An HIV-positive man with painless ulcer and pustules: mpox, syphilis, or both?

Mpox (formerly monkeypox) is a viral illness endemic in certain parts of the world such as Africa. Travel to these endemic areas has increased outbreaks in regions typically unaffected by this poxvirus. Mpox infection is characterized by prodromal symptoms including fever, chills, and lymphadenopathy, followed by a vesiculopustular exanthem. Genital lesions are common especially in vulnerable populations, such as those who engage in high-risk sexual behaviors. We report a 50-year-old man living with HIV who presented for evaluation of multiple painless genital lesions and later tested positive for both mpox and syphilis. With recent outbreaks, clinicians should evaluate genital lesions with a broad sexually transmitted infection differential. Rapid diagnosis and treatment are imperative to prevent more severe disease progression in immunocompromised patients.

Tapinarof cream 1% once daily for the treatment of plaque psoriasis: Patient-reported outcomes from the PSOARING 3 trial.

BACKGROUND: Tapinarof cream 1% once daily demonstrated significant efficacy versus vehicle and was well tolerated in two 12-week, phase 3 pivotal trials in adults with mild-to-severe plaque psoriasis. OBJECTIVE: To assess long-term, health-related quality of life and patient satisfaction with tapinarof. METHODS: Patients completing the 12-week trials were eligible for 40 weeks of open-label tapinarof based on Physician Global Assessment score in PSOARING 3, with a 4-week follow-up. Dermatology Life Quality Index was assessed at every visit; Patient Satisfaction Questionnaire responses were assessed at week 40 or early termination. RESULTS: Seven hundred sixty-three (91.6%) eligible patients enrolled; 78.5% completed the Patient Satisfaction Questionnaire. DLQI scores improved and were maintained. By week 40, 68.0% of patients had a DLQI of 0 or 1, indicating no impact of psoriasis on health-related quality of life. Most patients strongly agreed or agreed with all Patient Satisfaction Questionnaire questions assessing confidence in tapinarof and satisfaction with efficacy (62.9%-85.8%), application ease and cosmetic elegance (79.9%-96.3%), and preference for tapinarof versus prior psoriasis therapies (55.3%-81.7%). LIMITATIONS: Open-label; no control; may not be generalizable to all forms of psoriasis. CONCLUSIONS: Continued and durable improvements in health-related quality of life, high rates of patient satisfaction, and positive perceptions of tapinarof cream were demonstrated.

A Post Hoc Analysis of Efficacy Data on Sarecycline in Hispanics with Acne from Two Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trials.

Sarecycline is a novel, narrow-spectrum, third generation tetracycline class antibiotic approved by the Food and Drug Administration (FDA) for the treatment of moderate-to-severe acne in patients ages nine and older. Recently, focus has increased on whether treatment responses differ in acne in skin of color. Here, we aimed to analyze the efficacy of using sarecycline in Hispanics. We report pooled post hoc analysis of efficacy data on sarecycline in Hispanics with acne from two phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trials, SC1401 and SC1402. Of 2002 patients in the pooled trials with moderate-to-severe acne, 26.9% were Hispanic. Facial inflammatory lesion counts decreased as early as week 3 by 26% (p = 0.0279), with continued reduction by 41% by week 6 (p = 0.0003), by 51% by week 9 (p < 0.0001), and by 55% by week 12 (p < 0.0001). Acne is the most common skin condition diagnosed in Hispanics, and this study illustrates a statistically significant reduction in acne in Hispanic patients with moderate-to-severe acne treated with oral sarecycline. Therefore, oral sarecycline shows promising results as a safe and effective treatment for acne in Hispanics.

Effect of Sarecycline on the Acne Symptom and Impact Scale and Concerns in Moderate-to-Severe Truncal Acne in Open-Label Pilot Study.

Truncal acne is common, and the psychosocial burden may be underestimated as patients most often complain of facial acne. The Acne Symptom and Impact Scale (ASIS) is a 17-item patient-reported outcome (PRO) measure designed to assess the signs and impacts of acne vulgaris. ASIS has previously been validated in a prospective, non-interventional study as a reliable PRO instrument for facial acne. In a pilot study, ASIS, and an additional 10 new questions that focused on the concerns of patients (ASIS-C), were given to 10 patients with moderate-to-severe truncal acne vulgaris who received 3 months of monotherapy with oral sarecycline, a narrow-spectrum tetracycline-class antibiotic. ASIS-C questionnaires were also given to 10 acne-free control subjects. Average ASIS-C answers decreased by 4% for Signs, 15% for Impact, and 16% for Concerns in the 10 patients, with greater decreases of 5% for Signs, 20% for Impact, and 19% for Concerns in the 60% of patients whose truncal acne was clear or almost clear after 12 weeks of sarecycline treatment. In this study, sarecycline was effective in reducing the psychosocial burden associated with truncal acne based on the ASIS-C PRO measures.

Once-daily Dapsone 7.5% Gel for the Treatment of Acne Vulgaris in Preadolescent Patients: A Phase IV, Open-label, 12-week Study.

CLINICAL TRIALS ID: NCT02959970 BACKGROUND: Acne vulgaris in patients aged younger than 12 years is increasingly common and primarily noninflammatory (i.e., comedonal). Dapsone 7.5% gel is indicated for the topical treatment of acne vulgaris in patients nine years of age or older. OBJECTIVE: We sought to evaluate efficacy, safety, tolerability, and pharmacokinetics (PK) of once-daily topical dapsone 7.5% gel. METHODS: This was a Phase IV, multicenter, open-label study in patients with acne aged 9 to 11 years. Patients applied dapsone 7.5% gel once daily to the face and acne-affected areas on the upper chest, upper back, and shoulders for 12 weeks. Patients in the PK cohort applied dapsone 7.5% gel under maximal-use conditions for eight days and a thin layer for the remaining 11 weeks. Lesion counts and proportions of patients with an Investigator's Global Assessment score of zero points (clear) or one point (almost clear) were assessed. Plasma concentrations of dapsone and metabolites were evaluated after one week in the PK cohort. Safety and dermal tolerability were evaluated. RESULTS: After 12 weeks, facial acne was clear or almost clear in about 47 percent of patients. Inflammatory, noninflammatory, and total lesions decreased from baseline, with a greater reduction apparent in noninflammatory lesions. Systemic exposure to dapsone in PK patients was low. The overall rate of adverse events was low, and dermal tolerability scores indicated no or mild stinging/burning, dryness, scaling, and erythema. CONCLUSION: Once-daily topical dapsone 7.5% gel used for 12 weeks was safe, effective, and well tolerated in preadolescent patients with acne.

Tolerability of Photodynamic Therapy Using 10% 5-Aminolevulinic Acid Hydrochloride Gel for Treating Actinic Keratoses on Surface Areas Larger than 75cm2.

BACKGROUND: Photodynamic therapy (PDT) is a well-known treatment modality for actinic keratosis (AK). The largest surface area approved by the FDA is 20cm2 with 10% 5-aminolevulinic acid hydrochloride gel (10% ALA gel). OBJECTIVE: This retrospective study assessed the tolerability of PDT with 10% ALA gel in areas ranging from 75cm2 to 300cm2. METHODS: The medical records of 203 patients with AKs treated with 376 PDT sessions using 10% ALA gel were reviewed. Face and ears were incubated with 10% ALA gel for 60 minutes without occlusion while all other areas were incubated for 90 minutes with plastic wrap occlusion followed by 10J/cm2 blue light. Patients were given specific post-PDT care directions. Patient outcomes data was collected. RESULTS: Skin irritation was reported in 27 (7%) PDT sessions in 25 patients (12%). These occurred primarily on the face (n=17), hands (n=4,) and scalp (n=3). Of the 349 PDT treatments (93%) without irritation, these subjects reported adherence to a specific post-PDT regimen using zinc oxide and healing creams for 48 hours. LIMITATIONS: This was a retrospective study observing safety and tolerability. Clearance data was not collected. CONCLUSION: Based on this retrospective observational case series, PDT with ALA gel appears to be safe for treating patients with AKs covering surface areas 75 to 300cm2. Irritation might be mitigated by post-PDT care regimens.

Sarecycline: A Review of Preclinical and Clinical Evidence.

Sarecycline is a tetracycline-derived oral antibiotic, specifically designed for acne, and is approved by the Food and Drug Administration (FDA) in 2018 for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris (AV) in patients 9 years of age and older. It has been decades since a novel systemic antibiotic was approved to treat AV, a disease that affects up to 90% of teenagers and young adults worldwide and lasts well into adulthood. Sarecycline holds promise to yield fewer side effects than other commonly used broad-spectrum tetracyclines, including minocycline and doxycycline. The narrower spectrum of antibacterial activity of sarecycline, which specifically targets C. acnes and some Gram-positive bacteria with little or no activity against Gram-negative bacteria, suggests not only the potential for reduced emergence of antibiotic-resistant bacterial strains but also less disruption of the human gut microflora. Here, we review the key preclinical and clinical evidence on sarecycline.

Sarecycline: a narrow spectrum tetracycline for the treatment of moderate-to-severe acne vulgaris.

Sarecycline is a novel, narrow-spectrum, once-daily tetracycline-derived oral antibiotic that is FDA-approved in the US to be taken with or without food for moderate-to-severe acne vulgaris for ages 9 years of age and older. Sarecycline possesses anti-inflammatory properties and potent activity against Gram-positive bacteria, including activity against multiple strains of Cutibacterium acnes, while exhibiting minimal activity against enteric aerobic Gram-negative bacteria. Unlike many acne studies, sarecycline was investigated for chest and back acne. Significant reduction in inflammatory lesions was seen at week 12 at 1.5 mg/kg/day of sarecycline, with statistically significant improvement seen as early as week 3. No reports of phototoxicity, dizziness, pseudotumor cerebri or lupus but 1.2% nausea and 1.2% vaginal candidiasis was reported in the pivotal Phase III studies.

FV-100 versus valacyclovir for the prevention of post-herpetic neuralgia and the treatment of acute herpes zoster-associated pain: A randomized-controlled trial.

This prospective, parallel-group, randomized, double-blind, multicenter study compared the efficacy and safety of FV-100 with valacyclovir for reducing pain associated with acute herpes zoster (HZ). Patients, ≥50 years of age, diagnosed with HZ within 72 h of lesion appearance who had HZ-associated pain, were randomized 1:1:1 to a 7-day course of either FV-100 200 mg QD (n = 117), FV-100 400 mg QD (n = 116), or valacyclovir 1000 mg TID (n =117). Efficacy was evaluated on the basis of the burden of illness (BOI; Zoster Brief Pain Inventory scores); incidence and duration of clinically significant pain (CSP); pain scores; incidence and severity of post-herpetic neuralgia (PHN); and times to full lesion crusting and to lesion healing. Safety was evaluated on the basis of adverse event (AE)/SAE profiles, changes in laboratory and vital signs values, and results of electrocardiograms. The burden of illness scores for pain through 30 days were 114.5, 110.3, and 118.0 for FV-100 200 mg, FV-100 400 mg, and valacyclovir 3000 mg, respectively. The incidences of PHN at 90 days for FV-100 200 mg, FV-100 400 mg, and valacyclovir 3000 mg were 17.8%, 12.4%, and 20.2%, respectively. Adverse event and SAE profiles of the two FV-100 and the valacyclovir groups were similar and no untoward signals or trends were evident. These results demonstrate a potential for FV-100 as an antiviral for the treatment of shingles that could both reduce the pain burden of the acute episode and reduce the incidence of PHN compared with available treatments.

Brimonidine tartrate for the treatment of facial flushing and erythema in rosacea.

Rosacea is a chronic inflammatory dermatologic condition that can often be disfiguring with significant negative impact on patients' quality of life. Sanrosa (brimonidine tartate) is a novel therapeutic agent targeting the facial flushing and erythema of rosacea through its α2 adrenergic receptor agonist activity. The goal of this article is to discuss current treatment options for rosacea and the properties of brimonidine tartate as well as the evidence surrounding its efficacy and safety profile.

Clinical applications for topical 5-fluorouracil in the treatment of dermatological disorders.

Topical 5-fluorouracil (5-FU) has been used for the treatment of dermatological conditions for nearly half a century. Although the indications for 5-FU approved by the US Food and Drug Administration include actinic keratosis and superficial basal cell carcinoma, studies also have demonstrated therapeutic efficacy for 5-FU in the treatment of many other dermatological conditions, including squamous cell carcinoma in situ, warts, psoriasis of the nail, keratoacanthoma, and vitiligo. This review discusses clinical data which support the use of 5-FU for these disease states.

Sun exposure related methylation in malignant and non-malignant skin lesions.

We investigated the aberrant promoter methylation status of 12 genes in skin lesions, both malignant (basal cell carcinomas (BCCs), n=68 and squamous cell carcinomas (SCCs), n=35) and non-malignant (tags, n=58) skin lesions and compared the results of lesions from sun exposed (SE) and sun protected (SP) regions. Methylation was studied using a methylation specific PCR (MSP) and methylation of CDH1 was also measured using a semi-quantitative fluorescence based real-time MSP method. The methylation index (MI) was calculated as the methylated fraction of the genes examined. In this report, we found high frequencies of methylation of several known or suspected tumor suppressor genes in tags and skin cancers. Among the 12 genes, for the cadherin genes CDH1 and CDH3 and for two of the laminin 5 encoding genes LAMA3 and LAMC2 methylation frequencies greater than 30% were noted in one or more specimen types. We investigated whether methylation was tumor related. Surprisingly, the differences in the methylation profile of genes among the three specimen types were modest, and the MI, indicators of overall methylation frequencies, was nearly identical. However, significant differences were noted in the frequencies of methylation among the three specimen types for the genes RASSF1A (P=0.002), CDH1 (P=0.007) and one or more of three CAD genes (P=0.02). Methylation was highly significantly related to sun exposure, and sun protected specimens had little or no methylation. As methylation of CDH1 was completely SE specific we analyzed all the skin samples using a semi-quantitative real-time PCR assay for the CDH1 gene. The concordance between standard MSP and real-time MSP for all the samples (n=161) was 75% (P<0.0001). While weak signals were detected in the SP samples by real time PCR, the differences between SE and SP specimens were 148 fold for tags and 390 fold for BCCs. These differences were highly significant (P<0.0001). These findings suggest that methylation commences in UV exposed skin at a relatively early age and occurs in skin prior to the onset of recognizable preneoplastic changes.