Epigenetic switch reshapes epithelial progenitor cell signatures and drives inflammatory pathogenesis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a complex inflammatory skin disease with undefined mechanistic underpinnings. Here, we investigated HS epithelial cells and demonstrated that HS basal progenitors modulate their lineage restriction and give rise to pathogenic keratinocyte clones, resulting in epidermal hyperproliferation and dysregulated inflammation in HS. When comparing to healthy epithelial stem/progenitor cells, in HS, we identified changes in gene signatures that revolve around the mitotic cell cycle, DNA damage response and repair, as well as cell-cell adhesion and chromatin remodeling. By reconstructing cell differentiation trajectory and CellChat modeling, we identified a keratinocyte population specific to HS. This population is marked by S100A7/8/9 and KRT6 family members, triggering IL1, IL10, and complement inflammatory cascades. These signals, along with HS-specific proinflammatory cytokines and chemokines, contribute to the recruitment of certain immune cells during the disease progression. Furthermore, we revealed a previously uncharacterized role of S100A8 in regulating the local chromatin environment of target loci in HS keratinocytes. Through the integration of genomic and epigenomic datasets, we identified genome-wide chromatin rewiring alongside the switch of transcription factors (TFs), which mediated HS transcriptional profiles. Importantly, we identified numerous clinically relevant inflammatory enhancers and their coordinated TFs in HS basal CD49fhigh cells. The disruption of the S100A enhancer using the CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators. Our study not only uncovers the plasticity of epidermal progenitor cells in HS but also elucidates the epigenetic mechanisms underlying HS pathogenesis.

Advances in molecular pathogenesis of hidradenitis suppurativa: Dysregulated keratins and ECM signaling.

Hidradenitis suppurativa (HS) is characterized by deep-seated, highly inflamed, and painful lumps/abscesses, fistulae, and sinus tracts that grow extensively deep in the dermis and are highly immunogenic in nature. In about one-third of the HS patients there is strong evidence for the role of γ-secretase mutations along with dysregulated Notch signaling. However, the contribution of dysregulated Notch signaling in HS pathogenesis in relation to hair follicle alterations and hyper-activation of the immune system remains undefined. A genome-wide association study (GWAS), proteomic data and functional investigations of identified sequence variants in HS pathology are not fully revealing. The disease initiation or progression may involve bacterial infection besides intrinsic functional defects in keratinocytes, which may be key to further exacerbate immune cell infiltration and cytokine production in and around the lesional tissue. The absence of a suitable animal model that could fully recapitulate the pathogenesis of HS is a major impediment for proper understanding the underlying mechanisms and development of effective treatments. The presence of extracellular matrix (ECM) degradation products along with dysregulation in keratinocytes and, dermal fibroblasts ultimately affect immune regulation and are various components of HS pathogenesis. Bacterial infection further exacerbates the complexity of the disease progression. While anti-TNFα therapy shows partial efficacy, treatment to cure HS is absent. Multiple clinical trials targeting various cytokines, complement C5a and ECM products are in progress. This review provides state-of-the-art information on these aspects with a focus on dysregulated keratinocyte and immune cells; and role of ECM, and Keratin functions in this regard.

The NLRP3 Inflammasome Gene Is Overexpressed in Hidradenitis Suppurativa Lesions: A Preliminary Study on the Role of Pyroptosis in Disease Pathogenesis.

Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disorder, and its pathogenesis remains incompletely understood. This study aimed to investigate the role of the P2X7 receptor (P2X7R) and NLRP3 inflammasome in HS pathogenesis. RNA sequencing and real-time PCR were performed to assess the gene expression levels of P2X7R and NLRP3 in the skin biopsies of HS patients and healthy controls (HC). The results of our study revealed a significantly increased expression of the NLRP3 gene in both the lesional and perilesional skin of HS patients compared to healthy controls. Moreover, the mRNA levels of NLRP3 were significantly higher in lesional skin compared to non-lesional skin in HS patients, indicating the spread of inflammation to adjacent tissues. In contrast, no significant differences in P2X7R gene expression were observed between the three groups. These findings suggest the involvement of NLRP3 inflammasomes in HS pathogenesis, while P2X7R may not play a significant role in the disease. This research sheds light on the complex inflammatory pathways in HS, highlighting the potential of NLRP3 as a therapeutic target. Understanding the molecular mechanisms underlying HS is crucial for the development of targeted treatment modalities for this debilitating condition.

Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review.

This manuscript explores the role of pyroptosis, an inflammatory programmed cell death, in the pathogenesis of two chronic dermatoses, psoriasis and hidradenitis suppurativa (HS). The diseases, though clinically diverse, share common pathogenetic pathways involving the unbalanced interaction between the adaptive and innate immune systems. This review focuses on the molecular changes in psoriatic and HS skin, emphasizing the activation of dendritic cells, secretion of interleukins (IL-17, IL-22, and TNF-α), and the involvement of inflammasomes, particularly NLRP3. This manuscript discusses the role of caspases, especially caspase-1, in driving pyroptosis and highlights the family of gasdermins (GSDMs) as key players in the formation of pores leading to cell rupture and the release of proinflammatory signals. This study delves into the potential therapeutic implications of targeting pyroptosis in psoriasis and HS, examining existing medications like biologics and Janus kinase inhibitors. It also reviews the current limitations and challenges in developing therapies that selectively target pyroptosis. Additionally, the manuscript explores the role of pyroptosis in various inflammatory disorders associated with psoriasis and HS, such as inflammatory bowel disease, diabetes mellitus, and cardiovascular disorders. The review concludes by emphasizing the need for further research to fully elucidate the pathomechanisms of these dermatoses and develop effective, targeted therapies.

Metabolomic and lipidomic fingerprints in inflammatory skin diseases - Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis.

Auto-inflammatory skin diseases place considerable symptomatic and emotional burden on the affected and put pressure on healthcare expenditures. Although most apparent symptoms manifest on the skin, the systemic inflammation merits a deeper analysis beyond the surface. We set out to identify systemic commonalities, as well as differences in the metabolome and lipidome when comparing between diseases and healthy controls. Lipidomic and metabolomic LC-MS profiling was applied, using plasma samples collected from patients suffering from atopic dermatitis, plaque-type psoriasis or hidradenitis suppurativa or healthy controls. Plasma profiles revealed a notable shift in the non-enzymatic anti-oxidant defense in all three inflammatory disorders, placing cysteine metabolism at the center of potential dysregulation. Lipid network enrichment additionally indicated the disease-specific provision of lipid mediators associated with key roles in inflammation signaling. These findings will help to disentangle the systemic components of autoimmune dermatological diseases, paving the way to individualized therapy and improved prognosis.

Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study.

BACKGROUND: Hidradenitis suppurativa (HS), an inflammatory-based dermatological condition often associated with obesity, poses significant challenges in management. The very low-calorie ketogenic diet (VLCKD) has shown efficacy in addressing obesity, related metabolic disorders, and reducing chronic inflammation. However, its effects on HS remain underexplored. In this prospective pilot study, we aimed to investigate the impact of a 28-day active phase of VLCKD on HS in a sample of treatment-naive women with HS and excess weight. METHODS: Twelve women with HS and overweight or obesity (BMI 27.03 to 50.14 kg/m2), aged 21 to 54 years, meeting inclusion/exclusion criteria and agreeing to adhere to VLCKD, were included. Baseline lifestyle habits were assessed. The Sartorius score was used to evaluate the clinical severity of HS. Anthropometric parameters (waist circumference, weight, height, and body mass index), body composition via bioelectrical impedance analysis, levels of trimethylamine N-oxide (TMAO), oxidized low-density lipoprotein (oxLDL), and derivatives of reactive oxygen metabolites (dROMs) were assessed at baseline and after 28 days of the active phase of VLCKD. RESULTS: VLCKD led to general improvements in anthropometric parameters and body composition. Notably, a significant reduction in the Sartorius score was observed after the intervention (Δ%: - 24.37 ± 16.64, p < 0.001). This reduction coincided with significant decreases in TMAO (p < 0.001), dROMs (p = 0.001), and oxLDL (p < 0.001) levels. Changes in the Sartorius score exhibited positive correlations with changes in TMAO (p < 0.001), dROMs (p < 0.001), and oxLDL (p = 0.002). CONCLUSION: The 28-day active phase of VLCKD demonstrated notable improvements in HS severity and associated metabolic markers, highlighting the potential utility of VLCKD in managing HS and its association with metabolic derangements in women with overweight or obesity.

Detection of native, activated Notch receptors in normal human apocrine-bearing skin and in hidradenitis suppurativa.

Notch signalling has generated considerable interest as a pathogenetic factor and a drug target in a range of human diseases. The gamma-secretase complex is crucial in the activation of Notch receptors by cleaving the intracellular domain allowing nuclear translocation. In recent years several mutations in gamma-secretase components have been discovered in patients with familial hidradenitis suppurativa (HS). This has led to hypotheses that impaired Notch signalling could be an important driver for HS in general, not only in the monogenic variants. However, no study has examined in situ Notch activation per se in HS, and some reports with conflicting results have instead been based on expression of Notch receptors or indirect measures of Notch target gene expression. In this study we established immunostaining protocols to identify native, activated Notch receptors in human skin tissue. The ability to detect changes in Notch activation was confirmed with an ex vivo skin organ model in which signal was reduced or obliterated in tissue exposed to a gamma-secretase inhibitor. Using these methods on skin biopsies from healthy volunteers and a general HS cohort we demonstrated for the first time the distribution of active Notch signalling in human apocrine-bearing skin. Quantification of activated NOTCH1 & NOTCH2 revealed similar levels in non-lesional and peri-lesional HS to that of healthy controls, thus ruling out a general defect in Notch activation in HS patients. We did find a variable but significant reduction of activated Notch in epidermis of lesional HS with a distribution that appeared related to the extent of surrounding tissue inflammation.

Anti-IL17 Secukinumab in hidradenitis suppurativa: A long-term drug survival analysis.

Real-world data on the long-term effectiveness of the anti-IL17 agent secukinumab in treating moderate-to-severe Hidradenitis suppurativa (HS) are lacking. In this study, 24 patients with moderate-severe HS received five weekly subcutaneous injections followed by maintenance doses every 4 weeks. Primary outcomes included HiSCR, IHS4 reduction, and DLQI measures assessed at 12-week intervals. The median secukinumab drug survival was 16.0 months (range 3-51), with a 56.5% maximal response rate at 6 months and dropout exceeding 40% at 1 year. Baseline disease burden emerged as a key predictor of treatment response, overshadowing factors like sex or BMI. Prior systemic steroid use negatively impacts drug survival. The study underscores the critical 6-month window for assessing treatment efficacy, emphasizing the importance of initial induction dosing. Additionally, the newly developed scoring system, IHS4-55, showed analogies to the older HiSCR score in capturing treatment response. In this real-life scenario, challenges persist in HS management, necessitating innovative therapeutic approaches and predictive markers.

Eosinophils in hidradenitis suppurativa patients exhibit pro-inflammatory traits, implicating a potential pathogenic role in the disease.

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and purulent secretions in intertriginous regions. Intense pruritus frequently accompanies HS lesions, adding further discomfort for patients. While Th17 pathway activation is implicated in HS pathogenesis, disease mechanisms are still not fully understood, and therapeutics are lacking. Previous reports raise a potential role for eosinophils in HS, showing a strong association of eosinophil levels with disease severity. To investigate eosinophils in HS, we recruited patients and matched healthy controls and then performed flow-cytometry studies, eosinophil stimulation assays, and lesional skin staining for eosinophils. We found that HS patients reported similar levels of pain and itch. Compared to matched controls, HS blood exhibited decreased mature eosinophils and increased numbers of immature eosinophils, coupled with a significant increase in dermal eosinophilic infiltrates. Additionally, IL-17RA+ eosinophils were highly and significantly correlated with multiple HS-related clinical scores. In both stimulated and unstimulated conditions, HS eosinophils showed an inflammatory phenotype versus controls, including an increase in costimulatory T- and B-cell markers (e.g. CD5 and CD40) following all stimulations (TNFα/IL-17A/IL-17F). These findings highlight the significance of pruritus in HS and suggest a higher turnover of eosinophils in HS blood, potentially due to the consumption of eosinophils in skin lesions. Our data delineate the features and functions of eosinophils in HS and suggest that eosinophils participate in disease pathogenesis, advancing Th17-related inflammation. Further studies are needed to investigate eosinophils' response to current HS treatments and their potential as a therapeutic target in the disease.

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.

Comparative transcriptome analysis of acne vulgaris, rosacea, and hidradenitis suppurativa supports high-dose dietary zinc as a therapeutic agent.

Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.

Wound area severity index (WASI): A novel tool for assessing and predicting healing times in hidradenitis suppurativa postsurgical wounds.

Hidradenitis suppurativa (HS) presents challenges in management due to its chronic nature and high risk of recurrence. Post-surgical wound care plays a crucial role in treatment, even if standardized methods for assessing and predicting healing times are lacking. The aim of the study is to introduce the Wound Area Severity Index (WASI) as a novel tool to guide clinicians in assessing postsurgical wound progression and predicting potential healing times. A team of wound healing experts assessed 93 post-surgical HS wounds resulting from wide excision and secondary intention healing. For each wound healing time, wound area, wound bed score (WBS), and WASI were evaluated. WASI includes four parameters: area, temperature, depth and wound Bed, each with four severity levels. The total WASI score ranges from 4 to 16. Spearman correlation and Kruskal-Wallis tests were employed for statistical analysis. WASI strongly correlated with wound healing time (rho: 0.813, p < 0.001). Higher WASI scores were associated with prolonged healing, while lower scores indicated almost healed wounds. The WASI score has proven to be more highly predictive of healing times when compared to the individual parameter of the Area (moderate positive correlation, r: 0.77) and the WBS (negative correlation, r: -0.72). A total WASI score of 4 corresponded to a median healing time of 7 days, while a score exceeding 9 suggested a median healing time of 56 days. WASI has proven to be a valuable tool for assessing and predicting healing times in post-surgical HS wounds. Its simplicity, cost-effectiveness, and ability to integrate multiple parameters make it a promising addition to wound care practice.

Mast cells are upregulated in hidradenitis suppurativa tissue, associated with epithelialized tunnels and normalized by spleen tyrosine kinase antagonism.

Mast cells have traditionally been associated with allergic inflammatory responses; however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing-associated pathways; however, the role of mast cells in the disease is unexplored. We demonstrate that mast cell-associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive mast cells (identified using IHC) localize adjacent to epithelialized tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell-associated gene transcripts, associated biochemical pathways and the number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is paralleled with B cell/plasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.

Tape strips detect molecular alterations and cutaneous biomarkers in skin of patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) has a high unmet need for better treatments. Biopsies are considered the gold standard for studying molecular alterations in skin. A reproducible, minimally invasive approach is needed for longitudinal monitoring in trials and in pediatric populations. OBJECTIVE: To determine whether skin tape strips can detect molecular alterations in HS and identify biomarkers of disease activity. METHODS: We performed RNA sequencing on tape strips collected from lesional and healthy-appearing (nonlesional) HS skin (n = 22) and healthy controls (n = 21). We correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. RESULTS: Tape strips detected upregulation of known HS biomarkers (eg, Interleukin[IL]-17A) in nonlesional and/or lesional skin and also identified novel clinically actionable targets, including OX40 and JAK3. The expression of Th17 and tumor necrosis factor-α pathways were highly correlated between tape strips and biopsies. HS clinical severity was significantly associated with expression of biomarkers (eg tumor necrosis factor-α , IL-17 A/F, OX40, JAK1-3, IL-4R) in HS lesional and/or nonlesional skin. LIMITATIONS: Sample size. Tape stripping is limited in depth. CONCLUSION: This study validates tape strips as a minimally-invasive approach to identify cutaneous biomarkers in HS. This provides a novel avenue for monitoring treatment efficacy and a potential step toward individualized therapy in HS.

Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study.

BACKGROUND: Janus kinase 1 inhibition may alleviate hidradenitis suppurativa (HS)-associated inflammation and improve symptoms. OBJECTIVE: To assess efficacy and safety of povorcitinib (selective oral Janus kinase 1 inhibitor) in HS. METHODS: This placebo-controlled phase 2 study randomized patients with HS 1:1:1:1 to receive povorcitinib 15, 45, or 75 mg or placebo for 16 weeks. Primary and key secondary end points were mean change from baseline in abscess and inflammatory nodule count and percentage of patients achieving HS Clinical Response at week 16. RESULTS: Of 209 patients randomized (15 mg, n = 52; 45 mg, n = 52; 75 mg, n = 53; placebo, n = 52), 83.3% completed the 16-week treatment. At week 16, povorcitinib significantly reduced abscess and inflammatory nodule count from baseline (least squares mean [SE] change: 15 mg, -5.2 [0.9], P = .0277; 45 mg, -6.9 [0.9], P = .0006; 75 mg, -6.3 [0.9], P = .0021) versus placebo (-2.5 [0.9]). More povorcitinib-treated patients achieved HS Clinical Response at week 16 (15 mg, 48.1%, P = .0445; 45 mg, 44.2%, P = .0998; 75 mg, 45.3%, P = .0829) versus placebo (28.8%). A total of 60.0% and 65.4% of povorcitinib- and placebo-treated patients had adverse events. LIMITATIONS: Baseline lesion counts were mildly imbalanced between groups. CONCLUSION: Povorcitinib demonstrated efficacy in HS, with no evidence of increased incidence of adverse events among doses.

Synergizing pharmacometrics and pharmacovigilance for medication error management: the case of secukinumab.

PURPOSE: To demonstrate the effective integration of pharmacometrics and pharmacovigilance in managing medication errors, highlighted by a case involving secukinumab in a patient with hidradenitis suppurativa. METHODS: We present the case of a 41-year-old male with progressive hidradenitis suppurativa, unresponsive to multiple antibiotic regimens and infliximab treatment. Due to a medication error, the patient received 300 mg of secukinumab daily for 4 days instead of weekly, totaling 1200 mg. The regional pharmacovigilance center assessed potential toxicity, and a pharmacometric analysis using a population pharmacokinetic model was performed to inform dosing adjustments. RESULTS: Clinical data indicated that the received doses were within a non-toxic range. No adverse effects were observed. Pharmacometric simulations revealed a risk of underexposure due to the dosing error. Based on these simulations, it was recommended to restart monthly secukinumab injections on day 35 after the initial dose. Measured plasma concentrations before re-administration confirmed the model's accuracy. CONCLUSION: This case highlights the crucial collaboration between clinical services, pharmacovigilance, and pharmacometrics in managing medication errors. Such interdisciplinary efforts ensure therapeutic efficacy and patient safety by maintaining appropriate drug exposure levels.

The Global Hidradenitis Suppurativa Atlas Methodology: Combining Global Proportions in a Pooled Analysis.

INTRODUCTION: Data concerning the global burden of hidradenitis suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalences have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. METHODS: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital or a private/family medicine clinic. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Approximately ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). CONCLUSION: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation and synthesized using a random-effects model. The novel standardization of the Global Prevalence Studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies.

Belgian Patients of the European Registry for Hidradenitis Suppurativa (ERHS-Be): Data, Scores, and Phenotypes since 2015.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease, characterized by painful and recurrent lesions in apocrine gland-bearing skin areas. It is a heterogeneous disease, which makes assessment and data collection difficult. Questionnaires with detailed items, such as the Belgian European Registry for Hidradenitis Suppurativa (ERHS-Be), are useful to study HS and its associated comorbidities. The aim of this registry was to uncover new factors associated with HS and understand HS patients' clinical profiles and efficacy of treatments. MATERIAL AND METHODS: The ERHS-Be registry is based on questionnaires, with sections for sociodemographic data, medical and HS history, clinical examination, and treatment plan. It allows identification of different clinical phenotypes and automatic calculation of severity scores. RESULTS: At present, 606 patients are included in the ERHS-Be (67% women, 33% men). The mean age at the first visit is 38.5 years. Tobacco use is present in 72.6% of patients. A family history of HS is noted in 42% of patients. Comorbidities are documented in this cohort: depression is present in 43.8% of patients, arthritis in 27.8%, obesity in 31.5%, hypertension in 10.6%, diabetes mellitus in 6.4%, and dyslipidemia in 12.4%. Moreover, 7.7% of patients suffer from IBD and 27.4% have a pilonidal sinus. History of severe acne is found in 32.1% of patients and psoriasis in 9.3%. Thirteen percent of women in our cohort suffer from polycystic ovarian syndrome. Severity of disease is quantified in 533 patients: for instance, Hurley I, II, and III scores proportions are, respectively, 32.3%, 52.7%, and 15%, while the mean IHS4 score is 5.2. This registry also enables determination of relative phenotype proportions in our cohort, according to different classifications. CONCLUSION: The ERHS-Be questionnaires allow systematic and larger data collection, including detailed comorbidities, phenotypes, and severity of disease. Analysis of this large database will contribute to a better understanding and management of HS, at a time where new therapeutic options are becoming available.

Hidradenitis Suppurativa Is Associated with Severe Sexual Impairment.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of the pilosebaceous unit, often affecting and deforming intimate regions. HS is associated with severe pain, pruritus, and constant, purulent, malodorous discharge expected to impair sexual health of patients. METHODS: We performed a cross-sectional, multicentric study involving 199 German patients from the health services research project "Epidemiology and Care in Acne inversa (EpiCAi)." The sexual health, HS severity, and quality of life of the studied group were evaluated using a specially designed questionnaire. RESULTS: Regardless of gender, HS has an enormous impact on patients' sexual health. The patients scored, on average, 28.8 ± 5.3 points on the Relation and Sexuality Scale (RSS). Multiple linear regression revealed that females and patients with Hurley III stage had higher sexual dysfunction (p = 0.012). Sexual dysfunction is associated with pain (ß = 0.25), the number of active lesions, the affected areas (ß = 0.14), and psychosocial aspects, including low quality of life (ß = 0.404), stigmatization (ß = 0.411), depression (ß = 0.413), and anxiety (ß = 0.300). Patients already see a substantial decrease in sexual frequency in the early stages of HS, while functional impairment and fear increase with the severity of the disease. CONCLUSION: Sexual health and management of its dysfunctions should be part of a holistic approach to HS patients.

Correlation between PainDETECT Questionnaire and Quantitative Sensory Testing for the Detection of Neuropathic Pain in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that is often severely painful due to nociceptive mechanisms (i.e., stimulation of cutaneous nociceptors). However, patient-reported pain character suggests that neuropathy may also drive HS pain in a subset of patients. Quantitative sensory testing (QST) can help identify neuropathic pain by testing for heightened and paradoxical pain responses in patients, but it is less feasible for routine clinical use compared with brief questionnaires. We therefore tested the suitability of a standardized neuropathic questionnaire (PainDETECT; PD-Q) for use as a surrogate clinical measure by directly comparing it with QST-identified neuropathic pain in HS. METHODS: This observational, cross-sectional study included 22 adults with painful HS lesions who completed the PD-Q and underwent QST. A receiver operating characteristic curve was generated and Cohen's Kappa, sensitivity, and specificity were examined at three scoring thresholds. RESULTS: Of the 22 participants, 14 (64%) exhibited dynamic mechanical allodynia and/or paradoxical thermal sensations in QST, which are characteristically found in neuropathic pain. According to the PD-Q, 8 participants (36%) were unlikely, 8 (36%) were possible, and 6 (27%) were likely to have neuropathic pain. A PD-Q Score indicating possible or likely neuropathic pain (i.e., ≥13) demonstrated 82% agreement with QST-determined neuropathic pain (Cohen's Kappa = 0.61 [p = 0.004]; sensitivity = 86%; specificity = 75%). CONCLUSION: The PD-Q demonstrates moderate agreement with QST in screening for neuropathic pain in HS and may be a helpful clinical tool.