Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases.

Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-promoting from bystander immune cells. Here, we investigate the landscape of non-communicable inflammatory skin diseases (ncISD) by spatial transcriptomics resulting in a large repository of 62,000 spatially defined human cutaneous transcriptomes from 31 patients. Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.e. >125 times less compared to the mean expression of all other genes over lesional skin sections. Nevertheless, cytokine expression is limited to lesional skin and presented in a disease-specific pattern. Leveraging a density-based spatial clustering method, we identify specific responder gene signatures in direct proximity of cytokines, and confirm that detected cytokine transcripts initiate amplification cascades of up to thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and heterogeneous infiltrates of ncISD, only a low number of cytokine transcripts and their translated proteins promote disease by initiating an inflammatory amplification cascade in their local microenvironment.

[Differential diagnosis of common nail disorders in childhood]. / Differenzialdiagnose häufiger Nagelveränderungen im Kindesalter.

BACKGROUND: Correct diagnosis of nail changes in childhood may be challenging. Knowing the anatomy of the nail apparatus and some pathophysiologic principles helps to categorize nail disorders correctly. OBJECTIVES: This article gives a structured overview of nail disorders in childhood, thus, facilitating correct diagnosis of nail abnormalities in childhood. MATERIALS AND METHODS: A review of literature and our own experience are presented. RESULTS: In the first part we present fundamental anatomical characteristics of the nail apparatus based on embryonal development of the nails. In the main part we categorize nail disorders according to clinical presentation: transient nail changes, congenital nail abnormalities, infectious diseases of the nails, nail changes in the context of chronic inflammatory skin diseases, pigmented nail changes, tumors and nail changes due to trauma.

So close, and yet so far away: The dichotomy of the specific immune response and inflammation in psoriasis and atopic dermatitis.

Characterization of the complex interplay between cytokines, chemokines and microorganisms has led to a better understanding of the pathogenesis of both psoriasis and AD and resulted in new therapeutics targeting distinct immune responses. Psoriasis and AD share many characteristics: they are highly prevalent, chronic, cause primarily skin inflammation, but are associated with comorbidities, and come with a devastating quality of life due to itch and stigmatization. However, the pathogenesis of psoriasis and AD is opposing - psoriasis is dominated by a Th17 immune response that causes neutrophil migration, induction of innate immunity and exaggerated epithelial metabolism. Leading cytokines of this Th17 immune response are IL-17A and F, IL-22 and TNF-a. AD is characterized by Th2 immunity characterized by the signature cytokines IL-4 and IL-13 leading to an impaired epidermal barrier, dampened innate immunity and eosinophil migration. This review compares genetics, microbiome and T-cell infiltrate and resulting epithelial response in psoriasis and AD. Whilst the antagonistic course of psoriasis and AD is confirmed by response to specific biologics targeting the key cytokines of inflammation in psoriasis and AD, respectively, clinically overlapping phenotypes are challenging in our daily clinical practice. We conclude this review by summarizing what is known about these mixed phenotypes and how the identification of clinically relevant endotypes and molecular-driven decision-making is the next step in the field of dermato-immunology.

Is the humoral immunity dispensable for the pathogenesis of psoriasis?

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.

[Personalized medicine in the field of inflammatory skin diseases]. / Personalisierte Medizin im Bereich entzündlicher Hauterkrankungen.

BACKGROUND: For sufficient treatment of patients with chronic inflammatory skin diseases, new concepts need to be established and biomarkers must be identified. OBJECTIVE: Presentation of new markers, their quality and implications for the clinical daily routine. MATERIAL AND METHODS: This article presents a discussion of basic research and a review of current achievements of personalized medicine in the area of chronic inflammatory skin diseases. RESULTS: Promising biomarker for the various entities of chronic inflammatory skin diseases have been proposed; however, they need to be prospectively validated and translated into affordable and feasible tests. CONCLUSION: There is still a long way to go to establish personalized medicine in the field of chronic inflammatory skin diseases and its success is dependent on multicenter collaboration to validate and implement novel biomarkers.

Addiction: an underestimated problem in psoriasis health care.

BACKGROUND: Psoriasis is a disease of enormous socio-economic impact. Despite approval of numerous highly efficient and costly therapies, a minor proportion of severely affected patients actually receives sufficient treatment. OBJECTIVE: To investigate whether addictions are associated with psoriasis and to develop evidence-based recommendations for dermatologists in their daily clinical practice in order to improve medical assessment of psoriasis and patients' quality of life. PATIENTS AND METHODS: Psoriasis patients at the University Department of Dermatology were asked to fill out a paper-based self-reported anonymous questionnaire with 92 questions of validated screening tests for the six most common addictions in Germany (alcohol, nicotine, drugs and illegal drugs, gambling, food). Body weight and height as well as current Psoriasis Area and Severity Index (PASI) were documented as well. RESULTS: Between October 2015 and February 2016, 102 patients (65 males, 37 females; mean age 49.7 years (SD 13.4), range 18-83 years) participated in the study. Fifty-seven of the 102 patients showed addictive behaviour. Of these, 23.8% were high-risk drinkers, 41% regular smokers, 11% at risk of drug abuse, 4.1% at risk of food dependency and 19% compulsive gamblers. Compared with the general population, these results are significantly higher for alcohol abuse (P < 0.005), nicotine (P < 0.001) and gambling (P < 0.001). Body mass index was significantly higher in the study population (P < 0.001). CONCLUSION: Addictions and gambling are more prevalent in patients with psoriasis compared with the general population. Respective screening measures are recommended in daily practice for doctors treating psoriasis patients, and PeakPASI is suggested as a score to document patients' lifetime highest PASI. Parallel to new drug approvals and even more detailed insights into the pathomechanism of psoriasis, public health strategies and interdisciplinary approaches are essential for a general sustained psoriasis treatment.