Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials.

BACKGROUND: Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa. METHODS: BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed. FINDINGS: Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed. INTERPRETATION: Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa. FUNDING: UCB Pharma.

Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials.

BACKGROUND: Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials. METHODS: SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov. FINDINGS: Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1-2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0-2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1-2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2-3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected. INTERPRETATION: When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment. FUNDING: Novartis Pharma.

Initial steps towards developing a predictive algorithm of disease progression for hidradenitis suppurativa (HS): results from a Cox proportional hazard regression analysis on disease progression among a cohort of 335 Danish patients with HS.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory and scarring disease with a wide spectrum of disease severity. The amount of scarring is proportional to the preceding tissue damage and poses a challenge to patients. Severe HS is most often treatment recalcitrant, but hypothetically avoidable through early biologic treatment. Early prediction of individual risk of disease progression is therefore essential for patient management. OBJECTIVES: To investigate risk factors associated with disease progression and to design an algorithm capable of predicting disease -progression. METHODS: A prospective cohort study of 335 Hurley III-naïve patients with HS, not treated with biologics, was followed for a median of 2 years. Potential risk factors covered basic demographics, HS anamnestic factors and clinical HS factors collected during physical examination. Two separate Cox proportional hazard regression (CPHR) analyses were conducted. A summated 'progression score' was calculated and used in the predictive algorithm of severe disease. Subsequent bootstrap sampling was used to validate the predictability of the predictive algorithm. RESULTS: The CPHR analysis of Transition to severe disease found that active smoking [hazard ratio (HR) 4.01, 95% confidence interval (CI) 1.71-9.40, P = 0.001]; body mass index (BMI) points > 25 at baseline (each point: HR 1.06, 95% CI 1.02-1.09, P < 0.001); active disease in 2 (HR 4.26, 95% CI 1.23-14.84, P = 0.02) and ≥ 3 areas (HR 6.54, 95% CI 1.89-22.72, P = 0.003) all constituted substantial risk factors. Conversely, the CPHR analysis of Disease progression did not yield results of clinical relevance. A 'progression score' of 3.04 was used as a threshold in the predictive algorithm of Transition to severe disease and achieved the following test specifics: sensitivity = 0.51, specificity = 0.86, positive predictive value = 0.50, negative predictive value = 0.86. CONCLUSIONS: We found a disparity between factors increasing the risk of simple Disease progression and those increasing the risk of Transition to severe disease. For the latter, active smoking, BMI points > 25, active disease in 2 or ≥ 3 areas were all shown to be the clinically relevant factors that could be used to construct an algorithm that correctly predicted progression to severe HS in more than half of all instances.

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.

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.

Increased cancer incidence among patients with hidradenitis suppurativa - a Danish nationwide register study 1977-2017.

BACKGROUND: The chronic, inflammatory skin disease hidradenitis suppurativa (HS) (prevalence: 0.5%-1%, diagnostic delay: 7-10 years) primarily arises in younger adults and frequently coincides with autoimmune comorbidities and unhealthy life-styles (smoking and obesity). These factors are known to increase cancer risk, but despite this, information on cancer occurrence among HS patients is scarce. MATERIALS AND METHODS: A nationwide retrospective register-based study assessing relative risk of cancer - overall and by anatomical site - following HS diagnosis expressed as standardized incidence ratios (SIRs), which is ratios between observed cases among all Danes diagnosed with HS since 1977 and expected cases based on cancer incidence rates of the entire Danish population during the same period. RESULTS: Participants consisted of a cohort of 13,919 Danes with HS, who during an average of 14.2 years of follow-up developed a total of 1,193 incident cancers, corresponding to a 40% increased risk (SIR = 1.4, 95% CI: 1.3 to 1.4, p < 0.001). Increased risks were observed for cancers of the respiratory system, oral cavity and pharynx, digestive organs and peritoneum, urinary tract, and the lymphatic tissues. INTERPRETATION: These findings underline an unmet need for health monitoring, lifestyle interventions and cancer screening if and when relevant.

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.

Sex-related Variations in Comorbidities in Lichen Sclerosus: A Systematic Review and Meta-Analysis.

The comorbidities of lichen sclerosus (LS) are presumed but have not been analysed in detail. The purpose of this review was to identify evidence-based associated diseases in patients with LS and explore the potential need for sex-dependent screening protocols. A comprehensive search of the MEDLINE, Embase, and PsycINFO databases from inception to 29 February 2024 was conducted using the key search terms LS and all its synonyms. Pooled odds ratios and 95% confidence intervals of comorbidities were generated using the DerSimonian and Laird random-effects model. A total of 21 case-control studies met the inclusion criteria. Of the 75 comorbidities analysed, only 16 (21.3%) were studied in both sexes, revealing no contrasting associations based on sex. Both female and male LS patients showed significantly increased odds of common dermatological conditions (i.e., lichen planus, vitiligo, alopecia areata, atopic dermatitis, and psoriasis), various cardiovascular risk factors (i.e., essential hypertension, obesity, dyslipidaemia, diabetes mellitus, and diabetes mellitus type 2), genital warts, and hypothyroidism compared with controls. Overall, the scarcity of data currently does not support the implementation of sex-dependent screening strategies. The findings do, however, present significant associations with a range of potentially serious comorbidities, which warrants further elucidation and clinical vigilance.

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.

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.

Pharmacies Counselling of Patients in the Era of Antifungal Resistance.

BACKGROUND: Tinea pedis is one of the most prevalent superficial fungal infections. Initial antifungal treatment is often acquired over-the-counter (OTC) without previous consultation with a physician. OBJECTIVE: Lately, increasing antifungal terbinafine resistance has been documented in Denmark and globally and it is therefore of interest to assess how Danish pharmacies advise customers with tinea pedis. METHODS: One hundred Danish pharmacies were randomly selected and an employee interviewed from each. A structured question guide was followed, with the possibility to add further comments. RESULTS: Interviews of 94 pharmacies were conducted. Six pharmacies never replied. Terbinafine as standard dose or cutaneous solution terbinafine one time application (Lamisil Once (R)) were recommended by 99% of the pharmacy employees as first-line treatment. The customer was advised to seek medical attention when tinea pedis was recurring (93%), or when treatment duration was > 2 weeks (77%). The majority (88%) of the pharmacy employees had no knowledge about antifungal resistance. CONCLUSION: Only few pharmacy employees were aware of the current problem of antifungal resistance and the majority advised costumers to initiate treatment using OTC topical terbinafine. The problem of emerging antifungal resistance requires attention in order to provide customers with tinea pedis effective treatment and prevent further societal spread of resistance to antifungals.

Exploring treatment and antifungal resistance in an outbreak of tinea caused by Microsporum audouinii.

BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. OBJECTIVES: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). METHODS: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. CONCLUSION: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.

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.

New insights on hidradenitis suppurativa phenotypes and treatment response: An exploratory automated analysis of the SUNSHINE and SUNRISE trials.

BACKGROUND: Defining hidradenitis suppurativa (HS) subtypes was previously limited by small sample sizes and poor interrater reliability; no study has investigated subtype treatment responses. The objective of this analysis was to characterize HS clusters in adult patients with moderate to severe HS and evaluate secukinumab treatment responses between clusters. METHODS: Clusters were identified via an unsupervised machine learning clustering analysis using baseline data from the randomized, placebo-controlled SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) phase 3 trials. To assess treatment responses, patients received secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo, for 16 weeks, after which, placebo patients randomly switched to SECQ2W/SECQ4W, and SECQ2W/SECQ4W patients maintained their original treatment, until week 52. Baseline outcomes included patient characteristics, disease characteristics and severity, HS-associated comorbidities and previous treatment exposures. Treatment response was assessed via the HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flares and NRS30 (skin pain). RESULTS: Based on baseline data, three clusters were identified from 1084 patients (Cluster 1: 54.1%, Cluster 2: 17.8%, Cluster 3: 28.1%). Cluster 1 was predominantly female (65.4%) and was characterized by milder HS. Cluster 2 had more patients from the Asia Pacific, Middle East and Africa region (58.5%) and was characterized by moderate HS. Cluster 3 had the highest rates of previous exposure to biologics (45.9%) and prior HS-related surgeries (47.5%) and was characterized by severe HS. SECQ2W and SECQ4W demonstrated efficacy versus placebo in all clusters at week 16; SECQ2W and SECQ4W efficacy was maintained to week 52. SECQ2W treatment showed a trend for greater efficacy versus SECQ4W in Cluster 3 through week 52. CONCLUSIONS: Three HS clusters were identified. Secukinumab demonstrated benefit over placebo in all clusters. However, patients with more severe disease may take longer to respond and more frequent secukinumab dosing may be required for these patients. TRIAL REGISTRATION: SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).

Reporting of self-reported hand eczema as an occupational disease in hospital cleaners: A cross-sectional questionnaire-based study.

BACKGROUND: Hand eczema (HE) is a prevalent disease among professional cleaners. OBJECTIVES: To investigate how often cleaners have their self-reported HE, induced or worsened by cleaners' occupational activities, reported as an occupational disease to the authorities in Denmark and to identify reasons for underreporting. In addition, consultation by physicians and treatment for HE among cleaners were also investigated. METHODS: This cross-sectional questionnaire-based study included hospital cleaners at three different hospitals in Region Zealand, Denmark. RESULTS: We included 224 out of 234 cleaners from three hospitals (response rate: 96%). The lifetime prevalence of self-reported HE with onset in adulthood was 18.3% (n = 41), with cleaners believing every case to be caused or exacerbated by their occupation. Only 9.7% (n = 4/41) of the cases were reported as an occupational disease to the authorities. The most common reasons for non-reporting were a lack of perceived seriousness of the disease (40.5%) and unawareness of the risk of self-reported HE being of occupational origin (32.4%). Remarkably, only 75.7% (n = 28/37) of workers with unreported cases had consulted a physician at some point. Additionally, among cleaners who self-reported HE attributed or aggravated by their occupation, but not officially reported as such, only 56.8% (n = 21/37) had ever used hand moisturisers, while less than 45% had ever used topical steroids or calcineurin inhibitors. CONCLUSION: Our findings reveal substantial underreporting of self-reported HE, perceived to be induced or worsened by the cleaner's occupational activities, as an occupational disease to the authorities.

The correlation between self-reported hand eczema and clinically based diagnosis in professional cleaners.

BACKGROUND: Most studies investigating the prevalence of hand eczema (HE) in professional cleaners use self-reported questionnaire-based data. However, no validation studies of self-reporting of HE among professional cleaners have previously been conducted. OBJECTIVES: To investigate (1) the point prevalence of self-reported HE, (2) the point prevalence of HE estimated by physical examination of the hands and (3) the sensitivity and specificity of self-reporting of HE compared with the diagnosis based on physical examination among professional cleaners. METHODS: Professional cleaners at three different hospitals in Region Zealand were invited to fill out a questionnaire. The point prevalence of self-reported HE was estimated based on questions from the Nordic Occupational Skin Questionnaire. After completing the questionnaire, each cleaner underwent a physical examination of the hands by a dermatologist on the same day. RESULTS: In total, 234 cleaners were invited to participate in the study, and 224 (response rate = 96.0%) agreed to take part. Based on the self-reported questionnaires, 5.3% (n = 12) of the cleaners had current HE. Based on an examination by a physician, 19.2% (n = 43) of the cleaners had current HE. The sensitivity of self-reported HE was found to be 28.0%, while the specificity was found to be 100.0%. The positive predictive value was found to be 100.0%, while the negative predictive value was 85.0%. CONCLUSION: The true point prevalence of HE among professional cleaners is underestimated when based on self-reporting.

Cluster analysis identifies clinical phenotypes of primary hyperhidrosis.

Introduction Identifying subgroups of patients with primary hyperhidrosis (PHH) can improve the understanding of the disease pathophysiology. The study objective is to determine the naturally occurring subgroups of patients with PHH based on clinical characteristics. Methods In this retrospective cohort study, data was collected from participants included in a clinical trial. The data was collected between January 2020 and June 2021 from outpatients with PHH attending a dermatologic department in Denmark. Overall, 84 patients with PHH were screened for inclusion in the clinical trial. Of these, 41 met the eligibility criteria. Four participants were excluded because of missing data. The main outcome was the identification of subgroups of patients with PHH using an unsupervised hierarchical cluster analysis. Results Overall, 37 patients were included (28 [76.7%] females; median age at inclusion 28.0 [interquartile range (IQR) 24.0-38.3]; median body mass index 24.9 [IQR 20.9-27.4); median age of onset 13.0 [IQR 9.5-18.5]; and 26 [70.3%] had a familial disposition towards PHH). Two clusters of 18 and 17 patients were identified. The first cluster had, when compared to the second, a younger age of onset (median age 11.0 [IQR 0-13.0] vs. 17.0 [IQR 15.0-21.0], p=0.003) and higher sweat rates on gravimetry (median 175.0 [IQR 121.2-252.5] vs. 40.0 [IQR 20.0-60.0] milligrams of sweat/5 minutes, p<0.001) and transepidermal water loss (median 93.7 [IQR 91.2-97.8] vs. 59.0 [IQR 44.4-73.2] grams/meter2/hour, p<0.001). No differences were observed for the other variables. Conclusions This study identifies two subgroups of patients with PHH. The patients with an onset of PHH during childhood had a substantially higher sweat and evaporation rate in adulthood than those with an onset during adolescence. These findings may imply a changed understanding of the pathophysiology of PHH, by indicating that an early disease onset can lead to a worse disease course.

Tumor necrosis factor-α inhibitor treatment of acne fulminans - a clinical and literature review.

Acne fulminans (AF) is a rare, serious, sudden-onset and long-lasting skin disease that causes scarring of face and body. Standard treatment with combined long-term isotretinoin and prednisolone is not always sufficient and has a well-known propensity for adverse effects leaving an unmet need for improved therapy. Case reports suggest that tumor necrosis factor (TNF)-α inhibitors may play a role in the management of AF. In a 3-year retrospective data collection from two dermatology centers and literature review of clinical cases of acne fulminans treated with anti-TNF-α therapy, three clinical cases and twelve literature cases were identified. A total of five different TNF-α inhibitors have been tested, with adalimumab being the most commonly used. Clinical response was seen after 1 month in 2/3 (67%) clinical cases and 5/12 (42%) literature cases, respectively, and treatment was successful in 2/3 (67%) and 11/12 (92%) after a median 3-7 months. All reported adverse effects were mild and reversible. Anti-TNF-α treatment may provide rapid improvement in patients with AF when initial treatment with isotretinoin and prednisolone fails. However, randomized controlled trials are lacking, and exact dosage and timing need to be explored before clinical implementation.

Confocal microscopy and optical coherence tomography of inflammatory skin diseases in hairs and pilosebaceous units: A systematic review.

Common skin disorders such as acne vulgaris, rosacea and folliculitis are bothersome prevalent inflammatory diseases of hair follicles that can easily be investigated bedside using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) with micrometre resolution, opening a novel era for high-resolution hair follicle diagnostics and quantitative treatment evaluation. EMBASE, PubMed and Web of Science were searched until 5 January 2023 to identify all studies imaging hair follicle characteristics by RCM and OCT for diagnosis and monitoring of treatment in hair follicle-based skin disorders. This study followed PRISMA guidelines. After inclusion of articles, methodological quality was assessed using the QUADAS-2 critical appraisal checklist. Thirty-nine in vivo studies (33 RCM and 12 OCT studies) were included. The studies focused on acne vulgaris, rosacea, alopecia areata, hidradenitis suppurativa, folliculitis, folliculitis decalvans, lichen planopilaris, discoid lupus erythemasus, frontal fibrosing alopecia and keratosis pilaris. Inter- and perifollicular morphology including number of demodex mites, hyperkeratinization, inflammation and vascular morphology could be assessed by RCM and OCT in all included skin disorders. Methodological study quality was low, and interstudy outcome variability was high. Quality assessment showed high or unclear risk of bias in 36 studies. Both RCM and OCT visualize quantitative features as size, shape, content and abnormalities of hair follicles, and have potential to support clinical diagnosis and evaluate treatment effects. However, larger studies with better methodological quality are needed to implement RCM and OCT directly into clinical practice.

Prevalence of Hidradenitis Suppurativa in an African Population: Validation of a Screening Questionnaire in Lagos, Nigeria.

BACKGROUND: Epidemiologic hidradenitis suppurativa (HS) studies from Africa are lacking. This study aimed at uncovering the prevalence of HS in Lagos, Nigeria, to validate an HS screening questionnaire, and to contribute to the Global Hidradenitis Suppurativa Atlas (GHiSA). METHODS: This was a cross-sectional study of 802 healthy adults accompanying their relations to the outpatient clinic of Family Medicine and Ophthalmology at the Lagos State University Teaching Hospital in Lagos, Nigeria, following ethical approval. Verbal and written consents were obtained prior to inclusion of study participants. The study was conducted using a validated screening questionnaire. Screen-positive and randomly selected screen-negative participants were clinically examined. Severity was categorized using the Hurley score. RESULTS: The prevalence of HS in the sample was 2.2% (18/802; 95% CI: 1.4-3.5%) with no gender predominance. The mean age in the HS group was 34 years (IQR 28-42) and the median body mass index (BMI) of the HS patients was 27.0 (IQR 21.4-28.6). There was no significant difference in BMI between the HS and control group. The screening questionnaire had a sensitivity of 1 (18/18), specificity of 0.8 (20/25), positive predictive value of 0.8 (18/23), and a negative predictive value of 1 (20/20). The axilla was the predominant site of affection (66.7%), and all HS patients were classified as mild disease (Hurley score 1). CONCLUSION: The prevalence of HS in Lagos, Nigeria, was 2.2% and, in this population, BMI did not appear to be a risk factor. The axilla was the most affected site, and all patients had a mild disease severity (Hurley score 1). Finally, the HS screening questionnaire is a suitable tool in population surveys.