More than just dermatitis: The multifaceted nature of chronic itch through the historical perspective of Napoleon Bonaparte.

Derived from the survival advantage needed to eradicate harmful irritants from the skin's surface, itch, also known as pruritus, is an intriguing phenomenon and a key feature of many dermatologic diseases. The pathologic form, chronic itch, is a condition that precedes itself by its complex pathophysiology, numerous etiologies, and interplay of mechanisms that often make it difficult to diagnose and treat. One particular sufferer of this condition, the 18th-century French emperor Napoleon Bonaparte, makes for a compelling case study of the complexity of chronic itch. We delve into the many etiologies and mechanisms of chronic itch, using Napoleon's lifelong struggle with this condition as our model, identifying potential environmental, neurologic, psychiatric, and immunologic origins of his condition.

Stevens-Johnson syndrome/toxic epidermal necrolysis associated with natural thyroid medication.

Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare immunologic hypersensitivity reaction to stimuli that presents as widespread eruption with mucocutaneous detachment and involvement of other organs. Multiple causes have been noted in literature, including numerous medications. In this report, we present a 52-year-old woman who arrived at the emergency department with a complaint of rash, malaise, and pruritus. She subsequently developed diffuse cutaneous and mucosal detachment. Work-up supported a diagnosis of SJS/TEN secondary to her thyroid replacement therapy, derived from desiccated pig thyroid glands. The patient's natural thyroid medication was discontinued and she responded well to appropriate treatment. This case is unique in that thyroid replacement therapy is not a commonly reported trigger of SJS/TEN. Providers should be aware of the potential for natural thyroid and other animal-derived natural medications to cause adverse reactions such as SJS/TEN.

Severe cutaneous adverse reactions associated with the immune checkpoint inhibitors: A case/non-case analysis using the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND/OBJECTIVES: The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored. METHODS: A case/non-case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI-associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy. RESULTS: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS). CONCLUSIONS: Our results suggest an association between SCARs and the ICIs independent of cancer status.

Medication Associations With Severe Cutaneous Adverse Reactions: A Case/Non-Case Analysis Using the FDA Adverse Event Reporting System.

BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are potentially life-threatening severe cutaneous adverse reactions (SCARs). Although the classical causal agents of SCARs (antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol) are well characterized, there has been little update to this list to account for newly marketed medications. OBJECTIVE: To provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs. METHODS: A case/non-case analysis using the United States FDA Adverse Event Reporting System was performed. RESULTS: As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively). In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals. Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13). For TEN, we identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12). For AGEP, we identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37). For DRESS, we identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77) to have strong reporting odds. CONCLUSION: Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality.

Gender differences in pediatric and adolescent melanoma: A retrospective analysis of 4645 cases.

BACKGROUND: There is paucity of data on how gender impacts melanoma prognosis in pediatric and adolescent patients. OBJECTIVES: This study explores gender differences in presentation and survival among pediatric and adolescent patients with melanoma. METHODS: The National Cancer Database 2004-2018 was queried for cases of primary invasive cutaneous melanoma in pediatric and adolescent patients (birth to 21 years) for a retrospective cohort study. RESULTS: Of the 4645 cases, 63.4% were female. Median Breslow depth was 1.05 mm for males (interquartile range 0.50-2.31) and 0.80 mm for females (interquartile range 0.40-1.67; P < .001). Trunk was the most common primary site for females (34.3%) and males (32.9%). More females than males were diagnosed with stage I disease (67.8% vs 53.6%). Males had higher rates of regional lymph node positivity (27.9% vs 18.1%; P < .001) and ulceration (17.1% vs 11.4%; P < .001). Five-year overall survival was 95.9% for females and 92.0% for males (P < .001). After adjusting for confounders, male gender independently increased mortality risk (reference: females; adjusted hazard ratio 1.57; 95% confidence interval 1.32-1.86). LIMITATIONS: Retrospective study. CONCLUSION: Males exhibited more aggressive pathologic features including greater Breslow thickness and higher ulceration and lymph node positivity rates. Male gender independently increased mortality risk.

Limited Cutaneous Leishmaniasis as Ulcerated Verrucous Plaque on Leg, Tucson, Arizona, USA1.

We report a 34-year-old man who had a nonhealing, verrucous plaque with central ulceration on the lower leg. This case-patient is a rare example of endemic limited cutaneous leishmaniasis in Tucson, Arizona, USA. Clinicians should be aware of this disease because its manifestations can vary for individual patients.

Sex differences in initial treatment for genital extramammary Paget disease in the United States: A systematic review.

BACKGROUND: Surgery is the standard treatment for genital extramammary Paget disease (gEMPD). OBJECTIVE: To determine if gEMPD treatments and outcomes differ by sex and US region. METHODS: A systematic review was performed of all English-language studies on initial gEMPD treatment in Medline via PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. At least 2 reviewers performed title and abstract review and data extraction. Surgical categories included total skinning procedures, partial skinning procedures, Mohs micrographic surgery (MMS), or unspecified surgery. Chi-squared tests of association were used for comparisons. RESULTS: A total of 60 studies comprising 302 (79.7%) female and 77 (20.3%) male patients met criteria. Women were most often initially recommended partial skinning procedures. In all, 74 (24.5%) women and 0 men underwent a total skinning procedure. Men were more likely to be offered MMS than women (40.3% vs 1.9%, P < .0001), despite men having a significantly greater extent of disease involving the perineum and perianal skin (21.1% vs 1.7%, P < .0001). Treatment recommendations varied by US region. LIMITATIONS: Only 20 states were represented. CONCLUSION: Women are more frequently offered total skinning procedures for gEMPD while men are more frequently offered MMS. MMS offers less recurrence and morbidity than total skinning procedures and should be recommended equally to both female and male patients with gEMPD.

Hyperkalemia in women with acne exposed to oral spironolactone: A retrospective study from the RADAR (Research on Adverse Drug Events and Reports) program.

PURPOSE: The necessity of serum potassium monitoring for healthy women who are prescribed spironolactone for acne has been debated. The aim of this study was to compare the incidence of hyperkalemia in women 18 to 45 years of age to that in women 46 to 65 years of age, when treated with oral spironolactone for acne. METHODS AND MATERIALS: Data for all women 18 to 65 years of age who were prescribed oral spironolactone by a dermatologist for acne between January 2006 and October 2016 were extracted for analysis. Retrospective data were included for women who exhibited baseline serum potassium within the normal limits and who had repeat serum potassium monitoring within 12 months after initiation of spironolactone. The rate of incident hyperkalemia was determined. RESULTS: Of 618 women who received spironolactone for acne, 133 had serum potassium monitoring both before and after spironolactone initiation. Nine were excluded due to confounding comorbidities. Of the remaining 124 women, the mean age at initiation of spironolactone was 32 years (range, 18-57 years); 112 women were in the 18 to 45 years age group, and 12 were in the 46 to 65 years age group. All women had serum potassium within normal limits at baseline. Women in the 46 to 65 years age group had a significantly higher rate of incident hyperkalemia after spironolactone initiation compared with women 18 to 45 years of age (2 of 12 women [16.7%] vs. 1 of 112 women [< 1%]; p = .0245). CONCLUSIONS: Although controversy surrounds the clinical utility of serum potassium monitoring in healthy women exposed to spironolactone for acne, based on the findings from this large patient population, monitoring of serum potassium is warranted for women over 45 years of age given an age-related greater risk of hyperkalemia.

Viewing an ultra-brief chest compression only video improves some measures of bystander CPR performance and responsiveness at a mass gathering event.

BACKGROUND: CPR training at mass gathering events is an important part of health initiatives to improve cardiac arrest survival. However, it is unclear whether training lay bystanders using an ultra-brief video at a mass gathering event improves CPR quality and responsiveness. OBJECTIVE: To determine if showing a chest-compression only (CCO) Ultra-Brief Video (UBV) at a mass gathering event is effective in teaching lay bystanders CCO-CPR. METHODS: Prospective control trial in adults (age >18) who attended either a women's University of Arizona or a men's Phoenix Suns basketball game. Participants were evaluated using a standardized cardiac arrest scenario with Laerdal Skillreporter™ mannequins. CPR responsiveness (calling 911, time to calling 911, starting compressions within two minutes) and quality (compression rate, depth, hands-off time) were assessed for participants and data collected at Baseline and Post-intervention. Different participants were tested before and after the exposure of the UBV. Data were analyzed via the intention to treat principle using logistic regression for binary outcomes and median regression for continuous outcomes, controlling for clustering by venue. RESULTS: A total of 96 people were consented (Baseline=45; Post intervention=51). CPR responsiveness post intervention improved with faster time to calling 911 (s) and time to starting compressions (sec). Likewise, CPR quality improved with deeper compressions and improved hands-off time. CONCLUSIONS: Showing a UBV at a mass gathering sporting event is associated with improved CPR responsiveness and performance for lay bystanders. This data provides further support for the use of mass media interventions.

Alterations in gait parameters with peripheral artery disease: The importance of pre-frailty as a confounding variable.

Although poor walking is the most common symptom of peripheral artery disease (PAD), reported results are inconsistent when comparing gait parameters between PAD patients and healthy controls. This inconsistency may be due to frailty, which is highly prevalent among PAD patients. To address this hypothesis, 41 participants, 17 PAD (74±8 years) and 24 aged-matched controls (76±7 years), were recruited. Gait was objectively assessed using validated wearable sensors. Analysis of covariate (ANCOVA) tests were used to compare gait parameters between PAD and non-PAD groups, considering age, gender, and body mass index as covariates, while stratified based on frailty status. According to the Fried frailty index, 47% of PAD and 50% of control participants were non-frail and the rest were classified as pre-frail. Within non-frail participants, gait speed, body sway during walking, stride length, gait cycle time, double-support, knee range of motion, speed variability, mid-swing speed, and gait initiation were significantly different between PAD and control groups (effect size d = 0.75±0.43). In the pre-frail group, however, most of the gait differences were diminished except for gait initiation and gait variability. Results suggest that gait initiation is the most sensitive parameter for detecting gait impairment in PAD participants when compared to controls, regardless of frailty status (d = 1.30-1.41; p<0.050). The observed interaction effect between frailty and PAD on gait parameters confirms the importance of assessing functionality in addition to age to provide more consistency in detecting motor performance impairments due to PAD.

Viewing a brief chest-compression-only CPR video improves bystander CPR performance and responsiveness in high school students: A cluster randomized trial.

BACKGROUND: CPR training in schools is a public health initiative to improve out of hospital cardiac arrest (OHCA) survival. It is unclear whether brief video training in students improves CPR quality and responsiveness and skills retention. OBJECTIVES: Determine if a brief video is as effective as classroom instruction for chest compression-only (CCO) CPR training in high school students. METHODS: This was a prospective cluster-randomized controlled trial with three study arms: control (sham video), brief video (BV), and CCO-CPR class. Students were randomized and clustered based on their classrooms and evaluated using a standardized OHCA scenario measuring CPR quality (compression rate, depth, hands-off time) and responsiveness (calling 911, time to calling 911, starting compressions within 2min). Data was collected at baseline, post-intervention and 2 months. Generalized linear mixed models were used to analyze outcome data, accounting for repeated measures for each individual and clustering by class. RESULTS: 179 students (14-18 years) were consented in 7 classrooms (clusters). At post-intervention and 2 months, BV and CCO class students called 911 more frequently and sooner, started chest compressions earlier, and had improved chest compression rates and hands-off time compared to baseline. Chest compression depth improved significantly from baseline in the CCO class, but not in the BV group post-intervention and at 2 months. CONCLUSIONS: Brief CPR video training resulted in improved CPR quality and responsiveness in high school students. Compression depth only improved with traditional class training. This suggests brief educational interventions are beneficial to improve CPR responsiveness but psychomotor training is important for CPR quality.

Gait and balance assessments as early indicators of frailty in patients with known peripheral artery disease.

BACKGROUND: Peripheral artery disease is associated with increased morbidity and mortality, and frailty syndrome may mediate the risk of these adverse health outcomes to predict intervention results. The aim of this study was to determine the association between motor performance impairments based on in-clinic gait and balance measurements with frailty at intermediate stages (pre-frailty) in peripheral artery disease patients. METHODS: Seventeen participants with peripheral artery disease (≥ 55 years) were recruited and frailty assessed using Fried criteria. Gait and balance were quantified using wearable sensor technologies in the clinical setting. Between-group differences in frailty were assessed using analysis of variance, and independent associations between gait and balance parameters with frailty were determined using logistic regression models. FINDINGS: Based on Fried index nine (53%), participants were pre-frail and eight (47%) were non-frail. Although no between-group differences in demographics or clinical parameters was observed, gait parameters were worse among pre-frail compared to non-frail participants. The highest effect sizes for between-group differences were observed in double support during habitual normal walking (effect size=1.86, p<0.01), speed variability during dual-task (effect size=1.26, p=0.03), and trunk sway during fast walking (effect size=1.43, p=0.02). No significant difference was observed in balance parameters (p>0.07). The regression model using gait parameters demonstrated a high sensitivity and specificity in predicting pre-frailty. INTERPRETATION: A short 25-step sensor-based in-clinic overground gait test objectively identified pre-frailty independent of age. Double support was the most sensitive parameter in identifying pre-frail aging adults.