A Review on Sun Exposure and Skin Diseases

Abstract

Skin is the thin layer of tissue forming the natural integumentary system of the body that acts as a barrier to protect it from exogenous and endogenous factors that induce undesirable biological responses in the body. Among these risk factors, skin damage triggered by solar ultraviolet radiation (UVR) is an escalating problem in dermatology with an increased incidence of acute and chronic cutaneous reactions. Several epidemiological studies have provided evidence for both beneficial and harmful effects of sunlight, particularly the solar UVR exposure of human beings. Due to overexposure to solar UVR on the earth's surface, outdoor professionals such as farmers, rural workers, builders and road workers are most vulnerable to developing occupational skin diseases. Indoor tanning is also associated with increased risks for various dermatological diseases. Sunburn is described as the erythematic acute cutaneous response in addition to increased melanin and apoptosis of keratinocytes to prevent skin carcinoma. Alterations in molecular, pigmentary and morphological characteristics cause carcinogenic progression in skin malignancies and premature ageing of the skin. Solar UV damage leads to immunosuppressive skin diseases such as phototoxic and photoallergic reactions. UV-induced pigmentation persists for a longer time, called long-lasting pigmentation. Sunscreen is the most mentioned skin protective behaviour and it is the most promoted part of the sun smart message along with other effective skin protection strategies such as clothing, that is, long sleeves, hats and sunglasses.

Introduction

Skin, the integumentary system of the body, plays a vital role in body functions. It acts as a barrier toward harmful exogenous agents and produces responses. Stressors such as viral or bacterial infections, heat or cold exposure, solar ultraviolet radiation (UVR) and exogenous chemicals to biological tissues can affect skin health. Among these risk factors, skin damage induced by solar UVR is an escalating problem in dermatology, along with an increased incidence of skin cancer, especially non-melanoma skin cancer (NMSC), reported worldwide. Multiple environmental exposures may derange the regulatory and repair mechanisms of the skin and lead to dermatological diseases. The UV Index (UVI), which was launched by World Health Organization (WHO) and other partner organisations, measures the amount of UVR reaching the earth's surface. The UVI ranges from 0 to 11, and the higher values imply a higher risk of UVR-induced skin damage.[1]

An insight into the WHO report provides the incidence of 300 000 NMSCs due to chronic exposure to sunlight and a history of sunburn. According to data studies, an average of 18% of consultations in general practice are related to skin diseases. The global burden of skin disease study estimated that there was a slight female predominance (61% vs 48%) in the prevalence of skin disease during adolescence when harmful exposure to UV frequently occurs. There are no geographical limitations and boundaries of skin disease.[2] Yet cutaneous infestations are more common in developing countries whereas skin malignancies are more prevalent in developed countries. This review reveals the various skin diseases induced by solar UVR and a glance at the adoption of preventive measures for solar UV-induced dermatological diseases.

Discussion

Risks of solar UV exposure

Several epidemiological studies have provided evidence for the impact of the beneficial and harmful effects of sunlight, especially solar UVR exposure on overall human health status. These are topics that arouse great interest not only among physicians and scientists but also among the general public and the media.[3] According to a recent WHO review, the human skin is continuously exposed to UVR, and the damaging effects can be divided into acute damages represented by sunburn, erythema, pain oedema and photodermatoses, and more serious chronic damages represented by photoageing and premalignant skin lesions, for example, actinic keratosis and skin cancers: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM).[4]

Solar UVR reaches the earth's surface every day; therefore, professionals in the outdoor environment have a high risk of sun exposure and are the most vulnerable to developing occupational skin cancer.[5] Fitzpatrick's skin phototypes are based on the person's skin colour and its response to sun exposure in terms of burning and tanning. Fitzpatrick's type IV–VI is known as the skin of colour and type I–III is known as the fair white skin. The colour of the skin and the texture of the hair are the most apparent phenotypes to differentiate the different races; and these correlate closely with the geography and UVR of the sun. The main populations related to the risk of developing NMSC are rural workers, general services, trade and construction. According to various research studies conducted by Hammond et al., observed professions at risk of skin cancer were builders, gardeners and road workers.[6]

Agricultural populations are mainly affected by NMSC.[7] Continuous harmful UVR exposure to all outdoor workers, especially mountain guides and farmers, is high. Yet the protective measures for farmers are at a suboptimal level.[8] Attention to sun protection for outdoor workers across Europe in preventing UVR-induced skin cancer is still needed.[9] The biological responses related to skin photoageing (skin sagging and elastosis) could be around four-fold the equivalent of solar irradiance at midday in summer mid-latitudes, and they can be important in unprotected UVA exposures to sun beds.[10] Indoor tanning, another risk factor for melanoma that is popular among young and adult women, has been implicated in the rising incidence of skin cancers in the general US population. Indoor tanning is associated with increased risks of acute and chronic dermatological diseases.[11]

Sun exposure and sunburn

Sunburn is a type of radiation burn that affects skin due to overexposure to solar UVR. It is characterised by erythema, is a well-known acute cutaneous response to UVR, caused by an inflammatory reaction in the skin and the intensity of the erythema is correlated to the degree of UVR-induced DNA damage.[12] Sunburns appear to be equally risky at any age. There is more prevalence in people with lighter skin tone who have a greater risk of sunburn. Younger children and older adults are more sensitive to sunlight. The most frequent risk factor was exercise whereas sunbathing was the least frequent risky activity during the most recent sunburn.[13] In the multivariate analyses, younger age, non-Hispanic white ethnicity, higher income and excellent self-reported health were related to higher odds of any sunburn, whereas lower odds of any sunburn were associated with poor self-reported health.[14] Also include the symptoms like pain, general fatigue and mild dizziness. The primary inducer of erythema is the UVB rays, which have a short wavelength that reaches the epidermal layer of the skin more easily than UVA rays. There is a rapid elevation in the level of melanin, the photoprotective pigment, which acts as a natural defence against UVR-induced erythema in humans, and damage on a cellular level triggered by direct DNA damage along with destructed keratinocytes. Sunburn as a stand-in for radiation that causes cancer.

The term sunburn cell refers to keratinocytes undergoing apoptosis to prevent malignant transformation. Dying keratinocytes release autoantigens that are combined with the Langerhans cells on the skin.[15] By upregulating adhesion molecules on endothelial cells, Tumour necrosis factor α (TNF-α) helps support the migration of neutrophils and macrophages to UV-exposed skin for formation of sunburn cells. Phototoxic reactions, that is, sunburn type reactions that occur in all individuals are exposed to the photosensitiser which can increase the sensitivity of the skin to light. The similarity of action spectra for thymine dimers in human epidermis and erythema suggests that UVB is known to induce DNA damage through the creation of pyrimidine dimers as the chromophore for erythema. It is characterised by eruption due to exaggerated sunburn with erythema and blistering.[16] The erythema usually resolves within a few days, but a residual post-inflammatory hyperpigmentation may last for several weeks. Chronic exposure to sunburns due to UV exposure ultimately leads to increased risk of SCCs and actinic keratosis as benign precursors, both types of lesions with UV-signature mutations in p53 gene.[17]

Sun exposure and skin cancer

Kennedy et al.,[18] showed that sunburns, as well as chronic sun exposure, cause an increased risk of developing SCCs. Nowadays, skin cancer is becoming a serious health hazard that affects the quality of life of patients. According to the Brazilian National Cancer Institute, skin cancer, which can be caused by exposure to solar radiation, is cancer with the highest incidence in Brazil, and it can occur in all skin types and at any age.[18] Chronic exposure to solar UVR implies changes in molecular, pigmentary and morphological characteristics of the skin, leading to carcinogenic progression in skin malignancies. It has been suggested that the depletion of the ozone layer and the ageing population will only make skin cancer, particularly NMSC, a growing problem in the future.[19]

Unexposed or exposed population studies exacting with sun exposure cause melanoma's population attributable fraction. Minimally exposed cohort studies were applied to recent population numbers with age-specific incidence rates.[20] UVR -induced mutations in specific genes, that is, the p53 gene and alterations in cell proliferation and apoptosis, are important in the development of skin cancer. Large-scale deletions are a recognised type of damage sustained by mitochondrial DNA (mtDNA) because of exposure to UV light in sunlight. A group of patients was identified as having abnormally high levels of either a 4977 base pair deletion (mtDNA 4977) or a 3895 base pair deletion (mtDNA 3895), in mtDNA from sun-exposed skin or skin suspected to be NMSC.[19] UVR from sun exposure and the production of reactive oxygen species is known to be a pivotal factor in the aetiology of skin cancer. The carcinogenic effect of solar UVR on the skin can be mediated in two ways: directly, when it acts directly on the cell, causing DNA mutation; and indirectly, by causing induction of T lymphocytes. Involvement of oxidative stress and antioxidants in UVR-induced multistep carcinogenesis in human skin.[21]

The incidence of both MM and NMSC is on the rise, with an annual increase in MM of 0.6% among adults over 50 years.[22] Among all new cancer cases, the approximate number of new cases of skin melanoma in 2016 was 76 380, which represents 4.5% of the total. Sunburns are associated with a doubling of the risk of melanoma; non-burning sun exposure is associated with a reduced risk of melanoma. Excessive exposure to the sun during childhood is strongly associated with the development of skin cancer in the future if exposure to harmful UVR rate in childhood is high.[23] There is a lower rate of skin cancers in patients with alopecia areata, in particular SCC.[24]

The most prevalent malignancies, BCC, SCC and melanoma, are called after the type of skin cell from which they develop and have been associated with varying degrees of sun exposure, according to Randy G.[25] SCC is more prevalent in African Americans and Asian Indians than BCC, which has >1 million cases annually and is extremely specific to Hispanics and then blacks. Melanoma is not particularly frequent, but it does occur 63 000 times a year and is lethal if not treated immediately.[26] Several studies have found gender variations in melanoma prognosis, with women having a higher survival rate than men.[27] Sunbathing and sunburns are like smoking in that even one can raise your risk of developing cancer, regardless of skin tone. Skin cancer occurs more frequently in people who have received organ transplants, particularly kidney, and patients with HIV.[28] Certain medications, ranging from over-the-counter antibiotics to heart medications, can make the skin more sensitive to sunlight, causing it to burn more quickly and perhaps increasing the risk of developing skin cancer.[29]

Sun exposure and skin ageing

Ageing is a complex and time-dependent biological process that affects all organ systems and is characterised by a decline in function and a reduced ability of the body to respond to stress due to physical, biological and chemical agents.[30] In the area of ageing research, there is an ideal organ to identify the ageing process by a strong societal impact due to its visibility is the human skin.[31] In contrast, intrinsically, aged skin causes an overall reduction in cell numbers. Among all the environmental factors, solar UV irradiation is the most dominant in premature ageing of the skin, causing 80–90% of the morphological, structural and biochemical changes collectively termed chronic cutaneous photoageing. The most notable extrinsic ageing factor was sun exposure, which had dose-response associations with wrinkles and was significantly associated with a number of skin ageing symptoms which could be distinguished as independent of ethnic origin according to the meta-analysis carried out by Qi Yi Ambrose Wong et al.[32]

It is generally accepted that UVB (280–320 nm) and UVA (320–400 nm) irradiation generate severe oxidative stress in skin cells, resulting in transient and permanent genetic damage, increased Activator protein 1 (AP-1) activity, increased matrix metalloproteinase (MMP) expression, impaired Transforming growth factor β (TGF-b) signalling, enhanced collagen degradation and decreased collagen synthesis.[33] Chronically irradiated skin is metabolically hyperactive and is characterised by epidermal hyperplasia, reduced/disorganised collagen and enhanced inflammation. Extracellular matrix (ECM) degradation is the authentication of many chronic inflammatory diseases that can lead to a loss of function, ageing and disease progression. UV irradiation from the sun is widely considered the major cause of visible human skin ageing, causing increased inflammation and enhanced ECM degradation.[34] In addition to the carcinogenic effects, UVA is known to influence collagen, thereby causing wrinkles on the overall skin. Granzyme B, a serine proteinase with a substrate specificity similar to the caspase family of apoptotic cysteine proteinase, is capable of cleaving and activating several death proteins in target cells and mediating contributions to ECM degradation in the skin after UV irradiation through both direct cleavage of ECM proteins and indirect induction of other proteinases.[35]

Using a mouse model of chronic, low-grade UV irradiation over 20 weeks, demonstrated that granzyme B deficiency protects against wrinkle formation and a loss in collagen density, while granzyme B-mediated fibronectin and decorin cleavage contributed to increased MMP expression and collagen degradation. This review also demonstrates an important role for granzyme B in ageing skin, which may have implications in many other age-related chronic inflammatory diseases where ECM degradation is a hallmark. Due to environmental and endogenous lesions, the accumulation of somatic changes in human skin in the genome is associated with an increased risk of skin ageing.[36] UV-induced and endogenous DNA damage can have a commensurate impact on the somatic mutation that takes place in skin fibroblasts. Unlike UVB rays which are only capable of penetrating the epidermis, UVA rays can reach the dermal layer. Also, fibroblasts in sunlight-exposed skin are subject to UVA-induced damage producing wrinkles, solar elastosis and likely several forms of mutagenic DNA damage.[37]

Sun exposure and immunosuppressive skin diseases

UV light is intricately linked to the functional status of the cutaneous immune system. In susceptible individuals, UVR can explode pathogenic inflammatory pathways leading to hypersensitivity or autoimmunity. Solar UVR can directly activate keratinocytes and other cells to release inflammatory mediators such as cytokines and chemokines, causing redistribution and release of sequestered autoantigens from UV-damaged cells, alter self-proteins to make them more immunogenic, enhance the immunogenicity of externally-applied molecules and chemically alter systemically-administered medications whose distribution includes the skin.[38]

Granzyme B is a serine protease that has been traditionally studied in immune cell-mediated apoptosis once believed to be released exclusively and non-specifically to the extracellular space by lymphocytes and natural killer cells in the absence of target cell engagement and can be induced in many other types of immune cells (e.g. mast cells, basophils, dendritic cells, B lymphocytes) and non-immune cells (e.g. keratinocytes, chondrocytes) from cytotoxic lymphocytes and natural killer cells, along with the pore-forming protein perforin, to induce apoptotic cell death.[39] Of particular relevance to the skin and UV irradiation, both UVA and UVB irradiation induces granzyme B expression in keratinocytes, both in vitro and in human skin. The concomitant increase in mast cells in both genotypes along with similar increases in skin thickness indicates that granzyme B deficiency did not affect the immune cell recruitment and tissue response after UV exposure.[40]

Langerhans cells are very sensitive to UVR. These cells are antigen-presenting dendritic cells that have a cell surface phenotype poised to stimulate T cells, including autoreactive and allergen-specific T cells. Langerhans cell density correlates with the ability of the hapten 2,4-dinitrofluorobenzene to induce contact hypersensitivity. These cells are more sensitive to UVR than keratinocytes.[41]

Additionally, Nagano et al.[42] revealed comparable results in a study on a non-Caucasian population: those with skin cancer who have been exposed to the sun are more susceptible to immunosuppression and had a lower frequency of the low expression Interleukin (IL-10) promoter genotype. The research by Welsh and collaborators supports the notion that UV exposure has an effect on the development of skin cancer and UV-induced immunosuppression since skin type and burns were substantially related with the growth of tumours.[43] The concept of genetic susceptibility is also taken into consideration, as Yoshikawa in humans and Noonan and Hoffman in mice have long demonstrated. Increasing vitamin D levels alone may not have the desired effects, according to a clinical research on the use of vitamin D in autoimmune illnesses.[44]

Sun exposure and phototoxic and photoallergic reactions to skin

The photosensitiser is a medicinal substance, most commonly a psoralen which is ingested or externally applied to the skin, to absorb photons of a particular wavelength, enter a transient activation state and then elicit a chemical reaction by transferring the photon's energy to another molecule. By capturing photons and releasing their energy, photosensitisers increase the sensitivity of the skin to light.[45] These photosensitisers induce two types of reactions: phototoxic and photoallergic. Phototoxic drug reactions can be due to topical or internal exposure to photosensitising medications. In contrast to phototoxic reactions, photoallergic reactions are true immunological reactions. The photosensitiser may act like a hapten. When irradiated, the energy absorbed is used to chemically bond the photosensitiser/hapten to a self-protein, resulting in a novel immunogenic compound.[46] Various phototoxic and photoallergic reactions on the skin are detailed below.

Phytophotodermatitis

It is a chemical reaction which makes skin hypersensitive to UV light caused by contact with the photosensitising compounds most commonly a psoralen such as furanocoumarins found naturally in some plants, characterized by various symptoms including burning, itching and large blisters that slowly accumulate over time.[47] The search results primarily included case reports from 1980 to 2015. The bulk among the included case reports have been published in paediatric or dermatological publications; whereas very few have been written from the standpoint of family doctors.[48]

Photoallergic contact dermatitis

In photoallergic delayed-type hypersensitivity (DTH) reactions to the new photo allergen can be external and there is a delay in onset, sometimes in the range of weeks. This makes it difficult for patients to associate UV exposure with the eruption, which makes the photo-distribution of the rash key to its diagnosis.[49]

Pharmaceuticals come in a wide variety of forms, including anti-anxiety drugs, antibiotics, antidepressants, antifungal drugs, antihyperglycemic drugs, and antimalarial drugs, antipsychotic drugs, chemotherapeutic treatments, diuretics and prescriptions for acne, heart medications, analgesics for pain, irritants, coal tar, topical antibiotics like hexachlorophene and chlorhexidine, and more. Coal tar, topical antibiotics like hexachlorophene and chlorhexidine. Photoallergic reactions may also occur in response to sunscreen and fragrances that could irritate skin areas that have not been exposed to the sun. They frequently show up 24–72 hours after sun exposure.[50]

Idiopathic or primary photosensitivity disorders

There are also a variety of immune-mediated DTH-like reactions that occur hours or days after sun exposure in which the photo allergen is unknown but believed to be an endogenous self-molecule. These photodermatoses are called idiopathic or primary photosensitivity disorders. Vera Vera Izaguirre DS et al.[51] research revealed that patients with farm animal exposure had a much higher risk of having primary photosensitivity disorders than did the controls. These findings led to the suggestion that neglecting personal cleanliness and being exposed to animal pathogens and parasites are risk factors for contracting this illness.

Polymorphous light eruption

Among this group, it is the most common and characterised by an erythematous, mildly pruritic, papulovesicular eruption that appears on sun-exposed skin, especially the chest and upper extremities. Following sun exposure there is a delay in the onset of these eruptions, from hours to days. Thus, some patients do not attribute their rash to sun exposure. Once present, the eruption will last for days. Polymorphous light eruption (PMLE) is most common in the spring and summer and may recur annually. A variant of PMLE, called juvenile spring eruption, presents with vesicles on the helices of ears of young boys.[52] In the general population, the prevalence of PMLE is 10–20%, with women between the ages of 20 and 30 and school-age children being more frequently affected. Due to a higher ratio of UVA to UVB in temperate areas, PMLE usually arises there.[53]

Actinic prurigo

It is a persistent human leukocyte antigen (HLA)-restricted variant of PMLE. Its incidence is highest in the Native American population, especially young Native American girls. Clinically, it differs from PMLE with characters like papules and nodules that are sometimes lichenified or excoriated due to pruritus, a distribution that may include non-sun-exposed area and the presence of cheilitis or conjunctivitis that may accompany the skin lesions or be the only presentation of the disease. Although rare in Caucasians with only a few instances from Australia, Britain and France, the disease is well-known among Native Americans and in Central and South America.[54]

Chronic actinic dermatitis

It is another type of idiopathic or primary photosensitivity disorder characterized by severely itchy, red, inflamed and thickened dry skin, mainly in areas that have been exposed to sunlight. This persistent eczematous dermatitis of chronically sun-exposed skin commonly affects middle-age to elderly men.[55] In a retrospective analysis of 70 patients with persistent actinic dermatitis, it was discovered that, despite having equally severe phototest reactions, individuals with darker skin types tend to present at younger ages and are more likely to be women. Patients with chronic actinic dermatitis frequently experience reactions to photopatch testing.[56]

Sun exposure and skin pigmentation changes

In some individuals UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is uncertain whether LLP is an indicator of feasible risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, for example, solar lentigines or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. The potential long-term changes in the epidermis pigmentation was characterized in skin biopsy specimens from sunburn-inducing clinical studies.[57] Visually, the long-term LLP-positive individuals showed increased pigmentation and a hyperpigmented basal layer compared to their unexposed control and LLP-negative counterparts. It is known that very subtle changes in melanin content can produce dramatic differences in visible skin colour. The increased visual pigmentation along with the histopathological features of a hyperpigmented basal layer and the increased interdigitation highlight the similarities of this long-term phenomenon with other forms of UV-induced hyperpigmentation.

These modest changes at the basement membrane lead to sustained pigmentation increases potentially through feedback from the basement membrane components relaying signals to the nucleus to affect gene expression.[58] Sun-exposure dependent regulation of gene expression identified several examples of genetic and environmental interactions where genetic variants affect the gene expression response to sun exposure Local adaptation involving RASSF9, a gene involved in epidermal homoeostasis and differentiation, supports the idea that skin pigmentation is not the only trait shaped by adaptation to sun exposure. Preceding studies have found several skin pigmentation genes with exhibitory strong evolutionary pressures throughout human history, manifesting as large differences in the frequency of genomic variants across populations. But even within populations, individuals respond differently to sun exposure, suggesting variation in addition to the major differences in skin pigmentation across populations.[59]

Regardless of race or ethnicity, tanning contributed significantly to serum 25-hydroxy vitamin D (25(OH) D) concentration over the summer, but it was not enough to keep it at the level it reached with supplementation. Skin tone may contribute significantly to the difference in serum 25(OH)D levels between racial/ethnic groups.[60]

Conclusion

By contemplating on the aforementioned studies and data we can conclude that the lack of knowledge about solar UV-induced dermatological diseases and the necessity to stay away from chronic solar exposure may cause more undesirable skin problems. So numerous health promotion programmes should be encouraged, as well as easier access to the adoption of preventive measures based on studies conducted be provided. Very high UVI requires that prevention when considering solar protection be part of the daily care of the public. Avoiding exposure between 10 a.m. and 3 p.m., or when UV levels are at their peak, is not viable for the general public and is therefore probably ineffective. In addition to other effective skin protection techniques like wearing long sleeves, hats and sunglasses, sunscreen is the skin protective habit that is most frequently mentioned and is the most actively promoted as part of the Sunrise campaign. When counselling patients with a history of NMSC, physicians should encourage sunburn prevention, especially in younger adults, emphasising shade and sun avoidance over sunscreen.

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Conflicts of interest

There are no conflicts of interest.