Artificial intelligence and skin cancer.

Artificial intelligence is poised to rapidly reshape many fields, including that of skin cancer screening and diagnosis, both as a disruptive and assistive technology. Together with the collection and availability of large medical data sets, artificial intelligence will become a powerful tool that can be leveraged by physicians in their diagnoses and treatment plans for patients. This comprehensive review focuses on current progress toward AI applications for patients, primary care providers, dermatologists, and dermatopathologists, explores the diverse applications of image and molecular processing for skin cancer, and highlights AI's potential for patient self-screening and improving diagnostic accuracy for non-dermatologists. We additionally delve into the challenges and barriers to clinical implementation, paths forward for implementation and areas of active research.

Rural-Urban Differences in Sun Exposure and Protection Behaviors in the United States.

BACKGROUND: Evidence regarding whether rural residence is a risk factor for skin cancer is mixed. We compared sun exposure and protection behaviors between rural and urban residents by ethno-racial group in the United States. METHODS: We analyzed data from three (2013-2018) National Health and Nutrition Examination Survey cycles. We compared self-reported sun exposure and protection measures (sunburn, time spent outside, sunscreen use, wearing long sleeves, staying in shade) by rural-urban residential status using survey-weighted logistic regression models stratified by ethno-racial group, adjusting for age, sex, income, education, body mass index, and smoking. RESULTS: Hispanic rural versus urban residents more often reported sunburns in the past year [41.6% vs. 31.2%, adjusted OR (aOR): 1.46 (1.15-1.86)]. White rural versus urban residents more often spent 2+ hours outside on workdays [42.9% vs. 29.1%, aOR: 1.60 (1.27-2.01)] and non-workdays [72.2% vs. 64.8%, aOR: 1.45 (1.12-1.88)] and less often used sunscreen [26.0% vs. 35.1%, aOR: 0.74 (0.59-0.93)] and stayed in the shade [21.7% vs. 26.7%, aOR: 0.72 (0.57-0.89)]. Black rural versus urban residents stayed in the shade less often [31.6% vs. 43.9%, aOR: 0.60 (0.39-0.91)] but less often spent 2+ hours outside on non-workdays [47.6% vs. 56.8%, aOR: 0.67 (0.51-0.90)]. CONCLUSIONS: Across all ethno-racial groups included, rural residents reported greater sun risk behaviors than urban residents, with some nuances by ethno-racial identity, suggesting rural residence is a potential risk factor for skin cancer. IMPACT: Sun protection promotion programs should consider rural-urban settings while also accounting for ethno-racial identities.

Impact of climate change on atopic dermatitis: A review by the International Eczema Council.

Atopic dermatitis (AD), the most burdensome skin condition worldwide, is influenced by climatic factors and air pollution; however, the impact of increasing climatic hazards on AD remains poorly characterized. Leveraging an existing framework for 10 climatic hazards related to greenhouse gas emissions, we identified 18 studies with evidence for an impact on AD through a systematic search. Most climatic hazards had evidence for aggravation of AD the impact ranged from direct effects like particulate matter-induced AD exacerbations from wildfires to the potential for indirect effects like drought-induced food insecurity and migration. We then created maps comparing the past, present, and future projected burden of climatic hazards to global AD prevalence data. Data are lacking, especially from those regions most likely to experience more climatic hazards. We highlight gaps important for future research: understanding the synergistic impacts of climatic hazards on AD, long-term disease activity, the differential impact on vulnerable populations, and how basic mechanisms explain population-level trends.

Botfly myiasis after travel to Bolivia.

Following a trip to Bolivia, a 32-year-old woman developed a left lower leg ulcer with a sensation of movement within the lesion. After being seen by four primary care providers, she was referred to dermatology 7 weeks after her return from Bolivia. At that time, she was found to have a 5 mm weeping ulcer, with a live larva visible at the base. We conducted a punch biopsy for botfly removal, after which the patient healed well. Herein we discuss the ways in which clinical presentation, history of travel, dermoscopy, and ultrasound can contribute to diagnosing botfly myiasis. While treatment of botfly infestation is not required, we discuss the importance of shared decision-making in considering treatment, as well as methods for extraction, including mechanical or surgical removal, which may help to reduce patient anxiety and the risk for secondary infection. As global travel resumes to levels prior to the Covid-19 pandemic, it is important for dermatologists to be aware of the presenting symptoms and treatment of tropical skin disorders.

Spiny Keratoderma in Association with Melanoma.

Spiny keratoderma (SK) was first described by Brown in 1871 and is characterized by numerous 1-2 mm spines of keratin on the palms and soles, usually sparing the dorsal surfaces, or disseminated over the trunk. Histologically, the "spine" represents a column of hyperkeratosis. Several different forms are known, including familial, sporadic, post-inflammatory and paraneoplastic. Although an association of SK with melanoma has been reported, the significance of such co-occurrence remains unclear due to the limited number of cases. To increase the body of knowledge and shed further light on this rare condition, we present a case of SK in a patient with a recent history of melanoma in situ.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Air Pollution and Atopic Dermatitis, from Molecular Mechanisms to Population-Level Evidence: A Review.

Atopic dermatitis (AD) has increased in prevalence to become the most common inflammatory skin condition globally, and geographic variation and migration studies suggest an important role for environmental triggers. Air pollution, especially due to industrialization and wildfires, may contribute to the development and exacerbation of AD. We provide a comprehensive, multidisciplinary review of existing molecular and epidemiologic studies on the associations of air pollutants and AD symptoms, prevalence, incidence, severity, and clinic visits. Cell and animal studies demonstrated that air pollutants contribute to AD symptoms and disease by activating the aryl hydrocarbon receptor pathway, promoting oxidative stress, initiating a proinflammatory response, and disrupting the skin barrier function. Epidemiologic studies overall report that air pollution is associated with AD among both children and adults, though the results are not consistent among cross-sectional studies. Studies on healthcare use for AD found positive correlations between medical visits for AD and air pollutants. As the air quality worsens in many areas globally, it is important to recognize how this can increase the risk for AD, to be aware of the increased demand for AD-related medical care, and to understand how to counsel patients regarding their skin health. Further research is needed to develop treatments that prevent or mitigate air pollution-related AD symptoms.

Association of Wildfire Air Pollution With Clinic Visits for Psoriasis.

This cross-sectional study examines whether clinic visits and online search interest for psoriasis were associated with wildfire air pollution after a delayed lag period.

Association of Exposure to Wildfire Air Pollution With Exacerbations of Atopic Dermatitis and Itch Among Older Adults.

This cross-sectional study evaluates the association of exposure to wildfire air pollution with exacerbations of atopic dermatitis and itch among adults aged 65 years or older.

Ultraviolet A radiation exposure and melanoma: a review.

The incidence of cutaneous melanoma has been increasing worldwide, and melanoma disproportionately contributes to skin cancer mortality. The pathogenesis of melanoma involves genetic and environmental factors, and while the effects of ultraviolet B radiation on melanoma development are well researched, fewer studies have investigated the role of ultraviolet A (UVA) radiation. We comprehensively reviewed cell, animal and epidemiology studies on the association between UVA exposure and melanomagenesis. UVA radiation has been found to have negative effects on melanocytes due to the induction of oxidative stress, dysregulation of gene transcription and creation of mutagenic photoproducts in DNA. Animal studies demonstrate adverse effects of UVA on melanocytes, including the development of melanoma. Epidemiology studies, of varying quality, that examined participants' exposure to tanning devices which use UVA radiation primarily found that UVA exposure increased the risk for melanoma. Some studies reported larger associations with increased frequency of device use, suggestive of a dose-response relationship. Overall, we found that many studies supported a positive association between UVA exposure and melanoma on both molecular and population levels. Understanding the role of UVA in the development of melanoma will inform the implementation of preventive health interventions, such as those related to sunscreen development and use and increasing restrictions on indoor tanning.

Disparities in access for melanoma screening by region, specialty, and insurance: A cross-sectional audit study.

Background: Early detection of melanoma is critical for positive outcomes. However, access for the diagnosis of melanoma remains problematic for segments of the general population. Objective: To compare the rates of dermatology and family medicine practitioner acceptances for a public insurance (Medicaid) versus private insurance (Anthem Blue Cross) and clinic wait times for an appointment for a changing pigmented skin lesion concerning melanoma in rural and urban regions in California. Methods: Cross-sectional audit study between June 2017 and March 2019; scripted phone calls were made to dermatology and family medicine practices (FMPs). Results: Family medicine and dermatology practices in both regions had significantly decreased acceptance of Medicaid. Dermatology practices had 11.3% to 13.0% Medicaid acceptance rates that were less than FMP rates of 28% to 36%. In both regions, FMP wait times were 2.4- to 3.2-fold longer for public versus private insurance; there were little differences in wait times for the 2 insurance types in dermatology practices, in both regions. Limitations: Assessment of only 2 regions in the state of California. Conclusion: Delays at FMPs and insurance types limit access to melanoma screening in California for underserved segments of the general population, which has implications for melanoma outcomes and health policy.

BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB.

Benign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs-MIR211-5p and MIR328-3p-induced mitotic failure, genome duplication, and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate that BRAFV600E induces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically, BRAFV600E expression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Taken together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.

Lots of people have small dark patches on their skin known as moles. Most moles form when individual cells known as melanocytes in the skin acquire a specific genetic mutation in a gene called BRAF. This mutation causes the cells to divide rapidly to form the mole. After a while, most moles stop growing and remain harmless for the rest of a person's life. Melanoma is a type of skin cancer that develops from damaged melanocytes. The same mutation in BRAF that is found in moles is also present in half of all cases of melanoma. Unlike in moles, the melanoma-causing mutation makes the melanocytes divide rapidly to form a tumor that keeps on growing indefinitely. It remains unclear why the same genetic mutation in the BRAF gene has such different consequences in moles and melanomas. To address this question, McNeal et al. used genetic approaches to study melanocytes from moles and melanomas. The experiments identified some molecules known as microRNAs that are present at higher levels in moles than in melanomas. Increasing the levels of two of these microRNAs in melanocytes from human skin stopped the cells from growing and dividing by inhibiting a gene called AURKB. This suggested that these microRNAs are responsible for halting the growth of moles. Introducing the mutated form of BRAF into melanocytes also stopped cells from growing and dividing by inhibiting AURKB. However, changing the environment surrounding the cells reversed this effect and allowed the melanocytes to resume dividing. In this way the mutated form of BRAF acts like a switch that allows melanocytes in skin cancers to start growing again under certain conditions. Further experiments found that a drug called barasertib is able to inhibit the growth of melanoma cells with the mutant form of BRAF. Future work will investigate whether it is possible to use this drug and other tools to stop skin cancer tumors from growing, and possibly even prevent skin tumors from forming in the first place.

Patient and general public attitudes towards clinical artificial intelligence: a mixed methods systematic review.

Artificial intelligence (AI) promises to change health care, with some studies showing proof of concept of a provider-level performance in various medical specialties. However, there are many barriers to implementing AI, including patient acceptance and understanding of AI. Patients' attitudes toward AI are not well understood. We systematically reviewed the literature on patient and general public attitudes toward clinical AI (either hypothetical or realised), including quantitative, qualitative, and mixed methods original research articles. We searched biomedical and computational databases from Jan 1, 2000, to Sept 28, 2020, and screened 2590 articles, 23 of which met our inclusion criteria. Studies were heterogeneous regarding the study population, study design, and the field and type of AI under study. Six (26%) studies assessed currently available or soon-to-be available AI tools, whereas 17 (74%) assessed hypothetical or broadly defined AI. The quality of the methods of these studies was mixed, with a frequent issue of selection bias. Overall, patients and the general public conveyed positive attitudes toward AI but had many reservations and preferred human supervision. We summarise our findings in six themes: AI concept, AI acceptability, AI relationship with humans, AI development and implementation, AI strengths and benefits, and AI weaknesses and risks. We suggest guidance for future studies, with the goal of supporting the safe, equitable, and patient-centred implementation of clinical AI.

Association of Wildfire Air Pollution and Health Care Use for Atopic Dermatitis and Itch.

IMPORTANCE: Air pollution is a worldwide public health issue that has been exacerbated by recent wildfires, but the relationship between wildfire-associated air pollution and inflammatory skin diseases is unknown. OBJECTIVE: To assess the associations between wildfire-associated air pollution and clinic visits for atopic dermatitis (AD) or itch and prescribed medications for AD management. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional time-series study assessed the associations of air pollution resulting from the California Camp Fire in November 2018 and 8049 dermatology clinic visits (4147 patients) at an academic tertiary care hospital system in San Francisco, 175 miles from the wildfire source. Participants included pediatric and adult patients with AD or itch from before, during, and after the time of the fire (October 2018 through February 2019), compared with those with visits in the same time frame of 2015 and 2016, when no large wildfires were near San Francisco. Data analysis was conducted from November 1, 2019, to May 30, 2020. EXPOSURES: Wildfire-associated air pollution was characterized using 3 metrics: fire status, concentration of particulate matter less than 2.5 µm in diameter (PM2.5), and satellite-based smoke plume density scores. MAIN OUTCOMES AND MEASURES: Weekly clinic visit counts for AD or itch were the primary outcomes. Secondary outcomes were weekly numbers of topical and systemic medications prescribed for AD in adults. RESULTS: Visits corresponding to a total of 4147 patients (mean [SD] age, 44.6 [21.1] years; 2322 [56%] female) were analyzed. The rates of visits for AD during the Camp Fire for pediatric patients were 1.49 (95% CI, 1.07-2.07) and for adult patients were 1.15 (95% CI, 1.02-1.30) times the rate for nonfire weeks at lag 0, adjusted for temperature, relative humidity, patient age, and total patient volume at the clinics for pediatric patients. The adjusted rate ratios for itch clinic visits during the wildfire weeks were 1.82 (95% CI, 1.20-2.78) for the pediatric patients and 1.29 (95% CI, 0.96-1.75) for adult patients. A 10-µg/m3 increase in weekly mean PM2.5 concentration was associated with a 7.7% (95% CI, 1.9%-13.7%) increase in weekly pediatric itch clinic visits. The adjusted rate ratio for prescribed systemic medications in adults during the Camp Fire at lag 0 was 1.45 (95% CI, 1.03-2.05). CONCLUSIONS AND RELEVANCE: This cross-sectional study found that short-term exposure to air pollution due to the wildfire was associated with increased health care use for patients with AD and itch. These results may provide a better understanding of the association between poor air quality and skin health and guide health care professionals' counseling of patients with skin disease and public health practice.

Stress testing reveals gaps in clinic readiness of image-based diagnostic artificial intelligence models.

Artificial intelligence models match or exceed dermatologists in melanoma image classification. Less is known about their robustness against real-world variations, and clinicians may incorrectly assume that a model with an acceptable area under the receiver operating characteristic curve or related performance metric is ready for clinical use. Here, we systematically assessed the performance of dermatologist-level convolutional neural networks (CNNs) on real-world non-curated images by applying computational "stress tests". Our goal was to create a proxy environment in which to comprehensively test the generalizability of off-the-shelf CNNs developed without training or evaluation protocols specific to individual clinics. We found inconsistent predictions on images captured repeatedly in the same setting or subjected to simple transformations (e.g., rotation). Such transformations resulted in false positive or negative predictions for 6.5-22% of skin lesions across test datasets. Our findings indicate that models meeting conventionally reported metrics need further validation with computational stress tests to assess clinic readiness.

Dermoscopy Proficiency Expectations for US Dermatology Resident Physicians: Results of a Modified Delphi Survey of Pigmented Lesion Experts.

Importance: Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know. Objectives: To identify consensus-based learning constructs representing an appropriate foundational proficiency in dermoscopic image interpretation for dermatology resident physicians, including dermoscopic diagnoses, associated features, and representative teaching images. Defining these foundational proficiency learning constructs will facilitate further skill development in dermoscopic image interpretation to help residents achieve clinical proficiency. Design, Setting, and Participants: A 2-phase modified Delphi surveying technique was used to identify resident learning constructs in 3 sequential sets of surveys-diagnoses, features, and images. Expert panelists were recruited through an email distributed to the 32 members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group. Twenty-six (81%) opted to participate. Surveys were distributed using RedCAP software. Main Outcomes and Measures: Consensus on diagnoses, associated dermoscopic features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for US dermatology resident physicians. Results: Twenty-six pigmented lesion and dermoscopy specialists completed 8 rounds of surveys, with 100% (26/26) response rate in all rounds. A final list of 32 diagnoses and 116 associated dermoscopic features was generated. Three hundred seventy-eight representative teaching images reached consensus with panelists. Conclusions and Relevance: Consensus achieved in this modified Delphi process identified common dermoscopic diagnoses, associated features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for dermatology residency training. This list of validated objectives provides a consensus-based foundation of key learning points in dermoscopy to help resident physicians achieve clinical proficiency in dermoscopic image interpretation.

The role of technology in melanoma screening and diagnosis.

Melanoma presents challenges for timely and accurate diagnosis. Expert panels have issued risk-based screening guidelines, with recommended screening by visual inspection. To assess how recent technology can impact the risk/benefit considerations for melanoma screening, we comprehensively reviewed non-invasive visual-based technologies. Dermoscopy increases lesional diagnostic accuracy for both dermatologists and primary care providers; total body photography and sequential digital dermoscopic imaging also increase diagnostic accuracy, are supported by automated lesion detection and tracking, and may be best suited to use by dermatologists for longitudinal follow-up. Specialized imaging modalities using non-visible light technology have unproven benefit over dermoscopy and can be limited by cost, access, and training requirements. Mobile apps facilitate image capture and lesion tracking. Teledermatology has good concordance with face-to-face consultation and increases access, with increased accuracy using dermoscopy. Deep learning models can surpass dermatologist accuracy, but their clinical utility has yet to be demonstrated. Technology-aided diagnosis may change the calculus of screening; however, well-designed prospective trials are needed to assess the efficacy of these different technologies, alone and in combination to support refinement of guidelines for melanoma screening.