Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease.

BACKGROUNDKaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.METHODSThis was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were characterized for viral and human transcription, and KSHV genomes were determined when possible.RESULTSSeventy participants with pediatric KS were enrolled between June 2013 and August 2019 in Malawi and compared with adult patients with KS. They exhibited high KSHV genome copy numbers and IL-6/IL-10 levels. Four biopsies (16%) had a viral transcription pattern consistent with lytic viral replication.CONCLUSIONThe unique features of pediatric KS may contribute to the specific clinical manifestations and may direct future treatment options.FUNDINGUS National Institutes of Health U54-CA-254569, PO1-CA019014, U54-CA254564, RO1-CA23958.

Emerging infectious diseases of the skin: a review of clinical and histologic findings.

Emerging infectious diseases are of great importance to public health and clinical practice. This review aims to characterize the clinical and histopathologic features of emerging infectious diseases with cutaneous manifestations in order to increase awareness of these entities among dermatologists, pathologists, and dermatopathologists.

Divergent clinical presentations and outcomes among children and adolescents with Kaposi sarcoma in Malawi and Tanzania.

OBJECTIVES: The Kaposi sarcoma (KS) T0 versus T1 staging classification does not address the unique clinical features of paediatric KS in human gammaherpesvirus 8 (HHV-8) endemic regions of Africa. This study seeks to define patterns of childhood KS using a paediatric-specific approach. METHODS: The Lilongwe paediatric KS staging classification categorizes disease based on clinical phenotype: stage 1 = mild/moderate KS limited to cutaneous/oral involvement, stage 2 = primarily lymphadenopathic disease, stage 3 = woody edema KS, stage 4 = visceral and/or severe/disseminated mucocutaneous disease. Characteristics and outcomes were evaluated from paediatric referral centres in Lilongwe, Malawi, and Mbeya, Tanzania. RESULTS: Among 171 patients, the median age was 9.3 years, 37% (n = 63) were female, and 87% (n = 149) had HIV. Breakdown by stage was as follows: 18% (n = 31) stage 1, 33% (n = 56) stage 2, 19% (n = 33) stage 3, and 30% (n = 51) stage 4. Age (younger stage 2 and older stage 3), severe CD4 count suppression (lower CD4 for stages 1 and 4), and presence of severe anaemia and thrombocytopenia (worse for stages 2 and 4) differed across stages. Estimated 2-year event-free survival/progression-free survival/overall survival by stage was as follows: stage 1, 81%/81%/87%; stage 2, 50%/50%/63%; stage 3, 24%/49%/81%; and stage 4, 29%/34%/54%. Sub-analysis of stage 2 lymphadenopathic KS demonstrated superior long-term 6-year event-free survival of 70% (95% confidence interval [CI] 49-83) for younger children (aged <7 years) versus 27% (95% CI 8-51) for older children. CONCLUSIONS: This paediatric-specific staging classification categorizes patients with distinct characteristics and patterns of treatment response. This platform may guide clinicians to provide risk-stratified treatment with the hope of improving survival among children with KS.

Synchronous and asynchronous teledermatology: A narrative review of strengths and limitations.

The policy changes prompted by the COVID-19 pandemic caused synchronous models (primarily video visits) to supplant asynchronous models (store-and-forward or shared digital photographs) as the default and predominant modality of teledermatology care. Here, we call attention to the unique strengths and limitations of these models in terms of clinical utility, accessibility, and cost-effectiveness. Strengths of synchronous visits include direct physician-patient interaction and current reimbursement parity; limitations include variable video image quality, technological difficulties, and accessibility barriers. Strengths of asynchronous visits include greater convenience, especially for clinicians, and potential for image quality superior to video; limitations include less direct physician-patient communication, barriers to follow-up, and limited reimbursement. Both synchronous and asynchronous models have been shown to be cost-effective. Teledermatology is positioned to play a prominent role in patient care post-pandemic. Moving forward, dermatologists are challenged to optimize teledermatology use in order to improve outcomes, efficiency, and workflows to meet diverse patient needs. Future directions will depend on sustainable reimbursement of both teledermatology formats by government and private payers.

Long-term outcomes for children and adolescents with Kaposi sarcoma.

OBJECTIVES: Kaposi sarcoma (KS) is one of the most common childhood cancers in eastern and central Africa. It has become a treatable disease with increasing availability of antiretroviral therapy (ART) and chemotherapy. We aimed to fill the data gap in establishing whether long-term survival is achievable for children in low-income countries. METHODS: We retrospectively analysed data for children and adolescents aged ≤ 18.9 years diagnosed with HIV-related or endemic KS from 2006 to 2015 who received standardized institutional treatment regimens utilizing chemotherapy plus ART (if HIV-positive) at a tertiary care public hospital in Lilongwe, Malawi. Long-term survival was analysed and mortality was associated with KS for those with refractory/progressive disease at the time of death. RESULTS: There were 207 children/adolescents with KS (90.8% HIV-related); 36.7% were alive, 54.6% had died, and 8.7% had been lost to follow-up. The median follow-up time for survivors was 6.9 years (range 4.2-13.9 years). Death occurred at a median of 5.3 months after KS diagnosis (range 0.1-123 months). KS progression was associated with mortality for most (61%) early deaths (survival time of < 6 months); conversely, KS was associated with a minority (31%) of late-onset deaths (after 24 months). The 7-year overall survival was 37% [95% confidence interval (CI) 30-44%] and was higher for those diagnosed between 2011 and 2015 compared to 2006-2010: 42% (95% CI 33-51%) versus 29% (95% CI 20-39%), respectively (P = 0.01). Among the 66 HIV-positive survivors, 58% were still on first-line ART. CONCLUSIONS: Long-term survival is possible for pediatric KS in low-resource settings. Despite better survival in more recent years, there remains room for improvement.

Patient Factors Associated With Teledermatology Visit Type and Submission of Photographs During the COVID-19 Pandemic: Cross-sectional Analysis.

BACKGROUND: The COVID-19 pandemic necessitated the widespread adoption of teledermatology, and this continues to account for a significant proportion of dermatology visits after clinics have reopened for in-person care. Delivery of high-quality teledermatology care requires adequate visualization of the patient's skin, with photographs being preferred over live video for remote skin examination. It remains unknown which patients face the greatest barriers to participating in a teledermatology visit with photographs. OBJECTIVE: The aim of this study was to identify patient characteristics associated with type of telemedicine visit and the factors associated with participating in teledermatology visits with digital photographs versus those without photographs. METHODS: We performed a cross-sectional analysis of the University of Pennsylvania Health System electronic health record data for adult patients who participated in at least 1 teledermatology appointment between March 1, 2020, and June 30, 2020. The primary outcomes were participation in a live-interactive video visit versus a telephone visit and participation in any teledermatology visit with photographs versus one without photographs. Multivariable logistic regression was performed to evaluate the associations between patient characteristics and the primary outcomes. RESULTS: In total, 5717 unique patients completed at least 1 teledermatology visit during the study period; 68.25% (n=3902) of patients participated in a video visit, and 31.75% (n=1815) participated in a telephone visit. A minority of patients (n=1815, 31.75%) submitted photographs for their video or telephone appointment. Patients who submitted photographs for their teledermatology visit were more likely to be White, have commercial insurance, and live in areas with higher income, better education, and greater access to a computer and high-speed internet (P<.001 for all). In adjusted analysis, older age (age group >75 years: odds ratio [OR] 0.60, 95% CI 0.44-0.82), male sex (OR 0.85, 95% CI 0.75-0.97), Black race (OR 0.79, 95% CI 0.65-0.96), and Medicaid insurance (OR 0.81, 95% CI 0.66-0.99) were each associated with lower odds of a patient submitting photographs for their video or telephone visit. Older age (age group >75 years: OR 0.37, 95% CI 0.27-0.50) and Black race (OR 0.82, 95% CI 0.68-0.98) were also associated with lower odds of a patient participating in a video visit versus telephone visit. CONCLUSIONS: Patients who were older, male, or Black, or who had Medicaid insurance were less likely to participate in teledermatology visits with photographs and may be particularly vulnerable to disparities in teledermatology care. Further research is necessary to identify the barriers to patients providing photographs for remote dermatology visits and to develop targeted interventions to facilitate equitable participation in teledermatology care.

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.

Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: A registry-based study.

BACKGROUND: Cutaneous reactions after COVID-19 vaccination have been commonly reported; however, histopathologic features and clinical correlations have not been well characterized. METHODS: We evaluated for a history of skin biopsy all reports of reactions associated with COVID-19 vaccination identified in an international registry. When histopathology reports were available, we categorized them by reaction patterns. RESULTS: Of 803 vaccine reactions reported, 58 (7%) cases had biopsy reports available for review. The most common histopathologic reaction pattern was spongiotic dermatitis, which clinically ranged from robust papules with overlying crust, to pityriasis rosea-like eruptions, to pink papules with fine scale. We propose the acronym "V-REPP" (vaccine-related eruption of papules and plaques) for this spectrum. Other clinical patterns included bullous pemphigoid-like (n = 12), dermal hypersensitivity (n = 4), herpes zoster (n = 4), lichen planus-like (n = 4), pernio (n = 3), urticarial (n = 2), neutrophilic dermatosis (n = 2), leukocytoclastic vasculitis (n = 2), morbilliform (n = 2), delayed large local reactions (n = 2), erythromelalgia (n = 1), and other (n = 5). LIMITATIONS: Cases in which histopathology was available represented a minority of registry entries. Analysis of registry data cannot measure incidence. CONCLUSION: Clinical and histopathologic correlation allowed for categorization of cutaneous reactions to the COVID-19 vaccine. We propose defining a subset of vaccine-related eruption of papules and plaques, as well as 12 other patterns, following COVID-19 vaccination.

A systematic review of mobile health interventions in China: Identifying gaps in care.

INTRODUCTION: Mobile health has a promising future in the healthcare system in most developed countries. China's rapidly developing mobile technology infrastructure offers an unprecedented opportunity for wide adoption of mobile health interventions in the delivery of effective and timely healthcare services. However, there is little data on the current extent of the mobile health landscape in China. The aim of this study was to systematically review the existing mobile health initiatives in China, characterise the technology used, disease categories targeted, location of the end user (urban versus rural), and examine the potential effects of mobile health on health system strengthening in China. Furthermore, we identified gaps in development and evaluation of the effectiveness of mobile health interventions. METHODS: A systematic review of the literature published from 18 December 2015 - 3 April 2019 was conducted and yielded 2863 articles from English and Chinese retrieval database and trial registries, including PubMed, EMBASE, China National Knowledge of Infrastructure and World Health Organization International Clinical Trials Registry Platform. Studies were included if they used mobile health to support patient healthcare outcomes. RESULTS: A total of 1129 full-text articles were assessed and 338 were included in this study. The review found that most studies targeted client education and behaviour change via applications (apps) (65.4%), including WeChat, and text messaging (short text messages) (19.8%) to improve patient medical treatment outcomes such as compliance and appointment reminders. The most common disease-specific mobile health interventions focused primarily on chronic disease management and behaviour change in cardiology (13.3%), endocrinology/diabetes (12.1%), behavioural health (11.8%), oncology (11.2%) and neurology (6.8%). The mobile health interventions related to nutrition (0.6%) and chronic respiratory diseases (1.6%) are underrepresented in mobile health in comparison to the burden of disease in China. The majority (90.0%) of the mobile health interventions were conducted exclusively in urban areas, with few opportunities reaching rural populations. CONCLUSIONS: Overall, mobile health has a promising future in China, with recent rapid growth in initiatives. The majority are focused on education and behaviour change in the realm of chronic diseases and target patients in urban areas. The imbalance in mobile health between the urban and rural areas, as well as between population disease spectrum and health service delivery, pose substantial dilemmas. However, mobile health may be redirected to correct this imbalance, possibly improving access to healthcare services, and filling the gaps in order to improve health equity for the underserved populations in China.

Prospective Implementation of a Consultative Store-and-Forward Teledermatology Model at a Single Urban Academic Health System with Real Cost Data Subanalysis.

Background: Teledermatology may increase access to care but has not been widely implemented due, in part, to lack of insurance coverage and reimbursement. We assessed the impact of implementing a consultative store-and-forward teledermatology model on access to care, medical cost, and utilization. Materials and Methods: Prospective implementation of teledermatology occurred at five University of Pennsylvania Health System primary care practices from June 27, 2016, to May 25, 2017. Primary outcomes included time to case completion, proportion of patients completing in-person dermatology visits, and total outpatient costs. Medical and pharmacy claims data were used for utilization and cost subanalysis. Results: The study included 167 patients and 1,962 controls with a 6-month follow-up. Median time to definitive dermatologist response was 0.19 days (interquartile range [IQR]: 0.03-2.92) for intervention and 83.60 days (IQR: 19.74-159.73) for controls. In medical claims subanalysis, no significant differences in mean outpatient costs ($3,366 vs. $2,232, p = 0.1356) or total medical costs ($3,535 vs. $2,654, p = 0.2899) were detected. Conclusions: Implementation of teledermatology improved access to care, and within this small sample, remained comparable in terms of cost and utilization. Thus, these data suggest teledermatology may improve access without increasing utilization or cost.

Disseminated cysticercosis and Kaposi sarcoma in a child with HIV/AIDS: A case report.

BACKGROUND: Clinical manifestations of extraneural infection with the pork tapeworm Taenia solium typically affect the muscles, eyes, alimentary canal, and/or subcutaneous tissues. Children living with HIV are at increased risk for more widespread and severe manifestations of food-borne opportunistic infections, including T. solium, due to fluctuating levels of immunosuppression. We present a case of disseminated T. solium in a HIV-positive child with Kaposi sarcoma living in Tanzania with cysticercosis presenting as widespread subcutaneous nodules. CASE PRESENTATION: A 4-year-old HIV-positive boy in Southern Tanzania presented for evaluation of > 30 violaceous skin lesions, few subcutaneous nodules, and a circumferential violaceous penile lesion which rapidly grew after initiation of ART. The patient was clinically diagnosed with Kaposi sarcoma and started on chemotherapy with bleomycin, vincristine, and doxorubicin. He completed 10 cycles of chemotherapy, with full resolution of the violaceous skin and penile lesions but persistence of his subcutaneous nodules, thus paclitaxel was added. After 12 additional cycles of paclitaxel, his subcutaneous nodules enlarged, and biopsy of a scapular subcutaneous nodule was performed. Histopathology revealed a cystic structure with a central larval scolex and serrated spiral canal consistent with T. solium, which confirmed a diagnosis of disseminated cysticercosis. He completed a 10-day course of praziquantel and albendazole with resolution of the subcutaneous nodules. CONCLUSIONS: Disseminated cysticercosis is an unusual opportunistic infection which can present as subcutaneous nodules without other typical cysticercosis symptoms. Immunosuppression - from HIV and/or chemotherapy - may unmask cysticercosis in children in endemic regions and result in more severe manifestations of this disease. Cysticercosis should remain on a clinician's differential for subcutaneous nodules, especially in children living with HIV. Cysticercosis can mimic Kaposi sarcoma, and histopathology is essential to accurately diagnose and manage patients with concerning skin lesions.