Publications by authors named "Georgios Nikolakis"

31 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

LAight® Therapy Significantly Enhances Treatment Efficacy of 16 Weeks of Topical Clindamycin Solution in Hurley I and II Hidradenitis Suppurativa: Results from Period A of RELIEVE, a Multicenter Randomized, Controlled Trial.

Dermatology 2021 Sep 14:1-11. Epub 2021 Sep 14.

Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland.

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory, burdensome skin disease where medical first-line treatment is still limited to long-term, topical and/or systemic antibiotics. The RELIEVE study aimed at evaluating the efficacy of LAight® therapy - a combination of intense pulsed light and radiofrequency - as an adjunct treatment to first-line therapies in Hurley stage I and II HS.

Methods: The RELIEVE study was performed as a two-period multicenter randomized controlled trial with blinded assessment. For period A from week 0 to week 16, the 88 participating subjects were randomized into either an intervention group (IG) or a control group (CG). The IG received topical clindamycin 1% solution combined with 8 additional bi-weekly treatments with LAight® therapy. The CG was treated with topical clindamycin 1% solution only. After 16 weeks, patients entered open-label period B and both groups were treated exclusively with LAight® therapy for an additional 16 weeks (8 sessions). The primary efficacy endpoint was the change in International Hidradenitis Suppurativa Score System (∆IHS4) at week 16 to baseline. Secondary endpoints were DLQI, HiSCR, Pain-NRS, and HADS.

Results: In total, from the 88 patients enrolled in RELIEVE, 81 patients were included in the endpoint analysis after period A. After 16 weeks of treatment, the ∆IHS4 of the group treated with the combination of LAight® therapy and topical clindamycin 1% solution was -7.2 ± 6.7 (-60.0%), which was significantly higher in magnitude than the ∆IHS4 in the group treated with clindamycin 1% solution alone (-1.8 ± 5.6, -17.8%, p < 0.001). Secondary endpoints, including other clinical scores as well as patient-reported outcomes, confirmed that the efficacy of the combined treatment was superior to monotherapy.

Conclusion: The results of the primary endpoint analysis of period A of the RELIEVE study show that the combined therapy with LAight® and topical clindamycin 1% solution, resulted in a significantly higher decrease in disease severity and an improvement of quality of life in comparison to topical clindamycin 1% solution monotherapy. Treatment was well tolerated, and side effects were all mild and transitory. These data speak for the implementation of the combined treatment as a first-line therapy in Hurley stage I and II HS. LAight® therapy as long-term monotherapy (results from period B), will be analyzed in a consecutive paper.
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http://dx.doi.org/10.1159/000518540DOI Listing
September 2021

Experimental Intestinal Stenosis Alters Crohn's Disease-Like Intestinal Inflammation in Ileitis-Prone Mice.

Dig Dis Sci 2021 Aug 4. Epub 2021 Aug 4.

2nd Department of Surgery, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, Vasilissis Sofias Ave. 76, 11528, Athens, Greece.

Background: Clinical observations indicate that mechanical factors contribute to the expression or recurrence of Crohn's disease. We investigated whether the creation of an intestinal stenosis could alter the severity of the expected Crohn-like ileitis, in a Crohn's disease animal model, the TNF mouse.

Methods: Thirty-six, 6-weeks-old TNF mice, were divided into 3 intervention groups: triple suture, single suture and sham. In the terminal ileum, in the first group, a triple suture stenosis was created, whereas, in the second, a loose suture was placed. Same triple-suture stenosis was performed on twelve wild type mice. All animals were sacrificed at 6 weeks post-operatively and the ileum parts were evaluated histopathologically. A summative total ileitis score was applied in each sample using a bespoke semiquantitative histological scoring system for the Crohn-like changes.

Results: The triple suture stenosis induced significant muscular hypertrophy proximal to interventional site which was more prominent in TNF than wild type mice. In triple suture group, the total ileitis score was significantly increased proximal to the intervention as compared to the single suture (P: 0.004) and the sham groups (P: 0.013). The total ileitis score distally, was unaffected, regardless of the experimental intervention. Intestinal stenosis did not induce intestinal inflammation in wild type mice.

Conclusion: The creation of a stenosis in the terminal ileum of TNF mice alters Crohn-like inflammation. We assume that mechanical forces, such as intraluminal pressure, may contribute as important co-factors to the pathophysiology of Crohn's disease in genetically predisposed subjects.
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http://dx.doi.org/10.1007/s10620-021-07161-5DOI Listing
August 2021

Metabolic Disorders/Obesity Is a Primary Risk Factor in Hidradenitis Suppurativa: An Immunohistochemical Real-World Approach.

Dermatology 2021 Jul 22:1-9. Epub 2021 Jul 22.

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

Background: Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results.

Objectives: To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients.

Methods: Lesional skin specimens deriving from two groups of HS patients (BMI >30 and smokers, n = 12 vs. BMI <30 and non-smokers, n = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation.

Results: Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference.

Conclusions: The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected.
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http://dx.doi.org/10.1159/000517017DOI Listing
July 2021

Target molecules for future hidradenitis suppurativa treatment.

Exp Dermatol 2021 Jun;30 Suppl 1:8-17

European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany.

The registration of the tumour necrosis factor-α inhibitor adalimumab in 2015 was a major step forward in the treatment of hidradenitis suppurativa/acne inversa (HS). However, it soon became evident that the effectiveness of adalimumab in daily practice was highly variable. A significant unmet medical need of HS patients remained, and the search for novel therapeutic targets was intensified. During the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference, reknown international HS investigators virtually presented and discussed the published data on these potential target molecules for future HS treatment. This article addresses the most promising molecules currently under investigation from a pathophysiological and clinical point of view. With phase III trials ongoing, the anti- interleukin (IL)-17 biologics bimekizumab and secukinumab are in the most advanced stage of clinical development showing promising results. In addition, targeting IL-1α with bermekimab has shown encouraging results in two clinical trials. Directing treatment at neutrophil recruitment and activation by targeting IL-36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending. In contrast to in situ evidence, Complement 5a (C5a) and C5a receptor blockade have only shown greater clinical benefit in patients with severe HS. Inhibition of Janus kinase (JAK) 1 signalling in HS showed clinical efficacy only in the highest dosage, highlighting that careful surveillance of the balance between safety and efficacy of JAK inhibition is warranted. Overall, clinical efficacies of all novel treatments reported so far are modest. To guide drug development, more and better-defined translational data on the pathogenesis of this severe and enigmatic inflammatory skin disease are required.
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http://dx.doi.org/10.1111/exd.14338DOI Listing
June 2021

3D-SeboSkin Model for Human ex vivo Studies of Hidradenitis Suppurativa/Acne Inversa.

Dermatology 2021 Jun 2:1-8. Epub 2021 Jun 2.

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

Background: Hidradenitis suppurativa/acne inversa (HS) is a chronic, recurrent inflammatory skin disease. Its pivotal pathogenetic event is believed to be the occlusion of the hair follicle generating a perifollicular lympho-histiocytic inflammation. However, knowledge of the exact HS pathogenesis requires further research.

Objective: To develop a human HS model applicable in preclinical research which could help to understand the pathophysiology of HS and to determine the action of therapeutic candidates.

Methods: The 3D-SeboSkin technology was applied to maintain explants of involved and uninvolved skin of HS patients ex vivo for 3 days. Detection of differential expression of previously detected HS biomarkers was performed by immunohistochemistry in a group of female patients (n = 9, mean age 37.2 ± 8.4 years).

Results: The application of the 3D-SeboSkin model preserved the structural integrity of lesional and perilesional HS skin ex vivo, as previously described for healthy skin. Moreover, the HS 3D-SeboSkin setting maintained the differential expression and pattern of several HS biomarkers (S100A9, KRT16, SERPINB3) in epidermal and dermal tissue and the appendages.

Conclusion: We have validated HS 3D-SeboSkin as a reproducible, human model, which is appropriate for preclinical lesional and perilesional HS skin studies ex vivo.
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http://dx.doi.org/10.1159/000515955DOI Listing
June 2021

Prevalence of Hidradenitis Suppurativa: A Systematic Review and Meta-regression Analysis.

JAMA Dermatol 2021 Aug;157(8):924-931

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

Importance: Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are scarce data regarding the prevalence of HS.

Objective: To estimate overall HS prevalence.

Data Sources: This review and meta-regression analysis was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The academic search included PubMed, Cochrane registry, ClinicalTrials.gov, and evidence by NHS UK and Trip databases from inception through May 2020. To analyze HS prevalence, only cross-sectional studies or baseline assessments of longitudinal cohorts using census-based surveys or probabilistic and nonprobabilistic epidemiologic methods were considered. The search terms were (prevalence OR incidence OR epidemiology) AND (hidradenitis suppurativa OR acne inversa OR Verneuil's disease). No language restriction was applied.

Study Selection: Original investigations that reported HS prevalence were included. After exclusion criteria were applied, 17 studies qualified for qualitative analysis, but only 16 studies were quantitatively assessed.

Data Extraction And Measures: Two reviewers extracted data by age, diagnostic criteria, presence of any comorbidity, sample sizes, continent/location, sex, and other characteristics. Assessment of bias risk used the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.

Main Outcomes And Measures: Hidradenitis suppurativa prevalence (with 95% CI) among the overall population and among subgroups. Between-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).

Results: In 16 quantitatively assessed studies included, prevalence estimates were reported only from Western European and Scandinavian countries, the US, and Australia. Meta-analysis with random effects, after adjusting for publication bias in the prevalence estimates, revealed a 0.40% prevalence (95% CI, 0.26%-0.63%) for HS. Studies based on clinical samples revealed a higher pooled prevalence of HS (1.7%) than population-based studies (0.3%).

Conclusions And Relevance: The findings of this systematic review and meta-regression analysis may help facilitate policy formulation, channeling funding and guiding principles for better disease diagnosis using universal valid tools and management.
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http://dx.doi.org/10.1001/jamadermatol.2021.1677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156162PMC
August 2021

Quality-of-Life Impairment among Patients with Hidradenitis Suppurativa: A Cross-Sectional Study of 1795 Patients.

Life (Basel) 2021 Jan 8;11(1). Epub 2021 Jan 8.

Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland.

The chronic, inflammatory skin disorder hidradenitis suppurativa (HS) is associated well documented negative influences on patients' quality of life (QoL). The aim of this study was to present more robust data on patients' QoL impairment by demographic data and its correlation with well-known HS risk factors on a cohort of 1795 German patients. The instrument used for measuring QoL in this study was the Dermatology Life Quality Index (DLQI). Overall, patients reported a very large effect of HS on their QoL (mean DLQI: 13.2 ± 8.1 points), and 22% of the analyzed population even reported to consider the effect as extremely large. Women tended to experience significantly higher impairment than men ( < 0.001). QoL impairment correlated positively with pain (r = 0.581, < 0.001), HS severity (measured by the International Hidradenitis Suppurativa Severity Score System (IHS4)) as well as Hurley. Neck involvement tended to decrease QoL significantly more than any other location (14.7 ± 8.3 points). This study confirms the enormous influence of HS on patients' QoL in a large cohort. Knowledge of QoL impairment in such patients is crucial for proper understanding and holistic management of this disease.
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http://dx.doi.org/10.3390/life11010034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828046PMC
January 2021

Pain in Hidradenitis Suppurativa: A Cross-sectional Study of 1,795 Patients.

Acta Derm Venereol 2021 Jan 5;101(1):adv00364. Epub 2021 Jan 5.

Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, PL-51-165 Wrocław, Poland.

Hidradenitis suppurativa is a chronic, inflammatory skin disorder that affects the pilosebaceous unit of the intertriginous body areas. Pain is one of the most important problems in patients with hidradenitis suppurativa. The aim of this study, which included 1,795 patients, was to evaluate the prevalence and characteristics of pain. The intensity of pain was assessed with a numerical rating scale. In addition, pain intensity was correlated with various clinical features. Pain was reported by 83.6% of subjects. The majority of patients (77.6%) experienced mild pain; women and smokers tended to experience more intense pain. Pain intensity was greater in patients with multiple affected skin areas and correlated positively with the number of those affected areas (r = 0.151, p < 0.001). There was no difference in pain intensity between affected locations. The worst pain was observed in the patients with the most severe disease and it would weaken significantly along with the severity of hidradenitis suppurativa (assessed using the Hurley staging system and the International Hidradenitis Suppurativa Severity Score System).
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http://dx.doi.org/10.2340/00015555-3724DOI Listing
January 2021

[Persistent, unilateral eczema of the nipple in a man].

Hautarzt 2021 Jul;72(7):615-618

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.

A 69-year-old man presented with a 12-month history of unilateral eczematous changes of the left nipple and areola without any signs of systemic inflammation. His main complaints were mild, intermittent itching, and occasionally local pain or burning. An external initial treatment with topical corticosteroids combined with disinfectants/antibiotics did not lead to an improvement. Triggering factors or any other conditions that could affect the diagnosis could not be detected. Histopathological examination of a biopsy from the left nipple performed at admission confirmed the suspected diagnosis of Paget disease. Radical left breast mastectomy was performed and the patient is under regular follow-up.
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http://dx.doi.org/10.1007/s00105-020-04724-xDOI Listing
July 2021

What causes hidradenitis suppurativa ?-15 years after.

Exp Dermatol 2020 12;29(12):1154-1170

European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany.

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30-April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy." (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as "the only inflammatory skin disease than can be healed". This anniversary article of 43 research-performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future.
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http://dx.doi.org/10.1111/exd.14214DOI Listing
December 2020

Phenotypes and Pathophysiology of Syndromic Hidradenitis Suppurativa: Different Faces of the Same Disease? A Systematic Review.

Dermatology 2021 17;237(5):673-697. Epub 2020 Sep 17.

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

Background: There is growing evidence that (certain) hidradenitis suppurativa (HS) comorbidities comprise syndromes including HS as a key cutaneous manifestation. These apparently autoinflammatory syndromes and their diagnostic delay might have detrimental effects on affected patients.

Methods: A systematic review was performed on the databases MEDLINE, EMBASE, and CENTRAL utilizing a standardized extraction form according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Sixty-four eligible articles on syndromic HS were retrieved. The identified syndromes included already described ones (pyoderma gangrenosum-acne-suppurative hidradenitis, pyogenic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, psoriatic arthritis-pyoderma gangrenosum-acne-suppurative hidradenitis, pyoderma gangrenosum-acne vulgaris-hidradenitis suppurativa-ankylosing spondylitis, synovitis-acne-pustulosis-hyperostosis-osteitis) and further novel symptom constellations. Cutaneous signs, including HS lesions, usually precede signs from other organs. The cutaneous signs of a considerable proportion of patients appear refractory to conventional treatment, and monotherapy with biologics does not suffice to sustain remission.

Conclusion: The results are subsequently discussed with focus on the pathophysiology and treatment of the detected syndromes. The dermatologist's role in the precise diagnosis and early treatment administration of HS is pivotal. The purpose of the treatment should be the effective prevention or delay of the autoinflammatory march and its irreversible consequences.
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http://dx.doi.org/10.1159/000509873DOI Listing
September 2020

Experimental Models of Partial Intestinal Obstruction in Young Mice: Establishment, and Evaluation.

J Surg Res 2020 08 10;252:206-215. Epub 2020 Apr 10.

Second Department of Surgery, National and Kapodistrian University of Athens, Medical School, Aretaieion University Hospital, Athens, Greece.

Background: Partial small bowel obstruction (SBO) is a common, potentially hazardous, surgical entity caused by numerous factors in humans. A number of techniques have been reported as efficient to simulate partial SBO in murine models. However, there is little data concerning their long-term survival. Our study presents a novel technique and evaluates its long-term efficiency compared with other commonly used techniques.

Materials And Methods: Sixty C57BL/6 mice aged 6 to 8 wk were randomly divided into five intervention groups: ligation, intestinal ring, partial ligation, microclips, and the novel triple suture technique. The ring groups were subdivided into narrow, medium, and wide ring and partial ligation groups were subdivided at 1/3, 1/2, and 2/3 of the lumen. Survival cutoff time was set at 4 wk. Animals were then euthanized and small bowel muscle layer thickness was histopathologically evaluated.

Results: None of the animals of the ligation and the ring groups reached the cutoff survival time. The mortality rate of the partial ligation and the microclips groups at the 4-week period were 33.3% and 0%, respectively. However, elimination of the performed intervention was revealed at the time of euthanasia and no alterations of the muscle layer were revealed at histopathology. The "triple suture" group had a survival rate of 90% until euthanasia and the sutures were apparent in all cases. Macroscopic evaluation showed small to mild proximal lumen dilatation in 6 of 10 animals. Histopathological evaluation of the specimens confirmed the partial obstruction.

Conclusions: The "triple suture" technique is a new, robust, reliable, and inexpensive technique for experimental long-standing partial SBO, with very low mortality.
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http://dx.doi.org/10.1016/j.jss.2020.03.007DOI Listing
August 2020

Low Prevalence of GSC Gene Mutations in a Large Cohort of Predominantly Caucasian Patients with Hidradenitis Suppurativa.

J Invest Dermatol 2020 10 3;140(10):2085-2088.e14. Epub 2020 Mar 3.

Laboratory of Genetic Skin Diseases, INSERM UMR1163 Imagine Institute, Paris, France; Paris University, Paris, France; European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany; Department of Genetics, Necker-Enfants Malades Hospital, AP-HP, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2019.10.025DOI Listing
October 2020

When the skin is in the center of interest: An aging issue.

Clin Dermatol 2019 Jul - Aug;37(4):296-305. Epub 2019 Apr 30.

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

The skin represents the first bearer of marks of time as well as an easily accessible model for the assessment and determination of the involved molecular mechanisms. The deterioration of important skin functions due to intrinsic and extrinsic aging leads to clinical manifestations, which mirror several internal age-associated diseases, such as neurodegenerative, cardiovascular, skeletal, and endocrine/metabolic skin diseases. Current molecular data indicate that skin aging, especially intrinsic aging, mirrors age-related deficiencies in the entire human body. These data and the development of new biologic technologies highlight the importance of the skin in aging research and should enable future interdisciplinary projects on internal diseases, which could barely have been performed until recently due mainly to the lack of respective tissue.
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http://dx.doi.org/10.1016/j.clindermatol.2019.04.004DOI Listing
January 2020

Evaluating patients' unmet needs in hidradenitis suppurativa: Results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project.

J Am Acad Dermatol 2020 Feb 3;82(2):366-376. Epub 2019 Jul 3.

Department of Dermatology, Venereology and Allergology, Wrocław Medical University, Wrocław, Poland.

Background: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy.

Objective: To evaluate unmet needs from the perspective of HS patients.

Methods: Prospective multinational survey of patients between October 2017 and July 2018.

Results: Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% [n = 798]) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively.

Limitations: Data were self-reported. Patients with more severe disease may have been selected.

Conclusion: HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.
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http://dx.doi.org/10.1016/j.jaad.2019.06.1301DOI Listing
February 2020

Is There a Role for Antiandrogen Therapy for Hidradenitis Suppurativa? A Systematic Review of Published Data.

Am J Clin Dermatol 2019 Aug;20(4):503-513

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Auenweg 38, 06847, Dessau, Germany.

Background: Hidradenitis suppurativa/acne inversa is a disease with deep-seated chronic painful nodules, abscesses, and draining sinus tracts, which manifests on the apocrine gland-rich skin areas of the body. Observational findings demonstrate that the disease usually appears after puberty, exhibits pre-menstrual flares in women, improves in pregnancy, and worsens post-partum, which indicates a role of hormones and particularly of androgens in its pathophysiology. Because increased androgen levels in serum have not been widely reported, an end-organ androgen hypersensitivity has been postulated.

Objective: The aim of this systematic review was to identify and present evidence for antiandrogen therapeutic options for the treatment of hidradenitis suppurativa/acne inversa.

Methods: A literature search was conducted in different medical electronic databases using the keywords "hidradenitis", "suppurativa", "acne inversa", and "antiandrogen" on 1 December, 2018. The main therapeutic options were subsequently used as separate keywords with the disease terms in a separate search.

Results: The main therapeutic options yielded were cyproterone acetate, spironolactone, finasteride, and metformin. One randomized controlled crossover trial and seven case series were identified following use of a standard extraction form for eligibility.

Conclusion: The existing studies do not allow a robust evidence-based recommendation for the use of antiandrogens in the treatment of hidradenitis suppurativa/acne inversa. Further randomized controlled trials are needed to define the role of hormonal treatment as an alternative or concomitant therapy together with antibiotics or biologics.
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http://dx.doi.org/10.1007/s40257-019-00442-wDOI Listing
August 2019

[Enlarged mediastinal lymph nodes of a patient with malignant melanoma stage IV under pembrolizumab treatment].

Hautarzt 2019 Jun;70(6):443-446

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

A 40-year-old patient with malignant melanoma pT4bN0M1a stage IV (AJCC classification 2017) was treated with the PD-1/PD-L1 antibody pembrolizumab. Three months after treatment initiation the patient developed enlarged mediastinal lymph nodes despite the partial response of the cutaneous metastases. An elective lymph node extirpation was performed. The histopathological result was consistent with a sarcoid-like reaction. Treatment was discontinued and a pulse therapy with systemic steroids led to a significant remission of the lymphadenopathy. This side effect can manifest both during PD-1/PD-L1 antibody and CTLA-4 antibody therapy and should be included in the differential diagnosis of mediastinal lymphadenopathy.
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http://dx.doi.org/10.1007/s00105-019-4392-xDOI Listing
June 2019

Bacterial Colonization in Hidradenitis Suppurativa/Acne Inversa: A Cross-sectional Study of 50 Patients and Review of the Literature.

Acta Derm Venereol 2017 Apr;97(4):493-498

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.

It is unclear whether bacterial colonization in hidradenitis suppurativa/acne inversa (HS) comprises a primary cause, triggering factor or secondary phenomenon of the disease pathogenesis. Furthermore, the connection between certain bacterial species, the disease severity and its localization is unknown. Bacterial species were isolated from HS lesions to reveal a potential correlation with localization and disease severity. Ninety swab tests were prospectively obtained from 90 HS lesions of 50 consecutive patients. The material was cultured under aerobic and anaerobic conditions. The identified species were statistically correlated with Hurley stage and localization of the lesions. The most prevalent isolates were reported. Hurley stage significantly correlated with disease localization. Particular bacterial species were associated with "extended" disease and Hurley III stage with the detection of both aerobic and anaerobic bacteria and with a higher number of species. The presence of bacterial species is dependent on the local milieu, which correlates with the localization of the disease, its clinical manifestations and its extension.
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http://dx.doi.org/10.2340/00015555-2591DOI Listing
April 2017

Skin steroidogenesis in health and disease.

Rev Endocr Metab Disord 2016 09;17(3):247-258

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Auenweg 38, 06847, Dessau, Germany.

The skin is an important extra-gonadal steroidogenic organ, capable of metabolizing various hormones from their precursors, as well as of synthesizing de novo a broad palette of sex steroids and glucocorticoids from cholesterol. In this manuscript, we review the major steroidogenic properties of human skin and we suggest steroidogenesis' impairment as a cardinal factor for various pathological conditions such as acne, rosacea, atopic dermatitis, and androgenic alopecia.
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http://dx.doi.org/10.1007/s11154-016-9390-zDOI Listing
September 2016

Hidradenitis suppurativa/Acne inversa: an endocrine skin disorder?

Rev Endocr Metab Disord 2016 09;17(3):335-341

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Auenweg 38, 06847, Dessau, Germany.

Hidradenitis suppurativa / acne inversa (HS) is a chronic inflammatory, debilitating skin disorder with a largely unknown etiology. However, many observations such as the typical onset of the disease after puberty, the female predominance, the pre-menstrual flare ups and the improvement during pregnancy suggest a contribution of endocrinological factors to the emergence of the disease. In addition, the reported efficacy of anti-androgen treatment on HS indicates a possible involvement of androgens in the pathogenesis. Furthermore, the common comorbidity with metabolic syndrome points to possible interactions between endocrinological and metabolic alterations in the development of HS. Taking into account the endocrine functions of the human skin, several studies investigated the effects of hormones and the behavior of the pilosebaceous unit in the skin of patients with HS. In this review we describe the current view on the hormonal dysregulation and metabolic syndrome and their role in HS.
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http://dx.doi.org/10.1007/s11154-016-9366-zDOI Listing
September 2016

High Copy Numbers of β-Defensin Cluster on 8p23.1, Confer Genetic Susceptibility, and Modulate the Physical Course of Hidradenitis Suppurativa/Acne Inversa.

J Invest Dermatol 2016 08 7;136(8):1592-1598. Epub 2016 May 7.

Genome Analysis, Leibniz Institute on Aging-Fritz Lipmann Institute, Jena, Germany.

Hidradenitis suppurativa/acne inversa (HS) has a multifactorial pathogenesis, with many patients reporting positive family history. Nine β-defensin genes (among them DEFB4 and DEFB103, encoding for proinflammatory mediators human β-defensin-2 and human β-defensin-3, respectively) exist as a cluster (DEFB) affected by copy number (CN). We hypothesized that CNs are greater in patients with HS and that they are linked to genetic susceptibility. CNs of DEFB were studied in two independent patient cohorts: 163 patients from Greece and 98 from Germany. CNs were greater in patients than control subjects in both studied cohorts. Carriage of more than six CNs was associated with a 7.53 odds ratio for HS in the Greek cohort and a 5.76 odds ratio for HS in the German cohort. The common odds ratio after meta-analysis was 6.72 (P < 0.0001). However, presence of fewer than six copies was linked with disease onset at an earlier age (P = 0.048), less frequent presentation of permanent purulence of the affected skin lesions (P = 0.036), and fewer skin localizations (P = 0.042). A robust genetic trait for susceptibility to HS is provided, and this is confirmed in two independent cohorts. Susceptibility arises from carriage of more than six DEFB copies, which interferes directly with the HS phenotype.
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http://dx.doi.org/10.1016/j.jid.2016.04.021DOI Listing
August 2016

Multiple HPV-Induced Squamous Cell Carcinomas on the Fingers of a Patient with Systemic Lupus Erythematosus: A Case and Review.

Case Rep Dermatol 2015 Sep-Dec;7(3):329-34. Epub 2015 Nov 19.

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.

Human papilloma virus (HPV) infection is documented to be involved in the development of epithelial malignancies, mostly in cervical cancer. Systemic lupus erythematosus (SLE) patients have an increased prevalence of such an infection. We report the case of a 55-year-old female SLE patient who developed multiple in situ squamous cell carcinomas on her fingers, after chronic HPV infection. HPV-33 DNA was isolated from the lesions. The purpose of this case presentation is to raise awareness about HPV-induced malignancies for this high-risk group and propose an early HPV vaccination to efficiently prevent such comorbidities.
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http://dx.doi.org/10.1159/000442017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677700PMC
December 2015

Endocrinologic Aspects of Hidradenitis Suppurativa.

Dermatol Clin 2016 Jan;34(1):45-9

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Auenweg 38, 06847 Dessau, Germany. Electronic address:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of unknown etiology. The role of hormones in HS remains unclear, but the observation of premenstrual flares, female predominance, and improvement during pregnancy suggest a hormonal/metabolic background. The reported positive effects of antiandrogen therapy supports a possible role of androgens. The predominant onset of the disease years after puberty may indicate a metabolic disorder. Obesity contributes significantly to HS pathogenesis; diabetes, dyslipidemia, the metabolic syndrome, and polycystic ovarian syndrome are among the commonest comorbidities. More studies are required to clarify a potential hormonal dysregulation in HS.
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http://dx.doi.org/10.1016/j.det.2015.08.005DOI Listing
January 2016

Disseminated refractory pyoderma gangraenosum during an ulcerative colitis flare. Treatment with infliximab.

J Dermatol Case Rep 2015 Sep 30;9(3):62-6. Epub 2015 Sep 30.

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany; ; Division of Evidenced Based Dermatology, Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany;

Background: Pyoderma gangraenosum is an immune-mediated, inflammatory, neutrophilic dermatosis of unknown etiology, which represents one of the extraintestinal manifestations of inflammatory bowel disease. It is a rare disease that occurs in less than 1% of patients with inflammatory bowel disease and with the same ratio in patients with Crohn's disease and ulcerative colitis.

Main Observations: A 36-year-old woman was diagnosed with ulcerative colitis 6 years before admission to our dermatology department with an acute disseminated pyoderma gangraenosum with mucosal involvement, during a flare of ulcerative colitis. Disease progression was interrupted by intravenous administration of the tumor necrosis factor-α inhibitor infliximab at 5 mg/kg at weeks 0, 2, and 6 (1st cycle) and every 8 weeks thereafter. Improvement of intestinal, skin and oral manifestations was evident already after the 1st cycle of treatment and has been maintained since (at least 16 months).

Conclusions: This case report is one of very few on disseminated pyoderma gangraenosum with oral involvement complicating ulcerative colitis, where infliximab was shown to have a rapid efficacy on skin, mucosal and bowel symptoms.
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http://dx.doi.org/10.3315/jdcr.2015.1206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619161PMC
September 2015

Bacteriology of hidradenitis suppurativa/acne inversa: A review.

J Am Acad Dermatol 2015 Nov;73(5 Suppl 1):S12-8

European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany; Institut Pasteur, Centre Médical, Service de Pathologie Infectieuse et Tropicale, Paris, France; Centre d'Infectiologie Necker-Pasteur, Paris, France.

Given that follicular papules and pustules, as well as nodules and abscesses, are the clinical hallmarks of hidradenitis suppurativa (HS), an infectious, bacterial pathway has been suspected in the pathogenesis of this chronic, inflammatory condition. Elucidating the behavior and role of bacterial species in HS and their interaction with cutaneous innate immunity will provide more insight into the pathophysiology of this condition. This review of prospective investigations suggests a synergistic relationship between impaired innate immunity and microbial factors in the etiology of HS.
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http://dx.doi.org/10.1016/j.jaad.2015.07.041DOI Listing
November 2015

Ex vivo human skin and SZ95 sebocytes exhibit a homoeostatic interaction in a novel coculture contact model.

Exp Dermatol 2015 Jul 4;24(7):497-502. Epub 2015 May 4.

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.

The sebaceous gland displays key functions of the human skin, such as hormone synthesis in situ, antimicrobial activity and participation to inflammatory responses. Consequently, there is an emerging need of advanced in vitro models to study complex interactions between the sebaceous gland and the other skin compartments. Despite the evolution of both full-skin organ culture and reconstructed three-dimensional skin models, no satisfactory solutions have been provided for the integration of sebaceous glands and/or sebaceous gland cells in those models, probably due to their problematic maintenance both in vitro and ex vivo. We have developed a coculture model of explant skin in direct contact with immortalized SZ95 sebocytes, which resulted in overall improved structural integrity of the epidermis, higher percentage of proliferating basal epidermal cells and reduced apoptosis of differentiating keratinocytes after 6 days, as detected by Ki67 and TUNEL staining, respectively. Furthermore SZ95 sebocytes exhibited morphological and biochemical signs of normal differentiation and lipid accumulation, while interleukin-6 expression in the supernatant of the cocultures was decreased in comparison with the control. The data provide evidence of a beneficial interaction between sebocytes and skin explants and provide the rationale for their integration in future three-dimensional skin models.
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http://dx.doi.org/10.1111/exd.12712DOI Listing
July 2015

Skin mirrors human aging.

Horm Mol Biol Clin Investig 2013 Dec;16(1):13-28

Abstract Aged skin exhibits disturbed lipid barrier, angiogenesis, production of sweat, immune functions, and calcitriol synthesis as well as the tendency towards development of certain benign or malignant diseases. These complex biological processes comprise endogenous and exogenous factors. Ethnicity also markedly influences the phenotype of skin aging. The theories of cellular senescence, telomere shortening and decreased proliferative capacity, mitochondrial DNA single mutations, the inflammation theory, and the free radical theory try to explain the biological background of the global aging process, which is mirrored in the skin. The development of advanced glycation end-products and the declining hormonal levels are major factors influencing intrinsic aging. Chronic photodamage of the skin is the prime factor leading to extrinsic skin aging. The deterioration of important skin functions, due to intrinsic and extrinsic aging, leads to clinical manifestations, which mirror several internal age-associated diseases such as diabetes, arterial hypertension and malignancies.
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http://dx.doi.org/10.1515/hmbci-2013-0018DOI Listing
December 2013

Skin and glucocorticoids: effects of local skin glucocorticoid impairment on skin homeostasis.

Exp Dermatol 2014 Nov;23(11):807-8

Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.

The role of skin as a de novo source of glucocorticoids and the importance of cutaneous glucocorticoidogenesis as a homeostatic mechanism in human skin is highlighted by Slominski et al. in a recently published issue. Impairment of glucocorticoidogenesis through noxious stimuli, such as UVB, can explain pathophysiology of skin diseases (e.g. rosacea). In addition to keratinocytes, melanocytes and fibroblasts, cutaneous adnexes also play a significant role as targets and sources of glucocorticoids, because they express most of the enzymes required for steroidogenesis. Glucocorticoids are also involved in the pathogenesis of acne lesions, affecting sebum production in vivo and in vitro. Certain steroidogenic enzymes, such as 11β-hydroxysteroid dehydrogenase, are upregulated in acne lesions. On this background, the paper by Slominski et al. provides further insights into dermatoendocrinology, with emphasis on the importance of an impairment of the skin's own hypothalamic-pituitary-adrenal-like axis in the pathophysiology of several skin diseases.
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http://dx.doi.org/10.1111/exd.12519DOI Listing
November 2014

Steroidogenesis in the skin: implications for local immune functions.

J Steroid Biochem Mol Biol 2013 Sep 19;137:107-23. Epub 2013 Feb 19.

Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address:

The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7Δ-steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases. This article is part of a Special Issue entitled 'CSR 2013'.
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http://dx.doi.org/10.1016/j.jsbmb.2013.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674137PMC
September 2013
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