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Article ; Online: Hope for a new therapy for hidradenitis suppurativa: blocking of granulocyte colony-stimulating factor receptor.

Wolk, Kerstin

2023 Volume 188, Issue 5, Page(s) 590

MeSH term(s)	Humans ; Hidradenitis Suppurativa/drug therapy ; Receptors, Granulocyte Colony-Stimulating Factor ; Neutrophils
Chemical Substances	Receptors, Granulocyte Colony-Stimulating Factor
Language	English
Publishing date	2023-03-02
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1093/bjd/ljad056
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Book ; Online ; Thesis: Antimikrobielle und antivirale Proteine bei chronisch-inflammatorischen Hauterkrankungen und deren Regulation durch Zytokine

Wolk, Kerstin [Verfasser]

2018

Author's details	Kerstin Wolk
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Medizinische Fakultät Charité - Universitätsmedizin Berlin
Publishing place	Berlin
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Targeting Metabolic Syndrome in Hidradenitis Suppurativa by Phytochemicals as a Potential Complementary Therapeutic Strategy.

Witte, Katrin / Wolk, Kerstin / Witte-Händel, Ellen / Krause, Torben / Kokolakis, Georgios / Sabat, Robert

Nutrients

2023 Volume 15, Issue 17

Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the appearance of painful inflamed nodules, abscesses, and pus-draining sinus tracts in the intertriginous skin of the groins, buttocks, and perianal and axillary regions. ... ...

Abstract	Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the appearance of painful inflamed nodules, abscesses, and pus-draining sinus tracts in the intertriginous skin of the groins, buttocks, and perianal and axillary regions. Despite its high prevalence of ~0.4-1%, therapeutic options for HS are still limited. Over the past 10 years, it has become clear that HS is a systemic disease, associated with various comorbidities, including metabolic syndrome (MetS) and its sequelae. Accordingly, the life expectancy of HS patients is significantly reduced. MetS, in particular, obesity, can support sustained inflammation and thereby exacerbate skin manifestations and the chronification of HS. However, MetS actually lacks necessary attention in HS therapy, underlining the high medical need for novel therapeutic options. This review directs attention towards the relevance of MetS in HS and evaluates the potential of phytomedical drug candidates to alleviate its components. It starts by describing key facts about HS, the specifics of metabolic alterations in HS patients, and mechanisms by which obesity may exacerbate HS skin alterations. Then, the results from the preclinical studies with phytochemicals on MetS parameters are evaluated and the outcomes of respective randomized controlled clinical trials in healthy people and patients without HS are presented.
MeSH term(s)	Humans ; Hidradenitis Suppurativa/complications ; Hidradenitis Suppurativa/drug therapy ; Metabolic Syndrome/complications ; Metabolic Syndrome/drug therapy ; Skin ; Obesity/complications ; Obesity/drug therapy ; Inflammation ; Phytochemicals/therapeutic use
Chemical Substances	Phytochemicals
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15173797
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Article ; Online: Biology of Interleukin-17 and Novel Therapies for Hidradenitis Suppurativa.

Sabat, Robert / Gudjonsson, Johann Eli / Brembilla, Nicolo Costantino / van Straalen, Kelsey R / Wolk, Kerstin

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

2023 Volume 43, Issue 12, Page(s) 544–556

Abstract: Skin disorders affect ∼40% of the human population. One of the most debilitating cutaneous disorders is Hidradenitis suppurativa (HS), a noncommunicable chronic inflammatory disease with an estimated global prevalence of 0.4% to 2.5%. In January 2011, ... ...

Abstract	Skin disorders affect ∼40% of the human population. One of the most debilitating cutaneous disorders is Hidradenitis suppurativa (HS), a noncommunicable chronic inflammatory disease with an estimated global prevalence of 0.4% to 2.5%. In January 2011, high levels of IL-17 were discovered in skin lesions of HS patients. In the following years, translational and clinical research led to a better understanding of the pathogenesis of HS. In June 2023, more than 12 years after the initial note, secukinumab, an anti-IL-17A monoclonal antibody, was approved for the treatment of moderate to severe HS. This is the next milestone in improving the treatment of these patients after the approval of the anti-TNF-α monoclonal antibody adalimumab in 2015. In this review article, we present the IL-17 pathway in HS and discuss the use of secukinumab as a therapeutic option for this disease. Our review starts with a description of the epidemiology, clinical features, etiology, and pathogenesis of HS. An overview of the IL-17/IL-17 receptor system in general and a detailed description of the known facts about the expression and action of IL-17 in HS follow. Afterward, we consider the results of clinical trials evaluating the safety and efficacy of IL-17 inhibitors in HS. Finally, a comparison is made between secukinumab and adalimumab and the characteristics of the patients that may be particularly suitable for each of these biologics are described.
MeSH term(s)	Humans ; Hidradenitis Suppurativa/drug therapy ; Hidradenitis Suppurativa/pathology ; Adalimumab/therapeutic use ; Interleukin-17/metabolism ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Biology
Chemical Substances	Adalimumab (FYS6T7F842) ; Interleukin-17 ; Tumor Necrosis Factor Inhibitors
Language	English
Publishing date	2023-10-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1226675-9
ISSN	1557-7465 ; 1079-9907
ISSN (online)	1557-7465
ISSN	1079-9907
DOI	10.1089/jir.2023.0105
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Article ; Online: Molecular and functional changes in neutrophilic granulocytes induced by nicotine: a systematic review and critical evaluation.

Brembach, Theresa-Charlotte / Sabat, Robert / Witte, Katrin / Schwerdtle, Tanja / Wolk, Kerstin

Frontiers in immunology

2023 Volume 14, Page(s) 1281685

Abstract: Background: Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory ... ...

Abstract	Background: Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far. Objectives: The aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release. Material and methods: This review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed Results: Of the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (>3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of β-glucuronidase and myeloperoxidase. Conclusion: Nicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.
MeSH term(s)	Humans ; Extracellular Traps/metabolism ; Neutrophils/metabolism ; Nicotine/adverse effects ; Nicotine/metabolism ; Reactive Oxygen Species/metabolism ; Granulocytes/drug effects
Chemical Substances	Nicotine (6M3C89ZY6R) ; Reactive Oxygen Species
Language	English
Publishing date	2023-11-23
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1281685
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Article ; Online: The impact of hidradenitis suppurativa on professional life.

Schneider-Burrus, Sylke / Kalus, Stefanie / Fritz, Björn / Wolk, Kerstin / Gomis-Kleindienst, Susana / Sabat, Robert

The British journal of dermatology

2023 Volume 188, Issue 1, Page(s) 122–130

Abstract: Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin.: Objectives: To determine the extent of work ability and productivity impairment as a result of HS in Germany.: Methods: A prospective, ... ...

Abstract	Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin. Objectives: To determine the extent of work ability and productivity impairment as a result of HS in Germany. Methods: A prospective, multicentre, epidemiological, noninterventional study of patients with HS was conducted. Medical history, medical examination performed by dermatologists and patient-reported outcomes [Work Ability Index (WAI) and Work Productivity and Activity Impairment (WPAI)] were collected. Results: Of the 481 patients with HS included in the study, 99% were below the current statutory retirement age. In total, 53·3% of patients were working full time, 16·8% part time and 7·3% had retired. The unemployment rate was 12·6%, two times higher than in the general German population. Medical leave because of HS, within the last 6 months, was reported in 41·4% [95% confidence interval (CI) 36·9-46·0], with a duration of 39·3 days on average (95% CI 32·4-46·1). The mean HS-related WPAI absenteeism was 13.3% (95% CI 9·7-16·8), and the loss in productivity because of HS during working hours (WPAI presenteeism) was 25.2% (95% CI 21·8-28·6). Presenteeism was associated with HS disease severity. Overall work impairment because of HS was 33·4% (95% CI 29·3-37·6). The WAI score for patients was 32·2, ∼20% lower than for the average German employee. Only 62·8% of patients were relatively certain that they would be able to perform their work in the coming 2 years. Being more depressed and having more severe pain were associated with lower work ability and overall work impairment. The estimated annual loss of gross value added because of HS for Germany was ∼€12.6 billion (€3.3 billion related to a lower employment rate, €3.5 billion related to absenteeism and €5.8 billion related to presenteeism). Conclusions: HS leads to a substantial decrease in work ability and productivity and considerable loss of gross value added. Impairment during working hours correlates with disease severity, underlining the socioeconomic importance of early and adequate treatment. Furthermore, decreased work ability and productivity is linked to depressed mood and severe pain, aspects that need more attention in patient care.
MeSH term(s)	Humans ; Hidradenitis Suppurativa ; Prospective Studies ; Surveys and Questionnaires ; Efficiency ; Pain ; Absenteeism ; Quality of Life ; Severity of Illness Index
Language	English
Publishing date	2023-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1093/bjd/ljac027
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Article ; Online: Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?

Witte, Katrin / Schneider-Burrus, Sylke / Salinas, Gabriela / Mössner, Rotraut / Ghoreschi, Kamran / Wolk, Kerstin / Sabat, Robert

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its ... ...

Abstract	Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its pathogenetic mechanisms is a prerequisite for novel therapeutic developments. T cells are assumed to play a crucial role in HS pathogenesis. However, it is currently unknown whether blood T cells show specific molecular alterations in HS. To address this, we studied the molecular profile of CD4
MeSH term(s)	Humans ; Hidradenitis Suppurativa/pathology ; Dermatitis/pathology ; Skin/metabolism ; T-Lymphocytes, Helper-Inducer/metabolism ; Inflammation/pathology
Language	English
Publishing date	2023-05-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24108854
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Article: Sex-disaggregated population analysis in patients with hidradenitis suppurativa.

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

Frontiers in medicine

2022 Volume 9, Page(s) 1028943

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

Abstract	Background: Hidradenitis suppurativa (HS) is a common chronic inflammatory skin disease, which affects both sexes. Objectives: Identification of sex-specific risk factors, comorbidity, clinical manifestations, and treatments in HS patients. Methods: A 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. Results: There 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. Limitations: Data were obtained from a mono-centric study. Conclusion: Significant 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.
Language	English
Publishing date	2022-11-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.1028943
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Article ; Online: Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

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

International journal of molecular sciences

2022 Volume 23, Issue 16

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.
MeSH term(s)	Granulocyte Colony-Stimulating Factor/therapeutic use ; Hidradenitis Suppurativa/drug therapy ; Hidradenitis Suppurativa/pathology ; Humans ; Interleukin-17 ; Phytotherapy ; Plant Preparations/pharmacology ; Quality of Life ; Skin/pathology
Chemical Substances	Interleukin-17 ; Plant Preparations ; Granulocyte Colony-Stimulating Factor (143011-72-7)
Language	English
Publishing date	2022-08-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23169057
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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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