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.

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.

Compression Therapy for HIV-Associated Kaposi Sarcoma Leg Lymphedema: Results of the Kenyan Improvised Compression for Kaposi Sarcoma Randomized Controlled Trial.

PURPOSE: Evaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema. METHODS: A randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted. RESULTS: Of 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was -25.9 (34.6) for the control arm compared with -13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was -12.6 (-39.3 to 14.1). CONCLUSION: Future studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.

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 of tungiasis using a tea tree oil-based gel formulation: protocol for a randomised controlled proof-of-principle trial.

INTRODUCTION: Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment. METHODS AND ANALYSIS: This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6-15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction. ETHICS AND DISSEMINATION: The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

Implementing a Locally Made Low-Cost Intervention for Wound and Lymphedema Care in Western Kenya.

In Western Kenya, the burden of chronic wounds and lymphedema has a significant impact on functionality and quality of life. Major barriers to provision of care include availability, affordability, and accessibility of bandages. At the Academic Model Providing Access to Healthcare, dermatologists and pharmacists collaborated to develop a 2-component compression bandage modeled after the Unna boot, using locally available materials, that is distributed through a revolving fund pharmacy network. In partnership with nursing, use of these bandages at a national referral hospital and a few county facilities has increased, but increasing utilization to an expanded catchment area is needed.

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.

Implementation of an Ultraviolet Phototherapy Service at a National Referral Hospital in Western Kenya: Reflections on Challenges and Lessons Learned.

INTRODUCTION: In order to manage skin conditions at a national referral hospital level in Kenya, specialized dermatology services, such as dermatologic surgery, dermatopathology, phototherapy, and sub-specialty care, should be offered, as is typically available in referral hospitals around the world. A Kenyan patient with prurigo nodularis, whose severe itch remitted after phototherapy treatment at the University of California, San Francisco (UCSF), inspired the development of a phototherapy service at Academic Model Providing Access to Healthcare (AMPATH), a partnership in Western Kenya between Moi Teaching and Referral Hospital, Moi University College of Health Sciences, and a consortium of North American academic medical centers. METHODS: Initial project funds were raised through a crowdfunding campaign and fundraising events. A new narrowband ultraviolet B phototherapy unit and replacement bulbs were donated and air shipped to Eldoret, Kenya. A team of dermatologists and phototherapy nurses from UCSF conducted a 2-day training session. US-based dermatologists affiliated with AMPATH provide ongoing support through regular communication and on-site visits. RESULTS: Early in implementation, challenges faced included training clinical staff with limited experience in phototherapy and improving communication between nurses and clinicians. More recent challenges include frequent rotation of specialty clinic nurses in the dermatology clinic, adaptation of phototherapy guidelines to balance patient volume with service delivery capacity, and training assessment of disease activity in darkly pigmented skin. CONCLUSION: Strategies that have been helpful in addressing implementation challenges include: increasing on-site and remote training opportunities for clinicians and nurses, developing a tiered payment schema, educating patients to combat misconceptions about phototherapy, dynamic phototherapy referral guidelines to accommodate service delivery capacity, and prioritizing the engagement of a multidisciplinary team.

Randomized controlled trial to evaluate locally sourced two-component compression bandages for HIV-associated Kaposi sarcoma leg lymphedema in western Kenya: The Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study protocol.

BACKGROUND: HIV-associated Kaposi sarcoma (KS), among the most frequent cancers seen in sub-Saharan Africa, is associated with a high prevalence of lymphedema. Lymphedema causes progressive functional impairment marked by swelling, physical discomfort, disfiguring changes, skin hardening from fibrosis, poor wound healing, and recurrent skin infection. While compression therapy is considered a major component of lymphedema management, this intervention has never been evaluated in HIV-associated KS lymphedema. METHODS/DESIGN: The Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study is a randomized, controlled trial. Due to variable lymphedema stage, we will use block randomization with a 1:1 allocation to assign participants to one of two groups: "Immediate compression" or "Delayed compression." Those randomized to "Immediate compression" intervention arm will receive weekly two-component compression bandages while receiving chemotherapy, whereas those in the "Delayed compression" control arm will be followed during chemotherapy and then receive compression after chemotherapy is completed. The primary outcome is change in Lower Extremity Lymphedema Index from enrollment at Week 0 to blinded outcome assessment at Week 14 between intervention and control arms. Secondary outcomes are change in leg lymphedema-specific quality of life (LYMQOL) and change in overall health quality of life in cancer (EORTC QLQ C30). DISCUSSION: This represents the first study in sub-Saharan Africa to assess a lymphedema-directed intervention for KS, and the intervention-locally sourced two-component compression bandages-is affordable and available. Thus, the KICKS study is an important step towards developing an evidence-based path for regionally relevant management of HIV-associated KS lymphedema. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on January 19, 2018: identifier NCT03404297.

Development of Low-Cost Locally Sourced Two-Component Compression Bandages in Western Kenya.

INTRODUCTION: Compression therapy is well-established standard of care for chronic leg ulcers from venous disease and lymphedema. Chronic leg ulcers and lymphedema have a significant impact on quality of life, driven by pain, foul odor, and restricted mobility. Provision of layered compression therapy in resource-limited settings, as in Western Kenya and other regions of sub-Saharan Africa, is a major challenge due to several barriers: availability, affordability, and access to healthcare facilities. When wound care providers from an Academic Model Providing Access to Healthcare (AMPATH) health center in Western Kenya noted that a donated, finite supply of two-component compression bandages was helping to heal chronic leg ulcers, they began to explore the potential of finding a local, sustainable solution. Dermatology and pharmacy teams from AMPATH collaborated with health center providers to address this need. METHODS: Following a literature review and examination of ingredients in prepackaged brand-name kits, essential components were identified: elastic crepe, gauze, and zinc oxide paste. All of these materials are locally available and routinely used for wound care. Two-component compression bandages were made by applying zinc oxide to dry gauze for the inner layer and using elastic crepe as the outer layer. Feedback from wound clinic providers was utilized to optimize the compression bandages for ease of use. RESULTS: Adjustments to assembly of the paste bandage included use of zinc oxide paste instead of zinc oxide ointment for easier gauze impregnation and cutting the inner layer gauze in half lengthwise to facilitate easier bandaging of the leg, such that there were two rolls of zinc-impregnated gauze each measuring 5 inches × 2 m. Adjustments to use of the compression bandage have included increasing the frequency of bandage changes from 7 to 3 days during the rainy seasons, when it is difficult to keep the bandage dry. Continuous local acquisition of all components led to lower price quotes for bulk materials, driving down the production cost and enabling a cost to the patient of 200 KSh (2 USD) per two-component compression bandage kit. Wound care providers have provided anecdotal reports of healed chronic leg ulcers (from venous stasis, trauma), improved lymphedema, and patient tolerance of compression. CONCLUSIONS: Low-cost locally sourced two-component compression bandages have been developed for use in Western Kenya. Their use has been initiated at an AMPATH health center and is poised to meet the need for affordable compression therapy options in Western Kenya. Studies evaluating their efficacy in chronic leg ulcers and Kaposi sarcoma lymphedema are ongoing. Future work should address adaptation of compression bandages for optimal use in Western Kenya and evaluate reproducibility of these bandages in similar settings, as well as consider home- or community-based care delivery models to mitigate transportation costs associated with accessing healthcare facilities.

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.

Cutaneous malignancies in HIV.

PURPOSE OF REVIEW: As patients with HIV infection are living longer with their disease, we have seen the evolution of skin cancer in this population. Cancer registries have not documented the incidence and prevalence of these cancers but we do have relevant data from cohorts. This article attempts to bring to light the extent to which skin cancer is an issue in HIV disease both domestically and internationally. RECENT FINDINGS: Squamous cell cancer is increasing in incidence in the United States and elsewhere. The anatomic locations of skin cancer vary according to demographics, host factors, and environment. In this review, squamous cell cancer will be contrasted to the other skin cancers namely, melanoma, and basal cell cancers. SUMMARY: As our HIV population ages, clinicians should be informed as to the relevant risk factors for development of skin cancer. With the increasing incidence of these cancers in the modern era of HIV, clinicians and researchers will be informed with regard to prevention and treatment strategies.

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.

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.