Solar Ultraviolet Radiation, Skin Cancer and Photoprotective Strategies in South Africa†.

The most recent data relating to the incidence of, and mortality from, the three commonest forms of skin cancer, namely basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous melanoma (CM), in the Black African, Colored, Asian/Indian and White population groups in South Africa are reviewed. While exposure to solar ultraviolet radiation is the major environmental risk factor for BCC in all four groups, for SSC in the White and Asian/Indian groups and for CM in the White group, this is unlikely to be the case for most SCCs in the Black African group and for most CMs in the Black African and Asian/Indian groups. Strategies for practical personal photoprotection in South Africa are discussed with particular emphasis on people at heightened risk of skin cancer including the White population group, those with HIV or oculocutaneous albinism and outdoor workers.

More Than Effects in Skin: Ultraviolet Radiation-Induced Changes in Immune Cells in Human Blood.

Cells of the skin and circulation are in constant two-way communication. Following exposure of humans to sunlight or to phototherapy, there are alterations in the number, phenotype and function of circulating blood cells. In this review, only data obtained from human studies are considered, with changes induced by UV radiation (UVR) exposure described for phagocytic leukocytes and peripheral blood mononuclear cells plus their component T and B cells, natural killer cells and dendritic cells. These immune modulations illustrate the potential of UVR to have therapeutic effects beyond the skin, and that sunlight exposure is an important environmental influence on human health.

Health Risks Associated With Excessive Exposure to Solar Ultraviolet Radiation Among Outdoor Workers in South Africa: An Overview.

Exposure of outdoor workers to high levels of solar ultraviolet radiation (UVR) poses significant, well-known health risks including skin cancer and eye diseases. In South Africa, little is known about how many workers are potentially overexposed to solar UVR and what the associated impacts on their health might be. In this overview, the geography and solar UVR environment in South Africa are considered, as well as the different outdoor occupational groups likely to be affected by excessive solar UVR exposure. Sunburn, pterygium, cataract, keratinocyte cancers, and melanoma are discussed in the context of outdoor workers. Few studies in South Africa have considered these health issues and the most effective ways to reduce solar UVR exposure for those working outside. Several countries have developed policies and guidelines to support sun safety in the workplace which include training and education, in addition to the provision of personal protective equipment and managerial support. Several gaps in occupational sun protection and workplace sun safety for South Africa are identified. Legislation needs to recognize solar UVR exposure as an occupational health hazard, with sun safety guidelines and training provided for employers and employees.

Major climate change-induced risks to human health in South Africa.

There are many climatic changes facing South Africa which already have, or are projected to have, a detrimental impact on human health. Here the risks to health due to several alterations in the climate of South Africa are considered in turn. These include an increase in ambient temperature, causing, for example, a significant rise in morbidity and mortality; heavy rainfall leading to changes in the prevalence and occurrence of vector-borne diseases; drought-associated malnutrition; and exposure to dust storms and air pollution leading to the potential exacerbation of respiratory diseases. Existing initiatives and strategies to prevent or reduce these adverse health impacts are outlined, together with suggestions of what might be required in the future to safeguard the health of the nation. Potential roles for the health and non-health sectors as well as preparedness and capacity development with respect to climate change and health adaptation are considered.

The Multiple Roles of Urocanic Acid in Health and Disease.

Trans-urocanic acid (trans-UCA) is synthesized in the skin, liver, and brain. It is a major natural moisturizing factor in skin and maintains its acid pH. In skin, it isomerizes to cis-UCA following exposure to UVR. Both isomers fulfill multiple roles in health and disease. Cis-UCA has immunomodulatory properties linked with several cutaneous diseases such as skin cancer, atopic dermatitis, and urticaria and associates with systemic diseases including multiple sclerosis. The levels of UCA in the skin, brain, urine, and feces reflect some physiological processes and may be disease biomarkers. Both isomers of UCA have therapeutic potential for a range of disorders.

The Epidemiology of Skin Cancer and Public Health Strategies for Its Prevention in Southern Africa.

Skin cancer is a non-communicable disease that has been underexplored in Africa, including Southern Africa. Exposure to solar ultraviolet radiation (UVR) is an important, potentially modifiable risk factor for skin cancer. The countries which comprise Southern Africa are Botswana, Lesotho, Namibia, South Africa, and Swaziland. They differ in population size and composition and experience different levels of solar UVR. Here, the epidemiology and prevalence of skin cancer in Southern African countries are outlined. Information is provided on skin cancer prevention campaigns in these countries, and evidence sought to support recommendations for skin cancer prevention, especially for people with fair skin, or oculocutaneous albinism or HIV-AIDS who are at the greatest risk. Consideration is given to the possible impacts of climate change on skin cancer in Southern Africa and the need for adaptation and human behavioural change is emphasized.

Are there differences in immune responses following delivery of vaccines through acutely or chronically sun-exposed compared with sun-unexposed skin?

The majority of human vaccines are administered above the deltoid muscle of the arm, a site that is chronically sun-exposed in many people. It is known that exposure of the skin to the UV wavelengths in sunlight stimulates systemic immunosuppression, an outcome that is associated with reduced immunity to microbial infections in animal models. Here we consider whether immunization of humans through a UV-irradiated skin site will lead to a less effective immune response compared with immunization through an unexposed site. Studies showing that the efficacy of vaccination can be reduced when surrogates of increased levels of sun exposure, such as latitude of residence and season of the year, are considered. Results from a limited number of intervention experiments in humans demonstrate a similar pattern. To provide an explanation for these findings, changes in the number and functional potential of immune cells in chronically sun-exposed compared with unexposed skin are outlined. UV radiation-induced changes to skin cells are also relevant when considering skin sites for administration of immune-tolerizing peptides. The review provides the basis for further research into the effects of acute and chronic UV radiation exposure on skin cells in the context of vaccination.

Trends in Melanoma Mortality in the Population Groups of South Africa.

The incidence of cutaneous melanoma (CM) is increasing in countries around the world. However, little is known about melanoma trends in African countries by population group. We studied CM mortality in South Africa from 1997 to 2014 to partly address this knowledge gap. Unit record mortality data for all South Africans who died from CM (n = 8,537) were obtained from Statistics South Africa. Join-point regression models were used to assess whether there was a statistically significant change in the direction and/or magnitude of the annual trends in CM mortality. A significant increasing trend of 11% per year was observed in age-adjusted mortality rates in men between 2000 and 2005 (p < 0.01), rising from 2 to 3 per 100,000. There was also a statistically significant increase of 180% per year among White South Africans from 1997 to 1999 (p < 0.05) and of 3% from 1999 to 2014 (p < 0.01). These results may be used to inform CM awareness campaigns and will motivate efforts to improve the collection and analysis of relevant statistics regarding the present burden of CM in South Africa.

Exposure to Ultraviolet Radiation in the Modulation of Human Diseases.

This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that modulate psoriasis, atopic dermatitis, and vitiligo; suppresses cutaneous lesions of graft-versus-host disease; and regulates some infection and vaccination outcomes. While polymorphic light eruption and the cutaneous photosensitivity of systemic lupus erythematosus are triggered by UVR, polymorphic light eruption also frequently benefits from UVR-induced immunomodulation. For systemic diseases such as multiple sclerosis, type 1 diabetes, asthma, schizophrenia, autism, and cardiovascular disease, any positive consequences of UVR exposure are more speculative, but could occur through the actions of UVR-induced regulatory cells and mediators, including 1,25-dihydroxy vitamin D3, interleukin-10, and nitric oxide. Reduced UVR exposure is a risk factor for the development of several inflammatory, allergic, and autoimmune conditions, including diseases initiated in early life. This suggests that UVR-induced molecules can regulate cell maturation in developing organs.

The incidence and body site of skin cancers in the population groups of Astana, Kazakhstan.

BACKGROUND AND AIMS: Data on cutaneous malignant melanoma (CMM), squamous cell carcinoma of the skin (SCC), and basal cell carcinoma (BCC) in populations consisting of multi-racial groups in the Commonwealth of Independent States are limited. Here, the main aim was to analyse the incidence and body site of these cancers in the population groups of Astana, Kazakhstan (2007-2016). METHODS: Annual age standardised incidences and body sites of BCC, SCC, and CMM in Astana's population, divided into "Kazakhs and other Turkic/Asian" and "Russian and other European/Caucasian" groups, were calculated from histologically confirmed cases reported to Astana Oncology Centre. RESULTS: During the period January 2007 to October 2016, 647 skin cancers were diagnosed. The age and sex standardised incidence of BCC, SCC, and CMM increased significantly between 2007 to 2011 and 2012 to 2016. Higher incidences occurred in the Russian and other European/Caucasian group compared with the Kazakh and other Turkic/Asian group for the 3 skin cancers. BCC was the most common type of skin tumour, followed by SCC, and then CMM, in both population groups and sexes. The head/neck was the commonest site for BCC and SCC in all groups. For CMM, the most frequent site was the trunk in the Russian group and the head/neck in the Kazakh group. CONCLUSION: The incidence of skin tumours in Astana rose over the past 10 years. Differences in skin phototypes and sun exposure/ protection behaviours may account for the more frequent occurrence of skin tumours in the Russian population group compared with the Kazakh population group.

Ultraviolet radiation-induced immunosuppression and its relevance for skin carcinogenesis.

The realisation that UV radiation (UVR) exposure could induce a suppressed immune environment for the initiation of carcinogenesis in the skin was first described more than 40 years ago. Van der Leun and his colleagues contributed to this area in the 1980s and 90s by experiments in mice involving UV wavelength and dose-dependency in the formation of such tumours, in addition to illustrating both the local and systemic effect of the UVR on the immune system. Since these early days, many aspects of the complex pathways of UV-induced immunosuppression have been studied and are outlined in this review. Although most experimental work has involved mice, it is clear that UVR also causes reduced immune responses in humans. Evidence showing the importance of the immune system in determining the risk of human skin cancers is explained, and details of how UVR exposure can down-regulate immunity in the formation and progression of such tumours reviewed. With increasing knowledge of these links and the mechanisms of UVR-induced immunosuppression, novel approaches to enhance immunity to skin tumour antigens in humans are becoming apparent which, hopefully, will reduce the burden of UVR-induced skin cancers in the future.

Ultraviolet Radiation and Kaposi Sarcoma Incidence in a Nationwide US Cohort of HIV-Infected Men.

Background: Although ultraviolet radiation (UVR) is established as both an inducer of herpes simplex virus reactivation and as the primary risk factor for many common skin cancers, its relationship with human herpes virus 8 (HHV8) infection or risk of Kaposi sarcoma (KS) is unknown. Methods: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between ambient UVR, history of nonmelanoma skin cancer (NMSC; as a biomarker of personal cumulative UVR dose), and incidence of first primary KS in a nationwide US cohort of white and African American male veterans infected with HIV between 1986 and 1996 (prior to the widespread availability of treatment) using Cox regression. All statistical tests were two-sided. Results: Based on discharge records, there were 422 newly diagnosed KS cases among 17 597 HIV-infected veterans. Cohort members with prior NMSC had a statistically significantly increased risk of KS (HR = 8.64, 95% CI = 6.23 to 11.96) in the total population. Risk of KS was higher for quartile 4 vs 1 among the total population (HR = 1.49, 95% CI = 1.02 to 2.16, Ptrend UVR quartile [coded 1 to 4] = .02) and among whites (HR = 1.75, 95% CI = 1.11 to 2.78, Ptrend = .009), but not among African Americans (HR = 1.23, 95% CI = 0.71 to 2.15, Ptrend = .23). Conclusions: KS risk was elevated among HIV-infected men with NMSC diagnosis and in those living in locations with high ambient UVR at time of HIV diagnosis. Our novel findings suggesting that UVR exposure may increase KS risk warrant further investigation.

Vitamin D Status and Its Consequences for Health in South Africa.

In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor. Limited data exist regarding the impact of recent changes in lifestyles on vitamin D status, such as urbanisation. With regard to disease susceptibility, 11 of 22 relevant publications indicated association between low 25(OH)D levels and disease, with deficiency most notably found in individuals with tuberculosis and HIV-1. Information on the relationship between vitamin D receptor variants and ethnicity, disease or treatment response in the South African population groups demonstrated complex interactions between genetics, epigenetics and the environment. Whether vitamin D plays an important role in protection against the range of diseases that currently constitute a large burden on the health services in South Africa requires further investigation. Only then can accurate advice be given about personal sun exposure or dietary vitamin D supplementation.

Solar ultraviolet radiation in Africa: a systematic review and critical evaluation of the health risks and use of photoprotection.

Most information on the harmful health effects of solar ultraviolet radiation (UVR) has been obtained in populations in which the majority has fair skin. Here a systematic review of evidence on diseases related to solar UVR in Africa was undertaken, and the appropriateness of effective photoprotection for these people considered. There are few population-based studies on UV-induced skin cancers (melanoma, squamous and basal cell carcinomas) in Africa, although limited reports indicated that they occur, even in people with deeply pigmented skin. The incidence of melanoma is particularly high in the white population living in the Western Cape of South Africa and has increased significantly in recent years. Cataract is extremely common in people of all skin colours and is a frequent cause of blindness, particularly in the elderly. For both skin cancer and cataract, the proportion of the disease risk that is attributable to exposure to solar UVR in African populations, and therefore the health burden caused by UV irradiation is unclear. There was little published information on the use of sun protection in Africa. The potential disease burden attributable to solar UVR exposure of Africans is high, although accurate data to quantify this are sparse. Information is required on the incidence, prevalence and mortality for the range of UV-related diseases in different populations living throughout Africa. Photoprotection is clearly required, at least for those subpopulations at particularly high risk, but may be limited by cost and cultural acceptability.

A systematic review of the influence of skin pigmentation on changes in the concentrations of vitamin D and 25-hydroxyvitamin D in plasma/serum following experimental UV irradiation.

Defining whether skin pigmentation influences vitamin D photosynthesis is important for delivering accurate public health messages. Current evidence is contradictory. We undertook a systematic review of the published literature to examine the association between skin pigmentation and change in blood concentrations of vitamin D and 25-hydroxyvitamin D following experimental UV irradiation. Twelve studies fulfilled the inclusion criteria: human study in vivo with non-diseased participants; controlled artificial UV radiation; vitamin D or 25-hydroxyvitamin D measured in serum or plasma; full text in English. In seven studies, vitamin D photosynthesis was reduced in dark-skinned compared with fairer-skinned individuals. In the remaining five studies, only one of which was published after 1990, there was no difference in vitamin D photosynthesis according to skin type. The disparities in these results may be due to small sample sizes and variations in study methodology, including the source, dose and frequency of UV irradiation, phototype classification, and analysis of vitamin D and 25-hydroxyvitamin D. Of these, the spectrum emitted by the UV lamps may be significant. No study considered potential modifying factors, such as relevant genetic polymorphisms. On balance, we conclude that pigmented skin has less effective photoproduction of vitamin D and 25-hydroxyvitamin D. The quantity of sun exposure needed for dark-skinned, compared with light-skinned, people to achieve vitamin D sufficiency remains uncertain.

Oculocutaneous albinism in sub-Saharan Africa: adverse sun-associated health effects and photoprotection.

Oculocutaneous albinism (OCA) is a genetically inherited autosomal recessive condition. Individuals with OCA lack melanin and therefore are susceptible to the harmful effects of solar ultraviolet radiation, including extreme sun sensitivity, photophobia and skin cancer. OCA is a grave public health issue in sub-Saharan Africa with a prevalence as high as 1 in 1000 in some tribes. This article considers the characteristics and prevalence of OCA in sub-Saharan African countries. Sun-induced adverse health effects in the skin and eyes of OCA individuals are reviewed. Sun exposure behavior and the use of photoprotection for the skin and eyes are discussed to highlight the major challenges experienced by these at-risk individuals and how these might be best resolved.