Dermatology and Therapy最新文献

Acne and acne sequelae can have an important impact on patients' quality of life, affecting interpersonal relationships and social functioning. Acne-induced scars (AIS) and acne-induced macular hyperpigmentation (AIH), in particular, are a major concern for patients with acne, as their management is challenging and often unsatisfactory. Retinoids are considered the mainstay of acne treatment because of their action on multiple pathogenetic factors, and there is increasing evidence that they can also improve AIS and AIH. Trifarotene, a topical retinoid with selectivity for retinoic acid receptor (RAR)-γ, has undergone an extensive clinical development programme, demonstrating its efficacy in treating facial and truncal acne and improving acne sequelae. In this article, we review the main evidence supporting the use of trifarotene in patients with acne and acne sequelae and provide place-in-therapy suggestions based on the experience of the Italian Acne Board with this drug in real-life practice. Trifarotene can be used successfully, as monotherapy or in association with other treatments, in most clinical settings of acne, but it plays an essential role in patients with existing AIS and AIH, those with a clinical or personal history of scarring and those who are predisposed to AIH. Owing to its long-term efficacy and tolerability, trifarotene is also a good option as a maintenance treatment. As with other topical retinoids, patients undergoing trifarotene therapy should be given advice on how to minimise local irritation when starting treatment.

Introduction: Ultraviolet-induced fluorescence dermoscopy (UVFD) is increasingly utilized in dermatooncology and general dermatology. The objective of the study was to characterize the ultraviolet-induced fluorescence trichoscopy (UVFT) findings in a wide range of hair and scalp conditions.

Methods: Consecutive patients with non-scarring alopecias (alopecia areata, AA, n = 40; androgenetic alopecia, AGA, n = 40), scarring alopecias (frontal fibrosing alopecia, FFA, n = 20; lichen planopilaris, LPP, n = 20; folliculitis decalvans, FD, n = 14; discoid lupus erythematosus, DLE, n = 23), and inflammatory scalp conditions (psoriasis, n = 30; seborrheic dermatitis, n = 14) were included. Examinations were performed using polarized trichoscopy and UVFT.

Results: The following features were observed under UVFT: white-blue perifollicular fluorescence, white-blue interfollicular fluorescence, irregular confluent dark areas, dark follicular dots, dark perifollicular areas, regular/irregular pink-red follicular fluorescence, regular/irregular green follicular fluorescence, short white hair, black dots, exclamation mark hair, double/triple white follicular dots, pink-red fluorescence of the scales, pink-red fluorescence of the background. Non-scarring alopecias showed more frequently pink-red or green follicular fluorescence (p < 0.001), dark follicular dots (p < 0.001), short white hair (p < 0.001), and double/triple white follicular dots (p < 0.001). In scarring alopecias, white-blue perifollicular fluorescence (p < 0.001), dark perifollicular areas (p < 0.001), and dark confluent areas (p < 0.001) were more commonly observed. Psoriasis showed more frequently pink-red fluorescence of the scales than seborrheic dermatitis (p = 0.019).

Conclusion: UVFT supports the differentiation between scarring and non-scarring alopecia, as well as between psoriasis and seborrheic dermatitis. UVFT may hypothetically facilitate the biopsy site selection by highlighting the subclinical perifollicular and interfollicular inflammation.

Frontal fibrosing alopecia (FFA) is an inflammatory, scarring hair loss that commonly affects postmenopausal women and presents as frontal hairline recession, facial papules, loss of eyebrows, and facial hyperpigmentation. Because of the chronic, progressive nature of this disease and its important impact on aesthetic appearance, patients often consult dermatologists to improve unwanted FFA symptoms. Cosmetic practices including the use of non-ablative lasers, autologous fat injections, and oral isotretinoin can improve FFA-associated facial vein prominence, atrophic indentations, and facial papules, respectively. On the other hand, while exact etiology underlying FFA development remains unclear, some procedures including deep chemical peels and ablative laser therapies have been shown to induce facial scarring and are contraindicated in patients with FFA. In the same way, some cosmetic ingredients can possibly be a triggering or worsening factor for FFA as well. Therefore, it is essential for dermatologists to be aware of both the benefits and risks of cosmetic treatments in patients with diagnosed or suspected FFA. This comprehensive review aims to outline the key cosmetic products and procedures that may be useful in patients with FFA and those which should be considered contraindicated.

Introduction: Psoriasis is a systemic inflammatory disease with increased cardiometabolic risk including dyslipidaemia and diabetes. Biologic therapy effectively treats the cutaneous inflammatory burden of psoriasis and evolving evidence suggests potential to reduce systemic inflammatory sequalae that can elevate cardiovascular risk. This study aimed to assess the change in cardiometabolic risk markers in a cohort of patients with psoriasis treated with 1 year of continuous biologic treatment.

Methods: A retrospective review was conducted of patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Sydney, Australia. The effect of biologic therapy on psoriasis was assessed using the psoriasis area severity index (PASI). Cardiometabolic risk markers assessed included lipid profile (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and haemoglobin A1c (HbA1c). Measurements at baseline and 1 year were compared using paired t tests for analysis of the parameters which approximated normal distribution (TC, LDL, HDL) and Wilcoxon signed-rank test for analysis of those which did not (TG, HbA1c, PASI). Two-tailed P values < 0.05 were considered significant.

Results: A total of 200 patients were reviewed, of which 39 had complete data sets. The participants' ages ranged from 21 to 85 years (mean 51, SD 16.9). Of the 39 participants, 31 (79.5%) were male, 8 (20.5%) were female; 26 (67%) were biologic experienced (BE) and 13 (33%) were biologic naïve (BN). The mean PASI at baseline (for BN + BE) was 13.4 (SD 9.8). The biologic agents used, according to frequency, included risankizumab, with 14 participants (35.9%), secukinumab by 7 (17.9%), ustekinumab by 6 (15.4%), ixekizumab by 6 (15.4%), guselkumab by 3 (7.7%), infliximab by 2 (5.1%), and adalimumab by 1 (2.6%). After 12 months, significant skin improvement was seen [PASI reduced from 13.43 (SD 9.8) to 1.1 (SD 2.1), p < 0.001]. There was no significant change in lipid profile, including TC (mean difference - 0.1 mmol/L, p = 0.532), LDL-C (mean difference = - 0.1 mmol/L, p = 0.476), HDL (mean difference = - 0.1 mmol/L, p = 0.125), triglycerides (mean difference = 0.0 mmol/l, p = 0.748) or HbA1c (mean difference 0.38%, p = 0.468).

Conclusion: Markers of cardiometabolic risk (lipid profile and HbA1c) did not significantly improve after 1 year of biologic therapy despite significant reduction in psoriasis skin severity. Further research in larger cohorts is needed to elucidate the benefits, if any, of biologic therapy on cardiometabolic parameters in individuals with psoriasis, in order to optimise care for this vulnerable cohort.

Background: Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma. While multiple guidelines provide treatment recommendations, there are currently no clear treatment algorithms for MF. Chlormethine gel is recommended by major treatment guidelines as a first-line option for stage IA-IIA disease, and, on the basis of these guidelines, used in combination with other therapies in patients with advanced-stage MF in clinical practice.

Objectives: To provide guidance regarding the use of chlormethine gel for patients with all stages of MF, based on clinical expertise.

Methods: Opinions on best practices regarding the use of chlormethine gel were collected through discussions that involved eight clinicians with extensive experience in treating patients with MF.

Results: Chlormethine gel can be used as monotherapy in first- or second-line treatment of early-stage MF. In first-line, chlormethine gel monotherapy is prescribed for stage IA MF, and is particularly convenient for patients unable/unwilling to travel for hospital-based phototherapy, patients with thick plaques or palmoplantar involvement, when ultraviolet treatment is contraindicated, and for sanctuary sites. Chlormethine gel is also an appropriate first-line monotherapy for patients with stage IB or IIA MF; it may be used as part of combination regimens in these patients as well. For patients with late-stage MF, skin-directed treatments such as chlormethine gel should be combined with systemic therapies.

Conclusions: Chlormethine gel is a safe and effective treatment option that can be used in all stages of MF, either as monotherapy or in combination, depending on disease stage and patient characteristics and needs.

Introduction: Results from randomized controlled trials of upadacitinib, a Janus kinase (JAK) inhibitor, have led to its approval for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 12 years. The aim of this study was to report the effectiveness and safety of upadacitinib in real-world settings over a period of 96 weeks.

Methods: This retrospective study included all patients treated with upadacitinib at our centre between April 2022 and September 2024. Clinical and patient-reported outcomes were recorded and assessed at each follow-up visit and included the eczema area severity index (EASI), investigator global assessment (IGA), scoring atopic dermatitis (SCORAD), dermatology life quality index (DLQI) and the worst pruritus numerical scale score (WP-NRS). All drug-related adverse events (AEs) were documented.

Results: In total, 36 patients (44.4% female) were retrospectively included. After 4 weeks of treatment, the mean EASI was reduced from 29.97 to 3.72 with 83.3/52.8/19.4% achieving EASI75/90/100 respectively. Similar reductions were observed in the DLQI, which was reduced from 20.78 to 2.92, and in the WP-NRS, from 7.78 to 1.31. Further improvements were observed at week 16, with a mean EASI of 0.75 and 96.4% of the patients achieving EASI75 and EASI90. At week 48 of treatment, EASI75/90/100 were achieved by 100/93.8/81.3% along with a mean DLQI and pruritus NRS of 0.81. All nine patients that reached the 72- and 96-week timepoints had clear skin with no pruritus. Six (16.7%) patients experienced AEs with four of them discontinuing medication; no patient discontinued because of upadacitinib inefficacy.

Conclusion: This long-term real-world study of patients with moderate-to-severe AD receiving upadacitinib demonstrated that treatment success (EASI75/90/100) can be achieved in a high proportion of patients by week 16 and can be maintained for up to 96 weeks along with substantial improvements in pruritus and quality of life.

Introduction: Psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) may confer an increased risk for cardiovascular (CV) disease, including major adverse cerebro-cardiovascular events (MACE), deep vein thrombosis (DVT), and pulmonary embolism (PE). Patients with these conditions are often exposed for extended time periods to biologics, such as ixekizumab (IXE). Therefore, understanding the risk of CV events, especially MACE, in patients with PsO, PsA, and axSpA exposed to IXE is important.

Methods: The incidence of MACE (i.e., adjudicated cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), DVT, and PE was assessed in adults who received ≥ 1 dose of IXE across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA). Rates of CV events were analyzed for pooled studies by indication and analyzed from treatment initiation up to the end of the study program. Exposure-adjusted incidence rates per 100 patient-years (IR/100 PY) are reported.

Results: This integrated safety analysis included 6892 patients with PsO, 1401 with PsA, and 932 with axSpA. The median duration of IXE exposure was 478.5 days (1.3 years) for patients with PsO, 504.5 days (1.4 years) for patients with PsA, and 981.0 days (2.7 years) for patients with axSpA. The incidence of adjudicated MACE was low (IR/100 PY: PsO = 0.5; PsA = 0.5; axSpA = 0.3) and stable over the treatment periods. The most common types of MACE reported were non-fatal myocardial infarction (IR/100 PY: PsO = 0.3; PsA = 0.3; axSpA = 0.3), followed by non-fatal stroke (IR/100 PY: PsO = 0.1; PsA = 0.2; axSpA = 0.0), and cardiovascular death (IR/100 PY: PsO = 0.1; PsA = 0.1; axSpA = 0.0). The incidences of DVT (IR/100 PY: PsO = 0.1; PsA = 0.1; axSpA = 0.1) and PE (IR/100 PY: PsO = 0.1; PsA = 0.0; axSpA = 0.0) were low.

Conclusion: This integrated safety analysis of 25 randomized clinical trials showed that the incidence of adjudicated MACE was low among adult patients with PsO, PsA, and axSpA and that the rates did not increase with increasing IXE exposure.

Trial registration: The supplementary Table S1 provides a comprehensive list of clinical trials and their registration numbers.

Introduction: Tapinarof is a topical aryl hydrocarbon receptor (AhR) agonist in development for the treatment of atopic dermatitis (AD). In two phase 3 trials (ADORING 1 and 2), tapinarof cream 1% once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with AD. Here, we evaluate patient-reported outcomes (PROs), including family impact, with tapinarof in ADORING 1 and 2.

Methods: In ADORING 1 and 2, 813 patients were randomized to tapinarof or vehicle QD for 8 weeks. PROs were assessed using the Dermatology Life Quality Index (DLQI), Children's Dermatology Life Quality Index (CDLQI), Infants' Dermatitis Quality of Life Index (IDQOL), Dermatitis Family Impact Questionnaire (DFI), and Patient Oriented Eczema Measure (POEM).

Results: Mean baseline DLQI, CDLQI, IDQOL, and DFI scores indicated that the impact on families and patients' quality of life (QoL) of AD was moderate to very large. Mean POEM scores indicated moderate to severe AD symptoms at baseline. Tapinarof improved QoL versus vehicle across all endpoints at week 8: DLQI, - 6.2 vs - 3.5 (P = 0.0031) and - 5.5 vs - 3.5 (P = 0.0028); DFI, - 5.6 vs - 2.9 (P < 0.0001) and - 5.6 vs - 3.8 (P = 0.0037), in ADORING 1 and 2, respectively. Similar improvements in CDLQI and IDQOL were reported with tapinarof versus vehicle. Tapinarof also significantly improved CDLQI, DFI, and POEM sleep subdomain scores versus vehicle. POEM scores also improved with tapinarof versus vehicle: ≥ 12 years, - 9.4 vs - 5.3 and - 10.6 vs - 3.6 (both P < 0.0001); < 12 years, - 11.4 vs - 5.7 (P < 0.0001), and - 10.8 vs - 7.3 (P = 0.0005).

Conclusions: Tapinarof significantly improved QoL across PROs, including sleep and family impact, regardless of age, from week 1 (the earliest evaluation) through week 8. Tapinarof is a once-daily, non-steroidal cream that rapidly improves AD symptoms, sleep, and QoL in patients down to age 2 years with AD.

Trial registration: Clinical Trials.gov identifier: NCT05014568; NCT05032859.

Pemphigus vulgaris is a severe and often therapy-resistant bullous autoimmune disease. Standard therapy with steroids often administered together with another immunosuppressant does not respond in all patients or may not be a good therapeutic option in patients with severe underlying diseases. Intravenous immunoglobulins (IVIgs) represent a treatment alternative, often showing a rapid response which allows one to reduce concomitant immunosuppression. Here, we report on two patients with a complex disease history suffering from severe pemphigus vulgaris who received treatment with a new IVIg preparation (Yimmugo^®, 2 g per kg body weight every 4 weeks). IVIg preparations differ regarding manufacturing process and show a varying side effect profile. Both of our patients did not experience any side effects from IVIgs and showed a significant improvement of skin and mucosal erosions. More reports on IVIgs are desirable to help in selecting the optimal preparation and dosing regarding tolerability and effectiveness for individual patients.

Introduction: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the USA, brodalumab has a boxed warning regarding suicidal ideation and behavior and is only available under a Risk Evaluation and Mitigation Strategy, but no causal association has been established. To assess long-term safety of brodalumab, we summarize pharmacovigilance data from 6 years of real-world clinical practice.

Methods: Crude adverse event (AE) reporting rates per 100 patients were calculated for common AEs and AEs of special interest reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017 through August 14, 2023. Brodalumab exposure was estimated as time from the first to last prescription-dispensing authorization dates. Adverse events were defined by Medical Dictionary for Regulatory Activities v26.0 Preferred Terms and standardized MedDRA queries.

Results: Data were collected from 5138 US patients (estimated exposure of 6900 patient-years). Over 6 years, 13 cases of adjudicated major adverse cardiovascular events were reported (0.25 events/100 patients). The rate of serious infections was 2.20 events/100 patients. Since the 5-year report, there was one new case of Candida infection and a serious fungal infection of the elbow. Among 57 reported malignancies affecting 49 patients, 4 were deemed possibly related to brodalumab. One new case of indeterminate inflammatory bowel disease unrelated to brodalumab was reported. No new suicide attempts were reported in year 6, and there were no completed suicides throughout 6 years.

Conclusion: Pharmacovigilance data throughout 6 years are consistent with the safety profile of brodalumab established in clinical trials and previous US pharmacovigilance reports, with no completed suicides and a low fungal infection rate.