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Article ; Online: Sex-disaggregated population analysis in patients with hidradenitis suppurativa

Robert Sabat / Athanasia Tsaousi / Kamran Ghoreschi / Kerstin Wolk / Sylke Schneider-Burrus

Frontiers in Medicine, Vol

2022 Volume 9

Abstract: BackgroundHidradenitis suppurativa (HS) is a common chronic inflammatory skin disease, which affects both sexes.ObjectivesIdentification of sex-specific risk factors, comorbidity, clinical manifestations, and treatments in HS patients.MethodsA non- ... ...

Abstract	BackgroundHidradenitis suppurativa (HS) is a common chronic inflammatory skin disease, which affects both sexes.ObjectivesIdentification of sex-specific risk factors, comorbidity, clinical manifestations, and treatments in HS patients.MethodsA non-interventional, cross-sectional, mono-centric study with 500 HS patients. All patients were examined by dermatologists. Prospectively collected demographic, anamnestic, clinical data, and blood parameters were evaluated.ResultsThere were no significant differences in age at HS onset and in disease duration between female and male patients. Furthermore, no differences regarding the family history for HS were found between sexes. Regarding further risk factors for HS, central obesity was more frequent in women while extensive cigarette smoking and acne vulgaris were more commonly found among male patients. Regarding comorbidity, lower HDL-levels were significantly more frequent in men. Female patients were found to suffer significantly more often from back pain, especially in the neck/shoulder region and lower back. Analyzing the clinical manifestation of HS, the groin was more frequently involved in women and the axillae in men. Women showed a higher number of skin sites with inflammatory nodules, whereas fistulas were observed more frequently in men. Nevertheless, there was no difference in HS treatment applied to female vs. male patients.LimitationsData were obtained from a mono-centric study.ConclusionSignificant differences in HS risk factors, comorbidity, and clinical manifestation exist between female and male patients. Thus, sex-specific differences should be taken into account in the prevention as well as medical and surgical treatment of HS patients.
Keywords	acne inversa ; sex ; obesity ; smoking ; metabolic syndrome ; spondyloarthritis ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis

Katrin Witte / Robert Sabat / Ellen Witte-Händel / Kamran Ghoreschi / Kerstin Wolk

International Journal of Molecular Sciences, Vol 23, Iss 16, p

A Complementary Treatment Option for Hidradenitis Suppurativa?

2022 Volume 9057

Abstract: Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep- ... ...

Abstract	Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-α, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1β, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS.
Keywords	acne inversa ; IL-1 ; IL-17 ; G-CSF ; TNF-α ; LCN2 ; neutrophilic granulocytes ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Features Associated With Quality of Life Impairment in Hidradenitis Suppurativa Patients

Sylke Schneider-Burrus / Athanasia Tsaousi / Sebastian Barbus / Johannes Huss-Marp / Katrin Witte / Kerstin Wolk / Björn Fritz / Robert Sabat

Frontiers in Medicine, Vol

2021 Volume 8

Abstract: Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with an adverse impact on patients' quality of life (QoL).Objectives: To quantify QoL impairment in patients in Germany suffering from HS and to identify the parameters ... ...

Abstract	Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with an adverse impact on patients' quality of life (QoL).Objectives: To quantify QoL impairment in patients in Germany suffering from HS and to identify the parameters associated with QoL impairment.Methods: A non-interventional, cross-sectional, mono-centric study with 500 HS patients. QoL data (measured using the Dermatology Life Quality Index; DLQI) and demographic, anamnestic, clinical, and blood parameters were collected. All patients were examined by dermatologists that documented the skin alterations. QoL data from 462 HS patients were available and evaluated.Results: The mean (± standard deviation) DLQI score of HS patients was 13.18 ± 7.99. Approximately 40% and 20% of HS patients declared very large and extremely large QoL impairment, respectively. The degree of QoL disturbance correlated with the severity of skin alterations, blood leucocyte count and, in particular, with anogenital localization and the presence of nodules and fistulas. Furthermore, QoL impairment was associated with specific comorbidities, such as adiposity and back pain, but not with HS family history. QoL impairment was not influenced by whether or not the patients had undergone resection surgery or antibiotic treatment but was more severe in HS patients that had undergone abscess lancing compared to patients without such treatment in the past.Limitations: It was a mono-centric study and most data were obtained from self-administered patient questionnaires. The association of QoL with type of treatment was analyzed for abscess lancing, resection surgery, and antibiotic treatment. Further therapeutic modalities recommended in the guidelines were not investigated.Conclusion: A profound impairment in QoL was present in patients with HS, and this was higher than that observed in other studied dermatoses. The degree of impairment correlated with the extent of cutaneous and some extra-cutaneous alterations. Surgical and conventional medicamentous therapies ...
Keywords	skin disease ; quality of life ; dermatology life quality index ; obesity ; spondyloarthritis ; metabolic syndrome ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reprogramming Intestinal Epithelial Cell Polarity by Interleukin-22

Deborah Delbue / Lydia Lebenheim / Danielle Cardoso-Silva / Violaine Dony / Susanne M. Krug / Jan F. Richter / Subhakankha Manna / Melba Muñoz / Kerstin Wolk / Claudia Heldt / Markus M. Heimesaat / Robert Sabat / Britta Siegmund / Michael Schumann

Frontiers in Medicine, Vol

2021 Volume 8

Abstract: Background: Interleukin-22 (IL-22) impacts the integrity of intestinal epithelia and has been associated with the development of colitis-associated cancer and inflammatory bowel diseases (IBD). Previous data suggest that IL-22 protects the mucosal ... ...

Abstract	Background: Interleukin-22 (IL-22) impacts the integrity of intestinal epithelia and has been associated with the development of colitis-associated cancer and inflammatory bowel diseases (IBD). Previous data suggest that IL-22 protects the mucosal barrier and promotes wound healing and barrier defect. We hypothesized, that IL-22 modulates cell polarity of intestinal epithelial cells (IECs) acting on tight junction assembly. The aim of the study was to investigate IL-22-dependent mechanisms in the reprogramming of intestinal epithelia.Methods: IECs were exposed to IL-22 at various concentrations. IECs in Matrigel® were grown to 3-dimensional cysts in the presence or absence of IL-22 and morphology and expression of polarity proteins were analyzed by confocal microscopy. Epithelial cell barrier (TER and sandwich assay) and TJ assembly analysis (calcium-switch assay) were performed. TJ and cell polarity protein expression were assessed by western blotting and confocal microscopy. Cell migration and invasion assays were performed. Induction of epithelial-mesenchymal transition (EMT) was assessed by RT-qPCR analysis and western blotting. Signaling pathway analyses were performed by phosphoblotting and functional assays after blocking STAT3 and ERK signaling pathways. Using the toxoplasma-model of terminal ileitis, IL-22-knock-out mice were compared to wild-type littermates, analyzed for barrier function using one-path-impedance-analysis and macromolecular flux (H3-mannitol, Ussing-chambers).Results: IECs exhibited a barrier defect after IL-22 exposure. TJ protein distribution and expression were severely impaired. Delayed recovery in the calcium-switch assay was observed suggesting a defect in TJ assembly. Analyzing the 3D-cyst model, IL-22 induced multi-lumen and aberrant cysts, and altered the localization of cell polarity proteins. Cell migration and invasion was caused by IL-22 as well as induction of EMT. Interestingly, only inhibition of the MAPK pathway, rescued the TJal barrier defect, while blocking STAT3 was relevant for cell survival. In addition, ileal mucosa of IL-22 deficient mice was protected from the barrier defect seen in Toxoplasma gondii-induced ileitis in wild type mice shown by significantly higher Re values and correspondingly lower macromolecule fluxes.Conclusion: IL-22 impairs intestinal epithelial cell barrier by inducing EMT, causing defects in epithelial cell polarity and increasing cell motility and cell invasion. IL-22 modulates TJ protein expression and mediates tight junctional (TJal) barrier defects via ERK pathway.
Keywords	intestinal epithelial cells ; barrier function ; cell polarity ; IL-22 ; tight junctions ; MAPK ; Medicine (General) ; R5-920
Subject code	571
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8+ T cells

Lucie Loyal / Sarah Warth / Karsten Jürchott / Felix Mölder / Christos Nikolaou / Nina Babel / Mikalai Nienen / Sibel Durlanik / Regina Stark / Beate Kruse / Marco Frentsch / Robert Sabat / Kerstin Wolk / Andreas Thiel

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 12

Abstract: We classically consider the T cell compartment divided into cytotoxic CD8+ T cells and multiple, different helper CD4+ T cell subsets. Here the authors demonstrate that distinct memory CD8+ T cell subsets phenotypically inhabit CD4+ T cell like ... ...

Abstract	We classically consider the T cell compartment divided into cytotoxic CD8+ T cells and multiple, different helper CD4+ T cell subsets. Here the authors demonstrate that distinct memory CD8+ T cell subsets phenotypically inhabit CD4+ T cell like populations including some with helper-like characteristics.
Keywords	Science ; Q
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes.

Katrin Witte / Egon Koch / Hans-Dieter Volk / Kerstin Wolk / Robert Sabat

PLoS ONE, Vol 10, Iss 9, p e

2015 Volume 0138075

Abstract: Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human ... ...

Abstract	Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: BKV, CMV, and EBV Interactions and their Effect on Graft Function One Year Post-Renal Transplantation

Arturo Blazquez-Navarro / Chantip Dang-Heine / Nicole Wittenbrink / Chris Bauer / Kerstin Wolk / Robert Sabat / Timm H. Westhoff / Birgit Sawitzki / Petra Reinke / Oliver Thomusch / Christian Hugo / Michal Or-Guil / Nina Babel

EBioMedicine, Vol 34, Iss , Pp 113-

Results from a Large Multi-Centre StudyResearch in context

2018 Volume 121

Abstract: Background: BK virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivations are common after kidney transplantation and associated with increased morbidity and mortality. Although CMV might be a risk factor for BKV and EBV, the effects ... ...

Abstract	Background: BK virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivations are common after kidney transplantation and associated with increased morbidity and mortality. Although CMV might be a risk factor for BKV and EBV, the effects of combined reactivations remain unknown. The purpose of this study is to ascertain the interaction and effects on graft function of these reactivations. Methods: 3715 serum samples from 540 kidney transplant recipients were analysed for viral load by qPCR. Measurements were performed throughout eight visits during the first post-transplantation year. Clinical characteristics, including graft function (GFR), were collected in parallel. Findings: BKV had the highest prevalence and viral loads. BKV or CMV viral loads over 10,000 copies·mL−1 led to significant GFR impairment. 57 patients had BKV-CMV combined reactivation, both reactivations were significantly associated (p = 0.005). Combined reactivation was associated with a significant GFR reduction one year post-transplantation of 11.7 mL·min−1·1.73 m−2 (p = 0.02) at relatively low thresholds (BKV > 1000 and CMV > 4000 copies·mL−1). For EBV, a significant association was found with CMV reactivation (p = 0.02), but no GFR reduction was found. Long cold ischaemia times were a further risk factor for high CMV load. Interpretation: BKV-CMV combined reactivation has a deep impact on renal function one year post-transplantation and therefore most likely on long-term allograft function, even at low viral loads. Frequent viral monitoring and subsequent interventions for low BKV and/or CMV viraemia levels and/or long cold ischaemia time are recommended. Fund: Investigator Initiated Trial; financial support by German Federal Ministry of Education and Research (BMBF). Keywords: BK virus, Cytomegalovirus, Epstein-Barr virus, Kidney transplantation, Graft function, Combined reactivation
Keywords	Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unmet Medical Needs in Chronic, Non-communicable Inflammatory Skin Diseases

Hideyuki Ujiie / David Rosmarin / Michael P. Schön / Sonja Ständer / Katharina Boch / Martin Metz / Marcus Maurer / Diamant Thaci / Enno Schmidt / Connor Cole / Kyle T. Amber / Dario Didona / Michael Hertl / Andreas Recke / Hanna Graßhoff / Alexander Hackel / Anja Schumann / Gabriela Riemekasten / Katja Bieber /

Gant Sprow / Joshua Dan / Detlef Zillikens / Tanya Sezin / Angela M. Christiano / Kerstin Wolk / Robert Sabat / Khalaf Kridin / Victoria P. Werth / Ralf J. Ludwig

Frontiers in Medicine, Vol

2022 Volume 9

Abstract: An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, ... ...

Abstract	An estimated 20–25% of the population is affected by chronic, non-communicable inflammatory skin diseases. Chronic skin inflammation has many causes. Among the most frequent chronic inflammatory skin diseases are atopic dermatitis, psoriasis, urticaria, lichen planus, and hidradenitis suppurativa, driven by a complex interplay of genetics and environmental factors. Autoimmunity is another important cause of chronic skin inflammation. The autoimmune response may be mainly T cell driven, such as in alopecia areata or vitiligo, or B cell driven in chronic spontaneous urticaria, pemphigus and pemphigoid diseases. Rare causes of chronic skin inflammation are autoinflammatory diseases, or rheumatic diseases, such as cutaneous lupus erythematosus or dermatomyositis. Whilst we have seen a significant improvement in diagnosis and treatment, several challenges remain. Especially for rarer causes of chronic skin inflammation, early diagnosis is often missed because of low awareness and lack of diagnostics. Systemic immunosuppression is the treatment of choice for almost all of these diseases. Adverse events due to immunosuppression, insufficient therapeutic responses and relapses remain a challenge. For atopic dermatitis and psoriasis, a broad spectrum of innovative treatments has been developed. However, treatment responses cannot be predicted so far. Hence, development of (bio)markers allowing selection of specific medications for individual patients is needed. Given the encouraging developments during the past years, we envision that many of these challenges in the diagnosis and treatment of chronic inflammatory skin diseases will be thoroughly addressed in the future.
Keywords	medical need ; skin ; inflammation ; atopic dermatitis ; psoriasis ; alopecia areata ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Increased prevalence of metabolic syndrome in patients with acne inversa.

Robert Sabat / Akewit Chanwangpong / Sylke Schneider-Burrus / Deborah Metternich / Georgios Kokolakis / Agata Kurek / Sandra Philipp / Daniela Uribe / Kerstin Wolk / Wolfram Sterry

PLoS ONE, Vol 7, Iss 2, p e

2012 Volume 31810

Abstract: BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and ... ...

Abstract	BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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