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.

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.

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.

Cutaneous Ganglioneuromas With Overlying Epidermal Hyperplasia: A Case Series Presentation and Proposal of Potential Etiopathogenesis.

ABSTRACT: Cutaneous ganglioneuromas (GNs) are exceptionally uncommon tumors, and many reported cases describe association with overlying epidermal hyperplasia that may be interpreted as seborrheic keratosis (SK) or SK-like proliferation. We report 5 cases of cutaneous GN in adult patients; all of which were discovered incidentally in the immediate vicinity of epidermal hyperplasia. A review of the literature demonstrates the current-although likely imperfect-understanding of the etiopathogenesis of both SK and GN in the skin. We explore the putative pathophysiologies of other common, well-characterized skin lesions and, taking them into account, provide rationale for the coexistence of cutaneous GN with overlying SK and SK-like epidermal changes. However, we ultimately acknowledge a dilemma of causality and, given the rarity of their co-occurrence, objectively question whether occasional cameo appearances by GN lying subjacent to SK and SK-like hyperplasia may be due merely to chance.

Skin conditions among pediatric dermatology outpatients in Botswana.

BACKGROUND: An understanding of the prevalence patterns of skin diseases in children in Botswana is needed to guide national dermatological policy development, training, and resource allocation to improve patient care. OBJECTIVE: To describe local skin disease patterns in children aged 0-18 years presenting for dermatologic care in Botswana. METHODS: A retrospective review of records from 1st January 2011 to 31st December 2016 was conducted at the outpatient dermatology clinic of Princess Marina Hospital (PMH) in Gaborone, Botswana and outreach clinic sites. RESULTS: There were 4413 pediatric visits constituting 18.6% of all dermatology visits. There was a slight male predominance of 1.2:1. The majority of disorders were noninfectious 80.1% (3537/4413) versus infectious 14.6% (645/4413), with 5.2% (231/4413) unclassified. In the noninfectious category, two-thirds were inflammatory, followed by disorders of nails, skin appendages, and pigmentary disorders. Atopic dermatitis was the most common inflammatory disorder. Over half of infectious skin diseases were viral, followed by fungal and bacterial disorders. In the HIV-related disorders, the majority were verrucae 94% (108/115) followed by Kaposi sarcoma. The nine most common skin diagnoses accounted for close to 70% of all skin diseases seen at the clinic, and these included atopic dermatitis (almost half of all cases), followed by verruca, acne, and vitiligo. CONCLUSION: There is a high burden of skin disorders in children in Botswana. In our cohort, a small number of skin conditions made up the vast majority of pediatric diagnoses. This information can be used to guide dermatology training and resource allocation to better manage these common diseases.

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.

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.

Sexually acquired syphilis: Historical aspects, microbiology, epidemiology, and clinical manifestations.

Syphilis is caused by infection with the spirochetal bacterium Treponema pallidum subsp. pallidum. It was first recognized in the late 15th century. Since 2000, the incidence of sexually acquired syphilis has increased substantially in the developed world, with men who have sex with men and persons living with HIV infection disproportionately affected. Clinical manifestations of syphilis are protean and often include mucocutaneous manifestations. The first article in this continuing medical education series reviews historical aspects, microbiology, epidemiology, and clinical manifestations of sexually acquired syphilis.

Sexually acquired syphilis: Laboratory diagnosis, management, and prevention.

The methods used for the laboratory diagnosis of syphilis include direct detection of Treponema pallidum subspecies pallidum and serologic testing. Serologic testing relies on both nontreponemal and treponemal tests. In newly developed reverse-sequence screening algorithms, treponemal tests are performed before nontreponemal tests. The management of syphilis requires appropriate staging, treatment, and follow-up of patients along with the prompt reporting of infections to public health authorities to assist with prevention and control efforts. Benzathine penicillin G remains the treatment of choice for all stages of syphilis. Screening of populations at higher risk for syphilis is recommended by the US Centers for Disease Control and Prevention, the US Preventive Services Task Force, and the World Health Organization. The second article in this continuing medical education series reviews the testing for and the management of sexually acquired syphilis.

Clinical effectiveness and cost-effectiveness of teledermatology: Where are we now, and what are the barriers to adoption?

There has been rapid growth in teledermatology over the past decade, and teledermatology services are increasingly being used to support patient care across a variety of care settings. Teledermatology has the potential to increase access to high-quality dermatologic care while maintaining clinical efficacy and cost-effectiveness. Recent expansions in telemedicine reimbursement from the Centers for Medicare & Medicaid Services (CMS) ensure that teledermatology will play an increasingly prominent role in patient care. Therefore, it is important that dermatologists be well informed of both the promises of teledermatology and the potential practice challenges a continuously evolving mode of care delivery brings. In this article, we will review the evidence on the clinical and cost-effectiveness of teledermatology and we will discuss system-level and practice-level barriers to successful teledermatology implementation as well as potential implications for dermatologists.

Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries.

BACKGROUND: Increasing evidence suggests pernio-like lesions are cutaneous manifestations of coronavirus infectious disease 2019 (COVID-19). OBJECTIVE: To describe clinical and pathologic findings of pernio-like lesions in patients with confirmed or suspected COVID-19. METHODS: An international dermatology registry was circulated to health care providers worldwide through the American Academy of Dermatology, International League of Dermatologic Societies, and other organizations. RESULTS: We documented 505 patients with dermatologic manifestations associated with COVID-19, including 318 (63%) with pernio-like lesions. Patients with pernio-like lesions were generally young and healthy, with relatively mild COVID-19. Of 318 patients with confirmed or suspected COVID-19 by providers, 23 (7%) were laboratory-confirmed COVID-19 positive, and 20 others (6%) were close contacts of patients with confirmed COVID-19. Given current testing criteria, many patients lacked COVID-19 testing access. For 55% of patients, pernio-like lesions were their only symptom. In patients with other COVID-19 symptoms, pernio-like lesions typically appeared after other symptoms. Pernio-like lesions lasted a median of 14 days (interquartile range, 10-21 days). LIMITATIONS: A case series cannot estimate population-level incidence or prevalence. In addition, there may be confirmation bias in reporting. We cannot exclude an epiphenomenon. CONCLUSIONS: Pernio-like skin changes of the feet and hands, without another explanation, may suggest COVID-19 infection and should prompt confirmatory testing.

The spectrum of COVID-19-associated dermatologic manifestations: An international registry of 716 patients from 31 countries.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has associated cutaneous manifestations. OBJECTIVE: To characterize the diversity of cutaneous manifestations of COVID-19 and facilitate understanding of the underlying pathophysiology. METHODS: Case series from an international registry from the American Academy of Dermatology and International League of Dermatological Societies. RESULTS: The registry collected 716 cases of new-onset dermatologic symptoms in patients with confirmed/suspected COVID-19. Of the 171 patients in the registry with laboratory-confirmed COVID-19, the most common morphologies were morbilliform (22%), pernio-like (18%), urticarial (16%), macular erythema (13%), vesicular (11%), papulosquamous (9.9%), and retiform purpura (6.4%). Pernio-like lesions were common in patients with mild disease, whereas retiform purpura presented exclusively in ill, hospitalized patients. LIMITATIONS: We cannot estimate incidence or prevalence. Confirmation bias is possible. CONCLUSIONS: This study highlights the array of cutaneous manifestations associated with COVID-19. Many morphologies were nonspecific, whereas others may provide insight into potential immune or inflammatory pathways in COVID-19 pathophysiology.

Validation of Image Quality and Diagnostic Accuracy Using a Mobile Phone Camera Microscope Adaptor Compared With Glass Slide Review in Teledermatopathology.

New modalities of evaluating histopathology, such as whole-slide imaging, have been validated in the field of dermatopathology but are often unfeasible and unavailable in developing countries. Widely available across the globe, mobile phone camera technology represents a potential simple and inexpensive method of imaging histologic slides through the use of a mobile phone camera microscope adaptor. This study aims to validate the use of a commercially available adaptor in the diagnosis of inflammatory and infectious conditions in dermatopathology. Representative images were taken of slides for fifty-four cases using the adaptor and shared through a cloud-based platform with five dermatopathologists who rendered diagnoses and judged the quality of the images. After a washout period of 8 weeks, the same cases were assessed by the same dermatopathologists using the original glass slides. The intraobserver concordance rate was 93.3%, and the quality of the mobile phone images was rated as "excellent" or "diagnostic" in 94.4% of the cases. This study validates the use of this low-tech and low-cost adaptor as a reliable tool in teledermatopathology. Limitations of the study include those inherent to use of the adaptor and the limited panel of diagnoses. The primary value of this device may be in developing countries, but its practicality and ease of use lend itself to use in academic and consultative settings in the developed world as well.

Implementing a School Vision Screening Program in Botswana Using Smartphone Technology.

Purpose: Child eye health is a significant public health issue in low- and middle-income countries, such as Botswana, and the need for eye care requires a well-integrated and innovative approach. Traditional vision screening tools are costly, difficult to transport, and reliant on highly trained eye care professionals. Novel smartphone-based vision screening technologies, however, are low cost, portable, and easily operated by trained novice users. Peek Vision is a mobile health (m-Health) organization that creates smartphone applications that screen for visual acuity, generate referrals to eye care professionals, and send phone notifications to those being screened. Methodology: In 2016, the government of Botswana partnered with local and international stakeholders to implement Peek vision screening in a subset of schoolchildren. From June to December of 2016, teachers, health assistants, nurses, and other volunteers in 49 schools in the Goodhope Subdistrict utilized Peek applications to screen schoolchildren, using acuity <6/12 in the better eye as a threshold for visual impairment. Results: Among 12,877 children screened, the application identified 16% (2,065/12,877) as screening positive for visual impairment, and these students were referred for optometric care. Ultimately, 96% (1,985/2,065) attended optometry triage camps, during which 42% (835/1,985) were provided with spectacles, 5% (94/1,985) received ophthalmic medications, and 3% (63/1,985) were referred for ophthalmic care. These findings underscore the need for comprehensive vision screening in schoolchildren in Botswana. Furthermore, the successful implementation of Peek smartphone applications illustrates the potential of m-Health technology for enacting comprehensive vision screening programs at a national level in Botswana and other similar countries.

Kaposi Sarcoma Herpesvirus Inflammatory Cytokine Syndrome-like Clinical Presentation in Human Immunodeficiency Virus-infected Children in Malawi.

We describe 7 human immunodeficiency virus-infected Malawian children with Kaposi sarcoma who met criteria for Kaposi sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome. Each presented with persistent fevers, bulky lymphadenopathy, massive hepatosplenomegaly, and severe cytopenias. Plasma analyses were performed in 2 patients, both demonstrating extreme elevations of KSHV viral load and interleukin 6.

Cost analysis of a store-and-forward teledermatology consult system in Philadelphia.

BACKGROUND: Store-and-forward (SAF) teledermatology (TD) has the potential to increase access to timely, high-quality care for underserved populations. However, the cost-effectiveness of TD for underserved populations is uncertain. OBJECTIVE: This study evaluates the potential cost savings associated with an SAF TD program implemented for an underserved population in the city health clinics of urban Philadelphia. METHODS: We performed a retrospective analysis of SAF TD consultations for 700 outpatients managed in 12 Philadelphia primary care clinics. Primary care providers were asked to specify a treatment plan, as well as the type of care for the patient, in the absence of the TD service. Analysis compared the cost of each patient case with use of the TD consult model versus with conventional care. RESULTS: In all, 27% of in-person dermatology clinic visits (189 of 700) and 3.29% of emergency room visits (23 of 700) were avoided by using TD. Compared with conventional care, TD had a mean expected cost savings of $10.00 to $52.65 per TD consult. In sensitivity analyses, these estimated savings remained positive across a range of parameters. LIMITATIONS: The cost analysis relies on several assumptions regarding the cost of care, and indirect costs were not included. CONCLUSION: TD can be a cost-saving model while increasing access to dermatologic care.

Increasing Access to High Value Care: Preventing Complications in Common Disorders.

Most infantile hemangiomas (IHs), the most common vascular tumors of childhood, evolve without complications; however 10% to 12% require specialty referral for treatment. To emphasize the complications of late referral, we present a case of necrotizing infection within a segmental IH leading to sepsis. Early evaluation by a pediatric dermatologist could have prevented this life-threatening and disfiguring complication. We discuss how teledermatology would enable rapid triage of such critical cases in underserved areas, increasing access to high-value care and optimizing outcomes for our most vulnerable patients.

HIV-associated erythema elevatum diutinum: a case report and review of a clinically distinct variant.

A 24-year-old man with untreated human immunodeficiency virus (HIV) infection consulted our outreach clinic owing to the development of numerous asymptomatic nodules on his palms and fingers. Histopathologic evaluation revealed leukocytoclastic vasculitis and prominent fibrosis with a neutrophilic infiltrate consistent with erythema elevatum diutinum (EED). We referred the patient for initiation of antiretroviral therapy and started him on dapsone. The pathogenesis of EED is not completely understood, but it has been associated with numerous systemic conditions that may be infectious, inflammatory, or neoplastic. Only recently has EED been recognized as a defined reactive dermatosis of HIV. We present an exemplary case of HIV-associated EED and review the differential diagnosis, highlighting clinical features of EED that appear to be more frequently encountered in the HIV-infected population.