Question 1

Genetics & Genes

Accepted Answer

Genetics and Gene Auto-Inflammatory
 
Synopsis of Study: 
 
Both familial (hereditary) and sporadic (acquired, non- hereditary) cases of HS have been reported. It is thought that approximately 33% of HS cases are familial. Genetic variants of HS are heterogeneous, with several mutations identified throughout the genome, lacking a consistent genotype to phenotype correlation 39– 41. One study of 53 Chinese patients hypothesized to have familial HS were found to have a unique phenotype consisting of an increased male prevalence, earlier onset, and more severe disease involving atypical regions such as the neck and back 42. Because of the phenotypic variance in HS, Canoui-Poitrine et al. attempted to develop distinct phenotype-based subtypes of the disease, including axillary-mammary, follicular, and gluteal types. However, genetic analyses have not yet correlated with this grouping technique 43. Additionally, the specific phenotype “hidradenitis suppurativa fulminans” has been proposed to describe a specific, severe presentation of the disease 40. Phenotypic categorization will assist in future studies and determining a greater understanding of the varying presentations and genetics of this disease.
 
Some cases of HS are associated with syndromes, including pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome, related to mutations in proline-serine-threonine-phosphatase protein 1 (PSTPIP1). This gene is involved in the regulation of the inflammasome complex, a series of proteins and signaling pathways the body utilizes in response to inflammation-inducing stimuli 44. Another similar syndrome, pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) syndrome, is also associated with PSTPIP1 gene mutations 45. Similarly, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome has been associated with cases of HS. These relationships between HS and other auto-inflammatory diseases have bolstered the theory that HS may be auto-inflammatory in nature 46.
 
There is also evidence to support a relationship between familial HS and loss-of-function mutations in γ-secretase proteins, such as presenilin-1, presenilin enhancer-2, anterior pharynx defective 1, and nicastrin (NCSTN). These mutations were noted in variants of HS involving atypical regions such as the thighs and trunk 7, 47. The protease γ-secretase plays a role in the regulation of the canonical Notch signaling pathway, which is relevant to HS because Notch functions in the development of hair follicles, and as an immunomodulator in T-cell-mediated cellular immune responses. Inherited or acquired alterations in Notch signaling may play a pivotal role in HS disease pathogenesis 48. Cigarette smoking has been shown to decrease the activity of the Notch signaling pathway, further strengthening this association. Of note, having one of the above mutations does not guarantee disease development or progression 49.
 
Further, Xiao et al. analyzed the gene encoding NCSTN ( NCSTN) in a human keratinocyte cell line and found that NCSTN knockdown cells exhibited impaired γ-secretase activity, leading to more rapid proliferation and a greater proportion of cells in the S-phase of the cell cycle. This study bolstered the theory that a deficiency in the NCSTN gene in familial forms of HS may play a role in abnormal keratinocyte growth and proliferation 50. Interestingly, Duchatelet et al. discovered a NCSTN mutation in a patient with PASH syndrome, interrelating genetic and auto-inflammatory hypotheses of the pathogenesis of HS 51.
 
Finally, a retrospective study by Deckers et al. evaluated trends in early onset HS, defined as disease onset before age 13. A family history of HS was a significant factor in the diagnosis of early onset HS as well as more widespread disease. There were no reported differences in comorbidities in patients with early onset disease compared to controls with normal-onset HS 52.
 
The referees who approved this portion article are:
 
Geoffrey David Cains, Department of Dermatology, University of New South Wales, Sydney, Australia
 
No competing interests were disclosed.
 
Christopher Sayed, Department of Dermatology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Dermatology and Skin Cancer Center, Chapel Hill, NC, USA
 
Competing interests: Christopher Sayed has held roles with Abbvie Inc. as a speaker, Advisory Board Member and co-investigator.
 
Robert Micheletti, Department of Dermatology and Department of Medicine, University of Pennsylvania, Philadelphia, USA
 
No competing interests were disclosed.
 
Article information
Version 1. F1000Res. 2017; 6: 1272.
 
Published online 2017 Jul 28. doi: 10.12688/f1000research.11337.1
PMCID: PMC5538037
PMID: 28794864
 
Mallory K Smith,1 Cynthia L Nicholson,2 Angela Parks-Miller,2 and Iltefat H Hamzavia,2
 
1Wayne State University School of Medicine, Detroit, MI, USA
 
2Henry Ford Hospital Department of Dermatology, Detroit, MI, USA
aEmail: gro.shfh@1vazmahi
 
Mallory Smith and Cynthia Nicholson drafted and wrote the article. Angela Miller contributed expertise for the “Psychosocial impact” section, and Iltefat Hamzavi contributed expertise on disease management. All authors were involved in the manuscript revisions and agreed on the final submission.
​
Full Study: h(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538037/)ttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538037/(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538037/)
​

Question 2

Skin Transcriptome in HS Uncovers an Antimicrobial

Accepted Answer

Skin Transcriptome in HS Uncovers an Antimicrobial
 
Synopsis:
 
Hidradenitis suppurativa is a chronic and frequently debilitating cutaneous disorder that significantly impacts the quality of life of patients. Compared to other cutaneous disorders, such as psoriasis and atopic dermatitis, it is relatively poorly characterized. HS is significantly different from these classic inflammatory skin diseases through the clinical presentation of non-healing skin lesions and the formation of ducts and cysts that become highly inflamed. Our transcriptomic analysis of HS lesions suggests a significant role for innate antimicrobial immunity and altered sweat gland function in HS disease pathology and furthermore revealed a previously unknown set of DEG that overlap with healing wounds.
 
Recent studies have begun to illuminate the role of sweat gland cells, specifically sweat gland progenitors, in wound healing and re-epithelialization. Sweat glands contain multipotent progenitor cells that can migrate to epidermal layers of the skin and contribute to repair; in addition, eccrine ductal cells participate in re-epithelialization [98, 102]. Sweat glands may also contribute to cutaneous immunity beyond their role in wound repair through production of inflammatory cytokines and DCD, a sweat-gland associated AMP [59, 104]. Therefore, it is possible that sweat glands produce multiple host factors, including antimicrobial DCD that promote epithelial regeneration and that this pathway is dysregulated in HS prohibiting healing of severe HS lesions.
 
We also uncovered substantial transcriptional overlap between HS lesions and wounded skin, suggesting that HS may represent a wound-like environment. Our analysis could pave the way for development of new therapies for HS. For example, supplementation and activation of natural AMPs, such as DCD, may be promising therapeutic options for the treatment of HS.
​
Full Study Link:
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502346/(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502346/)

Question 3

Defining HS Phenotypes

Accepted Answer

Defining Hidradenitis Suppurativa Phenotypes
Based on the Elementary Lesion Pattern: Results of a Prospective Study
​
Synopsis:
​
Background: It has been proposed that two main phenotypes of hidradenitis suppurativa (HS) exist. This proposal is based upon different elementary structures detected in the skin, namely follicular subtypes and inflammatory subtypes. Having an accurate definition of these two variants could help us to better identify patients who may require an early intervention with currently approved targeted immunomodulatory therapies.
 
Objective: To define and distinguish between the epidemiological, clinical and analytic characteristics of these two HS phenotypes.
 
Methods: An observational, descriptive, non-randomized and prospective study was conducted. Patients diagnosed with HS between May 2012 and April 2017 by a specialized unit were included. Ultrasound evaluation was performed in all cases.
 
Results: About 197 patients were included, 100 women and 97 men, aged between 25 and 47 years. The mean age of onset was significantly different between phenotypes, ranging between 26.69 ± 9.05 in the inflammatory subtype and 17.62 ± 6.42 in the follicular subtype. Follicular subtype patients exhibited a significantly higher number of nodules combined with the presence of multiple commedons (5.65 ± 3.38 versus 0.89 ± 2.72). This contrasted with the higher count of abscesses and fistulas detected in the inflammatory subtype (respectively, 4 ± 2.74 and 3.11 ± 2.56 versus 0.56 ± 1.02 and 0.26 ± 0.56). IgA levels were significantly higher in the inflammatory subtype (497.71 ± 262.26 versus 232.38 ± 84.06). Mean IHS4 score evaluation was higher in the inflammatory subtype (21.04 ± 11.9) compared with the follicular phenotype (7.54 ± 4.66). The inflammatory subtype was found to be an independent risk factor for disease aggressiveness in the multivariate analysis (OR 0.034 [95% CI 0.015-0.072]).
 
Limitations: Small sample size.
 
Conclusion: Preliminary data suggest the existence of an inflammatory HS phenotype that is associated with higher aggressiveness and major risk of progression during natural history of the disease.
​
Full Study:
​
https://www.ncbi.nlm.nih.gov/m/pubmed/31919904/?i=1&from=hidradenitis%20suppurativ(https://www.ncbi.nlm.nih.gov/m/pubmed/31919904/?i=1&from=hidradenitis%20suppurativa)

Question 4

Inflammatory Role of Sex Steroids & Hormones in HS

Accepted Answer

Inflammatory Role of Sex Steroids in Hidradenitis Suppurativa:
An Androgenic Phenotype 
 
Synopsis:
​
Abstract: Hidradenitis Suppurativa (HS) is an autoinflammatory skin disease more common in women and associated with hyper-androgenic disorders such as polycystic ovary syndrome. HS is characterized by chronic recurrent deep-seated painful nodules and draining tunnels in skin areas that follow the distribution of pubertal terminal hair growth. In women, HS disease activity varies with hormonal fluctuation across the menstrual cycle and pregnancy. Anti-androgens have shown promise in treatment of HS, but the pathophysiologic link between sex hormones and HS is unclear. We sought to further elucidate the role of sex hormones in the pathogenesis of HS. 
 
Objective: To determine if there is differential estrogen and androgen regulated gene expression in lesional compared to non-lesional skin transcriptome in HS patients. Methods: (a) We analyzed mRNA microarray data from lesional and non-lesional HS skin (GEO, GSE72702) (Blok JL, Br J Dermatol. 2016;174(6):1392). Inflammatory lesional skin from affected axilla or groin and non-lesional skin from the upper arm or leg was obtained from 17 patients with moderate to severe HS. We then examined differential expression of hormone regulated genes identified in existing androgen and estrogen gene expression signatures from prostate cancer cells [(VCaP treated with dihydrotestosterone (DHT)] and breast cancer cells [MCF7 treated with 17 beta-estradiol, (E2)] in the lesional and non-lesional skin transcriptomes of the HS patients. We identified overlap between the sets of genes that were either both upregulated or both repressed in HS lesions and the hormone-responsive prostate and breast cancer cell line models. Significance of differential gene expression was defined as FDR-adjusted p-value for two-tailed Student t-test less than 0.05. (b) After overlapping genes were identified, we used GeneGo Metacore pathway analysis software to explore the functional significance of the identified genes. 
 
Results: (a) Of the 3379 E2-upregulated probe sets in MCF7 breast cancer cells, 647 were significantly upregulated and 584 of 2871 E2-downregulated probe sets were significantly downregulated in HS lesions. Of the 1328 DHT-upregulated probe sets in prostate cancer cells, 341 were significantly upregulated and 196 of the 1251 DHT-downregulated probe sets were significantly downregulated in HS lesions. (b) Initial pathway analysis indicates that DHT upregulated genes in HS lesions are strongly enriched in innate immunity pathways, specifically, type 1 interferon signaling and class I MHC antigen presentation. 
 
Conclusion: There is substantial overlap between the transcriptional programme of sex steroids and transcriptional changes observed in HS lesional skin. In particular, androgen target genes are significantly enriched in innate immunity pathways, suggesting a functional link between the androgen signaling and the inflammatory process in HS lesions.
 
Full Research Link:
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https://academic.oup.com/jes/article/3/Supplement_1/MON-218/5484195(https://academic.oup.com/jes/article/3/Supplement_1/MON-218/5484195)

Question 5

Role of Androgens & Estrogens

Accepted Answer

The Role of Androgens and Estrogens in Hidradenitis Suppurativa:
 A Systematic Review
 
Synopsis:
 
Hidradenitis suppurativa (HS) is an inflammatory skin disease. Several observations imply that sex hormones may play a role in its pathogenesis. HS is more common in women, and the disease severity appears to vary in intensity according to the menstrual cycle. In addition, parallels have been drawn between HS and acne vulgaris, suggesting that sex hormones may play a role in the condition. The role of androgens and estrogens in HS has therefore been explored in numerous observational and some interventional studies; however, the studies have often reported conflicting results. This systematic review includes 59 unique articles and aims to give an overview of the available research. Articles containing information on natural variation, severity changes during menstruation and pregnancy, as well as articles on serum levels of hormones in patients with HS and the therapeutic options of hormonal manipulation therapy have all been included and are presented in this systematic review. Our results show that patients with HS do not seem to have increased levels of sex hormones and that their hormone levels lie within the normal range. While decreasing levels of progesterone and estrogen seem to coincide with disease flares in premenopausal women, the association is speculative and requires experimental confirmation. Antiandrogen treatment could be a valuable approach in treating HS, however randomized control trials are lacking.
​
Full Research Link:
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https://www.ncbi.nlm.nih.gov/m/pubmed/28128074/(https://www.ncbi.nlm.nih.gov/m/pubmed/28128074/)

Question 6

HS Linked Mutations in Four Genes

Accepted Answer

Analysis of hidradenitis suppurativa-linked mutations in four genes and the effects of PSEN1-P242LfsX11 on cytokine and chemokine expression in macrophages.
​
Synopsis:
​
Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory skin disorder characterized clinically with acne-like lesions in apocrine gland–bearing skin, follicular occlusion and recurrent inflammation. Thirty-four unique mutations in patients with HS have been found in three genes encoding the γ-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endoplasmic reticulum O-glucosyltransferase involved in Notch signaling. We have carried out a system review and have performed a functional analysis of the 34 unique reported HS-linked mutations in NCSTN, PSEN1, PSENEN and POGLUT1. We have also examined the effects of the HS-linked PSEN1-P242LfsX11 mutation on cytokine and chemokine expression in macrophages. Mutations in NCSTN are predicted to cause loss of function, to result in loss of transmembrane (TM) domain, to affect NCSTN substrate recruitment sites, to cause loss or creation of new ligand binging sites and to alter post-translational modifications and disulfide bonds. PSEN1-P242LfsX11 occurs at the opposite side of TM5 from Alzheimer’s disease–linked PSEN1 mutations. All of the PSENEN mutations occur on TM regions that are predicted to disrupt membrane function. POGLUT1 mutations lead to an early termination of protein synthesis and are predicted to affect ligand binding function. In addition, PSEN1-P242LfsX11 mediates cytokine and chemokine expression and prolongs tumor necrosis factor α production on the inflammatory processes in THP-1 cells and phorbol-12-myristate-13-acetate–differentiated macrophages in response to lipopolysaccharide stimulation. These in silico analyses are instructive for functional studies of the HS-linked mutations. The PSEN1-P242LfsX11 mutation mediates cytokine and chemokine expression in macrophages.
​
Full Research Link:
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https://www.ncbi.nlm.nih.gov/m/pubmed/30544224/?i=13&from=hidradenitis%20occlusion(https://www.ncbi.nlm.nih.gov/m/pubmed/30544224/?i=13&from=hidradenitis%20occlusion)

Question 7

Nicastrin Mutation in a Three Generation Dutch Family

Accepted Answer

A novel nicastrin mutation in a three‐generation Dutch family
with hidradenitis suppurativa 
 
Synopsis:
​
Background
Mutations in the γ-secretase enzyme subunits have been described in multiple kindreds with familial hidradenitis suppurativa (HS).
 
Objective
In this study, we report a novel nicastrin (NCSTN) mutation causing HS in a Dutch family. We sought to explore the immunobiological function of NCSTN mutations using data of the Immunological Genome Project.
 
Methods
Blood samples of three affected and two unaffected family members were collected. Whole-genome sequencing was performed using genomic DNA isolated from peripheral blood leucocytes. Sanger sequencing was done to confirm the causative NCSTN variant and the familial segregation. The microarray data set of the Immunological Genome Project was used for thorough dissection of the expression and function of wildtype NCSTN in the immune system.
 
Results
In a family consisting of 23 members, we found an autosomal dominant inheritance pattern of HS and detected a novel splice site mutation (c.1912_1915delCAGT) in the NCSTN gene resulting in a frameshift and subsequent premature stop. All affected individuals had HS lesions on non-flexural and atypical locations. Wildtype NCSTN appears to be upregulated in myeloid cells like monocytes and macrophages, and in mesenchymal cells such as fibroblastic reticular cells and fibroblasts. In addition, within the 25 highest co-expressed genes with NCSTN we identified CAPNS1, ARNT and PPARD.
 
Conclusion
This study reports the identification a novel NCSTN gene splice site mutation which causes familial HS. The associated immunobiological functions of NCSTN and its co-expressed genes ARNT and PPARD link genetics to the most common environmental and metabolic HS risk factors which are smoking and obesity.
​
Full Research Link:
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https://onlinelibrary.wiley.com/doi/full/10.1111/jdv.16310(https://onlinelibrary.wiley.com/doi/full/10.1111/jdv.16310)

Question 8

Follicular Skin Microbiome

Accepted Answer

The Follicular Skin Microbiome in Patients With
Hidradenitis Suppurativa and Healthy Controls​
 
Synopsis:
​
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.
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Full Research Link:
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https://www.ncbi.nlm.nih.gov/m/pubmed/28538949/(http://www.ncbi.nlm.nih.gov/m/pubmed/28538949/)

Question 9

Apocrine Glands are Bystanders in HS and their Involvement is Gender-Specific

Accepted Answer

Apocrine glands are bystanders in hidradenitis suppurativa
and their involvement is gender-specific
​
Synopsis:
​
Background: Apocrine glands have been long considered as the initial targeted skin compartment in hidradenitis suppurativa/acne inversa (HS).
​
Objective: Detection of apocrine gland involvement in HS.
 
Methods: 
Apocrine glands were isolated from skin biopsies of involved and uninvolved skin of HS patients (n = 16, females : males 1 : 1) by laser capture microscopy and studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non-lesional skin obtained from female and male HS patients using the Agilent array platform. 
 
Results: 
SULF1 was the only gene, whose expression levels were found upregulated in apocrine glands of HS lesions of the entire group. Further dysregulated genes associated with vascular functions (FGF1, IL17D and S100A9) were detected. Genes, which are characteristic for glandular epithelia, confirmed the glandular origin of the studied tissue. The gene upregulation profile of female apocrine glands included several genes (MRO, DYRK3, SDK2, GLB1L, CATSPERB and PRPS2), which are specifically transcribed during testis differentiation and/or regulated by androgens. Genes related to lipid metabolism (AGPAT3, GAL, ELOVL3, THRSP, DGAT2L3, OLAH, THRSP, FADS1, NR2F2, FADS2, PTGDS and HAO2) were mostly downregulated in the apocrine glands of male patients. The levels of RECK and PCSK5, which are upstream genes of metalloproteinase-9 and -1, and of S100A9, which encodes calgranulin B, were commonly increased in the apocrine glands of female and male patients, respectively, and in our previous whole skin study.

Conclusion: 
Our findings indicate that apocrine glands are bystanders in HS. Inflammatory signalling is not prominent but a gender-specific response was detected, which is mostly associated with androgen-responsive genes in females and alterations of lipid metabolism in males.
© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
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Full Research Link:
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https://www.ncbi.nlm.nih.gov/m/pubmed/32031713/?i=12&from=hidradenitis(https://www.ncbi.nlm.nih.gov/m/pubmed/32031713/?i=12&from=hidradenitis)
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Question 10

The Bacteriology of HS: A Systematic Review

Accepted Answer

The bacteriology of hidradenitis suppurativa: a systematic review
​
Synopsis:
​
Included studies in the review
A total of 66 papers were identified and nine papers published between 1988 and 2014 matched the above-mentioned inclusion criteria (Fig. 1)(https://onlinelibrary.wiley.com/doi/full/10.1111/exd.12793#exd12793-fig-0001), yielding bacteriological data of a total of 324 patients with HS (mean age 36.8 years and female/male ratio 215/109).
​
Microbiological methods used in the included studies
As shown in Table S1, traditional microbiological techniques for culturing bacteria in aerobic and anaerobic environment have been applied to investigate the bacteriology of HS in eight of nine included studies. Three studies used biochemical tests and only one study used immunological identification technique (Lancefield group antigens). One study applied 16S gene ribosomal RNA gene sequencing along with metagenomics. Lastly, only one study investigated the bacteriology in blood samples in patients with HS using PCR (polymerase chain reaction) and DNA sequencing and analysis 24.(https://onlinelibrary.wiley.com/doi/full/10.1111/exd.12793#exd12793-bib-0024)
​
The Spectrum of Bacteria found in patients with HS
As displayed in Fig. 2,(https://onlinelibrary.wiley.com/doi/full/10.1111/exd.12793#exd12793-fig-0002) CoNS (34.1%) and mixed anaerobic bacteria (23.3%) are the most frequently encountered types of bacteria among the 324 patients. In addition, S. aureus also constitutes a considerable part of the overall isolated bacterial specimens (isolated in six of nine studies), and among the studies that identified S. aureus, the prevalence rate ranged from 13% to 56% (Table 1)(https://onlinelibrary.wiley.com/doi/full/10.1111/exd.12793#exd12793-tbl-0001).
​
Full Research:
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https://onlinelibrary.wiley.com/doi/full/10.1111/exd.12793(https://onlinelibrary.wiley.com/doi/full/10.1111/exd.12793)

Question 11

Alterations in Innate Immunity & Epithelial Cell Differentiation

Accepted Answer

Alterations in innate immunity and epithelial cell differentiation are the
molecular pillars of hidradenitis suppurativa
​
Synopsis:
 
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.
​
Full Research Link:
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https://onlinelibrary.wiley.com/doi/full/10.1111/jdv.16147(https://onlinelibrary.wiley.com/doi/full/10.1111/jdv.16147)

Question 12

Cutaneous Microbiome: Light at the End of the Microbiological Tunnel

Accepted Answer

The Role of the Cutaneous Microbiome in Hidradenitis Suppurativa
Light at the End of the Microbiological Tunnel
 
Synopsis:
​
Hidradenitis suppurativa is a chronic, debilitating inflammatory skin disease whose pathophysiology remains poorly understood [92](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072827/#B92-ijms-21-01205). Although the disease itself is relatively uncommon, it is frequently associated with significant physical and psychological morbidity [93](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072827/#B93-ijms-21-01205) and undoubtedly represents an area of unmet clinical need [2](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072827/#B2-ijms-21-01205). Whilst it has long been recognized that HS is associated with changes in the resident bacterial flora, only now are metagenomic studies starting to shed new light on the diversity, complexity and regulation of the cutaneous microbiome in HS. Ultimately, prospective, controlled, longitudinal studies of the microbiome in HS lesional and non lesional skin are required, potentially complemented by genetic studies [94,(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072827/#B94-ijms-21-01205)95](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072827/#B95-ijms-21-01205), to comprehensively determine the extent to which genetic and environmental factor contribute to dysbiosis and consequently disease pathology, but, more importantly, to identify much needed novel therapeutic targets.
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Full Research:
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072827/(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072827/)

Question 13

Bacterial Biofilm in Chronic Lesions

Accepted Answer

Bacterial biofilm in chronic lesions of hidradenitis suppurativa
​
Synopsis:
 
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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Full Research:
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https://pubmed.ncbi.nlm.nih.gov/27564400/(https://pubmed.ncbi.nlm.nih.gov/27564400/)

Gene Dysregulated / Expression / Mutation /
Genome Profiling & Microbiome Research

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Gene Dysregulated / Expression / Mutation / Genome Profiling & Microbiome Research

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Gene Dysregulated / Expression / Mutation /
Genome Profiling & Microbiome Research