A comparison of the safety and efficacy of tapinarof and roflumilast topical therapies in the management of mild-to-moderate plaque psoriasis.

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles. MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment. RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed more frequent but mild adverse effects, while roflumilast had less frequent but more severe side effects. DISCUSSION: Tapinarof and roflumilast offer once-daily dosing and successful treatment in restricted areas, potentially enhancing patient adherence. Cost remains a limiting factor, necessitating future comparative studies to evaluate the efficacy, safety, and cost-effectiveness between the two drugs. CONCLUSION: Tapinarof and roflumilast present promising topical treatments for psoriasis, showing efficacy and manageable safety profiles. Further research is crucial to fully elucidate their comparative benefits and drawbacks in clinical practice.

Treatment burden and the perspectives of patients with psoriasis using topical treatments: results from a national survey of adults with psoriasis in the United States.

BACKGROUND: Topical treatments are the foundation for patients with psoriasis; however, adherence can be limited by patient preferences and treatment burden. METHODS: The Harris Poll conducted an online survey of US patients with psoriasis who use prescription topical therapy to examine their preferences and perspectives on topical treatments. RESULTS: Among patients with psoriasis who use topical treatment (n = 507), most participants described their psoriasis symptoms as mild (31%) or moderate (59%). The body areas most often reported to be affected by psoriasis were the scalp, elbows, legs, intertriginous areas, arms, and knees. Participants reported psoriasis affecting the scalp (39%), elbows (20%), and legs (excluding knees; 19%) caused the greatest impact on quality of life. Most participants (76%) preferred topical therapies to treat their psoriasis, while 20% preferred pills, and 4% preferred injections. The most common product attributes that participants wanted in a topical psoriasis treatment and that would help them to continue to use the treatment were: improvement in plaques (68%), itch relief (68%), and easy to apply (63%). CONCLUSION: The respondents to this survey reported that they prefer topical treatments to pills or injections (76%) and most (89%) reported they are interested in trying a new topical treatment.

Unveiling the science behind erectile dysfunction topical therapy: investigating transdermal papaverine as a novel treatment approach.

INTRODUCTION: Erectile dysfunction is among the most prevalent urologic issues affecting men globally and is characterized by a high incidence rate. This condition significantly affects the quality of life of patients and their sexual partners. OBJECTIVES: Due to the interactions, contraindications, and side effects associated with systemic drugs, recent research has increasingly focused on topical and transdermal medications for the treatment of erectile dysfunction. METHODS: Based on previous studies, this article examines papaverine in terms of local effectiveness, methods of increasing therapeutic efficiency, possible local side effects, and evaluation of its various formulations. RESULTS: Among these approaches, notable strategies include using novel formulations and nanoformulations as compared with classic ones, employing permeation enhancers, and combining treatments with other oral and topical drugs with synergistic mechanisms. These methods aim to improve transdermal papaverine's bioavailability and therapeutic efficacy while minimizing side effects and enhancing patient compliance. CONCLUSION: Transdermal papaverine may not be as effective as its injectable form, but the treatment path is more pleasant, with less pain and fewer side effects for patients. For this reason, using solutions that remove the penile skin and fascial absorption barrier can be very effective.

Nano-based formulations of thymoquinone are new approaches for psoriasis treatment: a literature review.

Psoriasis, a persistent immune-mediated inflammatory skin condition, affects approximately 2-3% of the global population. Current treatments for psoriasis are fraught with limitations, including adverse effects, high costs, and diminishing efficacy over time. Thymoquinone (TQ), derived from Nigella sativa seeds, exhibits promising anti-inflammatory, antioxidant, and immunomodulatory properties that could prove beneficial in managing psoriasis. However, TQ's hydrophobic nature and poor bioavailability have hindered its usefulness as a therapeutic agent. Recent research has strategically addressed these challenges by developing nano-thymoquinone (nano-TQ) formulations to enhance delivery and efficacy in treating psoriasis. Preclinical studies employing mouse models have demonstrated that nano-TQ effectively mitigates inflammation, erythema, scaling, epidermal thickness, and cytokine levels in psoriatic lesions. Various nano-TQ formulations, including nanoemulsions, lipid vesicles, nanostructured lipid carriers, and ethosomes, have been explored to improve solubility, facilitate skin penetration, ensure sustained release, and achieve site-specific targeting. Although clinical trials are currently scarce, the outcomes from in vitro and animal models are promising. The potential co-delivery of nano-TQ with other anti-psoriatic agents also presents avenues for further investigation.

Frequency of Topical Immunomodulatory and Immunosuppressive Therapies for Ocular Chronic Graft-versus-Host Disease.

Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We included 95 adult patients (48 male, 47 female) with ocular chronic graft-versus-host disease (cGVHD) after alloHSCT (median age 49.5 years). Clinical ophthalmological findings and the grade of ocular cGVHD according to the NIH eye score and the German-Austrian-Swiss Consensus (GAS) Grading were analyzed. Systemic GVHD manifestations as well as the prevalence of topical and systemic (immunomodulatory) therapies were assessed. Results: A total of 74 of 95 patients (77.8%) had manifestations of systemic chronic graft-versus-host disease other than ocular GVHD. 68.42% (65/95) of patients were under systemic immunosuppressive therapy with at least one immunosuppressive medication. All patients (95/95) received lid-margin hygiene and phosphate- and preservative-free lubricating eye drops. Twenty-five percent of the cohort (24/95) were treated with autologous serum eye drops (ASEDs). In total, 80% (76/95) of patients required topical steroid therapy to treat acute exacerbation of inflammation at least once; continuous topical steroid therapy was only necessary for a minor part (12%) with refractory chronic inflammation. A total of 92.63% (88/95) were primarily treated with ciclosporin A 0.1% as Ikervis®, of whom at least one third did not continue the therapy because of intolerable side effects during follow-up and received alternative topical formulations. Conclusions: Our data show that patients with ocular cGVHD mostly need topical therapy including anti-inflammatory agents despite systemic immunosuppressive therapy. In our cohort, 80% of patients received topical steroids, and more than 90% received topical ciclosporin A eye drops, which were tolerated by only two thirds of patients due to side effects.

Local Therapy and Reconstruction in Penile Cancer: A Review.

Local therapy for penile cancer provides robust survival and can preserve the penis functionally and cosmetically. Interventions must target the appropriate clinical stage. We reviewed studies regarding the primary therapy in penile cancer, from topical therapy to radical penectomy, and reconstructive techniques. Topical therapy (5-FU or Imiquimod) provides a robust oncologic response in patients with Ta or Tis disease. Multiple laser therapies are available for localized patients and those with low-grade T1 disease. There is a non-trivial risk of progression and nodal metastases in poorly selected patients. Wide local excision provides an oncologically sound option in patient with up to T1 disease; less evidence exists for Mohs microsurgery in the setting of penile cancer. Increasingly aggressive approaches include glansectomy and partial/radical penectomy, which provide 5- and 10-year cancer-specific survival rates of over 80%. Meticulous reconstruction is necessary for the durable function of the remaining penis. Preservation of voiding and sexual function occurs via penile skin grafting, glans resurfacing, creation of a functional penile stump, and phalloplasty with a penile implant. Perineal urethrostomy provides an alternative in pathology demanding extensive partial or radical penectomy, and a durable option for seated voiding. Clinical suspicion and timely diagnosis are paramount in terms of management as less-invasive options for earlier-stage disease develop.

[Mycosis caused by Nannizzia incurvata in a traveler returning from Indonesia]. / Mykose durch Nannizzia incurvata bei einem Reiserückkehrer aus Indonesien.

Nannizzia incurvata is a geophilic dermatophyte that is rarely detected in Germany. We report on a 17-year-old traveler returning from Indonesia in whom Nannizzia incurvata was isolated as the causative agent of tinea corporis. Targeted, local antimycotic therapy and clinical follow-up was recommended. This report shows the importance of a detailed travel history and targeted mycological diagnostic workup.

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.

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.

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.

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.

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.

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.

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.

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.

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.