Adult Female Acne: Managing the Hormones.

Acne is a common inflammatory condition of the skin worldwide. The skin is an endocrine organ and hormones are a key pathogenic factor in all types of acne with a particularly important role in adult female acne pathogenesis and management. In females, we have the unique opportunity to manipulate hormones systemically to successfully manage acne and, more recently with the approval of clascoterone 1% cream, we can target the hormones topically in both genders. The intent of this paper is to provide physicians with an up-to-date clinically relevant review of the role of hormones in acne, the impact of currently available contraceptives and therapies available to target hormones in acne.

The UPDATE trial (UVB Phototherapy in Dermatology for ATopic Eczema): study protocol for a randomized controlled trial of narrowband UVB with optimal topical therapy versus optimal topical therapy in patients with atopic eczema.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is commonly prescribed for patients with moderate-to-severe atopic eczema (AE). The efficacy of NB-UVB, however, has not yet properly been established, as current evidence is of low certainty. Our aim is to assess the short-term and long-term (cost-)effectiveness and safety of NB-UVB in adult AE patients by performing a pragmatic, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial. This protocol outlines its methodology. METHODS: A pragmatic, multicenter, PROBE trial will be performed with 1:1 randomization of 316 adult patients with moderate-to-severe AE who have inadequate disease control with topical therapy and who are eligible for optimal topical therapy (OTT) or NB-UVB in combination with OTT as a next step. Participants in the interventional arm will receive a minimum of 3 months of OTT combined with 8 to 16 weeks of NB-UVB. The control group receives 3 months of OTT. Following the interventional phase, follow-up will continue for 9 months. Physician-reported and patient-reported outcomes (according to the Harmonising Outcome Measures for Eczema (HOME) Core Outcome Set) and adverse events are assessed at 4 weeks, 3, 6, 9, and 12 months. DISCUSSION: The UPDATE trial aims to provide high-quality evidence regarding the (cost-)effectiveness and safety of NB-UVB phototherapy in moderate-to-severe AE patients. Challenges that are addressed in the protocol include the possible bias arising from applying open-label treatment and the necessity of introducing OTT into the study design to prevent a high dropout rate. TRIAL REGISTRATION: ClinicalTrials.gov NCT05704205. Registered on December 8, 2022.

A methodological pipeline for the preclinical evaluation of novel topical agents for the treatment of CRS.

KEY POINTS: Novel topical therapeutics require extensive pre-clinical testing to assess efficacy and safety. Antibiofilm or immunosuppressant agents can utilize ex vivo models to measure ciliotoxicity. Agents that are found to be effective and non-toxic ex vivo warrant further investigation in vivo.

Canadian Expert Consensus on the Use of Halobetasol Propionate/Tazarotene Lotion for Plaque Psoriasis.

INTRODUCTION: An expert panel of Canadian dermatologists was assembled to develop consensus statements regarding the current landscape of topical therapies for plaque psoriasis and the place in therapy of the recently approved fixed-dose combination halobetasol propionate (HP)/tazarotene (TAZ) lotion (HP/TAZ) in the treatment algorithm for plaque psoriasis. METHOD: A modified nominal group technique, which combined both independent and group input from the expert panel, was used to develop the consensus statements. The expert panel completed surveys to elicit their independent views on the current landscape of topical therapies for plaque psoriasis in Canada. The first expert panel session was held to discuss the existing body of literature and develop draft consensus statements about topical therapies and the place in therapy of HP/TAZ. Independent feedback on the draft consensus statements was solicited from expert panel members prior to another expert panel session where the amended consensus statements were further discussed, edited and, finally, voted on. RESULTS: The expert panel reached consensus on 20 statements. CONCLUSION: Expert panel members agreed, based on the existing body of literature, that there is a place in therapy for HP/TAZ to address several current unmet treatment needs of patients with plaque psoriasis. Studies have shown that HP/TAZ is an effective and safe first-line treatment for moderate-to-severe plaque psoriasis. Due to its cosmetically pleasing vehicle and once-daily administration, HP/TAZ may improve patient acceptance and treatment adherence.

Patient Perspectives on the Prevalence and Burden of Intertriginous Psoriasis: Results from a National Survey of Adults with Psoriasis in the United States.

INTRODUCTION: A survey was conducted by The Harris Poll on behalf of Arcutis Biotherapeutics in the USA to understand perspectives and burden of patients with psoriasis using prescription topical treatments for their disease. This manuscript presents results from the subset of patients with intertriginous psoriasis. METHODS: The survey was conducted online October 21-November 24, 2021, among 507 US adults aged 18+ years with psoriasis diagnosed by a healthcare provider and currently using prescription topical treatment. Participants with intertriginous psoriasis were patients with plaque psoriasis reporting symptoms in the armpit, groin, under breast, stomach fold, or between the buttocks. RESULTS: Of the 507 respondents, 320 (64%) reported symptoms in intertriginous areas at some point, typically between the buttocks (31%). Most patients with intertriginous psoriasis reported it made them feel embarrassed (80%), anxious (79%), or depressed (69%). In addition, 45% of these patients reported intertriginous psoriasis caused a negative impact on sexual anxiety or distress. Quality of life impact was reported as "very strong negative impact" in 16% of patients with groin involvement vs. 6% in patients with no groin involvement and 15% in women vs. 6% in men. Patients with intertriginous psoriasis reported that itch (61%), scaling (53%), redness (49%), and skin cracking (46%) related to intertriginous psoriasis had the greatest negative impact on quality of life. Most (86%) of these patients said they would be more adherent if a single treatment option could be used to treat all affected areas of their body. CONCLUSION: Psoriasis involvement in intertriginous areas over the course of disease is common and has a negative impact on these patients' quality of life, particularly emotional well-being and sexual health.

Safety and adherence to self-administered intravaginal 5-fluorouracil cream following cervical intraepithelial neoplasia (CIN) 2/3 treatment among HIV-positive women in Kenya: A phase 1 clinical trial.

Objective: To determine the safety, tolerance, and adherence to self-administered intravaginal 5% fluorouracil (5FU) cream as adjuvant therapy following cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) treatment among women living with HIV (WLWH) in Kenya. Methods: A Phase I Pilot trial was performed among 12 WLWH in Kenya, aged 18-49 years between March 2023-February 2024 (ClinicalTrial.gov NCT05362955). Participants self-administered 2g of 5FU intravaginally every other week for eight applications. Safety was assessed using a standardized grading scale, and adherence was evaluated using self-report, inspection of used applicators, and weighing of the study drug. Results: The mean age and CD4 count were 43.9 years and 781 cells/mm3, respectively. Seven (58%) had an 8th-grade education or less. All 12 reported at least one grade I adverse event (AE), 1 (8%) reported a grade 2 AE, no grade 3 or 4 AEs were reported. Increased vaginal discharge (n=9, 75%) and irritation (n=5, 42%), with a mean duration of 3.2 and 2.8 days, respectively, were the most commonly reported AEs. Provider-observed AEs included grade 1 cervical erythema and superficial abrasions. All participants tolerated all eight 5FU doses, and 96% adherence was demonstrated. Conclusion: Self-administered 5FU following CIN2/3 treatment among WLWH in Kisumu, Kenya, was safe, tolerable, and associated with high adherence. Randomized trials are needed to investigate whether adjuvant 5FU can improve treatment outcomes or serve as primary cervical precancer treatment in sub-Saharan Africa. A self-administered therapy may be transformative in increasing access to treatment and, hence, secondary prevention of cervical cancer.

Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials.

BACKGROUND: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. OBJECTIVE: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD). METHODS: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials. RESULTS: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle. LIMITATIONS: Long-term efficacy was not assessed. CONCLUSION: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.

Atopic Dermatitis.

Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often located over the flexural surfaces. Treatment goals of AD include the reduction of itching and burning, as well as the reduction of skin changes. Treatment of AD includes emollients and skin care, topical therapies including topical corticosteroids and steroid-sparing therapies, systemic therapies, and phototherapy.

Diagnose und Therapie aktinischer Keratosen: Diagnosis and therapy of actinic keratosis.

Actinic keratosis (AK) is considered a chronic and recurring in situ skin neoplasia, with a possible transformation into invasive squamous cell carcinoma (SCC). Among others, predominant risk factors for development of AK are UV-light exposure and immunosuppression. Basal epidermal keratinocyte atypia (AK I) and proliferation (PRO Score) seem to drive malignant turnover, rather than clinical appearance of AK (Olsen I-III). Due to the invasiveness of punch biopsy, those histological criteria are not regularly assessed. Non-invasive imaging techniques, such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM) and line-field confocal OCT (LC-OCT) are helpful to distinguish complex cases of AK, Bowen's disease and SCC. Moreover, LC-OCT can visualize the epidermis and the papillary dermis at cellular resolution, allowing real-time PRO Score assessment. The decision-making for implementation of therapy is still based on clinical risk factors, ranging from lesion- to field-targeted and ablative to non-ablative regimes, but in approximately 85% of the cases a recurrence of AK can be observed after a 1-year follow-up. The possible beneficial use of imaging techniques for a non-invasive follow-up of AK to detect recurrence or invasive progression early on should be subject to critical evaluation in further studies.

Improved Treatment Outcome Following the Use of a Wound Dressings in Cutaneous Leishmaniasis Lesions.

Leishmaniasis, caused by Leishmania parasites, is a neglected tropical disease and Cutaneous Leishmaniasis (CL) is the most common form. Despite the associated toxicity and adverse effects, Meglumine antimoniate (MA) remains the first-choice treatment for CL in Brazil, pressing the need for the development of better alternatives. Bacterial NanoCellulose (BNC), a biocompatible nanomaterial, has unique properties regarding wound healing. In a previous study, we showed that use of topical BNC + systemic MA significantly increased the cure rate of CL patients, compared to treatment with MA alone. Herein, we performed a study comparing the combination of a wound dressing (BNC or placebo) plus systemic MA versus systemic MA alone, in CL caused by Leishmania braziliensis. We show that patients treated with the combination treatment (BNC or placebo) + MA showed improved cure rates and decreased need for rescue treatment, although differences compared to controls (systemic MA alone) were not significant. However, the overall time-to-cure was significantly lower in groups treated with the combination treatment (BNC+ systemic MA or placebo + systemic MA) in comparison to controls (MA alone), indicating that the use of a wound dressing improves CL treatment outcome. Assessment of the immune response in peripheral blood showed an overall downmodulation in the inflammatory landscape and a significant decrease in the production of IL-1a (p < 0.05) in patients treated with topical BNC + systemic MA. Our results show that the application of wound dressings to CL lesions can improve chemotherapy outcome in CL caused by L. braziliensis.

Practical considerations relevant to treatment with the gene therapy beremagene geperpavec-svdt for dystrophic epidermolysis bullosa.

BACKGROUND/PURPOSE: Dystrophic epidermolysis bullosa (DEB), a rare genetic skin disease caused by loss-of-function mutations in COL7A1, the gene encoding type VII collagen (COL7), is characterized by skin blistering, scarring, and extracutaneous manifestations that markedly reduce patient quality-of-life. Beremagene geperpavec-svdt ('B-VEC') is a gene therapy employing a non-integrating, replication-defective herpes simplex virus type 1 (HSV-1)-based vector encoding two copies of full-length human COL7A1 to restore COL7 protein after topical administration to DEB wounds. B-VEC was approved in the United States in 2023 as the first topical gene therapy and the first approved treatment for DEB. However, few providers have experience with use of this gene therapy. METHODS: Data was obtained through literature review and the experience of providers who participated in the B-VEC clinical study or initiated treatment after B-VEC approval. RESULTS: This review discusses the burden of disease, describes the clinical trial outcomes of B-VEC, and provides physician and patient/caregiver recommendations as a practical guide for the real-world use of B-VEC, which can be administered in-office or at the patient's home. CONCLUSIONS: By continuing to optimize the practical aspects of B-VEC administration, the focus will continue to shift to patient-centric considerations and improved patient outcomes.

Scoping review of nonsurgical treatment options for macular holes.

Macular holes (MH) are full-thickness retinal defects affecting central vision. While vitrectomy with inner limiting membrane (ILM) peel is the conventional MH treatment, non-surgical alternatives are gaining interest to mitigate surgical risks. This study conducted a comprehensive literature review and analysis of nonsurgical MH management. A systematic literature search was conducted on PubMed, Embase, Scopus, and the Cochrane Library from January 1, 1973, to September 13, 2023. Treatments included laser therapy, carbonic anhydrase inhibitors (CAIs), nonsteroidal antiinflammatory drugs (NSAIDs), steroids (topical, subtenons, peribulbar, intravitreal), intravitreal gas, anti-vascular endothelial growth factors and ocriplasmin injections. Data extraction covered study details, patient characteristics, MH features, treatment outcomes, and recurrence rates. The initial search yielded 3352 articles, refined to 83 articles that met inclusion criteria following screening. Overall reported anatomical closure rates were 36% with laser photocoagulation, 37% with intravitreal ocriplasmin, 55% with intravitreal gas. Closures were more frequently observed with topical NSAIDs (79%), steroids (84%) and CAIs (73%). Closures were more often observed in patients with smaller MH and in the presence of cystic macular oedema. Although non-surgical MH management approaches show potential for conservative therapy, evidence is limited to support routine use. Stage 1 and traumatic MH may benefit from a short period of observation, but the gold standard approach for full-thickness MH remains to be vitrectomy with ILM peel.

Phacomatosis pigmentokeratotica: Exploring extracutaneous comorbidities and topical therapy.

Phacomatosis pigmentokeratotica (PPK) is a RASopathy characterized by the presence of a sebaceous nevus and a papular speckled lentiginous nevus. This case report highlights the associated extracutaneous comorbidities, including life-threatening arrhythmia, and introduces topical rapamycin as a potential therapeutic avenue for sebaceous nevus in PPK patients.

Topical Treatments in Atopic Dermatitis: An Expansive Review.

Atopic dermatitis (AD) is a common inflammatory skin condition found worldwide. It impacts patient quality of life (QoL) and is thought to arise as an inflammatory response to epidermal barrier dysfunction and hypersensitivity. AD can lead to large out-of-pocket costs and increased healthcare expenses over a lifetime. An analysis of all randomized control trials conducted since 1990 on topical therapies for AD were reviewed, including 207 trials in the final analysis. It was found that an average of 226 patients were enrolled over 2.43 arms. Common topical treatments included corticosteroids, calcineurin inhibitors, JAK inhibitors, and phosphodiesterase inhibitors. The most utilized tools to identify treatment efficacy were the EASI, IGA, SCORAD, and PGA. There was a paucity of data on trials that evaluated efficacy, QoL, and cost of treatment simultaneously. This review highlights the need for comprehensive trials that evaluate multiple aspects of treatment, including financial cost and QoL impact, to ensure each patient has the best treatment modality for the management of their AD.

Burden of impaired sleep and its improvement through topical treatment in psoriasis and atopic dermatitis.

INTRODUCTION: Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking. PATIENTS AND METHODS: Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2 weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy. RESULTS: 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2 weeks (p < 0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r > 0.50, p < 0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r > 0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI. CONCLUSIONS: Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2 weeks of topical treatment.

Therapeutic Targets in the Management of Dry Eye Disease Associated with Sjögren's Syndrome: An Updated Review of Current Insights and Future Perspectives.

Dry eye disease (DED) is a continuing medical challenge, further worsened in the autoimmune inflammatory hyperactivation milieu of Sjögren's syndrome (SS) due to disturbances to innate and adaptive immunity with malfunctioning neuro-endocrine control. However, the pathogenetic mechanisms of SS DED are not fully established. This review summarized the available evidence, from systematic reviews, meta-analyses, and randomized clinical trials, for the efficacy and safety of the available ocular therapeutics for the management of SS DED. Relevant studies were obtained from major databases using appropriate keywords. The available largely empirical symptomatic, supportive, and restorative treatments have significant limitations as they do not alter local and systemic disease progression. Topical therapies have expanded to include biologics, surgical approaches, scleral lens fitting, the management of lid margin disease, systemic treatments, nutritional support, and the transplantation of stem cells. They are not curative, as they cannot permanently restore the ocular surface's homeostasis. These approaches are efficacious in the short term in most studies, with more significant variability in outcome measures among studies in the long term. This review offers an interdisciplinary perspective that enriches our understanding of SS DED. This updated review addresses current knowledge gaps and identifies promising areas for future research to overcome this medical challenge.

Antifungal Selection for the Treatment of Onychomycosis: Patient Considerations and Outcomes.

Onychomycosis, a common fungal nail infection, affects >20% of adults over age 60 and >50% of people over age 70. Onychomycosis may cause pain, psychosocial problems, and secondary infections, therefore meriting treatment. This review describes the range of treatment modalities, including FDA-approved systemic drugs and topical therapies. Additionally, new and emerging oral and topical therapies are discussed. We emphasize the importance of tailoring onychomycosis therapy to individual patient characteristics, comorbidities, preferences, extent of nail involvement, and fungal species, such that physicians may optimize treatment outcomes, patient satisfaction, and safety.

Diagnosis and therapy of actinic keratosis.

Actinic keratosis (AK) is considered a chronic and recurring in situ skin neoplasia, with a possible transformation into invasive squamous cell carcinoma (SCC). Among others, predominant risk factors for development of AK are UV-light exposure and immunosuppression. Basal epidermal keratinocyte atypia (AK I) and proliferation (PRO score) seem to drive malignant transformation, rather than clinical appearance of AK (Olsen I-III). Due to the invasiveness of punch biopsy, those histological criteria are not regularly assessed. Non-invasive imaging techniques, such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM) and line-field confocal OCT (LC-OCT) are helpful to distinguish complex cases of AK, Bowen's disease, and SCC. Moreover, LC-OCT can visualize the epidermis and the papillary dermis at cellular resolution, allowing real-time PRO score assessment. The decision-making for implementation of therapy is still based on clinical risk factors, ranging from lesion- to field-targeted and ablative to non-ablative regimens, but in approximately 85% of the cases a recurrence of AK can be observed after a 1-year follow-up. The possible beneficial use of imaging techniques for a non-invasive follow-up of AK to detect recurrence or invasive progression early on should be subject to critical evaluation in further studies.

Survey of European Blood and Marrow Transplant (EBMT) nurses to explore the current topical skin management of chronic cutaneous graft versus host disease in the real-world clinical environment.

PURPOSE: To understand the current practice in relation to the management of topical therapy for cutaneous chronic Graft versus Host Disease (ccGvHD) and access to extracorporeal photopheresis (ECP) within European allogeneic haematopoietic cell transplantation centres by a survey of nurses. METHOD: This was a multicentre cross-national study at eligible European Blood and Marrow Transplant centres. Eligibility required more than 30% of treated patients having allogeneic haematopoietic cell transplant. Centres performing only autologous stem cell transplants were excluded from the study. RESULTS: 12% of respondents were unaware of whether their centre had a policy or not for monitoring chronic cutaneous graft versus host disease. Over half had the affiliation of a dermatologist for referral, but only 19% had access to a specialist nurse. Patient education was routinely provided in most of the centres (86%). Results suggested as the severity of a patient's chronic cutaneous graft versus host disease increased, there was a reduction in the amount of topical emollients and steroids employed. Following topical therapies, systemic treatments, and other modalities such as ECP were employed with less focus directed towards topical care. CONCLUSIONS: Topical treatment is the backbone of any treatment paradigm for chronic cutaneous graft versus host disease, however, there is no universally agreed algorithm. Improved skin care may lead to a reduction in the amount of systemic therapy required, thus increasing patients' quality of life. There is little standardisation in the topical management of chronic cutaneous graft versus host disease, despite skin being the most cited organ affected by chronic graft versus host disease, this should be addressed.

Double blind randomized controlled trial measuring the efficacy of nebulized steroid at half dose in comparison to high volume squeeze bottle steroid irrigation in management of patients with chronic rhinosinusitis.

KEY POINTS: Nebulized budesonide is effective at half dose compared to budesonide irrigation in CRS. Nasal nebulizers provide an alternative for delivery of topical steroids to the sinuses.