Long-term efficacy and safety of stapokibart for moderate-to-severe atopic dermatitis: 52-week results from a phase 3 trial.

BACKGROUND: Management of moderate-to-severe atopic dermatitis (AD) needs long-term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor α subunit (IL-4Rα), a shared receptor for IL-4 and IL-13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2-point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long-term (52 weeks) efficacy and safety of stapokibart from this trial. METHODS: After 16-week double-blind treatment completed, patients in both stapokibart and placebo groups entered a 36-week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period. RESULTS: Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI-75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2-point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP-NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52-week treatment period, 88.1% of patients reported treatment-emergent adverse events, most were mild or moderate. CONCLUSION: Long-term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate-to-severe AD.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

Paeonol and glycyrrhizic acid in combination ameliorate the recurrent nitroglycerin-induced migraine-like phenotype in rats by regulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine. AIM OF THE STUDY: This research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats. MATERIALS AND METHODS: Using a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques. RESULTS: Following treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1ß and TNF-α. CONCLUSIONS: Our findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

Specific Knockdown of the NDUFS4 Gene Reveals Important Roles of Ferroptosis in UVB-induced Photoaging.

Ultraviolet (UV) irradiation significantly contributes to photoaging. Ferroptosis, an iron-dependent cell death mode recently identified, plays a key role in UVB-induced skin photoaging. This study examines the functions and regulatory mechanisms of ferroptosis in this regard. Characterized by increased intracellular iron and reactive oxygen species (ROS), ferroptosis is associated with mitochondrial function and structure. Through RNA sequencing, we identified NADH: ubiquinone oxidoreductase subunit S4 (NDUFS4), a gene implicated in UVB-mediated photoaging, and explored its role in ferroptosis by NDUFS4 knockdown. In vitro, inhibiting NDUFS4 reduced ferroptosis, decreased ROS and matrix metallopeptidase 1 levels, and increased collagen type I alpha 1 chain, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1, and solute carrier family 7 member 11 levels, suggesting a reinforced ferroptosis protective mechanism. Additionally, NDUFS4 regulates ferroptosis via the mitogen-activated protein kinase (MAPK) pathway, with its knockdown reducing p38 and ERK phosphorylation and elevating GPX4 levels, enhancing ferroptosis resistance. Animal experiments supported these findings, demonstrating that Ferrostatin-1, a ferroptosis inhibitor, significantly mitigated UVB-induced skin photoaging and related protein expression. This study uncovers NDUFS4's novel role in regulating ferroptosis and provides new insights into ferroptosis-mediated UVB-induced skin photoaging.

Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2 years with mild to moderate AD. METHODS: We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28 days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. RESULTS: Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. CONCLUSION: Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2 years with mild to moderate AD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04360187.

Clinical Characteristics and Pathogen Spectrum of Male Genital Fungal Infections in Nanchang Area, South China.

The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.

A Case of Verruciform Xanthoma of Labia in a Child.

Purpose: Verruciform xanthoma (VX) is a rare, chronic, and benign lesion affecting the skin and mucous membranes. We reported a case of VX in the vulva of a female child. Patients and Methods: A 12-year-old female had vulvar lesions for over 10 years without any discomfort. Physical examination revealed red lobulated patches on the left labia majora with a few scales attached to the surface. Histopathological examination indicated excessive and incomplete keratinization, hypertrophic spinous layer hyperplasia, neutrophil infiltration in the epidermis, and foam-like tissue could be seen in the dermal papilla. Lymphocyte-dominated inflammatory cell infiltration was scattered around the blood vessels. Immunohistochemical results showed positive CD68. Results: The final diagnosis confirmed the presence of VX. Conclusion: Surgical intervention proved successful in achieving favorable outcomes for the patient.

Verruciform xanthoma (VX) is a rare and non-cancerous skin condition that usually appears in the mouth but can occur on the genitals. In this case, a 12-year-old girl had red, warty lesions on her left labia majora for over 10 years. The cause of VX is not well understood but may be linked to inflammation, trauma, or immune disorders rather than lipid metabolism. The girl's condition was confirmed through a biopsy, and she underwent surgical removal with no recurrence after a year. VX in the genital area is known as Vegas xanthomas. Though VX can look like other skin issues, a detailed examination of tissue samples is crucial for an accurate diagnosis. Treatment options include surgery, laser therapy, or topical creams. While VX is generally benign, seeking medical attention is important to rule out other concerns.

Aseptic Skin Repair Dressing May Be a Vital Clinical Effect in Treatment of Facial Dermatitis.

Objective: This study aimed to explore the clinical application of aseptic skin repair dressing in facial dermatitis. Patients and Methods: A total of 80 patients with facial dermatitis admitted to Zhejiang Provincial People's Hospital from February 2020 to May 2021 were enrolled. And randomly assigned to the control group and study group, with 40 cases in each group. The control group received nicotinamide and narrow-band red light, while the study group received nicotinamide, narrow-band red light, and sterile skin repair dressing. The clinical efficacy, symptom score, erythema, transepidermal water loss (TEWL), and adverse reactions were compared after treatment. Results: After treatment, the study group exhibited significantly lower symptom scores, erythema amount, and TEWL value compared to the control group (P < .05). The clinical efficacy rate in the study group (97.5%) was significantly higher than that in the control group (82.5%) (P < .05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (2.5% vs. 5%) (P > .05). Conclusion: Aseptic skin repair dressing, employed as an adjunctive therapy for facial dermatitis, demonstrates a noteworthy capacity to effectively mitigate parameters such as patient symptom scores, facial erythema quantity, and TEWL values. Notably, the application of this dressing does not pose an elevated risk of adverse reactions. These merits substantiate the superior therapeutic efficacy of aseptic skin repair dressing in facilitating the treatment of facial dermatitis.

Integrating metabolomics and network pharmacology to assess the effects of Mahuang Xixin Fuzi decoction on migraine rats induced by nitroglycerin.

OBJECTIVES: This study was designed to investigate the pharmacological activity and therapeutic mechanism of Mahuang Xixin Fuzi decoction (MXFD) on migraine. METHODS: Migraine model rats induced by nitroglycerin were established, and then orally administered with MXFD for 7 days. Blood and urine samples were collected to identify differential metabolites with metabolomics. To integrate the findings from network pharmacology and metabolomics analysis, the metabolites and targets related to MXFD therapy for migraine were filtered. KEY FINDINGS: MXFD was found to alleviate the symptoms of migraines in rats. After treatment with MXFD, nine metabolites were found to be regulated and returned to normal levels. MXFD acted directly on nine key targets including MAOB, MAOA, ADRB1, ADRB2, ADRB3, ADORA2A, ADORA2B, DRD5, and HTR4 and regulated two out of nine metabolites, namely deoxycholic acid and 5-methoxyindoleacetate. CONCLUSIONS: The study found that MXFD can alleviate migraines through multitarget and multicomponent interaction networks.

Ferrostatin 1 ameliorates UVB-induced damage of HaCaT cells by regulating ferroptosis.

Ferroptosis, a type of programmed cell death, occurs when there is oxidative stress and lipid peroxides. This condition is marked by lipid peroxidation that relies on iron and the reduction of cellular defences against oxidation. To investigate the effect of UVB irradiation on ferroptosis of human keratinocytes HaCaT cells, the cells were pretreated with Ferrostatin 1 (Fer-1, 10 µM), an ferroptosis inhibitor and then irradiated with UVB (20 mJ/cm2 ) for 30 min to detect related indexes of ferroptosis through MTT assay, quantitative real-time polymerase chain reaction, flow cytometry, reactive oxygen species (ROS) assay, western blotting. Results showed that UVB significantly reduced cell activity, promoted apoptosis and ROS level, whereas Fer-1 significantly increased cell activity, and reduced apoptosis and ROS level. In addition, UVB significantly reduced levels of ferroptosis-related proteins and skin barrier-related proteins, and increased levels of γ-H2AX and iron, whereas Fer-1 significantly increased their protein levels, and reduced levels of γ-H2AX and iron. Conjoint analysis of transcriptomic and proteomic revealed that UVB significantly reduced the levels of TIMP metallopeptidase inhibitor 3 (TIMP3), and coagulation factor II thrombin receptor (F2R), whereas Fer-1 significantly promoted the levels of TIMP3, and F2R. Therefore, our results indicated that Fer-1 significantly ameliorates UVB-induced damage of HaCaT cells by regulating the levels of TIMP3 and F2R.

Real-Time Experience of Abrocitinib for the Treatment of Mucous Membrane Pemphigoid: A Case Report.

Background: Mucous membrane pemphigoid (MMP), a rare autoimmune vesiculous and erosive disorder, may affect multiple mucous membranes, with the oral cavity being the most commonly affected site. Its treatment depends on the site(s) of mucosal involvement and disease severity. Patients and Methods: A 62-year-old female patient with MMP that predominantly involved the oral cavity strongly rejected systemic corticosteroid or immunosuppressive agents and was successfully treated with abrocitinib, a highly selective JAK-1 inhibitor with a good safety profile. Results: The case demonstrated good efficacy and safety profile of abrocitinib for the treatment of MMP with predominant oral involvement. Conclusion: Abrocitinib is a promising agent for the treatment of MMP with oral involvement.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION: CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

Identification of the role of autophagy-related TNFSF10/ hsa-let-7a-5p axis in vitiligo development and potential herbs exploring based on a bioinformatics analysis.

Background: Vitiligo is a common clinical disorder caused by the destruction of epidermal melanocytes, which is often associated with autoimmune mechanisms. Autophagy plays a crucial role in maintaining cellular homeostasis and exhibits close associations with various autoimmune disorders. While dysautophagy of melanocytes is associated with vitiligo pathogenesis, there is a lack of studies on autophagy-related genes (ARGs) in blood samples from individuals with vitiligo. Methods: Blood samples from individuals with vitiligo and healthy controls were compared to identify differentially expressed genes (DEGs), which were subsequently subjected to further analysis. Then, miRNAs correlated with core genes were predicted by five distinct online tools, and those miRNAs that appeared in three or more tools at the same time were chosen for further enrichment analysis. Furthermore, in vitro experiments of targeting core genes were conducted. Results: The results showed that there were a total of 30 ARGs among DEGs, with 13 up-regulated genes and 17 down-regulated genes. Based on the functional enrichment analysis of DEGs and projected miRNAs, we hypothesized that autophagy and apoptosis may synergistically contribute to the progression of vitiligo, with the TNFSF10/hsa-let-7a-5p axis potentially playing an important role that should not be ignored. In addition, epigallocatechin-3-gallate (EGCG) was found to be the common component in BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI, which were discovered to be potential in vitiligo treatment by inducing cell autophagy and apoptosis targeting TNFSF10. Conclusion: It was the first time that TNFSF/hsa-let-7a-5p was discovered to be involved in the development of vitiligo through autophagy and apoptosis. Meanwhile, we observed that BAI GUO, CHA YE, and MEI ZHOU JIN LV MEI were promising to treat vitiligo by regulating autophagy and apoptosis via TNFSF10. These findings could lead to new directions for investigating the pathogenesis and therapy of vitiligo.

Successful Treatment of Granulomatous Rosacea by JAK Inhibitor Abrocitinib: A Case Report.

Granulomatous rosacea (GR) is a rare inflammatory skin disease characterized by persistent, hard, yellow, brown, red, or flesh-colored papules, plaques, or nodules on the face. Limited data are available on patients treated for GR, with only case reports and case series published. Herein, we describe the case of a 53-year-old woman who presented to the hospital with persistent red to brown and pink patches on both cheeks accompanied by a burning sensation for one month. Histopathological examination of a cutaneous biopsy revealed granulomatous inflammation in focal areas. Both acid-fast and Periodic acid-Schiff staining were negative. The patient was diagnosed with GR based on her clinical presentation and laboratory test results. She was treated with abrocitinib, a JAK-1 inhibitor, for 20 weeks. This resulted in substantial improvement in her rash and the associated burning sensation. Subsequent follow-up visits indicated no adverse effects or relapses. Additionally, a literature review was conducted to compare with the current case, which concluded that abrocitinib is a viable treatment option for GR, exhibiting a relatively high safety profile with minimal side effects.

Construction of a novel prognostic model in skin cutaneous melanoma based on chemokines-related gene signature.

Skin cutaneous melanoma, SKCM, is one of the most aggressive treatment-resistant tumours. Despite the fact that the BRAF oncogene and immunological checkpoints such as PD-1/PD-L1 and CTLA-4 have enhanced the therapeutic efficacy of SKCM, the subsequent resistance mechanisms and remedies have raised concerns. Chemokines have a significant role in the immunological milieu of tumor, which may increase the efficacy of checkpoint blockade and serve as a possible therapeutic intervention route. However, there is still no chemokine-based typing and risk model to provide a prognosis and therapeutic efficacy assessment for SKCM patients. In this study, we verified the distinct differences of prognostic stratification as well as immune characteristics between two chemokine-related clusters in SKCM patients. Two clusters of DEGs were discovered to be primarily enriched in B and T cell receptor signaling pathways as well as TNF signaling via NF-kappa-B. Based on 14 prognosis-related DEGs from aforementioned two clusters (CCL8, GBP2, GBP4, SRNG, HLA-DMB, RARRES3, HLA-DQA1, PARP12, APOL3, IRF1, HLA-DRA, UBE2L6, IL2RA and CD38), a chemokine-related 14-gene prognostic model was established. At the same time, researchers explored differences between the low-risk and high-risk groups in clinical traits, the proportion of infiltration of 22 different types of immune cells, and how well medications worked. The risk score model's immunotherapy and prognostic predictions were also confirmed in testing groups. Based on the finding, we can claim that there is a clear link between chemokines and TME in SKCM. The risk score may perform as a trustworthy prediction model, giving therapeutic benefits for both chemotherapy and immunotherapy, as well as being beneficial for clinical decision making in SKCM patients.

Current and Emerging Therapies for Atopic Dermatitis in the Elderly.

Atopic dermatitis (AD) in the elderly has recently emerged as a distinct subgroup of AD, garnering widespread concern due to its increasing global incidence rate. Epidermal barrier dysfunction, inflammatory response, and chronic pruritus interact with each other, contributing to the pathogenesis and pathophysiology of AD in the elderly. Although fundamental medications are essential for managing AD in the elderly, older adults often struggle with regular usage of moisturizing emollients, topical medications, and avoidance of environmental triggers, leading to recurrent or even exacerbated disease progression. Therefore, a systematic medication approach is necessary to control pruritus and skin lesions. Traditional systemic treatments may not adequately meet the treatment needs of moderate and severe AD in the elderly and may even pose certain safety risks. Biologics and Janus kinase (JAK) inhibitors, exhibiting excellent clinical efficacy, have made significant breakthroughs in AD treatment. Existing evidence suggests that dupilumab, a human monoclonal IgG4 antibody, has been confirmed as an effective and safe first-line systematic treatment for moderate to severe AD in the elderly, with no notable differences between adults and the elderly. However, the limited inclusion of elderly patients in related clinical studies hinders the generalizability of these findings. As older patients face a higher risk of adverse events with JAK inhibitors, JAK inhibitors are recommended when no other suitable treatment options are available. Obtaining population-specific data is crucial for making evidence-based treatment choices when managing AD in older adults with JAK inhibitors.

A Case of Perioral Dermatitis Successfully Treated with Abrocitinib.

Perioral dermatitis (POD) is a chronic inflammatory skin disease that primarily affects females between the ages of 16 and 45. Conventional therapies face the challenge of limited efficacy and a high recurrence rate. In this report, we present the case of a 26-year-old male patient with POD who was successfully treated using the Janus kinase (JAK) inhibitor, abrocitinib. This treatment exhibited both good efficacy and safety. Abrocitinib, as a JAK inhibitor, holds promise as a potential therapy for cases of POD that might be resistant to conventional therapies.

Lipid Metabolism Traits Mediate the Effect of Psoriasis on Myocardial Infarction Risk: A Two-Step Mendelian Randomization Study.

Mendelian randomization (MR) analysis was performed to explore the effect of psoriasis on lipid metabolism traits and myocardial infarction (MI) risk and to analyze the proportion of the mediatory effect of lipid metabolism traits. Publicly accessible summary-level data for psoriasis, lipid metabolism traits, and MI were provided by the genome-wide association studies (GWASs) of the FinnGen Biobank, UK Biobank, and CARDIoGRAMplusC4D, respectively. A two-sample MR was carried out to evaluate the association of psoriasis with lipid metabolism traits and MI. Furthermore, the current research focused on determining if the impact of psoriasis on MI is mediated by lipid metabolism traits. The outcomes of the random effect inverse-variance-weighted (IVW) technique indicated a substantial link between genetically predicted psoriasis and a higher risk of low-density lipoprotein (LDL) cholesterol (OR: 1.006, 95% CI: 1.005-1.007, p = 0.024), apolipoprotein B (OR: 1.018, 95% CI: 1.010-1.026, p = 0.015), lipoprotein A (OR: 1.006, 95% CI: 1.002-1.010, p = 0.039), and MI (OR: 1.066, 95% CI: 1.014-1.121, p = 0.012). The percentages of the mediatory effect of LDL cholesterol, apolipoprotein B, and lipoprotein A under psoriasis conditions on MI risk was 7.4%, 10.2%, and 4.1%, respectively. Psoriasis was causally linked to an elevated risk of lipid metabolism levels and MI. This study further demonstrated that LDL cholesterol, apolipoprotein B, and lipoprotein A mediated the effect of psoriasis on MI risk. And timely lipid-lowering treatment should be given to MI patients.