Short version of the Quality of Life Relevance-Acne questionnaire.

INTRODUCTION: The goal of the present study was to develop a Short Version (SV) of the Quality of Life Relevance-Acne (QOLRELEVANCE-ACNE) based on the identified most relevant items for acne patients. METHODS: Members of the international internet group for acne patients were asked to fill in the short prototype version of the QOLRELEVANCE-ACNE. Internal consistency was measured using Cronbach's alpha. RESULTS: The answers of 684 acne patients were collected. The analysis revealed that the internal consistency of the instrument could be improved by removing a single item. That item was removed and the final four-item short version of the QOLRELEVANCE-ACNE-SV was formed. There is minimal or no overlapping of the QOLRELEVANCE-ACNE-SV with other brief forms of acne-specific HRQoL instruments. CONCLUSION: The four-item QOLRELEVANCE-ACNE-SV questionnaire was developed and showed good internal consistency. An international validation study of the QOLRELEVANCE-ACNE-SV will be performed.

BAUSSS biomarker improves melanoma survival risk assessment.

BACKGROUND: The American Joint Committee on Cancer (AJCC) method of staging melanoma is dated and inaccurate. It ignores important prognostic melanoma features, especially the patient's age. BAUSSS is more accurate in determining survival risk for primary cutaneous melanoma patients who have no clinical or imaging evidence of nodal or distant metastases. BAUSSS is an algorithm incorporating analysis of Breslow thickness, Age, Ulceration, Subtype of melanoma, Sex and Site. These are the six features from the patient history along with the details from the melanoma pathology report that are most predictive of mortality outcome. OBJECTIVE: To develop a single-page document that allows the clinician to determine BAUSSS biomarker-predicted prognosis in consultation with the patient. METHOD: From various data sources, we developed an algorithm to predict melanoma mortality using the BAUSSS biomarker system. The single-page algorithm was made available to download at https://globalmelanoma.net/bausss-survival-chart, thus being readily available without charge to all clinicians and their patients. RESULTS: BAUSSS method of determining melanoma prognosis is more accurate and less costly than the AJCC staging system. The only surgery the patient requires is wide local excision of the primary tumour. This method of ascertaining melanoma risk does not require added surgery, costs, hospitalization, tests and anaesthesia, such as would be required if sentinel lymph node biopsy was undertaken. BAUSSS can be a useful tool in determining which primary melanoma patients are at sufficiently high risk to be considered for adjuvant drug therapy. CONCLUSION: We encourage clinicians to download and print in colour this single-page BAUSSS mortality prediction tool, laminate it, and use it face to face with the patient in consultations. Not only will the patient be able to recognize his/her long-term prognosis but will also be able to see how their tumour severity compares with others.

Comorbidities, Clinical Presentation, Subtypes, and Treatment of HS Patients in Lithuania.

Background: Hidradenitis suppurativa (HS) is a persistent, recurring skin inflammatory condition linked to various comorbidities. Management involves antibiotics, hormone therapy, immune-modulating drugs, surgery, and treatment of comorbidities. The objectives of the study were to assess the comorbidities, clinical presentation subtypes, and applied treatment of patients with HS. Methods: Patients with HS who visited the Centre of Dermatovenereology at Vilnius University Hospital Santaros Klinikos in Lithuania underwent evaluation based on the guidelines of the European Hidradenitis Suppurativa Foundation Registry questionnaire. Results: The study included 49 patients, and 61.22% (n = 30) had comorbidities. A strong positive correlation was found between a family history of inflammatory diseases (69.38% (n = 34)) and the severity of HS according to Hurley stage (r = 0.71 p < 0.05). A statistically significant correlation (r = 0.944, p = 0.02) was found between metabolic comorbidities and Hurley stage. Patients on biologic treatment had a mean IHS4 of 7.38 at the beginning of treatment and 3.22 at follow-up (p < 0.05). For patients not on biologics, the initial IHS4 score was 6.21 and 5.42 at follow-up (p > 0.05). Conclusions: A family history of inflammatory diseases and metabolic comorbidities showed a strong correlation with HS severity. Treatment with biologics showed significant improvement in HS scores compared to systemic antibiotics.

Unveiling the mechanism of photothermal therapy in acne man-agement: targeting sebaceous gland ferroptosis via umbilical cord mesenchymal stem cell membrane-encapsulated Au-Ag-PDA.

Background: Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal stem cell membranes (MSCM) as an effective drug delivery system, our preliminary studies investigated the suppression of sebum secretion in sebaceous glands using MSCM-coated Au-Ag-PDA nano-particles (Au-Ag-PDA@MSCM) combined with 808 nm laser irradiation, showing potential for dermatological applications in acne treatment. Methods: This study employs proteomic analysis, complemented by subsequent techniques such as Western blotting (WB), small interfering RNA (siRNA), and transmission electron microscopy, to further investigate the differential mechanisms by which Au-Ag-PDA and Au-Ag-PDA@MSCM-mediated photothermal therapy (PTT) suppress sebum secretion. Results: Our proteomic analysis indicated mitochondrial respiratory chain damage in sebaceous gland tissues post-PTT, with further validation revealing ferroptosis in sebaceous cells and tissues. Acyl-CoA Synthetase Long-Chain Family Member 4 (Acsl4) has been identified as a critical target, with Au-Ag-PDA@MSCM demonstrating enhanced ferroptotic effects. Conclusion: These findings significantly advance our understanding of how PTT mediated by Au-Ag-PDA@MSCM nanoparticles reduces sebum secretion and underscore the pivotal role of MSCM in inducing ferroptosis in sebaceous glands, thus providing a robust theoretical foundation for employing PTT via specific molecular pathways in acne treatment.

Standardized Protocols for Clinical and Histopathological Characterization of Hidradenitis Suppurativa Tissue Specimens.

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects.

A spatial portrait of the human sebaceous gland transcriptional program.

Sebaceous glands (SG) and their oily secretion (sebum) are indispensable for maintaining skin structure and function, and their deregulation causes skin disorders including but not limited to acne. Recent studies also indicate that sebum may have important immunomodulatory activities and may influence whole-body energy metabolism. However, the progressive transcriptional changes of sebocytes that lead to sebum production have never been characterized in detail. Here, we exploited the high cellular resolution provided by sebaceous hyperplasia and integrated spatial transcriptomics, pseudo time analysis, RNA velocity, and functional enrichment to map the landscape of sebaceous differentiation. Our results were validated by comparison with published SG transcriptome data and further corroborated by assessing the protein expression pattern of a subset of the transcripts in the public repository Human Protein Atlas. Departing from four sebocyte differentiation stages generated by unsupervised clustering, we demonstrate consecutive modulation of cellular functions associable with specific gene sets, from cell proliferation and oxidative phosphorylation via lipid synthesis to cell death. Both validation methods confirmed the biological significance of our results. Our report is complemented by a freely available and browsable online tool. Our data provide the first high-resolution spatial portrait of the SG transcriptional landscape and deliver starting points for experimentally assessing novel candidate molecules for regulating SG homeostasis in health and disease.

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.

S2k guideline for the treatment of hidradenitis suppurativa / acne inversa - Short version.

The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ± 9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method.

Development of the acne-specific quality of life questionnaire Quality of Life Relevance-Acne.

Background: Participating members of the European Academy of Dermatology and Venereology Task Forces on quality of life (QoL) and Patient Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa initiated data collection in 9 European countries and formed the list of the most relevant topics for acne patients. Objective: The aim of this study was to develop a new acne-specific health-related QoL instrument based on the list of the most relevant topics for acne patients. Methods: After assessment by acne patients (n = 715) on how clear and relevant the items in the prototype questionnaire were, a group of experts on acne and QoL performed discussions on items inclusion, which resulted in a series of 21 items. Then another group of acne patients (n = 1502) filled in the new version of the instrument. A factor analysis was conducted on the 21-item version. Results: Three-factor model with 19 items indicated a satisfactory fit. The three dimensions were called: Socioemotional; Symptoms; Stigma and Suicidal thoughts. Limitations: Included patients and experts may not fully represent acne patients and health care professionals worldwide. Conclusion: A final 19-item version of the Quality of Life Relevance-Acne was developed.

TRPV3 promotes sebocyte inflammation via transcriptional modulating TLR2 in acne.

Acne is a common chronic inflammatory disease of the pilosebaceous unit. Transient receptor potential vanilloid 3 (TRPV3) is an ion channel that is involved in inflammatory dermatosis development. However, the involvement of TRPV3 in acne-related inflammation remains unclear. Here, we used acne-like mice and human sebocytes to examine the role of TRPV3 in the development of acne. We found that TRPV3 expression increased in the skin lesions of Propionibacterium acnes (P. acnes)-injected acne-like mice and the facial sebaceous glands (SGs) of acne patients. TRPV3 promoted inflammatory cytokines and chemokines secretion in human sebocytes and led to neutrophil infiltration surrounding the SGs in acne lesions, further exacerbating sebaceous inflammation and participating in acne development. Mechanistically, TRPV3 enhanced TLR2 level by promoting transcriptional factor phosphorylated-FOS-like antigen-1 (p-FOSL1) expression and its binding to the TLR2 promoter, leading to TLR2 upregulation and downstream NF-κB signaling activation. Genetic or pharmacological inhibition of TRPV3 both alleviated acne-like skin inflammation in mice via the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebaceous inflammation and indicated its potential as an acne therapeutic target.

Discrepancies in hidradenitis suppurativa lesion characterization by providers and patients.

BACKGROUND: The hidradenitis suppurativa (HS) clinical response (HiSCR) has come under scrutiny as several HS clinical trials failed to meet primary endpoints with high placebo responses. This may be due to limitations of the tool and raters' ability to accurately characterize and count lesions, rather than lack of efficacy of the studied drug. Due to HS lesion complexity and potential differences in rater training, it was hypothesized that there would be discrepancies in how providers characterize and count lesions for HS clinical trials. OBJECTIVE: To evaluate how HS providers and patients name and count HS lesions and to identify discrepancies among providers to initiate the development of consensus-driven guidance for HS rater training. METHODS: An online survey was distributed to the members of HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Respondents were asked to classify lesion images composed of multiple and different morphology types and answer questions regarding inclusion of associated dermatological conditions. RESULTS: Forty-seven HISTORIC members responded (29 providers; 18 patients). There was variability in how respondents classified HS lesions. Of 12 questions containing images, four had ≥50% of respondents choosing the same answer. With an image of a lesion composed of different morphologies, 45% of providers counted it as a single lesion and 45% counted it as multiple distinct lesions. With an image of multiple interconnected draining tunnels, 7% of providers classified it as a single draining tunnel while 79% categorized it as multiple draining tunnels with the number estimated by visual inspection. There was also variability in deciding whether lesions occurring in associated conditions should be considered separately or included in HS lesion counts. Patient responses were also variable. CONCLUSIONS: The result of the current study reaffirms the gap in how providers characterize and count HS lesions for clinical trials and the need to develop consensus-driven rater training related to HS outcome measures.

Proof-of-concept study exploring the effect of spesolimab in patients with moderate-to-severe hidradenitis suppurativa: a randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies. OBJECTIVES: To explore the effects of spesolimab treatment in patients with HS. METHODS: This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS for ≥ 1 year before enrolment. Patients were randomized (2 : 1) to receive a loading dose of 3600-mg intravenous spesolimab (1200 mg at weeks 0, 1 and 2) or matching placebo, followed by maintenance with either 1200-mg subcutaneous spesolimab every 2 weeks from weeks 4 to 10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at week 12. Secondary endpoints were the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of 0, absolute change from baseline in the revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥ 1 flare (all at week 12) and patient-reported outcomes. RESULTS: In this completed trial, randomized patients (n = 52) received spesolimab (n = 35) or placebo (n = 17). The difference vs. placebo in least squares mean is reported. At week 12, the percentage change in total AN count was similar between treatment arms: -4.1% [95% confidence interval (CI) -31.7 to 23.4]. There was greater numerical improvement in the spesolimab arm, as measured by IHS4 (13.9, 95% CI -25.6 to -2.3); percentage change from baseline in dT count (-96.6%, 95% CI -154.5 to -38.8); and the proportion of patients achieving a dT count of 0 (18.3%, 95% CI -7.9 to 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 vs. placebo. Spesolimab demonstrated a favourable safety profile, similar to that observed in trials in other diseases. CONCLUSIONS: This exploratory PoCC study supports the development of spesolimab as a new therapeutic option in HS.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects approximately 0.4% to 1% of people worldwide. HS mainly affects areas where skin touches skin and can result in painful lumps and abscesses. Tunnel-shaped structures often form below the skin and discharge pus and can greatly affect a person's quality of life. In this study, we tested a drug called 'spesolimab' as a treatment for people with moderate-to-severe HS. Spesolimab is a medicine in development that affects the immune system. This 12-week study included 52 adults who had moderate-to-severe HS for at least 1 year, from North America, Europe and Australia. People who took part were selected at random to receive either spesolimab or placebo. Thirty-five people received spesolimab and 17 received placebo into a vein once a week for 3 weeks, starting at week 0. They then received four injections of spesolimab or placebo under the skin once every 2 weeks until week 10. The number of lumps and abscesses, tunnels and a score based on their combination, called the International Hidradenitis Suppurativa Severity Score System (IHS4), were evaluated before spesolimab or placebo were given, and at week 12. We found that spesolimab and the placebo had a similar effect on the number of lumps and abscesses. However, more people treated with spesolimab showed improvements in tunnels and IHS4 score than those who received the placebo. The safety of spesolimab was favourable, similar to when spesolimab has been used in studies of other diseases. Our findings support further research into the use of spesolimab as a medicine for HS.

Secukinumab in patients with moderate-to-severe hidradenitis suppurativa based on prior biologic exposure: an efficacy and safety analysis from the SUNSHINE and SUNRISE phase III trials.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate-to-severe HS. It is unknown whether prior biologic exposure affects the efficacy and safety of secukinumab. OBJECTIVES: To investigate the efficacy and safety of secukinumab in patients with moderate-to-severe HS based on prior exposure to -biologics. METHODS: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate-to-severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients on the SECQ2W and SECQ4W schedules remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included Hidradenitis Suppurativa Clinical Response (HiSCR), abscess and inflammatory nodule (AN) count, flare rates, HS-related pain [numerical rating scale 30 (NRS30)], 55% reduction in the International Hidradenitis Suppurativa Severity Score System (IHS4-55), Dermatology Life Quality Index, EuroQol-5D and safety. RESULTS: Overall, 1084 patients were randomized in the SUNSHINE and SUNRISE trials and included in this analysis; 255 (23.5%) were biologic-experienced [SECQ2W (n = 80); SECQ4W (n = 81); placebo (n = 94)] and 829 (76.5%) were biologic-naïve [SECQ2W (n = 281); SECQ4W (n = 279); placebo (n = 269)]. At week 16, responses were more efficacious for secukinumab than for placebo with regard to HiSCR in patients who were biologic-experienced {SECQ2W 37.0% [odds ratio (OR) 1.60, 95% confidence interval (CI) 0.83-3.08]; SECQ4W 38.8% [OR 1.67, 95% CI 0.86-3.22]; placebo 27.3%} and biologic-naïve [SECQ2W 45.6% (OR 1.64, 95% CI 1.15-2.33); SECQ4W 45.4% (OR 1.61, 95% CI 1.13-2.29); placebo 34.2%]. Similar results were observed for AN count, NRS30 and IHS4-55. The higher response seen at week 16 with secukinumab was sustained, with a trend toward improvement over time, through to week 52 in both subgroups. Additional efficacy was observed for quality-of-life assessments, and no differences in safety between subgroups were observed. CONCLUSIONS: Regardless of prior biologic exposure, secukinumab was efficacious in improving the signs and symptoms of HS. This finding positions secukinumab as the first option in patients who are biologic-naïve, as well as in patients who have previously been treated with other biologic therapy, based on individual patient needs.

Hidradenitis suppurativa (HS) is a chronic skin disease that causes painful boils. HS is common and affects about 0.4% of the world's population. Treating the condition is difficult, but drugs called 'biologics' can help to improve the symptoms. For example, secukinumab is a biologic drug that has been shown to be effective and well-tolerated for the treatment of HS. In this analysis, we investigated whether previous treatment with biologics could affect the effectiveness and tolerability of secukinumab. This analysis included data from two identical clinical trials (called SUNSHINE and SUNRISE) that recruited adult patients with HS who had moderate-to-severe disease. In these trials, patients took secukinumab 300 mg every 2 weeks or every 4 weeks for 1 year, or a placebo for 4 months and then switched to secukinumab until 1 year. At regular intervals, the effectiveness and tolerability of secukinumab were examined and the results were compared between patients who had previously used another biologic and patients who had never used a biologic before. After 16 weeks, patients who took secukinumab had better results than the patients who took a placebo, independent of previous biologic use. Secukinumab was still effective and had improved results over 1 year of treatment in both subgroups. Regardless of whether patients had previously been taking another biologic, secukinumab was just as tolerable as placebo and there were no new safety risks. Our analysis shows that secukinumab is effective and tolerable, regardless of whether patients have previously used another biologic drug.

Spatial transcriptomics reveals altered lipid metabolism and inflammation-related gene expression of sebaceous glands in psoriasis and atopic dermatitis.

Sebaceous glands drive acne, however, their role in other inflammatory skin diseases remains unclear. To shed light on their potential contribution to disease development, we investigated the spatial transcriptome of sebaceous glands in psoriasis and atopic dermatitis patients across lesional and non-lesional human skin samples. Both atopic dermatitis and psoriasis sebaceous glands expressed genes encoding key proteins for lipid metabolism and transport such as ALOX15B, APOC1, FABP7, FADS1/2, FASN, PPARG, and RARRES1. Also, inflammation-related SAA1 was identified as a common spatially variable gene. In atopic dermatitis, genes mainly related to lipid metabolism (e.g. ACAD8, FADS6, or EBP) as well as disease-specific genes, i.e., Th2 inflammation-related lipid-regulating HSD3B1 were differentially expressed. On the contrary, in psoriasis, more inflammation-related spatially variable genes (e.g. SERPINF1, FKBP5, IFIT1/3, DDX58) were identified. Other psoriasis-specific enriched pathways included lipid metabolism (e.g. ACOT4, S1PR3), keratinization (e.g. LCE5A, KRT5/7/16), neutrophil degranulation, and antimicrobial peptides (e.g. LTF, DEFB4A, S100A7-9). In conclusion, our results show that sebaceous glands contribute to skin homeostasis with a cell type-specific lipid metabolism, which is influenced by the inflammatory microenvironment. These findings further support that sebaceous glands are not bystanders in inflammatory skin diseases, but can actively and differentially modulate inflammation in a disease-specific manner.

Primary Cutaneous Melanoma-Management in 2024.

Background: Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age. Objective: to provide an update on melanoma management from the time of the decision to biopsy a suspicious skin lesion. Methods: We reviewed melanoma-management research published between 2018 and 2023 and identified where such findings impact and update the management of confirmed melanomas. Pubmed, Google Scholar, Ovid and Cochrane Library were used as search tools. Results: We identified 81 publications since 2017 that have changed melanoma management; 11 in 2018, 12 in 2019, 10 in 2020, 12 in 2021, 17 in 2022 and 18 in 2023. Discussion: Delayed or inaccurate diagnosis is more likely to occur when a partial shave or punch biopsy is used to obtain the histopathology. Wherever feasible, a local excision with a narrow margin should be the biopsy method of choice for a suspected melanoma. The Breslow thickness of the melanoma remains the single most important predictor of outcome, followed by patient age and then ulceration. The BAUSSS biomarker, (Breslow thickness, Age, Ulceration, Subtype, Sex and Site) provides a more accurate method of determining mortality risk than older currently employed approaches, including sentinel lymph node biopsy. Patients with metastatic melanomas and/or nodal disease should be considered for adjuvant drug therapy (ADT). Further, high-risk melanoma patients are increasingly considered for ADT, even without disease spread. Invasive melanomas less than 1 mm thick are usually managed with a radial excision margin of 10 mms of normal skin. If the thickness is 1 to 2 mm, select a radial margin of 10 to 20 mm. When the Breslow thickness is over 2 mm, a 20 mm clinical margin is usually undertaken. In situ melanomas are usually managed with a 5 to 10 mm margin or Mohs margin control surgery. Such wide excisions around a given melanoma is the only surgery that can be regarded as therapeutic and required. Patients who have had one melanoma are at increased risk of another melanoma. Ideal ongoing management includes regular lifelong skin checks. Total body photography should be considered if the patient has many naevi, especially when atypical/dysplastic naevi are identified. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet light are important. Management also needs to include the consideration of vitamin D supplementary therapy.

ALA-PDT promotes IL-1ß secretion from human SZ95 sebocytes via activation of the NLRP3 inflammasome.

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for pilosebaceous inflammatory diseases, such as acne vulgaris. In this study, we explored ALA-PDT's mechanisms against acne in vitro. METHODS: We treated human SZ95 sebocytes with ALA (0.2 mM) and subjected them to varied PDT doses (0, 5, 10, 20 J/cm²) over 12 h. We assessed cell viability post-treatment using the Annexin V FITC/PI apoptosis kit. ROS accumulation in the sebocytes was detected with a DCFDA probe. We quantified NLRP3 and caspase-1 mRNA via quantitative PCR and determined IL-1ß release following ALA-PDT by ELISA. Western blotting helped identify the levels of proteins associated with pyroptosis (NLRP3, caspase-1, and IL-1ß). To elucidate the mechanisms, we re-evaluated these parameters after administering various concentrations of NAC antioxidants (0, 0.4, 2, 10 mM) and the caspase inhibitor Z-VAD-FMK (0, 5, 10, 20 µM). RESULTS: Increasing PDT dose inversely affected SZ95 sebocyte survival, with a corresponding rise in ROS and pyroptosis-related proteins (NLRP3, caspase-1, and IL-1ß). Furthermore, NAC and Z-VAD-FMK modulated the expression and secretion of these molecules in a dose-responsive manner. CONCLUSION: Our findings suggest ALA-PDT's potential mechanism of action on sebaceous glands could involve ROS induction, leading to NLRP3 inflammasome assembly, thereby heightening caspase-1 activation and IL-1ß secretion. This cascade may amplify the local inflammatory response to break chronic inflammation in acne vulgaris treatment.

Exosomes from adipose-derived stem cells activate sebocytes through the PI3K/AKT/SREBP-1 pathway to accelerate wound healing.

Sebocyte regeneration after injury is considered a key element of functional skin repair. Exosomes from adipose-derived stem cells (ADSCs-EXO) accelerate wound healing by promoting the proliferation of fibroblasts. However, the effects of ADSCs-EXO on sebocytes are largely unknown. In this study, the effects of ADSCs-EXO on sebocyte proliferation and migration were evaluated. The levels of phosphorylated AKT (p-AKT), AKT, sterol regulatory-element binding protein (SREBP), and perilipin-1 (PLIN-1) were detected with immunofluorescence, quantitative PCR, and western blot analysis. RNA-Seq was used to analyze the differential gene expression between the ADSCs-EXO group and the control group under anaerobic conditions. Lipogenesis was assessed with Nile red staining. In animal studies, full-thickness skin wounds in BALB/c mice were treated with gelatin methacrylate (GelMA) hydrogel-loaded sebocytes alone or in combination with ADSCs-EXO. Histopathological assessments of the wound tissues were performed Masson Trichrome staining, Immunohistochemical staining and so on. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway blocker LY294002 inhibited the effects of ADSCs-EXO on p-AKT and sebocytes proliferation. ADSCs-EXO also regulated the expression of SREBP-1 and PLIN-1 through the PI3K/AKT pathway in an oxygen level-dependent manner. In BALB/c mice, ADSCs-EXO accelerated sebocyte-assisted wound healing and regeneration. These in vitro and in vivo results supported that ADSCs-EXO can promote the regeneration of fully functional skin after injury through the PI3K/AKT-dependent activation of sebocytes.