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Background: Imbalances of T‐cell subsets are hallmarks of disease‐specific inflammation in psoriasis. However, the relevance of B cells for psoriasis remains poorly investigated. Objective: To analyse the role of B cells and immunoglobulins for the disease‐specific immunology of psoriasis. Methods: We characterized B‐cell subsets and immunoglobulin levels in untreated psoriasis patients (n = 37) and compared them to healthy controls (n = 20) as well as to psoriasis patients under disease‐controlling systemic treatment (n = 28). B‐cell subsets were analysed following the flow cytometric gating strategy based on the surface markers CD24, CD38 and CD138. Moreover, immunofluorescence stainings were used to detect IgA in psoriatic skin. Results: We found significantly increased levels of IgA in the serum of treatment‐naïve psoriasis patients correlating with disease score. However, IgA was only observed in dermal vessels of skin sections. Concerning B‐cell subsets, we only found a moderately positive correlation of CD138+ plasma cells with IgA levels and disease score in treatment‐naïve psoriasis patients. Confirming our hypothesis that psoriasis can develop in the absence of functional humoral immunity, we investigated a patient who suffered concomitantly from both psoriasis and a hereditary common variable immune defect (CVID) characterized by a lack of B cells and immunoglobulins. We detected variants in three of the 13 described genes of CVID and a so far undescribed variant in the ligand of the TNFRSF13B receptor leading to disturbed B‐cell maturation and antibody production. However, this patient showed typical psoriasis regarding clinical presentation, histology or T‐cell infiltrate. Finally, in a group of psoriasis patients under systemic treatment, neither did IgA levels drop nor did plasma cells correlate with IgA levels and disease score. Conclusion: B‐cell alterations might rather be an epiphenomenal finding in psoriasis with a clear dominance of T cells over shifts in B‐cell subsets. [ABSTRACT FROM AUTHOR]

Background: Histopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the inclusion of all available diagnostic parameters., Objective: To identify the most impactful histological criteria for a predictive diagnostic model to discriminate MF from atopic dermatitis (AD)., Methods: In this multicentre study, two cohorts of patients with either unequivocal AD or MF were evaluated by two independent dermatopathologists. Based on 32 histological attributes, a hypothesis-free prediction model was developed and validated on an independent patient's cohort., Results: A reduced set of two histological features (presence of atypical lymphocytes in either epidermis or dermis) was trained. In an independent validation cohort, this model showed high predictive power (95% sensitivity and 100% specificity) to differentiate MF from AD and robustness against inter-individual investigator differences., Limitations: The study investigated a limited number of cases and the classifier is based on subjectively evaluated histological criteria., Conclusion: Aiming at distinguishing early MF from AD, the proposed binary classifier performed well in an independent cohort and across observers. Combining this histological classifier with immunohistochemical and/or molecular techniques (such as clonality analysis or molecular classifiers) could further promote differentiation of early MF and AD., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Mechanistic insight into ageing may empower prolonging the lifespan of humans; however, a complete understanding of this process is still lacking despite a plethora of ageing theories. In order to address this, we investigated the association of lifespan with eight phenotypic traits, that is, litter size, body mass, female and male sexual maturity, somatic mutation, heart, respiratory, and metabolic rate. In support of the somatic mutation theory, we analysed 15 mammalian species and their whole-genome sequencing deriving somatic mutation rate, which displayed the strongest negative correlation with lifespan. All remaining phenotypic traits showed almost equivalent strong associations across this mammalian cohort, however, resting heart rate explained additional variance in lifespan. Integrating somatic mutation and resting heart rate boosted the prediction of lifespan, thus highlighting that resting heart rate may either directly influence lifespan, or represents an epiphenomenon for additional lower-level mechanisms, for example, metabolic rate, that are associated with lifespan., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

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.)

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 T H 2-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., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Because hand eczema is a diagnostic challenge even for experienced dermatologists, a correct diagnosis is essential to ensure success of specific therapies., Objectives: Prerequisites for successful molecular diagnostics in general and in hand eczema in particular are discussed., Materials and Methods: Basic research and opinion statement on new developments in molecular diagnostics are considered with a special focus on hand eczema., Results: The first molecular classifier to distinguish psoriasis from (hand) eczema signature has been introduced as CE-marked in vitro diagnostics (CE-IVD); many more biomarkers associated with diagnostics, theranostics, or natural course of the disease are currently being investigated., Conclusions: Diagnosis of hand eczema will be supported by molecular diagnostics in the near future; we are at the beginning of the molecular era in dermatology., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Molecular diagnostics (MDx) has become an indispensable pillar of diagnostics in dermatology. Modern sequencing technologies allow for identification of rare genodermatoses, analysis of somatic mutations in melanoma are prerequisite for targeted therapies, and cutaneous infectious pathogens are quickly detected by PCR and other amplification methods. However, to push innovation in molecular diagnostics and tackle so far unmet clinical needs, research activities need to be bundled and the pipeline from idea to MDx product clearly rolled out. Only then, the requirements for technical validity and clinical utility of novel biomarkers can be fulfilled and the long-term vision of personalized medicine will be realized., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background and Objectives: Molecular diagnostics (MDx) increasingly gains importance in dermatology and its application is a prerequisite for personalized medicine. The goal of this cross-sectional study was to determine how MDx is implemented in dermatologists' offices in the three fields of oncology, inflammation and infectiology and which hurdles office-based dermatologists face in terms of MDx., Methods: Physician members of the Association of the German Dermatologists (Berufsverband der Deutschen Dermatologen e. V.; BVDD) were surveyed via an online questionnaire on MDx., Results: 39.6 % of the 192 participants reported using MDx. Of these, the vast majority used MDx for diagnosing infectious diseases (86.5 % and 44.3 % of users perform MDx for detection of funghi and sexually transmitted diseases, respectively). Only a small minority applied MDx to answer oncological or immunological questions. The major obstacles for non-users as compared to users were difficulties in implementation, lack of expertise as well as time, personnel, and technical availability. Reimbursement was a main issue in both groups., Conclusions: Despite availability of specific therapies requiring precision medicine, MDx has not yet been broadly implemented in office-based dermatology. To advance MDx, more needs to be done in terms of continuous education, availability of reliable and valid tests, and reimbursability., (© 2021 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

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.)