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.

Patient perspectives on topical minoxidil for hair loss: a survey-based study from the University of Michigan Alopecia Clinic.

Topical minoxidil is a widely used therapy for alopecia. Its availability over the counter in the United States makes it easily accessible. Various factors impact whether an individual decides to pursue treatment and/or continue long-term use. Our study aimed to investigate patient awareness, opinions, and hesitations regarding topical minoxidil use for hair loss treatment. The study also aimed to identify information sources influencing these viewpoints. A survey was administered to new patients seeking evaluation for alopecia aged 18 and above at the University of Michigan Alopecia Clinic. Data collection occurred between August 2022 and August 2023. Demographics, patient-reported hair loss diagnosis, history of minoxidil use, opinions on minoxidil, influential information sources, and concerns about minoxidil were collected. A total of 47 surveys were completed, primarily by females (78.7%) ages 18-40 years (44.7%). Respondents were aware of minoxidil (97.9%), with 63.8% reporting they had heard of minoxidil, but had not used it. Medical professionals were the most influential information source (34%), followed by close contacts (17%), internet searches (10.6%), and television (10.6%). Overall, positive opinions on minoxidil were expressed by 51.1%, negative opinions by 31.9%, and neutral opinions by 17%. Most common concerns included the need for continuous use (46.8%), required regular application (31.9%), skepticism about hair regrowth (29.8%), and expense (25.5%). Addressing personalized concerns and tailoring communication based on hair loss type and information sources may lead to more informed decisions and improved adherence. Gauging the opinions of this population provides valuable insights, aiding dermatologists in patient education and counseling strategies.

The ERAS Supplemental Application: Current Status and Recommendations for Dermatology Applicants and Programs.

The 2021-2022 dermatology residency program application cycle involved an optional common supplemental application piloted by the Association of American Medical Colleges' (AAMC) Electronic Residency Application Service (ERAS). In this article we present data on the utilization and opinions of applicants and programs regarding the supplemental application, discuss changes to the supplemental application for the upcoming application cycle, and offer recommendations to applicants and programs entering year 2 of the ERAS supplemental application.

Mutations in PERP Cause Dominant and Recessive Keratoderma.

Investigation of genetic determinants of Mendelian skin disorders has substantially advanced understanding of epidermal biology. Here we show that mutations in PERP, encoding a crucial component of desmosomes, cause both dominant and recessive human keratoderma. Heterozygosity for a C-terminal truncation, which produces a protein that appears to be unstably incorporated into desmosomes, causes Olmsted syndrome with severe periorificial and palmoplantar keratoderma in multiple unrelated kindreds. Homozygosity for an N-terminal truncation ablates expression and causes widespread erythrokeratoderma, with expansion of epidermal differentiation markers. Both exhibit epidermal hyperproliferation, immature desmosomes lacking a dense midline observed via electron microscopy, and impaired intercellular adhesion upon mechanical stress. Localization of other desmosomal components appears normal, which is in contrast to other conditions caused by mutations in genes encoding desmosomal proteins. These discoveries highlight the essential role of PERP in human desmosomes and epidermal homeostasis and further expand the heterogeneous spectrum of inherited keratinization disorders.

Patient interest in and familiarity with anti-aging therapies: A survey of the general dermatology clinic population.

BACKGROUND: The appearance of aging skin is a common complaint among dermatology patients. There is an expanding market for anti-aging therapies, but little information is available regarding which patients utilize these treatments and patient preferences regarding treatment. AIMS: To describe the patient population utilizing anti-aging therapies, assess patient familiarity with treatment options, and learn where treatment information is most often obtained. PATIENTS/METHODS: Three hundred patients were surveyed in the University of Michigan General Dermatology Clinic. RESULTS: Fifty-three percent of the general dermatology patient population has used an anti-aging treatment in the past; 66% reported interest in the future use. Interest is high among all genders, ages, and incomes. Most subjects obtained treatment information from magazines, but subjects were more likely to pursue treatment if information was obtained from a dermatologist. CONCLUSION: Demographics of anti-aging therapy are changing, and a wide variety of patients pursue treatment. Patients are largely unfamiliar with most treatment options and are more likely to pursue treatment after receiving treatment information from a dermatologist. The information presented in this study is helpful to both dermatologists and marketers of anti-aging products.

Topical and oral therapeutic approach to rosacea.

Rosacea is an inflammatory condition of the skin, primarily affecting the central convexities of the face. Various topical and oral therapeutic approaches exist. Most have been developed to treat the papulopustular subtype of rosacea; however, other approaches can be used to treat the erythematotelangiectatic, ocular, and phymatous subtypes. This review provides a summary of available topical and oral approaches for the treatment of rosacea.

Treatment of Acne in Pregnancy.

Acne vulgaris is a common disease of the pilosebaceous unit and affects adolescents and adults. Because high-quality guidelines regarding treatment of acne in pregnancy are scarce, management of this condition can be challenging. We describe the safety profile of common therapies and outline approaches based on available evidence. Topical azelaic acid or benzoyl peroxide can be recommended as baseline therapy. A combination of topical erythromycin or clindamycin with benzoyl peroxide is recommended for inflammatory acne. Oral erythromycin or cephalexin is generally considered safe for moderate to severe inflammatory acne when used for a few weeks. A short course of oral prednisolone may be useful for treating fulminant nodular cystic acne after the first trimester. In general, topical and oral antibiotics should not be used as monotherapy, but combined with topical benzoyl peroxide to decrease bacterial resistance. Oral retinoids are teratogenic and absolutely contraindicated for women who are pregnant or considering pregnancy. Although some complementary therapies including micronutrients and nonpharmacologic treatments seem to be well tolerated, limited data exist regarding their safety and efficacy, and they are not currently recommended during pregnancy. The risk-to-benefit ratio, efficacy, acceptability, and costs are considerations when choosing a treatment for acne in pregnancy.

A Qualitative Comparison of Symptoms and Impact of Varying Stages of Basal Cell Carcinoma.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common form of skin cancer; however, few data are available relating to patients' perspectives and experiences of this disease. This study explored the spectrum of BCC symptoms and their impact by disease stage to determine how BCC affects the overall health-related quality of life (HRQL) of patients. METHODS: This study comprised a cross-sectional, qualitative approach involving telephone interviews with patients with BCC who had been divided into two groups: group 1 (G1), patients with stage 1, non-advanced BCC (and of superficial or nodular histology); and group 2 (G2), patients with locally advanced or metastatic BCC. Patients were recruited from three clinical sites in the USA based on a separate qualitative interview study (I4J-MC-HHBB [1.3]) over a 10-month period. Techniques in qualitative methodology were used by applying 'open-ended' questions and probing techniques intended to elicit patients' own description of their experiences with BCC. Telephone interviews lasted between 60 and 90 mins. RESULTS: Thirty-four interviews were conducted (G1: N = 13; G2: N = 21). The majority of patients were aged either 55-64 years (32%, N = 11) or 76+ years (32%, N = 11) and were primarily male (82%, N = 28); most (75%, N = 24) patients were actively receiving BCC treatment. Both groups reported similar symptoms, with the most common being red lesions or open sores that failed to heal (41%, N = 14) and cancer-related stress (41%, N = 14). G2 reported more frequent and severe HRQL impact as a result of their cancer condition because most were affected in their daily activities (76%, N = 16) or emotional well-being (71%, N = 15). Cosmetic and functional impacts were relevant and important aspects of HRQL for both patient groups (G1: 31%, N = 4; G2: 48%, N = 10). CONCLUSIONS: Patients with non-advanced or locally advanced and metastatic BCC experience disease-related symptoms that affect their HRQL, activities of daily living, emotional well-being, and social and/or leisure activities. Qualitative descriptions of patient experiences can help healthcare providers and caregivers better understand the impact of BCC from the patient perspective. FUNDING: Eli Lilly and Company.

Clinical, Histologic, and Molecular Analysis of Differences Between Erythematotelangiectatic Rosacea and Telangiectatic Photoaging.

IMPORTANCE: Facial erythema and telangiectasia are commonly associated with the erythematotelangiectatic subtype of rosacea (ETR). It is important for clinicians to recognize that these findings can also be associated with a subtype of photoaging, which we term telangiectatic photoaging (TP). OBJECTIVE: To demonstrate that ETR and TP are distinct dermatologic disorders. DESIGN: A case-control observational study comparing clinical, histologic, and gene expression features of 26 participants with ETR, 20 with TP, and 11 age- and sex-matched controls in the Program for Clinical Research in Dermatology at University of Michigan. MAIN OUTCOMES AND MEASURES: Findings of clinical history and examination, light and electron microscopy, immunohistochemical analyses, and real-time quantitative reverse-transcriptase polymerase chain reaction gene expression. RESULTS: Transient erythema was greater in the ETR group (38% graded moderate to severe) than in the TP (0%; P < .001) and control groups (0%; P = .002). Nontransient erythema was also greater in the ETR group (50% graded moderate to severe) than in the TP (25%; P = .03) and control groups (0%; P < .001). Participants with ETR tended to have erythema and telangiectasia primarily on the central face (79%), whereas those with TP tended to have more lateral involvement (57%; P < .001). Those with ETR had significantly less clinical evidence of photodamage (0% graded 6-8 on a photonumeric scale) than those with TP (40% graded 6-8; P = .01). Histologically, there was less evidence of photodamage in ETR than in TP, which had wispy collagen and solar elastosis surrounding blood vessels. Immunohistologic analysis demonstrated greater geometric mean immunostained area by mast cell tryptase staining in ETR samples (0.018%) than in TP (0.004%; P = .01) or control samples (0.001%; P < .001) but no increase in mast cell number, indicative of greater mast cell degranulation. Gene expression of matrix metalloproteinase-3 was 4-fold greater in ETR samples than in TP samples (P = .004) and 5-fold higher than in control samples (P = .004). Gene expression of the neuropeptides calcitonin gene-related peptide (CGRP-α) and substance P was significantly increased in ETR compared with TP (9-fold [P < .001] and 5-fold [P = .002], respectively) and control samples (10-fold [P < .001] and 28-fold [P < .001], respectively). CONCLUSIONS AND RELEVANCE: Telangiectatic photoaging is characterized by less transient and nontransient erythema, a more lateral distribution of erythema and telangiectasia, less neurogenic mast cell activation, and less MMP-mediated matrix remodeling than ETR. These data demonstrate that TP is a distinct clinical entity from ETR that can be distinguished on the basis of clinical, histologic, and gene expression findings.

Rapid clinical change in lesions of atypical cutaneous lymphoproliferative disorder in an HIV patient: a case report and review of the literature.

BACKGROUND: HIV associated atypical cutaneous lymphoproliferative disorder (ACLD) is a rare condition characterized by a pruritic, often generalized, eruption of patches and plaques or erythroderma clinically simulating mycosis fungoides (MF) or Sézary syndrome. A polyclonal CD8+ T-cell infiltrate on biopsy can help differentiate ACLD from MF or Sézary syndrome, but the clinical and histopathologic appearance must also be considered. Accurate diagnosis is imperative because HAART therapy has been reported to improve this condition in some patients. OBSERVATION: We report a case of HIV associated ACLD, with an atypical presentation, initially consisting of diffuse papules, some with a dusky targetoid center. Two weeks after starting antiviral therapy the papules flattened, evolving to xerotic, hyperpigmented macules. CONCLUSION: The working-theory of a reactive etiology for this condition might explain the evolution in appearance following initiation of HAART. The presence of papules with a dusky targetoid center suggests that this condition should be considered in the differential diagnosis with syphilis or atypical erythema multiforme in HIV patients.

Effect of smoking on aging of photoprotected skin: evidence gathered using a new photonumeric scale.

OBJECTIVES: To develop a reproducible photonumeric scale to assess photoprotected skin aging and to determine whether health and lifestyle factors, such as smoking, affect skin aging in photoprotected sites. DESIGN: Using standard photographs of participants' upper inner arms, we created a 9-point photonumeric scale. Three blinded reviewers used the scale to grade the photographs. Participants answered multiple lifestyle questions. SETTING: Academic outpatient dermatology clinic. PARTICIPANTS: Eighty-two healthy men and women aged 22 to 91 years. Interventions A professional medical photographer took standardized photographs of each participant's upper inner arm. Participants answered standardized health and lifestyle questions. MAIN OUTCOME MEASURES: (1) Interobserver agreement and reproducibility using the photonumeric scale and (2) health and lifestyle factors most predictive of the degree of aging in photoprotected skin. RESULTS: There was good blinded interobserver agreement as measured by the maximum range of disagreement scores for each participant (mean, 0.91; 95% confidence interval, 0.76-1.06). Results were reproducible. We developed a multiple regression model showing that the best model for predicting the degree of aging in photoprotected skin includes 2 variables: age and packs of cigarettes smoked per day. CONCLUSIONS: This photonumeric scale demonstrates good interobserver agreement and good reproducibility. Using this scale, the degree of aging in photoprotected skin was significantly correlated with patient age and a history of cigarette smoking. Additional studies are needed to continue garnering information regarding independent risk factors for aging of photoprotected skin.

Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism.

An essential element of the innate immune response to injury is the capacity to recognize microbial invasion and stimulate production of antimicrobial peptides. We investigated how this process is controlled in the epidermis. Keratinocytes surrounding a wound increased expression of the genes coding for the microbial pattern recognition receptors CD14 and TLR2, complementing an increase in cathelicidin antimicrobial peptide expression. These genes were induced by 1,25(OH)2 vitamin D3 (1,25D3; its active form), suggesting a role for vitamin D3 in this process. How 1,25D3 could participate in the injury response was explained by findings that the levels of CYP27B1, which converts 25OH vitamin D3 (25D3) to active 1,25D3, were increased in wounds and induced in keratinocytes in response to TGF-beta1. Blocking the vitamin D receptor, inhibiting CYP27B1, or limiting 25D3 availability prevented TGF-beta1 from inducing cathelicidin, CD14, or TLR2 in human keratinocytes, while CYP27B1-deficient mice failed to increase CD14 expression following wounding. The functional consequence of these observations was confirmed by demonstrating that 1,25D3 enabled keratinocytes to recognize microbial components through TLR2 and respond by cathelicidin production. Thus, we demonstrate what we believe to be a previously unexpected role for vitamin D3 in innate immunity, enabling keratinocytes to recognize and respond to microbes and to protect wounds against infection.

A randomized, controlled, split-face clinical trial of 1320-nm Nd:YAG laser therapy in the treatment of acne vulgaris.

BACKGROUND: There is a need for additional effective treatments for acne vulgaris. Laser therapy has been explored as a therapeutic option for acne, but rigorously designed studies in this area have been limited. OBJECTIVE: We sought to examine the efficacy of an infrared laser in the treatment of acne. METHODS: We conducted a randomized, controlled, single-blind, split-face clinical trial of 46 patients with facial acne. Patients received a series of 3 nonablative laser treatments using a novel neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to half of the face. Serial blinded lesion counts and global acne severity rating of standardized bilateral patient photographs were performed. Sebum production was measured, and patient self-assessment surveys were administered. RESULTS: A transient but statistically significant improvement in lesion counts of open comedones was demonstrated in treated skin as compared with untreated skin. There were no significant differences between treated and control sides of the face in terms of changes in mean papule or pustule counts. Grading of serial photographs revealed no significant differences between treated and untreated skin. Patient surveys indicated that the majority of patients found the treatments to be at least mildly effective for both acne and oiliness. LIMITATIONS: The current study only addresses the efficacy of a single laser system employing a specific treatment regimen. CONCLUSIONS: Infrared laser therapy may improve comedonal acne. Additional work is needed to better define the degree and duration of the effect. Patients appear to positively view such therapy for both acne and oily skin.