Back when the very first sunscreen was introduced in 1928, it was believed that the short-term harmful effects of ultraviolet (UV) radiation exposure, specifically sunburn, were all we had to fear from the sun.1,2 In the succeeding decades, however, it has become clear that sunburn is only the beginning of the pathologic effects produced by solar exposure.1
Recent years have brought a much fuller understanding of the effects of photoexposure, their causes, and ways to protect against them. And, after more than 20 years without the introduction of a single significant new active sunscreen agent, new photoprotective agents and more substantive formulations have recently become available in the United States.3
This article will review recent developments in photoprotection. The content is based on the Clinical Council on Photo-protection, a roundtable meeting of experts in photoprotection held on Jan. 20, 2007, in New York, NY, and sponsored by La Roche-Posay Laboratoire Pharmaceutique.
UVA: A CURRENT FOCUS IN PHOTODAMAGE
Ultraviolet A (UVA) rays have long been thought to have minimal harmful effects, while only UVB rays were believed to have significant deleterious effects.4 Erythema (sunburn) and the delayed effect of suntanning are the most familiar symptoms associated with UVB overexposure, and its association with photocarcinogenesis is well established. Ultraviolet C poses virtually no threat because it is absorbed by the ozone layer of the earth’s atmosphere.
However, research is increasingly demonstrating that UVA is a threat, and a far greater one than has generally been believed.4
UVA radiation is much more abundant than UVB in natural sunlight; it accounts for up to 95% of all UV radiation that reaches Earth.4 Furthermore, whereas the amount of UVB in sunlight varies according to the season, location on the earth, and time of day, the intensity of UVA radiation is more uniform and is present all year round during all daylight hours.4
In addition, while UVB is blocked by window and automobile glass, UVA is not.5 Furthermore, UVA, which has a longer wavelength than UVB, penetrates more deeply into the skin. (See Figure 1.)6 With UVB radiation, it penetrates only into the stratum corneum and is almost fully absorbed before reaching the upper dermis. On the other hand, UVA readily penetrates into the mid-dermis.7
The many negative effects of UV radiation on the skin, including erythema, photoaging, carcinogenicity, and immunosuppression, are exhibited in both UVB and UVA by damage to DNA. Until recently, the genotoxic damage caused by UVA radiation has been thought to be less than that caused by UVB.7 But new research has called this thinking into question.
In a recent study using a highly accurate quantitative assay based on high-performance liquid chromatography combined with mass spectrometry, investigators examined the type and yield of DNA damage in human skin samples exposed to UVA and UVB radiation.8 Cyclobutane pyrimidine dimers, commonly associated with UVB-induced DNA damage, were found in substantial numbers in UVA-exposed skin as well. In addition, UVA-generated dimers were removed at a much lower rate than were UVB-induced dimers.
The researchers also demonstrated that while human skin protects itself very effectively against UVB-induced DNA damage, it protects itself only weakly against UVA-induced injury.8
The Role of UVA in Photoaging
Repeated skin exposure to UV radiation produces a phototrauma referred to as “dermatoheliosis, or photoaging. Although photoaging and intrinsic aging can occur simultaneously, the two processes differ significantly, and photoaged skin appears different from intrinsically aged skin, both macro- and microscopically.
Macroscopically, photoaged skin is characterized by fine and coarse wrinkling; dyspigmentation or hyperpigmentation spots, including freckles or lentigines; laxity; sallowness; telangiectasias; and actinic keratoses.7,2
Microscopically, in normally aging skin, the dermis becomes hypocellular; the epidermis atrophies; collagen forms a stable, cross-linked matrix; and the vasculature remains intact. In photoaged skin, by contrast, the epidermis thickens, the dermis becomes hypercellular (as a result of mast cell and fibroblast propagation), and the vasculature becomes dilated and twisted.2
All portions of the solar spectrum, including UVA, UVB, and infrared radiation, contribute to photoaging.2
However, UVA is now recognized as the single most important wavelength in causing photoaging.4,2 The ability of UVA to deeply penetrate the dermis may account for the primacy of its role in photoaging, as may the fact that UVA exposure does not produce an erythemal “warning signal,” so that higher cumulative doses of UVA radiation may be unknowingly obtained. The ability of UVA to penetrate glass is also a factor. Figure 2, illustrates the result of long-term indoor exposure to UVA radiation.9
The Role of UVA in Immunosuppression
Photoimmunosuppression, a well-documented phenomenon, may play an important role in the genesis of skin cancer; it increases the likelihood and severity of infectious diseases, and reduces the effectiveness of vaccines.7 Immunosuppression induced by UV appears to start with DNA damage and trans to cis-urocanic acid isomerization in the stratum corneum, which is associated with the production of cytokines, histamine, and neuropeptides.7
Recent research has shown that UVA plays a key role in immunosuppression. Ultraviolet A has been shown to suppress induction and elicitation of the contact and delayed-type hypersensitivity responses to recall antigens.7 So important is the impact of UVA on immunosuppression that a new sunscreen measure — immune protection factor — has been proposed for use along with the current sun protection factor (SPF) measure because the latter is not an indicator of degree of protection from UVA.10
The Role of UVA in Carcinogenesis
Strong evidence supports the role of UV exposure in the development of skin cancers, including not only non-melanoma skin cancers such as squamous cell and basal cell carcinomas,7 but also malignant melanoma.11
In the case of melanoma, several lines of epidemiologic evidence, in addition to other sources of evidence, point particularly to high, intermittent exposure to solar UV radiation as a significant risk factor. These data include findings that the incidence of the disease generally increases with decreasing latitude and the heightened intensity of the sun’s rays.
The highest recorded rate of melanoma in the world occurs in Australia, where the annual incidence is up to 20 times the incidence in Europe.11
It was long thought that UVB was primarily responsible for melanoma.12 However, increasing evidence indicates that UVA may also play a significant role.4 Based on an analysis of World Health Organization data from 45 countries, Garland and colleagues found that UVA was associated with melanoma mortality rates after controlling for UVB and average skin pigmentation.12
Limited but consistent data from studies of tanning salon users also show UVA exposure in these beds to be a risk factor for melanoma. A recent meta-analysis of case-control studies and one cohort study conducted between 1984 and 2004 demonstrated a significantly increased risk of cutaneous melanoma following the use of sunbeds and sunlamps.13 These results are supported by a prospective cohort study of 106,379 Swedish and Norwegian women demonstrating that the use of tanning devices once a month or more is statistically significantly associated with melanoma risk.14
In consideration of findings such as these, the American Academy of Dermatology has supported regulations prohibiting minors from using tanning devices, preventing facilities from advertising such devices as safe, and urging the placement of a Surgeon General’s warning on all such devices.15
Contemporary Considerations In Sunscreen Use: Broadening Our Patients’ Protection
In view of the magnitude of the sun’s negative impact on the skin, we might be tempted to advise our patients to entirely avoid UV exposure, both outdoor and indoor. However, given the impracticality of such advice, sunscreens are vital in providing protection from the photodamaging effects of UV rays.16
Since their inception, sunscreens have been known to protect against erythema, the acute effect of UV exposure. But they are now understood to protect against many of the long-term effects of UV exposure as well, including photoaging, actinic keratoses, and some skin cancers.17
Because UVA rays, especially the long-wavelength UVA-1, can pass through clouds and automobile and window glass, incidental exposure to UVA radiation is a daily risk. In view of research findings implicating UVA in the most severe consequences of sun exposure, many groups currently recommend universal, year-round, daily use of a broad-spectrum sunscreen — one that protects against both UVB and UVA — with an SPF of at least 15.18-20
We need to continue to educate patients about the need for daily sunscreen use, about proper sunscreen application, and about the other steps they need to take to protect themselves from UV exposure. (See the patient education handout titled, “Are You Really Protecting Yourself from the Sun’s Dangerous Rays?” and feel free to photocopy it to distribute to your patients.)
A Look at Common Sunscreen Ingredients
To provide broad-spectrum photoprotection, a sunscreen must include a combination of organic and inorganic filters. Advances in sunscreen technology have mimicked and built upon the body’s natural cutaneous defenses against UV radiation, which include the following:
Among the body’s endogenous defenses is the ability of the epidermis to scatter the majority of visible light rays, which is what inorganic UV filters in sunscreens do.17
A second endogenous defense mechanism is that urocanic acid in the skin undergoes UV-initiated isomerization, which is what organic filters cause to happen.17
A third endogenous defense shield is melanin, which protects the skin by filtering and scattering UV rays and changing the absorbed energy into heat energy rather than chemical energy — the same mechanism by which organic filters protect the skin.17 It is this mechanism that causes a sensation of warmth in sunscreen wearers, something about which many patients complain.21
In addition to having light filtering and scattering capabilities, as well as the others mentioned above, photostability is another important characteristic of an effective sunscreen. UV filters that are photolabile will be rapidly inactivated after exposure to UV rays, thus losing their effectiveness. Several factors contribute to photostability, including the filter, the presence of other filters in the product, and the vehicle or solvent. Most UV filters, including avobenzone, octinoxate, and octyl dimethyl para-amino benzoic acid (PABA), are photolabile. Thus, other filters, including zinc oxide, titanium dioxide, octocrylene, methylbenzylidene camphor, and the salicylates, are frequently used in sunscreen preparations to increase their photostability.17
Constructing the Ideal Broad-Spectrum Filter
The ideal broad-spectrum filter must be composed of compatible and complementary filters that can provide effective protection over the entire UVA and UVB spectrum. The aesthetics of the product also need to be optimized to increase the likelihood of adherence.17 The ideal sunscreen should also be photostable in order to ensure functional longevity on the skin. Finally, its vehicle should be resistant to shedding with rubbing, sweating, or water immersion.17
All UV filters have a particular absorption spectrum, which can be extended by combining complementary agents. The ideal sunscreen would combine UVA organic absorbers, UVB organic absorbers, and an inorganic filter. UVA organic absorbers include benzophenones (320 nm to 350 nm),2 avobenzone (357 nm), and, most recently, ecamsule (Mexoryl SX) (344 nm).22 UVB organic absorbers include salicylates (~300 nm) and cinnamates (310 nm to 311 nm).2 Inorganic filters, which act to reflect or scatter UVA and UVB, include titanium dioxide and zinc oxide.2
Both titanium dioxide and zinc oxide are inorganic white particulates, so they must be reformulated for aesthetic purposes for use in sunscreens, but there is an unfortunate trade-off involved: Smaller particles yield less white residue on the skin but poorer photoprotection, while larger particles offer more protection but more white residue, and hence the possibility of poor adherence.16,2
New Products Offering Broad-Spectrum Protection
After two decades without a significant breakthrough in sunscreen ingredients in the United States,3 two new options that promise to improve broad-spectrum, photostable UV protection have recently been introduced.
One is a new technology trade-named Helioplex. Several products are available using the Helioplex technology, which combines photostable UVB filters, and UVA filters avobenzone and oxybenzone in a formulation that slows the degradation of avobenzone to increase its photostability.23,3
Another new introduction features Mexoryl SX. Mexoryl SX was developed for use in combination with avobenzone and octocrylene for broad-spectrum protection. (See Figure 3.)
In this formulation, octocrylene acts to stabilize avobenzone. Available in Europe and Canada since 1993, Mexoryl SX is the first new photostable short-UVA filter in a sunscreen formula to be approved by the U.S. Food and Drug Administration and is now available in the United States in the new sunscreen product Anthelios SX.
Anthelios SX is an SPF15 lightweight moisturizing cream that is intended for daily use. The product protects against both UVB and UVA. Fragrance-free and allergy tested, it is suitable for sensitive skin and is oil-free and noncomedogenic.
Translating New Knowledge of UVA into Protection for Patients
A large and growing body of research has identified UVA as a key contributor to photoaging, immunosuppression, and carcinogenesis. Because UVA is present all year round and UVA-1 can pass through window glass, patients need to be advised to protect themselves every day from UVA.
Growing awareness of the importance of daily UV protection has led researchers and manufacturers to focus on the development of an ideal sunscreen, which would combine photostability with broad-spectrum, well-balanced UV protection. Recent advances in this regard have led to the introduction of important new photoprotective ingredients and products. It is hoped that advances will continue in the devolvement of new filters, improved photostability, and new application methods.
Back when the very first sunscreen was introduced in 1928, it was believed that the short-term harmful effects of ultraviolet (UV) radiation exposure, specifically sunburn, were all we had to fear from the sun.1,2 In the succeeding decades, however, it has become clear that sunburn is only the beginning of the pathologic effects produced by solar exposure.1
Recent years have brought a much fuller understanding of the effects of photoexposure, their causes, and ways to protect against them. And, after more than 20 years without the introduction of a single significant new active sunscreen agent, new photoprotective agents and more substantive formulations have recently become available in the United States.3
This article will review recent developments in photoprotection. The content is based on the Clinical Council on Photo-protection, a roundtable meeting of experts in photoprotection held on Jan. 20, 2007, in New York, NY, and sponsored by La Roche-Posay Laboratoire Pharmaceutique.
UVA: A CURRENT FOCUS IN PHOTODAMAGE
Ultraviolet A (UVA) rays have long been thought to have minimal harmful effects, while only UVB rays were believed to have significant deleterious effects.4 Erythema (sunburn) and the delayed effect of suntanning are the most familiar symptoms associated with UVB overexposure, and its association with photocarcinogenesis is well established. Ultraviolet C poses virtually no threat because it is absorbed by the ozone layer of the earth’s atmosphere.
However, research is increasingly demonstrating that UVA is a threat, and a far greater one than has generally been believed.4
UVA radiation is much more abundant than UVB in natural sunlight; it accounts for up to 95% of all UV radiation that reaches Earth.4 Furthermore, whereas the amount of UVB in sunlight varies according to the season, location on the earth, and time of day, the intensity of UVA radiation is more uniform and is present all year round during all daylight hours.4
In addition, while UVB is blocked by window and automobile glass, UVA is not.5 Furthermore, UVA, which has a longer wavelength than UVB, penetrates more deeply into the skin. (See Figure 1.)6 With UVB radiation, it penetrates only into the stratum corneum and is almost fully absorbed before reaching the upper dermis. On the other hand, UVA readily penetrates into the mid-dermis.7
The many negative effects of UV radiation on the skin, including erythema, photoaging, carcinogenicity, and immunosuppression, are exhibited in both UVB and UVA by damage to DNA. Until recently, the genotoxic damage caused by UVA radiation has been thought to be less than that caused by UVB.7 But new research has called this thinking into question.
In a recent study using a highly accurate quantitative assay based on high-performance liquid chromatography combined with mass spectrometry, investigators examined the type and yield of DNA damage in human skin samples exposed to UVA and UVB radiation.8 Cyclobutane pyrimidine dimers, commonly associated with UVB-induced DNA damage, were found in substantial numbers in UVA-exposed skin as well. In addition, UVA-generated dimers were removed at a much lower rate than were UVB-induced dimers.
The researchers also demonstrated that while human skin protects itself very effectively against UVB-induced DNA damage, it protects itself only weakly against UVA-induced injury.8
The Role of UVA in Photoaging
Repeated skin exposure to UV radiation produces a phototrauma referred to as “dermatoheliosis, or photoaging. Although photoaging and intrinsic aging can occur simultaneously, the two processes differ significantly, and photoaged skin appears different from intrinsically aged skin, both macro- and microscopically.
Macroscopically, photoaged skin is characterized by fine and coarse wrinkling; dyspigmentation or hyperpigmentation spots, including freckles or lentigines; laxity; sallowness; telangiectasias; and actinic keratoses.7,2
Microscopically, in normally aging skin, the dermis becomes hypocellular; the epidermis atrophies; collagen forms a stable, cross-linked matrix; and the vasculature remains intact. In photoaged skin, by contrast, the epidermis thickens, the dermis becomes hypercellular (as a result of mast cell and fibroblast propagation), and the vasculature becomes dilated and twisted.2
All portions of the solar spectrum, including UVA, UVB, and infrared radiation, contribute to photoaging.2
However, UVA is now recognized as the single most important wavelength in causing photoaging.4,2 The ability of UVA to deeply penetrate the dermis may account for the primacy of its role in photoaging, as may the fact that UVA exposure does not produce an erythemal “warning signal,” so that higher cumulative doses of UVA radiation may be unknowingly obtained. The ability of UVA to penetrate glass is also a factor. Figure 2, illustrates the result of long-term indoor exposure to UVA radiation.9
The Role of UVA in Immunosuppression
Photoimmunosuppression, a well-documented phenomenon, may play an important role in the genesis of skin cancer; it increases the likelihood and severity of infectious diseases, and reduces the effectiveness of vaccines.7 Immunosuppression induced by UV appears to start with DNA damage and trans to cis-urocanic acid isomerization in the stratum corneum, which is associated with the production of cytokines, histamine, and neuropeptides.7
Recent research has shown that UVA plays a key role in immunosuppression. Ultraviolet A has been shown to suppress induction and elicitation of the contact and delayed-type hypersensitivity responses to recall antigens.7 So important is the impact of UVA on immunosuppression that a new sunscreen measure — immune protection factor — has been proposed for use along with the current sun protection factor (SPF) measure because the latter is not an indicator of degree of protection from UVA.10
The Role of UVA in Carcinogenesis
Strong evidence supports the role of UV exposure in the development of skin cancers, including not only non-melanoma skin cancers such as squamous cell and basal cell carcinomas,7 but also malignant melanoma.11
In the case of melanoma, several lines of epidemiologic evidence, in addition to other sources of evidence, point particularly to high, intermittent exposure to solar UV radiation as a significant risk factor. These data include findings that the incidence of the disease generally increases with decreasing latitude and the heightened intensity of the sun’s rays.
The highest recorded rate of melanoma in the world occurs in Australia, where the annual incidence is up to 20 times the incidence in Europe.11
It was long thought that UVB was primarily responsible for melanoma.12 However, increasing evidence indicates that UVA may also play a significant role.4 Based on an analysis of World Health Organization data from 45 countries, Garland and colleagues found that UVA was associated with melanoma mortality rates after controlling for UVB and average skin pigmentation.12
Limited but consistent data from studies of tanning salon users also show UVA exposure in these beds to be a risk factor for melanoma. A recent meta-analysis of case-control studies and one cohort study conducted between 1984 and 2004 demonstrated a significantly increased risk of cutaneous melanoma following the use of sunbeds and sunlamps.13 These results are supported by a prospective cohort study of 106,379 Swedish and Norwegian women demonstrating that the use of tanning devices once a month or more is statistically significantly associated with melanoma risk.14
In consideration of findings such as these, the American Academy of Dermatology has supported regulations prohibiting minors from using tanning devices, preventing facilities from advertising such devices as safe, and urging the placement of a Surgeon General’s warning on all such devices.15
Contemporary Considerations In Sunscreen Use: Broadening Our Patients’ Protection
In view of the magnitude of the sun’s negative impact on the skin, we might be tempted to advise our patients to entirely avoid UV exposure, both outdoor and indoor. However, given the impracticality of such advice, sunscreens are vital in providing protection from the photodamaging effects of UV rays.16
Since their inception, sunscreens have been known to protect against erythema, the acute effect of UV exposure. But they are now understood to protect against many of the long-term effects of UV exposure as well, including photoaging, actinic keratoses, and some skin cancers.17
Because UVA rays, especially the long-wavelength UVA-1, can pass through clouds and automobile and window glass, incidental exposure to UVA radiation is a daily risk. In view of research findings implicating UVA in the most severe consequences of sun exposure, many groups currently recommend universal, year-round, daily use of a broad-spectrum sunscreen — one that protects against both UVB and UVA — with an SPF of at least 15.18-20
We need to continue to educate patients about the need for daily sunscreen use, about proper sunscreen application, and about the other steps they need to take to protect themselves from UV exposure. (See the patient education handout titled, “Are You Really Protecting Yourself from the Sun’s Dangerous Rays?” and feel free to photocopy it to distribute to your patients.)
A Look at Common Sunscreen Ingredients
To provide broad-spectrum photoprotection, a sunscreen must include a combination of organic and inorganic filters. Advances in sunscreen technology have mimicked and built upon the body’s natural cutaneous defenses against UV radiation, which include the following:
Among the body’s endogenous defenses is the ability of the epidermis to scatter the majority of visible light rays, which is what inorganic UV filters in sunscreens do.17
A second endogenous defense mechanism is that urocanic acid in the skin undergoes UV-initiated isomerization, which is what organic filters cause to happen.17
A third endogenous defense shield is melanin, which protects the skin by filtering and scattering UV rays and changing the absorbed energy into heat energy rather than chemical energy — the same mechanism by which organic filters protect the skin.17 It is this mechanism that causes a sensation of warmth in sunscreen wearers, something about which many patients complain.21
In addition to having light filtering and scattering capabilities, as well as the others mentioned above, photostability is another important characteristic of an effective sunscreen. UV filters that are photolabile will be rapidly inactivated after exposure to UV rays, thus losing their effectiveness. Several factors contribute to photostability, including the filter, the presence of other filters in the product, and the vehicle or solvent. Most UV filters, including avobenzone, octinoxate, and octyl dimethyl para-amino benzoic acid (PABA), are photolabile. Thus, other filters, including zinc oxide, titanium dioxide, octocrylene, methylbenzylidene camphor, and the salicylates, are frequently used in sunscreen preparations to increase their photostability.17
Constructing the Ideal Broad-Spectrum Filter
The ideal broad-spectrum filter must be composed of compatible and complementary filters that can provide effective protection over the entire UVA and UVB spectrum. The aesthetics of the product also need to be optimized to increase the likelihood of adherence.17 The ideal sunscreen should also be photostable in order to ensure functional longevity on the skin. Finally, its vehicle should be resistant to shedding with rubbing, sweating, or water immersion.17
All UV filters have a particular absorption spectrum, which can be extended by combining complementary agents. The ideal sunscreen would combine UVA organic absorbers, UVB organic absorbers, and an inorganic filter. UVA organic absorbers include benzophenones (320 nm to 350 nm),2 avobenzone (357 nm), and, most recently, ecamsule (Mexoryl SX) (344 nm).22 UVB organic absorbers include salicylates (~300 nm) and cinnamates (310 nm to 311 nm).2 Inorganic filters, which act to reflect or scatter UVA and UVB, include titanium dioxide and zinc oxide.2
Both titanium dioxide and zinc oxide are inorganic white particulates, so they must be reformulated for aesthetic purposes for use in sunscreens, but there is an unfortunate trade-off involved: Smaller particles yield less white residue on the skin but poorer photoprotection, while larger particles offer more protection but more white residue, and hence the possibility of poor adherence.16,2
New Products Offering Broad-Spectrum Protection
After two decades without a significant breakthrough in sunscreen ingredients in the United States,3 two new options that promise to improve broad-spectrum, photostable UV protection have recently been introduced.
One is a new technology trade-named Helioplex. Several products are available using the Helioplex technology, which combines photostable UVB filters, and UVA filters avobenzone and oxybenzone in a formulation that slows the degradation of avobenzone to increase its photostability.23,3
Another new introduction features Mexoryl SX. Mexoryl SX was developed for use in combination with avobenzone and octocrylene for broad-spectrum protection. (See Figure 3.)
In this formulation, octocrylene acts to stabilize avobenzone. Available in Europe and Canada since 1993, Mexoryl SX is the first new photostable short-UVA filter in a sunscreen formula to be approved by the U.S. Food and Drug Administration and is now available in the United States in the new sunscreen product Anthelios SX.
Anthelios SX is an SPF15 lightweight moisturizing cream that is intended for daily use. The product protects against both UVB and UVA. Fragrance-free and allergy tested, it is suitable for sensitive skin and is oil-free and noncomedogenic.
Translating New Knowledge of UVA into Protection for Patients
A large and growing body of research has identified UVA as a key contributor to photoaging, immunosuppression, and carcinogenesis. Because UVA is present all year round and UVA-1 can pass through window glass, patients need to be advised to protect themselves every day from UVA.
Growing awareness of the importance of daily UV protection has led researchers and manufacturers to focus on the development of an ideal sunscreen, which would combine photostability with broad-spectrum, well-balanced UV protection. Recent advances in this regard have led to the introduction of important new photoprotective ingredients and products. It is hoped that advances will continue in the devolvement of new filters, improved photostability, and new application methods.
Back when the very first sunscreen was introduced in 1928, it was believed that the short-term harmful effects of ultraviolet (UV) radiation exposure, specifically sunburn, were all we had to fear from the sun.1,2 In the succeeding decades, however, it has become clear that sunburn is only the beginning of the pathologic effects produced by solar exposure.1
Recent years have brought a much fuller understanding of the effects of photoexposure, their causes, and ways to protect against them. And, after more than 20 years without the introduction of a single significant new active sunscreen agent, new photoprotective agents and more substantive formulations have recently become available in the United States.3
This article will review recent developments in photoprotection. The content is based on the Clinical Council on Photo-protection, a roundtable meeting of experts in photoprotection held on Jan. 20, 2007, in New York, NY, and sponsored by La Roche-Posay Laboratoire Pharmaceutique.
UVA: A CURRENT FOCUS IN PHOTODAMAGE
Ultraviolet A (UVA) rays have long been thought to have minimal harmful effects, while only UVB rays were believed to have significant deleterious effects.4 Erythema (sunburn) and the delayed effect of suntanning are the most familiar symptoms associated with UVB overexposure, and its association with photocarcinogenesis is well established. Ultraviolet C poses virtually no threat because it is absorbed by the ozone layer of the earth’s atmosphere.
However, research is increasingly demonstrating that UVA is a threat, and a far greater one than has generally been believed.4
UVA radiation is much more abundant than UVB in natural sunlight; it accounts for up to 95% of all UV radiation that reaches Earth.4 Furthermore, whereas the amount of UVB in sunlight varies according to the season, location on the earth, and time of day, the intensity of UVA radiation is more uniform and is present all year round during all daylight hours.4
In addition, while UVB is blocked by window and automobile glass, UVA is not.5 Furthermore, UVA, which has a longer wavelength than UVB, penetrates more deeply into the skin. (See Figure 1.)6 With UVB radiation, it penetrates only into the stratum corneum and is almost fully absorbed before reaching the upper dermis. On the other hand, UVA readily penetrates into the mid-dermis.7
The many negative effects of UV radiation on the skin, including erythema, photoaging, carcinogenicity, and immunosuppression, are exhibited in both UVB and UVA by damage to DNA. Until recently, the genotoxic damage caused by UVA radiation has been thought to be less than that caused by UVB.7 But new research has called this thinking into question.
In a recent study using a highly accurate quantitative assay based on high-performance liquid chromatography combined with mass spectrometry, investigators examined the type and yield of DNA damage in human skin samples exposed to UVA and UVB radiation.8 Cyclobutane pyrimidine dimers, commonly associated with UVB-induced DNA damage, were found in substantial numbers in UVA-exposed skin as well. In addition, UVA-generated dimers were removed at a much lower rate than were UVB-induced dimers.
The researchers also demonstrated that while human skin protects itself very effectively against UVB-induced DNA damage, it protects itself only weakly against UVA-induced injury.8
The Role of UVA in Photoaging
Repeated skin exposure to UV radiation produces a phototrauma referred to as “dermatoheliosis, or photoaging. Although photoaging and intrinsic aging can occur simultaneously, the two processes differ significantly, and photoaged skin appears different from intrinsically aged skin, both macro- and microscopically.
Macroscopically, photoaged skin is characterized by fine and coarse wrinkling; dyspigmentation or hyperpigmentation spots, including freckles or lentigines; laxity; sallowness; telangiectasias; and actinic keratoses.7,2
Microscopically, in normally aging skin, the dermis becomes hypocellular; the epidermis atrophies; collagen forms a stable, cross-linked matrix; and the vasculature remains intact. In photoaged skin, by contrast, the epidermis thickens, the dermis becomes hypercellular (as a result of mast cell and fibroblast propagation), and the vasculature becomes dilated and twisted.2
All portions of the solar spectrum, including UVA, UVB, and infrared radiation, contribute to photoaging.2
However, UVA is now recognized as the single most important wavelength in causing photoaging.4,2 The ability of UVA to deeply penetrate the dermis may account for the primacy of its role in photoaging, as may the fact that UVA exposure does not produce an erythemal “warning signal,” so that higher cumulative doses of UVA radiation may be unknowingly obtained. The ability of UVA to penetrate glass is also a factor. Figure 2, illustrates the result of long-term indoor exposure to UVA radiation.9
The Role of UVA in Immunosuppression
Photoimmunosuppression, a well-documented phenomenon, may play an important role in the genesis of skin cancer; it increases the likelihood and severity of infectious diseases, and reduces the effectiveness of vaccines.7 Immunosuppression induced by UV appears to start with DNA damage and trans to cis-urocanic acid isomerization in the stratum corneum, which is associated with the production of cytokines, histamine, and neuropeptides.7
Recent research has shown that UVA plays a key role in immunosuppression. Ultraviolet A has been shown to suppress induction and elicitation of the contact and delayed-type hypersensitivity responses to recall antigens.7 So important is the impact of UVA on immunosuppression that a new sunscreen measure — immune protection factor — has been proposed for use along with the current sun protection factor (SPF) measure because the latter is not an indicator of degree of protection from UVA.10
The Role of UVA in Carcinogenesis
Strong evidence supports the role of UV exposure in the development of skin cancers, including not only non-melanoma skin cancers such as squamous cell and basal cell carcinomas,7 but also malignant melanoma.11
In the case of melanoma, several lines of epidemiologic evidence, in addition to other sources of evidence, point particularly to high, intermittent exposure to solar UV radiation as a significant risk factor. These data include findings that the incidence of the disease generally increases with decreasing latitude and the heightened intensity of the sun’s rays.
The highest recorded rate of melanoma in the world occurs in Australia, where the annual incidence is up to 20 times the incidence in Europe.11
It was long thought that UVB was primarily responsible for melanoma.12 However, increasing evidence indicates that UVA may also play a significant role.4 Based on an analysis of World Health Organization data from 45 countries, Garland and colleagues found that UVA was associated with melanoma mortality rates after controlling for UVB and average skin pigmentation.12
Limited but consistent data from studies of tanning salon users also show UVA exposure in these beds to be a risk factor for melanoma. A recent meta-analysis of case-control studies and one cohort study conducted between 1984 and 2004 demonstrated a significantly increased risk of cutaneous melanoma following the use of sunbeds and sunlamps.13 These results are supported by a prospective cohort study of 106,379 Swedish and Norwegian women demonstrating that the use of tanning devices once a month or more is statistically significantly associated with melanoma risk.14
In consideration of findings such as these, the American Academy of Dermatology has supported regulations prohibiting minors from using tanning devices, preventing facilities from advertising such devices as safe, and urging the placement of a Surgeon General’s warning on all such devices.15
Contemporary Considerations In Sunscreen Use: Broadening Our Patients’ Protection
In view of the magnitude of the sun’s negative impact on the skin, we might be tempted to advise our patients to entirely avoid UV exposure, both outdoor and indoor. However, given the impracticality of such advice, sunscreens are vital in providing protection from the photodamaging effects of UV rays.16
Since their inception, sunscreens have been known to protect against erythema, the acute effect of UV exposure. But they are now understood to protect against many of the long-term effects of UV exposure as well, including photoaging, actinic keratoses, and some skin cancers.17
Because UVA rays, especially the long-wavelength UVA-1, can pass through clouds and automobile and window glass, incidental exposure to UVA radiation is a daily risk. In view of research findings implicating UVA in the most severe consequences of sun exposure, many groups currently recommend universal, year-round, daily use of a broad-spectrum sunscreen — one that protects against both UVB and UVA — with an SPF of at least 15.18-20
We need to continue to educate patients about the need for daily sunscreen use, about proper sunscreen application, and about the other steps they need to take to protect themselves from UV exposure. (See the patient education handout titled, “Are You Really Protecting Yourself from the Sun’s Dangerous Rays?” and feel free to photocopy it to distribute to your patients.)
A Look at Common Sunscreen Ingredients
To provide broad-spectrum photoprotection, a sunscreen must include a combination of organic and inorganic filters. Advances in sunscreen technology have mimicked and built upon the body’s natural cutaneous defenses against UV radiation, which include the following:
Among the body’s endogenous defenses is the ability of the epidermis to scatter the majority of visible light rays, which is what inorganic UV filters in sunscreens do.17
A second endogenous defense mechanism is that urocanic acid in the skin undergoes UV-initiated isomerization, which is what organic filters cause to happen.17
A third endogenous defense shield is melanin, which protects the skin by filtering and scattering UV rays and changing the absorbed energy into heat energy rather than chemical energy — the same mechanism by which organic filters protect the skin.17 It is this mechanism that causes a sensation of warmth in sunscreen wearers, something about which many patients complain.21
In addition to having light filtering and scattering capabilities, as well as the others mentioned above, photostability is another important characteristic of an effective sunscreen. UV filters that are photolabile will be rapidly inactivated after exposure to UV rays, thus losing their effectiveness. Several factors contribute to photostability, including the filter, the presence of other filters in the product, and the vehicle or solvent. Most UV filters, including avobenzone, octinoxate, and octyl dimethyl para-amino benzoic acid (PABA), are photolabile. Thus, other filters, including zinc oxide, titanium dioxide, octocrylene, methylbenzylidene camphor, and the salicylates, are frequently used in sunscreen preparations to increase their photostability.17
Constructing the Ideal Broad-Spectrum Filter
The ideal broad-spectrum filter must be composed of compatible and complementary filters that can provide effective protection over the entire UVA and UVB spectrum. The aesthetics of the product also need to be optimized to increase the likelihood of adherence.17 The ideal sunscreen should also be photostable in order to ensure functional longevity on the skin. Finally, its vehicle should be resistant to shedding with rubbing, sweating, or water immersion.17
All UV filters have a particular absorption spectrum, which can be extended by combining complementary agents. The ideal sunscreen would combine UVA organic absorbers, UVB organic absorbers, and an inorganic filter. UVA organic absorbers include benzophenones (320 nm to 350 nm),2 avobenzone (357 nm), and, most recently, ecamsule (Mexoryl SX) (344 nm).22 UVB organic absorbers include salicylates (~300 nm) and cinnamates (310 nm to 311 nm).2 Inorganic filters, which act to reflect or scatter UVA and UVB, include titanium dioxide and zinc oxide.2
Both titanium dioxide and zinc oxide are inorganic white particulates, so they must be reformulated for aesthetic purposes for use in sunscreens, but there is an unfortunate trade-off involved: Smaller particles yield less white residue on the skin but poorer photoprotection, while larger particles offer more protection but more white residue, and hence the possibility of poor adherence.16,2
New Products Offering Broad-Spectrum Protection
After two decades without a significant breakthrough in sunscreen ingredients in the United States,3 two new options that promise to improve broad-spectrum, photostable UV protection have recently been introduced.
One is a new technology trade-named Helioplex. Several products are available using the Helioplex technology, which combines photostable UVB filters, and UVA filters avobenzone and oxybenzone in a formulation that slows the degradation of avobenzone to increase its photostability.23,3
Another new introduction features Mexoryl SX. Mexoryl SX was developed for use in combination with avobenzone and octocrylene for broad-spectrum protection. (See Figure 3.)
In this formulation, octocrylene acts to stabilize avobenzone. Available in Europe and Canada since 1993, Mexoryl SX is the first new photostable short-UVA filter in a sunscreen formula to be approved by the U.S. Food and Drug Administration and is now available in the United States in the new sunscreen product Anthelios SX.
Anthelios SX is an SPF15 lightweight moisturizing cream that is intended for daily use. The product protects against both UVB and UVA. Fragrance-free and allergy tested, it is suitable for sensitive skin and is oil-free and noncomedogenic.
Translating New Knowledge of UVA into Protection for Patients
A large and growing body of research has identified UVA as a key contributor to photoaging, immunosuppression, and carcinogenesis. Because UVA is present all year round and UVA-1 can pass through window glass, patients need to be advised to protect themselves every day from UVA.
Growing awareness of the importance of daily UV protection has led researchers and manufacturers to focus on the development of an ideal sunscreen, which would combine photostability with broad-spectrum, well-balanced UV protection. Recent advances in this regard have led to the introduction of important new photoprotective ingredients and products. It is hoped that advances will continue in the devolvement of new filters, improved photostability, and new application methods.
