The Skin Barrier and Moisturization: Function, Disruption, and Mechanisms of Repair.

BACKGROUND: The anatomic layers of the skin are well-defined, and a functional model of the skin barrier has recently been described. Barrier disruption plays a key role in several skin conditions, and moisturization is recommended as an initial treatment in conditions such as atopic dermatitis. This review aimed to analyze the skin barrier in the context of the function model, with a focus on the mechanisms by which moisturizers support each of the functional layers of the skin barrier to promote homeostasis and repair. SUMMARY: The skin barrier is comprised of four interdependent layers - physical, chemical, microbiologic, and immunologic - which maintain barrier structure and function. Moisturizers target disruption affecting each of these four layers through several mechanisms and were shown to improve transepidermal water loss in several studies. Occlusives, humectants, and emollients occlude the surface of the stratum corneum (SC), draw water from the dermis into the epidermis, and assimilate into the SC, respectively, in order to strengthen the physical skin barrier. Acidic moisturizers bolster the chemical skin barrier by supporting optimal enzymatic function, increasing ceramide production, and facilitating ideal conditions for commensal microorganisms. Regular moisturization may strengthen the immunologic skin barrier by reducing permeability and subsequent allergen penetration and sensitization. KEY MESSAGES: The physical, chemical, microbiologic, and immunologic layers of the skin barrier are each uniquely impacted in states of skin barrier disruption. Moisturizers target each of the layers of the skin barrier to maintain homeostasis and facilitate repair.

Are we contributing to the opioid epidemic? A systematic review on systemic opioid use in dermatology.

BACKGROUND: Although dermatologists treat many painful skin conditions and perform procedures that may require analgesic use, there is a lack of evidence synthesis on opioid use in dermatology. OBJECTIVE: To conduct a systematic review of the evidence on the use of opioid analgesics in dermatology. METHODS: We applied the PRISMA guidelines and systematically reviewed literature that examined opioid use in dermatology published between 1980 and 2020 in the PubMed, EMBASE, and Cochrane databases. This review was registered with PROSPERO (CRD42020204864). RESULTS: We identified 24 studies that analyzed 52,705,201 patients and 13,099 dermatologists. Between 34% and 87.5% of patients received opioids following dermatologic procedures; however, many did not use the entirety of their prescriptions, and 35-69% did not use any of their prescription. Top opioid prescribers were more likely to be Mohs surgeons, male, and practice in the South. Variability exists in the current evidence for opioid prescribing for nonprocedural dermatologic disease. CONCLUSION: While opioid prescribing in dermatology is low compared with other specialties, patients are not utilizing the entirety of their prescriptions. Opioid prescribing for nonprocedural dermatologic disease varies; treatments focused on targeting the pathogenesis of these diseases is important to minimize opioid use. Dermatologists should consider limiting opioid prescribing and utilizing nonnarcotic analgesics.

INDIVIDUAL ARTICLE: Safety and Tolerability of Topical Agents for Actinic Keratosis: A Systematic Review of Phase 3 Clinical Trials.

BACKGROUND: Topical agents for actinic keratosis (AK), along with cryotherapy and phototherapy, are the most commonly used therapies for areas of skin with multiple AKs. Multiple options for the topical treatment of AK exist; newer therapies aim to balance efficacy with an acceptable safety and tolerability profile for the patient. OBJECTIVE: To describe the safety and tolerability of FDA-approved topical agents for the treatment of AK. METHODS: A systematic review of phase III clinical trials of topical agents for AK available on PubMed and clinicaltrials.gov was conducted on January 10th, 2021. RESULTS: 29 phase III clinical trials meeting the inclusion criteria were included in the qualitative synthesis. No serious adverse events or systemic adverse events were determined to be due to topical therapies for AK. The highest rates of treatment-related application-site adverse events and local skin reactions occurred with the various formulations of topical 5-FU and imiquimod; newer topical agents such as ingenol mebutate and tirbanibulin had more favorable tolerability profiles. CONCLUSIONS: FDA-approved topical agents for the treatment of multiple AKs have minimal safety concerns. Tolerability profiles vary among the available options, and new agents such as tirbanibulin offer a favorable combination of safety, tolerability, and efficacy. J Drugs Dermatol. 2021;20:10(Suppl):s4-11.

Topical opioid use in dermatologic disease: A systematic review.

Topical opioid formulations offer a potential solution to manage pain and decrease the use of systemic opioids. Synthesis of use and efficacy of topical opioids in dermatological conditions has not been well characterized. We conducted a systematic search of the PubMed, Embase, and Cochrane databases from 1980 to February 2021. This study analyzed data from 14 articles and 263 patients on the use of topical opioids for pain related to chronic ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts. Topical opioids included in this review were topical morphine and diamorphine. Common formulations consisted of 0.2-10 mg of opioid compounded with hydrogel or IntraSite gel. Topical opioids were variably effective in the use for pain control related to chronic ulcers and other dermatologic conditions. For example, the use of topical opioids appears to be effective in the reduction of pain related to pressure ulcers. Topical opioids were generally well tolerated. Insufficient data exist to adequately evaluate the efficacy and safety of topical opioid use in the context of nonpressure ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts.

Bullous Dermatoses and Depression: A Systematic Review.

IMPORTANCE: There is a lack of evidence synthesis on the association between bullous skin disease and depression. OBJECTIVE: To synthesize and interpret the current evidence on the association between bullous skin disease and depression. EVIDENCE REVIEW: This review was conducted according to PRISMA guidelines and reviewed literature related to bullous skin disease and depression in the PubMed, Embase, PsycInfo, and Cochrane databases published between 1945 and February 2021. The quality of each included article was assessed via the Newcastle-Ottawa Scale. This review was registered with PROSPERO (CRD42021230750). FINDINGS: A total of 17 articles were identified that analyzed a total of 83 910 patients (55.2% female; specifically, 6951 patients with bullous pemphigoid, 1669 patients with pemphigus, and 79 patients with epidermolysis bullosa were analyzed). The prevalence of depressive symptoms among patients with bullous dermatoses ranged from 40% to 80%. The prevalence of depression diagnosis among patients with bullous dermatoses ranged from 11.4% to 28%. CONCLUSIONS AND RELEVANCE: In this systematic review, high rates of depression and depressive symptoms existed among patients with bullous skin disease. Adequate treatment of bullous dermatoses may be associated with a decrease in mental health burden on patients.

Differences in acne therapy prescribing patterns between dermatologists and pediatricians: A population-based study.

BACKGROUND/OBJECTIVES: Acne is a common skin condition that may be treated by both dermatologists and pediatricians. However, the treatments provided by dermatologists and pediatricians may differ. We aimed to describe acne therapy prescribing patterns of dermatologists and pediatricians. METHODS: We performed a population-based, cross-sectional analysis using data from the National Ambulatory Medical Care Survey from 2006 to 2016 for pediatric patients (age ≤ 18 years). RESULTS: There were approximately 30.5 million (weighted) outpatient acne visits between 2006 and 2016 for pediatric patients; 52% of visits were conducted by dermatologists, 29% by pediatricians, and 19% by other providers. Compared to pediatricians, dermatologists saw older patients (mean age 15.5 ± 0.12 vs 13.5 ± 0.35; P < .001), as well as a higher proportion of white patients (92.5% vs 76.3%; P < .001), non-Hispanic patients (89.5% vs 81.6%; P < .001), and patients with private insurance (84.6% vs 67.8%; P < .001). Compared to patients seen by dermatologists, patients seen by pediatricians were 68% less likely to receive topical retinoids (aOR 0.32, 95% CI 0.22-0.46), 38% less likely to receive topical antibiotics (aOR 0.62, 95% CI 0.41-0.95), and 48% less likely to receive oral antibiotics (adjusted aOR 0.52, 95% CI 0.36-0.75). CONCLUSIONS: Our findings demonstrate that pediatricians prescribe topical retinoids, topical antibiotics, and oral antibiotics less frequently compared to dermatologists. It is important to understand these differences in prescribing patterns for acne and to identify potential educational gaps.

Primary Tumor Location Predicts Survival in Melanoma: A Retrospective Cohort Study of 239,257 Melanoma Patients.

The link between primary tumor location and overall survival in melanoma has been studied in the past, but its associated population and prognostic significance is less understood. The purpose of this study was to characterize melanoma demographics and disease-specific survival (DSS) in relation to primary tumor site. Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program were retrospectively analyzed; from 1973 to 2015, 239,257 patients diagnosed with cutaneous melanoma were included in the study and separated into three cohorts based on primary tumor site. The effect of primary location on melanoma survival was evaluated using Cox proportional hazards models. Tumors were predominantly localized and had a depth of ≤1 mm. Patients diagnosed with tumors originating in the upper and lower extremities had significantly increased DSS probability compared to those of the head and neck. Characteristics, including woman sex, married or widowed status, treated on the Pacific coast, and increasing year of diagnosis, were associated with greater DSS. Conversely, non-white or Hispanic origin, higher age at diagnosis, tumors with increased depth, or nodular or acral melanoma histology were associated with lower DSS. Primary tumor site is a significant predictive factor of DSS in cutaneous melanoma along with additional characteristics supported in our study.

The Use of Biologics During the COVID-19 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, there has been considerable discussion regarding the use of biologics in patients with inflammatory skin conditions, such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. This article discusses clinical trial data, real-world evidence, and guidelines and recommendations for biologics that inhibit tumor necrosis factor, interleukin (IL)-12/23, IL-17, IL-23, and IL-4/13 during the COVID-19 pandemic. Across these inflammatory skin conditions, existing data generally suggest that biologics do not seem to increase the risk of COVID-19 infection or worsen COVID-19 outcomes. The impact of biologics on COVID-19 is an area of active exploration.

Mental health outcomes in White patients versus patients with skin of color with psoriasis.

OBJECTIVE: To evaluate the relationship between psoriasis and mental health in patients from different racial backgrounds. METHODS: We performed a nationwide, cross-sectional study evaluating 7,519,662 (weighted) patients, comparing White patients versus patients with skin of color (SOC), using the 2004-2017 Medical Expenditure Panel Survey (MEPS). RESULTS: Psychological distress (measured by Kessler 6-Item Psychological Distress Scale) was similar between White and SOC patients (4.132 [95% CI,3.679-4.586] and 3.710 [95% CI,2.932-4.488], P=0.407). Depression (measured by Patient Health Questionnaire 2) was similar between White and SOC patients (0.886 [95% CI,0.744-1.027] and 0.748 [95% CI,0.506-0.989], P=0.385). Overall mental health (measured by Mental Component Summary) was similar between White and SOC patients (49.959 [95% CI,48.979-50.939] and 50.257 [95% CI,48.449-52.065], P=0.789). Perceived mental health state (measured by Perceived Mental Health Status) was similar between White and SOC patients (2.159 [95% CI,2.065-2.253] and 2.103 [95% CI,1.911-2.294], P=0.603). CONCLUSION: There were no significant differences in mental health outcome scores between White and SOC patients with psoriasis. Clinicians should screen for and manage mental health comorbidities in psoriasis patients of all racial backgrounds.

A new era of moisturizers.

BACKGROUND: Moisturizers traditionally function to replenish both the intercellular lipid lamella and natural moisturizing factors, and form a hydrolipid film on the skin surface to decrease transepidermal water loss and improve hydration. As we continue to identify epidermal lipid imbalance in patients with atopic dermatitis, we turn to the use of bioactive ingredients in moisturizers for improving barrier repair and function. METHODS: This review aims to explore the modern use of moisturizers in targeting various components of the skin barrier, dampening immune response, and restoring microbial balance. We conducted a balanced and comprehensive narrative review of the literature. Studies were identified by searching electronic databases (MEDLINE and PubMed), focusing on studies and trials regarding moisturizers that include endocannabinoids, bioactive lipids, anti-inflammatory agents, antioxidants, and microbiome modulators. Only articles published in English language were included. RESULTS: The aforementioned ingredients exert additional biological effects to improve skin function by upregulating lipid synthesis, decreasing neurosensory transmission of itch signals, reversing oxidative stress, decreasing inflammatory cell activity and cytokine release, and modulating skin microbiota. The shift from traditional moisturizers to those with bioactive ingredients, anti-inflammatory agents, and microbiome modulating effects opens a realm of possible therapeutic options for patients with barrier-defective cutaneous conditions. CONCLUSION: Focusing on the disrupted skin barrier as a target for both prevention and treatment and incorporating a combined strategy that utilizes the aforementioned agents to tackle barrier dysfunction from different angles remains a promising area for clinical impact in dermatology.

Combined antibiotic, steroid, and moisturizer for atopic dermatitis: A two-year case series of patient-reported outcomes.

BACKGROUND: Eczema treatments that target Staphylococcus aureus include topical mixtures of antimicrobial agent and corticosteroid diluted in a moisturizer base, previously described in the literature as compounded antibacterial, steroid, and moisturizer (CASM). There have been no placebo-controlled blinded studies of CASM. Thus, patient-reported outcome data may prove valuable. OBJECTIVE: To determine the patient-reported clinical course of eczema treatment with CASM. METHODS: Longitudinal case series between May 2016 and August 2018 of CASM patients/parents. Patients completed surveys including the POEM measure at start of treatment, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, and 12 months thereafter. Response curves were fitted to severity measures over time and compared by patient age group; survival analysis was used to estimate time-to-clear status as a function of patient age and initial severity. RESULTS: A total of 2153 reports were received from 728 unique respondents with a median patient age of 7 and range of 0-85. Response curves showed significant improvement over time leading to plateaus between 30 and 60 days of treatment. Overall mean improvement between start and day 90 for POEM was 14.3 (from 20.0 [95% CI 11.4-28.8] to 5.7 [95% CI -3.2 to 14.8]). Improvement was seen in each age group. CONCLUSIONS: Patient-reported outcomes suggest efficacy of CASM. There were large reductions in POEM scores, mostly in the first 30 days of treatment for all age groups.

Drug eruptions associated with tumor therapy: Great imitators.

Many studies have investigated cutaneous reactions to antitumor drugs and found them to be quite numerous. We describe drug eruptions that may be associated with different therapies by class: antimetabolite chemotherapeutics, genotoxic agents, spindle inhibitors, signal transduction inhibitors, and immunotherapies. Methotrexate is most often associated with mucocutaneous reactions, alkylating antimetabolite agents with hyperpigmentation, and platinum antimetabolite agents with type I IgE-mediated hypersensitivity reactions. Anthracycline derivatives can induce the hand-foot syndrome in patients, and bleomycin is associated with a bleomycin-induced flagellate erythema. Taxane spindle inhibitors can result in acneiform eruptions, which may also be seen with use of epidermal growth factor receptor inhibitors. Imatinib and its derivatives can cause a truncal maculopapular eruption, whereas multikinase inhibitors can produce a hand-foot-skin reaction. Vemurafenib can result in squamous cell carcinomas and photosensitivity. First-generation mammalian target of rapamycin inhibitors may cause a maculopapular eruption initially involving the face and neck. Programmed death (PD)-1-ligand and receptor inhibitors are associated with bullous pemphigoid. Ipilimumab, targeting Cytotoxic -T- Lymphocyte- associated (CTLA-4) receptors, can cause a morbilliform reaction, whereas Interleukin -2 (IL-2) analogs can create the capillary leak syndrome. Chemotherapeutic drug eruptions classically can manifest in the aforementioned ways; however, it is important to understand that they are associated with myriad cutaneous adverse effects, which may be mistaken for organic skin disease. Oncologists prescribing these medications should be familiar with the cutaneous side effects of these medications, and so they may counsel patients to be on the lookout for them.