Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Natural Moisturizing Factor-Enriched Formulations Compared to a Ceramide-Based Cream.

BACKGROUND: We aimed to investigate the effects of 2 ceramide plus natural moisturizing factor-enriched formulations compared to a ceramide-based cream on skin moisturization. METHODS: Two double-blinded comparative studies were conducted, which enrolled 35 (n=29 females, n=6 males) and 33 (n=21 females, n=12 males) participants, respectively. Participants applied ceramide plus natural moisturizer cream or ceramide-based cream (study 1) or applied ceramide plus natural moisturizing factor lotion or ceramide-based cream (study 2) to each of their lower legs for 10 days with a 5-day regression period (no moisturizer applied). Skin hydration by corneometry after bilateral application was conducted once daily for each leg in both groups.   Results: An increase in corneometer units vs baseline for the ceramide plus natural moisturizing factor-enriched cream and natural moisturizing factor-enriched lotion were greater than the increase vs baseline for the ceramide-based cream at days 10 and 15; with an overall statistical significance in favor of the ceramide plus natural moisturizing factor-enriched formulations at day 10.  Conclusions: The marked improvement in skin moisturization following utilization of the ceramide plus natural moisturizing  factor-enriched cream and lotion compared to the ceramide-based cream can be attributed to the inherent properties of the natural moisturizing factors. These properties are known to maintain the humectancy and intercellular lipid membrane of the stratum corneum, which directly improves the permeability barrier function of human skin in reducing transepidermal water loss. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8172.

INDIVIDUAL ARTICLE: Impact of Acne Vulgaris and Sarecycline on Social/Emotional Functioning and Daily Activities: PROSES Study.

BACKGROUND: Concise patient-reported outcome (PRO) instruments addressing the consequences of facial acne vulgaris (AV) on patients’ functioning and activities of daily living (ADL) are needed. METHODS: A 12-week, single-arm, prospective cohort study was conducted in patients ≥9 years old with moderate/severe non-nodular facial AV prescribed sarecycline as part of usual care. The primary endpoint included AV-specific patient- and caregiver-reported outcomes assessed with the expert panel questionnaire (EPQ, developed by 10 experts using a Delphi method) in patients (>12 years) and caregivers (for patients 9-11 years). Additional assessments included parental/caregiver perspectives on children’s AV. RESULTS: A total of 253 patients completed the study. Following 12-weeks of treatment, there were significant (P ≤.0001) changes from baseline in the proportion of patients responding that they never or rarely: felt angry (31.6%), worried about AV worsening (28.9%), had thoughts about AV (20.9%), had a certain level of worries about AV (38.7%), altered their social media/selfie activity (23.7%), had an impact on real-life plans due to AV (22.9%), made efforts to hide AV (21.3%), felt picked-on/judged due to AV (15.0%), were concerned about their ability to reach future goals due to AV (13.8%), or had sleep impacted due to AV (18.2%). No significant change from baseline was observed for parent/caregiver’s understanding of the child’s AV concerns, from both patient and parent/caregiver perspectives. CONCLUSIONS: Over 12 weeks of AV management with oral sarecycline, patients reported significant reductions in AV-related effects on emotional/social functioning and ADL as measured by the EPQ, a simple PRO with potential for use in clinical practice. J Drugs Dermatol. 2024;23:1(Suppl 1):s4-11.

INDIVIDUAL ARTICLE: Sarecycline Improves Acne Severity, Symptoms, and Psychosocial Burden in Non-nodular Acne Vulgaris: PROSES Study.

BACKGROUND: Patient-reported outcomes (PROs) are emerging as a fundamental component of disease impact assessment in acne vulgaris (AV), complementing clinician-reported outcomes. No data is available on PROs for patients with AV using sarecycline in real-world settings. METHODS: A single-arm, prospective cohort study that included patients ≥9 years old diagnosed with moderate or severe non-nodular AV was implemented as part of routine care in clinical practices (N=30). Patients received oral sarecycline (60 mg, 100 mg, or 150 mg) for 12 weeks, as part of usual care. The primary endpoint was Acne Symptom and Impact Scale (ASIS) responses from patients (≥12 years) and caregivers (for patients 9-11 years) at week 12 and change from baseline (CFB). Investigator’s Global Assessment (IGA) of AV severity and adverse events (AEs) were also recorded. RESULTS: A total of 253 patients with AV completed the study (adults: 60.1%, females: 77.6%). ASIS mean scores significantly decreased (P <.0001) at week 12 for: signs (mean CFB ± standard deviation [SD]: –0.8 ± 0.7), impact (–1.0 ± 1.0), emotional impact (–1.2 ± 1.1), and social impact (0.6 ± 1.1). Significant reductions in AV severity (P <.0001) were reported by patients and caregivers. The IGA success rate was 58.9% and physician satisfaction with treatment outcomes was 88.1%. A total of 31 (10.3%) patients reported ≥1 AE during the study. CONCLUSIONS: Patients with moderate-to-severe AV receiving acne management with an oral antibiotic for 12 weeks experienced a significant improvement in AV-related symptoms and psychosocial burden. J Drugs Dermatol. 2024;23:1(Suppl 1):s12-18.

Fifty Years of Minocycline and Its Evolution: A Dermatological Perspective.

2021 is the 50th anniversary of the FDA approval of minocycline (MCN). While many other antibiotics have become obsolete during this time, MCN continues to be quite useful. In dermatology, MCN is used prominently in acne vulgaris, and is also employed in many other dermatological conditions because of its molecular and pharmacological properties. In this article, we review the history of minocycline, and outline the evolution of the drug since its inception. Based on its existing longstanding utility and continued innovations in formulation and delivery systems, we postulate that it will continue to have a prominent position in the dermatologist’s armamentarium. J Drugs Dermatol. 2021;20(10):1031-1036. doi:10.36849/JDD.6370.

Tazarotene 0.045% Lotion for Moderate-to-Severe Acne in Male and Female Participants: A Phase II Post-hoc Analysis.

CLINICAL TRIALS ID: NCT02938494 BACKGROUND: In a Phase II study, tazarotene 0.045% lotion was statistically superior to vehicle and comparable to tazarotene 0.1% cream in reducing acne lesions, with fewer treatment-related adverse events (TEAEs) than the cream. OBJECTIVE: We analyzed data from the aforementioned study post-hoc to evaluate the effects of sex on treatment outcomes. METHODS: Participants aged 12 years or older with moderate-to-severe acne were randomized to tazarotene (0.045% lotion or 0.1% cream) or vehicle (lotion or cream) for 12 weeks of double-blind treatment. Outcomes analyzed in male and female subgroups included changes from baseline in inflammatory/noninflammatory lesions and TEAEs. RESULTS: In the intent-to-treat population (94 males and 116 females), reductions in lesion count were greater with tazarotene (lotion or cream) than with vehicle. In participants receiving tazarotene 0.045% lotion, the least-squares mean percent changes from baseline to Week 12 were greater in females than males, but the differences were not statistically significant (inflammatory [-70.3% vs. -56.2%]; noninflammatory [-60.0% vs. -53.2%]). In both females and males, the TEAE incidence was lower with tazarotene 0.045% lotion than 0.1% cream. CONCLUSION: Tazarotene 0.045% lotion substantially reduced acne lesions in both female and male participants. This newest tazarotene formulation might benefit patients who cannot tolerate older formulations or other topical retinoids. Given the relatively small size of this study, however, the results of this post-hoc analysis are intended to be exploratory in nature.

Dumbbells for Dummies: A Simplified Approach to Managing Dumbbell-shaped Keloids of the Earlobe.

BACKGROUND: Keloids are dense, fibrous tumors that arise from the dysregulation of normal wound healing, ultimately outgrowing the initial traumatic lesion. OBJECTIVE: We present a modified technique for the excision of dumbbell-shaped keloids on the earlobe using tools common to every dermatologist's office. METHODS: This was an observational report on the outcomes of dumbbell keloid excision using a #15 blade and punch biopsy. Eligible individuals were those with dumbbell-shaped keloids located on the earlobe. All procedures were conducted at an urban dermatology clinic. RESULTS: When combining the technique with continual compression earrings and intralesional corticosteroids, excellent cosmetic outcomes and minimal recurrence were achieved. CONCLUSION: The pairing of a #15 blade and punch biopsy has been demonstrated to produce a more user-friendly method for dumbbell keloid excision by dermatologists and clinicians without advanced surgical training.

The creatine kinase conundrum: a reappraisal of the association of isotretinoin, creatine kinase, and rhabdomyolysis.

BACKGROUND: Isotretinoin has been reported to elevate creatine kinase, which may lead to fatal rhabdomyolysis. OBJECTIVE: To review the literature and propose practice guidelines for management of elevated creatine kinase during isotretinoin therapy. FINDINGS: Patients have intrinsic and extrinsic qualities that may synergistically work with isotretinoin to elevate serum creatine kinase. Darker skin types and males on isotretinoin are more likely to have elevated creatine kinase. Isotretinoin may induce oxidative stress within muscle tissue, thereby leading to elevations in serum creatine kinase. CONCLUSION: Evidence supports a tenuous correlation between isotretinoin, elevated creatine kinase, and exercise. Physicians should consider obtaining baseline creatine kinase on elite athletes and counseling patients on risk factors that may elevate creatine kinase. However, the potential for elevated CK is not a contraindication for isotretinoin therapy.

Rosacea: a wholistic review and update from pathogenesis to diagnosis and therapy.

Rosacea is a chronic inflammatory disorder of the central face with multiple overlapping presentations. Recent advancements are reshaping our understanding of rosacea from both a pathophysiologic perspective and clinical approach to therapy, introducing novel agents that have improved patient outcomes and reduced morbidity. In this article, we aim to outline the advancements in understanding, diagnosing, and managing rosacea and to familiarize physicians with the literature, thereby allowing us to better practice safe and effective medicine.

Erythema of Rosacea Affects Health-Related Quality of Life: Results of a Survey Conducted in Collaboration with the National Rosacea Society.

INTRODUCTION: Persistent facial erythema associated with rosacea may negatively impact quality of life (QoL), self-esteem, and self-confidence. We evaluated burden and health-related QoL (HRQoL) impacts of centrofacial erythema of rosacea. METHODS: A cross-sectional, Web-based survey conducted in collaboration with the National Rosacea Society enrolled adults who self-reported having received a physician diagnosis of rosacea and self-evaluated their current erythema as mild to severe on the validated Subject Self-Assessment for Rosacea Facial Redness. Sociodemographic and clinical characteristics, rosacea symptoms, and their impacts on QoL [validated Impact Assessment for Rosacea Facial Redness (IA-RFR)] and HRQoL [validated Dermatology Life Quality Index (DLQI)] were recorded. RESULTS: A total of 708 eligible respondents completed the survey (white/Caucasian, 93.5%; female, 83.1%; mean age, 52.4 years). Respondents had mild (59.2%), moderate (33.2%), or severe (7.6%) erythema. The most bothersome symptoms were persistent facial erythema (69.2%) and blushing/flushing (60.9%). Mean IA-RFR scores showed negative impacts across all severities of erythema. The mean (standard deviation) total DLQI score was 5.2 (6.0) overall [mild erythema, 3.8 (4.9); moderate, 5.7 (5.4); severe, 13.4 (8.9); P < 0.0001]. CONCLUSION: Centrofacial erythema of rosacea represents a substantial HRQoL burden, especially for those with more severe erythema. FUNDING: Allergan plc, Dublin, Ireland.

An Overview of Acne Therapy, Part 1: Topical therapy, Oral Antibiotics, Laser and Light Therapy, and Dietary Interventions.

Therapeutic actives for acne have changed little in the last decade. Recognition that acne is an inflammatory condition, not an infectious one, has led to a call for reduction in antibiotic use. This has culminated in a re-evaluation of highly efficacious combination topical therapy and improved vehicle technology. Laser and light modalities, although not sufficiently studied for first-line use, show promise for the future. The role that diet plays in the initiation and continuation of acne is unclear but remains one of our patients' most frequently asked questions.

An Overview of Acne Therapy, Part 2: Hormonal Therapy and Isotretinoin.

Therapeutic actives for acne have changed little in the last decade. Recognition that acne is an inflammatory condition, not an infectious one, has led to a call for reduction in antibiotic use, which has culminated in a re-evaluation of our nonantibiotic choices. Spironolactone and oral contraceptives have become more acceptable first-line choices, and earlier use of isotretinoin has been proposed.

New Concepts, Concerns, and Creations in Acne.

Laboratory monitoring for patients on isotretinoin should include creatinine kinase in athletic males and the more liver-specific gamma glutamyltransferase. There is mounting evidence that acne pathophysiology includes a barrier defect and subsequent microbiome disruption. Avoidance of acne scars with early and aggressive treatment is a more efficient and cost-effective option than subsequent treatment. Laser and light treatments for acne and acne scars are plentiful but poorly supported by evidence-based medicine. The acne pipeline is rich with new chemical entities, new formulations, and combinations of older agents. The gold standard for acne therapy may be changing its face.

Global epidemiology and clinical spectrum of rosacea, highlighting skin of color: Review and clinical practice experience.

Rosacea has been reported less frequently among individuals with skin of color than in those with white skin, but rosacea is not a rare disease in this population. In fact, rosacea might be underreported and underdiagnosed in populations with skin of color because of the difficulty of discerning erythema and telangiectasia in dark skin. The susceptibility of persons with highly pigmented skin to dermatologic conditions like rosacea, whose triggers include sun exposure, is probably underestimated. Many people with skin of color who have rosacea might experience delayed diagnosis, leading to inappropriate or inadequate treatment; greater morbidity; and uncontrolled, progressive disease with disfiguring manifestations, including phymatous rosacea. In this article, we review the epidemiology of rosacea in skin of color and highlight variations in the clinical presentation of rosacea across the diverse spectrum of patient populations affected. We present strategies to aid in the timely diagnosis and effective treatment of rosacea in patients with skin of color, with an aim of promoting increased awareness of rosacea in these patients and reducing disparities in the management of their disease.

Highlights of Skin Disease Education Foundations 42nd Annual Hawaii Dermatology Seminar.

Updates on managing some of the most common dermatologic conditions for which patients seek care illuminated presentations at the Skin Disease Education Foundation's 42nd Annual Hawaii Dermatology Seminar®. This educational supplement summarizes the highlights of clinical sessions presented during this CME/CE conference. Treatment of psoriasis has continued to advance, with three interleukin (IL)-17 antagonists approved by the US Food and Drug Administration (FDA) and a fourth in phase 3 trials. An authority on the use of biologics in psoriasis presents current data on the safety and efficacy of these therapies. Tumor necrosis factor (TNF) inhibitors also retain a place in the management of psoriasis, with records of long-term safety. A fourth TNF inhibitor awaits FDA approval for use in psoriasis, offering data on transmission during pregnancy and lactation. An expert on the use of this drug class presents the evidence. Topical therapies remain the cornerstone of care for many patients with psoriasis as well as those with rosacea. Our faculty update readers about new and investigational topical therapies for moderate or severe psoriasis, as well as for acne and rosacea. The current literature on monitoring patients receiving isotretinoin also is summarized. Aesthetic and cosmetic dermatology services form a sizable portion of some practices. Our faculty review data on safety of topical and procedural therapies for cellulite as well as safe injection of facial fillers.

Management of Severe Acne Vulgaris With Topical Therapy.

Acne vulgaris (acne) is the most common skin disease we see in dermatology practice. Although rare in childhood, severe acne can affect up to 12% of the adolescent population. A chronic disease, it requires both aggressive management and effective maintenance strategies. Oral antibiotics, in combination with topical agents are recommended for treatment, with topical agents being continued as maintenance therapy to minimize resistance and recurrence. However, concerns with systemic side effects have recently resulted in a greater focus on the potential of fixed combination topical therapies to treat severe acne. Here we review the available clinical evidence. There are no studies investigating the use of fixed combination topical therapy exclusively in severe acne. However, studies assessing the treatment of moderate-to-severe acne include subpopulation data in severe patients. Adapalene 0.3%-benzoyl peroxide (BP) 2.5% was found to be effective in patients with severe acne, whereas the fixed combination with a lower concentration of adapalene (0.1%) was no more effective than vehicle. Clindamycin-BP 1.2%/3.75% gel and clindamycin-BP 1.2%/2.5% gel were both found to be effective in severe acne with an apparent BP-dose response. Clindamycin phosphate 1.2%-tretinoin 0.025% demonstrated similar efficacy in severe acne, but with little benefit over individual monads. Realistic topical treatment options now exist for the management of severe acne where patient and physician preference can impact positive outcomes.

J Drugs Dermatol. 2017;16(11):1134-1138.

The Burden of Illness of Erythematotelangiectatic Rosacea and Papulopustular Rosacea: Findings From a Web-based Survey.

Objective: Evaluate patients' perceptions of rosacea symptoms and treatments. Design: Cross-sectional, web-based survey conducted from May 8 to July 1,2015. Setting: E-mail invitation. Participants: Male and female adults in the United States who self-reported having a physician's diagnosis of rosacea. Measurements: Sociodemographic and clinical characteristics were collected for eligible respondents using the Self-Assessment of Rosacea Facial Redness scale and the Symptom Assessment for Rosacea Facial Bumps and Pimples questionnaire. Respondents were instructed how to differentiate erythematotelangiectatic rosacea and papulopustular rosacea. Use of different treatments and satisfaction with treatment were assessed, as were coping mechanisms. Results: More than 4,000 individuals responded and 600 completed the survey. The participants' mean age was 51.7 years and more than 90 percent rated their rosacea severity as mild or moderate. Most practiced stress and/or anxiety management, used makeup to cover rosacea, used sun protection, and changed their exercise regimens to cope with rosacea flare-ups. Participants reported avoiding sun exposure, hot baths and saunas, and specific skin care products to circumvent potential rosacea flare-ups. More than half (55.7%) had used a prescribed topical agent for rosacea in the preceding month, and 26.3 percent had used a prescribed oral antibiotic. Fewer than half were satisfied with treatment outcomes. Conclusion: Despite the chronic nature of rosacea, participants commonly used prescription agents only to treat flare-ups and relied on sun protection and other avoidance mechanisms to reduce their frequency. Education is needed to communicate the long-term nature of rosacea and the need for continued treatment to maintain long-term control.

Evidence-based recommendations for the management of acne fulminans and its variants.

BACKGROUND: Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF. OBJECTIVE: To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research. METHODS: A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations. RESULTS: Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus. LIMITATIONS: Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available. CONCLUSION: These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.