Publications by authors named "C C Zouboulis"

644 Publications

Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab.

F1000Res 2021 13;10:381. Epub 2021 May 13.

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, 06847, Germany.

Syndromic hidradenitis suppurativa (HS) is a form of symptom constellations, which differs from the familial and genetic form and comprises predominantly osteoarticular manifestations. Many forms include pyoderma gangrenosum and acne (PASH), pyogenic arthritis (PAPASH), spondyloarthritis (PASS) and psoriatic arthritis (PsAPASH) and are categorized in the autoinflammatory syndromes. Anti-TNF-α and anti-IL-1a blockade are between the therapeutic approaches that improve skin symptoms and prevent permanent osteoarticular damage. This case report refers to the successful treatment of a mixed phenotype of the aforementioned symptoms using the IL-17A inhibitor secukinumab after initial treatment with adalimumab. The therapy improved both cutaneous and reported osteoarticular symptoms. Different approaches for these recalcitrant HS syndromes are essential in order to achieve long-term remission for those patients.
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http://dx.doi.org/10.12688/f1000research.52100.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424462PMC
May 2021

Interleukins 4 and 13 drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis.

Proc Natl Acad Sci U S A 2021 Sep;118(38)

Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390;

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin dryness, inflammation, and itch. A major hallmark of AD is an elevation of the immune cytokines IL-4 and IL-13. These cytokines lead to skin barrier disruption and lipid abnormalities in AD, yet the underlying mechanisms are unclear. Sebaceous glands are specialized sebum-producing epithelial cells that promote skin barrier function by releasing lipids and antimicrobial proteins to the skin surface. Here, we show that in AD, IL-4 and IL-13 stimulate the expression of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1), a key rate-limiting enzyme in sex steroid hormone synthesis, predominantly expressed by sebaceous glands in human skin. HSD3B1 enhances androgen production in sebocytes, and IL-4 and IL-13 drive lipid abnormalities in human sebocytes and keratinocytes through HSD3B1. Consistent with our findings in cells, HSD3B1 expression is elevated in the skin of AD patients and can be restored by treatment with the IL-4Rα monoclonal antibody, Dupilumab. Androgens are also elevated in a mouse model of AD, though the mechanism in mice remains unclear. Our findings illuminate a connection between type 2 immunity and sex steroid hormone synthesis in the skin and suggest that abnormalities in sex steroid hormone synthesis may underlie the disrupted skin barrier in AD. Furthermore, targeting sex steroid hormone synthesis pathways may be a therapeutic avenue to restoring normal skin barrier function in AD patients.
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http://dx.doi.org/10.1073/pnas.2100749118DOI Listing
September 2021

[Cutaneous leishmaniasis in Germany-still a travel-related disease].

Hautarzt 2021 Aug 30. Epub 2021 Aug 30.

Hochschulklinik für Dermatologie, Venerologie und Allergologie, Immunologisches Zentrum, Städtisches Klinikum Dessau, Medizinische Hochschule Brandenburg Theodor Fontane und Fakultät für Gesundheitswissenschaften Brandenburg, Auenweg 38, 06847, Dessau, Deutschland.

Cutaneous leishmaniasis is an infectious disease caused by several Leishmania species. It is transmitted to humans by the bite of the infected female phlebotomus sandfly. Today, more than 1 billion people in leishmaniasis endemic areas are at risk of infection. More than 1.5 million new cases of cutaneous leishmaniasis occur every year. On the basis of two cases, we show that cutaneous leishmaniasis is still an imported tropical disease in Germany. However, due to the increasing intercontinental travel, cases may increase. Therefore, cutaneous leishmaniasis should be considered in the differential diagnosis in patients with nonhealing wounds, ulcers, papules or nodules and the corresponding travel history.
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http://dx.doi.org/10.1007/s00105-021-04890-6DOI Listing
August 2021

[Erratum to: Clinical, pathology-associated and molecular biomarkers of hidradenitis suppurativa/acne inversa].

Hautarzt 2021 Sep;72(9):842

Hidradenitis Suppurativa Foundation e. V., Dessau, Deutschland.

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http://dx.doi.org/10.1007/s00105-021-04878-2DOI Listing
September 2021

Efficacy and Safety of Bimekizumab in Moderate to Severe Hidradenitis Suppurativa: A Phase 2, Double-blind, Placebo-Controlled Randomized Clinical Trial.

JAMA Dermatol 2021 Aug 18. Epub 2021 Aug 18.

UCB Pharma, Slough, United Kingdom.

Importance: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high burden for patients and limited existing therapeutic options.

Objective: To evaluate the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin 17A and 17F in individuals with moderate to severe HS.

Design, Setting, And Participants: This phase 2, double-blind, placebo-controlled randomized clinical trial with an active reference arm was performed from September 22, 2017, to February 21, 2019. The study included a 2- to 4-week screening period, a 12-week treatment period, and a 20-week safety follow-up. Of 167 participants screened at multiple centers, 90 were enrolled. Eligible participants were 18 to 70 years of age with a diagnosis of moderate to severe HS 12 months or more before baseline.

Interventions: Participants with HS were randomized 2:1:1 to receive bimekizumab (640 mg at week 0, 320 mg every 2 weeks), placebo, or reference arm adalimumab (160 mg at week 0, 80 mg at week 2, and 40 mg every week for weeks 4-10).

Main Outcomes And Measures: The prespecified primary efficacy variable was the proportion of participants with a 50% or greater reduction from baseline in the total abscess and inflammatory nodule count with no increase in abscess or draining fistula count (Hidradenitis Suppurativa Clinical Response [HiSCR] at week 12. Exploratory variables included proportion achieving a modified HiSCR with 75% reduction of HiSCR criteria (HiSCR75) or a modified HiSCR with 90% reduction of HiSCR criteria (HiSCR90), change in Patient's Global Assessment of Pain, and Dermatology Life Quality Index total scores.

Results: Eighty-eight participants received at least 1 dose of study medication (61 [69%] female; median age, 36 years; range, 18-69 years). Seventy-nine participants completed the study, including safety follow-up. Bimekizumab demonstrated a higher HiSCR rate vs placebo at week 12 (57.3% vs 26.1%; posterior probability of superiority equaled 0.998, calculated using bayesian analysis). Bimekizumab demonstrated greater clinical improvements compared with placebo. Improvements in the International Hidradenitis Suppurativa Severity Score (IHS4) were seen at week 12 with bimekizumab (mean [SD] IHS4, 16.0 [18.0]) compared with placebo (mean [SD] IHS4, 40.2 [32.6]). More bimekizumab-treated participants achieved positive results on stringent outcome measures compared with placebo. At week 12, 46% of bimekizumab-treated participants achieved HiSCR75 and 32% achieved HiSCR90, whereas 10% of placebo-treated participants achieved HiSCR75 and none achieved HiSCR90; in adalimumab-treated participants, 35% achieved HiSCR75 and 15% achieved HiSCR90. One participant withdrew because of adverse events. Serious adverse events occurred in 2 of 46 bimekizumab-treated participants (4%), 2 of 21 placebo-treated participants (10%), and 1 of 21 adalimumab-treated participants (5%).

Conclusions And Relevance: In this phase 2 randomized clinical trial, bimekizumab demonstrated clinically meaningful improvements across all outcome measures, including stringent outcomes. Bimekizumab's safety profile was consistent with studies of other indications, supporting further evaluation in participants with HS.

Trial Registration: ClinicalTrials.gov Identifier: NCT03248531.
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http://dx.doi.org/10.1001/jamadermatol.2021.2905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374742PMC
August 2021
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