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Cucu CI, Giurcăneanu C, Mihai MM, Andronic T, Ancuta I, Popa MI, Macovei IS, Popa LG. Unraveling the Skin Microbiome in Hidradenitis Suppurativa: Implications for Treatment and Disease Progression. J Clin Med 2025; 14:2424. [PMID: 40217873 PMCID: PMC11989415 DOI: 10.3390/jcm14072424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/21/2025] [Accepted: 03/30/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Hidradenitis suppurativa (HS) is a chronic, disabling, and disfiguring inflammatory disease with a complex, incompletely elucidated pathogenesis. The role of skin dysbiosis in the development and progression of HS has not yet been clarified. Methods: We performed an observational, prospective culture-based study that included 40 HS patients and analyzed the bacterial load and diversity in HS skin lesions, their correlation with disease severity, and several host and environmental factors. Additionally, we investigated the prevalence of antibiotic resistance and determined the resistance profile of bacterial strains isolated from chronic HS lesions. Results: An impressive number and diversity of bacterial strains were isolated from both superficial and deep HS lesions. 201 aerobic and anaerobic bacterial strains were isolated, polymicrobial growth being detected in the majority of samples. The most frequently isolated bacteria were Staphylococcus epidermidis, Staphylococcus aureus, Staphylococcus lugdunensis, Peptoniphilus spp., and Enterococcus faecalis in superficial lesions and Staphylococcus epidermidis, Staphylococcus aureus, and Corynebacterium tuberculostearicum in deep lesions. A significantly higher bacterial density and diversity was found in male patients, regardless of the affected area and in patients with severe HS. The proportion of bacterial strains resistant to antibiotics was lower in our study (8.95%) compared to the previously reported data. Conclusions: Our findings indicate dysbiosis as a key player in the initiation and maintenance of the inflammatory process in HS. Further large-scale, prospective studies are required to comprehensively characterize the microbiological landscape of HS and shed light on its contribution in the pathogenesis of the disease.
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Affiliation(s)
- Corina Ioana Cucu
- Department of Dermatology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.I.C.)
| | - Călin Giurcăneanu
- Department of Dermatology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.I.C.)
| | - Mara Madalina Mihai
- Department of Dermatology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.I.C.)
| | - Teodora Andronic
- Department of Dermatology, Colentina Clinical Hospital, 020125 Bucharest, Romania
| | - Ioan Ancuta
- Department of Internal Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mircea Ioan Popa
- Department of Microbiology II, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ioana Sabina Macovei
- Department of Microbiology II, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Liliana Gabriela Popa
- Department of Dermatology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (C.I.C.)
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Yu C, Yan W, Shucheng H, Huang Y, Jiang X. Roles of skin microbiota in hidradenitis suppurativa: insights from a two-sample mendelian randomization analysis. Arch Dermatol Res 2025; 317:346. [PMID: 39912928 DOI: 10.1007/s00403-024-03702-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 12/05/2024] [Accepted: 12/20/2024] [Indexed: 02/07/2025]
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with unique lesional dysbiotic features. However, the role of the microbiology in the pathogenesis of HS remains in dispute. We aimed to conduct a two-sample Mendelian randomization study to investigate the relationship between skin microbiota and HS. A two-sample Mendelian randomization study was performed using the summary statistics of skin microbiota from summary GWAS data of the European descent from two cross-sectional, population-based German cohorts, KORA FF4 (n = 324) and PopGen (n = 273). The summary statistics of hidradenitis suppurativa were obtained from the FinnGen DF10 (1,070 cases and 394,105 controls). Inverse variance weighted (IVW), MR-Egger regression, weighted median, simple mode, weighted mode, and MRPRESSO were used to examine the causal association between skin microbiota and hidradenitis suppurativa. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. Our study suggested that genus Corynebacterium in dry skin is significantly associated with HS after false discovery rate (FDR) correction (odds ratio (OR) = 1.04, 95% confidence interval (CI): 1.02-1.06, P = 0.0002, FDR adjusted P = 0.035). Additionally, we found genus Micrococcus in moist skin (OR = 1.10, 95% CI: 1.03-1.18, P = 0.0060, FDR adjusted P = 0.360), species Streptococcus salivarius in dry skin (OR = 1.03, 95% CI: 1.01-1.05, P = 0.0070, FDR adjusted P = 0.360), and species Propionibacterium granulosum (OR = 1.02, 95% CI: 1.00-1.04, P = 0.0460, FDR adjusted P = 0.970) are potentially associated with HS before FDR adjustment. No evidence of the effect in the reverse direction for HS on skin microbial features. This two-sample Mendelian randomization study found that genus Corynebacterium was causally associated with HS. Further studies are needed to clarify the protective effect of prebiotics, probiotics or microbiome transplants on HS.
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Affiliation(s)
- Chenyang Yu
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Wei Yan
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Huidi Shucheng
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yingzhao Huang
- Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of the University of Electronic Science and Technology of China, Chengdu, China.
| | - Xian Jiang
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China.
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
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Alotaibi H, Madani A, AlFada M, Alluhaybi A, Alsehli T, Almuhaideb Q, Alnasser S, Aldossari A, Barakeh M, AlKanaan R. Clinical Epidemiology and Phenotypic Characteristics of Hidradenitis Suppurativa Disease in the Central Region of Saudi Arabia: Findings from a Cross-Sectional. Clin Cosmet Investig Dermatol 2025; 18:129-141. [PMID: 39839355 PMCID: PMC11748051 DOI: 10.2147/ccid.s493638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 12/22/2024] [Indexed: 01/23/2025]
Abstract
Background Hidradenitis suppurativa (HS) is a complex condition that is often misdiagnosed, and regional data on its clinical features and risk factors are limited. This study aimed to explore the clinical epidemiology and phenotypic characteristics of HS in the central region of Saudi Arabia. Materials and Methods A cross-sectional study was conducted on HS patients at King Khalid University Hospital (KKUH) in Riyadh from December 2020 to December 2021. Clinical, epidemiological, and comorbidity data were collected, and the severity of HS was categorized with the Hurley staging system. Statistical analysis was performed with SPSS, with the significance level set to p < 0.05. Results Of the patients, 54.8% were aged 15-30 years, 57.04% were female, and 95.56% were Saudi. Obesity was present in 48.89% of the patients, and 34.07% were smokers. The comorbid conditions included acne (10.37%), asthma (8.15%), mental disorders (2.22%), and endocrine or noncommunicable diseases (18.52%). Most patients (80.74%) had multiple affected sites. No significant associations were found between these factors and HS severity (p > 0.05). Conclusion In conclusion, HS primarily affects young, unmarried Saudi female patients, many of whom are smokers and have comorbid conditions such as asthma and skin disorders. Clinicians should carefully assess the risk profiles of patients, particularly those with smoking habits and comorbidities, and consider screening for HS in high-risk groups.
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Affiliation(s)
- Hend Alotaibi
- Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
| | - Abdulaziz Madani
- Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed AlFada
- Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
| | | | - Turky Alsehli
- Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
| | - Qais Almuhaideb
- Department of Dermatology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Sultan Alnasser
- Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
| | - Abdulelah Aldossari
- Department of Dermatology, King Fahad Specialist Hospital, Buraydah, Saudi Arabia
| | - Maha Barakeh
- Department of Dermatology, King Saud University, Riyadh, Saudi Arabia
| | - Renad AlKanaan
- College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Huynh FD, Damiani G, Bunick CG. Rethinking Hidradenitis Suppurativa Management: Insights into Bacterial Interactions and Treatment Evolution. Antibiotics (Basel) 2024; 13:268. [PMID: 38534703 DOI: 10.3390/antibiotics13030268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/05/2024] [Accepted: 03/05/2024] [Indexed: 03/28/2024] Open
Abstract
Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory dermatological condition characterized by painful and recurrent nodules and purulent abscesses. HS can have a devastating impact on the quality of life of patients. This condition is commonly localized to the axilla, groin, perineal, and inframammary regions, and can develop fistulas and sinus tracts over time. Its pathogenesis remains elusive and is best characterized at the moment as multi-factorial. Additionally, questions remain about the role of cutaneous dysbiosis as a primary HS trigger or as a secondary perturbation due to HS inflammation. This article features works in relation to HS and its interplay with bacterial microflora. We address current treatment approaches and their impact on HS-related bacteria, as well as areas of therapeutic innovation. In the future, disease-modifying or remittive therapy will likely combine an advanced/targeted anti-inflammatory approach with one that effectively modulates cutaneous and deep tissue dysbiosis.
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Affiliation(s)
| | - Giovanni Damiani
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
- Italian Centre of Precision Medicine and Chronic Inflammation, 20122 Milan, Italy
| | - Christopher G Bunick
- Department of Dermatology and Program in Translational Biomedicine, Yale School of Medicine, New Haven, CT 06520, USA
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Jiminez V, Yusuf N. Bacterial Metabolites and Inflammatory Skin Diseases. Metabolites 2023; 13:952. [PMID: 37623895 PMCID: PMC10456496 DOI: 10.3390/metabo13080952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 08/11/2023] [Accepted: 08/14/2023] [Indexed: 08/26/2023] Open
Abstract
The microbiome and gut-skin axis are popular areas of interest in recent years concerning inflammatory skin diseases. While many bacterial species have been associated with commensalism of both the skin and gastrointestinal tract in certain disease states, less is known about specific bacterial metabolites that regulate host pathways and contribute to inflammation. Some of these metabolites include short chain fatty acids, amine, and tryptophan derivatives, and more that when dysregulated, have deleterious effects on cutaneous disease burden. This review aims to summarize the knowledge of wealth surrounding bacterial metabolites of the skin and gut and their role in immune homeostasis in inflammatory skin diseases such as atopic dermatitis, psoriasis, and hidradenitis suppurativa.
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Affiliation(s)
- Victoria Jiminez
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA;
| | - Nabiha Yusuf
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Lelonek E, Bouazzi D, Jemec GBE, Szepietowski JC. Skin and Gut Microbiome in Hidradenitis Suppurativa: A Systematic Review. Biomedicines 2023; 11:2277. [PMID: 37626773 PMCID: PMC10452269 DOI: 10.3390/biomedicines11082277] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/02/2023] [Accepted: 08/04/2023] [Indexed: 08/27/2023] Open
Abstract
Hidradenitis suppurativa (HS) is a chronic skin disease that significantly impairs the quality of life of affected individuals. The disease is characterized by persistent purulent lesions in specific anatomical areas, and its pathophysiology involves multiple factors, including inflammation, genetics, the microbiome, and environmental components. Recent research suggests a potential role for pathogenic bacteria in HS, highlighting the importance of the communication between the human host and the microbiome in maintaining homeostasis and immune system reactivity. However, the exact mechanisms underlying the gut-skin microbial interactions in HS remain unclear. This systematic review aims to examine the existing literature on the differences in skin and gut microbiome composition between HS patients and healthy controls. The review identifies methodological inconsistencies and calls for further research to elucidate the microbiome's role in HS pathogenesis and to explore new therapeutic interventions. The review highlights the need for advancements in microbiome research methodologies, such as metataxonomics and metagenomics, to improve our understanding of the microbiota's impact on health and disease.
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Affiliation(s)
- Edyta Lelonek
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
| | - Dorra Bouazzi
- Department of Dermatology, Zealand University Hospital, 4000 Roskilde, Denmark
| | - Gregor B. E. Jemec
- Department of Dermatology, Zealand University Hospital, 4000 Roskilde, Denmark
| | - Jacek C. Szepietowski
- Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, 50-368 Wroclaw, Poland;
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Rosi E, Guerra P, Silvi G, Nunziati G, Scandagli I, Di Cesare A, Prignano F. Consistency of Bacterial Triggers in the Pathogenesis of Hidradenitis Suppurativa. Vaccines (Basel) 2023; 11:vaccines11010179. [PMID: 36680023 PMCID: PMC9867521 DOI: 10.3390/vaccines11010179] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 12/29/2022] [Accepted: 01/11/2023] [Indexed: 01/19/2023] Open
Abstract
Hidradenitis suppurativa (HS) is an inflammatory skin disease whose pathogenesis remains poorly defined. Over the past decades, the bacterial role in HS patients has been a focus of research. According to the literature, the HS skin (and probably gut) bacterial composition is different to that of healthy controls. To date, a key question is whether compositional changes in the microbial populations are responsible for the development of HS (primum movens), or only secondarily reflect the ongoing inflammatory process. The great diversity of methodologies that have been used to study microbial role in HS have led to an accumulation of conflicting results. Thus, in view of these considerations, the aim of this article is to provide the reader with an overview about different hypotheses proposed to explain the bacterial role in HS pathogenesis.
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Luck ME, Tao J, Lake EP. The Skin and Gut Microbiome in Hidradenitis Suppurativa: Current Understanding and Future Considerations for Research and Treatment. Am J Clin Dermatol 2022; 23:841-852. [DOI: 10.1007/s40257-022-00724-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2022] [Indexed: 11/30/2022]
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Hwang J, Rick J, Hsiao J, Hamzavi IH, Shi VY. Microbiome in Hidradenitis Suppurativa: Current Evidence and Practice. CURRENT DERMATOLOGY REPORTS 2022. [DOI: 10.1007/s13671-021-00349-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Bronnec V, Alexeyev OA. In vivo model of Propionibacterium (Cutibacterium) spp. biofilm in Drosophila melanogaster. Anaerobe 2021; 72:102450. [PMID: 34619359 DOI: 10.1016/j.anaerobe.2021.102450] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 08/27/2021] [Accepted: 09/14/2021] [Indexed: 01/12/2023]
Abstract
OBJECTIVES Acne vulgaris is a common inflammatory disorder of the pilosebaceous unit and Propionibacterium acnes biofilm-forming ability is believed to be a contributing factor to the disease development. In vivo models mimicking hair follicle environment are lacking. The aim of this study was to develop an in vivo Propionibacterium spp. biofilm model in Drosophila melanogaster (fruit fly). METHODS We created a sterile line of D. melanogaster able to sustain Propionibacterium spp. biofilms in the gut. In order to mimic the lipid-rich, anaerobic environment of the hair follicle, fruit flies were maintained on lipid-rich diet. Propionibacterium spp. biofilms were visualized by immunofluorescence and scanning electron microscopy. We further tested if the biofilm-dispersal activity of DNase I can be demonstrated in the developed model. RESULTS We have demonstrated the feasibility of our in vivo model for development and study of P. acnes, P. granulosum and P. avidum biofilms. The model is suitable to evaluate dispersal as well as other agents against P. acnes biofilm. CONCLUSIONS We report a novel in vivo model for studying Propionibacterium spp. biofilms. The model can be suitable for both mechanistic as well as interventional studies.
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Affiliation(s)
- Vicky Bronnec
- Department of Pathology, Medical Biosciences, Umeå University, Umeå, Sweden
| | - Oleg A Alexeyev
- Department of Pathology, Medical Biosciences, Umeå University, Umeå, Sweden.
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Mintoff D, Borg I, Pace NP. The Clinical Relevance of the Microbiome in Hidradenitis Suppurativa: A Systematic Review. Vaccines (Basel) 2021; 9:1076. [PMID: 34696185 PMCID: PMC8537933 DOI: 10.3390/vaccines9101076] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/18/2021] [Accepted: 09/20/2021] [Indexed: 12/21/2022] Open
Abstract
Hidradenitis suppurativa is a chronic disease of the pilosebaceous unit. The name of the condition is a testament to the presumed relationship between the disease and the microbiome. The pathophysiology of hidradenitis suppurativa is, however, complex and believed to be the product of a multifactorial interplay between the interfollicular epithelium, pilosebaceous unit, microbiome, as well as genetic and environmental factors. In this review we assimilate the existing literature regarding the role played by the human microbiome in HS in various contexts of the disease, including the pathophysiologic, therapeutic, and potentially, diagnostic as well prognostic. In conclusion, the role played by the microbiome in HS is extensive and relevant and can have bench-to-bedside applications.
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Affiliation(s)
- Dillon Mintoff
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
- Department of Dermatology, Mater Dei Hospital, Triq Id-Donaturi tad-Demm, MSD 2090 Msida, Malta
| | - Isabella Borg
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
- Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
- Medical Genetics Unit, Department of Pathology, Mater Dei Hospital, MSD 2090 Msida, Malta
| | - Nikolai Paul Pace
- Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta;
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Wark KJL, Cains GD. The Microbiome in Hidradenitis Suppurativa: A Review. Dermatol Ther (Heidelb) 2021; 11:39-52. [PMID: 33244661 PMCID: PMC7859000 DOI: 10.1007/s13555-020-00465-w] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disease. It is characterised by the development of abscesses and nodules in intertriginous anatomical sites. Whilst it is now recognised as an autoinflammatory condition rather than an infective disease, bacteria are implicated in disease pathogenesis. METHODS We performed a search of the literature from inception to 12 August 2020 using the search terms "hidradenitis suppurativa", "Verneuil's disease", "acne inversa", "microbiome", "bacteriology" and "microbiology". Studies were included if they assessed the cutaneous, gut or oral bacteria, bacteriology or microbiome in hidradenitis suppurativa. RESULTS Twenty-one studies examining the cutaneous microbiome and two studies examining the gastrointestinal microbiome in HS were identified. No studies examining the oral microbiome in HS were identified. A total of 972 patients and 46 healthy controls were included across studies examining the cutaneous microbiome. A total of 100 patients and 36 controls were included across both gut microbiome studies. Coagulase-negative Staphylococcus, anaerobes such as Porphyromonas and Prevotella, and Staphylococcus aureus species were commonly encountered organisms across the included cutaneous microbiome studies. The studies examining the gut microbiome were limited, with one small study demonstrating an alteration in the gut microbiome composition compared to controls. The other study found no alteration to the gut microbiome in patients with HS compared to those with inflammatory bowel disease (IBD) and HS, and IBD and/or psoriasis. CONCLUSION Research should be undertaken into the oral microbiome in HS. Further research should be undertaken examining the cutaneous and gut microbiome in HS, and its relationship with documented co-morbidities. Additionally, metagenomics-focused studies may help identify the relationship between microorganisms and host, and this may shed light on new pathways of disease pathogenesis. This may help identify potential future therapeutic targets.
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Affiliation(s)
- Kirsty J L Wark
- Department of Dermatology, Liverpool Hospital, Sydney, Australia.
- School of Medicine, University of New South Wales, Sydney, Australia.
| | - Geoffrey D Cains
- Department of Dermatology, Liverpool Hospital, Sydney, Australia
- School of Medicine, University of New South Wales, Sydney, Australia
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13
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Hidradenitis suppurativa. J Am Acad Dermatol 2020; 82:1045-1058. [PMID: 31604104 DOI: 10.1016/j.jaad.2019.08.090] [Citation(s) in RCA: 267] [Impact Index Per Article: 53.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/14/2019] [Accepted: 08/15/2019] [Indexed: 12/17/2022]
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Zouboulis CC, Nogueira da Costa A, Makrantonaki E, Hou XX, Almansouri D, Dudley JT, Edwards H, Readhead B, Balthasar O, Jemec GBE, Bonitsis NG, Nikolakis G, Trebing D, Zouboulis KC, Hossini AM. Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa. J Eur Acad Dermatol Venereol 2020; 34:846-861. [PMID: 31838778 DOI: 10.1111/jdv.16147] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 11/20/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting. OBJECTIVE Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. METHODS Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non-lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real-time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS-involved skin compartments were also recognized by immunohistochemistry. RESULTS Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1α and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin-A, calgranulin-B and serpin-B4 were detected in the hair root sheath, koebnerisin and connexin-32 in stratum granulosum, transcobalamin-1 in stratum spinosum/hair root sheath, small prolin-rich protein-3 in apocrine sweat gland ducts/sebaceous glands-ducts and matrix metallopeptidase-9 in resident monocytes. CONCLUSION Our findings highlight a panel of immune-related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.
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Affiliation(s)
- C C Zouboulis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany.,European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany
| | | | - E Makrantonaki
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
| | - X X Hou
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
| | - D Almansouri
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
| | - J T Dudley
- Department of Genetics and Genomic Sciences, Institute of Next Generation Healthcare, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - H Edwards
- Translational Medicine, UCB SA, Slough, UK
| | - B Readhead
- Department of Genetics and Genomic Sciences, Institute of Next Generation Healthcare, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - O Balthasar
- Institute of Pathology, Dessau Medical Center, Dessau, Germany
| | - G B E Jemec
- European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany.,Department of Dermatology, Zealand University Hospital, University of Copenhagen, Roskilde, Denmark
| | - N G Bonitsis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
| | - G Nikolakis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany.,European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany
| | - D Trebing
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
| | - K C Zouboulis
- Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland
| | - A M Hossini
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
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15
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Jørgensen AHR, Thomsen SF, Karmisholt KE, Ring HC. Clinical, microbiological, immunological and imaging characteristics of tunnels and fistulas in hidradenitis suppurativa and Crohn's disease. Exp Dermatol 2019; 29:118-123. [PMID: 31519056 DOI: 10.1111/exd.14036] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 08/19/2019] [Accepted: 09/09/2019] [Indexed: 12/20/2022]
Abstract
Hidradenitis suppurativa (HS) tunnels and Crohn's disease (CD) fistulas are a challenge to treat. Although pathogenic similarities have been described between HS and CD, recent studies indicate that clinical, microbiological, immunological and imaging characteristics differ between these diseases. This review highlights the differences between HS tunnels and CD fistulas. Next-generation sequencing studies demonstrate a microbiome in HS tunnels dominated by Porphyromonas spp., Prevotella spp. whereas no specific bacteria have been associated with cutaneous CD. Immunologically, TNF has been found upregulated in HS tunnels along with various interleukins (IL-8, IL-16, IL-1α and IL-1β). In CD fistulas, Th1, Th17, IL-17, IFN-ɤ, TNF and IL-23 are increased. US imaging is an important tool in HS. US of HS tunnels depict hypoechoic band-like structure across skin layers in the dermis and/or hypodermis connected to the base of a widened hair follicle. In CD, MR imaging of simple perianal fistulas illustrates a linear, non-branching inflammatory tract relating to an internal opening in the anus or low rectum and an external opening to the skin surface. An increased awareness of the immediate potential differences between HS tunnels and CD fistulas may optimize treatment regimens of these intractable skin manifestations.
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Affiliation(s)
| | - Simon Francis Thomsen
- Department of Dermato-Venereology & Wound Healing Centre, Bispebjerg Hospital, Copenhagen, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Hans Christian Ring
- Department of Dermato-Venereology & Wound Healing Centre, Bispebjerg Hospital, Copenhagen, Denmark
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16
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Photodynamic therapy combined with surgery for hidradenitis suppurativa: A case report. Photodiagnosis Photodyn Ther 2019; 28:8-9. [PMID: 31362110 DOI: 10.1016/j.pdpdt.2019.07.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 07/19/2019] [Accepted: 07/26/2019] [Indexed: 11/21/2022]
Abstract
Hidradenitis Suppurativa (HS) is a distressing painful chronic inflammatory skin follicular condition. It is a challenge to achieve better therapeutic effect and lower recurrence rate. In this report, ALA-PDT combined with surgery for the treatment achieved ulcer healing, pain elimination, with no relapse during our follow-up.
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17
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A review of microscopy-based evidence for the association of Propionibacterium acnes biofilms in degenerative disc disease and other diseased human tissue. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2019; 28:2951-2971. [PMID: 31359216 DOI: 10.1007/s00586-019-06086-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 07/18/2019] [Accepted: 07/20/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE Recent research shows an increasing recognition that organisms not traditionally considered infectious in nature contribute to disease processes. Propionibacterium acnes (P. acnes) is a gram-positive, aerotolerant anaerobe prevalent in the sebaceous gland-rich areas of the human skin. A ubiquitous slow-growing organism with the capacity to form biofilm, P. acnes, recognized for its role in acne vulgaris and medical device-related infections, is now also linked to a number of other human diseases. While bacterial culture and molecular techniques are used to investigate the involvement of P. acnes in such diseases, definitive demonstration of P. acnes infection requires a technique (or techniques) sensitive to the presence of biofilms and insensitive to the presence of potential contamination. Fortunately, there are imaging techniques meeting these criteria, in particular, fluorescence in situ hybridization and immunofluorescence coupled with confocal laser scanning microscopy, as well as immunohistochemistry. METHODS Our literature review considers a range of microscopy-based studies that provides definitive evidence of P. acnes colonization within tissue from a number of human diseases (acne vulgaris, degenerative disc and prostate disease and atherosclerosis), some of which are currently not considered to have an infectious etiology. RESULTS/CONCLUSION We conclude that P. acnes is an opportunistic pathogen with a likely underestimated role in the development of various human diseases associated with significant morbidity and, in some cases, mortality. As such, these findings offer the potential for new studies aimed at understanding the pathological mechanisms driving the observed disease associations, as well as novel diagnostic strategies and treatment strategies, particularly for degenerative disc disease. These slides can be retrieved under Electronic Supplementary Material.
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18
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Alikhan A, Sayed C, Alavi A, Alhusayen R, Brassard A, Burkhart C, Crowell K, Eisen DB, Gottlieb AB, Hamzavi I, Hazen PG, Jaleel T, Kimball AB, Kirby J, Lowes MA, Micheletti R, Miller A, Naik HB, Orgill D, Poulin Y. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management. J Am Acad Dermatol 2019; 81:76-90. [PMID: 30872156 PMCID: PMC9131894 DOI: 10.1016/j.jaad.2019.02.067] [Citation(s) in RCA: 223] [Impact Index Per Article: 37.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 02/21/2019] [Accepted: 02/27/2019] [Indexed: 01/28/2023]
Abstract
Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.
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Affiliation(s)
| | - Christopher Sayed
- Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
| | - Afsaneh Alavi
- Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Ontario, Canada
| | - Raed Alhusayen
- Department of Medicine, Division of Dermatology, University of Toronto, Toronto, Ontario, Canada
| | - Alain Brassard
- Department of Dermatology, University of California at Davis, Sacramento, California
| | - Craig Burkhart
- Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Karen Crowell
- Health Sciences Library, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Daniel B Eisen
- Department of Dermatology, University of California at Davis, Sacramento, California
| | - Alice B Gottlieb
- Department of Dermatology, Icahn School of Medicine at Mt Sinai Hospital, New York, New York
| | - Iltefat Hamzavi
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan
| | | | - Tara Jaleel
- Department of Dermatology, Duke University School of Medicine, Durham, North Carolina
| | - Alexa B Kimball
- Department of Dermatology, Harvard Medical School, Boston, Massachusetts
| | - Joslyn Kirby
- Department of Dermatology, Penn State Hershey Medical Center, Hershey, Pennsylvania
| | | | - Robert Micheletti
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Angela Miller
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan
| | - Haley B Naik
- Department of Dermatology, University of California San Francisco, San Francisco, California
| | - Dennis Orgill
- Division of Plastic Surgery, Brigham and Women's Hospital, Boston, Massachusetts
| | - Yves Poulin
- Centre de Recherche Dermatologique du Quebec Metropolitain, Quebec City, Quebec, Canada
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19
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Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes ( Cutibacterium acnes) in acne. F1000Res 2018; 7. [PMID: 30613388 PMCID: PMC6305227 DOI: 10.12688/f1000research.15659.1] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/12/2018] [Indexed: 01/08/2023] Open
Abstract
The skin commensal
Propionibacterium acnes, recently renamed
Cutibacterium acnes, along with the other major pathophysiological factors of increased seborrhea, hyperkeratinization of the pilosebaceous unit, and inflammation, has long been implicated in the pathogenesis of acne. Recent advances have contributed to our understanding of the role of
P. acnes in acne. Although there are no quantitative differences in
P. acnes of the skin of patients with acne compared with controls, the
P. acnes phylogenic groups display distinct genetic and phenotypic characteristics,
P. acnes biofilms are more frequent in acne, and different phylotypes may induce distinct immune responses in acne.
P. acnes plays a further important role in the homeostasis of the skin’s microbiome, interacting with other cutaneous commensal or pathogenic microorganisms such as
Staphylococcus epidermidis,
Streptococcus pyogenes, and
Pseudomonas species. In the era of increasing antimicrobial resistance, the selection of acne treatment targeting
P. acnes and the prevention of antibiotic resistance play a key role in improving outcomes in acne patients and public health.
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Affiliation(s)
- Eftychia Platsidaki
- Department of Dermatology, Andreas Syggros Hospital, University of Athens, Athens, Greece
| | - Clio Dessinioti
- Department of Dermatology, Andreas Syggros Hospital, University of Athens, Athens, Greece
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20
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Chapman S, Delgadillo III D, Barber C, Khachemoune A. Cutaneous squamous cell carcinoma complicating hidradenitis suppurativa: a review of the prevalence, pathogenesis, and treatment of this dreaded complication. ACTA DERMATOVENEROLOGICA ALPINA PANNONICA ET ADRIATICA 2018. [DOI: 10.15570/actaapa.2018.5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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21
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Jones D, Banerjee A, Berger PZ, Gross A, McNish S, Amdur R, Shanmugam VK. Inherent differences in keratinocyte function in hidradenitis suppurativa: Evidence for the role of IL-22 in disease pathogenesis. Immunol Invest 2018; 47:57-70. [PMID: 28972431 PMCID: PMC6207448 DOI: 10.1080/08820139.2017.1377227] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. Defective keratinocyte function has been postulated to play a role in HS pathogenesis. Using an in vitro scratch assay, differences between normal, HS, and chronic wound (CW) keratinocytes were evaluated. Normal keratinocytes exhibited faster scratch closure than HS or CW, with normal samples showing 93.8% closure at 96 hours compared to 80.8% in HS (p = 0.016) and 71.5% in CW (p = 0.0012). The keratinocyte viability was similar in normal and HS (91.12 ± 6.03% and 86.55 ± 3.28%, respectively, p = 0.1583), but reduced in CW (72.34 ± 13.12%, p = 0.0138). Furthermore, apoptosis measured by annexin V/propidium iodide, was higher in CW keratinocytes (32.10 ± 7.29% double negative cells compared to 68.67 ± 10.37% in normal and 55.10 ± 9.46% in HS, p = 0.0075). Normal keratinocytes exhibited a significantly higher level of IL-1α (352.83 ± 42.79 pg/ml) compared to HS (169.96 ± 61.62 pg/ml) and CW (128.23 ± 96.61 pg/ml, p = 0.004). HS keratinocytes exhibited significantly lower amounts of IL-22 (8.01 pg/ml) compared to normal (30.24 ± 10.09 pg/ml) and CW (22.20 ± 4.33 pg/ml, p = 0.0008), suggesting that defects in IL-22 signaling may play a role in HS pathogenesis. These findings support intrinsic differences in keratinocyte function in HS which cannot be attributed to reduced keratinocyte viability or increased apoptosis.
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Affiliation(s)
- Derek Jones
- a Division of Rheumatology , Ideas to Health Laboratory, School of Medicine and Health Sciences, The George Washington University , Washington , DC , USA
| | - Anirban Banerjee
- a Division of Rheumatology , Ideas to Health Laboratory, School of Medicine and Health Sciences, The George Washington University , Washington , DC , USA
| | - Peter Z Berger
- a Division of Rheumatology , Ideas to Health Laboratory, School of Medicine and Health Sciences, The George Washington University , Washington , DC , USA
| | - Alexandra Gross
- a Division of Rheumatology , Ideas to Health Laboratory, School of Medicine and Health Sciences, The George Washington University , Washington , DC , USA
| | - Sean McNish
- a Division of Rheumatology , Ideas to Health Laboratory, School of Medicine and Health Sciences, The George Washington University , Washington , DC , USA
| | - Richard Amdur
- a Division of Rheumatology , Ideas to Health Laboratory, School of Medicine and Health Sciences, The George Washington University , Washington , DC , USA
| | - Victoria K Shanmugam
- a Division of Rheumatology , Ideas to Health Laboratory, School of Medicine and Health Sciences, The George Washington University , Washington , DC , USA
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22
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García-Martínez F, López-Martín I, Pascual J. Respuesta de los autores. Semergen 2017; 43:596-597. [DOI: 10.1016/j.semerg.2017.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 03/20/2017] [Indexed: 11/28/2022]
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23
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Shanmugam VK, Zaman NM, McNish S, Hant FN. Review of Current Immunologic Therapies for Hidradenitis Suppurativa. Int J Rheumatol 2017; 2017:8018192. [PMID: 28912816 PMCID: PMC5585618 DOI: 10.1155/2017/8018192] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 07/18/2017] [Indexed: 01/23/2023] Open
Abstract
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. The disease is more common in women and patients of African American descent and approximately one-third of patients report a family history. Obesity and smoking are known risk factors, but associations with other immune disorders, especially inflammatory bowel disease, are also recognized. The pathogenesis of HS is poorly understood and host innate or adaptive immune response, defective keratinocyte function, and the microbial environment in the hair follicle and apocrine gland have all been postulated to play a role in disease activity. While surgical interventions can be helpful to reduce disease burden, there is a high recurrence rate. Increasingly, data supports targeted immune therapy for HS, and longitudinal studies suggest benefit from these agents, both when used alone and as an adjunct to surgical treatments. The purpose of this review is to outline the current data supporting use of targeted immune therapy in HS management.
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Affiliation(s)
- Victoria K Shanmugam
- Division of Rheumatology, Ideas to Health Laboratory, The George Washington University, School of Medicine and Health Sciences, 701 Ross Hall, 2300 Eye Street, NW, Washington, DC 20037, USA
| | - Nadia Meher Zaman
- Division of Rheumatology, Ideas to Health Laboratory, The George Washington University, School of Medicine and Health Sciences, 701 Ross Hall, 2300 Eye Street, NW, Washington, DC 20037, USA
| | - Sean McNish
- Division of Rheumatology, Ideas to Health Laboratory, The George Washington University, School of Medicine and Health Sciences, 701 Ross Hall, 2300 Eye Street, NW, Washington, DC 20037, USA
| | - Faye N Hant
- Division of Rheumatology and Immunology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 822, Charleston, SC 29425, USA
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24
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Kravvas G, Veitch D, Al-Niaimi F. The increasing relevance of biofilms in common dermatological conditions. J DERMATOL TREAT 2017; 29:202-207. [DOI: 10.1080/09546634.2017.1360989] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- G. Kravvas
- Department of Dermatology, University College London Hospital, London, UK
| | - D. Veitch
- Department of Dermatology, University College London Hospital, London, UK
| | - F. Al-Niaimi
- Department of Dermatologic Surgery and Laser Unit, St. Thomas' Hospital, St. John's Institute of Dermatology, London, UK
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25
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Smith MK, Nicholson CL, Parks-Miller A, Hamzavi IH. Hidradenitis suppurativa: an update on connecting the tracts. F1000Res 2017; 6:1272. [PMID: 28794864 PMCID: PMC5538037 DOI: 10.12688/f1000research.11337.1] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/24/2017] [Indexed: 12/18/2022] Open
Abstract
Hidradenitis suppurativa (HS) is a devastating disease involving abscesses, sinus tracts, and inflammation classically affecting the axilla, groin, and/or anogenital region. Although the disease pathogenesis is not fully understood, recent advances suggest that HS pathology runs much deeper than the cutaneous manifestations. It is now believed that HS is a systemic inflammatory disease that gives rise to the characteristic cutaneous manifestations. This disease is problematic for both patients and physicians to manage because of a variety of diagnostic and management difficulties. This article seeks to provide updates on the current understanding of HS to increase awareness and improve management.
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26
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Ring HC, Theut Riis P, Bay L, Kallenbach K, Bjarnsholt T, Jemec GBE. Haematoxylin and eosin staining identifies medium to large bacterial aggregates with a reliable specificity: A comparative analysis of follicular bacterial aggregates in axillary biopsies using peptide nucleic acid-fluorescence in situ hybridization and haematoxylin and eosin staining. Exp Dermatol 2017; 26:943-945. [PMID: 28266778 DOI: 10.1111/exd.13338] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2017] [Indexed: 11/28/2022]
Abstract
Although peptide nucleic acid (PNA), fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy (CLSM) are the reference tools in the study of bacterial aggregates/biofilms, it may also be rather time-consuming. This study aimed to investigate the sensitivity and specificity between bacterial aggregates identified by haematoxylin and eosin (HE) staining vs bacterial aggregates in corresponding PNA-FISH samples. Axillary biopsies were obtained in 24 healthy controls. HE-stained and PNA-FISH samples were investigated using traditional light microscopy and CLSM, respectively. The data demonstrate that HE staining identifies large bacterial aggregates (>10 μm) with a sensitivity of 0.43 and specificity of 1. The methods, however, are not equivalent as demonstrated by a McNemar's test (P=.04). Where bacterial aggregates >10 μm in diameter, HE staining may offer a rapid and practical low-cost tool to evaluate bacterial aggregates.
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Affiliation(s)
- Hans Christian Ring
- Department of Dermatology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
| | - Peter Theut Riis
- Department of Dermatology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
| | - Lene Bay
- Department of Immunology and Microbiology, Costerton Biofilm Centre, University of Copenhagen, Copenhagen, Denmark
| | - Klaus Kallenbach
- Department of Pathology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
| | - Thomas Bjarnsholt
- Department of Pathology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark.,Department for Clinical Microbiology, Copenhagen University Hospital, Copenhagen, Denmark
| | - Gregor B E Jemec
- Department of Dermatology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
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27
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Napolitano M, Megna M, Timoshchuk EA, Patruno C, Balato N, Fabbrocini G, Monfrecola G. Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment. Clin Cosmet Investig Dermatol 2017; 10:105-115. [PMID: 28458570 PMCID: PMC5402905 DOI: 10.2147/ccid.s111019] [Citation(s) in RCA: 157] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body and presenting with painful nodules, abscesses, sinus tracts, and scarring. HS is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture, and immune responses (perifollicular lympho-histiocytic inflammation), finally leading to the development of clinical HS lesions. HS has a destructive impact on the patient’s quality of life, being a very challenging disease. Available treatments are limited, mostly off-label and with high variability in the reported efficacy. Fortunately, a monoclonal antibody against tumor necrosis factor alpha has been recently approved for treatment of moderate to severe HS, offering patients a promising new option. This review focuses on the main features of HS, including epidemiology, clinical aspects, pathogenesis, severity classifications, comorbidities, and currently available treatments.
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Affiliation(s)
- Maddalena Napolitano
- Dipartimento di Medicina e Scienze della Salute "Vincenzo Tiberio", Università degli Studi del Molise, Campobasso
| | - Matteo Megna
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Elena A Timoshchuk
- Department of Dermatovenereology, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia
| | - Cataldo Patruno
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Nicola Balato
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Giuseppe Monfrecola
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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28
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Scuderi N, Monfrecola A, Dessy LA, Fabbrocini G, Megna M, Monfrecola G. Medical and Surgical Treatment of Hidradenitis Suppurativa: A Review. Skin Appendage Disord 2017; 3:95-110. [PMID: 28560220 DOI: 10.1159/000462979] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Accepted: 02/10/2017] [Indexed: 12/27/2022] Open
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease presenting with painful nodules, abscesses, sinus tracts, and scarring primarily affecting apocrine gland-rich intertriginous areas. HS prevalence ranges from 0.05 to 1%. The central pathogenic event in HS is believed to be the occlusion of the upper part of the folliculopilosebaceous unit, leading to the rupture of the sebofollicular canal with the consequent development of perifollicular lymphohistiocytic inflammation. The HS treatment choices are influenced by disease severity and its individual subjective impact, involving both medical and surgical interventions. However, given the chronic nature of HS, its destructive impact on social, working, and daily life of patients, its management is often frustrating for both the patient and physician. Hence, prompt and effective management strategies are urgently needed and a multidisciplinary approach is advocated. Therefore, in this article, we highlighted the main features of HS (clinical aspects, epidemiology, pathogenesis, diagnostic criteria, classifications, comorbidities, and treatments), so that awareness of this disease might be heightened in primary care physicians and surgeons, who may be the first health care providers to see patients with this disease owing to its characteristic clinical presentation (inflammatory nodules, abscesses, sinus tract, etc.).
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Affiliation(s)
- Nicolò Scuderi
- Department of Plastic, Reconstructive and Aesthetic Surgery, University of Rome "Sapienza," Rome, Naples, Italy
| | - Ambra Monfrecola
- Department of Plastic, Reconstructive and Aesthetic Surgery, University of Rome "Sapienza," Rome, Naples, Italy
| | - Luca Andrea Dessy
- Department of Plastic, Reconstructive and Aesthetic Surgery, University of Rome "Sapienza," Rome, Naples, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Matteo Megna
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Giuseppe Monfrecola
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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29
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Ring HC, Bay L, Nilsson M, Kallenbach K, Miller IM, Saunte DM, Bjarnsholt T, Tolker-Nielsen T, Jemec GB. Bacterial biofilm in chronic lesions of hidradenitis suppurativa. Br J Dermatol 2017; 176:993-1000. [PMID: 27564400 DOI: 10.1111/bjd.15007] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND Chronic nonhealing or recurrent inflammatory lesions, reminiscent of infection but recalcitrant to antibiotic therapy, generally characterize biofilm-driven diseases. Chronic lesions of hidradenitis suppurativa (HS) exhibit several characteristics, which are compatible with well-known biofilm infections. OBJECTIVES To determine and quantify the potential presence of bacterial aggregates in chronic HS lesions. METHODS In 42 consecutive patients with HS suffering from chronic lesions, biopsies were obtained from lesional as well as from perilesional skin. Samples were investigated using peptide nucleic acid-fluorescence in situ hybridization in combination with confocal laser scanning microscopy. In addition, corresponding histopathological analysis on haematoxylin and eosin slides was performed. RESULTS Biofilms were seen in 67% of the samples of chronic lesions and in 75% of the perilesional samples. The mean diameter of aggregates in lesional skin was significantly greater than in perilesional skin (P = 0·01). Large biofilms (aggregates > 50 μm in diameter) were found in 42% of lesional samples and in only 5% of the perilesional samples (P = 0·009). The majority of the large biofilms were situated in sinus tracts (63%) or in the infundibulum (37%). The majority of the sinus tract samples (73%) contained active bacterial cells, which were associated with inflammation. CONCLUSIONS This study suggests that biofilm formation is associated with inflammation of chronic HS lesions. The aggregates most likely occur as a secondary event, possibly due to predisposing local anatomical changes such as sinus tracts (tunnels), keratinous detritus and dilated hair follicles.
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Affiliation(s)
- H C Ring
- Department of Dermatology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
| | - L Bay
- Department of Immunology and Microbiology, Costerton Biofilm Centre, University of Copenhagen, Denmark
| | - M Nilsson
- Department of Immunology and Microbiology, Costerton Biofilm Centre, University of Copenhagen, Denmark
| | - K Kallenbach
- Department of Pathology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
| | - I M Miller
- Department of Dermatology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
| | - D M Saunte
- Department of Dermatology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
| | - T Bjarnsholt
- Department of Immunology and Microbiology, Costerton Biofilm Centre, University of Copenhagen, Denmark.,Department for Clinical Microbiology, Section 9301, Copenhagen University Hospital, Denmark
| | - T Tolker-Nielsen
- Department of Immunology and Microbiology, Costerton Biofilm Centre, University of Copenhagen, Denmark
| | - G B Jemec
- Department of Dermatology, Zealand University Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, Denmark
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Matard B, Cavelier‐Balloy B, Reygagne P. Epidermal psoriasiform hyperplasia, an unrecognized sign of folliculitis decalvans: A histological study of 26 patients. J Cutan Pathol 2017; 44:352-357. [DOI: 10.1111/cup.12892] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 12/25/2016] [Accepted: 01/03/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Bruno Matard
- Hôpital Saint‐LouisCentre Sabouraud Paris France
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31
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Banerjee A, McNish S, Shanmugam VK. Interferon-gamma (IFN-γ) is Elevated in Wound Exudate from Hidradenitis Suppurativa. Immunol Invest 2016; 46:149-158. [PMID: 27819528 DOI: 10.1080/08820139.2016.1230867] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory disease of apocrine glands which affects 1-4% of young adults. The purpose of this study was to investigate inflammatory cytokines in effluent from HS lesions and to identify potential local drivers of inflammation in HS. Wound fluid specimens from HS patients (n = 8) and age-matched chronic wound patients (n = 8) were selected for analysis. The hidradenitis suppurativa score (HSS) was used to determine the extent of HS activity. Cytokine analysis was conducted using Meso Scale Discovery cytokine and proinflammatory panels. Interferon-gamma (IFN-γ) was significantly elevated in the HS effluent compared to chronic wounds (1418 ± 1501 pg/ml compared to 102.5 ± 138 pg/ml, p = 0.027). HS effluent also had significantly higher levels of tumor necrosis factor-β (TNF-β) (9.24 ± 7.22 pg/ml compared to 1.65 ± 2.14 pg/ml, p = 0.03). There was no significant difference in any other cytokines. There was no significant difference in demographics in the HS compared to chronic wound cohorts. Mean HSS in the HS cohort was 68.88 (SD ± 41.45). In this proof-of-concept pilot study, IFN-γ was significantly elevated in HS effluent. TNF-β/LT-α levels were also elevated in HS, although the levels were more modest. Further studies should focus on molecular drivers of tissue injury in HS and the relationship between HS effluent cytokine profile and disease activity.
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Affiliation(s)
- Anirban Banerjee
- a Division of Rheumatology , The George Washington University, School of Medicine and Health Sciences , Washington , DC , USA
| | - Sean McNish
- a Division of Rheumatology , The George Washington University, School of Medicine and Health Sciences , Washington , DC , USA
| | - Victoria K Shanmugam
- a Division of Rheumatology , The George Washington University, School of Medicine and Health Sciences , Washington , DC , USA
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Omer H, McDowell A, Alexeyev OA. Understanding the role of Propionibacterium acnes in acne vulgaris: The critical importance of skin sampling methodologies. Clin Dermatol 2016; 35:118-129. [PMID: 28274348 DOI: 10.1016/j.clindermatol.2016.10.003] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Acne vulgaris is a chronic inflammatory skin condition classified by the Global Burden of Disease Study as the eighth most prevalent disease worldwide. The pathophysiology of the condition has been extensively studied, with an increase in sebum production, abnormal keratinization of the pilosebaceous follicle, and an inflammatory immune response all implicated in its etiology. One of the most disputed points, however, is the role of the gram-positive anaerobic bacterium Propionibacterium acnes in the development of acne, particularly when this organism is also found in normal sebaceous follicles of healthy skin. Against this background, we now describe the different sampling strategies that have been adopted for qualitative and quantitative study of P acnes within intact hair follicles of the skin and discuss the strengths and weaknesses of such methodologies for investigating the role of P acnes in the development of acne.
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Affiliation(s)
- Hélène Omer
- Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden
| | - Andrew McDowell
- Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, C-TRIC Building, Altnagelvin Area Hospital, University of Ulster, Londonderry, UK
| | - Oleg A Alexeyev
- Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.
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Abstract
Although the clinical presentation of Hidradenitis Suppurativa (HS) is strongly reminiscent of bacterial infection, the role of bacteria remains controversial. Studies have isolated an array of different bacterial specimens as well as biofilm formation in lesional HS skin. Consistent findings of Gram-positive cocci and -rods including Staphylococus aureus, Coagulase-negative staphylococci (CoNS) and Corynebacterium species (spp) in deep tissue samples have been demonstrated in HS. Although efficacy of antibiotics, i.e., rifampicin, clindamycin or tetracycline may support a microbial role in disease pathogenesis, the most often isolated bacterial specimens are commensal bacteria (CoNS).
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Affiliation(s)
- Hans Christian Ring
- Department of Dermatology, Roskilde Hospital, University of Copenhagen, Køgevej 7-13, Roskilde 4000, Denmark.
| | - Lennart Emtestam
- Department of Dermatology & Venereology, Karolinska University Hospital, Stockholm, Sweden
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Agut-Busquet E, Romaní J, Gilaberte Y, García-Malinis A, Ribera-Pibernat M, Luelmo J. Photodynamic therapy with intralesional methylene blue and a 635 nm light-emitting diode lamp in hidradenitis suppurativa: a retrospective follow-up study in 7 patients and a review of the literature. Photochem Photobiol Sci 2016; 15:1020-8. [PMID: 27417568 DOI: 10.1039/c6pp00082g] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hidradenitis suppurativa is a chronic inflammatory skin disease which has an estimated prevalence of 1%. It is characterized by the formation of recurrent painful suppurative nodules and abscesses in the flexural areas of the body. It is believed that its pathogenesis involves an aberrant, genetically-determined activation of innate immunity against the bacterial commensal flora of intertriginous areas. It has been found that the formation of antibiotic-resistant bacterial biofilms is a common finding in hidradenitis lesions. Photodynamic therapy with different compounds and light sources has demonstrated its efficacy in a number of infectious diseases such as nail mycosis and chronic periodontitis. We retrospectively report our experience in the treatment of hidradenitis with photodynamic therapy using intralesional methylene blue and a 635 nm light-emitting diode lamp in 7 patients. Two patients received one session whereas 5 patients received two sessions. At one month follow-up good response was achieved in 6 patients. After 6 months, 5 patients (71%) maintained remission of the disease in the treated area. In view of the results and literature review, we regard methylene blue as an ideal photosensitizer for photodynamic therapy in this disease.
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Hessam S, Sand M, Georgas D, Anders A, Bechara FG. Microbial Profile and Antimicrobial Susceptibility of Bacteria Found in Inflammatory Hidradenitis Suppurativa Lesions. Skin Pharmacol Physiol 2016; 29:161-7. [DOI: 10.1159/000446812] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 05/11/2016] [Indexed: 11/19/2022]
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Miller IM, Ring HC, Prens EP, Rytgaard H, Mogensen UB, Ellervik C, Jemec GB. Leukocyte Profile in Peripheral Blood and Neutrophil-Lymphocyte Ratio in Hidradenitis Suppurativa: A Comparative Cross-Sectional Study of 462 Cases. Dermatology 2016; 232:511-9. [DOI: 10.1159/000446021] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 04/05/2016] [Indexed: 11/19/2022] Open
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Principi M, Cassano N, Contaldo A, Iannone A, Losurdo G, Barone M, Mastrolonardo M, Vena GA, Ierardi E, Di Leo A. Hydradenitis suppurativa and inflammatory bowel disease: An unusual, but existing association. World J Gastroenterol 2016; 22:4802-4811. [PMID: 27239107 PMCID: PMC4873873 DOI: 10.3748/wjg.v22.i20.4802] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 04/11/2016] [Accepted: 05/04/2016] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) could be associated with several extra-intestinal manifestations (EIMs) involving musculoskeletal, hepatopancreatobiliary, ocular, renal, and pulmonary systems, as well as the skin. In the last years, hidradenitis suppurativa (HS) is acquiring an increasing interest. IBD, especially Crohn's disease (CD), is among the most reported associated diseases in HS patients. The aim of this paper is to give a brief overview of data showing a possible epidemiologic and pathogenetic association between IBD and HS. We performed a pooled-data analysis of four studies and pooled prevalence of HS in IBD patients was 12.8%, with a 95%CI of 11.7%-13.9%. HS was present in 17.3% of subjects with CD (95%CI: 15.5%-19.1%) and in 8.5% of UC patients (95%CI: 7.0%-9.9%). Some items, especially altered immune imbalance, are generally involved in IBD pathogenesis as well as invoked by HS. Smoking is one of the most relevant risk factors for both disorders, representing a predictor of their severity, despite, actually, there being a lack of studies analyzing a possible shared pathway. A role for inheritance in HS and CD pathogenesis has been supposed. Despite a genetic susceptibility having been demonstrated for both diseases, further studies are needed to investigate a genetic mutual route. Although the pathogenesis of IBD and HS is generally linked to alterations of the immune response, recent findings suggest a role for intestinal and skin microbiota, respectively. In detail, the frequent finding of Staphylococcus aureus and coagulase-negative staphylococci on HS cutaneous lesions suggests a bacterial involvement in disease pathogenesis. Moreover, microflora varies in the different cutaneous regions of the body and, consequently, two different profiles of HS patients have been identified on these bases. On the other hand, it is well-known that intestinal microbiota may be considered as "the explosive mixture" at the origin of IBD despite the exact relationship having not been completely clarified yet. A better comprehension of the role that some bacterial species play in the IBD pathogenesis may be essential to develop appropriate management strategies in the near future. A final point is represented by some similarities in the therapeutic management of HS and IBD, since they may be controlled by immunomodulatory drugs. In conclusion, an unregulated inflammation may cause the lesions typical of both HS and IBD, particularly when they coexist. However, this is still a largely unexplored field.
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Hotz C, Boniotto M, Guguin A, Surenaud M, Jean-Louis F, Tisserand P, Ortonne N, Hersant B, Bosc R, Poli F, Bonnabau H, Thiébaut R, Godot V, Wolkenstein P, Hocini H, Lévy Y, Hüe S. Intrinsic Defect in Keratinocyte Function Leads to Inflammation in Hidradenitis Suppurativa. J Invest Dermatol 2016; 136:1768-1780. [PMID: 27206704 DOI: 10.1016/j.jid.2016.04.036] [Citation(s) in RCA: 127] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 03/17/2016] [Accepted: 04/08/2016] [Indexed: 01/06/2023]
Abstract
Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating, follicular disease of the skin. Despite a high prevalence in the general population, the physiopathology of HS remains poorly understood. The use of antibiotics and immunosuppressive agents for therapy suggests a deregulated immune response to microflora. Using cellular and gene expression analyses, we found an increased number of infiltrating CD4(+) T cells secreting IL-17 and IFN-γ in perilesional and lesional skin of patients with HS. By contrast, IL-22-secreting CD4(+) T cells are not enriched in HS lesions contrasting with increased number of those cells in the blood of patients with HS. We showed that keratinocytes isolated from hair follicles of patients with HS secreted significantly more IL-1β, IP-10, and chemokine (C-C motif) ligand 5 (RANTES) either constitutively or on pattern recognition receptor stimulations. In addition, they displayed a distinct pattern of antimicrobial peptide production. These findings point out a functional defect of keratinocytes in HS leading to a balance prone to inflammatory responses. This is likely to favor a permissive environment for bacterial infections and chronic inflammation characterizing clinical outcomes in patients with HS.
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Affiliation(s)
- Claire Hotz
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France
| | - Michele Boniotto
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France
| | - Aurélie Guguin
- Plateforme de Cytométrie en flux, IMRB, UFR de Médecine, Créteil, France
| | - Mathieu Surenaud
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France
| | - Francette Jean-Louis
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France
| | - Pascaline Tisserand
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France
| | - Nicolas Ortonne
- Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Pathology Department, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France; Assistance publique, Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris Est Créteil, Val-de Marne (UPEC), Créteil, France
| | - Barbara Hersant
- Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Assistance publique, Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris Est Créteil, Val-de Marne (UPEC), Créteil, France; Plastic, Reconstructive and Aesthetic Surgery Department, Henri Mondor Hospital, Créteil, France
| | - Romain Bosc
- Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Assistance publique, Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris Est Créteil, Val-de Marne (UPEC), Créteil, France; Plastic, Reconstructive and Aesthetic Surgery Department, Henri Mondor Hospital, Créteil, France
| | - Florence Poli
- Assistance publique, Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris Est Créteil, Val-de Marne (UPEC), Créteil, France; Dermatology Department, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France
| | - Henri Bonnabau
- Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France; INSERM U897, INRIA SISTM, Univ. Bordeaux Segalen ISPED, Bordeaux, France
| | - Rodolphe Thiébaut
- Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France; INSERM U897, INRIA SISTM, Univ. Bordeaux Segalen ISPED, Bordeaux, France
| | - Véronique Godot
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France
| | - Pierre Wolkenstein
- Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Assistance publique, Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris Est Créteil, Val-de Marne (UPEC), Créteil, France; Dermatology Department, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France
| | - Hakim Hocini
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France
| | - Yves Lévy
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Assistance publique, Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris Est Créteil, Val-de Marne (UPEC), Créteil, France; Service d'Immunologie Clinique, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France.
| | - Sophie Hüe
- INSERM U955, Team 16, Créteil, France; Vaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France; Assistance publique, Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris Est Créteil, Val-de Marne (UPEC), Créteil, France; Service d'Immunologie Biologique, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France
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Nikolakis G, Join-Lambert O, Karagiannidis I, Guet-Revillet H, Zouboulis CC, Nassif A. Bacteriology of hidradenitis suppurativa/acne inversa: A review. J Am Acad Dermatol 2016; 73:S12-8. [PMID: 26470608 DOI: 10.1016/j.jaad.2015.07.041] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2015] [Accepted: 07/16/2015] [Indexed: 01/30/2023]
Abstract
Given that follicular papules and pustules, as well as nodules and abscesses, are the clinical hallmarks of hidradenitis suppurativa (HS), an infectious, bacterial pathway has been suspected in the pathogenesis of this chronic, inflammatory condition. Elucidating the behavior and role of bacterial species in HS and their interaction with cutaneous innate immunity will provide more insight into the pathophysiology of this condition. This review of prospective investigations suggests a synergistic relationship between impaired innate immunity and microbial factors in the etiology of HS.
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Affiliation(s)
- Georgios Nikolakis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany; European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany
| | - Olivier Join-Lambert
- Laboratory of Clinical Microbiology, Necker-Enfants Malades Hospital, Assistance publique - Hôpitaux de Paris, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Inserm U1151, équipe 11 "Physiopathologie des infections systémiques", Paris, France; Centre d'Infectiologie Necker-Pasteur, Paris, France
| | - Ioannis Karagiannidis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany; European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany
| | - Hélène Guet-Revillet
- Laboratory of Clinical Microbiology, Necker-Enfants Malades Hospital, Assistance publique - Hôpitaux de Paris, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Inserm U1151, équipe 11 "Physiopathologie des infections systémiques", Paris, France; Centre d'Infectiologie Necker-Pasteur, Paris, France
| | - Christos C Zouboulis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany; European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany.
| | - Aude Nassif
- European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany; Institut Pasteur, Centre Médical, Service de Pathologie Infectieuse et Tropicale, Paris, France; Centre d'Infectiologie Necker-Pasteur, Paris, France
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Join-Lambert O, Duchatelet S, Delage M, Miskinyte S, Coignard H, Lemarchand N, Alemy-Carreau M, Lortholary O, Nassif X, Hovnanian A, Nassif A. Remission of refractory pyoderma gangrenosum, severe acne, and hidradenitis suppurativa (PASH) syndrome using targeted antibiotic therapy in 4 patients. J Am Acad Dermatol 2016; 73:S66-9. [PMID: 26470620 DOI: 10.1016/j.jaad.2015.07.040] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 07/18/2015] [Indexed: 11/16/2022]
Abstract
Pyoderma gangrenosum, severe acne, and suppurative hidradenitis (PASH) syndrome can prove refractory to treatment and is characterized by relapses and recurrences. The combination of antibiotic therapy and surgery can produce success in the management of the syndrome. Acute treatment is required, but maintenance therapy is also necessary to prevent disease relapse. The response to antibiotic therapy is hypothesis generating, raising the issue of a modified host response. To date, anecdotal reports support the use of surgery and medical therapy, but controlled investigations with extended follow-up are necessary to substantiate preliminary data observed with individual cases.
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Affiliation(s)
- Olivier Join-Lambert
- INSERM U1151 eq. 11, Université Paris Descartes - Sorbonne Paris Cité, Laboratory of Microbiology, Necker-Enfants Malades Hospital, Paris, France
| | - Sabine Duchatelet
- INSERM UMR 1163, Laboratory of Genetic Skin Diseases: from Disease Mechanism to Therapies, Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris, France
| | - Maïa Delage
- Institut Pasteur, Medical Center, Paris, France
| | - Snaigune Miskinyte
- INSERM UMR 1163, Laboratory of Genetic Skin Diseases: from Disease Mechanism to Therapies, Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris, France
| | - Hélène Coignard
- Department of Infectious Diseases, Hôpital Necker-Enfants Malades, Paris, France
| | - Nicolas Lemarchand
- Institut de Proctologie Léopold Bellan, Hôpital St Joseph, Paris, France
| | | | - Olivier Lortholary
- Department of Infectious Diseases, Hôpital Necker-Enfants Malades, Paris, France
| | - Xavier Nassif
- INSERM U1151 eq. 11, Université Paris Descartes - Sorbonne Paris Cité, Laboratory of Microbiology, Necker-Enfants Malades Hospital, Paris, France
| | - Alain Hovnanian
- INSERM UMR 1163, Laboratory of Genetic Skin Diseases: from Disease Mechanism to Therapies, Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris, France
| | - Aude Nassif
- Institut Pasteur, Medical Center, Paris, France.
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Kirschke J, Hessam S, Bechara FG. Hidradenitis suppurativa/Acne inversa. COLOPROCTOLOGY 2015. [DOI: 10.1007/s00053-015-0050-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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42
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[Scalp folliculitis: Dissequans or decalvans?]. Ann Dermatol Venereol 2015; 142:629-32. [PMID: 26428395 DOI: 10.1016/j.annder.2015.08.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 03/16/2015] [Accepted: 08/05/2015] [Indexed: 01/10/2023]
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Ring HC, Riis Mikkelsen P, Miller IM, Jenssen H, Fuursted K, Saunte DM, Jemec GBE. The bacteriology of hidradenitis suppurativa: a systematic review. Exp Dermatol 2015; 24:727-31. [PMID: 26119625 DOI: 10.1111/exd.12793] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/28/2015] [Indexed: 12/14/2022]
Abstract
Hidradenitis suppurativa (HS) is a chronic inflammatory disabling skin disease consisting of recurrent nodules, sinuses, fistulas and scarring involving the intertriginous regions. HS is often a therapeutic challenge and most treatments are off-label. A better understanding of aetiology and pathogenesis of HS may facilitate the development of effective treatment. Although the clinical presentation is strongly reminiscent of bacterial infection, the role of bacteria remains controversial. Studies have isolated an array of different bacteria specimens. Consistent findings of Gram-positive cocci and Gram-positive rods including Staphylococus aureus, coagulase-negative staphylococci (CoNS) and Corynebacterium species in deep tissue samples have been demonstrated in HS and may constitute a central target for the immune system. Efficacy of antibiotics, that is rifampicin, clindamycin or tetracycline, supports a microbial role in disease pathogenesis. However, these antibiotics also work as immunomodulators of especially T cells, and the underlying mechanisms may therefore be more complex. We performed a systematic review of previous studies investigating the bacterial flora in hidradenitis suppurativa. We searched PubMed, EMBASE, Royal Danish Library and Cochrane library (search date 11 December 2014). A total of 66 papers were identified and nine papers published between 1988 and 2014 matched our inclusion criteria, yielding bacteriological data of a total of 324 patients with HS (mean age 36.8 years and female/male ratio 215/109). This overview of the bacteriology may aid researchers and physicians exploring the potential role of bacteria in HS. Furthermore, to stimulate a broader debate, we also present different viewpoints on the possible role of bacteria in HS.
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Affiliation(s)
- Hans Christian Ring
- Department of Dermatology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark
| | - Peter Riis Mikkelsen
- Department of Dermatology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark
| | - Iben Marie Miller
- Department of Dermatology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark
| | - Håvard Jenssen
- Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark
| | - Kurt Fuursted
- Department of bacteriology, Statens Serum Institut, Copenhagen, Denmark
| | - Ditte Marie Saunte
- Department of Dermatology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark
| | - Gregor B E Jemec
- Department of Dermatology, Roskilde Hospital, University of Copenhagen, Roskilde, Denmark
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45
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Tüzün Y, Wolf R, Engin B, Keçici AS, Kutlubay Z. Bacterial infections of the folds (intertriginous areas). Clin Dermatol 2015; 33:420-428. [PMID: 26051056 DOI: 10.1016/j.clindermatol.2015.04.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The axillary, inguinal, post-auricular, and inframammary areas are considered skin folds, where one skin layer touches another. Skin fold areas have a high moisture level and elevated temperature, both of which increase the possibility of microorganism overgrowth. A massive amount of bacteria live on the surface of the skin. Some are purely commensal; thus, only their overgrowth can cause infections, most of which are minor. In some cases, colonization of pathogenic bacteria causes more serious infections. This contribution reviews the bacterial infections of the skin fold areas.
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Affiliation(s)
- Yalçın Tüzün
- Department of Dermatology, Cerrahpaşa Medical Faculty, Istanbul University, 34098, Fatih, Istanbul, Turkey.
| | - Ronni Wolf
- Dermatology Unit, Kaplan Medical Center, Rehovot, Israel affiliated with the School of Medicine, Hebrew University and Hadassah Medical Center, Jerusalem, Israel
| | - Burhan Engin
- Department of Dermatology, Cerrahpaşa Medical Faculty, Istanbul University, 34098, Fatih, Istanbul, Turkey
| | - Ayşegül Sevim Keçici
- Department of Dermatology, Cerrahpaşa Medical Faculty, Istanbul University, 34098, Fatih, Istanbul, Turkey
| | - Zekayi Kutlubay
- Department of Dermatology, Cerrahpaşa Medical Faculty, Istanbul University, 34098, Fatih, Istanbul, Turkey
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Abstract
Hidradenitis suppurativa (HS) is a burdensome disease and has the potential to affect the life course of patients. It is a rare disease in children, and the recorded literature is correspondingly scarce. This article reviews the therapeutic options for HS in children and adolescents, and highlights particular differences or challenges with treating patients in this age group compared with adults. The work-up of paediatric patients with HS should include considerations of possible endocrine co-morbidities and obesity. Medical therapy of lesions may include topical clindamycin. Systemic therapy may include analgesics, clindamycin and rifampicin, finasteride, corticosteroids or tumour necrosis factor alpha (TNFα) blockers. Superinfections should be appropriately treated. Scarring lesions generally require surgery.
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Affiliation(s)
- Peter Riis Mikkelsen
- Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Copenhagen, Denmark,
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Gill L, Williams M, Hamzavi I. Update on hidradenitis suppurativa: connecting the tracts. F1000PRIME REPORTS 2014; 6:112. [PMID: 25580266 PMCID: PMC4278191 DOI: 10.12703/p6-112] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Hidradenitis suppurativa (HS) is a debilitating skin disease characterized by recurrent abscesses, sinus tract formation, and scarring. Prevalence estimates range from 0.053% to 4.1%, although HS is likely an underdiagnosed disease. Although the first reports of HS date back to the mid-19th century, the disease continues to plague patients and physicians desperate for a definitive treatment. Advances in the understanding of the disease process include the possibility of a defective basement membrane at the sebofollicular junction of the folliculopilosebaceous unit (FPSU; that is, where the sebaceous gland empties into the hair follicle) as an initiating event followed by secondary bacterial colonization. New evidence suggests that bacteria living in a community, known as a biofilm, rather than single planktonic bacteria in HS lesions may explain why HS can be resistant to current antibiotic treatment regimens. Available treatment options have expanded to include triple-antibiotic therapy, tumor necrosis factor (TNF-α) and interleukin-1 (IL-1) inhibitors (biologics), laser therapy, and surgical excision, including the skin tissue-sparing excision with electrosurgical peeling procedure. Despite the array of treatments available, many patients continue to struggle with the embarrassment, pain, odor, and frustration that accompany this often isolating disease. Physicians should address comorbidities in HS, including the psychosocial issues patients with HS frequently encounter. Patients can be directed to HS support groups, where they can openly discuss their frustrations, share their experiences in dealing with HS, and band together to advocate for themselves. HS is misunderstood by both patients and physicians, often resulting in a delay in clinical presentation and diagnosis. Patients and physicians across multiple specialties must work together to expand awareness of and interest in HS, so that one day, individuals with HS can be freed from this crippling disease.
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Affiliation(s)
- Liza Gill
- College of Human Medicine, Michigan State University965 Fee Road, Room A110, East Lansing, MI 48824USA
| | - Melissa Williams
- Department of DermatologyHenry Ford Hospital, 3031 W. Grand Boulevard, Suite 800, Detroit, MI 48202USA
| | - Iltefat Hamzavi
- Department of DermatologyHenry Ford Hospital, 3031 W. Grand Boulevard, Suite 800, Detroit, MI 48202USA
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