Dermatology and Therapy最新文献

Introduction: Orismilast is a novel oral selective inhibitor of phosphodiesterase 4B and 4D subtypes (PDE4B/D) in clinical development for treatment of atopic dermatitis (AD) and other inflammatory skin conditions. Herein, we describe a pharmacokinetic/pharmacodynamic (PK/PD) analysis comparing predicted exposure data of orismilast and apremilast in AD patients and place these data in the context of their IL-13 secretion data generated in a human whole-blood assay.

Methods: A PK/PD assessment of orismilast and apremilast in AD was performed. In a human whole blood assay, the levels needed to inhibit IL-13 production were measured for orismilast and apremilast head-to-head. These data were then contextualized with simulated exposure of clinically relevant doses of the two drugs.

Results: The analysis shows that orismilast has potential to significantly inhibit IL-13 production at all three clinical doses trialed in AD (20 mg bid, 30 mg bid, and 40 mg bid) as the drug has a predicted C_average plasma concentration exceeding the IL-13 IC₉₀ value of the human whole-blood assay and a predicted C_min above the IL-13 IC₅₀ value. Apremilast, in contrast, is predicted to reach C_average plasma concentrations below the IL-13 IC₅₀ value for both doses (30 mg bid and 40 mg bid) and only exceeding the IL-13 IC₅₀ value at peak concentrations for the highest dose.

Conclusion: The outcome of the analysis supports the observed clinical effect of orismilast in patients with AD and could explain the lack of efficacy of apremilast in the same indication.

Introduction: Psoriatic arthritis (PsA) affects 10-30% of individuals with psoriasis. Early detection of PsA is crucial to prevent potential irreversible joint damage. The Psoriasis Epidemiology Screening Tool (PEST) has proven to be an effective tool in daily clinical practice, but limited data is available on the analysis of positive responses. Our study aimed to determine the combination of positive responses to individual questions and characterize patients with positive PEST results based on specific anatomical sites of psoriasis, duration of the disease, and epidemiological parameters that could potentially predict PEST positivity.

Methods: The PEST questionnaire was randomly administered to patients with psoriasis without psoriatic arthritis attending the outpatient unit for psoriasis treatment. A total of 351 patients completed the PEST questionnaire over a 24-month period. Patients undergoing various types of therapy were included. Each patient completed the PEST questionnaire once, and epidemiological data (such as age, weight, height, body mass index, smoking status, age of disease onset, disease duration, and family history of psoriasis) were collected, as well as types of therapy.

Results: We included 242 men and 109 women with an average age of 49.4 years and duration of psoriasis of 23.3 years. A positive PEST questionnaire result was found in 28.5% of patients; 13.1% had a score of 3, 8.0% a score of 4 and 7.4% a score of 5. Nail psoriasis, higher age, and therapy with biological/targeted therapy were associated with PEST positivity. The most frequently observed positive response was nail involvement.

Conclusion: The PEST questionnaire is a well-established screening tool for identifying patients at risk of having undiagnosed psoriatic arthritis in daily dermatological practice. Patients with nail involvement, higher age, or treated with modern systemic therapy should be closely monitored, as these factors indicate a higher risk of a positive PEST result and consequently higher risk of having psoriatic arthritis.

Introduction: The impact of chronic spontaneous urticaria (CSU) on patients' health-related quality of life (HRQoL) is well documented. However, considerable gaps remain in understanding the experience, perception and needs of patients with CSU. In this study, we investigate the perspective of patients with CSU about the disease journey, treatment and management of the condition as well as the physical and psychosocial impact of the disease.

Methods: A multinational, cross-sectional online survey was completed by patients with chronic urticaria (CU) and physicians treating CU. This analysis focuses on data from the patients with CSU. The patient survey included customized questions and a validated patient-reported outcomes measure, the Urticaria Control Test (UCT).

Results: A total of 582 patients with CSU (62% women; mean [standard deviation, SD] age: 42.2 [11.9] years) completed the online survey. Patients reported a mean (SD) diagnostic delay of 2 (5.4) years and saw 6.1 (8.9) physicians. The majority (79%) of patients were on antihistamines, of which 84% were inadequately controlled (UCT score of < 12) and reported a significantly higher negative impact of CSU on the HRQoL domains than adequately controlled patients, with the highest impact on mental and emotional well-being and social life and intimate relationships. More than half (55%) of the patients experienced angioedema with a mean (SD) of 7.7 (14.0) episodes per year. In addition, sleeping problems (62%), pain (55%) and fatigue (49%) were frequently reported physical symptoms during an exacerbation.

Conclusion: Patients with CSU experience substantial burden due to delayed diagnosis, insufficient symptom control (despite treatment) as well as mental and emotional well-being and social impact, particularly when uncontrolled. Early diagnosis and patient-centered approaches to symptom management and disease control should be prioritized to minimize the negative impact of CSU on patients' life.

This article explores the ongoing research into the complex pathogenesis of hidradenitis suppurativa (HS) and the persistent challenges in finding effective treatments. With 113 clinical studies currently listed on ClinicalTrials.gov, the quest for novel therapeutic approaches for HS remains vigorous. In this context, bimekizumab stands out as a promising option-a fully humanized IgG monoclonal antibody that selectively targets both interleukin (IL)-17A and IL-17F, showing rapid and significant improvements in HS disease activity. The case study presented in this article features a 24-year-old woman with HS, whose previous treatments had been unsuccessful until she began therapy with bimekizumab. While the patient experienced marked improvement in her HS symptoms, she developed paradoxical scalp psoriasis, complicating her treatment plan. This case highlights not only the therapeutic potential of bimekizumab but also the need for careful monitoring and management of possible adverse effects. Furthermore, the article emphasizes the need for additional research to confirm the efficacy of bimekizumab in larger patient groups, possibly through phase 3 clinical trials and real-world studies. It also underscores the importance of developing comprehensive management strategies for paradoxical reactions, which may become more common as new treatment options for HS are introduced. In summary, the article reflects the evolving landscape of HS treatment, with bimekizumab representing a promising advancement. However, it calls for careful consideration of potential adverse events and the need for further research to solidify its role in HS management.

Tumoral melanosis (TM) is a rare entity thought to result from the complete regression of melanoma. Clinically, TM resembles malignant melanocytic lesions, presenting as hyperpigmented flat or papulonodular lesions. Histologically, TM lacks melanocytes, instead showing inflammation, fibrosis, and melanophages. Diagnosing melanoma without melanocytes is challenging, and TM may also represent other regressed benign or malignant pigmented lesions. This study retrospectively analyzed 12 TM cases focusing on the clinical course, management, and potential for malignancy. Among the cases, 50% were associated with advanced or metastatic melanoma, supporting TM's potential as a regressed melanoma. Conversely, in 50% of cases, TM occurred without primary or metastatic melanoma, suggesting possible regression of a benign or malignant epithelial lesion such as pigmented basal cell carcinoma (BCC) or seborrheic keratosis (SK) or confinement of melanoma by the immune system. Management included surgical excision and follow-up similar to that of melanoma. Sentinel lymph node biopsy (SLNB) was selectively performed based on clinical suspicion and multidisciplinary team discussions. In conclusion, TM should be considered potentially regressed melanoma, especially in patients with high disease burden, and the possibility of derivation from high-grade melanomas must always be considered. Given the inability to distinguish TM from completely regressed melanoma, clinicians must remain vigilant and suspect this origin during staging and follow-up. Comprehensive management and close monitoring are crucial to address TM's clinical implications.

Introduction: The National Comprehensive Cancer Network (NCCN) recommends excision of the primary tumor using 1-2-cm surgical margins and sentinel lymph node biopsy (SLNB) as the initial management of early-stage Merkel cell carcinoma (MCC). However, there is no clear consensus on the appropriate size of the surgical margins and/or the use of Mohs micrographic surgery (MMS). Our aim was to demonstrate that, independent of the type of surgery, obtaining negative surgical margins is associated with enhanced overall survival (OS).

Methods: A retrospective study was performed using early-stage MCC patients from the National Cancer Database (NCDB) who were diagnosed between 2004 and 2020 and underwent surgical excision (SE) of their primary tumor. Patients were stratified into three groups based on the surgical treatment they received: < 1 cm excision margin, ≥ 1 cm excision margin, or MMS. OS was assessed with Kaplan-Meier curves, log-rank tests, and multivariable risk-adjusted Cox proportional-hazards regression.

Results: Of the 4,607 patients included in this study; 53% underwent SE of ≥ 1 cm (n = 2,474), 41% had SE < 1 cm (n = 1,905), and the remainder had MMS (n = 228). 75% of patients had an SLNB, and 56% received adjuvant radiation to the primary site and/or nodal basin. While no difference in OS was observed between the three surgical treatments, negative surgical margins (hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.65-0.94) and receipt of radiation to the primary site (HR 0.82; 95% CI 0.73-0.92) were both independently associated with improved OS.

Conclusion: Achieving negative surgical margins is associated with improved OS in MCC, suggesting that MMS and conventional excision are both suitable approaches for the treatment of primary MCC.

Introduction: There is growing evidence that ultraviolet-induced fluorescence (UVF) dermoscopy may improve diagnostic accuracy in non-neoplastic dermatoses, yet data on hair disorders are scarce. The aim of this observational retrospective study was to compare the accuracy of polarized dermoscopy and UVF-dermoscopy in characterizing and distinguishing scarring and nonscarring alopecias.

Methods: A total of 84 patients were enrolled, with 43 and 41 patients suffering from nonscarring and scarring alopecias, respectively. Analyzed variables included scarring findings (i.e., dotted/globular, structureless or perifollicular bright white areas on both polarized and UVF-dermoscopy) and follicular unit (i.e., hair or follicular ostia, with the latter appearing as empty follicular openings and follicular red/blue fluoresce on polarized and UVF-dermoscopy, respectively). Comparative analysis between polarized and UVF-dermoscopy in detecting the abovementioned features and differentiating scarring from nonscarring alopecias were performed, also assessing possible differences according to the skin tone. Interobserver agreement was evaluated for both dermoscopic settings.

Results: UVF-dermoscopy was superior (p < 0.01) to polarized dermoscopy in detecting follicular ostia and white bright areas in general and fair-skinned patients, while only follicular ostia were better seen under this setting in skin of color. Additionally, UVF-dermoscopy was found to be more accurate (p < 0.01) in differentiating nonscarring from scarring alopecias when considering all and light phototypes. Finally, Kappa values were 0.57 and 0.83 for polarized and UVF-dermoscopy, respectively.

Conclusions: UVF-dermoscopy may be a valuable and reliable complementary tool in differentiating scarring and nonscarring alopecias, especially in light phototypes.

Acne vulgaris affects nearly 50 million people in the USA, ranking as the eighth most prevalent disease globally. This chronic inflammatory skin condition often results in sequelae, including atrophic acne scars, acne-induced macular erythema and acne-induced hyperpigmentation, impacting patients' quality of life. This commentary article reviews the use of topical retinoids, with a particular emphasis on trifarotene cream 0.005%, for managing both acne and acne sequelae. Topical retinoids are considered central to improving treatment outcomes because of their established efficacy, safety and tolerability. Adapalene, tretinoin and tazarotene have demonstrated efficacy in reducing acne and acne sequelae in several studies. Trifarotene has been extensively studied in Phase 3 trials, demonstrating notable success in treating mild-to-moderate acne. Recently, two large-scale, randomized, blinded, Phase 4 clinical trials investigated trifarotene cream 0.005% in patients with atrophic acne scarring and acne-induced hyperpigmentation across all Fitzpatrick phototypes. The START study found that there was a greater reduction in total atrophic acne scar count in the trifarotene group compared with the vehicle group at Week 24 (55.2% vs 29.9%) with statistical significance established as early as Week 2 (P = 0.001). Based on this evidence, we recommend that topical retinoids should be introduced as first-line therapy for the treatment of acne and acne sequelae. Retinoids should be implemented into a treatment routine as early as possible, especially for patients with darker Fitzpatrick phototypes or patients at risk of atrophic acne scarring. Furthermore, retinoids should be incorporated within a comprehensive skincare regimen that includes adequate photoprotection when treating patients with darker Fitzpatrick phototypes. Finally, management of acne and acne sequelae should include maintenance therapy with topical retinoids. This article supports the American Academy of Dermatology's call for acne sequelae treatment guidance and emphasizes the need for continued research to optimize patient care.

Introduction: Bimekizumab and brodalumab are characterized by a different mechanism of action if compared to the other anti-interleukin (IL)-17s which target IL-17A. Indeed, brodalumab acts on IL-17RA whereas bimekizumab acts on IL-17A, IL-17F, and IL-17AF cytokines. Currently, despite real-life data on the efficacy and safety of bimekizumab and brodalumab have been reported, data comparing these two drugs are absent. However, these data are mandatory to evaluate whether a different target of the same IL can be correlated with a different profile in terms of effectiveness and safety. Moreover, it should be underlined that bimekizumab and brodalumab stood out as the psoriasis treatments with the fastest onset of action, delivering quicker therapeutic responses compared to other drugs acting on IL-17.

Methods: A monocentric retrospective study was carried out enrolling patients affected by moderate to severe psoriasis undergoing treatment with brodalumab or bimekizumab. At baseline, clinical demographic details were collected. Clinical improvement [Psoriasis Area Severity Index (PASI), body surface area (BSA)] was collected at weeks 4, 16, and 36. Safety data were analyzed at the same timepoints.

Results: A total of 125 patients were enrolled in the study [bimekizumab: 53 (42.40%); brodalumab: 72 (57.6%)]. Psoriasis severity at baseline was similar between the two cohorts. Both PASI and BSA significantly reduced at each follow-up for both treatment cohorts. The bimekizumab group reached a higher percentage of PASI90/PASI100 response at each timepoint as compared to the brodalumab cohort. In particular, the percentage of PASI100 response was significantly higher in the bimekizumab group as compared to the brodalumab cohort at week 4 (41.5% vs 23.6%, p < 0.05) and at week 16 (67.9% vs 48.6%). Discontinuation for ineffectiveness was higher in the brodalumab cohort (8.3%) as compared to the bimekizumab group (3.8%), without statistical significance. As regards safety, two cases of eczematous reactions (bimekizumab: 2, brodalumab: 0), and five cases of candidiasis (bimekizumab: 4, brodalumab: 1) were collected. Overall, 3 (5.7%) and 1 (1.4%) patients discontinued bimekizumab and brodalumab because of adverse events, respectively.

Conclusion: Our study confirmed the efficacy and safety of both bimekizumab and brodalumab, up to 36 weeks of treatment. Although both drugs showed a significant improvement of the investigated scores from week 4, some differences in terms of PASI90 and PASI100 responses (higher for bimekizumab at each follow-up, with only PASI100 response significantly higher at week 4 and 16) were registered. No statistical significance was found for safety data and treatment failure.

Introduction: The effectiveness of psoriasis treatment is assessed by standardized tools such as the Dermatology life Quality Index (DLQI) and Psoriasis Area Severity Index (PASI). However, discrepancies between patients and physicians in terms of treatment success and goals, along with the growing importance of shared decision-making in healthcare, highlight the need for tools specifically designed for psoriasis. Such tools can enhance communication between patients and physicians, encouraging shared decision-making and improving the assessment of patient treatment expectations.

Methods: Comparison of the new PSO-TARGET grid, which consists of 12 therapeutic goals evenly distributed across 4 major components commonly used in quality of life (QoL) studies for chronic diseases, with DLQI as a standard tool, was utilized.

Results: A total of 143 adult patients with moderate-to-severe psoriasis and treated with brodalumab were included. On the basis of a blind assessment, dermatologists were not able to identify the patients' chosen PSO-TARGET goal in more than 50% of cases. The comparison after 12/16 weeks of treatment revealed some discrepancies between the two QoL tools. Compared with the rest of the population, the patients who achieved their PSO-TARGET goal, but still reported a DLQI > 1, had higher baseline PASI scores (18.6 versus 14.8; p = 0.067), higher DLQI scores (14.1 versus 10.1; p = 0.004), and a higher number of hard-to-treat locations (median of 2 versus 1; p = 0.004). In addition, patients who had not reached their PSO-TARGET goal but reported a DLQI ≤ 1, all had psoriasis on the scalp at the baseline and were generally younger (median of 31 versus 52 years, p = 0.001).

Conclusions: This study highlights the importance of considering patient characteristics of those with psoriasis and perspectives when evaluating treatment outcomes. Using shared decision-making tools such as the PSO-TARGET grid can improve communication and understanding between dermatologists and patients.

Trial registration: ClinicalTrials.gov identifier, NCT04765332.