Fazleenah A Hussain, Arti Bakshi, Paul D Yesudian, Stuart N Cohen
{"title":"Overtreatment of dysplastic naevi: results of a multiregional UK questionnaire study.","authors":"Fazleenah A Hussain, Arti Bakshi, Paul D Yesudian, Stuart N Cohen","doi":"10.1093/bjd/ljae382","DOIUrl":"https://doi.org/10.1093/bjd/ljae382","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thierry Passeron, Maximilian Reinhardt, Benjamin Ehst, Jonathan Weiss, Jason Sluzevich, Michael Sticherling, Pascal Reygagne, Johannes Wohlrab, Michael Hertl, Nasim Fazel, Elisa Muscianisi, Heng Fan, Isabelle Hampele, Nicolò Compagno
{"title":"Secukinumab in adult patients with lichen planus: efficacy and safety results from the randomized placebo-controlled proof-of-concept PRELUDE study.","authors":"Thierry Passeron, Maximilian Reinhardt, Benjamin Ehst, Jonathan Weiss, Jason Sluzevich, Michael Sticherling, Pascal Reygagne, Johannes Wohlrab, Michael Hertl, Nasim Fazel, Elisa Muscianisi, Heng Fan, Isabelle Hampele, Nicolò Compagno","doi":"10.1093/bjd/ljae181","DOIUrl":"10.1093/bjd/ljae181","url":null,"abstract":"<p><strong>Background: </strong>Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments.</p><p><strong>Objectives: </strong>To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids.</p><p><strong>Methods: </strong>PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16.</p><p><strong>Results: </strong>Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3-57.2] vs. 23.1% (95% Crl 6.5-49.2)} and LPP cohorts [37.5% (95% Crl 20.2-57.3) vs. 30.8% (95% Crl 10.8-57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals.</p><p><strong>Conclusions: </strong>PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"680-690"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristina Hagenström, Theresa Klinger, Katharina Müller, Charlotte Willers, Matthias Augustin
{"title":"Utilization and related harms of systemic glucocorticosteroids for atopic dermatitis: claims data analysis.","authors":"Kristina Hagenström, Theresa Klinger, Katharina Müller, Charlotte Willers, Matthias Augustin","doi":"10.1093/bjd/ljae250","DOIUrl":"10.1093/bjd/ljae250","url":null,"abstract":"<p><strong>Background: </strong>Systemic glucocorticosteroids (SGCs) are used in the short-term treatment of atopic dermatitis (AD), but are not recommended for long-term use because they are associated with severe side-effects.</p><p><strong>Objectives: </strong>This study aimed to characterize the utilization and potentially negative effects of SGC use for AD in German statutory health insurance (SHI) claims data.</p><p><strong>Methods: </strong>Cross-sectional and longitudinal analysis of a large nationwide SHI dataset. SGC drug prescriptions and incidences of predefined comorbidities after drug initiation that were known to be potentially harmful side-effects were analysed. SGC use was quantified by (-definition 1) the number of quarters with at least one SGC prescription and (definition 2) the defined daily doses (DDD). Comparisons were adjusted for age, sex and morbidity.</p><p><strong>Results: </strong>The AD prevalence was 4.07% in 2020 (4.12% women, 3.42% men). During this period 9.91% of people with AD were prescribed SGCs compared with 5.54% in people without AD (P < 0.01). Prescribing of SGCs was significantly higher in women (10.20% vs. 9.42% in men, P < 0.01) and in the elderly. AD and SGC prevalence varied regionally. In a 3-year follow-up period, 58% of people with AD receiving a SGC were prescribed SGCs in > one quarter and 15% in > six quarters. The odds of developing osteoporosis [odds ratio (OR) 3.90 -(definition 1) and 1.80 (definition 2)] and diabetes [OR 1.90 (definition 1) and 1.38 (definition 2)] were significantly higher in people with AD on SGCs, especially in the frequently prescribed group compared with the rarely prescribed group, regardless of quantified use.</p><p><strong>Conclusions: </strong>A considerable number of people with AD in Germany are prescribed long-term SGCs. The onset of medical conditions known to be harmful effects of steroids was significantly more frequent in those who were frequently prescribed SGCs, indicating the need for optimized healthcare.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"719-727"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing care in epidermolysis bullosa: insights from qualitative research.","authors":"Marjolein Lugtenberg, Marlies Wakkee","doi":"10.1093/bjd/ljae280","DOIUrl":"10.1093/bjd/ljae280","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"655-656"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"'Live long and prosper': living guidelines for immune-mediated inflammatory diseases.","authors":"Zenas Z N Yiu, Emma McFarlane, Samuel L Whittle","doi":"10.1093/bjd/ljae324","DOIUrl":"10.1093/bjd/ljae324","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"647-649"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Orsolya Kiss, Rajia Bahri, Rachel E B Watson, Chidera Chike, Abigail K Langton, Victoria L Newton, Mike Bell, Christopher E M Griffiths, Silvia Bulfone-Paus, Suzanne M Pilkington
{"title":"The impact of irritant challenge on the skin barrier and myeloid-resident immune cells in women who are postmenopausal is modulated by hormone replacement therapy.","authors":"Orsolya Kiss, Rajia Bahri, Rachel E B Watson, Chidera Chike, Abigail K Langton, Victoria L Newton, Mike Bell, Christopher E M Griffiths, Silvia Bulfone-Paus, Suzanne M Pilkington","doi":"10.1093/bjd/ljae226","DOIUrl":"10.1093/bjd/ljae226","url":null,"abstract":"<p><strong>Background: </strong>Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear.</p><p><strong>Objectives: </strong>To examine how menopause and HRT affect the skin barrier and immune cell composition in postmenopausal women following irritant challenge.</p><p><strong>Methods: </strong>Two cohorts of postmenopausal women were recruited to the study. The first cohort consisted of 10 untreated women [HRT-; mean (SEM) age 56.5 (1.6) years (range 48-63)] and the second was composed of 8 women receiving HRT [HRT+; mean (SEM) age 54.0 (2.1) years (range 48-63)]. Skin irritation was induced by applying topical sodium lauryl sulfate (SLS) 1.25% to occluded buttock skin for 48 h. Clinical assessment was conducted after 24 h, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence.</p><p><strong>Results: </strong>Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in transepidermal water loss (P < 0.05), filaggrin deposition and cytokeratin 10 (K10)+ cell layers (P < 0.01) was observed in individuals receiving HRT compared with the HRT- group. Following SLS challenge in individuals taking HRT, a significant (P < 0.01) reduction in CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans cells (LCs). Significantly fewer migrating LCs were found in those who were not receiving HRT (P < 0.01). Furthermore, the numbers of dermal dendritic cells (DCs), macrophages, and CD11c+CD206- and CD68+CD206- subsets were found to be significantly (P < 0.05) higher in those taking HRT following SLS challenge.</p><p><strong>Conclusions: </strong>Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased K10+ epidermal cell layers. Following challenge, HRT users exhibited elevated LC, inflammatory DC and macrophage counts in the dermis. These may render skin both more prone to inflammation and more capable of resolving it, while also promoting skin repair.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"746-759"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Rutkowski, Rachel Scholey, John Davies, Derek Pye, Fiona Blackhall, Richard B Warren, Francisco Jimenez, Christopher E M Griffiths, Ralf Paus
{"title":"Epidermal growth factor receptor/mitogen-activated kinase inhibitor treatment induces a distinct inflammatory hair follicle response that includes collapse of immune privilege.","authors":"David Rutkowski, Rachel Scholey, John Davies, Derek Pye, Fiona Blackhall, Richard B Warren, Francisco Jimenez, Christopher E M Griffiths, Ralf Paus","doi":"10.1093/bjd/ljae243","DOIUrl":"10.1093/bjd/ljae243","url":null,"abstract":"<p><strong>Background: </strong>Inhibitors of epidermal growth factor receptor (EGFRi) or mitogen-activated kinase (MEKi) induce a folliculitis in 75-90% of patients, the pathobiology of which remains insufficiently understood.</p><p><strong>Objectives: </strong>To characterize changes in the skin immune status and global transcriptional profile of patients treated with EGFRi; to investigate whether EGFRi affects the hair follicle's (HF) immune privilege (IP); and to identify early proinflammatory signals induced by EGFRi/MEKi in human scalp HFs ex vivo.</p><p><strong>Methods: </strong>Scalp biopsies were taken from patients exhibiting folliculitis treated long term with EGFRi ('chronic EGFRi' group, n = 9) vs. healthy scalp skin (n = 9) and patients prior to commencing EGFRi treatment and after 2 weeks of EGFRi therapy ('acute EGFRi' group, n = 5). Healthy organ-cultured scalp HFs were exposed to an EGFRi (erlotinib, n = 5) or a MEKi (cobimetinib, n = 5). Samples were assessed by quantitative immunohistomorphometry, RNA sequencing (RNAseq) and in situ hybridization.</p><p><strong>Results: </strong>The 'chronic EGFRi' group showed CD8+ T-cell infiltration of the bulge alongside a partial collapse of the HF's IP, evidenced by upregulated major histocompatibility complex (MHC) class I, β2-microglobulin (B2 M) and MHC class II, and decreased transforming growth factor-β1 protein expression. Healthy HFs treated with EGFRi/MEKi ex vivo also showed partial HF IP collapse and increased transcription of human leucocyte antigen (HLA)-A, HLA-DR and B2 M transcripts. RNAseq analysis showed increased transcription of chemokines (CXCL1, CXCL13, CCL18, CCL3, CCL7) and interleukin (IL)-26 in biopsies from the 'chronic EGFRi' cohort, as well as increased IL-33 and decreased IL-37 expression in HF biopsies from the 'acute EGFRi' group and in organ-cultured HFs.</p><p><strong>Conclusions: </strong>The data show that EGFRi/MEKi compromise the physiological IP of human scalp HFs and suggest that future clinical management of EGFRi/MEKi-induced folliculitis requires HF IP protection and inhibition of IL-33.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"791-804"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sissel B T Sørensen, Dóra K Farkas, Christian Vestergaard, Sigrun A J Schmidt, Lise Maria Lindahl, Kathryn E Mansfield, Sinead M Langan, Henrik T Sørensen
{"title":"Urticaria and the risk of cancer: a Danish population-based cohort study.","authors":"Sissel B T Sørensen, Dóra K Farkas, Christian Vestergaard, Sigrun A J Schmidt, Lise Maria Lindahl, Kathryn E Mansfield, Sinead M Langan, Henrik T Sørensen","doi":"10.1093/bjd/ljae264","DOIUrl":"10.1093/bjd/ljae264","url":null,"abstract":"<p><strong>Background: </strong>Urticaria has been tentatively linked to cancer, but epidemiological evidence supporting this link is sparse and conflicting. We conducted a population-based cohort study using healthcare databases covering the Danish population (January 1980-December 2022). We followed 87 507 people for a median of 10.1 years after their first hospital contact for urticaria.</p><p><strong>Objectives: </strong>To examine associations of a hospital diagnosis of urticaria with incident cancer.</p><p><strong>Methods: </strong>We computed the absolute risk of cancer and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) standardized to Danish national cancer rates. In a cross-sectional analysis, we examined whether the extent of cancer spread differed between people with vs. without a previous urticaria diagnosis.</p><p><strong>Results: </strong>The overall SIR for all types of cancer was 1.09 (95% CI 1.06-1.11) based on 7788 observed vs. 7161 expected cases. The risk for any cancer was 0.7% (95% CI 0.6-0.7) for the first year of follow-up. Cancer was diagnosed in 588 people with urticaria during the first year of follow-up (SIR 1.49, 95% CI 1.38-1.62) and in 7200 people thereafter (SIR 1.06, 95% CI 1.04-1.09). During the first year of follow-up, we found strong associations with haematological cancers (e.g. non-Hodgkin lymphoma; SIR 2.91, 95% CI 1.92-4.23). Cancer stage was similar in people with vs. without a previous urticaria diagnosis.</p><p><strong>Conclusions: </strong>At the time of urticaria diagnosis, or in the first year afterward, we found a large increase in the risk of cancer. In subsequent years, a persistent 6% increase in risk remained. Diagnostic efforts may partly explain the elevated short-term risk, but occult cancer may promote urticaria, or cancer and urticaria share common risk factors.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"706-712"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Louisa Schielein, Stefanie Ziehfreund, Tilo Biedermann, Alexander Zink
{"title":"'When you do not feel comfortable in your skin, you cannot get out of it'; a qualitative interview study exploring psychosocial impact and coping strategies among patients with prurigo nodularis.","authors":"Louisa Schielein, Stefanie Ziehfreund, Tilo Biedermann, Alexander Zink","doi":"10.1093/bjd/ljae274","DOIUrl":"10.1093/bjd/ljae274","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"845-846"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cutaneous squamous cell carcinoma progression: what does a meta-analysis of transcriptomic studies tell us?","authors":"Barbara Rentroia-Pacheco, A Hunter Shain","doi":"10.1093/bjd/ljae293","DOIUrl":"10.1093/bjd/ljae293","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"656-657"},"PeriodicalIF":11.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}