Dermatology and Therapy最新文献

Psoriasis is a chronic inflammatory skin disease characterized by well-demarcated erythematous plaques with silvery scales that affects 2-3% of the global population. Beyond its dermatological manifestations, psoriasis has recently been recognised as a significant cardiovascular risk factor, patients with psoriasis have an approximately 50% increased relative risk of major cardiovascular events compared with the general population. This review examines the complex relationship between psoriasis and cardiovascular disease, exploring the epidemiological evidence, underlying pathophysiological mechanisms, clinical implications and therapeutic considerations. The inflammatory milieu characteristic of psoriasis, involving T cell activation, cytokine dysregulation and systemic inflammation, creates a pro-atherogenic environment that accelerates cardiovascular disease development. Understanding the mechanisms of cardiovascular risk is crucial for clinicians managing psoriatic patients, as it necessitates comprehensive risk assessment and preventive strategies beyond traditional dermatological care.

Introduction: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease frequently associated with other immune-mediated inflammatory diseases (IMIDs), such as systemic lupus erythematosus (SLE) and psoriasis. Although advanced therapies have improved HS outcomes, many patients continue to experience suboptimal control, particularly when managing concurrent comorbidities. Combination therapy with biologics and small molecules may offer an effective strategy in select complex cases.

Methods: We present three female patients with moderate-to-severe HS and systemic comorbidities (two with paradoxical palmoplantar psoriasis, one with SLE) who were treated with a combination of secukinumab and upadacitinib. All had previously failed at least two conventional systemic therapies. Secukinumab 300 mg was initiated first, followed by the addition of upadacitinib (15-30 mg) after 5-6 months.

Results: The combination achieved significant improvement in HS activity and complete or near-complete resolution of comorbid conditions. Treatment was well tolerated, with no discontinuations or adverse events reported over 3-6 months of follow-up.

Conclusion: Our findings suggest that dual targeted therapy may represent a viable approach for patients with refractory disease and multiple immune-mediated conditions, warranting further investigation in larger cohorts.

Copper (Cu) and zinc (Zn) are trace elements required for a multitude of physiological processes, including wound healing, and there has been a long history of including both metal ions in topical skin repair formulations. Wound healing involves complex and dynamic cellular mechanisms in the main phases of platelet hemostasis, inflammation, granulation tissue formation, re-epithelialization, and extracellular matrix remodeling. This process is influenced by the balance in the skin's commensal microbiota, and the risk of microbes becoming pathogenic through migration and colonization of the deeper tissues. We examine the antimicrobial effects of Cu/Zn versus their roles in the innate immune response that prevents the invasion and proliferation of microorganisms and in the cellular mechanisms that promote wound healing. Cu/Zn modulates macrophage polarization, promoting the transition from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype, which is critical for tissue repair. Both elements also act as cofactors that modulate the activities of important growth factors, mediators, and enzymes, including antioxidant enzymes, such as superoxide dismutase, which have a role in the innate immune response to pathogens and protect cells from oxidative damage, reducing inflammation and promoting healing. These divalent ions stimulate angiogenesis, and the Cu/Zn combination can also modulate integrin expression in keratinocytes, which are needed for re-epithelialization, supporting cellular mobility and differentiation, and enhancing the healing process. The synergistic roles of Cu/Zn in preventing infection while stimulating the skin's natural immune defenses encourage efficient tissue repair after injury. Topical Cu/Zn-containing formulations therefore hold promise for improving wound management.

Introduction: Both topical and systemic treatments can be used to manage atopic dermatitis (AD) in patients with moderate AD. This study evaluates the cost of ruxolitinib cream versus dupilumab in patients with moderate AD eligible for topical or systemic therapy.

Methods: An economic model based on a post hoc analysis of the TRuE-AD1/2 trials compared costs of topical and systemic treatments for moderate AD. It included patients aged ≥ 12 years with Investigator's Global Assessment (IGA) = 3, Eczema Area and Severity Index (EASI) ≥ 16, and body surface area (BSA) ≥ 10%, matching dupilumab trial criteria. The 2-year model, from a payer perspective, considered only medication acquisition costs.

Results: Patients meeting the target profile averaged 26.5 years old, with 53% female. In addition to IGA = 3, they had mean (SD) BSA of 18% (1.9%) and EASI of 19.3 (2.9). They had lived with AD for 18.2 years on average; 68.8% had facial involvement, 65.6% had used high-potency topical corticosteroids, and 40.6% had used systemic corticosteroids. Under model assumptions, patients using 1.5% ruxolitinib cream would utilize on average 9.0 tubes (60 g each) in year 1, costing $18,407 (95% CI $15,296-$21,518). Fully adherent dupilumab users would need 27 injections, costing $51,343. In year 2, estimated costs were $10,582 (95% CI $7955-$13,209) for ruxolitinib cream and $49,442 for dupilumab. Differences persisted across all sensitivity analyses.

Conclusions: This model demonstrates that 1.5% ruxolitinib cream reduces treatment costs by over 80% compared to dupilumab in patients with moderate AD eligible for systemic therapy. Combined with comparable efficacy, these savings position ruxolitinib cream as a cost-effective treatment option.

Introduction: Calcipotriol and betamethasone dipropionate (Cal/BDP) PolyAphron dispersion (PAD) cream and Cal/BDP foam have demonstrated superior efficacy to Cal/BDP gel in patients with plaque psoriasis exhibiting a more severe profile defined by the Rule of Tens in different studies. However, its comparative efficacy in this subgroup of patients needs to be studied.

Methods: An indirect treatment comparison (ITC) using individual patient data for Cal/BDP PAD cream and available aggregated data for Cal/BDP foam was conducted for three outcome measures: Physician's Global Assessment (PGA) success, modified Psoriasis Area and Severity Index 75 (mPASI75), and Dermatology Life Quality Index (DLQI) satisfaction. Bucher's method was used for the ITC base case, and alternative analyses were performed using an anchored matching-adjusted indirect comparison (MAIC). Odds and risk ratios were calculated for each outcome.

Results: After adjustment to the Rule of Tens, Cal/BDP PAD cream showed no differences vs. Cal/BDP foam in the three outcomes. Similar results were found for the MAIC scenarios after population matching, supporting the validity of the results.

Conclusion: In this ITC analysis, no significant differences in the clinical efficacy of Cal/BDP PAD cream and Cal/BDP foam in patients with plaque psoriasis meeting the Rule of Tens were observed considering their recommended treatment durations.

Chronic hand eczema (CHE) is a chronic inflammatory skin disease defined as hand eczema that occurs for more than three consecutive months or relapses at least twice per year. For patients with CHE, quality of life can be negatively affected by the severity of symptoms, such as pain and itch, and the appearance of the affected skin on the hands and wrists which are highly visible. This article is coauthored by a patient who shares her lifelong journey with CHE. She details the physical, mental, and social impacts she experienced throughout her life with this chronic disease, as well as her struggles in navigating clinical care and finding an effective treatment. A dermatologist then reflects on the patient's story, highlighting five key lessons to clinicians regarding the burdens of living with CHE and the crucial role of empathy in guiding clinicians to provide more holistic care. Additionally, the current clinical understanding of CHE and treatment options are briefly discussed. Altogether, combining effective treatments with patient-centered holistic care can enhance the quality of life for patients with CHE, by not only improving the physical symptoms of CHE but also their overall well-being.

Introduction: Moderate-to-severe plaque psoriasis can be difficult to treat; not all patients respond to treatment. POETYK PSO-1 and PSO-2 were 52-week, phase 3, multinational, double-blinded trials in plaque psoriasis. We determined deucravacitinib efficacy in PSO-1/PSO-2 patients who did not respond to apremilast.

Methods: PSO-1/PSO-2 were conducted between July 2018 and November 2020; this analysis includes data from both trials. Adults with moderate-to-severe plaque psoriasis (baseline Psoriasis Area and Severity Index [PASI] ≥ 12, static Physician Global Assessment [sPGA] ≥ 3, body surface area involvement ≥ 10%) were included and randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Clinical endpoints included ≥ 75%/90% reduction from baseline PASI (PASI 75/90), sPGA score of 0 (clear) or 1 (almost clear) (sPGA 0/1) response rates, and mean percent change from baseline PASI and BSA involvement. Patient-reported outcomes included Dermatology Life Quality Index 0 (no effect) or 1 (little effect) (DLQI 0/1) and mean change from baseline Psoriasis Symptoms and Signs Diary (PSSD) symptom score.

Results: Of 168 (PSO-1) and 254 (PSO-2) patients randomized to apremilast, 54 (32.1% [PSO-1]) and 111 (43.7% [PSO-2]) did not achieve PASI 50 (PSO-1) and PASI 75 (PSO-2) at Week 24 and were switched to deucravacitinib. PASI 75 response rates improved from 0% at Week 24 to 46.3% (PSO-1) and 42.3% (PSO-2) at Week 52. From Weeks 24-52, PASI 90, sPGA 0/1, and DLQI 0/1 response rates increased; mean percent change from baseline PASI decreased by 60% (PSO-1) and 26% (PSO-2); mean change from baseline in PSSD symptom score decreased by ≈20% in both studies; mean percent change from baseline BSA involvement decreased by 65% (PSO-1) and 25% (PSO-2).

Conclusion: Deucravacitinib was efficacious in patients with moderate-to-severe plaque psoriasis who did not respond to apremilast.

Trial registration: ClinicalTrials.gov identifier, NCT03624127, NCT03611751.

Introduction: This research presents a novel, scientifically validated facial aging simulator. It integrates two published methodologies for personalized aging predictions, particularly concerning the impact of tobacco. This contrasts with widespread simulations on social network and gaming applications, often lacking scientific rigor and transparent methodology.

Methods: This simulator combines elicited knowledge from 28 expert dermatologists with an AI-powered image generation system. Based on this knowledge, the model predicts 15-year facial aging signs according to various intrinsic and extrinsic factors, providing personalized probabilities of reaching specific aging stages (e.g., wrinkles, pigmentation). This work couples these 15-year predictions with a machine learning model (AMGAN) that generates personalized facial aging simulation images. The AMGAN was initially trained on a dataset of 600 individuals with sign scores averaged from 15 expert graders.

Results: We present predicted independent probabilities of reaching grades for different facial aging signs as a function of cumulative tobacco consumption. A simulation was performed using a 43-year-old subject's facial image to demonstrate the tool's capabilities in illustrating the impact of tobacco consumption. Confounding variables such as sun exposure, sunscreen use, and body mass index (BMI) were controlled, while cumulative smoking (less than 10 or greater than 20 pack-years) was varied. This tool effectively visualizes the known effects of smoking on aging and provides personalized quantification of its impact on specific facial wrinkles. Recognizing that individuals prioritize different facial signs, the simulator allows users to focus on areas of personal concern.

Conclusion: By focusing on preserving skin longevity and preventing premature aging, the simulator, which can quantify the impact of smoking on individual aging trajectories, effectively motivates positive lifestyle changes. This personalized approach offers a promising preventative messaging strategy, particularly for audiences resistant to traditional methods, and strengthens the scientific rationale regarding the impact of tobacco on specific aging signs.

Introduction: Melasma is a chronic pigmentary disorder that often recurs after treatment, particularly in people with darker skin who are more prone to pigmentary side effects.

Methods: This prospective study evaluated the efficacy and safety of a 675-nm laser for melasma in individuals with darker skin types. Twenty-eight Thai women with Fitzpatrick skin types (FSTs) III-V underwent three monthly laser sessions using dual Moveo and Standard modes without anesthesia. Clinical severity, pigmentation, patient satisfaction, and safety were assessed up to 6 months after treatment.

Results: The modified Melasma Area and Severity Index (mMASI) showed a 41% improvement at 3 months and 34% at 6 months post-treatment. Antera 3D imaging confirmed progressive melanin reduction, and over 70% of participants reported at least 50% improvement. Adverse effects were mild and transient, including mild erythema or small scabs, with no postinflammatory hyperpigmentation (PIH) observed.

Conclusion: The 675-nm laser achieved sustained lightening of melasma and skin tone improvement with minimal discomfort and no downtime. These findings support the 675-nm laser as a safe and effective treatment for melasma in darker skin types, offering a potential new approach for managing this persistent condition.

Introduction: Nonmelanoma skin cancer (NMSC) risk may be increased in patients with immune-mediated inflammatory disorders. Although atopic dermatitis (AD), an inflammatory immune-mediated chronic skin disease, has been associated with the risk of skin cancer, data on the underlying risk of NMSC in patients with AD in the USA are unclear. The objective of this analysis was to evaluate NMSC incidence and risk in patients with AD generally and those with moderate-to-severe disease specifically compared with a non-AD matched control cohort and patients with rheumatoid arthritis (RA).

Methods: This retrospective observational study examined US claims data (2017-2023) from Optum's de-identified Clinformatics® Data Mart Database of adults with AD and RA, as well as non-AD control cohorts matched 1:1 to patients with AD and patients with moderate-to-severe AD.

Results: This analysis included data from 391,753 patients with AD and 97,445 patients with RA. The matched AD and non-AD cohorts each included 381,221 patients. Patients with AD had a higher NMSC incidence rate (cases/100 person-years [95% CI]) than non-AD matched controls (2.12 [2.10, 2.15] vs 1.74 [1.72, 1.77]) and greater relative NMSC risk (adjusted hazard ratio 1.32 [1.30, 1.35]). NMSC incidence and relative risk were similar between patients with AD and RA. Patients with AD were at greater risk of NMSC if they had a history of NMSC, other malignancies, or organ transplantation. Trends were similar among patients with moderate-to-severe disease.

Conclusion: Patients with AD and those with moderate-to-severe AD had a higher incidence and risk of NMSC than matched individuals without AD.