Novel ANKRD26 and PDGFRB gene mutations in pediatric case of non-Langerhans cell histiocytosis: Case report and literature review.

Cutaneous non-Langerhans cell histiocytosis (NLCH) is a rare and biologically benign entity that can be broadly classified into two categories: xanthogranuloma and non-xanthogranuloma. The xanthogranuloma family is characterized by a proliferation of histiocytes with both macrophage and dendritic cell differentiation, negative BRAF mutation, and rare Touton-type giant cells. Molecular studies have reported that mutations involved in the MAPK signaling pathways are implicated in the pathophysiology of histiocytoses. While LCH is associated with the somatic mutation of BRAF v600e, however, mutations and gene fusions in NLCH cases are undefined. We hereby present a 19-month-old female with recalcitrant nodular rashes diagnosed as NLCH with associated novel genetic mutation involving ANKRD26 and PDGFRB genes, as well as PDGFRB::CD74 fusion mRNA. Immunohistochemical staining showed strong and diffuse CD68 and CD163 positivity, and negative CD1a, CD207, ALK D5F3, S100 protein, and BRAF V600E (VE1). Albeit unknown significance, this case of an ANKRD26 and PDGFRB gene mutation in cutaneous NLCH has not been reported prior in the literature. Our case highlights the advantage of pathology and genetic studies in cutaneous NLCH to increase the understanding of this heterogeneous enigmatic disorder and identify further options in management.

Verrucous venous malformation with thrombocytopenia in a neonate.

Verrucous venous malformations (VVM) are rare, congenital, slow-flow vascular anomalies that have been historically difficult to characterize due to clinical mimics and unclear histological evaluation. A life-threatening complication of VVMs is localized intravascular coagulation. Herein, we describe a male neonate who presented with a congenital VVM on the left lower extremity with associated severe thrombocytopenia. We discuss the multifaceted diagnostic approach used to identify this VVM, while highlighting the use of WT-1 as a negative predictive marker; we additionally outline novel treatment options and management beyond cutaneous involvement.

Use of Oral Supplements and Topical Adjuvants for Isotretinoin-Associated Side Effects: A Narrative Review.

Acne is a chronic inflammatory disease of the pilosebaceous unit with a multifactorial etiology and is one of the most common conditions treated by dermatologists and primary care physicians. Within an extensive and evolving treatment landscape, oral isotretinoin has demonstrated efficacy for treatment of severe, recalcitrant acne. Several side effects of isotretinoin have been reported, including laboratory abnormalities, mucocutaneous, and musculoskeletal effects, which may reduce compliance and patient satisfaction with treatment. In this narrative review, we aim to review the efficacy and safety profile of oral supplements or topical adjuvant therapies in mitigating isotretinoin-associated mucocutaneous and musculoskeletal side effects. Oral supplements reviewed include omega-3 fatty acids, vitamin E, folic acid and vitamin B12, antihistamines, l-carnitine, biotin, and combined oral supplements. Topical adjuvants include a hyaluronic acid, biosaccharide gum-2, and glycerine gel-cream; a nongreasy, noncomedogenic, fragrance-free moisturizing cream; dexpanthenol; trichloroacetic acid; and a combination cream. Most of the supplements and topical adjuvants demonstrated efficacy with an adequate level of supporting evidence and no reported adverse events, indicating an adequate safety profile. Patients on isotretinoin may benefit from using oral supplements and topical adjuvants to minimize primarily mucocutaneous side effects, increase adherence to treatment, and thereby improve overall outcomes.

Experiencing Workplace Bullying in Patients with Alopecia Areata: A Cross-Sectional Survey Study.

Introduction: Alopecia areata (AA) is an immune-mediated hair loss condition with substantial psychosocial impact. The impact of AA on social interactions at work has not been established. Methods: We administered the Negative Acts Questionnaire-Revised Scale to the National Alopecia Areata Foundation database to evaluate workplace bullying in patients with AA. Results: Ultimately, 673/1,120 individuals who met inclusion criteria completed the survey. Most respondents were female (n = 537, 79.8%), Caucasian (n = 508, 75.5%), with an average age of 46.8 ± 14, and employed full-time (n = 427, 63.4%). Our results demonstrate 21.7% (n = 146) of respondents experienced workplace bullying. Participants most frequently faced having their opinions ignored (53.8%, n = 362), being excluded (47.7%, n = 321), and having gossip spread about them (44.0%, n = 296). Notably, 75.0% (n = 120/160) of individuals who self-reported bullying addressed the behavior; however, 30.8% of participants noted the bully continued (30.8%, n = 37). Stress associated with filing a complaint (43.5%, n = 293) and effect on future career options (36.1%, n = 243) were common barriers to report bullying. Conclusion: This study expands our understanding of the psychosocial impact of AA by confirming individuals with AA experience workplace bullying. Stigma against patients may play a role in this phenomenon. Future work is warranted to identify strategies to reduce bullying against patients with AA.

Assessing Patient's Values When Selecting Treatments for Alopecia Areata: A Cross-Sectional Survey Study.

Introduction: Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. There is currently only one Food and Drug Administration (FDA)-approved treatment for AA; as a result, a wide range of treatments are commonly administered. This study aimed to determine how patients with AA prioritize treatment characteristics when choosing a therapy. Methods: A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to rank the importance of five treatment domains. Results: Of the 1,074 completed surveys (completion rate 77.4%), most respondents were female (85.4%) and white (77.8%) with an average age of 49.3 ± 15.4 years. Respondents had AA for an average of 17.7 ± 15.4 years, with 90.0% experiencing current active hair loss. 95.6% of respondents considered the treatment's ability to achieve hair regrowth as important, 93.9% listed the availability of information about the treatment (e.g., via doctor or online) as important, 89.1% ranked the treatment side effects as important, 75.7% the cost, and 68.0% the convenience of use. A sub-analysis was performed examining responses between respondents who identify as white versus nonwhite, which showed that while the order of importance was the same between groups, a significantly larger proportion of nonwhite respondents attributed higher importance to cost (white: 73.8%, nonwhite: 82.4%; p = 0.006) and convenience (white: 65.3%, nonwhite: 77.3%; p < 0.001) than their white counterparts. Discussion/Conclusion: These findings identify key domains that can serve as a starting point in shared decision-making between patients and physicians. This knowledge can streamline dermatologist delivery of key information and highlight areas of improvement for future therapeutics. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations.

Evaluation of the Safety and Effectiveness of Nutritional Supplements for Treating Hair Loss: A Systematic Review.

Importance: Despite the widespread use of nutritional supplements and dietary interventions for treating hair loss, the safety and effectiveness of available products remain unclear. Objective: To evaluate and compile the findings of all dietary and nutritional interventions for treatment of hair loss among individuals without a known baseline nutritional deficiency. Evidence Review: The MEDLINE, Embase, and CINAHL databases were searched from inception through October 20, 2021, to identify articles written in English with original findings from investigations of dietary and nutritional interventions in individuals with alopecia or hair loss without a known baseline nutritional deficiency. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. Outcomes of interest were disease course, both objectively and subjectively measured. Data were evaluated from January 3 to 11, 2022. Findings: The database searches yielded 6347 citations to which 11 articles from reference lists were added. Of this total, 30 articles were included: 17 randomized clinical trials (RCTs), 11 clinical studies (non-RCT), and 2 case series studies. No diet-based interventional studies met inclusion criteria. Studies of nutritional interventions with the highest-quality evidence showed the potential benefit of Viviscal, Nourkrin, Nutrafol, Lamdapil, Pantogar, capsaicin and isoflavone, omegas 3 and 6 with antioxidants, apple nutraceutical, total glucosides of paeony and compound glycyrrhizin tablets, zinc, tocotrienol, and pumpkin seed oil. Kimchi and cheonggukjang, vitamin D3, and Forti5 had low-quality evidence for disease course improvement. Adverse effects were rare and mild for all the therapies evaluated. Conclusions and Relevance: The findings of this systematic review should be interpreted in the context of each study's design; however, this work suggests a potential role for nutritional supplements in the treatment of hair loss. Physicians should engage in shared decision-making by covering the potential risks and benefits of these treatments with patients experiencing hair loss. Future research should focus on larger RCTs with active comparators.

Public Perceptions, Factors, and Incentives Influencing Patient Willingness to Share Clinical Images for Artificial Intelligence-Based Healthcare Tools.

INTRODUCTION: The use of artificial intelligence (AI) as a diagnostic and decision-support tool is increasing in dermatology. The accuracy of image-based AI tools is incumbent on images in training sets, which requires patient consent for sharing. This study aims to understand individuals' willingness to share their images for AI and variables that influence willingness. METHODS: In an online survey administered via Amazon Mechanical Turk, sketches of the hand, face, and genitalia assigned to two use cases employing AI (research vs. personal medical care) were shown. Participants rated willingness to share the image on a 7-point Likert scale. RESULTS: Of the 1010 participants, individuals were most willing to share images of their hands (81.2%), face (70.3%), and lastly genitals (male: 56.8%, female: 46.7%). Individuals were more willing to share for personal care versus research (OR 0.77 [95% CI 0.69-0.86]). Willingness to share was higher among males, participants with higher education, tech-savvy participants, and frequent social media users. Most participants were willing to share images if offered monetary compensation, with face images requiring the highest payment (mean $18.25, SD 20.05). Only 38.7% of individuals refused image sharing regardless of any monetary compensation, with the majority of this group unwilling to share images of the genitals. CONCLUSIONS: This study demonstrates overall public support for sharing images to AI-based tools in dermatology, with influencing factors including image type, context, education level, technology comfort, social media use, and monetary compensation.

Post-Traumatic Stress Disorder in Patients with Alopecia Areata: A Survey Study in the USA.

Introduction: Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. AA is comorbid with mental health disorders including anxiety and depression. This study aimed to evaluate the presence of post-traumatic stress disorder (PTSD) in relation to hair loss in patients with AA. Methods: A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to complete the PTSD Checklist for the DSM-5 (PCL-5), a validated screening tool for PTSD in the context of their AA. Results: Of the 1,449 completed surveys (completion rate 79.6%), most respondents were female (83.8%) and white (76.6%) with an average age of 50.6 ± 15.6 years. Respondents had AA for an average of 17.7 ± 15.8 years, with 91.4% experiencing current active hair loss. A total of 33.9% of respondents screened positively for PTSD, with an average score of 48.8 ± 12.3 on the PCL-5 in participants who screened positively. Participants with alopecia totalis have the highest average PCL-5 score of 30.1 ± 19.2, followed by participants with alopecia universalis with an average score of 26.0 ± 19.9, and lastly patchy AA with an average score of 24.5 ± 18.3 (p = 0.003). Feelings of intrusion and avoidance were the predominant reported symptoms. Total PTSD scores were significantly higher in respondents who were younger and identified as Black or African American and Hispanic when compared to white and non-Hispanic respondents, respectively. Conclusion: These findings identify that one in 3 patients with AA in this cohort meet the screening criteria for PTSD specifically relating to their hair loss experience. These results further highlight the mental health comorbidities associated with AA and emphasize that these symptoms may persist even after hair regrowth. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations. Finally, respondent's baseline mental health was not assessed; therefore, a causal relationship between AA and PTSD cannot be deduced.

An Assessment of Current Clinician-Reported and Patient-Reported Outcome Measures for Alopecia Areata: A Scoping Review.

Although progress has been made in developing outcome measures for AA, the use of these measures remains unstandardized. A scoping review was conducted to identify the clinician-reported outcome measures (ClinROMs) and patient-reported outcome measures (PROMs) used in assessing and treating AA, the results of which revealed heterogeneity in AA outcome measures. Of 23 research studies ultimately included, only 2 ClinROMs were used by >15% of studies; likewise, of 110 clinical trials evaluated, numerous outcome instruments were used, but only one ClinROM was used by >5% of trials (Severity of Alopecia Tool). These results suggest the need for consensus and standardization in both research and trial settings.

New Developments in Topical Acne Therapy.

Acne vulgaris is a common chronic inflammatory disease with a multifactorial pathogenesis. Although myriad acne treatments are available, current options may not be sufficient because of a lack of efficacy, limited tolerability, or burden of cost to patients. In this review, we highlight recently approved topical acne treatments, as well as those currently in clinical trials. Novel formulations of tretinoin, tazarotene, and minocycline provide modifications of and improvements to existing products. Trifarotene, a novel fourth-generation retinoid, has demonstrated improved tolerability compared with existing topical retinoids. Clascoterone is a novel first-in-class antiandrogen that topically addresses the hormonal etiology of acne. The late-phase clinical trials pipeline consists of agents with bactericidal and anti-sebum mechanisms. Although it is evident that acne treatments continue to evolve, it is important to recognize the need for further comparative studies among new and existing agents to define optimal treatment algorithms that address not only safety and efficacy but also cost-effective care.

Shared Decision-Making, Therapeutic Choice, and Decisional Regret in Patients With Alopecia Areata.

Importance: Alopecia areata (AA) is an autoimmune disorder of hair loss with a complex and evolving treatment landscape, making it an ideal setting for shared decision-making (SDM) between patients and physicians. Given the varying efficacy, experience, and risks of treatments for AA, we sought to evaluate patient preferences for SDM and the association of SDM with decisional regret. Objective: To evaluate patient preferences for SDM and the association of SDM with decisional regret. Design, Setting, and Participants: A cross-sectional online survey using the validated SDMQ9 scale for shared decision-making and Decisional Regret Scale (DRS) was distributed using the National Alopecia Areata Foundation (NAAF) with the aim of assessing (1) patient preferences in SDM when making treatment decisions, (2) how patients perceived the last decision to have been made, (3) which components of SDM were incorporated into the last decision, and (4) decisional regret related to their last treatment decision. The survey was distributed from July 12, 2021, to August 2, 2021, and data analysis occurred from October 2021 to March 2022. Main Outcomes and Measures: Primary outcomes included (1) patient preferences in incorporation of SDM, (2) how patients made their most recent treatment decision, (3) which components of SDM were incorporated into their most recent treatment decision measured with the validated SDMQ9, and (4) an assessment of decisional regret in relation to SDM components and the most recent treatment modality used by the patient as measured by the validated DRS. Results: Of 1387 individuals who initiated the survey, 1074 completed it and were included in the analysis (77.4% completion rate). Overall, 917 respondents were women (85.4%). There were 5 American Indian or Alaska Native respondents (0.5%), 33 were Asian (3.1%), 112 Black or African American (10.4%), 836 White (77.8%), and 36 were multiracial (3.4%) or other (36 [3.4%]). The mean age (SD) was 49.3 (15.4) years. Most respondents preferred making the final treatment decision themselves after considering their physician's opinion (503 [46.8%]). Of those who preferred to make treatment decisions using SDM, most made the last AA treatment decision with their physician (596 [55%]; 95% CI, 53%-58%; P < .001). The components of SDM implemented by the patients' dermatologists most identified were the physician "explained the advantages and disadvantages of treatment options" (472 [44%]), and the physician "asked me which treatment option I prefer" (494 [45.9%]). Incorporation of SDM by physicians was generally associated with decreased decisional regret (all ORs with 95% CIs greater than 1.1; P < .01). The treatments associated with the lowest decisional regret were Janus kinase (JAK) inhibitors, followed by biologics, and deciding not to treat; whereas, the highest decisional regret was reported with anthralin and minoxidil. Conclusions and Relevance: The findings of this cross-sectional survey study suggest that patients with AA prefer to make treatment decisions with their dermatologist using SDM. When SDM is used, patients report less decisional regret, indicating that SDM may help improve the patient-reported quality of treatment decisions. Newer, more efficacious therapies such as JAK inhibitors may be related to lower decisional regret. Future studies should seek to devise solutions to implement SDM as the AA treatment landscape continues to evolve.

Isotretinoin Associated Rhabdomyolysis: Monitoring Creatine Kinase and Educating Patients.

Monitoring specific values at baseline and throughout treatment is standard of care for isotretinoin therapy; however, creatine kinase (CK) blood monitoring is often excluded. Herein, we describe the importance of CK monitoring during isotretinoin therapy to assess the risk of rhabdomyolysis and potential renal damage, regardless of muscle-related symptom presentation. We present 2 patients with hyperCKemia: a 16-year-old male on isotretinoin whose CK levels were elevated (7,325 U/L) when rhabdomyolysis symptoms were present, and an asymptomatic 18-year-old male with elevated CK levels (35,000 U/L) before starting isotretinoin. Based on our experience, we strongly recommend obtaining CK levels to monitor for and potentially prevent rhabdomyolysis and its associated complications.