Hidradenitis suppurativa and cardiovascular diseases: A bidirectional Mendelian randomization study.

BACKGROUND: Prior investigation has indicated a link between Hidradenitis suppurativa (HS) and cardiovascular diseases (CVDs), yet the causal relationship (CR) between these conditions remains unresolved. METHODS: This investigation utilized bidirectional Mendelian randomization (MR) analysis to determine the CR between HS and CVDs. Genetic instruments for both conditions were sourced from genome-wide association studies (GWAS). The GWAS summary data for CVD comprised coronary artery disease (CAD), myocardial infarction (MI), coronary atherosclerosis (CA), ischemic stroke (IS), and chronic heart failure (CHF). Four new approaches were added to the inverse variance weighted (IVW) method for the main analysis: weighted median, weighted MR-Egger, simple mode, and weighted mode. The validity of the causal conclusions was verified by sensitivity tests that included leave-one-out analysis, heterogeneity, and pleiotropy. RESULTS: HS and CAD (OR = 1.024; 95%CI: 1.002-1.046, P = 0.033), MI (OR = 1.001; 95%CI: 1.000-1.002, P = 0.033), and CA (OR = 1.001; 95%CI: 1.000-1.002, P = 0.022) were identified to have a positive CR, according to the IVW analysis. Conversely, no significant association was identified between HS and either IS or CHF. Furthermore, the bidirectional analysis indicated no reverse causation between these diseases. CONCLUSION: The findings of this study suggest a potential CR between HS and CAD, MI, and CA. Additional research is warranted to elucidate the biological mechanisms underlying these associations.

Efficacy of spironolactone in treating hidradenitis suppurativa in women of childbearing age: a single-center retrospective analysis.

Background: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent nodules that affect areas with a high density of apocrine sweat glands, such as the axillae and groin. Androgens are implicated in the pathophysiology of HS. Therefore, spironolactone, an antiandrogen therapy, is recommended. However, data on its use in women of childbearing age are limited, especially since its antiandrogenic effects may affect menstruation, fertility, and pubertal development. Objective: To evaluate the efficacy and safety of spironolactone in the treatment of hidradenitis suppurativa in women of childbearing age and to identify factors associated with treatment response. Methods: A retrospective analysis was conducted on female patients aged 12 to 50 with HS treated with spironolactone at Michigan Medicine dermatology clinics from 2000 to 2021. The patients' demographic data, HS characteristics, and spironolactone responses were examined. Statistical assessments were performed to determine the efficacy indicators. Results: Of the 157 patients reviewed, 31 showed an improvement in treatment. Variables such as axillary involvement, previous treatment failures, and use of intralesional steroids were linked to a lack of improvement in spironolactone. Through adjusted multiple logistic regression analysis, a significant association was observed between improvement status and Hurley stage 3 (odds ratio = 0.15 [95% CI: 0.02-0.79], P = .036), suggesting that patients with Hurley stage 3 were 85% less likely to exhibit improvement in spironolactone therapy. Limitations: The study's retrospective nature and reliance on single-center data can limit generalizability. The sample size is limited and therefore affects the study's statistical power. Conclusion: Thus, spironolactone may offer therapeutic benefits for HS in women of childbearing age. However, patients with severe disease (Hurley stage 3) had reduced response rates. Further prospective studies are recommended to validate these findings and determine the most suitable patient profile for spironolactone therapy for HS.

Hidradenitis suppurativa and psychosocial well-being: a cross-sectional survey analysis from the All of Us research program.

Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease that often leads to decreased quality of life. Prior research assessing stress and discrimination related to stigmatization of those with HS is limited. The aim of this study was to examine the association between HS and the following factors related to psychosocial well-being: stress, discrimination, and loneliness. We performed secondary analysis of participants 18 years and older registered in the National Institutes of Health's All of Us Research Program in March 2024. The study sample was limited to individuals who had completed ≥ 1 of 4 psychosocial well-being surveys. Among 1,352 individuals with HS, 135 were included in the sample. Among 208,290 individuals without HS, 56,902 were included. The following surveys assessed loneliness, stress, perceived discrimination in everyday settings, and perceived discrimination in medical settings, respectively: the UCLA Loneliness Scale, Cohen Perceived Stress Scale, Everyday Discrimination Scale, and Discrimination in Medical Settings Scale. The association between HS and survey scores was modeled using multivariable linear regression adjusted for self-reported sex, self-reported race and ethnicity, age, and income. In an unadjusted model, those with HS reported a significantly higher degree of stress (MeanHS (SD) = 21.5 (4.74); Meannon-HS (SD) = 19.8 (3.98); p < 0.001), discrimination in everyday settings (MeanHS (SD) = 18.9 (8.16); Meannon-HS (SD) = 16.0 (7.06); p < 0.0001), and discrimination in healthcare settings (MeanHS (SD) = 1.77 (0.64); Meannon-HS (SD) = 1.56 (0.62); p < 0.001). After adjusting for sex, race, age, and income, the association between HS and discrimination in healthcare settings was non-significant; however, associations between HS and increased levels of perceived stress and everyday discrimination remained significant. Low survey completion rates and demographic differences between those who did and did not complete the study surveys may limit generalizability of results. Findings suggest that those with HS may benefit from regular screening for psychosocial well-being and provision of support resources.

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.

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.

Anakinra in Pyogenic Arthritis, Acne, Pyoderma Gangrenosum, and Suppurative Hidradenitis (PAPASH) Spectrum Disorder: A Case Report and Literature Review.

Pyogenic arthritis, acne, pyoderma gangrenosum, and suppurative hidradenitis (PAPASH); pyogenic arthritis, pyoderma gangrenosum (PG), and acne; PG, acne, hidradenitis suppurativa; and PG, acne, spondylarthritis (PASS) are all part of a spectrum of autoinflammatory disorders that share similar pathogenesis. They are related to various mutations in the proline-serine-threonine phosphatase interacting protein 1, leading to dysregulation of the innate immune system and overproduction of interleukin (IL)-1, IL-17, and IL-23 and tumor necrosis factor (TNF)-α. Targeting these cytokines with biologics plays an important role in treatment. Here, we are describing the case of a young male with PAPASH syndrome who was treated with TNF-α and IL-1 inhibitor.

Ultrasonography of Facial and Submandibular Hidradenitis Suppurativa and Concomitance with Acne Vulgaris.

OBJECTIVES: To describe the ultrasound characteristics of facial and submandibular hidradenitis suppurativa (HS) and detect acne vulgaris (AV) concomitance in these cases. METHODS: We performed a retrospective study of the ultrasound images of patients with facial HS who had been clinically evaluated by dermatologists. The reported ultrasound diagnostic criteria, severity (mSOS-HS), and activity (US-HAS) staging of HS were used to categorize the patients. The finding of fragments of hair tracts within the key lesions (dilated hair follicles, pseudocysts, fluid collections, and tunnels) was considered a pivotal sign to discriminate HS from AV. Demographic and morphological analysis of the images were considered. RESULTS: Thirty-three patients met the criteria (78.8% male/21.2% female). Of these, the mSOS- HS scoring was stage I in 51.5%, stage II in 27.3%, and stage III in 21.2%. Dilation of the hair follicles and the presence of pseudocysts, fluid collections, and tunnels were detected in the HS cases; 63.1% of pseudocysts, 62.4% of tunnels, and 46.2% of fluid collections contained fragments of hair tracts. In all HS cases, there was a key lesion(s) with fragments of hair tracts. Four (12.1%) patients showed concomitant facial HS and acne ultrasound lesions. The acne lesions were pseudocysts without inner hair tract fragments in all cases, and the SOS-Acne scoring was stage II for all of them. CONCLUSION: Facial HS can be detected on ultrasound and shows a morphology similar to that of HS in other corporal regions. In some cases, facial HS could be concomitant with AV. The subclinical ultrasonographic information can support a better management of these cases.

Comorbidities, Clinical Presentation, Subtypes, and Treatment of HS Patients in Lithuania.

Background: Hidradenitis suppurativa (HS) is a persistent, recurring skin inflammatory condition linked to various comorbidities. Management involves antibiotics, hormone therapy, immune-modulating drugs, surgery, and treatment of comorbidities. The objectives of the study were to assess the comorbidities, clinical presentation subtypes, and applied treatment of patients with HS. Methods: Patients with HS who visited the Centre of Dermatovenereology at Vilnius University Hospital Santaros Klinikos in Lithuania underwent evaluation based on the guidelines of the European Hidradenitis Suppurativa Foundation Registry questionnaire. Results: The study included 49 patients, and 61.22% (n = 30) had comorbidities. A strong positive correlation was found between a family history of inflammatory diseases (69.38% (n = 34)) and the severity of HS according to Hurley stage (r = 0.71 p < 0.05). A statistically significant correlation (r = 0.944, p = 0.02) was found between metabolic comorbidities and Hurley stage. Patients on biologic treatment had a mean IHS4 of 7.38 at the beginning of treatment and 3.22 at follow-up (p < 0.05). For patients not on biologics, the initial IHS4 score was 6.21 and 5.42 at follow-up (p > 0.05). Conclusions: A family history of inflammatory diseases and metabolic comorbidities showed a strong correlation with HS severity. Treatment with biologics showed significant improvement in HS scores compared to systemic antibiotics.

Prevalence and association of polycystic ovary syndrome and hidradenitis suppurativa in underrepresented groups.

Hidradenitis suppurativa (HS) is an inflammatory disorder of follicular biology; androgens are believed to be involved in its pathogenesis. Polycystic ovary syndrome (PCOS) is similarly characterized by hyperandrogenism. Previous studies have found a lasting association of HS and PCOS. Socioeconomic status (SES) has been described as a comorbidity for both HS and PCOS that has not been accounted for in prior studies; we sought to investigate this association while adjusting for this. We also analyzed the prevalence of PCOS among HS patients. Using the All of Us database, female HS patients were stratified by PCOS diagnosis and compared by age, race, and ethnicity. Female HS patients were also nearest-neighbor propensity-score matched to controls at a 4:1 ratio, selecting for race, ethnicity, age, ever smoker, alcohol use disorder, obesity, type II diabetes, Medicaid status, and community deprivation index. Univariable and multivariable logistic regression was conducted to estimate the effect of HS on the presence of PCOS. The distribution of race among HS patients with PCOS was significantly different than HS patients without PCOS. A total of 1,022 female HS patients and 4,088 matched female controls were included. Significantly more patients carried a diagnosis of PCOS compared to controls (8.8% versus 4.3%, p < .001). In multivariable logistic regression, PCOS was significantly associated with HS [OR 1.71 (95% CI 1.34-2.17)]. This is the first study investigating the association of HS and PCOS within the All of Us database. We found that females with HS had a 1.34- to 2.17-fold increased odds of having PCOS, which is consistent with previous analyses. However, our analysis, in addition to controlling for common medical co-morbidities found in both HS and PCOS, also accounts for markers of SES at an individual and community level, further strengthening the association of HS with PCOS.

Real-world effectiveness and safety of bimekizumab for hidradenitis suppurativa: An ambispective observational study.

In this original research, we present the results in terms of effectiveness and safety of bimekizumab for hidradenitis suppurativa in real clinical practice. Results indicated significant improvement in all activity scores and patient-reported outcomes at week 16, including a notable decrease in mean IHS4 from 27.1 to 15.6 (p < 0.001), HS-PGA from 5.1 to 3.2 (p < 0.001), VAS pain from 8.3 to 4.7 (p < 0.001) and DLQI from 21.6 to 12.6 (p < 0.001). Bimekizumab, administered every 2 or 4 weeks, was well-tolerated with no discontinuations and no new safety concerns identified. These findings corroborate the drug's effectiveness and favourable safety profile observed in phase 3 clinical trials, supporting its use in real-world clinical practice for treating HS.

Insights into the Window of Opportunity and Outcome Measures in Patients with Moderate to Severe Hidradenitis Suppurativa Treated with Secukinumab: A Real-World Study.

INTRODUCION: The concept of a window of opportunity in hidradenitis suppurativa (HS) management suggests that early initiation of biological therapy leads to better outcomes, though its timing remains uncertain. METHODS: We conducted a retrospective observational multicenter study, including consecutive patients with moderate to severe HS who initiated secukinumab treatment following prior failure with systemic antibiotics or adalimumab. Therapeutic burden was defined as the sum of previous systemic treatment cycles and previous major surgical interventions for HS. Patients were followed up for 24 weeks. Main outcomes were safety and effectiveness, assessed through the proportion of patients achieving HS Clinical Response (HiSCR) and a 55% reduction in International HS Severity Score System (IHS4-55). Additionally, potential predictors of response to secukinumab were studied. Analysis was performed on an intention-to-treat basis. RESULTS: A total of 67 patients (33 men, 34 women) were included, with a mean age of 41.55 (11.94) years and a mean baseline IHS4 of 17.88 (11.13). The mean therapeutic burden was 6.06 (3.49). At week 24, 10.45% (7/67) of patients experienced adverse events, with three leading to treatment discontinuation. At week 24, 41.79% (28/67) of patients achieved HiSCR, and 44.78% (30/67) of patients achieved IHS4-55. HiSCR could not be calculated in 12 patients with a baseline AN count < 3. A lower therapeutic burden was significantly associated with a higher likelihood of achieving HiSCR and IHS4-55 at week 24. CONCLUSIONS: Secukinumab showed safety and efficacy in real-world patients with HS, and the inverse correlation found between therapeutic burden and treatment response supports the concept of a window of opportunity, offering insights into its timing.

Causal relationship between metabolic syndrome and hidradenitis suppurativa: A two-sample bidirectional Mendelian randomization study.

Observational studies have suggested an association between metabolic syndrome (MetS) and hidradenitis suppurativa (HS), but whether this relationship is causal remains unclear. Elucidating the causal direction could provide insights into disease mechanisms and potential interventions. We performed bidirectional two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) of MetS and HS. For validation, we replicated the MetS analysis using data from an independent GWAS. We applied multiple MR methods, primarily inverse variance-weighted (IVW) regression, and conducted sensitivity analyses to assess heterogeneity and pleiotropy. The MR analysis demonstrated MetS causally increased HS risk (IVW odds ratio [OR], 1.428 [95% CI, 1.193-1.710]; p < 0.001), with consistent evidence from sensitivity analyses. However, HS did not appear to causally influence MetS risk (IVW OR, 1.008 [95% CI, 0.988-1.028]; p = 0.438). This study provides evidence that MetS causally increases the risk of developing HS. However, we found no evidence for a causal relationship in the reverse direction from HS to MetS. Further research is warranted to elucidate the mechanisms underlying the identified causal association between MetS and subsequent HS development.

Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome: a single-institution case series with a focus on management.

BACKGROUND: Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome is a rare condition characterized by clinical features of all three dermatologic conditions. The management of PASH syndrome is difficult, with no consensus on treatment guidelines. Since PASH syndrome can increase morbidity and adversely impact quality of life, better characterization of effective therapies is needed. METHODS: A retrospective cohort study was conducted to identify all patients with pyoderma gangrenosum (PG) treated at The Ohio State University Wexner Medical Center between 2015 and 2021. PG diagnosis was confirmed via PARACELSUS score. Subsequent chart review identified eight patients with concomitant hidradenitis suppurativa (HS) and acne who were clinically diagnosed with PASH syndrome. RESULTS: Eight patients were clinically diagnosed with PASH syndrome based on their clinical presentation at our institution. Seven patients had failed some type of medical therapy prior to presentation, including topical corticosteroids, oral corticosteroids, oral antibiotics, and biologics. One patient had also tried surgical drainage at an outside institution. Six patients were effectively treated with biologics, usually in combination with other therapies. One patient experienced improvement of her skin lesions after diagnosis and treatment of her underlying hematologic malignancy. CONCLUSIONS: Medical management with biologics in combination with corticosteroids and/or antibiotics was effective in the management of most patients. Diagnosis and treatment of an underlying condition should be prioritized in refractory cases. If workup is negative, surgical management may be considered. Further investigation with a greater number of patients is required to develop management guidelines for PASH syndrome.

Predictability of Insulin Resistance Based on the Clinical Manifestations Among Male Medical Students of a Private College in Saudi Arabia.

Background Numerous clinical signs and symptoms are thought to be associated with insulin resistance. The purpose of this study was to examine the prevalence of insulin resistance among male medical students attending a private Saudi Arabian institution, based on clinical indications. Methods A convenient non-probability sample consisting of 241 male medical students was used to conduct cross-sectional research. Each participant had an in-person interview as well as anthropometric measurements. The interview consisted of a questionnaire that was used to assess demographic data and clinical manifestations related to insulin resistance. Results The study demonstrated the connection between a few dermatological symptoms and waist circumference as an indicator of insulin resistance. In both the high and normal waist circumference groups, acne was the most common symptom. There was no correlation found between waist circumference and psoriasis, hidradenitis suppurativa, androgenic alopecia, alopecia areata, or vitiligo. Nevertheless, as an indicator of insulin resistance, waist circumference was statistically significantly correlated with both skin tags and acanthosis nigricans. Most students had excessive day sleep, foggy brains, struggled with planning and solving problems, and had a memory that became worse in the past few years. In addition, many students feel hungry even after eating some sweets and usually have extreme thirst. Conclusion Among medical students, skin tags, acanthosis nigricans, and acne were the most prevalent dermatological manifestations. Clinicians need to be aware that skin conditions, sleep difficulties throughout the day, changes in cognition, and food cravings might all be indicators of internal changes and/or illnesses such as diabetes and prediabetes.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens.

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.