An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma.

In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16-32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Diagnostic accuracy of a short-form version of the diagnostic criteria for primary hyperhidrosis.

INTRODUCTION: The gold standard method for diagnosing primary hyperhidrosis (PHH) is based on seven patient-reported criteria. By determining an individual criterion's diagnostic accuracy, one can identify short-version classification models. METHODS: In this cross-sectional study, data were collected from Danish blood donors in 2021. Cohen's kappa and diagnostic accuracy were determined by comparing each criterion with the gold standard method. RESULTS: The study included 1,039 participants. Of them, 59 (5.7%) had PHH and 980 (94.3%) were classified as control individuals. The PHH major criterion "focal visible excessive sweating for at least 6 months without an apparent cause" had the highest prevalence in the participants with PHH compared to the control individuals (100% vs. 0.6%; p < 0.0001). The agreement between this criterion and PHH was Cohen's kappa = 0.95 (95% confidence interval [CI] 0.91-0.99), and its sensitivity was 1.00 (95% CI 0.94-1.00) and specificity 0.99 (95% CI 0.99-1.00). The other criteria showed lower agreement and diagnostic accuracy. CONCLUSIONS: The PHH major criterion showed near-perfect agreement and near-equal diagnostic accuracy compared with the gold standard method. This single criterion can be used as a short-form version to screen for PHH. Determination of reproducibility in independent populations is warranted.

Professional Cleaners' and Healthcare Workers' Ability to Recognize Hand Eczema.

Timely intervention reduces the risk of a poor prognosis in hand eczema, making early recognition of symptoms important in high-risk professions. However, limited data exist regarding the ability of cleaners and healthcare workers to recognize hand eczema. The aim of this study was to examine cleaners' and healthcare workers' ability to recognize hand eczema in clinical photographs and to assess the severity of the disease. Cleaners and healthcare workers completed a questionnaire consisting of 16 questions and participated in a structured interview referring to a validated photographic severity guide for chronic hand eczema, which comprised clinical photographs of hand eczema at varying levels of severity. Eighty cleaners and 201 healthcare workers (total N = 281) participated in the study. The rates of correctly identified hand eczema in clinical photographs (cleaners/ healthcare workers) were: 41.2%/57.7% (mild hand eczema), 81.2%/92.0% (moderate hand eczema), 85.0%/94.5% (severe hand eczema) and 82.5%/97.0% (very severe hand eczema). The proficiency of healthcare workers in recognizing hand eczema was significantly higher than that of cleaners. The results indicate that a large proportion of cleaners and healthcare workers fail to recognize mild hand eczema in clinical photographs. Healthcare workers had higher success rates in recognizing hand eczema in all severity categories. Symptom underestimation may lead to under-reporting of the true prevalence of hand eczema, with consequent loss of opportunities for prevention.

The Global Hidradenitis Suppurativa Atlas (GHiSA) 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 prevalence rates 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. 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. 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.

Global consensus process to establish a core dataset for hidradenitis suppurativa registries.

BACKGROUND: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate. OBJECTIVES: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments. METHODS: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus. RESULTS: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally. CONCLUSIONS: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants.

Hidradenitis suppurativa: new insights into disease mechanisms and an evolving treatment landscape.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with a high unmet medical need. The prevalence of HS reported in most studies is 1-2%, although it is likely to be under-reported and estimates vary globally owing to variance in data collection methods, ethnicity, geographical location and under-diagnosis. HS is characterized by persistent, painful cutaneous nodules, abscesses and draining tunnels commonly affecting the axillary, anogenital, inguinal and perianal/gluteal areas. Over time, chronic uncontrolled inflammation results in irreversible tissue destruction and scarring. Although the pathophysiology of HS has not been fully elucidated, the tumour necrosis factor (TNF)-α and interleukin (IL)-17 pathways have an important role, involving multiple cytokines. Currently, treatment options include topical medications; systemic therapies, including repeated and/or rotational courses of systemic antibiotics, retinoids and hormonal therapies; and various surgical procedures. The anti-TNF-α antibody adalimumab is currently the only biologic approved by both the US Food and Drug Administration and the European Medicines Agency for HS; however, its efficacy varies, with a clinical response reported in approximately 50% of patients in phase III trials. HS is a rapidly evolving field of discovery, with a diverse range of agents with distinct mechanisms of action currently being explored in clinical trials. Several other promising therapeutic targets have recently emerged, and agents targeting the IL-17 and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways are the most advanced in ongoing or completed phase III clinical trials. Alongside limited therapeutic options, significant challenges remain in terms of diagnosis and disease management, with a need for better treatment outcomes. Other unmet needs include significant diagnostic delays, thus missing the therapeutic 'window of opportunity'; the lack of standardized outcome measures in clinical trials; and the lack of established, well-defined disease phenotypes and biomarkers.

Hidradenitis suppurativa associated telomere-methylome dysregulations in blood.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating disease with a significant burden of both organic and psychological comorbidities. It has been shown that certain telomere-related genes (TRGs) affect a wide range of diseases, including HS and its associated comorbidities, but their exact role in HS pathogenesis is still unknown. OBJECTIVES: To determine whether TRG methylomes can be used as biomarkers in HS. METHODS: Using the Illumina HumanMethylation450 BeadChip array, we examined methylation variations associated with TRGs in HS cases and age-, sex- and ethnicity-matched healthy controls. The study utilized integrated bioinformatics statistical methods, such as a false discovery rate (FDR), the area under the receiver operating characteristic curve (AUC) and principal component analysis. RESULTS: There were a total of 585 different differentially methylated CpG sites identified in 585 TRGs associated with HS (474 hypomethylated and 111 hypermethylated) (FDR p-value < 0.05). A number of these CpGs have been identified as being involved in increased pain sensitivity including EPAS1, AHR, CSNK1D, DNMT1, IKBKAP, NOS3, PLCB1 and PRDM16 genes; GABRB3 as a potential alcohol addiction marker; DDB1, NSMCE2 and HNRNPA2B1 associated with cancers. Pathway analysis identified 67 statistically significant pathways, including DNA repair, telomere maintenance, mismatch repair and cell cycle control (p < 0.001). CONCLUSION: The disruption of TRGs leads to the shortening of telomeres, which is associated with HS progression, ageing, cellular senescence and an increased risk of various diseases, including cancer and associated comorbidities, such as metabolic syndrome, cardiovascular disease and inflammatory disorders. Further research is necessary to better understand the underlying mechanisms and establish causal links between TRGs and HS. The present study is the first effort to comprehend potential pathomechanisms of sporadic HS cases concentrating on PBMC methylome since ours.

Viewpoint on the evaluation of severity and treatment effects in mild hidradenitis suppurativa: the cumulative IHS4 (IHS4-C).

Hidradenitis suppurativa (HS) is a chronic, recurrent and debilitating inflammatory skin disease, characterized by painful inflamed nodules, abscesses and tunnels in the skin folds. Up to 66% of HS patients can be classified as having mild disease. However, currently, most clinical trials are focusing on patients with moderate to severe disease, resulting in more available treatment options for this smaller group of patients. This difference in treatment options and lack of clinical trials for patients with mild HS has been noticed and additional focus on milder HS cases is requested. However, an important hurdle to overcome studying treatment efficacy in mild HS is an adequate treatment outcome. Patients with mild HS sometimes have no lesions due to waxing and waning of the disease. Furthermore, the difference in aim of a clinical trial for patients with mild disease should be taken into consideration. Where treatment of moderate to severe patients focusses on lowering the number of draining tunnels, abscesses and inflammatory nodules, in patient with mild disease, we focus on prevention of new lesions and progression to moderate and severe disease. This clinical characteristic of mild HS and difference in aim of clinical trials are the key challenges for efficacy measurement in mild HS. To overcome these challenges, we propose to measure the continuous international hidradenitis suppurativa severity score (IHS4) monthly and use the cumulative IHS4 score (IHS4-C) over all these visits as a primary outcome in clinical trials in patients with mild HS, to increase the probability to detect the inflammatory lesions with a temporary nature. We argue that this novel application of the IHS4, has the potential to better facilitate assessment of treatments or interventions in patients with mild HS and should be tested in future studies.

Dynamic Optical Coherence Tomography of Blood Vessels in Cutaneous Melanoma-Correlation with Histology, Immunohistochemistry and Dermoscopy.

Dermoscopy adds important information to the assessment of cutaneous melanoma, but the risk of progression is predicted by histologic parameters and therefore requires surgery and histopathologic preparation. Neo-vascularization is crucial for tumor progression and worsens prognosis. The aim of this study was the in vivo evaluation of blood vessel patterns in melanoma with dynamic optical coherence tomography (D-OCT) and the correlation with dermoscopic and histologic malignancy parameters for the risk assessment of melanoma. In D-OCT vessel patterns, shape, distribution and presence/type of branching of 49 melanomas were evaluated in vivo at three depths and correlated with the same patterns in dermoscopy and with histologic parameters after excision. In D-OCT, blood vessel density and atypical shapes (coils and serpiginous vessels) increased with higher tumor stage. The histologic parameters ulceration and Hmb45- and Ki67-positivity increased, whereas regression, inflammation and PD-L1-positivity decreased with risk. CD31, VEGF and Podoplanin correlated with D-OCT vasculature findings. B-RAF mutation status had no influence. Due to pigment overlay and the summation effect, the vessel evaluation in dermoscopy and D-OCT did not correlate well. In summary, atypical vessel patterns in melanoma correlate with histologic parameters for risk for metastases. Tumor vasculature can be noninvasively assessed using D-OCT before surgery.

Outcome Measures for the Evaluation of Treatment Response in Hidradenitis Suppurativa for Clinical Practice: A HiSTORIC Consensus Statement.

Importance: Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. Objective: To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. Evidence Review: Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. Findings: Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). Conclusions and Relevance: An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.

Laser and intense pulsed light in the treatment of hidradenitis suppurativa.

Treatment of hidradenitis suppurativa (HS) requires a combination of medical, surgical, and lifestyle interventions. Intense pulsed light (IPL) and lasers have been reported to be useful. The aim of this review is to find the evidence supporting IPL and laser treatment of HS and to provide guidance for the management of specific HS lesions. We searched PubMed and Web of Science for "laser" and "hidradenitis suppurativa" on April 6, 2022. Inclusion criteria were >10 patients, reported follow-up, English language, and human subjects with a diagnosis of HS. A total of 724 articles were screened, but only 17 studies qualified for inclusion (IPL (n = 4), Nd:YAG (n = 6), CO2 laser (n = 6), and intralesional treatment (n = 2). The majority of the studies had a low (n = 10) or moderate (n = 7) evidence level. Treatment effect was noticed in studies using IPL and Nd:YAG (hair reduction). CO2 laser was used for surgery with a success rate ranging from 70.7% to 96.7%. CO2 laser is useful for surgery of stationary HS lesions, but it is difficult to draw a conclusion on the use of IPL and Nd:YAG (hair reduction) as the studies were too heterogeneous to perform a meta-analysis.

Skin and Gut Microbiome in Hidradenitis Suppurativa: A Systematic Review.

Hidradenitis suppurativa (HS) is a chronic skin disease that significantly impairs the quality of life of affected individuals. The disease is characterized by persistent purulent lesions in specific anatomical areas, and its pathophysiology involves multiple factors, including inflammation, genetics, the microbiome, and environmental components. Recent research suggests a potential role for pathogenic bacteria in HS, highlighting the importance of the communication between the human host and the microbiome in maintaining homeostasis and immune system reactivity. However, the exact mechanisms underlying the gut-skin microbial interactions in HS remain unclear. This systematic review aims to examine the existing literature on the differences in skin and gut microbiome composition between HS patients and healthy controls. The review identifies methodological inconsistencies and calls for further research to elucidate the microbiome's role in HS pathogenesis and to explore new therapeutic interventions. The review highlights the need for advancements in microbiome research methodologies, such as metataxonomics and metagenomics, to improve our understanding of the microbiota's impact on health and disease.

Quality of life in individuals with primary hyperhidrosis: a systematic review and meta-analysis.

PURPOSE: Hyperhidrosis can be a debilitating disease that leads to the deterioration of well-being. In this study, the objective was to compare the health-related quality of life (HRQOL) in individuals with and without hyperhidrosis by conducting a systematic review and meta-analysis. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Meta-analysis Of Observational Studies in Epidemiology checklist were employed. We systematically searched Cochrane Library, Embase and PubMed. Two authors independently assessed the literature and extracted the data. The risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was employed. The heterogeneity was determined using I2. RESULTS: Eleven studies met the eligibility criteria comprising 4297 and 147,604 participants with and without hyperhidrosis, respectively. The risk of bias ranged from high quality to very high risk of bias. The individuals with hyperhidrosis had a higher Dermatology Life Quality Index (mean difference 8.53; 95% confidence interval 3.47, 13.58; p = 0.0009) and a lower mental component summary of the short form-12 or -36 (mean difference -6.15; 95% confidence interval -9.00, -3.30; p < 0.0001) than the control individuals. No difference was found for the physical component summary score of the short form-12 or -36 (mean difference -0.88; 95% confidence interval -1.88, 0.12; p = 0.085). Studies using patient-reported outcomes, not included in the meta-analysis, showed similar results. CONCLUSION: Individuals with hyperhidrosis experience a reduced HRQOL that is clinically meaningful and leads to perceivable deteriorations in their well-being. The evidence shows a high degree of heterogeneity, which warrants additional studies.