Dysregulation of the Skin-Liver Axis in Prurigo Nodularis: An Integrated Genomic, Transcriptomic, and Population-Based Analysis.

Pruritus has long been linked to hepatic dysfunction; however, there are limited data characterizing the association between liver disease and prurigo nodularis (PN), a chronic inflammatory skin disease featuring severe pruritis. We thus conducted a cross-sectional analysis of hepatic comorbidities in PN patients using TriNetX, a large global health research network. This analysis revealed that PN patients had a higher risk (p < 0.001) of developing liver cirrhosis, acute and subacute hepatic failure, inflammatory liver disease, chronic hepatitis, nonalcoholic steatohepatitis, portal hypertension, fatty liver, chronic passive congestion of the liver, and hepatocellular carcinoma compared with healthy controls. The cumulative incidence of liver disease was about three times higher in PN patients compared with healthy controls. These findings provided the basis for translational studies to investigate a genetic mechanism for this association. Cutaneous transcriptomic analysis performed on PN patients revealed the dysregulation of genes related to hepatic failure in lesional PN compared with both nonlesional PN and control skin. Similarly, gene set variation analysis (GSVA) revealed a significantly increased (p < 0.05) activation of liver metabolism, chronic hepatic failure, acute hepatic failure, cholestatic liver disease, polycystic liver disease, and hepatocellular carcinoma pathways in lesional PN compared with control skin. A subsequent genome-wide association study (GWAS) identified shared single-nucleotide polymorphisms (SNPs) in the genes AR, EDIL3, MACROD2, PCSK5, RUNX1T1, TENM4, and ZEB2 between PN and liver disease from the FinnGen cohort. Significant dysregulation of the skin-liver axis in PN patients may explain the increased incidence and severity of hepatic comorbidities and help identify future therapeutic targets for PN.

Frequency and characteristics of chemotherapy-associated thrombotic microangiopathy: Analysis from a large pharmacovigilance database.

We used the information component (IC), a disproportionate Bayesian analysis comparing the number of observed versus expected adverse drug reactions, to determine the potential association between anti-neoplastic agents and thrombotic microangiopathy (TMA). The IC025 indicates the lower end of 95% of IC, in which a value >0 suggests a disproportionality signal between the drug of interest and the adverse drug reaction. Carfilzomib had the highest IC025 for TMA among all studied chemotherapies followed by gemcitabine, mitomycin, bevacizumab, and bortezomib.

Influence of melanoma type on incidence and downstream implications of cutaneous immune-related adverse events in the setting of immune checkpoint inhibitor therapy.

BACKGROUND: Emerging evidence suggests that cutaneous immune-related adverse events (cirAEs) are associated with a survival benefit in the setting of advanced melanoma treated with immune checkpoint inhibitor (ICI) therapy. Previous studies have not examined the role of melanoma subtypes on cirAE development and downstream therapeutic outcomes. OBJECTIVE: Examine the impact of melanoma subtypes on cirAE onset and survival among ICI recipients. METHODS: Retrospective multi-institutional cohort study. Multivariate time-series regressions were utilized to assess relationships between melanoma subtype, cirAE development, and survival. RESULTS: Among 747 ICI recipients, 236 (31.6%) patients developed a cirAE. Patients with acral melanoma were less likely to develop a cirAE (hazard ratio [HR] = 0.41, P = .016) compared to patients with nonacral cutaneous melanoma. Across all melanoma subtypes, cirAEs were associated with reduced mortality (HR = 0.76, P = .042). Patients with acral (HR = 2.04, P = .005), mucosal (HR = 2.30, P < .001), and uveal (HR = 4.09, P < .001) primaries exhibited the worst survival. LIMITATIONS: Retrospective cohort study. CONCLUSION: This is the first study to demonstrate differences in cirAE development among melanoma subtypes. The presence of cirAEs was associated with better survival. Further, the lower incidence of cirAEs may be a marker of immunotherapy response, which is reflected in the association between acral melanoma and mortality.

Asian American Self-Reported Discrimination in Healthcare and Having a Usual Source of Care.

BACKGROUND: Self-reported racial or ethnic discrimination in a healthcare setting has been linked to worse health outcomes and not having a usual source of care, but has been rarely examined among Asian ethnic subgroups. OBJECTIVE: We examined the association between Asian ethnic subgroup and self-reported discrimination in a healthcare setting, and whether both factors were associated with not having a usual source of care. DESIGN: Using the California Health Interview Survey (CHIS) 2015-2017, we used logistic regression models to assess associations among Asian ethnic subgroup, self-reported discrimination, and not having a usual source of care. Interactions between race and self-reported discrimination, foreign-born status, poverty level, and limited English proficiency were also analyzed. PARTICIPANTS: Respondents represented adults age 18 + residing in California who identified as White, Black, Hispanic, American Indian/Alaska Native, Asian (including Chinese, Filipino, Japanese, Korean, Vietnamese, and Other Asian), and Other. MAIN MEASURES: We examined two main outcomes: self-reported discrimination in a healthcare setting and having a usual source of care. KEY RESULTS: There were 62,965 respondents. After survey weighting, Asians (OR 1.78, 95% CI 1.19-2.66) as an aggregate group were more likely to report discrimination than non-Hispanic Whites. When Asians were disaggregated, Japanese (3.12, 1.36-7.13) and Koreans (2.42, 1.11-5.29) were more likely to report discrimination than non-Hispanic Whites. Self-reported discrimination was marginally associated with not having a usual source of care (1.25, 0.99-1.57). Koreans were the only group associated with not having a usual source of care (2.10, 1.23-3.60). Foreign-born Chinese (ROR 7.42, 95% CI 1.7-32.32) and foreign-born Japanese (ROR 4.15, 95% CI 0.82-20.95) were more associated with self-reported discrimination than being independently foreign-born and Chinese or Japanese. CONCLUSIONS: Differences in self-reported discrimination in a healthcare setting and not having a usual source of care were observed among Asian ethnic subgroups. Better understanding of these differences in their sociocultural contexts will guide interventions to ensure equitable access to healthcare.

US medical student perspectives on asian american patient inclusion in medical education: a qualitative Study.

BACKGROUND: Asian American (AsAm) representation is lacking in conversations surrounding cultural humility in healthcare. We aimed to investigate US medical student perspectives on AsAm patient inclusion in cultural humility training in medical education. METHODS: This qualitative study analyzed free-text responses to an optional, open-ended question presented at the conclusion of an online survey assessing medical student experiences with and perceptions regarding AsAm patients in their medical education. This survey was distributed to a convenience sample of nine US medical schools. Medical students who completed at least one clinical rotation were eligible to participate in the survey. Qualitative analysis of free-text responses was conducted in an iterative process to generate emergent themes. RESULTS: There was a total of 195 optional free-text responses from 688 participants (28%). Motivation to learn about AsAm population included shared identity and desire to better serve the AsAm population in their local community and future careers. Topics of interest included healthcare-related cultural preferences, healthcare delivery strategies, and health disparities for the AsAm population and other minority patients. Students reported that they drew on personal experiences and some pre-clinical or clinical exposures to learn about AsAm patients. Respondents cited the lack of exposure in the medical school curriculum and clinical experiences as the main challenge to learning about AsAm health and provided suggestions for the delivery of this education in their pre-clinical and clinical education. Respondents emphasized that AsAms are treated as a monolith in medical education and healthcare, despite their heterogeneity. CONCLUSIONS: Medical students identified a need and interest for greater inclusion of AsAm topics in medical education on cultural humility and minority health.

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.

Association of Cutaneous Immune-Related Adverse Events With Increased Survival in Patients Treated With Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Therapy.

IMPORTANCE: Despite the efficacy of immune checkpoint inhibitors (ICIs), cutaneous immune-related adverse events (cirAEs) occur in 20% to 40% of all treated patients. To our knowledge, little is known about the predictive value of these cutaneous eruptions and their subtypes regarding cancer survival. OBJECTIVE: To determine the association of developing cirAEs following treatment with anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy with patient survival. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the TriNetX Diamond Network, a database of health records and claims data from more than 200 million US and European patients, to conduct a population-level cohort analysis. The study included 7008 eligible patients who developed cirAEs after treatment with anti-PD-1 or anti-PD-L1 therapy for malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract who were identified through the TriNetX Diamond Network along with 7008 matched controls. EXPOSURES: Development of cirAEs within 6 months following anti-PD-1 or anti-PD-L1 therapy. MAIN OUTCOMES AND MEASURES: A 6-month analysis using a Cox proportional hazards model was performed to determine the association of cirAEs with overall survival after adjusting for demographic characteristics, cancer type, and cancer stage. RESULTS: A total of 7008 patients (3036 women [43.3%]; mean [SD] age, 68.2 [11.2] years) were matched to 7008 (3044 women [43.4%]; mean [SD] age, 68.3 [11.1] years) controls. Pruritus (hazard ratio [HR], 0.695; 95% CI, 0.602-0.803; P < .001), drug eruption (HR, 0.755; 95% CI, 0.635-0.897; P = .001), xerosis (HR, 0.626; 95% CI, 0.469-0.834; P = .001), nonspecific rashes (HR, 0.704; 95% CI, 0.634-0.781; P < .001), and appearance of any cirAE (HR, 0.778; 95% CI, 0.726-0.834; P < .001) were significantly protective of mortality using a Benjamini-Hochberg correction with a significance level of .05. Additionally, psoriasis (HR, 0.703; 95% CI, 0.497-0.994; P = .045) and lichen planus/lichenoid dermatitis (HR, 0.511; 95% CI, 0.279-0.939; P = .03) were significant. Eczematous dermatitis (HR, 0.612; 95% CI, 0.314-1.195), vitiligo (HR, 0.534; 95% CI, 0.254-1.123), bullous pemphigoid (HR, 0.524; 95% CI, 0.140-1.956), and Grover disease (HR, 0.468; 95% CI, 0.115-1.898) were all associated with strong protective clinical effects. CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that the development of cirAEs is strongly associated with response to ICI therapy and patient survival.

Cutaneous adverse events of immune checkpoint inhibitor therapy: incidence and types of reactive dermatoses.

BACKGROUND: Dermatoses are common and potentially serious complications of programmed cell death receptor PD-1 immune checkpoint inhibitor (anti-PD-1 ICI) therapy. Understanding their incidence is necessary to support clinical awareness, diagnosis, and management. OBJECTIVE: To examine the incidence and odds of reported non-cancerous dermatoses in the setting of anti-PD-1 ICI therapy. METHODS: Cross-sectional study of anti-PD-1 (pembrolizumab or nivolumab) treated patients at a tertiary healthcare institution. Selected dermatologic events following immunotherapy were identified in the electronic medical record. Comparator arm were patients that developed these same dermatoses without receiving anti-PD-1 ICI therapy. RESULTS: There were 13.7% (254/1857) patients that developed one of 28 dermatoses. Compared with the general population, patients treated with anti-PD-1 had a greater risk for development of mucositis (OR 65.7, 95% CI 35.0-123.3), xerostomia (OR 11.9, 95% CI 8.4-16.8), pruritus (11.3, 95% CI 8.9-14.3), and lichen planus/lichenoid dermatitis (OR 10.7, 95% CI 5.6-20.7). CONCLUSIONS: We report the frequency of dermatoses encountered in the setting of ICI therapy, both common (pruritus, rash, vitiligo) and uncommon (scleroderma, urticaria).

Health-related quality of life and economic burden of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is an understudied, pruritic inflammatory skin disease. Little is known about the effect of PN on quality of life and its associated economic burden. OBJECTIVE: To quantify the impact of PN on quality of life and its economic implications. METHODS: A cohort study of PN patients (n = 36) was conducted using the Health Utilities Index Mark 3 questionnaire. Control data from US adults (n = 4187) were obtained from the 2002-2003 Joint Canada/United States Survey of Health. Quality-adjusted life year loss and economic costs were estimated by comparing the Health Utilities Index Mark 3 scores of the PN patients with those of the controls. RESULTS: The PN patients had lower overall health performance compared to the controls, (mean ± SE, 0.52 ± 0.06 vs 0.86 ± 0.003, respectively, P < .001). In multivariable regression, PN was found to be associated with worse health performance (coefficient -0.34, 95% CI [-0.46 to -0.23]), most prominent in the pain subdomain (coefficient -0.24, 95% CI [-0.35 to -0.13]). This correlated to an average of 6.5 lifetime quality-adjusted life years lost per patient, translating to an individual lifetime economic burden of $323,292 and a societal burden of $38.8 billion. CONCLUSION: These results demonstrate that PN is associated with significant quality-of-life impairment, similar to the level of other chronic systemic conditions. PN is also associated with a substantial individual economic burden, emphasizing the necessity of research on effective treatment options.

Tinea capitis: advances and a needed paradigm shift.

PURPOSE OF REVIEW: Tinea capitis, a superficial infection of the scalp, is the most common pediatric dermatophyte fungal infection worldwide and is particularly common in the USA in low-income, low-resource settings. There are still gaps in knowledge and heterogeneities in practice in terms of diagnostic and management strategies. Furthermore, there are no clinical guidelines for management and treatment of tinea capitis in the USA. This review aims to summarize recent advances, recommend optimal management for the practicing pediatrician, and identify areas for future research for tinea capitis. RECENT FINDINGS: Trichophyton tonsurans infections are best treated with terbinafine and Microsporum canis infections are best treated with griseofulvin. Trichophyton tonsurans is the predominant cause of tinea capitis in the USA, although the main gold standard of treatment in the USA is griseofulvin. Dermatophyte antifungal resistance is an active area of investigation but seems to not be of current concern for tinea capitis in the USA. SUMMARY: We recommend all clinical providers ascertain the causative organism in fungal infection, either through fungal culture or newer methods which may become more readily available and cost-effective in the future, such as polymerase chain reaction assay. We also recommend terbinafine as first-line treatment of tinea capitis, with adjustment as necessary after species identification.

A Retrospective Study of Tinea Capitis Management in General Pediatric Clinics and Pediatric Emergency Departments at 2 US Centers.

We examine management practices of tinea capitis at 2 US academic centers. The majority of providers treated tinea capitis with the oral antifungal agent griseofulvin and did not obtain a fungal culture. We recommend newer antifungal treatments such as terbinafine and fluconazole and obtaining a fungal culture for effective treatment.

Knowledge and attitudes of U.S. medical students regarding the care of Asian American patients: a cross-sectional survey study.

BACKGROUND: Asian Americans (AsAm) are a rapidly growing population in the U.S. With this growing population, U.S. healthcare providers must be equipped to provide culturally competent care for AsAm patients. This project surveyed U.S. medical students on their knowledge of and attitudes towards AsAm to assess predictors of readiness to care for AsAm patients. METHOD: This cross-sectional study surveyed medical students who had completed at least one clinical rotation. The survey was distributed online to nine medical schools throughout the U.S. The survey measured self-rated knowledge of, comfort with, cultural competency (CC) towards, and explicit biases towards AsAm patients. The first three domains were analyzed in a multivariate regression model including sociodemographic characteristics and past clinical, curricular, and social experiences with AsAm. Explicit bias questions were reported descriptively. RESULTS: There were 688 respondents. Asian race, AsAm-prevalent hometown, AsAm-related extracurricular activities, Asian language knowledge, and having taken a population health course predicted increased AsAm knowledge. Social interactions with AsAm increased comfort with AsAm patients. Increasing year in medical school, more frequent exposure to AsAm patients on rotations, and prior travel to an Asian country were predictors of increased CC toward AsAm. Importantly, having completed a CC course was a significant predictor in all domains. In terms of explicit bias, students felt that AsAm patients were more compliant than Caucasian patients. Students also believed that Caucasian patients were generally more likely to receive self-perceived "preferred" versus "acceptable" care, but that in their own clinical experiences neither group received preferred care. CONCLUSION: Experience with and exposure to AsAm prior to and during medical school and CC courses may increase medical student knowledge, comfort, and CC with AsAm patients. Standardized and longitudinal CC training, increased simulations with AsAm patients, diverse student recruitment, and support for students to engage in AsAm-related activities and interact with AsAm may improve CC of future physicians towards AsAm patients and possibly other minority populations.

Relationship Between Conventional Medicine Chapters in ICD-10 and Kampo Pattern Diagnosis: A Cross-Sectional Study.

Objectives: The newest revision to the International Classification of Diseases, the 11th edition (ICD-11) includes disease classifications from East Asian medicine, including traditional Japanese medicine (Kampo medicine). These disease classifications allow for comparisons between disease classifications from conventional medicine and Kampo medicine. Design/Location/Subjects/Interventions: This is an exploratory, cross-sectional study exploring the relationship between conventional medicine diagnoses and Kampo medicine diagnoses at a large Kampo clinic in Japan. Patients were seen from October 1st, 2014 to June 30th, 2019 and were 20 years of age or older. Outcome measures: Patients presented with one or more conventional medicine ICD-10 codes into the clinic and were given one descriptor from the ICD-11 within the heat-cold module, excess-deficiency module, and an optional body constituents module. The distribution of these Kampo medicine codes was examined in relation to conventional medicine chapters. Results: 1,209 patients were included in our final analysis. Patient number, ages, sex ratio, and BMI varied within conventional medicine ICD-10 chapters and Kampo medicine descriptor codes. Certain conventional medicine chapters are related to specific Kampo medicine descriptor codes, such as chapter IV (endocrine, nutritional, and metabolic diseases) with excess, heat, and kidney qi deficiency. Conclusion: The advent of the ICD-11 allows for systematic, standardized comparisons between Kampo medicine, and contemporary medicine. In this exploratory study, our findings support the independence of Kampo medicine pattern descriptors with ICD-10 conventional medicine chapters. Code overrepresentations in relation to conventional medicine diseases and by age and sex should be an area of future investigation to best understand how to synergize and improve patient care.