Dengue NS1 antibodies are associated with clearance of viral NS1.

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Association between psoriasis and cardiometabolic comorbidities in a racially and ethnically diverse low-income primary care population.

Psoriasis is associated with cardiometabolic comorbidities, including obesity, diabetes, hyperlipidaemia and hypertension. Many studies that established these associations originated from primarily White and/or relatively affluent populations. To evaluate whether there is a differential risk for cardiometabolic comorbidities in racial/ethnic minorities, we performed a cross-sectional analysis comparing cardiometabolic comorbidities between those with and without psoriasis in a racially and ethnically diverse population of 56 987 low-income patients, stratified by race/ethnicity, and assessed whether race/ethnicity acts as an effect modifier for cardiometabolic comorbidities. We found that psoriasis was statistically significantly associated with obesity, diabetes, hyperlipidaemia and hypertension. The association of psoriasis with comorbidities did not differ significantly by race/ethnicity; thus, we did not find evidence of effect modification. However, our diverse, low-income population had an extremely high baseline prevalence of cardiometabolic comorbidities compared with previous populations studied. Our results suggest education and intervention regarding modifiable risk factors are particularly important among vulnerable populations.

Evaluation of a pilot forensic dermatology curriculum in the USA.

Physician participation in asylum medicine through forensic medical evaluations increases the likelihood that asylum seekers are granted legal status. Based on a review of existing literature and input from content experts, we designed and implemented a forensic dermatology curriculum for dermatology residents at University of California, San Francisco. Our pilot curriculum led to improvements in learners' attitudes regarding physician participation in asylum medicine and their confidence in describing skin findings of torture or abuse.

Novel Education Modules Addressing the Underrepresentation of Skin of Color in Dermatology Training.

BACKGROUND: Representative images of pathology in patients with skin of color are lacking in most medical education resources. This particularly affects training in dermatology, which relies heavily on the use of images to teach pattern recognition. The presentation of skin pathology can vary greatly among different skin tones, and this lack of representation of dark skin phototypes challenges providers' abilities to provide quality care to patients of color.In Botswana and other countries in sub-Saharan Africa, this challenge is further compounded by limited resources and access to dermatologists. There is a need for improved and accessible educational resources to train medical students and local medical providers in basic skin lesion description and diagnosis. OBJECTIVES: We examined whether online Perceptual and Adaptive Learning Modules (PALMs) composed of representative dark skin images could efficiently train University of Botswana medical students to more accurately describe and diagnose common skin conditions in their community. METHODS: Year 4 and 5 medical students voluntarily completed PALMs that teach skin morphology, configuration, and distribution terminology and diagnosis of the most common dermatologic conditions in their community. Pre-tests, post-tests and delayed-tests assessed knowledge acquisition and retention. RESULTS: PALMs training produced statistically significant (P < .0001) improvements in accuracy and fluency with large effect sizes (1.5, 3.7) and good retention after a 12.5-21-week median delay. Limitations were a self-selected group of students, a single institution, slow internet connections, and high drop-out rates. CONCLUSIONS: Overall, population-specific PALMs are a useful tool for efficient development of pattern recognition in skin disease description and diagnosis.

Treatment practices in the management of scabies in infants younger than two months.

BACKGROUND/OBJECTIVES: Efficacy and safety data of scabies treatments in infants are limited. Although topical permethrin is used in the treatment of scabies in adults, it is not approved for use in infants younger than 2 months of age in many parts of the world. This study aimed to describe treatment practices in the management of scabies in infants younger than 2 months. METHODS: An online survey was developed and distributed to physicians worldwide through the Society of Pediatric Dermatology and the Pediatric Dermatology Research Alliance. Data collected included demographics, medication availability, experience using medications, deterrents to medication use, medication administration preferences, perceived and experienced medication side effects, and preferred treatment agent in this population. RESULTS: In total, 57 physicians from seven countries responded. The majority of respondents were board-certified in pediatric dermatology (48/57, 84.2%) and resided in the United States (44/57, 77.2%). Respondents had experience using permethrin (47/57, 82.5%) and precipitated sulfur (35/57, 61.4%) most frequently. Most (38/57, 66.7%) preferred permethrin as their treatment of choice. Among those who did not use permethrin, potential side effects (8/10, 80%) were most frequently reported as a deterrent from its use. However, only 4.3% (22/47) of those who used permethrin reported side effects, including itching, erythema, and xerosis. CONCLUSIONS: Permethrin is frequently used in the treatment of infants younger than 2 months with scabies. Furthermore, our results demonstrate that permethrin is the preferred treatment agent among sampled dermatologists for infants younger than 2 months. Few side effects were reported, and none were serious.

The public health control of scabies: priorities for research and action.

Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary.

Ectoparasites: Pediculosis and tungiasis.

Pediculosis is an infestation of lice on the body, head, or pubic region that occurs worldwide. Lice are ectoparasites of the order Phthiraptera that feed on the blood of infested hosts. Their morphotype dictates their clinical features. Body lice may transmit bacterial pathogens that cause trench fever, relapsing fever, and epidemic typhus, which are potentially life-threatening diseases that remain relevant in contemporary times. Recent data from some settings suggest that head lice may harbor pathogens. The epidemiology, clinical manifestations, and management of body, head, and pubic louse infestation are reviewed. New therapies for head lice and screening considerations for pubic lice are discussed. Tungiasis is an ectoparasitic disease caused by skin penetration by the female Tunga penetrans or, less commonly, Tunga trimamillata flea. It is endemic in Latin America, the Caribbean and sub-Saharan Africa and seen in travelers returning from these regions. Risk factors for acquiring tungiasis, associated morbidity, and potential strategies for prevention and treatment are discussed.

Ectoparasites: Scabies.

Scabies is an ectoparasitic dermatosis caused by Sarcoptes scabiei var. hominis and is a public health issue in all countries regardless of socioeconomic status. In high-income countries, delays in diagnosis can lead to institutional outbreaks; in low- and middle-income countries, poor access to health care contributes to disease undertreatment and long-term systemic sequelae. With scabies now recognized as a neglected tropical disease by the World Health Organization, increased awareness and systematic efforts are addressing gaps in diagnosis and treatment that impede scabies control. This review summarizes the available data and provides an update on scabies epidemiology, clinical features, diagnosis, management, and public health considerations.

Augmented Zika and Dengue Neutralizing Antibodies Are Associated With Guillain-Barré Syndrome.

The role of neutralizing antibodies in Zika-induced Guillain-Barré syndrome (GBS) has not yet been investigated. We conducted a case-control study using sera from the 2016 Zika epidemic in Colombia to determine the neutralizing antibody activity against Zika virus (ZIKV) and dengue virus serotype 2 (DENV2). We observed increased neutralizing antibody titers against DENV2 in ZIKV-infected individuals compared with uninfected controls and higher titers to both ZIKV and DENV2 in ZIKV-infected patients diagnosed with GBS compared with non-GBS ZIKV-infected controls. These data suggest that high neutralizing antibody titers to DENV and to ZIKV are associated with GBS during ZIKV infection.

Teledermatology as a Means to Provide Multispecialty Care: A Case of Global Specialty Collaboration.

Telemedicine can serve as a platform for specialty collaboration and potentially address the lack of specialized and subspecialized care globally. In this article we present a case in which the use of teledermatology facilitated global collaboration between multiple specialists and subspecialists, resulting in high-quality care of a child from a remote area of Botswana. We present the lessons learned and factors that should be considered when engaging in global specialty collaboration, especially between developed and developing countries. We also discuss the potential limitations of telemedicine when used within a global context. With these considerations in mind, global specialty collaboration facilitated by telemedicine can provide a potential solution to the lack of access to specialized and subspecialized care.

Management Considerations in Extraocular Sebaceous Carcinoma.

BACKGROUND: Extraocular sebaceous carcinoma (SC) is a rare malignancy with metastatic potential. The authors present a case of a rapidly growing extraocular SC with equivocal radiographic imaging to highlight challenges in tumor management. OBJECTIVE: To examine the existing literature for evaluation and management recommendations of extraocular SC. METHODS AND MATERIALS: A comprehensive review of relevant English articles in PubMed through May 2015. RESULTS: Tumor-specific staging system and management guidelines do not currently exist for extraocular SC. Mohs micrographic surgery or wide local excision are the most commonly used surgical treatments. Regional/distant metastasis occurs infrequently, but systemic workup with radiographic imaging or sentinel lymph node biopsy may be warranted in select cases. Adjuvant radiation therapy can be considered for recurrent and metastatic tumors. CONCLUSION: Extraocular SCs present unique challenges that may benefit from multidisciplinary management. Surgical removal with negative pathologic margins is the mainstay treatment of extraocular SC. Additional studies will help clarify the optimal diagnostic workup and adjuvant treatment of patients.

Association of Countries' Atopic Dermatitis Burden and Sociodemographic Index with Topical Calcineurin Inhibitor Utilization.

Background: There is limited knowledge on international trends in topical calcineurin inhibitor (TCI) utilization. Objective: To describe international TCI utilization trends from 2012 to 2019 and evaluate the relationship of country-level economic status, geographic location, and atopic dermatitis (AD) disease burden with drug utilization. Methods: We used IQVIA MIDAS® pharmaceutical quarterly sales data to attain country-level purchasing of TCIs in grams from 2012 to 2019. A multivariable linear regression estimated the association between countries' sociodemographic index (SDI), AD disability-adjusted life year (DALY) rates, and geographic location with TCI utilization. Results: A total of 68 countries were included in our analysis. From 2012 to 2019, overall TCI utilization increased by 66% but remained 11.2 times higher in high-sociodemographic compared with low-middle/low-sociodemographic countries. SDI and geographic location were associated with greater TCI utilization in multivariable analyses, whereas AD DALY rates were not. High-SDI countries used 21,476 grams (95% confidence interval [CI]: 11,915 to 31,036) and high-middle SDI countries used 9,403 grams (95% CI: -393 to 19,200) more TCIs per 100,000 people compared with low-middle/low-SDI countries, respectively. Northern hemisphere countries used 8,588 grams more TCIs per 100,000 people (95% CI: 612 to 16,564). Conclusions: We demonstrated greater TCI utilization among high-SDI compared with lower SDI countries.

International time trends and differences in topical actinic keratosis therapy utilization.

Background: Actinic Keratoses (AK) are precancerous lesions that can lead to Squamous Cell Carcinoma. International differences in the utilization of topical medications to treat AK are not well described. Objectives: To describe international differences in topical AK medication utilization, including associations of countries' economic status with AK medication utilization. Methods: We used IQVIA MIDAS pharmaceutical sales data for 65 countries (42 high-income, 24 middle-income) from April 2011 to December 2021. We calculated each country's quarterly utilization of medications in grams per 1000 population. We used univariable linear regression to assess the association between country economic status and AK medication utilization. Results: High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60). Limitations: Missing medication utilization data for some countries. Conclusion: High-income countries use more topical AK therapies than middle-income countries.

Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin-Angiotensin System.

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin-angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin-angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin-angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin-angiotensin system.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

Characterization of clinical photosensitivity in cutaneous lupus erythematosus.

BACKGROUND: Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. OBJECTIVE: We sought to characterize self-reported PS in cutaneous LE (CLE). METHODS: The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. RESULTS: In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). LIMITATIONS: PS was inferred from patient report and not directly observed. CONCLUSIONS: Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology.