Gram-negative anaerobes elicit a robust keratinocytes immune response with potential insights into HS pathogenesis.

Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.

Follicular Skin Disorders, Inflammatory Bowel Disease, and the Microbiome: A Systematic Review.

Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn's disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD.

A systematic review and critical appraisal of metagenomic and culture studies in hidradenitis suppurativa.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disease with still largely unknown pathogenesis. While infectious organisms have been identified in lesions of the disease since the 1980s, questions remain over the role that bacteria and microbiome play. Recent studies using 16S ribosomal RNA gene sequencing and larger culture-based studies have begun to paint a clearer picture of the microbial world of HS. With this systematic review, we summarize all the work that has been done to date in HS bacteriology, analyse potential pitfalls and limitations of the current studies, and address future directions of investigation. This systematic review attempted to collate and analyse all bacteriology studies done to date. This review was prospectively registered with PROSPERO (1670769) performed in line with the PRISMA checklist. Twenty two studies were identified comprising 862 individual HS patients for culture studies and 206 HS patients for 16S rRNA gene sequencing studies. Methodology tended to be varied, with different sampling, culturing and sequencing methods as well as amount of analysis and stratification of patients. Bacteria identified as elevated in HS lesions in sequencing studies as well as grown from HS lesions in culture studies are identified and discussed. These primarily included the anerobic Gram-negative bacilli Prevotella, Porphyromonas and Fusibacterium, the Gram-positive bacilli Corynebacterium, and the Gram-positive cocci Staphylococcus, Streptococcus and Parvimonas. Potential interactions, as well as work in other disease models with related bacteria are also discussed. Areas of further investigation include in vitro studies of interactions between bacteria and keratinocytes, gut and oral microbiome studies and deep sequencing studies for virulence and phage factors.

Yin and Yang: A disrupted skin microbiome and an aberrant host immune response in hidradenitis suppurativa.

The skin microbiome plays an important role in maintaining skin homeostasis by controlling inflammation, providing immune education and maintaining host defense. However, in many inflammatory skin disorders the skin microbiome is disrupted. This dysbiotic community may contribute to disease initiation or exacerbation through the induction of aberrant immune responses in the absence of infection. Hidradenitis suppurativa (HS) is a complex, multifaceted disease involving the skin, innate and adaptive immunity, microbiota and environmental stimuli. Herein, we discuss the current state of HS skin microbiome research and how microbiome components may activate pattern recognition receptor (PRR) pathways, metabolite sensing pathways and antigenic receptors to drive antimicrobial peptide, cytokine, miRNA and adaptive immune cell responses in HS. We highlight the major open questions that remain to be addressed and how antibiotic therapies for HS likely influence both microbial burden and inflammation. Ultimately, we hypothesize that the two-way communication between the skin microbiome and host immune response in HS skin generates a chronic positive feed-forward loop that perpetuates chronic inflammation, tissue destruction and disease exacerbation.

Irrelevance of Panton-Valentine leukocidin in hidradenitis suppurativa: results from a pilot, observational study.

Panton-Valentine leukocidin (PVL) appears to be a virulence factor which, among others, can exacerbate the pathogenicity of Staphylococcus aureus infections, especially inducing severe necrotic, deep-seated skin infections, abscesses, and recurrences. These peculiarities have some overlaps with hidradenitis suppurativa (HS). Our main aim was to assess if S. aureus producing PVL could have some role in influencing clinical features and/or course of HS, specifically in the suppuration and recurrence of lesions. This pilot, mono-centric, observational study included all adult subjects affected with HS consecutively referring to our HS clinic over a 3-month period. Clinically evident suppuration and at least 2 weeks wash out from any antibiotic were the main inclusion criteria. Purulent material from HS skin lesions was collected with swabs in order to isolate micro-organisms, with specific regard to S. aureus. Detection of PVL was performed by real-time quantitative PCR (RT-qPCR). We also analyzed purulent material from suppurative skin lesions other than HS, as a control. Thirty HS patients were included; 29 purulent lesions (96.7%) harbored at least one bacterial species. Five (16.7%) swab samples were positive for S. aureus, none of which was positive for PVL genes. Among the 30 purulent disorders included as controls, 8 (26.3%) were positive for S. aureus; of these, 4 strains (50%) expressed LPV. The study results seem to exclude the pathogenetic involvement of S. aureus producing PVL in HS; as a result, PVL does not seem to represent a potential target in the future development of HS treatments.

Staphylococcus aureus Carriage in Hidradenitis Suppurativa: Impact on Response to Adalimumab.

BACKGROUND: Several patients with hidradenitis suppurativa (HS) present flare-ups during treatment with adalimumab (ADA), the cause of which is not clear. ADA is the only FDA-approved biologic for the therapy of moderate-to-severe HS. A previous study of our group has shown that Staphylococcus aureus stimulation of whole blood affects the production of human ß-defensin 2 and modulates HS severity. It is, therefore, hypothesized, that carriage of S. aureus may drive HS flare-ups. OBJECTIVE: To explore the association between carriage of S. aureus and loss of response to ADA. PATIENTS AND METHODS: Among patients with moderate-to-severe HS without carriage of S. aureus at start of treatment with ADA, we investigated for carriage of S. aureus from the nares when flare-ups occurred. Flare-ups were pre-defined as at least 25% increase of inflammatory lesions (sum of inflammatory nodules and abscesses) from baseline. Samplings were also done after completion of 12 weeks of ADA treatment from all patients who did not present flare-ups. Clinical response to ADA was assessed by the HS Clinical Response score (HiSCR). RESULTS: Thirty-nine patients were studied; 24 with Hurley II stage HS and 15 with Hurley III stage HS. Twenty-nine patients achieved HiSCR after 12 weeks of treatment without any flare-ups; 10 patients had flare-ups and failed HiSCR. Three (10.3%) and 5 (50%) patients, respectively, had nasal carriage of S. aureus (odds ratio 8.67; 95% CI 1.54-48.49; p = 0.014). Among 32 patients reaching follow-up week 48, 20 patients achieved HiSCR and 12 had flare-ups leading to ADA failure; 2 (10%) and 5 (41.7%) patients, respectively, had positive culture for S. aureus (odds ratio 6.42; 95% CI 1.00-41.20; p = 0.05). CONCLUSION: Nasal carriage of S. aureus may be associated with loss of response to ADA. Findings need confirmation in larger series of patients.

Clinical, microbiological, immunological and imaging characteristics of tunnels and fistulas in hidradenitis suppurativa and Crohn's disease.

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-1ß). 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.

Staphylococcus aureus Carriage Status in Patients with Hidradenitis Suppurativa: An Observational Cohort Study in a Tertiary Referral Hospital in Athens, Greece.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory disease that affects the pilosebaceous unit in apocrine gland-bearing areas. Bacteria are thought to play a role in the development and progression of disease. In addition, antibiotics are frequently used as first-line management for HS. We sought to determine the carriage status of Staphylococcus aureus and its resistance to antibiotics among patients with HS in a tertiary referral hospital in Athens, Greece. METHODS: In this observational cohort study, 68 consecutive patients attending the HS clinic of "Attikon" General University Hospital in Athens, Greece, during a 9-month period were enrolled. All patients had not received any antibiotic therapy for any reason during the previous 3 months before enrollment. Nasal and oropharyngeal samplingwere obtained, and specimens were tested for the presence of S. aureus.Antibiotic susceptibility testing was performed using the VITEK 2 system. Standard statistical tests, descriptive statistics tests, and χ2 and Pearson correlation tests were performed, using IBM SPSS Statistics 25.The level of significance was set at a pvalue <0.05. RESULTS: Sixty-eight patients with HS were studied. There were 44 females (64.7%) and 24 males (35.3%). The mean age was 36.63 ± 13.0 (IQR = 21), and the mean age at onset of disease was 23.90 ± 11.53 (IQR = 14). The mean duration of disease was 12.74 ± 10.20 years (IQR = 15). Fifteen (22.1%) of the patients were Hurley stage I, 22 (32.4%) were Hurley stage II, and 31 (45.6%) were Hurley stage III. S. aureus carriage was detected in 17 patients (25%). Six of them (35.3%) had MRSA strains. There was an increased prevalence of S. aureus colonization (p = 0.058) and MRSA (p = 0.101) in Hurley stage III patients, but this result was not statistically significant. CONCLUSIONS: We found a 25% prevalence of S. aureus colonization (17/68 patients) and a 35.3% prevalence of MRSA (6/17) among our HS patients. There was an increased prevalence of S. aureusand MRSA positivity in HS patients with Hurley stage III. Further studies are needed to clarify the possible clinical significance of S. aureus carriage in the disease development and progression as well as in the treatment outcome.

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa-Light at the End of the Microbiological Tunnel.

The development of next generation sequencing, coupled with advances in bio-informatics, has provided new insights into the role of the cutaneous microbiome in the pathophysiology of a range of inflammatory skin diseases. In fact, it has even been suggested that the identification of specific skin microbial signatures may not only be useful in terms of diagnosis of skin diseases but they may also ultimately help inform personalised treatment strategies. To date, research investigating the role of microbiota in the development of inflammatory skin diseases has largely focused on atopic eczema and psoriasis vulgaris. The role of the microbiome in Hidradenits suppurativa (HS)-also known as acne inversa-a chronic auto-inflammatory skin disease associated with significant morbidity, has received comparatively little attention. This is despite the fact that antimicrobial therapy plays a central role in the treatment of HS. After briefly outlining the clinical features of HS and current treatment strategies, we move on to review the evidence of microbial dysbiosis in HS pathophysiology. We conclude by outlining the potential for metagenomic studies to deepen our understanding of HS biology but more importantly to identify novel and much needed treatment strategies.

Bacterial biofilm is associated with higher levels of regulatory T cells in unaffected hidradenitis suppurativa skin.

BACKGROUND: The role of bacterial biofilm in hidradenitis suppurativa (HS) is highly debated. Less biofilm is found in clinically unaffected axillary perilesional skin of HS patients compared with healthy controls. OBJECTIVE: To study the correlation between biofilm and the phenotypical characterization of the preclinical inflammatory infiltrate. MATERIALS AND METHODS: An exploratory comparative study of punch biopsies from unaffected axillary HS skin compared to similarly biopsies from healthy controls underwent standard staining procedures for CD4, CD8, CD25, FoxP3 and IL17. Standard-sized inflammatory histological hotspots were identified manually. Slides were scanned into Leica Biosystems' Digital Image Hub. Number of stained cells per slide and hotspot was found using an algorithm. RESULTS: 12.5% of HS had biofilm compared to 85% of controls. For full slides, HS patients had more CD4+ cells than controls; HS patients with biofilm had higher CD4+ cell number than controls with or without biofilm and HS patients without biofilm. For hotspots, HS patients with biofilm had higher number of CD4+FoxP3+ cells than HS patients without biofilm and controls with biofilm. CONCLUSION: The association between biofilm and the number of regulatory T cells in HS patients supports the concept of dysbiosis as a factor in the preclinical HS lesions.

The microbiome of tunnels in hidradenitis suppurativa patients.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels and scarring involving the intertriginous regions. Recent next-generation sequencing (NGS) studies suggest genera such as Prevotella spp., Peptoniphilus spp. and Porphyromonas spp. are associated with chronic and early HS lesions. However, a systematic investigation of the bacterial microbiome in HS tunnels remains unexplored using NGS. OBJECTIVE: We aimed to investigate the bacterial composition of the luminal white gelatinous material found in HS tunnels using NGS. METHODS: An exploratory study of patients with diagnosis of HS (n = 32) with tunnels. The tunnels were present either in the groin (n = 17) or in the axilla (n = 15). During deroofing of the tunnels, a sterile E-swab was taken of the luminal gelatinous material. The samples were investigated using NGS targeting 16S ribosomal RNA. RESULTS: The skin microbiome was characterized in 32 HS patients. Overall, five microbiome types were identified: Porphyromonas spp. (type I), Corynebacterium spp., (type II), Staphylococcus spp. (type III), Prevotella spp. (type IV) and Acinetobacter spp (type V). Porphyromonas spp. (type I) and Prevotella spp. (IV) were the most frequent genera found the tunnels. CONCLUSION: This study points to a potential association between the presence of certain anaerobic bacteria (Porphyromonas spp., Prevotella spp.) and HS tunnels. It may be speculated that these two genera are associated with the pathogenesis in HS either as drivers or as biomarkers.

Rates of antibiotic resistance/sensitivity in bacterial cultures of hidradenitis suppurativa patients.

BACKGROUND: Antibiotic (AB) treatment is one of the first steps in the management of hidradenitis suppurativa (HS). Bacteria, in HS patients, may play a double role, as triggering factors of inflammatory reactions and/or agents of infection. OBJECTIVES: The aims of this study are as follows: (i) to assess prevalence and AB resistance of bacterial growths in HS patients (ii) assessment of the clinical relevance of obtained data in guiding the selection of the most effective AB therapy. METHODS: Purulent material from 137 skin lesions of HS patients was collected with swabs. Bacterial flora and AB sensitivity were determined using microbiological cultures for aerobic and anaerobic bacteria. RESULTS: A total of 114 samples resulted positive for bacteria. Sample was collected from the axillae, groin and perianal areas. A total of 163 single bacterial growths were observed; 55% were Gram-positive and 44% were Gram-negative. Among them, 18.4% were anaerobic. The most frequent bacterial families included enterobacteriaceae (30.7%), Staphylococcus (25.2%) and Streptococcus (14.1%). The most frequent genus or species were proteus spp. (13.5%) and Escherichia coli (9.8%). The prevalence of AB resistance observed was clindamycin 65.7%, rifampicin 69.3%, penicillin 70.0%, ciprofloxacin 74%, tetracycline 84.7% and erythromycin 89.0%. A limitation of the study is represented the short culture period adopted which may have impaired the isolation of anaerobes. CONCLUSIONS: Bacterial growth in HS patients has shown a high level of resistance to ABs, including rifampicin, clindamycin and tetracyclines, cited as an empiric choice in HS therapeutic guidelines. A targeted and specific AB therapy, driven by microbiological evaluations with prolonged culture periods, seems more appropriate than empiric, generic, non-specific, therapeutic approaches. Current knowledge regarding HS bacterial AB resistance should be considered in the update of current therapeutic guidelines for HS.

Biofilm production and antibiotic susceptibility of Staphylococcus epidermidis strains from Hidradenitis Suppurativa lesions.

BACKGROUND: An aberrant interaction between commensal skin bacteria and the host skin immune system is considered important in the pathogenesis of hidradenitis suppurativa (HS). OBJECTIVE: In this study, we investigated the antibiotic susceptibility and biofilm-forming capabilities of S. epidermidis strains isolated from HS patients. METHODS: Skin biopsies were taken from active HS lesions such as inflammatory nodules and/or sinuses and non-involved skin from 26 patients and cultured under optimal microbiological conditions for 24 h. Planktonic growth, biofilm production, antibiotic susceptibility and biofilm eradication by clindamycin, doxycycline, rifampicin and tetracycline were tested including a laboratory control strain of S. epidermidis for reference. RESULTS: Staphylococcus epidermidis was cultured in 16 of 26 HS patients (62%). In total 27 different S. epidermidis isolates were identified; 16 (59%) from non-involved skin and 11 (41%) from HS lesions. All bacterial strains showed planktonic growth. Twenty-four of 27 (89%) isolates were strong biofilm producers in vitro. The biofilm-forming capability varied amongst the strains from non-involved skin and lesional skin. Twenty-four strains had an intermediate to resistant antibiotic susceptibility to clindamycin (89%). Rifampicin was the most effective antibiotic at inhibiting planktonic growth and at eradication of biofilm (P < 0.05). CONCLUSION: We observed a slight increase in S. epidermidis virulence, characterized by resistance to commonly used antibiotics, increased biofilm production and resistance to biofilm eradication. In particular, the reduced sensitivity to tetracycline and clindamycin, two standard antibiotics in the treatment of HS, is alarming. Rifampicin, also important in HS treatment, showed the greatest efficacy at eradicating the biofilm at low MIC concentrations.

Moderate to severe hidradenitis suppurativa patients do not have an altered bacterial composition in peripheral blood compared to healthy controls.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels and scarring involving the intertriginous skin. Patients with HS often report an array of systemic symptoms such as fatigue and malaise. The aetiology of these symptoms remains unclear. Previously, various bacteria have been associated with mature HS lesions, and bacteraemia has been reported in patients with HS using traditional culturing methods. Thus, we hypothesized that a low-grade bacteraemia contributes to the symptomatology in patients with HS. OBJECTIVE: To explore the potential presence of bacteraemia in patients with HS and healthy controls. METHOD: A case-control study. Compositions of bacteria in the blood of 27 moderate to severe HS patients and 26 healthy controls were investigated using next-generation 16S ribosomal RNA gene sequencing (NGS) and routine anaerobic and aerobic blood culturing. None of the participants received any antibiotics (systemic or topical therapy) within 1 month prior to the study. HS patients with a recent flare were randomly selected by consecutive recruitment of eligible patients from the Department of Dermatology, Zealand University Hospital, Denmark. Healthy controls were recruited from the University of Copenhagen as well as from the healthcare staff. RESULTS: The different bacterial compositions were investigated using NGS and traditional anaerobic and aerobic blood culturing. Our NGS analysis provided a previously unreported characterization of the bacterial composition in peripheral blood from patients with HS and healthy controls. Overall, our data demonstrated that patients with HS do not have a different bacterial composition in their peripheral blood than healthy controls. CONCLUSION: The study suggests that the self-reported symptoms in HS such as malaise and fatigue may not be linked to bacteraemia.

The Microbiological Landscape of Anaerobic Infections in Hidradenitis Suppurativa: A Prospective Metagenomic Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a frequent and severe disease of the skin, characterized by recurrent or chronic skinfold suppurative lesions with a high impact on quality of life. Although considered inflammatory, antimicrobial treatments can improve or lead to clinical remission of HS, suggesting triggering microbial factors. Indeed, mixed anaerobic microbiota are associated with a majority of HS lesions. Our aim in this study was to characterize the landscape of anaerobic infections in HS using high-throughput sequencing. METHODS: We sampled and cultured 149 lesions and 175 unaffected control skinfold areas from 65 adult HS patients. The microbiome of 80 anaerobic lesions was compared to that of 88 control samples by 454 high-throughput sequencing after construction of 16S ribosomal RNA gene libraries. RESULTS: Bacterial cultures detected anaerobes in 83% of lesions vs 53% of control samples, combined with milleri group streptococci and actinomycetes in 33% and 26% of cases, respectively. High-throughput sequencing identified 43 taxa associated with HS lesions. Two gram-negative anaerobic rod taxa, Prevotella and Porphyromonas, predominated, contrasting with a reduced abundance of aerobic commensals. These rare taxa of normal skinfold microbiota were associated with lesions independently of gender, duration and familial history of HS, body mass index, and location. Two main additional taxa, Fusobacterium and Parvimonas, correlated with the clinical severity of HS. CONCLUSIONS: In this study we reveal the high prevalence and particular landscape of mixed anaerobic infection in HS, paving the way for rationale targeted antimicrobial treatments.

Bacterial biofilm in chronic lesions of hidradenitis suppurativa.

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.

Patterns of antimicrobial resistance in lesions of hidradenitis suppurativa.

BACKGROUND: Antibiotic therapy is commonly used to treat hidradenitis suppurativa (HS). Although concern for antibiotic resistance exists, data examining the association between antibiotics and antimicrobial resistance in HS lesions are limited. OBJECTIVE: We sought to determine the frequency of antimicrobial resistance in HS lesions from patients on antibiotic therapy. METHODOLOGY: A cross-sectional analysis was conducted on 239 patients with HS seen at the Johns Hopkins Medical Institutions from 2010 through 2015. RESULTS: Patients using topical clindamycin were more likely to grow clindamycin-resistant Staphylococcus aureus compared with patients using no antibiotics (63% vs 17%; P = .03). Patients taking ciprofloxacin were more likely to grow ciprofloxacin-resistant methicillin-resistant S aureus compared with patients using no antibiotics (100% vs 10%; P = .045). Patients taking trimethoprim/sulfamethoxazole were more likely to grow trimethoprim/sulfamethoxazole-resistant Proteus species compared with patients using no antibiotics (88% vs 0%; P < .001). No significant antimicrobial resistance was observed with tetracyclines or oral clindamycin. LIMITATIONS: Data on disease characteristics and antimicrobial susceptibilities for certain bacteria were limited. CONCLUSIONS: Antibiotic therapy for HS treatment may be inducing antibiotic resistance. These findings highlight the importance of stewardship in antibiotic therapy for HS and raise questions regarding the balance of antibiotic use versus potential harms associated with antibiotic resistance.

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

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

Normal Skin Microbiota is Altered in Pre-clinical Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels (sinus tracts) and scarring involving the intertriginous regions. The clinical course of HS is compatible with a biofilm-driven disease, and biofilm has been described in lesional HS skin. We therefore hypothesized that clinically unaffected HS skin would also have an increased presence of biofilm compared with that of healthy controls. We conducted a case-control study, investigating the morphology of the axillary skin microbiota. Peptide nucleic acid - fluorescence in situ hybridization probes were used in combination with confocal laser scanning microscopy. Significant differences were found in both distribution and quantity of the cutaneous microbiota in clinically non-affected axillary skin of patients with HS compared with healthy controls. Surprisingly, we detected fewer bacteria and less biofilm in patients with HS. The reduced microbiota in patients with HS may play an important role in the early course of the disease.

Actinotignum schaalii subcutaneous abscesses in a patient with hidradenitis suppurativa: Case report and literature review.

Actinotignum schaalii (formerly Actinobaculum schaalii) is a Gram-positive, facultative anaerobic rod that is typically involved in urinary tract infections in elderly patients or those with underlying urological pathologies. In contrast, abscess formation caused by A. schaalii is very rare. We present a case of multiple abscesses in the perineal area in a young patient with hidradenitis suppurativa associated with A. schaalii and Prevotella melaninogenica and review the relevant literature on the topic.