability, as well as levels of NOS2 expression, positively correlated with the disease hallmarks of psoriasis and negatively with eczema hallmarks. Furthermore, minimally invasive tape strips and microbiopsies were effectively used to differentiate psoriasis from eczema. In summary, the molecular classifier offers broad usage in pathology laboratories as well as outpatient settings and can support the differential diagnosis of noncommunicable chronic inflammatory skin diseases on a molecular level using formalin-fixed and paraffin-embedded tissue, microbiopsies, and tape strips., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

T cells are key drivers of autoimmunity in numerous noncommunicable inflammatory skin diseases by directly harming host tissue or through helping B cells in producing autoantibodies. Technological advances have contributed to identifying autoantigens, the Holy Grail of autoimmunity, in many inflammatory disorders of the skin. Novel therapeutic approaches such as chimeric (auto)antibody receptor T cells are a milestone on the way to finding individualized, well-tolerated, targeted therapies. This review summarizes the current knowledge on pathogenesis, immune response pattern‒related ontology, diagnostic approaches, and treatment options of autoimmune skin diseases., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Reactivation of latent Epstein‒Barr virus (EBV) and/or Cytomegalovirus (CMV) infection is a dreaded complication in immunocompromised patients receiving hematopoietic stem cell transplantation. Evidence is sparse on whether subclinical reactivation of viral infection may also be of clinical relevance in dermatological patients. We screened patients (N = 206) suffering from chronic skin diseases for subclinical reactivation of EBV and CMV infection. We found that immunocompromised patients with therapy-refractory chronic skin diseases showed higher rates of subclinical reactivation of CMV and EBV infection (6.7% vs. 0% for EBV and 16.7% vs. 5.6% for CMV) and a higher prevalence of virus-specific DNA in skin tissue (30.8% vs. 0% for EBV and 21.4% vs. 0% for CMV) than nonimmunocompromised patients with chronic skin diseases. T cells isolated from lesional skin exhibited up to 14-fold increased proliferation with production of T helper type 1 and T helper type 17 cytokines on stimulation with viral proteins, providing evidence for possible aggravation of the underlying skin diseases by viral infection. Improvement of skin lesions in patients with reactivation of CMV infection (n = 4) was observed on antiviral treatment. Our data suggest that subclinical reactivation of EBV and/or CMV infection is an under-recognized condition in the dermatological patient population with chronic skin diseases., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

IFN-1s are early sentinels of potential danger in skin. Two interconnected axes exist: plasmacytoid dendritic cells (DCs) secreting IFN-α in response to single strand RNA or DNA and keratinocytes secreting IFN-κ after stimulation with double strand RNA or other IFNs. Both IFN-α and IFN-κ induce macrophages and DC subpopulations to secrete master regulators of cytotoxicity or wound healing, the latter related to psoriasis pathogenesis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Psoriasis is a T helper type 17-mediated immune disease. Initial triggers that lead to T helper type 17 production and inflammatory cell recruitment into skin are being delineated. Autoantigens that stimulate T helper type 17 cells are also being identified. A new and important piece of the puzzle indicates that keratinocytes not only amplify inflammation, but that they are essential for a full-blown IL-17-mediated psoriatic phenotype in mice., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Interface dermatitis is a characteristic histological pattern that occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different interface dermatitis positive skin diseases, lichen planus and lupus erythematosus. The shared transcriptome signature pointed toward a strong type I immune response, and biopsy-derived T cells were dominated by IFN-γ and tumor necrosis factor alpha (TNF-α) positive cells. The transcriptome of keratinocytes stimulated with IFN-γ and TNF-α correlated significantly with the shared gene regulations of lichen planus and lupus erythematosus. IFN-γ, TNF-α, or mixed supernatant of lesional T cells induced signs of keratinocyte cell death in three-dimensional skin equivalents. We detected a significantly enhanced epidermal expression of receptor-interacting-protein-kinase 3, a key regulator of necroptosis, in interface dermatitis. Phosphorylation of receptor-interacting-protein-kinase 3 and mixed lineage kinase domain like pseudokinase was induced in keratinocytes on stimulation with T-cell supernatant-an effect that was dependent on the presence of either IFN-γ or TNF-α in the T-cell supernatant. Small hairpin RNA knockdown of receptor-interacting-protein-kinase 3 prevented cell death of keratinocytes on stimulation with IFN-γ or TNF-α. In conclusion, type I immunity is associated with lichen planus and lupus erythematosus and induces keratinocyte necroptosis. These two mechanisms are potentially involved in interface dermatitis., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)