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

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144284/1/jocd12386.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144284/2/jocd12386_am.pd

Ocular side effects of systemic isotretinoin – a systematic review and summary of case reports

Background: Isotretinoin is frequently used for treatment of severe nodulocystic and papulopustular acne, however use is limited by mucocutaneous, ocular, and systemic side effects. Objective: (1) provide a systematic meta-analysis of ocular side effects during isotretinoin use and their corresponding incidences; (2) provide a narrative summary of ocular side effects during isotretinoin use reported in case reports. Methods: A systematic database search using predefined search terms was performed in PubMed, EMBASE, and Scopus from inception to 5 March, 2021. Predetermined inclusion and exclusion criteria were used to select included studies. In total, 53 original studies qualified for meta-analysis, and 41 case reports/series qualified for narrative results. Results: The studies included in the meta-analysis reported incidences of various ocular side effects including dry eye, eye sensitivity, vision changes, and ocular inflammatory conditions. Incidences across studies did vary, leading to considerable heterogeneity. The narrative results summarize more uncommon, but equally important, ocular side effects. Conclusions: Dry eye is the most commonly reported ocular side effect. Other less common, but more serious, ocular side effects including vision changes can occur. We recommend that isotretinoin prescribers monitor for dry eye. Limitations include the heterogeneity of reported incidences of ocular side effects between studies

Dermatology residency preparation curriculum: a model for initiating new residents into dermatology clinical care

Entering dermatology residency is an immersive experience requiring new specialty-specific skills. There is no standard Accreditation Council for Graduate Medical Education (ACGME) protocol for orienting new dermatology residents. We aimed to design, develop, and evaluate a curriculum for incoming first-year dermatology residents focusing on practical introduction to dermatologic clinical care emphasizing ACGME dermatology milestones. A concentrated 8-hour residency preparation course for first-year dermatology residents was designed and developed by faculty. The course encompassed clinical competencies, procedural techniques, and professionalism and collegiality principles. Teaching methods included lectures, video demonstrations, simulated patient experiences, and one-on-one practical instruction. Surveys were distributed before, immediately after, and 6-months following the course from 2016-2018 to assess participants’ skill-based confidence level and perceived usefulness of the course. A total of 24 first-year dermatology residents participated in the residency preparation course over 3 years from 2016-2018. Residents’ confidence levels in performing dermatology-specific skills immediately increased following the course and continued to increase 6 months into training. The majority of first-year residents “agreed” or “strongly agreed” that the course was helpful for improving clinical competence. Our residency preparation course increased first-year residents’ confidence and perceived competence in performing clinical skills related to ACGME dermatology milestones

Development of an Illustrated Scale for Acute Radiation Dermatitis in Breast Cancer Patients

PURPOSE: Scales for rating acute radiation dermatitis (ARD) have not been validated despite decades of clinical use, and little is known regarding the relationship between toxicity scores and patient-reported symptoms. Skin tone also complicates assessment of ARD, and as such we sought to design an illustrated scale to consistently describe ARD across several skin tone types in breast cancer patients undergoing radiation (RT). METHODS: Patients undergoing RT for breast cancer were enrolled on a prospective study with photographs obtained at 2-week intervals. Photographs were clustered according to the apparent severity of acute radiation dermatitis and a descriptive photonumeric scale was developed. Four clinically experienced raters used both the illustrated photonumeric scale and the CTCAE to independently score the collection of photographs in two independent sessions. RESULTS: Among 80 unique patients with 192 photographs, 47 patients (59%) completed questionnaires about their symptoms during RT. Physicians completed toxicity forms at the point-of-care for 52 patients (65%). Photonumeric ratings compared against patient reports of dry and moist desquamation demonstrated high specificity (95% and 93%, respectively) and negative predictive value (84% and 92%), indicating correct identification of patients who did not report dry or moist desquamation. The sensitivity and positive predictive value for separate measures of dry and moist desquamation were considerably lower. A combined measure of any desquamation (dry or moist) portrayed higher diagnostic accuracy, resulting in 72% sensitivity, 93% specificity, 75% PPV, and 92% NPV. Photonumeric ratings of dry or moist desquamation were significantly associated with patient reports of itching, burning/stinging, hurting, and swelling. CONCLUSION: The xxx scale for acute radiation dermatitis is a simple grading rubric that is distinguished by characterization of its intra- and inter-rater reliability and diagnostic accuracy, correlation with patient-reported symptoms of bother and pain, and applicability across the spectrum of skin pigmentation

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 D(3) (1,25D3; its active form), suggesting a role for vitamin D(3) 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 D(3) (25D3) to active 1,25D3, were increased in wounds and induced in keratinocytes in response to TGF-β(1). Blocking the vitamin D receptor, inhibiting CYP27B1, or limiting 25D3 availability prevented TGF-β(1) 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 D(3) in innate immunity, enabling keratinocytes to recognize and respond to microbes and to protect wounds against infection

Cytokine responses in nonlesional psoriatic skin as clinical predictor to anti-TNF agents

BackgroundA major issue with the current management of psoriasis is our inability to predict treatment response.ObjectiveOur aim was to evaluate the ability to use baseline molecular expression profiling to assess treatment outcome for patients with psoriasis.MethodsWe conducted a longitudinal study of 46 patients with chronic plaque psoriasis treated with anti-TNF agent etanercept, and molecular profiles were assessed in more than 200 RNA-seq samples.ResultsWe demonstrated correlation between clinical response and molecular changes during the course of the treatment, particularly for genes responding to IL-17A/TNF in keratinocytes. Intriguingly, baseline gene expressions in nonlesional, but not lesional, skin were the best marker of treatment response at week 12. We identified USP18, a known regulator of IFN responses, as positively correlated with Psoriasis Area and Severity Index (PASI) improvement (P = 9.8 × 10-4) and demonstrate its role in regulating IFN/TNF responses in keratinocytes. Consistently, cytokine gene signatures enriched in baseline nonlesional skin expression profiles had strong correlations with PASI improvement. Using this information, we developed a statistical model for predicting PASI75 (ie, 75% of PASI improvement) at week 12, achieving area under the receiver-operating characteristic curve value of 0.75 and up to 80% accurate PASI75 prediction among the top predicted responders.ConclusionsOur results illustrate feasibility of assessing drug response in psoriasis using nonlesional skin and implicate involvement of IFN regulators in anti-TNF responses

Noninvasive Tape-Stripping with High-Resolution RNA Profiling Effectively Captures a Preinflammatory State in Nonlesional Psoriatic Skin

Tape stripping is a minimally invasive, nonscarring method that can be utilized to assess gene expression in the skin but is infrequently used given technical constraints. By comparing different tape stripping technologies and full-thickness skin biopsy results of lesional and nonlesional psoriatic skin from the same patients, we demonstrate that tape stripping with optimized high-resolution transcriptomic profiling can be used to effectively assess and characterize inflammatory responses in the skin. Upon comparison with single-cell RNA-sequencing data from psoriatic full-thickness skin biopsies, we illustrate that tape-stripping efficiently captures the transcriptome of the upper layers of the epidermis with sufficient resolution to assess the molecular components of the feed-forward immune amplification pathway in psoriasis. Notably, nonlesional psoriatic skin sampled by tape stripping demonstrates activated, proinflammatory changes when compared to healthy control skin, suggesting a prepsoriatic state, which is not captured on full-thickness skin biopsy transcriptome profiling. This work illustrates an approach to assess inflammatory response in the epidermis by combining noninvasive sampling with high throughput RNA-sequencing, providing a foundation for biomarker discoveries and mechanism of action studies for inflammatory skin conditions