Skin Microbiota Perturbations Are Distinct and Disease Severity-Dependent in Hidradenitis Suppurativa.
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ABSTRACT:
SUBMITTER: Naik HB
PROVIDER: S-EPMC7075718 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hidradenitis suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway of tryptophan catabolism in dermal fibroblasts, correlating with the release of kynurenine pathway-inducing cytokines by inflammatory cell infiltrates. Notably, overactivation of the kynurenine pathway in lesional skin was associated with local and systemic depletion in tryptophan. Yet the skin microbiota normally degrades host tryptophan into indoles regulating tissue inflammation via engagement of the aryl hydrocarbon receptor (AHR). In HS skin lesions, we detected contextual defects in AHR activation coinciding with impaired production of bacteria-derived AHR agonists and decreased incidence of AHR ligand-producing bacteria in the resident flora. Dysregulation of tryptophan catabolism at the skin-microbiota interface thus provides a mechanism linking the immunological and microbiological features of HS lesions. In addition to revealing metabolic alterations in patients with HS, our study suggests that correcting AHR signaling would help restore immune homeostasis in HS skin.
| S-EPMC7605522 | biostudies-literature
Project description:ImportanceThe variation in both clinical appearance and responses to diverse treatment options emphasize the importance of an accurate, clinically relevant, yet easy-to-use scoring system in hidradenitis suppurativa.ObjectiveTo propose and provide validation data for the newly designed Severity Assessment of Hidradenitis Suppurativa score.Design, setting, and participantsWe prospectively assessed disease severity using Hurley staging and the modified Hidradenitis Suppurativa Score in 355 patients referred to Ruhr-University Bochum Department of Dermatology between March 2016 and June 2017. We also assessed disease severity via the Severity Assessment of Hidradenitis Suppurativa score.Main outcomes and measuresEvaluation and assessment of convergent validity and responsiveness to treatment of the Severity Assessment of Hidradenitis Suppurativa score.ResultsEighty-eight of the 355 patients (134 [37.7%] men and 221 [62.3%] women with a median [IQR] age of 40 [30-49] years) were classified as Hurley stage I, 221 were Hurley stage II, and 46 were Hurley stage III, with an overall median modified Hidradenitis Suppurativa Score of 31 (interquartile range [IQR], 19.3-53). The median total Severity Assessment of Hidradenitis Suppurativa score was 6 (IQR, 4-9), significantly different among the 3 Hurley groups. The median SAHS score for patients in Hurley stage I was 5 (IQR, 3-6), 6 (IQR, 5-9) for patients in Hurley stage II, and 9 (IQR, 7-12) for patients in Hurley stage III (P < .001, Kruskal-Wallis test). Correlation analysis showed a significant correlation between the modified Hidradenitis Suppurativa Score and the Severity Assessment of Hidradenitis Suppurativa score (r = 0.79, P < .001). Disease severity assessment before and after 3 months of conservative systemic treatment showed a significant correlation between the Severity Assessment of Hidradenitis Suppurativa score and modified Hidradenitis Suppurativa Score. Both the mHSS (P = .001) and the SAHS score (P < .001) significantly differed between the baseline visit (median mHSS, 33 [IQR, 24-52]; median SAHS score, 6 [IQR, 5-9]) and the 3-month visit (median mHSS, 28 [IQR, 15-43.5]; median SAHS score, 5 [IQR, 4-6.3]). The 2 patient-reported items demonstrated excellent test-retest reliability with intraclass correlation coefficient values greater than 0.8.Conclusions and relevanceOur validation data demonstrated that the Severity Assessment of Hidradenitis Suppurativa score is a disease severity instrument that significantly correlates with Hurley staging and the modified Hidradenitis Suppurativa Score, and is responsive enough to measure treatment outcome.
| S-EPMC5885841 | biostudies-literature
Project description:BackgroundHidradenitis suppurativa (HS) is a chronic, inflammatory skin disease with a large impact on patients' health-related quality of life. However, reliable and consistent outcome measures to assess body surface area (BSA) of HS have not been established.ObjectivesTo develop and assess the reliability and validity of a novel outcome instrument for assessment of HS BSA in a clinical trial setting.MethodsQualitative interviews and focus groups were conducted from July to August 2015 and October 2017 to January 2018. Evaluation of the measurement was assessed during a single-day grading session with patients in April 2018. Participants, who included clinicians or patients, were recruited from academic medical centres in the U.S. mid-Atlantic region.ResultsConcept elicitation included input from 10 providers, of which 60% (n = 6) were female, 80% (n = 8) dermatology specialists and 20% (n = 2) gynaecology specialists. Cognitive debriefing was conducted with 11 providers, of which 82% (n = 9) were dermatologists and 18% (n = 2) gynaecologists. The evaluation stage included 10 clinicians and 23 patients. The intraclass correlation coefficient (ICC) for inter-rater reliability was 0·60 [95% confidence interval (CI) 0·44-0·74]. The ICC for intrarater reliability was 0·98 (95% CI 0·94-1·00). Transformation of the BSA score resulted in an increase in inter-rater reliability to 0·75 (95% CI 0·62-0·85) or 0·76 (95% CI 0·62-0·85). Scores all demonstrated concurrent validity, with statistically significant correlations with extant scoring methods.ConclusionsThis novel scale is a reliable and valid HS outcome instrument and may capture a wide range of patients by assessing BSA. Future research is necessary to demonstrate its responsiveness. What's already known about this topic? The major HS disease activity scales rely on lesions counts and have moderate-to-good reliability. Body surface area (BSA) is one of the physical signs included in the Core Outcome Set for HS, but is not a part of existing HS disease activity scales. What does this study add? A novel disease severity scale, the Severity and Area Score for Hidradenitis (SASH), was developed and the psychometric properties assessed. There was high inter-rater reliability of 0·75 and 0·76 when BSA was scored on an ordinal scale, and an excellent intrarater reliability of 0·98. The SASH score also demonstrated convergent validity with extant instruments. What are the clinical implications of this work? The ability of clinicians to accurately assess disease status will be improved. Implementation of the SASH score will help guide and assess the effectiveness of appropriate treatment choice.
| S-EPMC6928447 | biostudies-literature
Project description:To acquire a better understanding of the molecular pathogenesis of HS, we performed mRNA microarray studies to compare gene expression in lesional skin to healthy skin of HS patients. A significant difference was observed in mRNA expression between lesional and clinically healthy skin of HS patients. Skin biopsy samples (n=30, LS: lesion, NL: non-lesion) were collected at baseline from patients with hidradenitis for RNA extraction and microarray analysis.
2016-01-11 | E-GEOD-72702 | biostudies-arrayexpress
Project description:Hidradenitis suppurativa (HS) is a chronic debilitating disorder that can affect any areas bearing apocrine glands. Perineal HS is associated with high morbidity compared with other anatomic regions. Early-stage disease may mimic various other forms of cutaneous disorders, but as HS progresses pathognomonic skin changes occur. Clinical stage can guide the therapeutic approach, but the lowest recurrence rate is obtained by removing all involved skin and subcutaneous fat. Pruritus ani is a complex disease with a multitude of etiologies. Its management can be frustrating and disappointing for the patient and doctor alike. The key is to start with simple treatment options focusing on perianal hygiene and avoidance of the most common offending foods and beverages. If these measures fail, topical medications should be attempted before graduating to perianal injections of methylene blue as a last resort.
| S-EPMC3140336 | biostudies-other
Project description:Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease resulting in non-healing wounds affecting body areas of high hair follicle and sweat gland density. The pathogenesis of HS is not well understood but appears to involve dysbiosis-driven aberrant activation of the innate immune system leading to excessive inflammation. Marked dysregulation of antimicrobial peptides and proteins (AMPs) in HS is observed, which may contribute to this sustained inflammation. Here, we analyzed HS skin transcriptomes from previously published studies and integrated these findings through a comparative analysis with a published wound healing data set and with immunofluorescence and qPCR analysis from new HS patient samples. Among the top differently expressed genes between lesional and non-lesional HS skin were members of the S100 family as well as dermcidin, the latter known as a sweat gland-associated AMP and one of the most downregulated genes in HS lesions. Interestingly, many genes associated with sweat gland function, such as secretoglobins and aquaporin 5, were decreased in HS lesional skin and we discovered that these genes demonstrated opposite expression profiles in healing skin. Conversely, HS lesional and wounded skin shared a common gene signature including genes encoding for S100 proteins, defensins, and genes encoding antiviral proteins. Overall, our results suggest that the pathogenesis of HS may be driven by changes in AMP expression and altered sweat gland function, and may share a similar pathology with chronic wounds.
| S-EPMC6502346 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) is a Th1/17-driven inflammatory skin disease of the apocrine gland-rich (AGR) skin regions, where keratinocytes seem to be the crucial drivers of the initial pathogenic steps. However, the possible role of permeability barrier alteration in activating keratinocytes during HS development has not been clarified. We compared the major permeability barrier elements of non-lesional HS (HS-NL; n = 10) and lesional HS (HS-L; n = 10) skin with healthy AGR regions (n = 10) via RT-qPCR and immunohistochemistry. Stratum corneum components related to cornified envelope formation, corneocyte desquamation and (corneo)desmosome organization were analyzed along with tight junction molecules and barrier alarmins. The permeability barrier function was also investigated with transepidermal water loss (TEWL) measurements (n = 16). Junction structures were also visualized using confocal microscopy. At the gene level, none of the investigated molecules were significantly altered in HS-NL skin, while 11 molecules changed significantly in HS-L skin versus control. At the protein level, the investigated molecules were similarly expressed in HS-NL and AGR skin. In HS-L skin, only slight changes were detected; however, differences did not show a unidirectional alteration, as KRT1 and KLK5 were detected in decreased levels, and KLK7, KRT6 and DSG1 in increased levels. No significant differences in TEWL or the expression of junction structures were assessed. Our findings suggest that the permeability barrier is not significantly damaged in HS skin and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease.
| S-EPMC9855647 | biostudies-literature
Project description: Not available
| S-EPMC7769071 | biostudies-literature
Project description: Not available
| S-EPMC6464653 | biostudies-literature
Project description:Importance:Although the pathogenesis of hidradenitis suppurativa (HS) remains enigmatic, several factors point to potential involvement of the cutaneous microbiome. Insight into the cutaneous microbiome in HS using next-generation sequencing may provide novel data on the microbiological diversity of the skin. Objective:To investigate the follicular skin microbiome in patients with HS and in healthy controls. Design, Setting, and Participants:This case-control study obtained punch biopsy specimens from patients with HS (lesional and nonlesional) and healthy controls between October 1, 2014, and August 1, 2016. Data were analyzed from March to November 2016. Patients with HS were recruited from the Department of Dermatology, Zealand University Hospital, Roskilde, Denmark. Biopsy specimens were analyzed at the Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. None of the participants received any antibiotics (systemic or topical therapy) within 1 month before the study. In patients with HS, biopsy specimens were obtained from lesional skin (axilla or groin) and nonlesional skin. Only nodules containing at least 1 visible hair follicle were biopsied. Biopsy specimens from healthy controls were obtained from the axilla only. Main Outcomes and Measures:The different microbiomes were investigated using next-generation sequencing targeting 16S and 18S ribosomal RNA. Results:The skin microbiome was characterized in 30 patients with HS (mean [SD] age, 46.9 [14.0] years; 19 [63% female]) and 24 healthy controls (mean [SD] age, 32.2 [12.0] years; 13 [54% female]). The next-generation sequencing data provided a previously unreported (to our knowledge) characterization of the skin microbiome in HS. The study demonstrated that the microbiome in HS differs significantly from that in healthy controls in lesional and nonlesional skin. Overall, the following 5 microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). In lesional skin, microbiome types consisted predominantly of type I or type IV. Microbiome type IV was not detected in healthy controls. Several taxa, including Propionibacterium, showed a significantly higher relative abundance in healthy controls vs HS skin, indicating that Propionibacterium may be part of the pathogenesis in HS. Conclusions and Relevance:The study findings suggest a link between a dysbiotic cutaneous microbiome and HS.
| S-EPMC5710430 | biostudies-literature