Commonly prescribed medications associated with alopecia.

BACKGROUND: The diagnosis and treatment of medication-associated alopecia often challenges patients and physicians. While numerous studies on the topic exist, limited information on the strength and magnitude of these studies exists. OBJECTIVES: We investigated the most commonly prescribed medications with high levels of evidence to support associations with alopecia. METHODS: A list of most commonly prescribed medications was compiled using the "Top 100 Prescriptions, Sales" (Intercontinental Marketing Services) and "Top 200 Names Searched" (RxList.com). PubMed, Embase, and Web of Science were searched for "generic drug name" AND "alopecia" and "generic drug name" AND "hair loss." Two reviewers independently reviewed articles for drug, study type and level of evidence, and number of alopecia cases. RESULTS: A total of 192 unique drugs were investigated, with 110 yielding positive search results. Of these, 13 were associated with alopecia in studies with strong levels of evidence (adalimumab, infliximab, budesonide, interferon ß-1α, tacrolimus, enoxaparin, zoster vaccine, lamotrigine, docetaxel, capecitabine, erlotinib, imatinib, and bortezomib). LIMITATIONS: Only full-length articles available in the English language were included. The methodology used relied on lists of drugs based on their sales rather than number of prescriptions, which likely overrepresented expensive drugs. CONCLUSIONS: Few studies with high levels of evidence have been conducted on the topic of medication-associated alopecia. The mechanisms of hair loss must be further identified to provide effective management.

Prioritising Cochrane reviews to be updated with health equity focus.

BACKGROUND: The prioritisation of updating published systematic reviews of interventions is vital to prevent research waste and ensure relevance to stakeholders. The consideration of health equity in reviews is also important to ensure interventions will not exacerbate the existing inequities of the disadvantaged if universally implemented. This study aimed to pilot a priority setting exercise based on systematic reviews of interventions published in the Cochrane Library, to identify and prioritise reviews to be updated with a focus on health equity. METHODS: We conducted a priority setting exercise with a group of 13 international stakeholders. We identified Cochrane reviews of interventions that showed a reduction in mortality, had at least one Summary of Findings table and that focused on one of 42 conditions with a high global burden of disease from the 2019 WHO Global Burden of Disease report. This included 21 conditions used as indicators of success of the United Nations Universal Health Coverage in attaining the Sustainable Development Goals. Stakeholders prioritised reviews that were relevant to disadvantaged populations, or to characteristics of potential disadvantage within the general population. RESULTS: After searching for Cochrane reviews of interventions within 42 conditions, we identified 359 reviews that assessed mortality and included at least one Summary of Findings table. These pertained to 29 of the 42 conditions; 13 priority conditions had no reviews with the outcome mortality. Reducing the list to only reviews showing a clinically important reduction in mortality left 33 reviews. Stakeholders ranked these reviews in order of priority to be updated with a focus on health equity. CONCLUSIONS: This project developed and implemented a methodology to set priorities for updating systematic reviews spanning multiple health topics with a health equity focus. It prioritised reviews that reduce overall mortality, are relevant to disadvantaged populations, and focus on conditions with a high global burden of disease. This approach to the prioritisation of systematic reviews of interventions that reduce mortality provides a template that can be extended to reducing morbidity, and the combination of mortality and morbidity as represented in Disability-Adjusted Life Years and Quality-Adjusted Life Years.

Tocilizumab Treatment in COVID-19 Patients: Comparing Cutaneous Disease and Adverse Drug Effects.

Actemra (tocilizumab) received emergency use authorization for the treatment of coronavirus disease 2019 (COVID-19) in June 2021. Literature has linked numerous cutaneous adverse effects to tocilizumab. In this current survey, investigators reviewed and compared these adverse effects to the common cutaneous manifestations of COVID-19. While similarities in patient presentation exist, important distinctions are made to aid dermatologists in their clinical diagnosis.  J Drugs Dermatol. 2023;22(12):e42-e43.     doi:10.36849/JDD.6532e.

Nirmatrelvir-ritonivir, COVID-19, and possible adverse cutaneous reactions.

Nirmatrelvir-ritonivir (Paxlovid) recently received emergency use authorization for the treatment of coronavirus disease 2019 (COVID-19). Literature has linked numerous cutaneous adverse effects to nirmatrelvir and ritonavir, the copackaged tablets within Paxlovid. A review and comparison of these adverse effects to the common cutaneous manifestations of COVID-19 is provided. Numerous drug-to-drug interactions exist between nirmatrelvir-ritonivir and commonly-used medications within dermatology.

Holistic dermatology: An evidence-based review of modifiable lifestyle factor associations with dermatologic disorders.

BACKGROUND: Holistic dermatology focuses on treating the human body as a whole and implementing lifestyle changes to enhance the treatment and prognosis of skin disease. Understanding the interplay between modifiable lifestyle factors and patients' dermatologic health will help physicians better inform patients on self-care methods to mitigate the burden of their skin disease(s). OBJECTIVE: To review the current scientific literature on the relationship between modifiable lifestyle factors and the dermatologic outcome of skin disorders. METHODS: A systematic literature search on PubMed, Cochrane, and Web of Science was conducted to identify research articles examining the relationship between dermatology and 6 major categories of modifiable lifestyle factors: diet, sleep, exercise, stress, alcohol, and smoking. RESULTS: A substantial amount of evidence supports the relationship between modifiable lifestyle factors and dermatologic outcomes. There were the most studies on diet, stress, alcohol, and smoking, but all lifestyle factors were supported by some degree of scientific evidence. CONCLUSION: All modifiable lifestyle factors explored in this review play a critical role in modulating the onset and progression of skin disease. We anticipate more research studies in the future and an increasing integration of holistic dermatology into patient care.

Focused update: Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AKs) are rough scaly patches that arise on chronically UV-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: In 2021, the American Academy of Dermatology published guidelines to assist in clinical decision-making for the management of AK. The purpose of this focused guideline update is to incorporate recently available evidence on the use of topical tirbanibulin to treat AK. METHODS: A multidisciplinary work group conducted a systematic review to evaluate data on the use of tirbanibulin for AK and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading a clinical recommendation. The graded recommendation was voted on to achieve consensus. RESULTS: Two trials were identified, and analysis of the evidence resulted in 1 recommendation. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. Long-term efficacy and safety data are not currently available. CONCLUSIONS: A strong recommendation for the use of topical tirbanibulin to join the currently recommended list of topical therapies for AK was made on the basis of the available evidence.

Dermatologic Research Potential of the Observational Health Data Sciences and Informatics (OHDSI) Network.

BACKGROUND: The Observational Health Data Sciences and Informatics (OHDSI) network enables access to billions of deidentified, standardized health records and built-in analytics software for observational health research, with numerous potential applications to dermatology. While the use of the OHDSI has increased steadily over the past several years, review of the literature reveals few studies utilizing OHDSI in dermatology. To our knowledge, the University of Colorado School of Medicine is unique in its use of OHDSI for dermatology big data research. SUMMARY: A PubMed search was conducted in August 2020, followed by a literature review, with 24 of the 72 screened articles selected for inclusion. In this review, we discuss the ways OHDSI has been used to compile and analyze data, improve prediction and estimation capabilities, and inform treatment guidelines across specialties. We also discuss the potential for OHDSI in dermatology - specifically, ways that it could reveal adherence to available guidelines, establish standardized protocols, and ensure health equity. Key Messages: OHDSI has demonstrated broad utility in medicine. Adoption of OHDSI by the field of dermatology would facilitate big data research, allow for examination of current prescribing and treatment patterns without clear best practice guidelines, improve the dermatologic knowledge base and, by extension, improve patient outcomes.

Sexual orientation and gender identity (SOGI) data in dermatologic studies and opportunities for inclusion.

Dermatologists serve a vast array of patients with unique backgrounds. The National Institutes of Health (NIH) designated members of sexual and gender minorities as underrepresented in scholarly literature. Our study examines the past 10 years of studies published in highly-cited dermatologic journals, surveying each study for common data collection of sexual orientation and gender identity (SOGI) in dermatological studies. We found representation of sexual and gender minorities to be increasing in dermatological studies but recommend that SOGI data be collected regularly just as any other common variable in dermatological patient studies.

Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Guidelines of care for the management of actinic keratosis: Executive summary.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. OBJECTIVE: This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. METHODS: A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. LIMITATIONS: The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. CONCLUSIONS: Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment.

BACKGROUND: The innate immune system is recognized as an essential aspect of COVID-19 pathogenesis. Toll-like receptors (TLRs) are important in inducing antiviral response, triggering downstream production of interferons (IFNs). Certain loss-of-function variants in TLR7 are associated with increased COVID-19 disease severity, and imiquimod (ImiQ) is known to have immunomodulating effects as an agonist of TLR7. Given that topical imiquimod (topImiQ) is indicated for various dermatologic conditions, it is necessary for dermatologists to understand the interplay between innate immunity mechanisms and the potential role of ImiQ in COVID-19, with a particular focus on TLR7. SUMMARY: Our objective was to survey recent peer-reviewed scientific literature in the PubMed database, examine relevant evidence, and elucidate the relationships between IFNs, TLR7, the innate immune system, and topImiQ in the context of COVID-19. Despite limited studies on this topic, current evidence supports the critical role of TLRs in mounting a strong immune response against COVID-19. Of particular interest to dermatologists, topImiQ can result in systemic upregulation of the immune system via activation of TLR7. Key Message: Given the role of TLR7 in the systemic activation of the immune system, ImiQ, as a ligand of the TLR7 receptor, may have potential therapeutic benefit as a topical immunomodulatory treatment for COVID-19.

A Review of the Current Evidence Connecting Seborrheic Dermatitis and Parkinson's Disease and the Potential Role of Oral Cannabinoids.

Parkinson's disease (PD) is a neurodegenerative disorder associated with multiple comorbidities, including seborrheic dermatitis (SD), which develops in more than half of PD patients. SD in patients with PD can be severe and frequently intractable by traditional topical therapy. Cannabinoids possess anti-inflammatory and neuromodulatory properties working within the intrinsic endocannabinoid system, the activation of which may alleviate the motor symptoms of PD. The effect of cannabinoids on SD is unknown. Here we explore the pathophysiological mechanisms and possible therapeutic role of oral cannabinoids in PD patients with SD, and review speculative mechanisms underlying the association of PD and SD. Current data supporting the use of cannabinoids in both PD and SD, as well as oral cannabinoid safety and tolerability, are presented. Cannabinoids may provide the possibility of simultaneous treatment of both SD and PD. Specific SD studies and additional safety data on oral cannabinoids are needed.

Response to "Assessing a Paradigm Shift: Perceptions of the USMLE Step 1 Scoring Change to Pass/Fail".

We commend Wei et al1 for highlighting the fundamental shift that dermatology program directors (PDs) and students alike will experience following the change of the USMLE Step 1 to pass/fail.

Leprosy: Treatment and management of complications.

In the second article in this continuing medical education series, we review the treatment of leprosy, its immunologic reactions, and important concepts, including disease relapse and drug resistance. A fundamental understanding of the treatment options and management of neuropathic sequelae are essential to reduce disease burden and improve patients' quality of life.

Leprosy: Clinical aspects and diagnostic techniques.

Leprosy, also known as Hansen's disease, is a curable infectious disease that remains endemic in >140 countries around the world. Despite being declared "eliminated" as a global public health problem by the World Health Organization in the year 2000, approximately 200,000 new cases were reported worldwide in 2017. Widespread migration may bring leprosy to nonendemic areas, such as North America. In addition, there are areas in the United States where autochthonous (person-to-person) transmission of leprosy is being reported among Americans without a history of foreign exposure. In the first article in this continuing medical education series, we review leprosy epidemiology, transmission, classification, clinical features, and diagnostic challenges.

The association of metformin use with keratinocyte carcinoma development in high-risk patients.

Keratinocyte carcinoma (KC) is the most common malignancy in white skinned populations. Metformin one of the most commonly prescribed drugs and has been reported to protect against solid cancers. The association between metformin and KC has not been studied in patients at high risk for a subsequent KC. The purpose of this study is to evaluate the association between metformin and KC development in high-risk patients. We performed a secondary analysis of patients enrolled in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial to compare risk for KC development between metformin users and non-users. Metformin-users compared to non-users had a significantly lower risk for squamous cell carcinoma with an adjusted Hazard ratio (HR): 0.45, (CI: 0.24-0.84, P < .01) and basal cell carcinoma (HR: 0.70, CI: 0.49-0.97, P < .03). Patients at high risk might benefit from metformin use against a subsequent KC.

An Analysis of Skin of Color Dermatology Related Content on Instagram.

Importance: Social media is making information about skin of color more readily available to those unfamiliar with ethnic skin and hair. Objectives: To answer: 1) what skin of color-related dermatology content is being posted on Instagram? And 2) who is producing this content? Design: Cross-sectional epidemiologic study analyzing the content of posts associated with 31 Instagram skin of color dermatology-related topics (hashtags). Setting: Population-based Participants: The Instagram accounts linked with the top 9 posts as generated by the Instagram algorithm associated with each search term. Exposures: Instagram account holders. Main Outcomes and Measures: [1] The number of posts associated with each skin of color dermatology hashtag search term. [2] Classification of posts as either educational or promotional. [3] Classification of posts as a photo or video. [4] Classification of Instagram accounts that produced the posts (American board-certified dermatologists, dermatology residents, foreign dermatologists, patients, medical interest groups, or other). [5] Quantification of the number of post likes and comments. [6] Comparison of number of educational and promotional posts between board-certified dermatologists and other Instagram users. Results: The 31 sampled hashtags were associated with a total of 9,087,589 posts as of January 16, 2020. 219 of the 288 top posts generated from these queries met inclusion criteria. Board-certified dermatologists (26 posts) only generated 12% of top posts, whereas individuals not certified in dermatology produced 88% of top content. Of this group, social media influencers were the largest subcategory (37 posts). A majority of the top posts were promotional (135 posts, 61.6%) and formatted as photos (181 posts, 82.6%). While there was a significant difference in the number of likes for content posted by board-certified dermatologists vs non-dermatologists (P=0.027), these differences became non-significant after stratifying by the intention of the post (promotional P=0.13, educational P=0.17). Conclusions and Relevance: Board-certified dermatologists are underrepresented among people generating top skin of color dermatology-related content on Instagram. Board-certified dermatologists should establish a more prominent presence on social media platforms so that patients have greater access to accurate, evidenced-based educational resources regarding dermatologic conditions, treatment options, and treatment risks from reliable sources. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.5142.

An Observational Study of the Application of a Topical Cannabinoid Gel on Sensitive Dry Skin.

Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus, erythema and excoriation. While AD has a multifactorial etiology, neuro-signaling pathways are now recognized to play an essential role in the pathogenesis of AD, particularly pruritus. Neuromodulators, such as topical naltrexone, are being utilized in AD treatment. Another class of neuromodulator, Palmitoylethanolamide (PEA), has demonstrated effectiveness in the treatment of itch, excoriation and erythema in AD patients. Phytocannabinoids including cannabidiol (CBD) are becoming increasingly accessible to the public and continue to be advertised for their efficacy to treat inflammatory skin disorders such as eczema. However, no human studies have been conducted to support the claim. Therefore, this study aimed to explore the effects of CBD in individuals with self-reported eczema. Twenty individuals consented to participate and 16 completed a 28-item online questionnaire assessing subjects’ disease severity using Patient Oriented Eczema Measure (POEM) and psychosocial burden of their disease through the emotional domain of Quality of Life Hand Eczema Questionnaire (QOLHEQ). Findings demonstrated a significant reduction in the mean score of POEM from baseline (mean ±SE: 16±1.35) and at a two weeks interval (8.25 ±1.80), P<0.0007. Similar reduction was seen in emotional domain of QOLHEQ from a mean score of 20.9±2.06 to 8.375 ±1.609 at 2 week-interval, P<0.004. 67% of subjects reported a decrease in itch and 50% perceived an improvement in their eczema by more than 60%. This observational study shed light on the potential clinical utility of topical CBD in the treatment of atopic dermatitis. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5464.

Canadian Burden of Skin Disease From 1990 to 2017: Results From the Global Burden of Disease 2017 Study [Formula: see text].

BACKGROUND: Skin diseases can have high morbidity that can be costly to society and individuals. To date, there has been no comprehensive assessment of the burden of skin disease in Canada. OBJECTIVES: To evaluate the burden of 18 skin and subcutaneous diseases from 1990 to 2017 in Canada using the Global Burden of Disease (GBD) data. METHODS: The 2017 GBD study measures health loss from 359 diseases and injuries in 195 countries; we evaluated trends in population health in Canada from 1990 to 2017 using incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs). Data are presented as rates (per 100 000), counts, or percent change with the uncertainty interval in brackets. RESULTS: From 1990 to 2017 for all skin diseases, DALY rates increased by 8% to 971 per 100 000 (674-1319), YLD rates increased by 8% to 897 per 100 000 (616-1235), YLL rates increased by 4% to 74 per 100 000 (53-89), and death rates increased by 18% to 5 per 100 000 (3-6). DALY rates for melanoma increased by 2% to 54 per 100 000 (39-68), for keratinocyte carcinoma by 14% to 17 per 100 000 (16-19), and for skin and subcutaneous disease by 8% to 900 per 100 000 (619-1233). The observed over expected ratios were higher for skin and subcutaneous disease (1.37) and keratinocyte carcinoma (1.17) and were lower for melanoma (0.73). CONCLUSIONS: The burden of skin disease has increased in Canada since 1990. These results can be used to guide health policy regarding skin disease in Canada.

Orchestrating a virtual conference amidst the COVID-19 pandemic.

The current Coronavirus Disease 2019 (COVID-19) pandemic has impacted individuals and groups all across the globe as countries and cities face widespread lockdown to limit transmission of the virus. Many have adapted quickly, utilizing virtual platforms for interviews, employment, and academic/social events. Academic conferences, such as the annual Cochrane Skin Conference, faced similar challenges as large gatherings have been banned. The in-person conference was cancelled several days prior to its hosting at the University of Colorado, leading conference organizers to employ a virtual platform to continue the conference as scheduled. In this letter, logistics, troubleshooting, and conversion of an NIH-funded conference from an in-person to a successful virtual conference are discussed. We hope this letter may serve as a guide for future hosting of academic conferences, and to those dedicated to collaboration and the sharing of information during such unprecedented times.