Severe HS Research Articles

Selection of Reference Genes and HSP17.9A Expression Profiling in Heat-Stressed Grapevine Varieties

Background: “Touriga Franca” (TF) and “Touriga Nacional” (TN) are grapevine varieties cultivated in the ‘Douro Superior’ subregion (Northern Portugal) that experience stressful environmental conditions during the summer. Objectives: Aiming to profile the expression of stress-responsive genes by quantitative real-time PCR (qPCR) in TF and TN plants growing naturally, three candidate reference genes were first tested under controlled conditions. Methods: To simulate a summer’s day, TF and TN in vitro plants were exposed to 32 °C–3 h (heat acclimation) and 42 °C–1 h (severe heat stress, HS) followed by two recovery periods (32 °C–3 h and 24 °C–24 h). Leaf samples were collected at the end of each phase. Control plants were kept at 24 °C. Results: Among the candidate reference genes, the UBC and VAG pair showed the highest stability. The suitability of these genes for qPCR was validated by heat shock protein 17.9A (HSP17.9A) gene profiling. The HSP17.9A expression was up-regulated in both varieties and all experimental phases except in TF control plants. TN showed the highest HSP17.9A relative expression ratio after severe HS. Conclusions: TN responded faster than TF to the induced heat shocks. The UBC, VAG, and HSP17.9A genes revealed to be suitable for further qPCR assays in TF and TN grapevine varieties.

The efficacy of antiviral treatment in chronic hepatitis B patients with hepatic steatosis

Background & aimsWith a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. MethodsCHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. ResultsIn total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245–0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. ConclusionsAmong CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Triglyceride-glucose index: a novel evaluation tool for all-cause mortality in critically ill hemorrhagic stroke patients-a retrospective analysis of the MIMIC-IV database

BackgroundHemorrhagic stroke (HS), including non-traumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), constitutes a substantial proportion of cerebrovascular incidents, accounting for around 30% of stroke cases. The triglyceride-glucose index (TyG-i) represents a precise insulin resistance (IR) indicator, a crucial metabolic disturbance. Existing literature has demonstrated an association between TyG-i and all-cause mortality (ACM) among individuals suffering from ischemic stroke (IS). Yet, the TyG-i prognostic implications for severe HS patients necessitating intensive care unit (ICU) admission are not clearly understood. Considering the notably elevated mortality and morbidity associated with HS relative to IS, investigating this association is warranted. Our primary aim was to investigate TyG-i and ACM association among critically ill HS patients within an ICU context.MethodsHerein, patients with severe HS were identified by accessing the Medical Information Mart for Intensive Care-IV (MIMIC-IV, version 2.2) database, using the International Classification of Diseases (ICD)-9/10 as diagnostic guidelines. Subsequently, we stratified the subjects into quartiles, relying on their TyG-i scores. Moreover, we measured mortality at ICU, in-hospital, 30 days, 90 days, and 1 year as the outcomes. Cox proportional hazards regression analysis and restricted cubic splines (RCS) were deployed for elucidating the relation between the TyG-i and ACM while utilizing the Kaplan-Meier (K-M) method to estimate survival curves. The findings’ robustness was assessed by conducting subgroup analysis and interaction tests employing likelihood ratio tests.ResultsThe analysis included 1475 patients, with a male predominance of 54.4%. Observed mortality rates in the ICU, hospital, 30 days, 90 days, and 1 year were 7.3%, 10.9%, 13.8%, 19.7%, and 27.3%, respectively. Multivariate Cox regression analysis results manifested that heightened TyG-i was significantly related to ACM at 30 days (adjusted hazard ratio [aHR]: 1.32; 95% confidence interval [CI]: 1.05–1.67; P = 0.020), 90 days (aHR: 1.27; 95% CI: 1.04–1.55; P = 0.019), and 1 year (aHR: 1.22; 95% CI: 1.03–1.44; P = 0.023). The results of RCS analysis demonstrated a progressive elevation in ACM risk with rising TyG-i levels. Interaction tests found no significant effect modification in this relationship.ConclusionIn summary, TyG-i exhibits a significant correlation with ACM among patients enduring critical illness due to HS. This correlation underscores the probable utility of TyG-i as a prognostic tool for stratifying HS patients according to their risk of mortality. Applying TyG-i in clinical settings could enhance therapeutic decision-making and the management of disease trajectories. Additionally, this investigation augments existing research on the linkage between the TyG-i and IS, elucidating the TyG-i’s role in predicting mortality across diverse stroke categories.

Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa

BackgroundHidradenitis suppurativa (HS) is a debilitating, inflammatory skin disease with limited treatment options and partially understood pathophysiology. Using an umbrella trial design, three kinase inhibitor immunomodulators with different mechanisms of action were evaluated.MethodsThis phase 2a, double-blind, parallel-group trial enrolled adults with moderate to severe HS who were then randomly assigned (1:1:1:1) to once-daily brepocitinib 45 mg (a JAK1/TYK2 inhibitor), zimlovisertib 400 mg (an IRAK4 inhibitor), ropsacitinib 400 mg (a TYK2 inhibitor), or matching placebo for 16 weeks. The primary end point was the percentage of participants achieving HS clinical response (HiSCR) at week 16. Safety, including treatment-emergent adverse events (TEAEs), was monitored throughout.ResultsTotals of 52, 47, 47, and 48 participants were assigned to brepocitinib, zimlovisertib, ropsacitinib, and placebo, respectively. At week 16, 28% were lost to follow-up and assumed to be nonresponders; HiSCR occurred in 33.3% (16/48) of participants receiving placebo and in 51.9% (27/52), 34.0% (16/47), and 37.0% (17/46) of those receiving brepocitinib, zimlovisertib, and ropsacitinib (difference in percentage points vs. placebo [90% confidence interval], 18.7 [2.7 to 34.6], 0.7 [−15.2 to 16.7], and 3.5 [−12.6 to 19.6]), respectively. TEAEs occurred more frequently with active treatment (brepocitinib, 30 [57.7%]; zimlovisertib, 26 [55.3%]; ropsacitinib, 29 [61.7%]; placebo, 23 [47.9%]). Most TEAEs (infections, skin disorders, and gastrointestinal symptoms) were mild; there were no deaths.ConclusionsParticipants with moderate to severe HS treated with brepocitinib experienced greater clinical response, whereas those on zimlovisertib and ropsacitinib did not, compared with placebo. These results favor the JAK/STAT pathway as an immunologic target in HS and did not confirm a role for selective IRAK4 or TYK2 inhibition. These results should be confirmed in larger studies with longer follow-up. (Funded by Pfizer; ClinicalTrials.gov registration number, NCT04092452.)

Determinants of appointment nonattendance among outpatients with hidradenitis suppurativa

AbstractBackgroundHidradenitis suppurativa (HS) is associated with several comorbidities and significant impairment of quality of life. Moderate to severe HS patients have often prolonged treatment courses at various hospitals. We investigated various factors that may be related to missed follow‐up visits during prolonged treatment courses among HS outpatients.ObjectivesTo highlight potential predictors for appointment absenteeism among HS patients.MethodsDuring a 12‐month period at a university hospital dermatology outpatient clinic, absenteeism and related factors were obtained for each visit at the hospital.ResultsOut of 161 unique follow‐up visits during a 12‐month period at a university hospital dermatology outpatient clinic, 37 patients (23.0%) were absentees. Patients with non‐attendance were more likely to be males (p = 0.02). Patients who were on biologic treatment for HS were less likely to miss appointments (p = 0.06).ConclusionsOur study showed that almost one in four hospital outpatients with HS fail to show up for their scheduled appointments. The data suggest an increased awareness of high risk of missed follow‐up visits during treatment of HS patients.

Artículo traducido] Efectividad de guselkumab en pacientes con hidradenitis supurativa en condiciones de práctica clínica: estudio retrospectivo y multicéntrico en España

BackgroundHidradenitis suppurativa (HS) is a chronic skin condition causing lesions in which high levels of interleukin (IL)-23 and T-helper17 cells are found. Adalimumab remains the only approved treatment. Guselkumab, an antibody targeting the p19 protein subunit of extracellular IL-23, is approved for the treatment of moderate-severe psoriasis, but evidence on its efficacy in treating HS is limited. ObjectivesTo assess the effectiveness and safety of guselkumab in treating moderate-severe HS under clinical practice conditions. MethodsA multicentre retrospective observational study was carried out in 13 Spanish hospitals including adult HS patients treated with guselkumab within a compassionate use programme (March 2020-March 2022). Data referred to patient demographic and clinical characteristics at treatment initiation (baseline), patient-reported outcomes (Numerical Pain Rating Scale [NPRS] and Dermatology Life Quality Index [DLQI]), physician scores (International Hidradenitis Suppurativa Severity Score System [IHS4], HS Physical Global Score [HS-PGA] and Hidradenitis Suppurativa Clinical Response [HiSCR]) were recorded at baseline and at 16, 24, and 48weeks of treatment. ResultsA total of 69 patients were included. Most (84.10%) had severe HS (HurleyIII) and had been diagnosed for over ten years (58.80%). The patients had been subjected to multiple non-biological (mean: 3.56) or biological (mean: 1.78) therapies, and almost 90% of those treated with biologics had received adalimumab. A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores was observed from baseline to 48weeks of guselkumab treatment (all P<.01). HiSCR was achieved in 58.33% and 56.52% of the patients at 16 and 24weeks, respectively. Overall, 16 patients discontinued treatment, mostly due to inefficacy (n=7) or loss of efficacy (n=3). No serious adverse events were observed. ConclusionsOur results indicate that guselkumab may be a safe and effective therapeutic alternative for patients with severe HS that fail to respond to other biologics.

PA33 Paediatric and adolescent hidradenitis suppurativa: a snapshot of a single centre’s experience

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory debilitating condition that primarily affects younger people. Its exact prevalence is unknown, but it is estimated to affect at least 1% of the Irish and UK population. Onset is late adolescence and the early 20s in the majority. The impact of early-onset HS (&amp;lt; 18 years) is increasingly recognized, but awareness and knowledge of disease prevalence and severity in Ireland remain sparse. Studies in adults highlight association with a raised body mass index (BMI) and smoking, in addition to an increased prevalence in young females with African American or mixed ancestry. Presently, there is an absence of specific guidelines for management in those aged &amp;lt; 18 years. With rising obesity levels, combined with decreasing pubertal age, we may encounter early-onset HS more often in future. We present a snapshot of patients with HS attending a single paediatric hospital who were considered for systemic therapy. Ten patients were included (eight females). Mean (SD) age of symptom onset was 12.4 (1.9) years, mean (SD) age of presentation was 14 (2.1) and mean duration of symptoms prior to presentation was 1.5 years. Nine received systemic therapy (nine antibiotics and four biologics). Disease severity, defined by Hurley stage, was mild in one, moderate in five and severe in four. All patients had achieved puberty, one was defined as early-onset (age 10 years) and another as precocious (age 9 years). The BMIs varied: one was normal, two were above a healthy weight, five were very overweight and three were severely overweight according to UK centiles. Most patients experienced comorbidities, including, but not limited to, Crohn disease (n = 1), hepatic steatosis (n = 2), pilonidal sinus (n = 3) and acne (n = 5). One had diabetes, two impaired fasting glucose and one hypercholesterolaemia. No patient reported smoking. Passive smoking and blood pressure were not documented. Four patients had positive family histories. Six patients identified as Black Irish (one Irish Caribbean and five Irish Nigerian), two were White Irish, one patient was from India and one was from Poland. We describe a group of individuals aged ≤ 16 years, the majority of whom had moderate–severe HS. They had similar comorbidities to internationally reported literature in early-onset HS. More skin of colour ethnicities are represented than seen in the general Irish population, which probably reflects both the catchment area and severity of the skin conditions experienced. The limitations of our study include under-representation of milder disease due to an inability to perform a full cross-sectional study at present. Further prospective studies are required to capture the prevalence and characteristics of HS fully in our population of children and young adults. Considering the lifetime impact of this condition, guidelines for the management of HS under the age of 18 years should be considered.

The Effectiveness of Guselkumab in Patients With Hidradenitis Suppurativa Under Clinical Practice Conditions: A Spanish Multicentre Retrospective Study

BackgroundHidradenitis suppurativa (HS) is a chronic skin condition causing lesions in which high levels of interleukin (IL)-23 and T-helper 17 cells are found. Adalimumab remains the only approved treatment. Guselkumab, an antibody targeting the p19 protein subunit of extracellular IL-23, is approved for the treatment of moderate–severe psoriasis, but evidence on its efficacy in treating HS is limited. ObjectivesTo assess the effectiveness and safety of guselkumab in treating moderate–severe HS under clinical practice conditions. MethodsA multicentre retrospective observational study was carried out in 13 Spanish Hospitals including adult HS patients treated with guselkumab within a compassionate use programme (March 2020–March 2022). Data referred to patient demographic and clinical characteristics at treatment initiation (baseline), patient-reported outcomes (Numerical Pain Rating Scale [NPRS] and Dermatology Life Quality Index [DLQI]), physician scores (International Hidradenitis Suppurativa Severity Score System [IHS4], HS Physical Global Score [HS-PGA] and Hidradenitis Suppurativa Clinical Response [HiSCR]) were recorded at baseline and at 16, 24, and 48 weeks of treatment. ResultsA total of 69 patients were included. Most (84.10%) had severe HS (Hurley III) and had been diagnosed for over ten years (58.80%). The patients had been subjected to multiple non-biological (mean 3.56) or biological (mean 1.78) therapies, and almost 90% of those treated with biologics had received adalimumab. A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores was observed from baseline to 48 weeks of guselkumab treatment (all p<0.01). HiSCR was achieved in 58.33% and 56.52% of the patients at 16 and 24 weeks, respectively. Overall, 16 patients discontinued treatment, mostly due to inefficacy (n=7) or loss of efficacy (n=3). No serious adverse events were observed. ConclusionsOur results indicate that guselkumab may be a safe and effective therapeutic alternative for patients with severe HS that fail to respond to other biologics.

Spatial Transcriptomic Profiling Reveals the Pathophysiology of Early Stage Hidradenitis Suppurativa

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that ranges from superficial nodules and deep abscesses to draining dermal tunnels in the intertriginous regions. It causes significant pain, scarring, and a poor quality of life, yet there are currently no effective treatment options. The role of tunnels or sinus tracts—a unique feature of moderate to severe HS—was reported that the epidermal tunnels are the source of inflammatory mediators in Hurley stages II and III. However, the pathophysiology of early stage HS needs further investigation. Here, we examined the intradermal epithelial cells surrounding these nodules in early HS in order to explore their features and function. Utilizing spatial transcriptomics, a cutting-edge technique that offers both spatial information of cells and their gene expression profiles, we compared the intradermal epithelial cell of HS patients in the early Hurley stage with the dermal wall of epidermal cysts in epidermal cyst patients. As expected, keratinocytes in the epidermis of individuals with HS were significantly activated, with increased levels of inflammatory cytokines, including IL-36G and CXCL8. In addition, the increase of IL-4R and IL-13RA1 suggests the increase of the sensitivity of Th2 cytokine on the epidermis and in dermal-infiltrating immune cells. Moreover, genes associated with B lymphocytes were highly expressed in the infiltrating immune cells of HS, implicating the importance of “epidermis-derived” inflammatory cytokines and the role of B cell infiltration in the pathomechanism of early HS.

Physiological and Metabolic Adaptation to Heat Stress at Different Altitudes in Yaks.

Yaks have strong adaptability to extremely cold and hypoxic conditions but are susceptible to high ambient temperature when yaks are raised in low-altitude areas during the high-temperature season. Twenty-four adult male yaks with similar weights and ages were randomly divided into TN (Thermoneutral, altitude = 3464 m), LHS (Light heat stress, altitude = 1960 m), and MHS (Medium heat stress, altitude = 906 m) groups to evaluate adaptation strategies to HS. Non-targeted and targeted metabolomics were applied to investigate the effects of different extents of HS on yaks. LHS- and MHS-yaks showed higher rectal temperatures and respiratory rates than TN-yaks. MHS-yaks had higher levels of red blood cells (RBCs), hemoglobin (Hb), whole blood relative index of middle shear at a shear rate of 5 S-1 (WMS), whole blood relative index of high shear at a shear rate of 200 S-1 (WHS), Casson viscosity (CV), middle shear flow resistance at a shear rate of 5 S-1 (MSFR), and high shear flow resistance at a shear rate of 200 S-1 (HSFR) as compared to TN- and LHS-yaks. Differential metabolites and metabolic pathways, including fatty acid metabolism, lipid metabolism, glucose metabolism, and amino acid metabolism, were altered by HS. Metabolites in the glucose metabolism pathway in LHS- and MHS-yaks were lower than those in TN-yaks. However, LHS-yaks showed higher levels of metabolites in the HIF-1 signaling pathway compared to TN- and MHS-yaks. Most of the tricarboxylic acid cycle (TCA) intermediates and fatty acids were significantly decreased in MHS-yaks compared to the other two groups. As a whole, yaks raised at a low altitude (25.6 °C) suffered from severe HS, but they adapted to HS with vasodilatation for dissipating heat and the increased antioxidants and metabolite levels of energy substrates.

32834 Patient and dermatologist perspectives on unmet needs in hidradenitis suppurativa

Objective: To report patient journey and disease management of HS from the perspectives of US dermatologists and patients. Methods: Dermatologists with expertise in HS, general dermatologists, and patients with HS participated in this prospective web-based survey study. Dermatologists completed a 33-question survey focused on disease awareness, referral practices, and treatment patterns. Patients completed a 46-question survey that included demographics, disease characteristics, journey to care, treatment history, and HS awareness. Results: Overall, 47 patients and 30 dermatologists (6 of whom were HS experts) participated in this study. The majority of patients (73%) experienced first HS symptoms before the age of 20 years, and 47% of patients reported >10 years from symptom onset to HS diagnosis. Dermatologists and patients both reported challenges with the referral process, with 47% of referred patients reporting the process as “very difficult.” Patients reported they were most frequently (51%) diagnosed by a dermatologist. Before seeking medical help, 70% of patients tried nonprescription therapies for their symptoms. Topical therapy and antibiotics were the most commonly prescribed first-line treatment for mild to moderate HS, and biologics were for severe HS. Most patients (63%) reported that biologic treatment improved their condition, and 41% of patients reported that time to initiate a biologic was >2 years from diagnosis. Additionally, patients and dermatologists both reported high levels of psychological burden experienced by patients. Conclusion: Increased awareness of HS is necessary to address unmet needs, including reducing diagnosis delays and optimizing treatment strategies, to ensure comprehensive care and improved outcomes.

PSV-17 The Interaction Between Heat Stress and Zearalenone Toxicity in Porcine Skeletal Muscle

Abstract Heat stress (HS) and Zearalenone (Zen) exposure negatively impact growth, production efficiency, animal welfare, and both can be lethal. Zearalenone, a mycotoxin, can contaminate a variety of feedstuffs. As both HS and Zen independently can cause oxidative stress, we hypothesized that concomitant exposure to HS and Zen would cause oxidative stress in pig skeletal muscle more than either agent alone. Prepubertal gilts (n = 26) were fed placebo or Zen (40 ug/kg) twice daily and exposed to thermoneutral conditions (TN; 21.0 °C) or a 12 h diurnal HS challenge (simulated night - 32.2 °C; simulated day - 35.0 °C) for 7 d. Immediately following the environmental challenge, pigs were euthanized and the oxidative (STR) portion of the semitendinosus muscle was collected. Heat stress increased rectal temperature following the simulated nighttime (TN: 38.9 ± 0.04 °C; HS: 39.3 ± 0.04; P &amp;lt; 0.0001) and daytime (TN: 39.2 ± 0.09 °C; HS: 39.9 ± 0.08 °C; P &amp;lt; 0.0001) conditions. In STR, malondialdehyde-modified protein abundance (P = 0.1) and concentration (P &amp;lt; 0.1), markers of oxidative stress, tended to increase following Zen exposure, largely driven by the HS-Zen group. Heat stress increased protein expression of antioxidant enzymes catalase (p&amp;lt; 0.05) and superoxide dismutase 1 (P &amp;lt; 0.05), while Zen decreased glutathione peroxidase 1 (P &amp;lt; 0.05) transcript (P &amp;lt; 0.05) and protein (P &amp;lt; 0.05) abundance and enzymatic activity (P &amp;lt; 0.05). Although a mild HS paradigm and low Zen exposure were employed, oxidative stress markers were altered suggesting oxidative skeletal muscle is susceptible to HS- and Zen-mediated changes in redox balance. In total, these data raise the possibility that more severe HS exposures and greater Zen doses, similar to those sometimes encountered in production settings, may compromise muscle health.

Super-Selective Partial Splenic Embolization for Hereditary Spherocytosis in Children: A Single-Center Retrospective Study.

BackgroundHereditary spherocytosis (HS) is the most common hemolytic anemia due to erythrocyte membrane defects. Total splenectomy is the most effective treatment for moderate or severe HS. As a conservative alternative, partial splenic embolization (PSE) can preserve part of the spleen's function, thus reducing the risk of overwhelming post-splenectomy infection (OPSI) or sepsis, especially for pediatric patients. However, it is not easy to precisely control the scope of interventional embolization, limiting PSE applications. The present study aims to optimize the PSE procedure on smaller, which is named super-selective PSE (SPSE), to improve the controllability and assess the feasibility and effectiveness of SPSE.ResultsThis study was conducted by retrospectively reviewing clinical data from HS patients treated by surgical treatments, which were diagnosed at the children's hospital of Chongqing medical university from January 2015 to December 2019. Patients were divided into two groups according to their treatment preference: SPSE (16 patients) group and total splenectomy (41 patients) group. The mean proportion range of splenic embolism by SPSE was 82.4%, close to the expected value (70–85%). The average hemoglobin value was increased significantly from 6.85 (5.6–8.0) g/dl before SPSE to 12.4 (10.4–13.3) g/dl after SPSE (p < 0.001). All children after SPSE suffered mild post-embolization syndrome, such as pain, fever, and vomiting, which could easily be controlled with appropriate supportive therapy.ConclusionsSuper-selective partial splenic embolization is a safe and effective treatment for moderate or severe HS in children. However, with a longer follow-up, more patients further assess the value of SPSE.

Biologics and small molecule inhibitors for hidradenitis suppurativa

AbstractBackgroundHidradenitis suppurativa (HS) is a debilitating, chronic inflammatory dermatosis that is often recalcitrant to first‐line treatments. Though mechanisms underlying its pathology remain unclear, a number of upregulated inflammatory cytokines (including tumor necrosis factor‐α [TNF‐α], interleukin [IL]‐1, IL‐17, IL‐12, and IL‐23) have been identified in HS, leading to a growing investigation of targeted biologic therapies in moderate‐to‐severe HS.ObjectiveWe aim to review the current literature on biologics and small molecule inhibitors that have been used to treat HS and discuss mechanisms of action, dosing, safety considerations, and recommendations for use.FindingsBiologics that have been reported to treat HS include TNF‐α inhibitors (adalimumab, infliximab, golimumab, and certolizumab), IL‐1 inhibitors (anakinra and canakinumab), IL‐12/23 inhibitor (ustekinumab), IL‐23 inhibitors (guselkumab, risankizumab, and tildrakizumab), IL‐17 inhibitors (secukinumab, ixekizumab, and brodalumab), and small molecule inhibitors (tofacitinib and sirolimus). Though adalimumab is currently the only FDA‐approved agent to treat HS, those who do not have an optimal response may still benefit from a different anti‐TNF agent, particularly high dose infliximab. A number of other targeted treatments have also shown promising results in small prospective studies for consideration in HS patients. Additional considerations in biologic therapy include mitigating patient concerns about injection reactions and choosing agents that may also treat comorbid conditions.ConclusionThis review summarizes the current literature on the use of biologics and small molecule inhibitors in HS. There remains a significant and continued need to expand the treatment armamentarium for moderate to severe HS

Extensive hidradenitis suppurativa treatment with wide radical excision and skin grafting: a case report

Acne inversa, also referred to as purulent apocrine gland inflammation (hidradenitis suppurativa – HS), is a chronic inflammation of the skin, causing painful and purulent lesions that usually appear in the areas with a large number of apocrine glands, such as axillae, inguinal regions and inframammary folds. This study involves the case of a 46-year-old woman suffering from the treatment resistant Hurley Stage III HS. The patient underwent a series of surgeries using wide radical excision of the entire involved tissue, as well as graft procedures to treat extensive HS lesions in various body areas. Numerous treatment modalities regarding HS have been established, although their effects are not permanent enough to prevent recurrence. Therefore, surgery is regarded as the most effective, or even the only effective treatment of severe HS. Nevertheless, following the standard pharmacological and surgical treatment, it is crucial to ensure optimization of the nutritional parameters, reduction of friction and pressure in the affected area, appropriate wound care, weight loss and smoking cessation.

Validating controlled attenuation parameter in the assessment of hepatic steatosis in living liver donors.

Hepatic steatosis (HS) negatively impacts transplant outcomes in living liver donors. To date, liver biopsy is preferred for HS evaluation. This study aims to evaluate the measurement of controlled attenuation parameter (CAP) as a diagnostic tool of HS in living liver donors. Candidates recruited to this study, conducted from April 2016 to February 2020, were potential donors who had undergone transient elastography using Fibroscan® and CAP measurements at liver segments VI and VII, followed by liver biopsy. The HS grades from liver biopsy were classified as S0 (<5%), S1 (5-33%), S2 (33-66%), and S3 (>66%). For CAP, they were S0 (≤218dB/m), S1 (218-249dB/m)), S2 (250-305dB/m)), and S3 (>305dB/m)). The CAP measurements were compared with the liver biopsy results. Of the 150 potential donors [male, 73.3%; mean age, 30.0±7.0 years; body mass index (BMI), 24.7±3.5kg/m2], 92 (61.3%) had no or mild HS, while 58 (38.7%) and 10% had moderate to severe HS based on CAP and liver biopsy, respectively. Subjects with moderate to severe HS per CAP were mostly males (0.014), and had higher BMI (p = .006), alanine aminotransferase (ALT) (.001), gamma-glutamyl transferase (.026), and high-density lipoprotein (.008). On multivariate analysis, high ALT (OR, 1.051; 95% CI, 1.016-1.087; p = .004) was a predictor of significant HS. The sensitivity, specificity, positive and negative predictive values of CAP to detect significant HS were 93.3%, 67.4, 24.1%, and 98.9%, respectively. The high sensitivity and negative predictive values of CAP make it a good screening test to exclude significant HS in potential living liver donors which, in turn, can help avoid unnecessary liver biopsies.

The measurement performance of the EQ-5D-5L versus EQ-5D-3L in patients with hidradenitis suppurativa

PurposeHidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects up to 1% of the population in Europe. The EQ-5D is the most commonly used generic instrument for measuring health-related quality of life among HS patients. This study aims to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with HS.MethodsWe recruited 200 consecutive patients with HS (mean age 37 years, 38% severe or very severe HS) to participate in a multicentre cross-sectional survey. Patients completed the EQ-5D-3L, EQ-5D-5L, Dermatology Life Quality Index (DLQI) and Skindex-16 questionnaires.ResultsMore than twice as many different health state profiles occurred in the EQ-5D-5L compared to the EQ-5D-3L (101 vs. 43). A significant reduction in ceiling effect was found for the mobility, self-care and usual activities dimensions. A good agreement was established between the EQ-5D-3L and EQ-5D-5L with an intraclass correlation coefficient of 0.872 (95% CI 0.830–0.903; p < 0.001) that was confirmed by a Bland-Altman plot. EQ-5D-5L improved both the absolute and relative informativity in all dimensions except for anxiety/depression. EQ-5D-3L and EQ-5D-5L demonstrated similar convergent validity with DLQI and Skindex-16. EQ-5D-5L was able to better discriminate between known groups of patients based on the number of comorbidities and disease severity (HS-Physician's Global Assessment).ConclusionIn patients with HS, the EQ-5D-5L outperformed the EQ-5D-3L in feasibility, ceiling effects, informativity and known-groups validity for many important clinical characteristics. We recommend using the EQ-5D-5L in HS patients across various settings, including clinical care, research and economic evaluations.

Atherogenic index of plasma is associated with the severity of Hidradenitis Suppurativa: a case-control study

BackgroundHidradenitis suppurativa (HS) is a chronic inflammatory disease associated with several comorbidities and vascular risk factors, such as dyslipidemia. The present study aimed to assess the possible associations between the lipid profile and atherogenic indexes and the severity of HS.MethodsThis case-control study enrolled 78 HS patients and 62 healthy controls. Classic lipid profile and lipoprotein ratios, including the atherogenic index of plasma (AIP), were evaluated. The severity of HS was measured by the HS Physician Global Assessment (PGA).ResultsHS-patients had lower serum total cholesterol and HDL-C levels and higher AIP than the control group. AIP was positively correlated to BMI, waist circumference, systolic and diastolic blood pressure, LDL-C, triglycerides, non-HDL-C, ApoB, HOMA, and hs-CRP and negatively to HDL-C and ApoA1. For the overall lipid profile, only AIP was related to a more severe HS (PGA ≥ 3) after controlling for age, sex, BMI, insulin resistance (IR), active smoking, and statin use (r = 0.268; p = 0.023). Multiple logistic regression adjusted for age, sex, BMI, IR, smoking status and statin use, showed that AIP ≥ 0.11 was significantly associated with the severity of HS (OR, 4.38; CI 95%, 1.09–17.50; p = 0.037).ConclusionsIn conclusion, these results showed that AIP is significantly and independently associated with HS severity.

The effect of subcutaneous brodalumab on clinical disease activity in hidradenitis suppurativa: An open-label cohort study

Hidradenitissuppurativa is an autoinflammatory disorder of keratinization, with dysregulation of T helper type 17 cytokines. Brodalumab is a monoclonal antibody that targets the interleukin (IL) 17 receptor A receptor. To assess the safety and tolerability and clinical response at weeks 12 and 24 of brodalumab in moderate to severe HS. Ten participants with no history of inflammatory bowel diseasewere administered brodalumab 210mg/1.5mL subcutaneously at weeks 0, 1, and 2 and every 2weeks thereafter until week 24. Participants were assessed for adverse events (grade 2/3 adverse events) andclinical response (Hidradenitis Suppurativa Clinical Response [HiSCR], Sartorius, International Hidradenitis Suppurativa Severity Scoring System [IHS4]), including ultrasonography and skin biopsies. All 10 participants completed the study. No grade 2/3 adverse events associated with the use of brodalumab were reported. All patients (100%) achieved HiSCR, and 80% achieved IHS4 category change at week 12. HiSCR achievement occurred as early as week 2, likely due to the unique blockade of IL-17A, IL-17C, and IL-17F by brodalumab. Significant improvements were seen in pain, itch, quality of life, and depression. Brodalumab was well tolerated in this HS cohort, with no serious adverse events and improvement in clinical outcomes. Alterations in dose frequency may be required in those with advanced disease, which requires further exploration.

Anemia in Hidradenitis Suppurativa, Hepcidin as a Diagnostic Tool

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, and dermal tracts. We recently reported a high prevalence of anemia in HS patients. These data led to the hypothesis that chronic inflammation in HS predominantly causes anemia of chronic disease (ACD) through upregulation of IL-6 and hepcidin, a key regulator of iron homeostasis. Hepcidin is widely accepted as a marker distinguishing ACD from iron deficiency anemia (IDA) in inflammatory conditions. The purpose of this study was to measure serum hepcidin in HS patients to classify the type of anemia observed in this cohort. We measured hematologic data, inflammatory markers, and serum hepcidin using an enzyme-linked immunosorbent assay (ELISA; R&amp;D Systems) in 55 patients with varying degrees of HS severity. Independent Student t tests and one-way ANOVA were used to compare hepcidin levels in HS patients with anemic and nonanemic states. Of 55 HS patients evaluated in this study, 42 (76%) were female and the average age was 37.6 ± 13.2 years. The mean hemoglobin (Hb) was 12.2 ± 2.0 g/dL and mean hepcidin was 19.5 ± 12.9 ng/mL. Anemic patients (n = 26) with reduced iron stores (ferritin ≤30 ng/mL) had significantly lower hepcidin than anemic patients with adequate iron stores (9.7 ± 15.8 ng/mL vs 23.8 ± 11.1, P = .03). Elevated hepcidin in this subset suggests that ACD is the predominant cause of anemia. Analysis by ANOVA also found that hepcidin levels were significantly greater in patients with more severe HS, as measured by HS-Physician Global Assessment scores (P = .005). Hepcidin may serve as a surrogate biomarker for active disease and inflammation in HS. These findings affirm the utility of hepcidin as a promising tool for distinguishing IDA from ACD and, in turn, help identify HS patients in whom dietary iron supplementation is unlikely to be beneficial.