Demographics, Cutaneous Manifestations, and Comorbidities Associated with Progressive Cutaneous Sarcoidosis: A Retrospective Cohort Study.

Background: Sarcoidosis is a multisystem granulomatous disease with a wide variety of presentations and clinical courses. Cutaneous manifestations and comorbidities associated with sarcoid prognosis remain understudied. Methods: An EPIC query was run for patients age 18+ at the Johns Hopkins Hospital with a diagnosis of sarcoidosis of the skin according to the ICD-10-CM code D86.3. Data were obtained from a population-based sample of 240 patients from 2015 to 2020. Results: A total of 240 patients were included in the cohort study. The mean (SD) age was 43.76 (11.72) years, and 30% of participants were male; 76.25% of patients identified as black, 19.58% as white, and 4.17% as other. The average age of onset in remissive patients was significantly higher than progressive (47 ± 12 vs. 40 ± 10, p = 0.0005); 49% of black patients experienced progressive sarcoid compared to 32.6% of white patients (p = 0.028). Progressive disease was associated with the presence of lupus pernio (aOR = 3.29, 95% CI, 1.60-6.77) and at least one autoimmune comorbidity (aOR 6.831, 95% CI 1.819-11.843). Conclusions: When controlling for patient demographics, lupus pernio and the presence of at least one autoimmune condition were associated with progressive cutaneous sarcoidosis.

Risk of incident sleep disorders in patients with prurigo nodularis: A population-level analysis using The Health Improvement Network.

Background: Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy and often painful bumps on the arms, legs, and trunk. It is unknown whether patients with PN have increased risk of developing sleep disorders. Objective: To evaluate the association of PN with sleep disorders. Methods: This retrospective, population-level, matched-cohort study was conducted using The Health Improvement Network. The study included 4193 patients with newly diagnosed PN and 4193 age, sex, and race/ethnicity-matched controls. A Cox regression model was used to assess the development of sleep disorders, including insomnia, sleep apnea, and restless legs syndrome, in patients with PN compared with control patients. Results: Compared with controls, PN was associated with insomnia (adjusted hazard ratio [aHR] = 1.77; 95% CI = 1.48-2.12) and overall sleep disorder (aHR = 1.72; 95% CI = 1.46-2.02), but not with sleep apnea (aHR = 1.51; 95% CI = 0.93-2.44) or restless legs syndrome (aHR = 1.54; 95% CI = 0.92-2.57). Limitations: As a retrospective cohort study, our analysis is subject to potential confounders not already included. Conclusions: PN was associated with subsequent development of insomnia. Thus, clinicians should consider insomnia among patients with PN and develop strategies for treatment and prevention.

A Polygenic Risk Score for Predicting Racial and Genetic Susceptibility to Prurigo Nodularis.

Prurigo nodularis (PN) is an understudied inflammatory skin disease characterized by pruritic, hyperkeratotic nodules. Identifying the genetic factors underlying PN could help to better understand its etiology and guide the development of therapies. In this study, we developed a polygenic risk score that predicts a diagnosis of PN (OR = 1.41, P = 1.6 × 10-5) in two independent and continentally distinct populations. We also performed GWASs, which uncovered genetic variants associated with PN, including one near PLCB4 (rs6039266: OR = 3.15, P = 4.8 × 10-8) and others near TXNRD1 (rs34217906: OR = 1.71, P = 6.4 × 10-7; rs7134193: OR = 1.57, P = 1.1 × 10-6). Finally, we discovered that Black patients have over a two-times greater genetic risk of developing PN (OR = 2.63, P = 7.8 × 10-4). Combining the polygenic risk score and self-reported race together was significantly predictive of PN (OR = 1.32, P = 4.7 × 10-3). Strikingly, this association was more significant with race than after adjusting for genetic ancestry. Because race is a sociocultural construct and not a genetically bound category, our findings suggest that genetics, environmental influence, and social determinants of health likely affect the development of PN and may contribute to clinically observed racial disparities.

A propensity score matched cohort study identifying an association of acne, but not oral antibiotic or isotretinoin use, with risk of incident inflammatory bowel disease.

BACKGROUND: Concerns remain regarding whether oral antibiotic or isotretinoin use for acne is associated with increased risk of inflammatory bowel disease (IBD); little is known about whether acne itself is associated with IBD. OBJECTIVE: To determine whether isotretinoin exposure, oral tetracycline-class antibiotic exposure, and/or acne itself are associated with IBD. METHODS: A propensity score matched cohort study was performed using TriNetX between 2001 and 2022 to compare the 1-year incidence of IBD between those without acne compared to those with acne managed without systemic medications, acne managed with oral tetracycline-class antibiotics, and acne managed with isotretinoin. RESULTS: There was a statistically significant association between acne and risk of incident IBD (odds ratio: 1.42; 95% confidence interval: 1.23-1.65). There was no statistically significant association between oral tetracycline-class antibiotic or isotretinoin exposure and IBD. LIMITATIONS: Use of electronic health data; potential for misclassification bias. CONCLUSION: This matched cohort study identifies an association between acne and IBD. These data provide further reassurance regarding the use of isotretinoin in the treatment of acne.

Reduced serum pyridoxine and 25-hydroxyvitamin D levels in adults with chronic pruritic dermatoses.

Little is known about the role nutritional factors play in the pathogenesis of chronic pruritic dermatoses (CPD). In this study, we analyzed nutritional deficiencies in CPD patients compared to matched controls. We conducted a population-based study from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2006. The main outcomes of the study were laboratory data on serum vitamin levels in participants who answered affirmatively to the questionnaires on CPD as well as matched healthy controls. We identified 877 cases of CPD among 9817 adults in the US aged 20 to 59 years. These findings revealed a slightly higher percentage of females with CPD. Low vitamin B6 (OR 0.697; 95% CI: 0.696-0.699, p = 0.025) and vitamin D (OR 0.794; 95% CI: 0.789-0.799, p = 0.037) levels were associated with a higher rate of CPD compared to healthy controls. Our study suggests that low levels of Vitamin B6 and Vitamin D inversely correlates with the presence of CPD. These vitamin deficiencies suggest further studies on the effect of vitamin supplementation may help in patients with CPD.

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.

Racial differences in dysregulation of the renin-angiotensin-aldosterone system in patients with prurigo nodularis.

BACKGROUND: There are limited data characterizing the association between renal disease and prurigo nodularis (PN). OBJECTIVE: To characterize the association and describe mechanistic disease linkages between PN and renal comorbidities. METHODS: We conducted a cross-sectional analysis of renal comorbidities in PN using TriNetX, a global health research network providing access to medical records. Epidemiological findings provided the basis for translational studies on plasma and skin biopsy samples from PN patients stratified by race. RESULTS: PN was associated with stages 1-5 of chronic kidney disease (CKD), end-stage renal disease, nephritic syndrome, nephrotic syndrome, glomerular disease, and tubulointerstitial disease, but the associations were significantly stronger in black patients. Compared to controls, CKD progression was faster (HR 2.88, 95% CI: 1.01-8.26) only in black PN (10-year survival: 63.5% black vs. 85.5% white). Circulating plasma angiotensinogen levels were dysregulated (P < 0.001) only in black PN patients. Cutaneous transcriptomic analysis of genes related to the renin-angiotensin-aldosterone system (RAAS) revealed considerable dysregulation in PN lesions with greater dysregulation in black patients. CONCLUSIONS: Significant dysregulation of the cutaneous and systemic RAAS in black PN patients may explain the increased incidence and severity of renal disease.

Use of Triggers to Detect Adverse Events After Outpatient Orthopedic Surgery at a Single Ambulatory Surgery Center.

Literature on adverse events (AEs) after outpatient orthopedic surgery is relatively sparse, and efforts to detect, measure, and track AEs after outpatient surgery lag behind those for the inpatient setting. Detection of AEs has traditionally relied on patient safety indicators (from billing data) and self-reporting, but these methods have been shown to have low sensitivity, missing up to 90% of AEs. There is growing recognition that the trigger method, which uses "triggers" as red flags to initiate more detailed chart audits, can serve as a more sensitive alternative to detect AEs. Moreover, the recent widespread adoption of electronic health records (EHRs) can provide faster automated methods for identifying triggers and estimating AE rates. This study evaluates the ability of 6 separate EHR-based triggers to predict AEs after outpatient orthopedic surgery and compares this trigger method with AE self-reporting. Triggers have the potential to decrease postoperative morbidity after outpatient orthopedic surgery and may lead to quality improvement. Further research is needed to qualify triggers as screening tools in the outpatient setting. [Orthopedics. 2022;45(2):116-121.].

Most common pediatric skin conditions managed in outpatient dermatology clinics in the United States stratified by race and ethnicity.

A better understanding of what skin conditions are most commonly diagnosed in different pediatric racial and ethnic groups in outpatient dermatology clinics could help guide the development of pediatric dermatology educational initiatives for primary care providers and general dermatologists who have limited access to pediatric dermatologists. Using a nationally representative dataset, we evaluated the most common diagnoses in patients younger than 15 years of age (children) and 15-24 years of age (youth) who present to outpatient dermatology clinics, stratified by race and ethnicity. While acne and dermatitis were among the top ten most common diagnoses in all racial and ethnic groups studied, Black children were also commonly diagnosed with dermatophytosis and impetigo, and Black and Hispanic children were often diagnosed with seborrheic dermatitis; pigmentary disorders were among the top three most common diagnoses in Black, Asian, and Hispanic youth. Training more physicians how to evaluate and treat common skin conditions in children and youth of diverse racial and ethnic backgrounds may improve access to care for skin disease in the United States.

Outpatient prescribing of opioids to adults diagnosed with mental disorders in the United States.

BACKGROUND: Adults with mood and anxiety disorders have an increased likelihood of being prescribed opioids. The influence of other mental disorders, such as psychotic and attention disorders, on opioid prescribing patterns is less known. METHODS: We studied a population-representative sample of 166,927 outpatient visits for adults with painful conditions from the 2002-2016 National Ambulatory Medical Care Survey and the 2002-2011 National Hospital Ambulatory Medical Care Survey. Logistic regression analyses examined the likelihood of opioid prescription among visits with specific mental disorder diagnoses (anxiety, attention, mood, psychotic, post-traumatic stress disorder (PTSD), opioid use, and non-opioid substance use), adjusted for covariates and weighted for the complex survey design. Secondary analyses stratified results by whether opioids were newly initiated or continued. RESULTS: Opioids were prescribed at 16.8 % of visits. Mood, anxiety, and non-opioid substance use disorders were associated with higher likelihoods of opioid prescriptions, particularly for continued rather than first-time prescriptions. Psychotic disorders were strongly negatively associated with opioid prescriptions (adjusted odds ratio 0.44, 95 % CI 0.22-0.86). Diagnoses of PTSD and attention disorders were not associated with opioid prescribing. CONCLUSIONS: Outpatient physicians are more likely to prescribe and refill opioids for adults with pain who present with mood, anxiety, and non-opioid substance use disorders, but not for those who present with PTSD or attention disorders. Patients with psychotic disorders and pain are markedly less likely to be prescribed opioids.

Trends in Off-Label Drug Use in Ambulatory Settings: 2006-2015.

BACKGROUND: Off-label drug use in children is common and potentially harmful. In most previous off-label use research, authors studied hospitalized children, specific drug classes, or non-US settings. We characterized frequencies, trends, and reasons for off-label systemic drug orders for children in ambulatory US settings. METHODS: Using nationally representative surveys of office-based physicians (National Ambulatory Medical Care Surveys, 2006-2015), we studied off-label orders of systemic drugs for children age <18 based on US Food and Drug Administration-approved labeling for age, weight, and indication. We characterized the top classes and diagnoses with off-label orders and analyzed factors and trends of off-label orders using logistic regression. RESULTS: Physicians ordered ≥1 off-label systemic drug at 18.5% (95% confidence interval: 17.7%-19.3%) of visits, usually (74.6%) because of unapproved conditions. Off-label ordering was most common proportionally in neonates (83%) and in absolute terms among adolescents (322 orders out of 1000 visits). Off-label ordering was associated with female sex, subspecialists, polypharmacy, and chronic conditions. Rates and reasons for off-label orders varied considerably by age. Relative and absolute rates of off-label orders rose over time. Among common classes, off-label orders for antihistamines and several psychotropics increased over time, whereas off-label orders for several classes of antibiotics were stable or declined. CONCLUSIONS: US office-based physicians have ordered systemic drugs off label for children at increasing rates, most often for unapproved conditions, despite recent efforts to increase evidence and drug approvals for children. These findings can help inform education, research, and policies around effective, safe use of medications in children.

Comparing record linkage software programs and algorithms using real-world data.

Linkage of medical databases, including insurer claims and electronic health records (EHRs), is increasingly common. However, few studies have investigated the behavior and output of linkage software. To determine how linkage quality is affected by different algorithms, blocking variables, methods for string matching and weight determination, and decision rules, we compared the performance of 4 nonproprietary linkage software packages linking patient identifiers from noninteroperable inpatient and outpatient EHRs. We linked datasets using first and last name, gender, and date of birth (DOB). We evaluated DOB and year of birth (YOB) as blocking variables and used exact and inexact matching methods. We compared the weights assigned to record pairs and evaluated how matching weights corresponded to a gold standard, medical record number. Deduplicated datasets contained 69,523 inpatient and 176,154 outpatient records, respectively. Linkage runs blocking on DOB produced weights ranging in number from 8 for exact matching to 64,273 for inexact matching. Linkage runs blocking on YOB produced 8 to 916,806 weights. Exact matching matched record pairs with identical test characteristics (sensitivity 90.48%, specificity 99.78%) for the highest ranked group, but algorithms differentially prioritized certain variables. Inexact matching behaved more variably, leading to dramatic differences in sensitivity (range 0.04-93.36%) and positive predictive value (PPV) (range 86.67-97.35%), even for the most highly ranked record pairs. Blocking on DOB led to higher PPV of highly ranked record pairs. An ensemble approach based on averaging scaled matching weights led to modestly improved accuracy. In summary, we found few differences in the rankings of record pairs with the highest matching weights across 4 linkage packages. Performance was more consistent for exact string matching than for inexact string matching. Most methods and software packages performed similarly when comparing matching accuracy with the gold standard. In some settings, an ensemble matching approach may outperform individual linkage algorithms.