bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study
Authors: Kern Johannes S , Sprecher Eli , Fernandez Maria Florencia , Schauer Franziska , Bodemer Christine  , Cunningham Tracy , Löwe Sandra , Davis Charles , Sumeray Mark , Bruckner Anna L , Murrell Dédée F ,   for the EASE investigators
Published: January 2023

Abstract

Background
Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death.

Objectives
EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited.

Methods
Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and &lt; 9 months that was 10–50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel – both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of patients with first complete closure of target wound within 45 days.

Results
A total of 223 patients were enrolled and treated (109 treated with Oleogel-S10, 114 with control gel). The primary endpoint was met; Oleogel-S10 resulted in 41·3% of patients with first complete target wound closure within 45 days, compared with 28·9% in the control gel arm (relative risk 1·44, 95% confidence interval (CI) 1·01–2·05; P = 0·013). Adverse events (AEs) occurred with similar frequency for Oleogel-S10 (81·7%) compared with control gel (80·7%). AEs were predominantly of mild-to-moderate intensity (4·6% were severe).

Conclusions
Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB. Oleogel-S10 was well ­tolerated.
Pain experiences among those living with hidradenitis suppurativa: a qualitative study
Authors: Orenstein Lauren A V , Salame Nicole , Siira Meron R , Urbanski Megan , Flowers Nyla I , Echuri Harika , Garg Amit , McKenzie-Brown Anne Marie , Curseen Kimberly A , Patzer Rachel E , Kavalieratos Dio , Chen Suephy C 
Published: January 2023

Abstract

Background
Pain is rated by patients with hidradenitis suppurativa (HS) as the disease’s most impactful symptom. HS therapies are often insufficient to control inflammatory disease activity and pain. A better understanding of patient experiences with pain may improve patient–provider relationships and help identify strategies for addressing HS pain.

Objectives
This qualitative study sought to characterize lived pain experiences of those with HS.

Methods
English-speaking patients ≥ 18 years old with a dermatologist-confirmed diagnosis of HS and an average numerical rating scale pain score of ≥ 1 over the preceding week were recruited from a single academic medical centre in Atlanta, Georgia, USA. Semistructured interviews were conducted from November 2019 to March 2020 to explore participants’ HS pain experiences and the subsequent impact on their lives. Thematic saturation was reached after interviewing 21 participants. Interviews were audio recorded, transcribed, and analysed using thematic analysis.

Results
Among 21 study participants, the median 7-day average pain score was 6 (interquartile range 3–7; scale ranges from 0 to 10, with 10 being most pain). Participants’ descriptions of pain were consistent with nociceptive pain, neuropathic pain and itch. Pain impacted multiple life domains, including physical limitations (decreased mobility and impaired sleep), decreased psychological wellbeing (irritability, depression, loss of control, and difficulty communicating pain experiences) and impaired social relationships (social isolation, intimacy problems and difficulty fulfilling social responsibilities). Although participants reported chronic discomfort, acutely painful and unpredictable HS disease flares caused more distress and quality-of-life (QoL) burden. Participants frequently treated their pain without input from the medical team, sometimes with unsafe medication doses or combinations. Factors contributing to self-management of pain included difficulty accessing timely outpatient care during disease flares and fear of stigma from healthcare providers.

Conclusions
When present, HS-related pain may impact not only physical wellbeing but also mental health and relationships. In addition to therapies that target the inflammatory disease burden, treating the symptom of pain may improve patients’ QoL and wellbeing. Because patients with HS have difficulty explaining their pain, proactively asking them about pain may identify unmet needs, facilitate better pain control and improve QoL. Further, the influence of HS-related pain on numerous aspects of QoL suggests the need for multidisciplinary, patient-centred approaches to HS pain management.
Pathogenic variants in the SPTLC1 gene cause hyperkeratosis lenticularis perstans
Authors: Jägle Sabine , Hsu Hao-Hsiang , Juratli Hazem A , Zimmer Andreas D , Prieschl Amelie , Alter Svenja , Wiedenhofer Bernhard , Metze Dieter , Emmert Steffen , Fischer Judith 
Published: January 2023

Abstract

Background
Hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease, is a rare skin disease presenting with asymptomatic small hyperkeratotic papules. The lesions often appear on the dorsal feet and lower legs, and typically develop after the fourth decade of life. A genetic basis for HLP is suspected; however, so far no gene defect linked to the development of HLP has been identified.

Objectives
We aimed to identify the genetic cause of HLP.

Methods
For mutational analysis we studied a cohort of five patients with HLP using next-generation sequencing (NGS). We used DNA ­extracted from fresh skin biopsies alongside ethylenediamine tetraacetic acid (EDTA) blood samples from two patients, and formalin-fixed ­paraffin-embedded skin biopsy material from three patients. In addition, immunofluorescence staining of HLP lesions from four patients was investigated.

Results
In all samples from the five patients with HLP we identified by NGS rare variants in the SPTLC1 gene. In four patients we detected small deletions/frameshift variants and in one patient a splicing variant, predicted to disturb the splicing process. In blood samples the detected variants were heterozygous with an allele frequency of 49% and 50%, respectively. In skin biopsies the allele frequency was within the range of 46–62%. Immunofluorescence staining revealed reduced SPTLC1 protein levels in skin of patients.

Conclusions
Our findings suggest that pathogenic variants in the SPTLC1 gene are the underlying genetic cause of HLP. Of note, the identified variants were either frameshift- or splicing variants probably leading to nonsense-mediated mRNA decay and thus reduced SPTLC1 protein levels. We conclude that diminished SPTLC1, the key enzyme in sphingolipid biosynthesis, leads to the development of HLP, which highlights the sphingolipid pathway as a new therapeutic target.
The impact of hidradenitis suppurativa on professional life
Authors: Schneider-Burrus Sylke , Kalus Stefanie , Fritz Björn , Wolk Kerstin , Gomis-Kleindienst Susana , Sabat Robert 
Published: January 2023

Abstract

Background
Hidradenitis suppurativa (HS) is a chronic inflammatory disease that affects intertriginous skin.

Objectives
To determine the extent of work ability and productivity impairment as a result of HS in Germany.

Methods
A prospective, multicentre, epidemiological, noninterventional study of patients with HS was conducted. Medical history, medical examination performed by dermatologists and patient-reported outcomes [Work Ability Index (WAI) and Work Productivity and Activity Impairment (WPAI)] were collected.

Results
Of the 481 patients with HS included in the study, 99% were below the current statutory retirement age. In total, 53·3% of patients were working full time, 16·8% part time and 7·3% had retired. The unemployment rate was 12·6%, two times higher than in the general German population. Medical leave because of HS, within the last 6 months, was reported in 41·4% [95% confidence interval (CI) 36·9–46·0], with a duration of 39·3 days on average (95% CI 32·4–46·1). The mean HS-related WPAI absenteeism was 13.3% (95% CI 9·7–16·8), and the loss in productivity because of HS during working hours (WPAI presenteeism) was 25.2% (95% CI 21·8–28·6). Presenteeism was associated with HS disease severity. Overall work impairment because of HS was 33·4% (95% CI 29·3–37·6). The WAI score for patients was 32·2, ∼20% lower than for the average German employee. Only 62·8% of patients were relatively certain that they would be able to perform their work in the coming 2 years. Being more depressed and having more severe pain were associated with lower work ability and overall work impairment. The estimated annual loss of gross value added because of HS for Germany was ∼€12.6 billion (€3.3 billion related to a lower employment rate, €3.5 billion related to absenteeism and €5.8 billion related to presenteeism).

Conclusions
HS leads to a substantial decrease in work ability and productivity and considerable loss of gross value added. Impairment during working hours correlates with disease severity, underlining the socioeconomic importance of early and adequate treatment. Furthermore, decreased work ability and productivity is linked to depressed mood and severe pain, aspects that need more attention in patient care.
Variants in KLK11, affecting signal peptide cleavage of kallikrein-related peptidase 11, cause an autosomal-dominant cornification disorder
Authors: Gong Zhuoqing , Dai Shangzhi , Jiang Xingyuan , Lee Mingyang , Zhu Xuejun , Wang Huijun , Lin Zhimiao 
Published: January 2023

Abstract

Background
Mendelian disorders of cornification (MeDOC) are a group of heterogeneous genodermatoses with different genetic bases. The pathogenesis of a substantial group of MeDOC remains to be elucidated.

Objectives
To identify a new causative gene and the pathogenesis of a previously undescribed autosomal-dominant cornification disorder.

Methods
Whole-exome sequencing was performed in three families with the novel cornification disorder to identify the disease-causing variants. As the variants were located around the signal peptide (SP) cleavage site of a kallikrein-related peptidase, SP cleavage, subcellular localization and extracellular secretion of the variants were evaluated in eukaryotic overexpression systems by Western blotting or immunocytochemistry. Then the trypsin-like and chymotrypsin-like proteolytic activity of the peptidase and degradation of its catalytic substrate were assayed using the patients’ stratum corneum (SC) samples. The morphology of the lamellar bodies and corneodesmosomes (CDs) in the patients’ SC was ultrastructurally examined. A mouse model harbouring the equivalent variant was constructed and evaluated histologically.

Results
We identified two heterozygous variants affecting Gly50 in kallikrein-related peptidase (KLK)11 in a familial case and two sporadic cases with the new disorder, which is characterized by early-onset ichthyosiform erythroderma or erythrokeratoderma. KLK11 belongs to the family of kallikrein-related peptidases participating in skin desquamation by decomposing CDs, a process essential for shedding of the SC. In vitro experiments demonstrated that the variants perturbed the SP cleavage of KLK11, leading to subcellular mislocalization and impaired extracellular secretion of the KLK11 Gly50Glu variant. Both trypsin-like and chymotrypsin-like proteolytic activities were significantly decreased in the patients’ SC samples. Reduced proteolysis of desmoglein 1 and delayed degeneration of CDs were detected in patients’ SC, indicating delayed skin desquamation. Consistently, the patients showed a thickened, dense SC, indicating abnormal skin desquamation. Mice harbouring the homozygous c.131G&gt;A (p.Gly44Glu) Klk11 variant, which is equivalent to KLK11 c.149G&gt;A (p.Gly50Glu) in humans, exhibited hyperkeratosis and abnormal desquamation, partially recapitulating the phenotype.

Conclusions
We provide evidence that variants at Gly50 affecting the SP cleavage of KLK11 cause a new autosomal-dominant cornification disorder with abnormal desquamation. Our findings highlight the essential role of KLKs in maintaining homeostasis of skin keratinization and desquamation.
Trends in incidence, treatment and survival of Merkel cell carcinoma in England 2004–2018: a cohort study
Authors: Mistry Khaylen , Levell Nick J , Hollestein Loes , Wakkee Marlies , Nijsten Tamar , Knott Craig S , Steven Neil M , Craig Paul J , Venables Zoe C 
Published: January 2023

Abstract

Background
Merkel cell carcinoma (MCC) is a rare tumour with neuroendocrine differentiation and high associated mortality. Studies that describe the epidemiology of MCC are often limited by small sample size, short duration of follow-up, absence of nationwide data and paucity of data on different risk factors.

Objectives
To determine the incidence, demographics and survival for MCC in England between 2004 and 2018.

Methods
This national retrospective cohort study identified all cases of MCC in England from 2004 to 2018 using national population-based data from the National Disease Registration Service. Crude counts, European age-standardized incidence rates (EASRs) and joinpoint analysis were conducted. Patient demographics and treatments received were described. Multivariable Cox regression analysis was used to study risk factors for MCC-specific mortality, by including a priori defined demographic factors, tumour characteristics and immunosuppression. Treatment data were not included in the Cox regression analysis.

Results
A total of 3775 MCC tumours were registered. The median age at diagnosis was 81 years (interquartile range 74–87). Overall, 96·6% of patients identified as White ethnicity, and 8·3% of patients were immunosuppressed. The most common site was the face (27·4%). Patients most often presented with stage one disease (22·8%); however, stage was unknown in 31·0%. In total, 80·7% of patients underwent surgical excision, 43·5% radiotherapy and 9·2% systemic therapy. The EASR increased from 0·43 per 100 000 person-years (PYs) to 0·65 per 100 000 person-years between 2004 and 2018, representing a significant annual percentage change of 3·9%. The EASR was greater in men than in women for all years, with an overall male-to-female ratio of 1·41 : 1. The highest EASR was in South West England. Five-year disease-specific survival was 65·6% [95% confidence interval (CI) 63·8–67·4], with a median follow-up of 767 days. MCC-specific mortality increased with age [hazard ratio (HR) 1·02, 95% CI 1·02–1·03], deprivation (HR 1·43, 95% CI 1·16–1·76), immunosuppression (HR 2·80, 95% CI 2·34–3·34) and stage at diagnosis (HR 8·24, 95% CI 5·84–11·6).

Conclusions
This study presents the largest national MCC dataset in Europe, and the most complete reporting of MCC incidence and survival ever published. With the EASR of MCC increasing and high associated mortality, this study encourages further research into the pathology, diagnosis and therapeutic options for MCC to support management guidelines.
Atopic dermatitis across the life course
Authors: Abuabara Katrina , Langan Sinéad M 
Published: January 2023

Abstract
Atopic dermatitis, the most common chronic inflammatory skin disease, can occur at any age, and patterns of disease activity vary over time. Both prevalence and incidence are highest in infancy and early childhood, followed by a second peak in older adulthood. Birth cohort studies from European countries following children through adolescence have identified subgroups of patients with early-onset persistent disease, early-onset resolving disease, and later-onset disease. Parental history of atopy and genetic factors are among the most consistent predictors of more persistent disease. Studies have begun to examine whether molecular markers differ by age group, although longitudinal data are lacking. Breastfeeding, probiotics and skin-directed therapies such as emollients have been investigated as potential preventive measures, but randomized trials have not found consistent long-term benefit. Future research should focus on patterns of disease activity beyond early adulthood and the role of treatments on long-term disease activity.
Bimekizumab efficacy and safety in patients with moderate-to-severe plaque psoriasis who switched from adalimumab, ustekinumab or secukinumab: results from phase III/IIIb trials
Authors: Kokolakis Georgios , Warren Richard B , Strober Bruce , Blauvelt Andrew , Puig Luis , Morita Akimichi , Gooderham Melinda , Körber Andreas , Vanvoorden Veerle , Wang Maggie , de Cuyper Dirk , Madden Cynthia , Nunez Gomez Natalie , Lebwohl Mark 
Published: January 2023

Abstract

Background
Discontinuation of biologics is common among patients with psoriasis due to treatment failure or adverse events. To achieve improvements in disease management, patients and clinicians may choose to switch biologics.

Objectives
To evaluate the efficacy and safety of switching to bimekizumab from adalimumab, ustekinumab and secukinumab.

Methods
Data are reported for up to 80 weeks after patients switched to bimekizumab from adalimumab at week 24 in BE SURE, ustekinumab at week 52 in BE VIVID [upon entry into the BE BRIGHT open-label extension (OLE)] and secukinumab at week 48 in BE RADIANT (upon entry into the BE RADIANT OLE). Efficacy outcomes are reported by number of weeks after switching to bimekizumab and were split based on whether patients had achieved a ≥ 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at the time of switch. Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years. Trial registration: BE SURE (NCT03412747), BE VIVID (NCT03370133), BE BRIGHT (NCT03598790), BE RADIANT (NCT03536884).

Results
Rapid and durable improvements in clinical responses and benefits in health-related quality of life were observed among PASI 90 nonresponders who switched to bimekizumab. Most PASI 90 nonresponders achieved PASI 90 4 weeks after switching to bimekizumab from adalimumab (67%), ustekinumab (79%) and secukinumab (53%). After 48 weeks of bimekizumab, 91%, 90% and 79% of PASI 90 nonresponders had achieved PASI 90 after switching from adalimumab, ustekinumab or secukinumab, respectively. Durable improvements were also observed for PASI 100, Investigator’s Global Assessment score 0/1, body surface area affected by psoriasis ≤ 1%, absolute PASI ≤ 2, and Dermatology Life Quality Index 0/1. Among PASI 90 responders, existing treatment responses were maintained or improved after switching to bimekizumab. The majority of TEAEs were mild or moderate. EAIRs were generally similar between active-comparator treatment periods and after switching to bimekizumab. EAIRs typically decreased with a longer duration of bimekizumab exposure.

Conclusions
High proportions of patients who did not adequately respond to adalimumab, ustekinumab or secukinumab achieved high levels of skin clearance after switching to bimekizumab. Bimekizumab was well tolerated and there were no new safety findings.
Bridging knowledge gaps in paediatric chronic urticaria through a video-based educational tool
Authors: Karim Jumanah , Gabrielli Sofianne , Mule Pasquale , Torabi Bahar , Byrne Adam , De Schryver Sarah , Gadoury-Lévesque Vanessa , Alizadehfar Reza , McCusker Christine , Zhang Xun , Ben-Shoshan Moshe 
Published: January 2023

AbstractBackgroundThere is a lack of patient educational resources about chronic urticaria (CU).AimsTo develop and test the effectiveness of an education tool to help paediatric patients and their families better understand CU and its management.MethodsFrom July 2020 to May 2022, paediatric patients with a history of CU who presented to the allergy outpatient clinics at our institution were recruited. Consenting families and patients were asked to complete five questions related to the definition, causes and management of CU at the time of presentation to the clinic. Participants were shown a 5-min animated video addressing the main knowledge gaps about CU. At the end of the video, participants were redirected to the same five questions to respond again. The scores were recorded as a proportion of correct answers (range 0·0–1·0).ResultsIn total, 53 patients [30 girls (56·6%), 23 boys (43·4%); mean age 9·7 ± 5·1 years, range 1·4–18·5 years] were recruited. The mean baseline pre-video education questionnaire score was 0·67 ± 0·2 (range 0·2–1·0), while the mean post-video score was 0·94 ± 0·1 (range 0·4–1·0), a mean score difference of 0·27, which was statistically significant (P &lt; 0·001). At the 1-year follow-up, 14 (26·4%) patients answered the questionnaire again to assess retention of knowledge; the mean score was 0·83 ± 0·2 (range 0·2–1·0).ConclusionsOur educational video was successful in educating patients and their families to better understand urticaria. Future studies should aim to optimize patient education through nontraditional tools such as videos, and compare knowledge gain using different methods of education.
Mental health burden of patients with activity-limiting skin conditions: a national analysis
Authors: Yang Kevin , Kaundinya Trisha , Kassamali Bina , Pan Catherina X , Zhou Guohai , Nambudiri Vinod E 
Published: January 2023

Abstract
Cutaneous diseases are the fourth leading cause of nonfatal disease burden globally. In this study, we aimed to investigate the psychological symptom burden in patients with chronic activity-limiting cutaneous diseases. Our findings suggest that this patient population experience a wide range of interference with their daily lives and exhibit higher psychological burdens and lower quality of life. This study also identified that patients with activity-limiting skin conditions do not seem to seek more professional help or take more medications, which may suggest a potential gap in adequate mental health support and resources.