SA07_62-67_SunProtection.qxd 7/11/07 12:45 PM Page 62 UVA: GRASPING A BETTER UNDERSTANDING OF THIS FORMIDABLE OPPONENT Leading dermatologists discuss what is now known about the harmful effects of UVA, and they highlight recent clinical advancements in photoprotection technology. BY HENRY W. LIM, M.D., AND DARRELL S. RIGEL, M.D. Back when the very first sunscreen was substantive formulations have recently effects.4 Erythema (sunburn) and the introduced in 1928, it was believed that become available in the United States.3 delayed effect of suntanning are the most the short-term harmful effects of ultravi- This article will review recent develop- familiar symptoms associated with UVB olet (UV) radiation exposure, specifically ments in photoprotection. The content is overexposure, and its association with sunburn, were all we had to fear from the based on the Clinical Council on Photo- photocarcinogenesis is well established. sun.1,2 In the succeeding decades, howev- protection, a roundtable meeting of experts Ultraviolet C poses virtually no threat er, it has become clear that sunburn is in photoprotection held on Jan. 20, 2007, in because it is absorbed by the ozone layer only the beginning of the pathologic New York,NY,and sponsored by La Roche- of the earth’s atmosphere. effects produced by solar exposure.1 Posay Laboratoire Pharmaceutique. However, research is increasingly demon- Recent years have brought a much strating that UVA is a threat, and a far fuller understanding of the effects of pho- UVA: A CURRENT FOCUS IN greater one than has generally been believed.4 toexposure, their causes, and ways to pro- PHOTODAMAGE UVA radiation is much more abundant tect against them.And, after more than 20 Ultraviolet A (UVA) rays have long than UVB in natural sunlight; it accounts years without the introduction of a single been thought to have minimal harmful for up to 95% of all UV radiation that significant new active sunscreen agent, effects, while only UVB rays were reaches Earth.4 Furthermore, whereas the new photoprotective agents and more believed to have significant deleterious amount of UVB in sunlight varies accord- 62 JULY 2007 SKIN & AGING SA07_62-67_SunProtection.qxd 7/11/07 12:45 PM Page 63 UVA: A BETTER UNDERSTANDING OF THIS FORMIDABLE OPPONENT ing 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, at right.)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 radia- tion on the skin, including erythema, pho- toaging, carcinogenicity, and immunosup- pression, 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-perform- ance 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 sub- stantial numbers in UVA-exposed skin as Figure 1. Penetration of various wavelengths of light into human skin. well. In addition, UVA-generated dimers were removed at a much lower rate than were UVB-induced dimers. Microscopically, in normally aging tion may be unknowingly obtained. The researchers also demonstrated that skin, the dermis becomes hypocellular; The ability of UVA to penetrate glass is while human skin protects itself very effec- the epidermis atrophies; collagen forms also a factor. Figure 2, next page, tively against UVB-induced DNA damage, a stable, cross-linked matrix; and the illustrates the result of long-term it protects itself only weakly against UVA- vasculature remains intact. In photoaged indoor exposure to UVA radiation.9 induced injury.8 skin, by contrast, the epidermis thickens, the dermis becomes hypercellular (as a The Role of UVA in The Role of UVA in Photoaging result of mast cell and fibroblast propa- Immunosuppression Repeated skin exposure to UV radia- gation), and the vasculature becomes Photoimmunosuppression, a well-docu- tion produces a phototrauma referred to as dilated and twisted.2 mented phenomenon, may play an impor- “dermatoheliosis, or photoaging.Although All portions of the solar spectrum, tant role in the genesis of skin cancer; it photoaging and intrinsic aging can occur including UVA, UVB, and infrared increases the likelihood and severity of simultaneously, the two processes differ radiation, contribute to photoaging.2 infectious diseases, and reduces the effec- significantly, and photoaged skin appears However, UVA is now recognized as tiveness of vaccines.7 Immunosuppression different from intrinsically aged skin, both the single most important wavelength induced by UV appears to start with DNA macro- and microscopically. in causing photoaging.4,2 The ability of damage and trans to cis-urocanic acid iso- Macroscopically, photoaged skin is UVA to deeply penetrate the dermis merization in the stratum corneum, which characterized by fine and coarse wrin- may account for the primacy of its role is associated with the production of kling; dyspigmentation or hyperpigmen- in photoaging, as may the fact that cytokines, histamine, and neuropeptides.7 tation spots, including freckles or lentig- UVA exposure does not produce an Recent research has shown that UVA ines; laxity; sallowness; telangiectasias; erythemal “warning signal,” so that plays a key role in immunosuppression. and actinic keratoses.7,2 higher cumulative doses of UVA radia- Ultraviolet A has been shown to sup- JULY 2007 SKIN & AGING 63 SA07_62-67_SunProtection.qxd 7/11/07 12:45 PM Page 64 UVA: A BETTER UNDERSTANDING OF THIS FORMIDABLE OPPONENT Figure 2. Unilateral cutaneous elastosis, one of the best-known manifestations of helioderma, caused by UVA radiation. The patient had worked for 15 years in the same room with the same orientation to a window, so that the left side of her face had been con- tinuously exposed to UVA radiation, while the right side had not. Reprinted with permission from Moulin G et al. Ann Dermatol Venereol. 1994;121:721-723. press induction and elicitation of the con- It was long thought that UVB was pri- CONTEMPORARY tact and delayed-type hypersensitivity marily responsible for melanoma.12 CONSIDERATIONS IN responses to recall antigens.7 So important However, increasing evidence indicates SUNSCREEN USE: BROADENING is the impact of UVA on immunosuppres- that UVA may also play a significant role.4 OUR PATIENTS’ PROTECTION sion that a new sunscreen measure — Based on an analysis of World Health In view of the magnitude of the sun’s immune protection factor — has been pro- Organization data from 45 countries, negative impact on the skin, we might be posed for use along with the current sun Garland and colleagues found that UVA tempted to advise our patients to entirely protection factor (SPF) measure because the was associated with melanoma mortality avoid UV exposure, both outdoor and latter is not an indicator of degree of protec- rates after controlling for UVB and aver- indoor. However, given the impracticality tion from UVA.10 age skin pigmentation.12 of such advice, sunscreens are vital in pro- Limited but consistent data from studies of viding protection from the photodamag- The Role of UVA in Carcinogenesis tanning salon users also show UVA exposure ing effects of UV rays.16 Strong evidence supports the role of in these beds to be a risk factor for Since their inception, sunscreens have UV exposure in the development of skin melanoma. A recent meta-analysis of case- been known to protect against erythema, cancers, including not only non- control studies and one cohort study con- the acute effect of UV exposure. But they melanoma skin cancers such as squamous ducted between 1984 and 2004 demonstrat- are now understood to protect against many cell and basal cell carcinomas,7 but also ed a significantly increased risk of cutaneous of the long-term effects of UV exposure as malignant melanoma.11 melanoma following the use of sunbeds and well,including photoaging,actinic keratoses, In the case of melanoma, several lines sunlamps.13 These results are supported by a and some skin cancers.17 of epidemiologic evidence, in addition to prospective cohort study of 106,379 Swedish Because UVA rays, especially the other sources of evidence, point particu- and Norwegian women demonstrating that long-wavelength UVA-1, can pass larly to high, intermittent exposure to the use of tanning devices once a month or through clouds and automobile and solar UV radiation as a significant risk more is statistically significantly associated window glass, incidental exposure to factor. These data include findings that with melanoma risk.14 UVA radiation is a daily risk. In view of the incidence of the disease generally In consideration of findings such as these, research findings implicating UVA in the increases with decreasing latitude and the the American Academy of Dermatology has most severe consequences of sun expo-