Feb 10, 2016 - Volume 25 Supplement 2 February 2016 ..... Experimental Dermatology, 2016, 25 (Suppl. ...... Clinical characteristics and HS registration ..... Advantages of this method are: Not technically difficult, cheap and suitable as an office ...... anger in its different domains (experience, expression and control); FDLQI ...
Experimental Dermatology Volume 25 Supplement 2 February 2016
5th Conference of the EHSF 2016 February 10–12, 2016 Langenbeck-Virchow Haus, Berlin, Germany
Disclaimer This abstract book has been produced using author-supplied copy. Editing has been restricted to some corrections of spelling and style where appropriate. The publisher assumes no responsibility for any claims, instructions, methods or drug dosages contained in the abstracts. It is recommended that these are verified independently. The contents contained herein are correct at the time of printing and may be subject to change.
DOI: 10.1111/exd.12954
Abstracts
www.wileyonlinelibrary.com/journal/EXD
Orals Innovative research: from the bench to the bedside O01-1 A role of lipocalin-2 in acne inversa K. Wolk1,2, E. Witte1,2, A. Tsaousi1, K. Witte2,3, H.-D. Volk3,4, W. Sterry5, J. Wenzel6, S. SchneiderBurrus5 and R. Sabat1,2 1Department of Dermatology and Allergy and Institute of Medical Immunology, Psoriasis Research and Treatment Center, University Medicine Charite´, Berlin, Germany; 2Interdisciplinary Group of Molecular Immunopathology, Department of Dermatology and Allergy and Institute of Medical Immunology, University Medicine Charite´, Berlin, Germany; 3Berlin-Brandenburg Center for Regenerative Therapies, University Medicine Charite´, Berlin, Germany; 4Institute of Medical Immunology, University Medicine Charite´, Berlin, Germany; 5Department of Dermatology and Allergy, University Medicine Charite´, Berlin, Germany; 6Department of Dermatology and Allergy, University of Bonn, Bonn, Germany Acne inversa (AI)/Hidradenitis suppurativa is a chronic inflammatory skin disease with common onset in the second decade of life. It mainly affects the intertriginous skin of perianal, inguinal, and axillary body sites and leads to painful and disabling skin lesions including inflamed nodules, abscesses, and fistula. Furthermore, AI is frequently associated with metabolic alterations that might increase the risk of cardiovascular disorders. The AI pathogenesis is still not understood and biomarkers reflecting the inflammatory process are missing. We individually quantified the levels of 40 parameters including proteins and microRNAs in blood of AI patients. These analyses revealed lipocalin-2 (LCN2) as one of the most significantly upregulated mediators compared to blood of healthy participants. Accordingly, strongly elevated LCN2 expression was also found in AI lesions. Regarding the cellular sources of LCN2, we demonstrated that, beside immune cells, keratinocytes but not fibroblasts or endothelial cells expressed LCN2 after stimulation with pro-inflammatory cytokines like TNF-a. IL-17, which was also highly expressed in AI lesions, strengthened the TNF-alpha-induced LCN2 production in keratinocytes. Correspondingly, LCN2 levels positively correlated with TNF-a levels in blood. LCN2 blood levels also showed positive correlation with disease severity assessed by Sartorius score. In-depth analyses revealed a link between LCN2 blood levels and the number of regions with inflammatory nodes and fistulas, but not the scar numbers. No association between LCN2 and patient age, AI duration, or age at AI onset was detected. In addition to the known local role of LCN2 in macrophage activation and chronic inflammatory pain, we found evidences for its role in cardiovascular alterations as deduced from the correlation between LCN2 and both resistin and chemerin blood levels in AI patients. In summary, we demonstrate elevated LCN2 levels in lesions and blood of AI patients, shed light on their cellular sources, suggest their role in metabolic comorbidities, and recommend LCN2 as blood biomarker for AI disease activity.
O01-2 Serum amyloid A plasma levels as marker for cutaneous inflammation in acne inversa E. Witte1,2, A. Tsaousi2, C. Zelenak1, H.-D. Volk3,4, W. Sterry5, S. Schneider-Burrus5, K. Wolk1,2 and R. Sabat1,2 1Interdisciplinary Group of Molecular Immunopathology, Department of Dermatology and Allergy and Institute of Medical Immunology, University Medicine Charite´, Berlin, Germany; 2Department of Dermatology and Allergy and Institute of Medical Immunology, Psoriasis Research and Treatment Center, University Medicine Charite´, Berlin, Germany; 3Institute of Medical Immunology, University Medicine Charite´, Berlin, Germany; 4Berlin-Brandenburg Center for Regenerative Therapies, University Medicine Charite´, Berlin, Germany; 5Department of Dermatology and Allergy, University Medicine Charite´, Berlin, Germany Acne inversa (AI)/Hydradenitis supparativa is a chronic inflammatory skin disease characterized by nodular inflammation, abscesses and fistulae leading to excessive destruction and scarring of the skin. AI severely affects the physical and mental health of patients and is frequently associated with metabolic alterations that might increase their risk of cardiovascular disorders and reduce their life expectancy. The pathogenesis of AI is poorly understood. This study aimed at establishing an easy-to-use marker for assessing the cutaneous inflammation in AI. To this aim, we first individually quantified the expression of a broad range of cytokines in AI lesions and compared their levels with those in skin from healthy participants. These analyses revealed a strong expression of several cytokines including IL-1beta, IL-6, IL17A, and IL-22. Measurements of blood concentrations of selected cytokines demonstrated that lesional upregulation of IL-1beta, IL-6 and IL-22 was accompanied by elevated blood levels of these mediators. Although significantly elevated, however, these levels appeared to be too low for their use as biomarkers in daily routine. Therefore, we looked for markers that were synergistically induced by these cytokines. At this, serum amyloid A (SAA) was identified as such parameter, and its production was studied in details in vitro. Importantly, its blood levels in AI were strongly elevated in comparison to blood from healthy participants and positively correlated with IL-6 blood levels, supporting our in vitro findings. Interestingly, SAA blood levels also showed a significant inverse correlation with HDL-cholesterol levels, suggesting that SAA contributes to the cardiovascular comorbidities in AI patients. In summary, we propose SAA as blood biomarker of the inflammation activity in AI lesions.
O01-3 Circulating endothelial progenitor cells (EPCs) in hidradenitis suppurativa patients L. Matusiak, A. Batycka-Baran, A. Bieniek and J. C. Szepietowski Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland Background: Hidradenitis suppurativa (HS) is nowadays regarded as systemic disease, associated with metabolic syndrome. Some recent studies have also demonstrated an increased cardiovascular risk in patients with HS. Circulating endothelial progenitor cells (EPCs) play an integral role in the regulation and protection of the endothelium and in the maintenance of vascular homeostasis. Objective: This study was undertaken to determine the possible alterations in the number of EPCs in patients with HS compared to the controls. Methods: The number of EPCs, identified as CD133+/KDR+ cells, was determined with flow cytometry in peripheral blood of 25 HS patients and 31 controls. Results: The number of EPCs was significantly reduced in HS sufferers compared with controls (P < 0.0001). The mean number of EPCs within the control group was approximately three and half times lower. No statistical dependences were observed between EPCs count and disease duration, its severity (according to the Hurley grading system), smoking habits and BMI. It should be highlighted that except for HS, the presence of arterial hypertension and obesity were independent factors responsible for decrease in EPCs. Moreover, there was also significant additive interaction between HS and arterial hypertension in relation to EPC count. Conclusion: We demonstrate for the first time that EPCs count is reduced in blood of patients with HS. Thus, it may be assumed that the decreased number of EPCs contributes to higher cardiovascular risk in patients with HS and constitutes a mechanistic link between the inflammatory process and endothelial malfunction. However, further studies are required to confirm this hypothesis. It seems that EPCs may represent a potential therapeutic approach to reduce the increased cardiovascular risk in HS sufferers.
O01-4 Dysregulated cytokine expression in lesional and non-lesional skin in hidradenitis suppurativa C. Sweeney1, G. Kelly2, R. Hughes2, T. McGarry3, A. M. Tobin2 and B. Kirby2 1Education and Research Centre, St Vincents University Hospital, University College Dublin, Dublin, Ireland; 2St Vincent’s University Hospital, Dublin, Ireland; 3University College Dublin, Dublin, Ireland Hidradenitis suppurativa, (HS) is a relapsing, inflammatory disease characterised by recurrent abscesses, fistula formation and cribiform scarring in the axillary, inguinal, submammary and perineal areas. The exact aetiology of HS is unknown but a role for immune dysregulation has been proposed since HS is associated with Crohn’s disease and pyoderma gangrenosum, recognised conditions of immune dysfunction. Whilst the nature of the immune dysregulation in HS is unclear, recent studies have indicated a role of IL-17 and its associated cytokines in the disease. Aims: This study sought to determine the nature of the immune response in HS. Methods: Skin biopsies [lesional, perilesional (2 cm away) and uninvolved (10 cm away)] were obtained from HS patients and from healthy controls. The expression of various cytokines was determined by enzyme-linked immunosorbant assay (ELISA), flow cytometry and real time-PCR. Results: IL-17, IL-1b and TNF-a was enhanced in lesional skin of HS patients. In addition, IL-17 and IL-1b mRNA was enhanced in clinically normal perilesional skin. CD4+ T cells produced IL-17 in HS whilst CD11c+CD1a CD14+ were sources of IL-1b. Activated caspase-1 was detected in HS skin and was associated with an enhanced expression of NLRP3 and IL-18. Inhibition of caspase-1 decreased IL1b and IL-18 production suggesting that the caspase-1 pathway participates in IL-1b and IL-18 expression in HS. Abnormal cytokine expression was detected in perilesional and uninvolved skin which may suggest that subclinical inflammation is present in HS skin prior to the formation of an active lesion. Conclusion: This study demonstrates that CD4+ T cells produce IL-17 in HS and that the IL-17 pathway may be important in HS pathogenesis. CD11c+CD1a CD14+ are sources of IL-1b in HS, the production of which was shown to be mediated in part, via a caspase-1 dependent pathway. These results suggest that IL-17 and the caspase-1 associated cytokines IL-1b and IL-18 may play a role in the pathogenesis of HS. This study was funded by Abbvie and the British Skin Foundation.
O01-5 Effects of benzo(a)pyrene on lipid synthesis and inflammatory cytokines via aryl hydrocarbon receptor signal pathway on SZ95 sebocytes in vitro – the possible hint between cigarette smoking and hidradenitis suppurativa/ acne inversa Q. Ju1, T. Hu1 and C. C. Zouboulis2 1Dermatology, Shanghai Jiaotong University, Shanghai, China; 2 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany Scientific research question: Almost 90% of the patients with hidradenitis suppurativa/acne inversa (HS) has history of cigarette smoking, which is the most identified environmental pathogenetic factor of HS, but its mechanism is still unclear. Previous studies of HS pathology have proven the diminution and disappearance of sebaceous glands in patients with HS. Methodology: In this study, we determined the effects of benzo(a)pyrene (BaP), an important toxic compound of cigarette smoking, on lipidogenesis and inflammatory cytokine expression of SZ95 sebocytes in vitro. Findings: A concentration-dependent inhibitory effect on lipid synthesis from 10 8 to 10 5 M was found, and BaP (10 5 M) exerted a stimulatory activity on interleukin (IL)-6 secretion. These two effects were partially antagonistic after aryl hydrocarbon receptor (AhR) was silenced in SZ95 sebocytes. Furthermore, AhR expression was enhanced at mRNA level, while it was inhibited in protein level after exposure of SZ95 sebocytes to BaP (10 5 M) and the classical AhR downstream gene, cytochrome P450 1A1 (CYP1A1) was up-regulated at both mRNA and protein levels. Conclusion: This study demonstrates that BaP may have an inhibitory activity on lipidogenesis and stimulatory effect on inflammation (inhibition of IL-6) via the AhR signaling pathway, which is likely to be the possible mechanism of HS induction by cigarette smoking.
Immunology O02-1 Lymphoma development in HS E. Prens, A. Vossen, I. Deckers, M. van Doorn, H. van der Zee and A. Stubbs Departments of Dermatology and Bioinformatics, Erasmus MC, Rotterdam, The Netherlands Research question: Development of squamous cell carcinoma is a well-known long-term sequela of HS. Recently lymphoma has also been reported (up to 2%) as a comorbidity of HS.1 Because the diagnosis of stage IV large B-cell (plasmablastic) non-Hodgkin’s Lymphoma was made in a patient in our department we investigated the mechanism of lymphoma development in HS. Methodology: We analyzed the tumor of the patient together with RNA-Seq data from 25 lesional biopsy samples of otherwise healthy HS patients and compared them with matching samples from healthy volunteers (N = 10) for signs of B cell activation. Findings: In the lymphoma patient histology of the tumor showed a dense proliferation of tumor cells with mitotic figures and substantial nuclear debris. Immunohistochemistry showed that the tumor cells expressed CD38, CD138, CD79a, CD10, MUM-1, C-MYC and IgM. The proliferation marker MIB-1 (a Ki67 analog) was expressed by virtually a 100% of tumor cells and EBER also. Intermediate expression of BCL2, BCL6 was observed, but no expression of CD35, CD56 and HHV-8. We performed in situ hybridization with a break-probe for the C-MYC-, BCL2, BCL6 genes, which only showed a break in the C-MYC gene. RNA-sequencing on mRNA extracted from biopsies from lesional skin of otherwise healthy HS patients showed that each HS patient expressed a significant and dominant plasma cell and B cell signature together with strong induction of immunoglobulin genes. Conclusion: We previously reported on the occurrence of many B cells, plasma cells and even ectopic B cell follicles in hidradenitis suppurativa lesions. This is confirmed in the present study, where, in addition, we show at the mRNA level by RNA-sequencing strong B cell activation and proliferation together with strong upregulation of immunoglobulin genes. We postulate that the development of lymphoma in HS is based on the chronic immune activation and proliferation of these inflammatory B cells in HS lesions, which may lead to oncogenic mutations in B cells and plasma cells. This process is comparable with the development of squamous cell carcinoma in HS, which is based on the induction of oncogenic mutations due to chronic activation and proliferation of keratinocytes. Keywords: B-cel NHL, B cell and plasma cell activation, HS comorbidities. References: 1. Shlyankevich J, Chen AJ, Kimball AB et al. Hidradenitis suppurativa is a systemic disease with substantial comorbidity burden: a chart-verified case-control analysis. J Am Acad Dermatol. 2014 Dec;71(6):1144–50. 2. Dufour DN, Emtestam L, Jemec GB. Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease. Postgrad Med J. 2014 Apr;90(1062):216–21. 3. Ekstr€ om-Smedby K. Epidemiology and etiology of non-Hodgkin lymphoma-a review. Acta Oncol. 2006;45(3):258–71.
ª 2016 The Authors. Experimental Dermatology, 2016, 25 (Suppl. 2), 1–13 © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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4. Pavlovic S, Wiley E, Guzman G et al. Marjolin ulcer: an overlooked entity. Int Wound J. 2011 Aug;8(4):419–24. 5. Blombery PA, Wall M, Seymour JF. The molecular pathogenesis of B-cell non-Hodgkin lymphoma. Eur J Haematol. 2015 May 21. doi: 10.1111/ejh.12589.
O02-2 Hyperproduction of tumour necrosis factor-alpha from tissue macrophages of patients with Hurley III disease stage T. Kanni, A. Pistiki, M. Georgitsi and E. Giamarellos-Bourboulis 4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece Scientific research question: In a previous study (Kanni T et al., PLoS ONE, 2015) we have shown that ex vivo stimulation of circulating monocytes in patients with hidradenitis suppurativa (HS) is characterized by down-regulation of the production of tumour necrosis factor-alpha (TNFa). The present study aimed to investigate if this is compensatory to exaggerated production of TNFa by tissue macrophages. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 10 patients with HS and from another nine healthy volunteers matched for age and gender after whole blood centrifugation over Ficoll. PBMCs were incubated at a density of 5 9 106/ml for 1 day in RPMI supplemented with 2 mM glutamine at 37°C and 5% CO2. After 24 h of incubation non-adherent lymphocytes were discarded and adherent monocytes were grown into macrophages after addition in the growth medium of either fetal bovine serum (FBS) 10% or 10% individual’s own serum. Incubation was prolonged for another 4 days when culture supernatant was discarded and adherent macrophages were stimulated with RPIM1640 enriched with 2 mM glutamine without/with 10 ng/ml of lipopolysaccharide of Escherichia coli O55:B5. TNFa was measured in the supernatants of macrophages after 24 h of incubation by an immunosorbent assay. Results: Mean SE production of TNFa by macrophages developed with FBS of healthy controls, of patients with Hurley I/II stage and of patients with Hurley II stage after medium stimulation was 56.1 16.3, 146.0 126.0 and 60.0 26/3 pg/ml respectively. Respective production from macrophages developed with FBS after LPS stimulation was 688.0 240.0, 204.0 82.8 and 537.3 358.6 pg/ml. Respective production from macrophages developed with own serum after medium stimulation was 157.8 120.5, 48.0 28/0 and 38.0 18.0 pg/ml. Respective production from macrophages developed with own serum after LPS stimulation was 463.0 150.1, 292.0 185.7 and 1538.0 755.8 pg/ml (P = 0.019 vs controls; P = 0.047 vs Hurley I/II). Conclusions: Circulating monocytes that migrate to tissues of patients with Hurley II stage HS are transformed into macrophages overproducers of TNFa. This necessitates the presence of own patient serum.
O02-3 Cytokines as potential biomarkers for hidradenitis suppurativa D. A. Vekic1, J. Woods1 and G. D. Cains1,2 1Dermatology, Liverpool Hospital, Liverpool, NSW, Australia; 2 Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia Aims: Hidradenitis Suppurativa (HS) is a chronic autoinflammaoty disease manifesting in recurrent painful deep-seated nodules and abscesses with variable heterogenous phenotypic presentation. HS has profound physical and psychological consequences, affecting the patients’ quality of life and causing significant disability. The central concept underpinning HS is the inflammasome, first conceptualized by Jurg Tschoop in Switzwerland as a model for Interlukin-1beta (IL-1b) processing. This group of protein complexes recognize stimuli which control the production of proinflammatory cytokines that regulate important aspects of inflammation, tissue repair and tissue death. Assembly of the inflammasome is induced by dysregulation of endogenous (including notch receptor, gamma secretase and TNF-alpha polymorphisms; endogenous hormones; and insulin resistance) and exogenous (including smoking, visceral adiposity, dietary factors, and the microbiome) signals that result in IL-1b release. Tissue analysis of cytokines in patients affected with HS show high levels of IL-1b in involved and peripheral skin. HS would benefit from a specific biomarker for diagnosis, prognosis, comorbidity assessment, prediction of relapse, and for tailoring individual patient therapy. Given the complexity and heterogeneous nature of HS, it is unlikely that a single cytokine will meet all these criteria; and instead multiple biomarkers may represent a more realistic approach for the future of personalized medicine in HS. Methods: Over fifty HS patients were included in analysis of cytokine levels using a panel of the following cytokines: TNF-alpha, IL-1, IL-17, IL-8, IL-10. Cytokine levels were taken prior to commencement of any therapy, and at three-month intervals thereafter. Results: Majority of patients showed a decrease in cytokine levels over time with use of effective therapy. An initial spike in cytokine levels was noted in a number of patients after commencement of therapy, with most of these cases showing a fall in cytokine levels over time. Conclusions: Cytokines are potentially useful biomarkers in HS, and may effective in assisting diagnosis, prognosis, comorbidity assessment, prediction of relapse, and tailoring individual therapy.
Microbiology O03-1 Bacterial involvement in hidradenitis suppurativa/acne inversa G. Nikolakis1,2, A. Liakou1, S. Bonovas3, I. Karagiannidis1,2, H. Seltmann1, N. Bonitsis1, O. Join-Lambert4,5,6, A. Nassif2,6,7, S. Zolke-Fischer8, K. Langner8 and C. C. Zouboulis1,2 1Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany; 2 European Hidradenitis Suppurativa Foundation e.V, Dessau, Germany; 3Department of Pharmacology, National and Kapodistrian University of Athens, Athens, Greece; 4Sorbonne Paris Cite´, Universite´ Paris Descartes, Paris, France; 5Inserm U1151, e´quipe 11 “Physiopathologie des infections syste´miques”, Paris, France; 6Institut Pasteur, Centre Me´dical, Service de Pathologie Infectieuse et Tropicale, Paris, France; 7 Centre d’Infectiologie Necker-Pasteur, Paris, France; 8Dessau Medical Center, Institute for Clinical Chemistry and Microbiology, Dessau, Germany Introduction: Bacterial isolations and cultures from hidradenitis suppurativa/acne inversa (HS) lesions have been performed and reported over the last 20 years. A bacterial infection has been postulated but the exact pathogenic role of bacteria in HS has not yet been elucidated. Scientific research question: Correlation of diverse microbial species with HS, its extension and the involved localizations of the body. Methodology: Ninety swab tests were obtained non-invasively from 85 lesions of consecutive series of 50 patients in a prospective manner. Anaerobic and aerobic cultures of the specimens were performed and the identified bacterial species were statistically correlated with the Hurley stage of the disease and the localization of the lesions. Findings: Staphylococcus aureus, Prevotella bivia, Proteus mirabilis, Escherichia coli, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli and Prevotella disiens were the most prevalent isolates. Hurley stage significantly correlated with the localization of the disease. Isolation of particular species
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was associated with ‘extended’ disease. Hurley III stage was statistically associated with isolation of both aerobic and anaerobic bacteria and with higher number of species. Conclusion: Bacterial colonization may be implicated in the worsening of HS. The presence of bacterial species is dependent on the local milieu that correlates with the localization, the clinical manifestations and the extension of the disease.
O03-2 Prevotella and Porphyromonas spp. constitute the core microbiome of anaerobic hidradenitis suppurativa lesions H. Guet-Revillet1, J.-P. Jais2, H. Coignard-Biehler3, M. Delage4, O. Lortholary3, M.-N. Ungeheuer5, X. Nassif1, A. Nassif4 and O. Join-Lambert1 1Laboratoire de Microbiologie, Hoˆpital Necker-Enfants Malades, Paris Descartes University, Paris, France; 2De´partement de Biostatistiques et d’Informatique me´dicale, Hoˆpital Necker-Enfants Malades, Paris Descartes University, Paris, France; 3Service des Maladies Infectieuses et Tropicales, Hoˆpital Necker-Enfants Malades, Paris Descartes University, Paris, France; 4 Institut Pasteur, Centre Me´dical, Paris, France; 5Institut Pasteur, ICAReB, Paris, France Scientific research question: HS is a chronic inflammatory disease of the skin of unclear pathophysiology. Improvement or clinical remissions of the disease can be obtained using wide spectrum antibiotics, suggesting that inflammation in HS may be triggered by infectious factors. In a previous culture based study, we identified two microbiological profiles associated with HS lesions: (i) a pure or predominant culture of Staphylococcus lugdunensis and (ii) a polymorph anaerobic flora, frequently associated with milleri group streptococci (MGS) and anaerobic actinomycetes. The aim of this work was to better characterize the microbiology of HS lesions using high throughput sequencing. Methodology: 65 patients with active HS (30, 18 and 17 Hurley stage 1, 2 and 3 patients, respectively) were prospectively included in this study. 149 lesions (50 Hurley stage 1, 58 Hurley stage 2 and 41 Hurley stage 3) were sampled by biopsy or aspiration (n = 43) or swabbing (n = 106). 175 normal skin fold swabs were obtained as controls. All samples were cultured. The bacterial diversity and composition of 80 representative anaerobic lesions samples was compared to that of 88 controls by high throughput sequencing using the 454 Roche technology after 16S ribosomal gene libraries preparation. Findings: Bacterial cultures showed that the anaerobic and S. lugdunensis profiles were associated with 54 and 22% of Hurley stage 1 lesions, respectively. Only 2 lesions were sterile. Anaerobes were overrepresented in Hurley stage 2 and 3 lesions compared to control samples (97% vs 53%, respectively, P < 0.001), with a decreased prevalence and abundance of normal skin commensals. High throughput sequencing showed that four predominant anaerobic genera originating from the oropharyngeal and digestive commensal microflora were associated with HS lesions: Prevotella, Porphyromonas, Fusobacterium and Parvimonas spp. (92.5%, 95.2%, 56.3% and 65% of samples, respectively). Lesions microbiome did not depend on patients’ gender, familial history of HS, body mass index, and localization of lesions. However, the richness and bacterial diversity of lesions increased with the clinical severity and duration of the disease with a higher proportion of Fusobacterium and Parvimonas spp. (P < 0.05). MGS and Actinomycetes spp. were associated with anaerobes in 40% and 45% of cases (P < 0.001 vs controls). Conclusion: A vast majority of HS lesions is associated with a polymorph anaerobic microflora. Prevotella and Porphyromonas spp. are the most prevalent and abundant species, whereas Fusobacterium and Parvimonas spp. correlate with the clinical severity of the disease. These data suggest that these bacterial species may play a key role in the pathophysiology of the disease and provide a rationale for the efficacy of antibiotics in HS.
Endocrinology O04-1 Hidradenitis suppurativa/acne inversa (HS): an endocrine disorder? I. Karagiannidis, G. Nikolakis and C. C. Zouboulis Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disorder of unknown etiology. The role of hormones in pathogenesis of HS is still unclear, but the observation of premenstrual flare ups, female predominance and improvement during pregnancy indicate a metabolic background. The occurrence of the disease in a narrow age spectrum after puberty also suggests that endocrinological factors may play a role in HS pathogenesis. Furthermore, obesity is a well known exacerbating factor of HS and diabetes, dyslipidemia, metabolic syndrome, polycystic ovarian syndrome and thyreoid disease belong to the commonest comorbid disorders of HS. Metformin, an antidiabetic drug has been proposed as an effective treatment in patients with HS, who have not responded to standard therapies. Although its pathophysiology is still unclear, HS, similar to acne, is a disease of follicular plugging and subsequent inflammation. Based on this fact, endocrinological disorders associated with follicular diseases could be proposed to be involved in the pathophysiological pathway of HS. Moreover, the reported positive effects of anti-androgen therapy on HS support a possible involvement of androgens in the disease pathogenesis. Since the majority of patients with HS exhibit normal androgen levels, it has been proposed that the pathophysiology of the disease is associated with an enhanced peripheral conversion of androgens by the apocrine glands, introducing the idea of HS being a disease based in in situ hormonal dysregulation.
Genetics O05-1 Familial acne inversa, a genetic disease of c-secretase inversa impact keratinocyte proliferation and differentiation through Notch and PI3K-AKT signaling pathways B. Wang Chinese Academy of Medical Sciences and Peking Union Medical College, Institute of Dermatology, Hospital of Plastic Surgery, Beijing, China Acne inversa, or hidradenitis suppurativa is a chronic recurrent inflammatory skin disease. Previous studies proved that loss-of-function mutations of nicastrin (NCT), presenilin 1 (PS1) and presenilin enhancer 2 (PEN2), the genes encoding essential components of c-secretase (GS) complex are responsible for familial AI. In our recent studies, we collected 20 families and 50 sporadic individuals of AI in Chinese and performed mutation detection of c-Secretase (GS) with PCR and direct DNA sequencing. It was found that all patients from familiar AI had gene mutation of GS while non of individuals of sporadic patients had the mutation. Further analysis revealed that nicastrin (NCT) mutation in 17 families and 3 mutation of presenilin enhancer-2 (PEN2) in the other 3 families. Our results highlights the fact that NCT gene may play an important role in AI. Further study with microarray data revealed the impact of knockdown of NCT on cell proliferation and differentiationassociated biological processes and pathways in HaCaT cells. The potential anti-proliferative and prodifferentiating profiles of NCT may be mainly a consequence of its activation on Notch pathway and inhibition of PI3K-AKT pathway in human keratinocytes.
ª 2016 The Authors. Experimental Dermatology, 2016, 25 (Suppl. 2), 1–13 © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Abstracts
O05-2 Familial hidradenitis suppurativa: genetic analysis of an Australian kindred using a newly developed 41-gene autoinflammatory disease panel and whole exome sequencing D. A. Vekic1, J. Woods1 and G. D. Cains1,2 1Dermatology, Liverpool Hospital, Liverpool, NSW, Australia; 2 Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia Aims: Hidradenitis Suppurativa (HS) is a chronic autoinflammaoty disease manifesting in recurrent painful deep-seated nodules and abscesses with variable heterogenous phenotypic presentation. HS has profound physical and psychological consequences, affecting the patients’ quality of life and causing significant disability. Approximately one third of HS patients have shown to have a genetic basis to their disease; presenting early and with a positive family history. In familial cases, HS shows an autosomal dominant pattern of inheritance and appears to be genetically heterogeneous. The pathogenesis of HS appears to involve mutations in genes encoding for gamma secretase transmembrane complex which is composed of four essential subunits: presenilin, presenilin enhancer, nicastrin, and anterior pharynx defective 1. Gamma secretase targeted therapy is a potential new focus for the management of HS. The restoration of the Notch signaling pathway in these individuals could bring much anticipated relief to HS patients who suffer significant disabilities as a result of their chronic inflammatory condition. Further understanding of the genetic basis of HS is vital to establishing pathophysiological mechanisms underlying this debilitating disease. Methods: Five individuals (four affected and one unaffected) from a Caucasian pedigree affected with severe HS were recruited. All five individuals were clinically assessed and DNA was extracted from venous blood for genetic analysis. In collaboration with our international colleagues in Genova, Italy, a newly developed 41-gene panel responsible for autoinflammatory diseases was utilized. Whole exome sequencing (WES) was conducted for all individuals. Results: Initial results using a 41 gene panel responsible for autoinflammatory diseases indicated individual variants in each affected family member. There were no similarities in variants found, suggesting the lack of causative mutations among these 41 genes. Whole exome sequencing (WES) results are pending. Conclusions: Understanding of the genetic basis of HS is vital to establishing pathophysiological mechanisms underlying this debilitating disease.
O05-3 High copy numbers of beta-defensin cluster on 8p23.1 confer genetic susceptibility for hidradenitis suppurativa E. Giamarellos-Bourboulis1, M. Platzer2, I. Karagiannidis3, T. Kanni1, G. Nikolakis3, J. Ulrich4, M. Belutti5, H. Gollnick5, M. Bauer6, C. C. Zouboulis3 and K. Huse2 14th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2Genome Analysis, Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena, Germany; 3Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany; 4 Department of Dermatology and Allergiology, Harzklinikum Dorothea Christiane Erxleben, Quedlinburg, Germany; 5Department of Dermatology and Venereology, Otto-von-Guericke-University, Magdeburg, Germany; 6Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany Scientific research question: Hidradenitis suppurativa/acne inversa (HS) has multifactorial pathogenesis with many patients reporting positive family history. Nine beta-defensin genes (among them DEFB4 and DEFB103 encoding for pro-inflammatory mediators hBD-2 and hBD-3, respectively) exist as a cluster (DEFB) affected by copy number variations (CNs). We hypothesized that CNs are greater in HS and they are linked with genetic susceptibility. Methods: CNs of DEFB were studied by the paralog ratio test in genomic DNA of two independent patient cohorts: 163 from Greece and 98 from Germany. The study primary endpoint was the link of CNs with genetic susceptibility to HS. Results: CNs were greater in patients than controls in both studied cohorts. Carriage of more than 6 CNs was associated with 7.53 odds ratio for HS in the Greek cohort and 5.76 odd ratio for HS in the German cohort. The common odds ratio after meta-analysis was 6.72 (P < 0.0001). Conclusions: A robust genetic trait for susceptibility to HS is provided for the first time and this is confirmed in two independent cohorts. Susceptibility arises by carriage of more than 6 DEFB copies.
O05-4 Elucidating the pathogenesis of hidradenitis suppurativa/acne inversa C. C. Zouboulis1, A. Hossini1, N. G. Bonitsis1 and E. Makrantonaki1 1Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany Scientific question: Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease of the hair follicles, classically of the intertriginous areas. HS has been associated with smoking, obesity, increased risk of metabolic syndrome and a variety of co-morbid diseases, including inflammatory bowel diseases, spondylarthropathy and cardiovascular disorders. Therefore, this project planned to elucidate the pathogenesis of HS, identify signaling pathways responsible for the initiation of the disease and highlight any specific biomarkers which could act as new targets for treatment. Methodology: Whole genome gene profiling was employed in lesional and healthy skin obtained from European Caucasian female HS patients [mean age 37.4 8.5 years (n = 8)] using the Agilent array platform. The study was approved by the Ethics Committee of the Charite´ Universitaetsmedizin Berlin and was conducted according to the Helsinki Declaration. Findings: Amongst 1186 differentially regulated genes 704 showed an upregulation and 482 a downregulation in involved versus healthy skin of HS patients. Significantly regulated signaling pathways which may play a key role in the pathogenesis of HS were the atherosclerosis signaling, the LXR/RXR pathway, the aryl hydrocarbon receptor signaling, fatty acid oxidation, the cross talk between dendritic cells and natural killer cells, retinol biosynthesis, protein ubiquitination, IL-4, IL-6, IL-8, Il-10, IL-12, IL-15, IL-17 signaling, CREB signaling and tight junction signaling. Conclusion: Our data provide first evidence on the gene pathways in HS and highlight the major role of inflammation, metabolic and environmental factors in the pathogenesis of the disease.
Comorbid disorders O06-1 High prevalence of axial spondyloarthropathy in patients with hidradenitis suppurativa S. Schneider-Burrus1, E. Witte2,3, G. Diederichs4 and R. Sabat2,3,5 1Department of Dermatology and Allergy, University Hospital Charite´, Berlin, Germany; 2Interdisciplinary Group of Molecular Immunopathology, University Hospital Charite´, Berlin, Germany; 3Department of Dermatology and Allergy and Institute of Medical Immunology, Psoriasis Research and Treatment Center, University Hospital Charite´, Berlin, Germany; 4Department of Radiology, University Hospital Charite´, Berlin, Germany; 5Research Center Immunosciences, University Hospital Charite´, Berlin, Germany Aims: Hidradenitis suppurativa is a chronic inflammatory disease of terminal hair follicles, which affects the intertriginous skin of axillary, genitofemoral and perianal sites. It causes painful, fistulating sinuses with malodorous purulence and scars and is frequently accompanied by profound metabolic alterations. Since some chronic inflammatory diseases affecting epithelial tissues like psoriasis are
frequently associated with spondyloarthropathies (SpA) that strongly reduce the quality of life of respective patients, we asked for an association of HS and SpA. Methods: A prospective questionnaire-survey regarding the presence, degree and location of back pain was conducted in 100 HS patients. In order to identify the basic cause for back pain in HS patients, we evaluated magnetic resonance imaging (MRI) scans of the pelvis in 26 men and 20 women suffering from HS. Results: 71% of the interviewed HS patients stated suffering from back pain. 34% of them even reported about very frequent or permanent back pain. The evaluation of anamnestic and clinical parameters showed no differences in age at onset of HS, disease duration, BMI, or disease severity between HS patients without back pain, patients with occasional pain, and patients with very frequent or permanent back pain. Analyzing the MRI scans of the pelvis, typical changes indicative for SpA were found in a total of 56% of patients. 39% of HS patients showed characteristics of acute inflammation, consisting in various degrees of joint effusion, synovitis, erosions and subchondral oedema. Furthermore, MRI-scans of 33% of HS patients showed signs of chronic SpA activity at the sacroiliacal joints. These signs were various degrees of manifestation of subchondral sclerosis and widening or narrowing of the joint space as far as definitive ankylosis bilaterally. In most cases, acute or chronic alterations were of first grade. 15% of HS patients simultaneously presented signs of acute and chronic SpA. Significant differences between patients with and without SpA were not obvious regarding the following parameters: age at time of MRI, age at onset of HS, disease duration, smoking habits, and BMI. Furthermore, there was no correlation between these parameters and the degree of SpA. Conclusions: Our study demonstrates that SpA is very common among HS patients and that neither history nor clinical parameters of HS provide any hints for the presence of SpA. Furthermore, it strongly suggests that HS patients should be evaluated for SpA presence and affected patients should systemically treat (e.g. TNF-alpha blockers) in order to avoid chronic joint alterations.
O06-2 Inflammatory bowel disease is common in patients with hidradenitis suppurativa, but not a distinct phenotype H. van der Zee1, I. Deckers1, F. Benhadou2, M. Koldijk3, V. del Marmol2, B. Horvath3, J. Boer4 and E. Prens1 1Dermatology, Erasmus MC, Rotterdam, The Netherlands; 2Dermatology, Hoˆpital Erasme, Bruxels, Belgium; 3Dermatology, University Medical Center Groningen, Groningen, The Netherlands; 4 Dermatology, Deventer ziekenhuis, Deventer, The Netherlands Scientific research question: In Europe the prevalence of Hidradenitis suppurativa (HS) is approximately 1%. Inflammatory bowel disease (IBD) is a umbrella term for Crohn’s disease (CD) and ulcerative colitis (UC). IBD has an estimated prevalence between 0.4% and 0.7%. HS is a wellestablished comorbidity in IBD patients. Possibly up to 23% of IBD patients have comorbid HS as suggested by a questionnaire. However, the prevalence of IBD in patients with HS is unknown. Our primary aim is to determine the prevalence of IBD in patients with HS. Our Secondary aim is to determine if HS with associated IBD is a distinct HS phenotype. Methodology: For this multi-center cross-sectional study data were collected between 2007 and 2015 in the Departments of Dermatology. In the Netherlands at Erasmus Medical Center Rotterdam, Deventer Hospital and the University Medical Center Groningen and in Begium at Hoˆpital Erasme, Bruxels. The diagnosis HS was made based on the patients history of HS symptoms and physical examination. All HS patients were actively asked if they suffered from CD or UC. The affirmative responses were confirmed as IBD when the diagnosis IBD was made by a gastroenterologist based on endoscopy. Findings: Data were collected of 1100 HS patients, 337 males (30.6%) and 763 females (69.4%), with a mean age of 38.5 12.7 years. Most patients had Hurley Stage I (43.6%) or stage II (44.8%) and suffered from HS for a median period of 12.0 years (IQR: 5.0–21.0). In 36 out of 1100 HS patients the diagnosis IBD could be confirmed, resulting in a prevalence of 3.3% (95% CI, 2.2–4.3). Of these 36 HS-IBD patients, 27 suffered from CD (75.0%) and nine from UC (25.0%), resulting in a prevalence of 2.5% (95% CI, 1.5–3.4) and 0.8% (95% CI, 0.3–1.4) respectively. When comparing the clinical characteristics of 36 HS-IBD patients with the 1064 HS patients, we found that obesity was significantly less frequent among HS-IBD patients (13.9% vs 31.0%, P = 0.04). In addition, HS-IBD patients were more often affected in the genital area (44.4% vs 31.0%), whereas less frequently affected in the atypical body areas (19.4% vs 35.3%), however these differences were not significant. There was no difference in gender, family history for HS, disease severity, disease duration or smoking status. Conclusion: In this study we show a prevalence of 3.3% of IBD in patients with HS, which is four to eight times higher than in the general Northern European population. However it is not possible to clinically identify IBD patients by their HS phenotype. We therefore advisable to ask about abdominal complaints, such as recurrent abdominal pain and bloody stool, in all patients with HS. If IBD is suspected or patients have intersfincteric fistulas, an endoscopy is advisable to exclude IBD.
O06-3 Prevalence of pilonidal sinus disease in hidradenitis suppurativa patients F. Benhadou1, P. Guillem2 and V. Del Marmol1 1Department of Dermatology, Hoˆpital Erasme, Universite´ Libre de Bruxelles, Brussels, Belgium; 2Department of Surgery, Clinique du Val d’Ouest, Ecully, France Background and aims: As part, along hidradenitis suppurativa (HS), of the follicular occlusion triade and tetrade, pilonidal sinus disease (PSD) is a classical lesion associated with HS. Whether HSassociated PSD has specific characteristics has been rarely explored and specific data are by far imprecise. For example, its prevalence among HS patients has been reported with a very wide range from 10% to 60%, and frequently in small cohorts. The aim of the study is to evaluate PSD prevalence in a large cohort of HS patients and to identify whether this prevalence is influenced by gender and whether it appears before or after HS onset. Methods: Two prospectively-built databases of HS patients were used. The charts of HS patients followed from 2006 to 2015 were retrospectively reviewed and data were collected about gender, the presence of an associated SPD, and its onset as regards HS onset. Results: The charts of 653 patients were reviewed. There were 402 women (62%) and 251 men (38%). A SPD was associated with HS in 186 patients (28%), 104 men (56%) and 82 women (44%). It occurred in 41% of the men and 20% of the women (P < 0.001). In the 180 patients with associated SPD and available data, it occurred before the first HS lesion in 74 patients (24%). This proportion was the same between men (42%) and women (40%). Conclusions: While prevalence of SPD is usually reported as 30), smoking, comorbidities, family history of HS, HS duration, Hurley stage and previous treatments for HS. Results: From 2011 to 2015, data were available for 71 patients with HS. The mean age of patients was 33 years old and the majority were females (58%). Most patients were overweight (32%) or obese (37%), and smokers (86%). Comorbidities were noted in the majority of patients (87%), including acne, pilonidal cyst, diabetes, arterial hypertension and depression. Only 1 patient had concomitant Crohn’s disease. Among 49 patients with available laboratory blood results, 12 patients (24.5%) had metabolic syndrome (presence of 3 or more criteria of the following: obesity, hypertriglyceridemia, decreased high density lipoprotein cholesterol (HDL), increased fasting blood glucose, and hypertension). Patients had a mean duration of HS of 9 years and 30% had a family history of HS. Worst Hurley stage was evaluated and 20% of our patients had Hurley stage I, 60% had Hurley stage II and 20% had Hurley stage III disease. Previous treatments for HS included topicals only (4%), systemic antibiotics (49%), systemic isotretinoin (6%), surgery (3%), and multiple systemics or combination of systemics with surgery (28%), while 10|% of patients had received no treatment. Conclusions: Most patients in our study had moderate or severe HS (Hurley stage II or III). Among them, the majority were overweight or obese and smokers. Smoking and obesity are risk factors associated with hidradenitis suppurativa as well as with cardiovascular diseases. Part of our HS patients had received no prior treatment, highlighting the need of education about the disease and the therapeutic choices for HS.
O10-3 Describe the hidradenitis suppurativa lesions? More complex than it looks! M. Daxhelet1, M. Suppa1, F. Benhadou1, V. del Marmol1 and J. Revuz2 1Dermatology, Universite´ Libre de Bruxelles, Bruxelles, Belgium; 2Private Practice, Paris, France Scientific research question: Although hidradenitis suppurativa (HS) is not a rare disease, it is still often unrecognized. The diagnosis is based on three clinical criteria: typical lesions, typical topography, and chronicity/recurrence. Since one of the elements for the diagnosis is the presence of HS typical lesions (nodules, abscesses, sinus tracts, hypertrophic scars, comedos), a clear definition and description of such elementary lesions typical of HS is vital in order to avoid diagnostic mistakes. We
6
therefore reviewed the scientific literature in search of descriptive definitions of these typical, primary or secondary, lesions. Methodology: A review of the HS literature published in English between January 1996 and December 2015 was performed on Medline (Pubmed), with particular focus on the description of HS typical lesions. Results: We found that the number of publications concerning HS increased constantly over the last two decades but very few descriptive definitions of HS lesions has been published so far. Conclusion: Although a formal definition of primary and secondary lesions typical of HS is crucial to correctly diagnose the disease, such definitions are not provided by the scientific literature. Therefore, we hereby suggest formal definitions of HS typical lesions. In a second time, we also propose to validate these proposed definitions to obtain a clear and uniform description of the disease and its lesions. This could become a helpful educational tool not only for physicians but also for patients.
Quality of life O11-1 Perception of French patients of the impact of hidradenitis suppurativa on their quality of life P. Guillem1, Z. Reguiai2, A. Nassif3, M.-F. Bru4, H. Raynal5 and P.-A. Becherel6 1Department of Surgery, Clinique du Val d’Ouest, Ecully, France; 2Department of Dermatology, CHU de Reims, Reims, France; 3Institut Pasteur, Medical Center, Paris, France; 4Association Francßaise de Recherche sur l’Hidrosade´nite, Paris, France; 5Solidarite´ Verneuil, Lyon, France; 6Department of Dermatology, Hoˆpital Prive´, Antony, France Introduction: Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis with typical symptoms such as abscesses and sore inflammatory nodules usually located in skin folds and perineal region. Its chronicity and unpredictable flares can have a deep impact on patients’ quality of life. The scope of this study is to define the impact of HS on quality of life from French patients’ perspective. Method: Transversal and multicentric study conducted from November 2014 to February 2015. A standardized questionnaire approved by a scientific medical committee was proposed to patients suffering from HS. Patients were recruited by 2 Patient Organizations (AFRH and Solidarite´ Verneuil) and by physicians (dermatologists and surgeons) who are highly involved in HS management. The questionnaire consisted of 48 questions aiming at defining patients’ medical journey from diagnosis to care, and the impact of the disease on their quality of life. It was completed by each included patient without physician implication. Results: 244 patients suffering from HS answered the study: 149 recruited by patient organizations and 95 recruited by physicians. Most patients had moderate to severe HS. The mean age of patients was 37 years and the average duration of the disease evolution was 16 years. 92% of the patients have had an antibiotherapy and have undergone an average of 3 surgeries. Main discomforts of HS were: pain (for 87% of patients), location (86%), and recurrence of wound (85%). The restriction of mobility (62%), seepage (59%) and smell (49%) were the other most quoted embarrassments. An important impact on sentimental relationships (VAS 7.7/10), on hobbies (7.4/10) and on professional life (7.3/10) was highlighted. 53% of patients were deeply affected by HS impact on their social life. 64% of patients had a medical leave at work related to their condition (mean duration: 3 months). Discussion: Hidradenitis Suppurativa may be stigmatizing and highly impact patients’ quality of life. The clinical manifestations of HS affect mobility, private life and professional life with a consequent loss of productivity. HS is perceived as a daily life burden by patients and implies to change their lifestyle (hobbies, clothing. . .) Conclusion: The burden of disease affects numerous facets of patients’ life and physicians must be more aware of it, especially regarding the psycho-sociological impact of HS. This last dimension needs to be included in a multidisciplinary approach of patients management (psychological support and therapeutic education for instance).
O11-2 Psychological support for patients with hidradenitis suppurativa V. Hauet1, P. Guillem2 and M. Delaigue1 1Department of Psychology, Clinique du Val d’Ouest, Lyon, France; 2Department of Surgery, Clinique du Val d’Ouest, Lyon, France Aims: The quality of life is profoundly affected in patients with hidradenitis suppurativa (HS). Psychological support is therefore usually recommended but has rarely been evaluated. Methods: Between 2014 and 2015, 50 patients (34 women, 16 men) surgically managed for HS were invited to participate in face to face single interviews of 30–45 min with a psychologist. The interviews were open and explorative with a focus on the psychological impact of HS in familial and work relationships, and the possibility of preexisting psychological difficulties that could worse HS-related ones. Results: The main expressed emotions during the interviews were psychological breakdown (42%), anger (40%) and worry (6%) while 26 of the 50 patients expressed little emotion (52%). While half of the patients reported good relationship with the spouse, 9 (18%) reported instability or sexual difficulties and 3 (6%) had a toxic relationship with spousal violence. Intrafamilial (family breakdown, misunderstanding) and social (isolation at work, misunderstanding, and conflicts) relations were reported as complex by 20 (40%) and 14 patients (28%), respectively. Overall, suffering at work was reported by 66% of the patients. Pain was ‘tolerated’ in 42% and considered as intolerable by 58% of them. Psychological traumas unrelated to HS were reported in about half of the patients including childhood traumas (54%: ill-treatment, parental divorce, sexual abuses, emotional void), adulthood traumas (58%: divorce or separation, spousal violence, bullying at work), and sexual traumas (14%, rape). Two patients reported simultaneous childhood, adulthood and sexual traumas. Conclusion: Psychological support is warranted in patients with HS. To what extent the disease affect both the familial and work relationship has to be explored with a high rate of profound difficulties. Whether HS-independent or preexisting psychological difficulties coexist also deserves to be systematically questioned. It remains to be determined whether these psychological conditions can participate in disease severity and maintenance.
Socioeconomic approach – prevention O12-1 Hidradenitis suppurativa is associated with a low socioeconomic status: a cross-sectional reference study I. E. Deckers1, I. C. Janse2, H. H. van der Zee1, T. Nijsten1, J. Boer3, B. Horvath2 and E. P. Prens1 Dermatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; 2Dermatology, University Medical Center, University of Groningen, Groningen, The Netherlands; 3Dermatology, Deventer Hospital, Deventer, The Netherlands Research question: Hidradenitis suppurativa (HS) is a chronic debilitating disease. HS is associated with a diminished quality of life. School attendance and employment can be disrupted because of HS, and patients miss up to 34 days of work per year because of their HS. Therefore we determined the socioeconomic status (SES) in patients with HS relative to dermatologic patients, and whether specific clinical HS characteristics correlate with the SES. 1
ª 2016 The Authors. Experimental Dermatology, 2016, 25 (Suppl. 2), 1–13 © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Abstracts
Methodology: For this multicenter cross-sectional reference study, data were collected of HS patients and sex and age matched dermatologic patients in a 1:2 ratio. SES was based on an indicator developed by Statistics Netherlands, which is derived from the mean household income and mean real estate value on a neighborhood level (six-digit postal code area). Univariate and multivariate ordinal logistic regression were used to determine which clinical characteristics were associated with SES in patients with HS. Findings: The SES distribution among 1018 HS patients was significantly lower (low SES: 46.4%, medium SES: 39.0%, high SES: 14.6%), than among 2039 age and sex matched dermatologic control patients (low SES: 34.3%, medium SES: 40.1%, high SES: 25.6%, P < 0.001). In HS patients a low SES was associated with axillary involvement (OR 1.42, 95% CI 1.03–1.99, P = 0.04), and lower current age (OR 0.98, 95% CI 0.97–0.99, P = 0.001). We anticipated that if HS would lead to a lower SES, patients with a more severe disease or younger age of onset would have a lower SES because of missed education or job opportunities, or frequent sick leave HS. However, we did not observe an association between SES and disease severity or age of onset. Therefore it is possible that the lower SES was preexistent to HS. HS patients with low SES had a higher body mass index than HS patients with a high SES (OR 1.03, 95% CI 1.01–1.06, P = 0.003). In the general population, smoking and obesity are more prevalent in people with low SES. Therefore, it could be that people with a low SES have a higher risk of developing HS. Conclusion: Patients with HS have a significantly lower SES than patients with other dermatologic disease. Low SES might be a risk factor for developing HS, because in the general population low SES is associated with an unhealthy life-style such as smoking and obesity. However, a prospective cohort study is needed to determine causality.
O12-2 Secondary prevention of hidradentitis suppurativa/acne inversa H. Kurzen1,2 1Haut- und Laserzentrum Freising, Freising, Germany; 2Dermatology, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany The advent of new therapeutic options for severe HS has turned the focus of the dermatologic society on the treatment of this debilitating disease. Despite intensive research, the true pathogenesis has remained obscure and hence primary prevention is not possible. What do we need to tell our patients in order to prevent progression from Hurley 1 to more advanced stages, i.e. how do we enforce secondary prevention of HS? We know obesity, stress and smoking to be the most important aggravating factors of HS that should be addressed. However, we do not know whether these factors are equally important for different subtypes of HS that have been described. Therefore, it is important for the patient to understand the basic problem of HS skin, which is the inability to ‘turn down’ an inflammatory process once it has started. Small follicular irritations that occur, do not heal properly but develop into follicular abscesses that undermine the tissue and turn into sinuses and fistulas. Thus, the patients have to learn to avoid irritations and strengthen their epidermal barrier by wearing soft underclothes and applying skin care lotions regularly. Shaving should be discouraged. If hairlessness is a desired state, laser or IPL assisted depilation should be encouraged. Topical antibiotics, antiseptics, steroids or combinations thereof may be helpful if applied consequently to early lesions. The crucial point for secondary prevention is improvement of patient education in this respect.
Selected case reports O13-1 PASH syndrome R. Kova´cs, E. Varga and L. Keme´ny Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary Background: Pyoderma gangrenosum is an inflammatory disease which has been associated with many systemic disorders. The clinical triad of pyoderma gangrenosum (PG), acne and suppurative hidradenitis (PASH syndrome) is a recently described autoinflammatory syndrome. This group of autoinflammatory syndromes are not well defined yet, and most of the time difficult to control with currently available treatment modalities. Objectives/findings: We present a 20-years-old male patient with a 3-year history of hidradenitis suppurativa (HS) and a seven-year history of severe acne conglobata. His medical history also included scoliosis and lack of the right lower limb from birth. He was not overweight, and a non-smoker. Family history was positive. Previously he had oral isotretinoin, then oral clindamycin therapy, but neighter had any effect on his HS symptoms. Pain was controlled with NSAIDs. We have changed his therapy to adalimumab. Later he also got isotretinoin courses to controll his acne lesions as well. During treatment course, just before adalimumab treatment was started, he developed two pyoderma gangrenosum like lesions on the lower leg. Histology was consistent with PG. We set up the diagnosis of PASH (Pyoderma gangrenosum – Acne – Suppurative Hidradenitis) syndrome. While on adalimumab therapy for HS, his PG-like lesions ameliorated as well. Conclusion: With this case report where we have described a patient with PASH syndrome and have reported about the successful treatment with adalimumab, we add some more information on treatment of this rare disease.
O13-2 Prevalence and a case report of hidradenitis suppurativa in the hospital of Lithuanian University of Health Sciences V. Kucinskiene1, V. Vilkickaite1, V. Kaikaris2, S. Kontautiene1 and S. Valiukeviciene1 1Department of Skin and Venereal Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania; 2Department of Plastic and Reconstructive Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania Introduction: We present the prevalence data of hidradenitis suppurativa in the in-patient departments of the Hospital of Lithuanian University of Health Sciences (LUHS) during the last 5 years and a severe case of hidradenitis suppurativa in order to introduce a successful combined surgery and medical treatment. Results: According to statistical evaluation in the last 5 years (2011–2015) there were treated 57 patients (38 female/19male) in the in-patient departments of the Hospital of LUHS. The majority of patients were female adolescents of the average age 16 years. Case report: A 20-years old obese (II obesity) woman for about 7 years was feeling discomfort of facial acne vulgaris and nearly 2 years suffering from acne conglobata on the chest. On the area between and under the breasts hidradenitis supurrativa recurred. To help the patient the surgical methods – incision, lavage and drainage of sinus pilonidalis were applied. After that, oral contraceptives Diane 35 were prescribed. After a year the patient underwent surgery once again – radical excision of apocrine glands and autodermoplastic reconstruction on the chest region was made.
After surgery the patient got antibiotic therapy with doxycycline 100 mg twice a day for 14 days, later contraceptives Diane 35 were continued for about 1 year. Our patient was suggested to keep normal body weight, to avoid friction of tight clothes, sweating, hair removal, and other. The clinical signs of the patient’s acne remain slight, only residual scarring and solitary papules left. Conclusion: Hidradenitis suppurativa, especially the form with abscesses, scarring and sinus tract formation, is difficult to treat. Often severe cases need adequate surgical treatment: radical excision of apocrine glands and autodermoplastic reconstruction. It is important to avoid the recurrence of the disease after surgery so the patient should be suggested to visit dermatovenereologist repeatedly for further recommendations and rational medical treatment.
O13-3 Hidradenitis suppurativa – autoimmune, autoinflammatory or both? F. S. Delli State Clinic for Skin and Venereal Diseases, General Hospital Hippokratia, Thessaloniki, Greece Scientific research question: Two major groups of disorders are possibly comorbid with HS, namely chronic hyperergic inflammatory diseases and acquired and inherited follicular occlusion. A number of case reports correlate HS with rare acantholytic diseases, such Galli-Galli, Grover and pemphigus. We investigated the coexistence of HD with acantholytic diseases. Methodology: The patients with HS who visited our Hospital for the last 7 years were investigated for the coexistence of any acantholytic diseases (AD). Findings: Three of ten patients presented an acantholytic disease. A 38 year old woman with HS in both armpits had a history of pemphigus vulgaris from the age of 32. A 53 year old man with severe HS since childhood presented at the same time Darier disease. A 56 year old female patient presented Grover disease 10 years after the diagnosis of mild HS with a reduced number of lesions in both armpits. Conclusion: It seems that a separate group of patients where HD coexists with acantholytic diseases defines a different profile of disease, in the neighbourhood of inherited follicular occlusion diseases and not directly related with hormonal influence. The observations that anti TNF therapies are used for cases of pemphigus with resistance at usual therapies, and in the same time are suspected of triggering pemphigus in some case reports were it was used for the therapy of inflammatory bowel diseases, may locate HD at the crossroad of autoimmune and autoinflammatory diseases.
O13-4 Hidradenitis suppurativa, amyloidosis AA and renal disease A. Hafner1 and E. Sprecher1,2 1Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2 Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv, Israel Hidradenitis suppurativa is a chronic devastating disease which typically feature abscesses, inflammatory nodules, draining sinuses and scarring affecting body folds. The disease is often accompanied by systemic and visceral complications including anemia, lymphedema, squamous cell carcinoma, arthropathy and rarely systemic amyloidosis. We describe a 64 year old man with severe hidradenitis suppuartiva involving mainly the buttocks, thighs and lower abdomen who developed chronic renal failure with nephrotic range proteinuria. Histopathological examination of a renal biopsy revealed amyloidosis AA. Although renal transplantation was indicated, the procedure raised a medical and ethical dilemma as the patient’s son was selected as potential donor but was also affected with hidradenitis suppurativa. Systemic amyloid A is a serious complication of chronic inflammatory diseases, including hidradenitis suppurativa. It should be suspected in every hidradenitis suppurativa patient with new onset and progressive renal failure. The present case, together with a steadily growing body of data regarding other systemic complications and co-morbidities associated with the disease, underscores the fact that hidradenitis suppurativa is much more than a skin disease.
Conservative treatment O14-1 Remission and follow-up of 12 severe HS patients under a targeted antibiotherapy M. Delage-Toriel1, S. Duchatelet2, H. Coignard3, S. Miskinyte2, S. Marc4, K. Amazzough3, O. Lortholary3, X. Nassif5, A. Hovnanian2, A. Nassif1 and O. Join-Lambert5 1Institut Pasteur, Centre Me´dical, Paris, France; 2Institut Imagine, Inserm U1163, Paris, France; 3Service de Maladies Infectieuses, Hoˆpital Necker-Enfants Malades, Paris, France; 4Dermatologie, Hoˆpital Avicenne, Bobigny, France; 5 Laboratoire de Microbiologie, Hoˆpital Necker-Enfants Malades, Paris, France Scientific research question: Hurley stage 3 hidradenitis suppurativa (HS) is the most severe form of the disease. The best strategy to obtain and maintain remission is still controversial. Currently recommended treatment for severe HS relies on wide excision or biotherapies, which efficacy is variable and obtains at the most an improvement of clinical scores. Since our team established that an anaerobic pathogenic flora is associated with severe HS lesions, a targeted antibiotherapy was proposed in these patients at our center. We retrospectively report the follow-up (clinical evolution and side effects) of 12 severe HS patients for whom clinical remission was obtained with a prolonged wide spectrum antibiotherapy, in combination with surgery in 5 patients. Methodology: Clinical history was retrospectively analysed in 12 initially inoperable stage 3 HS patients. The treatment strategy used in our center was first developed on a compassionate basis by a multi-disciplinary team involving microbiologists, dermatologists, infectious diseases specialists and surgeons and relied on the bacteriology of stage 3 HS lesions. It includes: ertapenem 1 g/d (6 weeks), then rifampicin-moxifloxacin-metronidazole (6 weeks), then rifampicin-moxifloxacin (6 weeks). In case of persistance of active lesions, a second antibiotic cycle can be introduced, adapted to the microbiology. Surgery is planned in case of resistant/relapsing area(s), with a 2– 3 weeks pre-operative ertapenem course. When remission is obtained, defined as total absence of clinical inflammation/suppuration, a preventive long-term cotrimoxazole treatment is prescribed. Minor relapses are treated with a 3 weeks course of pristinamycin metronidazole. Results are expressed in median [IQR]. Findings: The 12 patients (9 men and 3 women, with a median age of 45 years) had a median of 6 active sites [5; 8], constant symptoms for the past 4 years [3; 11] and 8 previous surgeries [6; 18]. Under wide spectrum antibiotherapy, median time for remission was 11.5 months [8; 17], in association with surgery in 5 cases. After remission, the median follow-up length was 16.5 months [14; 31], with 1–2 minor relapses/year, usually involving only one site and requiring a short medical treatment. Main side-effects were: gastro-intestinal disorders, candidiasis, tendonitis (moxifloxacin), asthenia. Conclusion: This series demonstrates that a prolonged and targeted antibiotherapy can obtain remission in previously severe and inoperable HS patients, limits the number of areas requiring surgery and that the benefit is maintained on a long term with only minor relapses. For such an invalidating disease, this strategy seems to be an option to consider and to compare with biotherapies. These results on a small series need to be confirmed by larger prospective controlled studies.
ª 2016 The Authors. Experimental Dermatology, 2016, 25 (Suppl. 2), 1–13 © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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Abstracts
O14-2 Hidradenitis suppurativa: an unrecognized paradoxical effect of biological agents used in chronic inflammatory diseases C. Faivre1, A. Villani1, F. Aubin2, D. Lipsker3, M. Bottaro4, J. D. Cohen5, F. Durupt6, G. Jeudy7, E. Sbidian8, E. Toussirot9, V. Badot10, S. Barbarot11, S. Debarbieux12, E. Delaporte13, G. Goegebeur14, J. Morel15, A. Nassif16, G. Duru17 and D. Jullien1 1Hoˆpital Edouard Herriot, Universite´ Claude Bernard Lyon I, Lyon, France; 2Univsersite´ de Franche Comte´, Besancßon, France; 3Universite´ de Strasbourg, Strasbourg, France; 4Centre Hospitalier de Valence, Valence, France; 5Universite´ de Montpellier, Montpellier, France; 6Hoˆpital de la Croix Rousse, Lyon, France; 7Universite´ de Dijon, Dijon, France; 8Centre HospitaloUniversitaire Henri Mondor, Cre´teil, France; 9Universite´ de Franche-Comte´, Besancßon, France; 10Universite´ Libre de Bruxelles, Bruxelles, Belgium; 11Centre Hospitalier Universitaire de Nantes, Nantes, France; 12Centre Hospitalier Lyon-Sud, Pierre-Be´nite, France; 13Hoˆpital Claude Huriez, Universite´ Lille II, Lille, France; 14 Centre Hospitalier Loire Vende´e Oce´an, Challans, France; 15CHU Lapeyronie, Universite´ de Montpellier, Montpellier, France; 16Infectious Diseases Center Necker-Pasteur, Pasteur Institute, Assistance PubliqueHoˆpitaux de Paris, Paris, France; 17Universite´ Claude Bernard Lyon I, Lyon, France Background: Paradoxical hidradenitis suppurativa (HS) induced by biological agents (BA) has only rarely been reported. Objective: To describe the clinical characteristics and outcome of patients developing paradoxical HS under BA. Methods: This is a multicenter nationwide retrospective study asking physicians to report all cases of HS, confirmed by a dermatologist, occurring under treatment of an inflammatory disease with a BA. Results: We included 25 patients (15 inflammatory rheumatisms, 9 Crohn’s disease, 1 psoriasis) treated by 5 different BA (adalimumab = 12, infliximab = 6, etanercept = 4, rituximab = 2, tocilizumab = 1). The median duration of BA exposure before HS onset was 12 months (range 1– 120 months). Patients were mostly Hurley stage I (n = 13) or II (n = 11). Simultaneously to HS or within 1 year, 11 patients developed additional inflammatory diseases, including paradoxical reactions (psoriasis = 9, Crohn’s disease = 3, alopecia areata = 1, erythema elevatum diutinum = 1). Improvement of HS was more frequently obtained after BA discontinuation or switch (n = 6/10, 60%) rather than maintenance (n = 1/14, 7%). Reintroducing the same BA resulted in HS relapse in 3/3 patients. Limitations: This is a retrospective study with incomplete follow-up for some patients. Conclusion: HS is a rare paradoxical adverse effect of BA, although a fortuitous association cannot be excluded in some cases. We observed a trend toward better outcome when the BA was discontinued or switched.
O14-3 How do hidradenitis suppurativa patients actually use supportive care? A. de l’Escaille1, H. Raynal2, M. Lagarde3, M. Delaigue4, V. Hauet4, S. Arnaud5, C. Saulnier5 and P. Guillem6 1Clinique du Val d’Ouest, Ecully, France; 2Solidarite´ Verneuil, Lyon, France; 3Clinique du Val d’Ouest, Ecully, France; 4Department of Psychology, Clinique du Val d’Ouest, Ecully, France; 5Equipe de Liaison et de Soins en Addictologie Lyon-Ouest, L’Arbresle, France; 6Department of Surgery, Clinique du Val d’Ouest, Ecully, France Aim: Hidradenitis suppurativa (HS) is associated with overweight, tobacco consumption and psychological difficulties. In our centre, hospitalized patients are theoretically systematically invited by the nursing team to meet an addictologist, a dietician, a psychologist, a representative of a patient organization as well as other volunteer patients. The aim of this study was to evaluate whether these supportive cares were effectively proposed to the patients and how the patients effectively used them. Methods: A specific questionnaire was retrospectively send to all HS patients who have been hospitalized for surgery within a 6-month-period. Results: 61 patients were identified (38 women, 23 men) and 38 replied (62%). 18/38 patients (47%) underwent outpatient surgery. Interviews with the psychologist, the dietician, the addictologist, the organization representative and other patients were actually proposed to 76%, 45%, 39%, 92%, and 50%, respectively. Interviews with the psychologist and the patient organization were significantly more proposed by the nursing team than the others. There was a trend (not statistically significant) for a lesser proportion of patients who were proposed for interviews during an outpatient surgery. When proposed to the patients, interviews with the organization representative (94%), other patients (89%), and the dietician (76%) were significantly more frequently accepted than the interviews with the psychologist (55%) and the addictologist (20%). Conclusion: It is worthy to note that despite the small size of our cohort, some differences are already high enough to gain statistical significance. Even in a centre specialized in HS, educational efforts have to been made in organizing the cares to (i) increase the proportion of interviews for outpatient surgery and, (ii) ameliorate the knowledge and trust of the nursing team about some aspects of the supportive cares (dietician, addictologist). In the context of surgery, patients are greedy for contacts with other patients (in particular mediated by a patient organization) and nutritional support, but are reluctant for cigarette withdrawal and psychological support.
Surgical treatment O15-1 MIBHS: a concept to distinguish between medical and surgical treatment in hidradenitis suppurativa F. G. Bechara Department of Dermatologic Surgery, Ruhr-University Bochum, Bochum, Germany Although new medical treatment options have been established, surgery plays an essential role in the treatment of hidradenitis suppuartiva (HS) and is still regarded as the treatment of choice in severe cases. The severity is mainly based on the Hurley stages, with Hurley stage II and II being considered as ‘surgical candidates’. However there is still uncertainty in clinical routine, whether medical or surgical treatment has to be applied and how extensive surgery has to be performed. Therefore the socalled MIBHS concept is presented, which clearly defines 5 mandatory surgical indications: fistulas/ sinus tracts, accordion-like scars, contracted scars, mutilating HS and suspected malignancy. If the mentioned mandatory surgical indications (MIBHS) are present, surgery is unavoidable. Surgical removal of MIBHS, however, does not necessarily include resection of surrounding inflammatory lesions. In these cases a combination with medical treatment options is to be demanded, although until today it remains unclear whether conservative treatment should start before, during or after surgery.
O15-2 Pre-, intra-, and post-operative treatment procedure for hidradenitis suppurativa M. Podda, E. Hasche, H. Friedl and S. Karsai Department of Dermatology, Klinikum Darmstadt, Darmstadt, Germany Surgery is a mainstay in the treatment of hidradenitis suppurativa (HS). Complete wide excision and healing by secondary intention with or without split-skin grafting is a widely accepted surgical modality for HS patients. Various variables exist regarding pre- intra-, and postoperative surgical procedures in HS. They differ largely depending on each clinic, specialties and countries. However, clinical results, complications, and recurrence rates largely depend upon these variables. We therefore
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present, based on our long-term follow up study of 13 years, a complete surgical treatment approach algorithm. This approach includes indications, preoperative measures, intraoperative procedures, and postoperative care in the clinic and at home. The harmonization of the complete surgical treatment procedures in HS will bolster the quality of treatment not just in surgically treated patients, but even more in HS cases requiring preoperative antinflammatory therapeutic measures.
O15-3 Deroofing for hidradenitis suppurativa J. Boer Department of Dermatology, Deventer Hospital, Deventer, The Netherlands Scientific research question: The severity of Hidradenitis Suppurativa (HS) is often defined by the classical 3 clinical stages by Hurley. This classification can be very useful in the decision to treat the patient with medication or surgery. In severe cases (Hurley III and serious Hurley II) extensive surgery is considered mandatory. In mild and moderate cases (Hurley I and II), patients may benefit from topical and systemic treatment and/or limited surgery. There are several distinct surgical methods for HS, such as incision plus drainage, limited or extensive surgery and CO2 laser therapy. A new surgical approach is the deroofing technique. Methodology: Staging of the disease activity in the separate localisations (axilla, groin) is made in the patients. Furtheron, the patiens is asked whether the recurrence of the lesions are located at exactly the same fixed locations or at various locations or both. Lesions at fixed locations and assessed as Hurley I or II are considered suitable for deroofing. Under local anaesthesia the complete roof of a lesion, i.e. an abscess, nodule or sinus tract is electrosurgically removed using a blunt probe as a guide, leaving the floor, covered with epithelium intact for more rapid healing. The lesions are fully probed again for remaining side passages, until all residual tracts and gelatinous material have been cleared. Postoperative wound care consisted of once daily application of petrolatum, dressed with gauze. Findings and conclusions: The deroofing technique is an effective treatment for recurrent HS lesions such as nodules, abscesses and tunnels (sinus tracts) at fixed locations in Hurley I and II areas. Advantages of this method are: Not technically difficult, cheap and suitable as an office procedure, it is tissue-saving with limited recurrence and good long-term results; there is a high patient satisfaction rate and recommending rate.
O15-4 Management of complications in patients treated with CO2-laser L. Emtestam Department of Dermatology, Karolinska University Hospital, Stockholm, Sweden Complications following CO2-laser surgery of hidradenitis suppurativa include secondary infection, bleeding, hypergranulation, hypertrophic scar formation, pyoderma gangraenosum and nerve damage. Procedural recommendations with the purpose to minimize risks of, as well as the management of recurrencies and complications will be discussed.
O15-5 Severe hidradenitis suppurativa treated with wide excision: a meaningful local cure rate and high patient satisfaction I. E. Deckers, Y. Dahi, H. H. van der Zee and E. P. Prens Dermatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands Research question: Hidradenitis suppurativa is a chronic disease. Surgical treatment under general anesthesia whereby all affected tissue is excised if often needed to achieve remission. However, studies on wide surgical excision in large cohorts of HS patients are scarce. Therefore we investigated the clinical characteristics, recurrence rate and patient satisfaction in patients with severe HS who had undergone wide excision under general anesthesia. Methodology: The records of patients who underwent wide excision surgery between 2007 and 2014 in the department of Dermatology at Erasmus University Medical Center in Rotterdam, The Netherlands, were retrospectively reviewed. In addition, for each patient an individual HS-specific questionnaire was made, based on the number of surgical procedures undergone and locations that were treated. The questionnaire comprised questions on recurrence and patient’s satisfaction. Findings: 86 patients responded, who underwent in total 122 surgical procedures whereby 260 locations were treated. The inguinal (n = 95, 36.5%) and gluteal/perianal region (n = 67, 25.8%) were the most frequently treated anatomical areas. In most cases healing occurred by secondary intention (n = 253, 97.3%). After a mean follow-up of 36.2 19.1 months, 50.8% of the treated anatomical areas remained disease-free, natural disease progression was seen in 12.7%, and recurrence within or ≤0.5 cm from the surgical scar in 36.5% of the cases. Most patients were glad they had the operation (91.8%) and would recommend it to other HS patients (91.8%). Conclusion: Wide surgical excision induced remission in 51% of the affected HS anatomical areas in patients with severe HS. This remission rate might seems low because previously remission rates between 37% and 98% have been reported. However, all our patients had severe HS with a mean disease duration of 18 years resulting in a high disease burden before they underwent surgery. Direct comparison of our results to other surgical treatment studies is very difficult because different surgical techniques, definitions of recurrence and follow-up times have been used. A prospective study is needed to determine the best surgical and closure techniques in severe HS.
O15-6 Genital elephantiasis associated with hidradenitis suppurativa E. Lelonek, L. Matusiak, A. Bieniek and J. C. Szepietowski Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland Background: Hidradenitis suppurativa (HS) is a recurrent inflammatory disease manifested by the presence of fistulas, abscesses and scarring. HS, especially in extremely severe cases is often accompanied by complications such as contractures of the limbs, lesional squamous cell carcinomas, fistulas into the joints and urinary tract, anemia, thrombocytopenia, amyloidosis, renal failure, genital elephantiasis, etc. Objective: The presentation and assessment of the outcomes of genital elephantiasis surgical management in HS patients in the light of the improvement of quality of life (QoL). Methods: The surgical treatment was conducted in 7 HS patients (4 men, 3 women) aged from 32 to 58 years (mean, 41 9.4 years). The disease duration in the studied group was of 5–30 years (mean, 14 8.2 years). All included patients were heavy smokers (mean, 22.4 9.9 pack-years), overweighted (BMI on average 31.6 3.7) and Hurley III sufferers. The validated questionnaires, including DLQI (Dermatology Life Quality Index), 13-item BDI (Beck Depression Inventory), FACITF (Functional Assessment of Chronic Illness Therapy – Fatigue scale), the scale of stigmatization by A. Evers (6-item scale) and the EQ-5D health questionnaire were used for the evaluation of QoL aspects. Results: As a result of the surgery, the assessed group of patients experienced statistically significant improvement of both social and professional QoL aspects, and reduction of general fatigue caused by the illness. Moreover, the sufferers also experienced positive impact of surgical approach on the depression and stigmatization levels. Conclusion: Surgical management of genital elephantiasis secondary to HS could be regarded as an efficacious treatment modality of this complication. This kind of therapy was characterized by a significant improvement of QoL and yielded satisfactory functional and cosmetic outcomes accompanied by an acceptable level of discomfort associated with perioperative period.
ª 2016 The Authors. Experimental Dermatology, 2016, 25 (Suppl. 2), 1–13 © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Abstracts
Wound healing O16-1 Hidradenitis suppurativa and wound management M. Romanelli and V. Dini Department of Dermatology, University of Pisa, Pisa, Italy Hidradenitis suppurativa (HS) is a chronic, burdensome, debilitating disease of the hair follicle. It presents with recurrent painful inflamed and non-inflamed lesions usually in specific body areas such as axillary, inguinal, perineal and genital areas. It is associated with a large range of other diseases and conditions, such as obesity, arthropathy, inflammatory bowel diseases and squamous cell carcinoma. Medical therapy may be systemic or topical, mainly based on antibiotics, retinoids, hormones and immunosuppressive drugs, including biological therapies. Surgical and laser therapies could be a valid therapeutic approach to treat locally recurring lesions. The aim of the author is to review the wound healing options after skin excision and laser treatments, with a focus on lesions left healing by secondary intention, analyzing the efficacy of moist wound dressings, negative pressure wound therapy (NPWT), bioactive dressings, such as platelet-rich plasma gel and hyalomatrix or autologous keratinocyte suspension in platelet concentrate and skin-grafting tecniques.
O16-2 Management after surgical treatment of hidradenitis suppurativa E. Hristakieva1, R. Lavcheva1, R. Paskaleva2, D. Gancheva1 and P. Kohl3 1Dermatology and Venereology, Medical Faculty, University Hospital, Trakia University, Stara Zagora, Bulgaria; 2Department of Medical Rehabilitation and Occupational Therapy, Physical Medicine and Sports, Medical Faculty, Trakia University, Stara Zagora, Bulgaria; 3Department of Dermatology and Venereology, Vıvantes Klinikum Neuk€olln (Region South), Berlin, Germany Hidradenitis suppurativa (HS) is a debilitating, painful chronic inflammatory disease, which produces richly deforming and contracting fibrotic scar tissue with subsequent functional defects and leads to major negative impact on quality of life. Radical excisionis in refractory and extensive cases is essential and recommended as early as possible. The large wounds recover by secondary healing. The late sequelae involve different types of problems related to scar formation and contractures, especially when in the axilla. Aims: To develop a model of wound healing and kinesitherapeutic program in early and late postoperative period in patients with severe Hidradenitis suppurativa; to assess pain, muscle imbalance and the formation of coarse postoperative scarring; to evaluated and compare the quality of life before surgery, in early and late postoperative period of the patient. Methods: We are presenting the concluded results from post-operative period of 13 patients with HS, II-III Hurley stage. Surgical method is wide excision with secondary healing, 7 day antibiotic prevention of secondary infection. The local wound treatment includes antiseptic baths and adherent dressing materials to complete epithelialization with prevention of postoperative keloid formation. Patients and their relatives are informed and trained how to treat the wound after leaving hospital. The period of observation and measurement of indicators to increase physical activity is for 50 days. Kinesitherapeutic programs include special exercise to increase physical activity of patients in the early and late postoperative period tailored to their individual capacities. Patients are consulted to follow proper dietary regime, to reduce weight if needed and to stop smoking. Weekly follow up controls the process of healing. We used QoL questionnaires concomitantly with a visual analog score (VAS) for pain before surgery and in the postoperative period. Results: All included patients (13) experienced full epithelialization without keloid formation maximum to 8 weeks after surgery. Patients were satisfied with the cosmetic appearance of scars. Complete remission was defined as no new lesions appeared for 6 months or more. The QoL scores were significantly improved after treatment and strongly and positively correlated with the pain. Conclusions: Proper wound healing and kinesitherapy program after excision with secondary healing in HS patients is an important part of the complex treatment that helps overcoming muscle imbalance, improves function of affected limbs, prevents the risk of a postoperative pathological scarring and facilitates activities of daily life. Interdisciplinary approach is crucial for a good therapeutic response.
O16-3 Hyperbaric oxygen therapy for wound management after surgery for hidradenitis suppurativa P. Guillem1, T. Joffre2, K. Tazarourte3, R. Soldner2 and B. Delafosse2 1Department of Surgery, Clinique du Val d’Ouest, Ecully, France; 2Hoˆpital Edouard Herriot, Hospices Civils de Lyon, Centre of Hyperbaric Medicine, Lyon, France; 3Hoˆpital Edouard Herriot, Universite´ Claude Bernard Lyon I, Centre of Hyperbaric Medicine, Lyon, France Background and aims: Hyperbaric oxygen therapy (HOT) has been proposed to accelerate wound healing after surgery for many diseases. It has been seldom reported after surgery for hidradenitis suppurativa (HS). The aim of this observational study is to evaluate how HOT has been used in a surgical centre specialized in HS patient management. Methods: The medical charts of all patients addressed for HOT after surgery for HS were retrospectively reviewed. Demographic data were collected as well as Hurley’s stage, number and size of lesions, and results of the HOT procedure. Results: 70 HOT procedures were performed in 56 patients (31 women, 25 men; median age 30, ranges: 18–60). Up to 204 HS lesions were removed (ranges: 1–9). The median wound area was 9 cm2 (ranges: 0.4–500). Three procedures were interrupted at 6, 7 and 8 days but completed in another center (healing was obtained for all 3). Twenty procedures were interrupted within the 3 postoperative weeks because of lassitude, claustrophobia or adverse events (essentially ear pain). The 47 remaining procedures were completed with a median duration of 49 days (ranges: 22–402). Complete healing was obtained in 42 (89%) while 5 failed. Patients with incomplete healing trended to be younger (median age: 21 vs 32 years), to have a higher number of removed lesions (4 vs 2) and a higher BMI (27.4 vs 26.5). Conclusions: Although this study is observational and based on a relatively small number of completed procedures, it can be inferred that HOT can be used to favour wound healing after surgery for HS. Further studies are warranted using multicentre recruitment to achieve statistical significance and determine factors able to predict HOT success.
Poster P01 Nicastrin mutations prevalence in a French cohort of patients with hidradenitis suppurativa S. Duchatelet1, S. Miskinyte1, O. Join-Lambert2, M. Delage3, A. Nassif3 and A. Hovnanian1,4 1INSERM UMR1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris Descartes – Sorbonne Paris Cite´ University, Paris, France; 2Laboratoire de Microbiologie, Hoˆpital Necker-Enfants Malades, Paris, France; 3 Centre Me´dical, Institut Pasteur, Paris, France; 4Department of Genetics, Necker-Enfants Malades Hospital, Paris, France Scientific research question: Hidradenitis suppurativa (HS) is a chronic skin disease observed in 1% of the population and characterized by nodules, cysts and abscesses in apocrine gland-bearing sites.
Heterozygous mutations in three c-secretase genes, mainly in nicastrin (NCSTN) and rarely in presenilin enhancer gamma secretase subunit (PSENEN) and presenilin 1 (PSEN1) genes, have been identified in the pathogenesis of autosomal dominant forms of HS. We previously identified loss-of-function mutations in NCSTN in 3 out of 14 multiplex French HS pedigrees. In contrast to this previous study, which has focussed on the identification of mutations in multiplex kindreds, the aim of this study was to determine the prevalence of NCSTN mutations among a large French cohort of familial and sporadic HS cases. Methodology: We performed mutational analysis of NCSTN gene by Sanger sequencing of all coding regions. This study involved 52 unrelated patients including 14 sporadic HS cases, 26 familial HS cases, 5 patients (three familial cases, one sporadic patient and one adopted child) with the triad pyoderma gangrenosum, acne, and HS (PASH syndrome) and 7 patients (6 familial and 1 sporadic cases) with HS associated with severe acne. Findings: We identified one heterozygous frameshift mutation (NM_015331.2: c.344_351del, p.Thr115Asn*20) within NCSTN in one PASH patient out of the 52 unrelated HS patients studied. Conclusion: In total, we examined the NCSTN gene for mutations in 66 unrelated French individuals with HS. We identified four loss-of-function mutations in the coding regions in three familial HS cases and one adopted child with PASH syndrome. Our data demonstrate that NCSTN mutations are only responsible for a small proportion of French HS cases (10 flares: male (m): 14.3% female (f): 30.0%, P < 0.001) (genital: >10 flares: m: 5%, f: 12%, P < 0.001) and (mammary: >10 flares: m: 2%, f: 7%, P = 0.04). Perianal flares and flares in other locations were significantly more common in men than in women (perianal: >10 flares: m: 8%, f: 5%, P = 0.04) and (other: >10 flares: m: 10% f: 4%, P = 0.02) Conclusions: This observation supports the notion that HS may be further classified, as the findings support the clinical impression that the front of the body is most often affected in female patients and the back of the body is most often affected in male patients. The findings support the development of a further sub-classification of HS. Sub-classifications are known in many other diseases such as e.g. psoriasis, where they have shown utility in guiding choice of treatment. The observations imply that the pattern of where lesions are located may be an important element in a future system for sub-classifications of HS. The creation of a valid classification system will help us conduct studies on both the aetiology of the disease and on the development of effective treatment options in the future.
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P07 Bacterial biofilm in chronic lesions of hidradenitis suppurativa H. C. Ring1, L. Bay2, P. Theut Riis1 and G. B. Jemec1 1Dermatology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark; 2Costerton Biofilm Center, University of Copenhagen, Copenhagen, Denmark Aim: We aimed to investigate the potential presence of biofilm formation in chronic HS lesions. Method: The present study comprised a total of 55 HS patients, which contributed with skin biopsies containing a minimum of one hair follicle. One 4 mm punch biopsy was obtained from lesional skin as well as from adjacent healthy skin. The biopsy was stored in formalin and subsequently paraffin embedded according to the standard operating procedure. In order to identify the pilosebaceous units each paraffin block was sectioned at 5 + levels, each level consisting of seven slides (4 lm thick), and processed until a representative pilosebaceous unit was identified. In order to visualize bacteria a universal bacterial specific Peptide Nucleic Acid (PNA) – Fluorescence in situ Hybridization (FISH) probe was used in combination with Confocal Laser Scanning Microscopy (CLSM). Furthermore, the samples were also stained with hematoxylin and eosin (HE) and examined by standard light microscopy for the presence of representative areas of pilosebaceous units and subsequent identification of bacteria and grading of inflammation. Results: Bacterial aggregates were seen in 70% of the lesional samples; mainly present in hair follicles (67%) and in sinus tract (11%). The large bacterial aggregates reaching >50 lm in diameter were primarily present in the infundibulum of the hair follicles (50%) and in sinus tracts (19%). Biofilm formations were not detected in adjacent healthy skin. Conclusion: This study has demonstrated the presence of biofilm in chronic HS lesions. This may indeed contribute to the intractable nature of the disease. The biofilm formations may inhibit the wound healing process as well as the efficacy of antibiotics. To increase efficacy of treatment, the future management of chronic HS lesions may include drugs that specific target biofilm.
P08 Association between hidradenitis suppurativa and spondyarthritis Z. Reguiai1,2, M. Fauconnier3, J.-H. Salmon3, D. Guillaume3 and ResoVerneuil 1Dermatology, Hoˆpital Robert Debre´, Reims University Hospital, Reims, France; 2ResoVerneuil, Paris, France; 3Rheumatology, Hopital Maison Blanche, Reims University Hospital, Reims, France Background: A few publications have reported the association of Hidradenitis suppurative (HS) and other chronic inflammatory diseases especially inflammatory bowel disease and spondyloarthritis (SpA). Objectives: We sought to Better characterize the association between HS and SpA. Methods: Monocentric prospective case-control study including all the HS patients seen consecutively for their disease in our dermatology department. Controls were matched to cases on age and gender. All patients were examined by a dermatologist and a rheumatologist. Data collection was performed using a standardized questionnaire referring patient (age, sex, BMI, comorbidities . . .) and HS characteristics (topography, severity, HS treatments . . .). Biological samples (standard Biology, CRP, HLA B27. . .) and a 1.5 Tesla sacro-iliac MRI were performed. The images were read in a blinded, independent manner by two experienced readers. Afterward, patients were listed according to the ASAS criteria for SpA. Results: 98 patients were included (mean age 36 11.3; 70% women). 78 were analysed (39 patients with HS). 11 of them (28%) fulfilled the ASAS criteria for SpA, although 4 of them were already known. Only 1 patient (2%) fulfilled those criteria in the control group. Axial spondyloarthritis was the most common form of SpA observed with 9 patients of 11. There was no significant association with HLA B27 haplotype. After adjustment for age, gender and personal or familial history of psoriasis or inflammatory bowel disease, we proved that HS is an independent risk factor for SpA (OR 19.5; 95% CI 1.7; 216). Conclusions: A recent French prospective study identified a prevalence of SpA estimated at 3.7% in HS patients. In our study, the link between HS and SpA is clearly highlighted. Dermatologists have a critical role in the management of HS. They can also play a key role in screening for comorbidities associated with this disease (metabolic syndrome, depression, smoking. . .) including inflammatory joint manifestations that may be suggestive of SpA. This could have a diagnostic but also therapeutic interest (avoiding NSAIDs and potentially using anti-TNF a)
P09 A recurrent, severe hidradenitis suppurativa/acne inversa: a chronic pathway to disability I. Karagiannidis, M. Brunner and C. C. Zouboulis Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany We report on a 31 year-old male patient from Bulgaria, who was admitted to our department with a severe hidradenitis suppurativa/acne inversa (HS). The patient had since 12 years inflammatory nodules on the left groin. Multiple incisions of abscesses in his country brought a temporary improvement in the past, but over the years he developed an increasing number of inflammatory lesions with fistulas. Incisions of these lesions did not hinter the disease to further worsen, whereas multiple courses of antibiotics have been administered without success. In addition, isotretinoin over 6 months has been ineffective. The patient was heavy smoker until 2 years before his presentation (40 cigarettes/day). His Body Mass Index was normal and there was no familial HS. A coloscopy in the past excluded a chronic inflammatory bowel disease. The patient had massive movement restriction due to severe involvement and pain in the perineal region. He presented with multiple nodules with purulent secretion, fistulas and extensive scarring of the whole gluteal region, scrotum and both axillar regions. Because of a penis deformation and scarring synechiae on the root of penis and mons pubis, a miction was impossible. Laboratory evaluation revealed leukocytosis, iron deficiency anaemia and a blood sedimentation rate of 90/100 mm/h, whereas Proteus mirabilis und Bacteroides fragilis were detected in the microbiologic smears. Histopathologic examination of a skin lesion demonstrated a massive inflammation with abscess formation and granulomatous reaction. In the context of preoperative preparation we administered an antibiotic therapy with clindamycin/rifampicin over 21 days and conducted a magnetic tomography imaging, where we confirmed a pronounced fistulation with abscess formation at the precoccygeal area and additional signs of inflammation of the proximal musculature of the right thigh. Because of advancing dysuria, a suprapubic catheter was placed under general anesthesia. After a gradual reduction of the purulent secretion and improvement of the inflammatory blood parameters, a surgical excision of the scars at the left groin was conducted under general anaethesia with secondary healing. Postoperatively, pain was alleviated through nonsteroidal antiinflammatory drugs and opioids. Dressing changes were performed under general anaesthesia. During subsequent hospitalizations the patient underwent wide surgical excisions at the right groin, the root of penis, the foreskin with a flap reconstruction from the genital region as well as of the gluteal area. Parellelly, the patient psychology improved, he gained weight, got married and has in the meantime a healthy child. The described case shows that HS is an under- estimated and not adequately treated skin disease, especially in male patients. It often has a huge impact on the quality of life of young patients, as it can lead to morphologic changes, functional deficits of the genital region and sexual impairment.
ª 2016 The Authors. Experimental Dermatology, 2016, 25 (Suppl. 2), 1–13 © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Abstracts
P10 Hidradenitis suppurativa and erythema nodosum A. F. Massa Department of Dermatology, CHVN Gaia/Espinho, Vila Nova de Gaia, Portugal Introduction: Hidradenitis suppurativa has an inflammatory background and its comorbidities and disease associations are widely known but not entirely understood. Clinical case: A 22 year-old women, obese (IMC of 43 and a family history of HS) who had HS for 8 years, hurley II with a mild PGA (with an axillary surgery 6 years ago for HS and perimenstrual HS worsening), with a past history of Erythema nodosum (1 year ago) and who was medicated with metformin 500 mg tid, doxycline 100 mg od, Ethinylestradiol/chlormadinone acetate 0.03/2 mg od (and had previously done Clindamycin 600 mg/day for 2 weeks) presented to the consultation with tender subcutaneous nodules and erythematous plaques on the pretibial areas. At this time there was just an inflammatory lesion on her right axilla. There were no signs of infection (altought a tooth devitalisation whas been done 1 month before), no bowel or respiratory symptoms were present and angiotensin conversion enzyme was normal. The anticonceptive pill and the minocycline were stopped and naproxen 500 mg bid was started. Three weeks after a worsening of HS was noted with pubic and left inguinal inflammatory, painful lesions and a moderate PGA. The Erythema nodosum lesions were better. Clindamycin and Rinfampicin were started and naproxen was interrupted. Discussion: HS is not usually associated with EN, but EN can have multiple causes including infections, inflammatory bowel disease and half of the cases are idiopathic. The interruption of the antiandrogenic and the antibiotic therapy as well as the introduction of an NSAID may have contributed for the disease flare-up. Anti-TNF treatment could be an alternative although its efficacy in erythema nodosum can be variable and even worse it. Another anti-inflammatory therapy should be kept in mind, trying to control both diseases and whether discontinuance of the antiandrogenic and antibiotic therapy in a well controlled HS patient is appropriate should be a matter of debate.
P11 Hidradenitis suppurativa intralesional injections with corticosteroids – HILIC P. Theut Riis1, J. Boer2, I. Deckers3, E. P. Prens3, L. Emstedam4, D. M. L. Saunte1 and G. B. E. Jemec1 Department of Dermatology, Roskilde Hospital, Roskilde, Denmark; 2Department of Dermatology, Deventer Hospital, Deventer, The Netherlands; 3Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; 4Section of Dermatology and Venerelogy, Department of Medicine, Karolinska Institute, Stockholm, Sweden Aims: Present study compares patient-reported VAS for pain, and physician evaluated redness, edema, suppuration and size for abscesses before and after injection with a mix of triamcinolon and lidocaine. The main objective of this pilot study is to determine if a randomized controlled trail for triamcinolone injection for acute abscesses in HS is viable. Methods: Thirty consecutive HS patients, with acute abscesses, were recruited in three different centres. The abscesses were injected with 0.2–2.0 ml of a 50/50 mix of triamcinolone 1% and lidocaine 5%. Injection volume were dependent on the particular lesion and left to investigator discretion. VAS scores used an anchored scale, with 0 representing no pain, 5 moderate pain and 10 unbearable pain. VAS scores were collected at: day 0 (preinjection), and at the same time for each day until follow-up. Redness, suppuration and edema were physician evaluated using a 5 point anchored scale with 0 representing normal skin and 4 representing dark red skin, massive suppuration and very pronounced edema respectively. Size of the lesion were physician evaluated using a 4 point scale i.e. 0.0001). Patients had a reduction in pain from day 1 to day 2 (P = 0.07) and a trend towards reduction from day 2 to day 3 (P = 0.0502). Medians at day 0 were for: Redness 2.5, suppuration 2, size 1–1.5 cm and edema 2. Medians at follow-up were for: Redness 1, suppuration 1, size less than 0.5 cm and edema 1.At followup patients had a statistically significant reduction in redness, suppuration, size and edema (P > 0.0001 for all). Conclusion: This study shows a significant reduction in pain for an abscess just 1 day after injection, a further reduction the following day. It also demonstrates a reduction in redness, suppuration, size and edema after 6.7 days. This suggest an effect of the injection. This was a pilot study with few cases, but the results were for the most part highly significant despite the small number of cases. The lack of a control group is the major weakness of the study, but this was a pilot study designed to determine if a randomized controlled trail is recommended, which it is. 1
P12 Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa in three female Caucasian patients M. Antohe1, R. Popescu2, M. Balaban1, A. Calinescu1 and C. M. Popescu2 1Dermatology Department, Colentina Hospital, Bucharest, Romania; 2Dermatology Department, Carol Davila University of Medicine and Pharmacy, Colentina Hospital, Bucharest, Romania Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory cutaneous disease involving apocrine gland-bearing areas of the skin, with a prevalence of 1%. It consists of recurring painful abcesses, fistulating sinus tract and scarring, typically involving the axillae and the anogenital-inguinal area. Although various medical and surgical therapies have been proposed, optimal management of the disease remains unclear. Methodology: We report 3 cases of HS, in female Caucasian patients, with active disease for 2–4 years, treated with combination therapy of clindamycin 300 mg twice daily and rifampicin 300 mg twice daily for 10 weeks. According to Hurley’s classification, based on the assessment of scarring and inflammation, one patient had stage 1 lesions and the other two had stage 2 lesions. The patients had undergone previous treatments with topical and systemic antibiotics without significant improvement. Outcomes were classified according to the effect of the treatment on inflammatory lesions. Total remission was defined as total clearance or improvement by more than 80% whereas partial improvement was defined as
