The health impact of solar radiation and prevention strategies

FROM

THE

ACADEMY

This report reflects current information available at the time the report was prepared, but caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations set forth in this report.

The health impact of solar radiation and prevention strategies Report of the Environment Council, American Academy of Dermatology Coordinators: Henry W. Lim, MD, and Kevin Cooper, MD Contributors: Henry W. Lim, MD, Kevin Cooper, MD, Reva Rubenstein, PhD, Drusilla Hufford, MBA, Thomas Downham II, MD, Ron Trancik, PhD, Robert Swerlick, MD, Martin A. Weinstock, MD, PhD, Vincent DeLeo, MD, Rex Amonette, MD, James M. Spencer, MD, Cheryl Rosen, MD, FRCPC, Jason K. Rivers, MD, FRCPC, Wilma Bergfeld, MD, Alvin James Miller, Sandra Gordon, Paul Gross, Allan Eustis, Howard Koh, MD

TABLE OF CONTENTS Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 82 I. The health impact of solar radiation A. Stratospheric ozone depletion: Major or minor skin health risk? . . . . . . . . . . . . . . . . . . . . . . . . p. 82 Reva Rubenstein, PhD, Drusilla Hufford, MBA, Thomas Downham II, MD, Ron Trancik, PhD, Robert Swerlick, MD B. Tanning, tanning booths, and melanoma: Risky or protective? . . . . . . . . . . . . . . . . . . . . . . . . . . p. 84 Martin A. Weinstock, MD, PhD, Henry W. Lim, MD, Vincent DeLeo, MD, Rex Amonette MD, and James M. Spencer, MD C. Unanswered questions on the use of sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 87 Cheryl Rosen, MD, FRCPC D. Increased incidence of melanoma: Real or epiphenomenon?. . . . . . . . . . . . . . . . . . . . . . . . . . . p. 93 Jason K. Rivers, MD, FRCPC II. Prevention A. Prevention strategies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 95 Henry W. Lim, MD, and Wilma Bergfeld, MD B. Public messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . p. 96 Alvin James Miller, Sandra Gordon, Paul Gross, Kevin Cooper, MD, Allan Eustis, Thomas Downham, MD, Howard Koh, MD, and Drusilla Hufford, MBA

From the American Academy of Dermatology, Inc. *A list of the affiliations for all contributors may be found at the end of the article. J AM A C A D D ERMATOL

Reprint requests: American Academy of Dermatology, PO Box 4014, Schaumburg, IL 60168-4014. Copyright © 1999 by the American Academy of Dermatology, Inc. 0190-9622/99/$8.00 + 0 16/1/98493

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It is well recognized that exposure to solar radiation is a major risk factor for the development of skin cancer, photoaged skin, and immune system alterations. However, major questions remain regarding the specific wavelengths and type of exposure that incur risk. The purpose of this article is to critically examine, on the basis of current knowledge, the impact of stratospheric ozone depletions, tanning bed skin cancer risk, the safety of sunscreens as an important element of our solar protection strategies, the wavelengths of solar radiation responsible for melanoma, and the incidence of melanoma. Recommendations are made on prevention stategies and public health messages. (J Am Acad Dermatol 1999;41:81-99.)

I. THE HEALTH IMPACT OF SOLAR RADIATION A. Stratospheric ozone depletion: Major or minor skin health risk? Reva Rubenstein, PhD, Drusilla Hufford, MBA, Thomas Downham II, MD, Ron Trancik, PhD, and Robert Swerlick, MD Ultraviolet radiation The sun emits two types of ultraviolet (UV) light, UVB (290-320 nm) and UVA (320-400 nm), that can reach the earth’s surface. Exposure to UVB and, to a lesser extent, UVA can cause adverse health effects, including increased incidence of skin cancers, cataracts, and immune suppression. Most UVB is absorbed by the stratospheric ozone layer, although some UVB does reach the surface of the earth. Most UVA radiation is not absorbed by the stratospheric ozone layer; however, some of the more energetic wavelengths of UVA (UVA II, 320-340 nm) are partly absorbed by ozone. The quantity of UV striking the earth’s surface depends on several factors, including the following: Atmospheric and environmental conditions: The ozone layer forms a natural shield in the stratosphere that absorbs much of the biologically damaging UV radiation from the sun before it can reach the earth’s surface. The presence of clouds and atmospheric pollutants can strongly affect the UV levels reaching the earth’s surface. For instance, the pristine Antarctic troposphere absorbs less UVB than the more polluted American troposphere. Time of day: UV levels are usually greatest around the noon hour because the sun is at its highest point in the sky; thus the sun’s rays have the least distance to travel through the atmosphere before striking the earth’s surface. Altitude: UV intensity increases with altitude because there is less atmosphere to absorb the radiation. Season: The angle of the sun in relation to the surface of the earth varies with the seasons, resulting in changes in UV radiation reaching the surface. In the Northern hemisphere, UV intensity is highest during the summer months when incident angle is close to 90 degrees.

Latitude: The sun’s rays are strongest at the equator, where the sun is most directly overhead and the UV radiation travels the least distance through the atmosphere. Ozone is also naturally thinner near the equator, so there is less ozone to absorb the UV radiation as it passes through the atmosphere. Conversely, at higher latitudes the sun is at a lower angle in the sky, so UV radiation travels a greater distance through the ozone-rich portion of the atmosphere and in turn exposes those latitudes to less UV radiation. All other things being equal, therefore, one would expect to see greater health effects from UV radiation near the equator. In the 1980s, scientists began accumulating significant evidence that the ozone layer was being depleted by chlorofluorocarbons (CFCs) and other manmade chemicals that are used in a variety of industrial sectors and are released into the atmosphere. The destruction of ozone has been exceeding its natural formation, resulting in increased UV radiation reaching the earth’s surface, particularly in Antarctica. Ozone is extensively catabolized over the polar regions because the reaction requires the concurrence of CFCs, frozen stratospheric clouds (to provide a solid matrix for the reaction), ozone, and sunlight; these conditions come together to varying degrees each spring, followed by a partial, but incomplete replenishment of ozone over the rest of the year via diffusion from the rest of the earth’s ozone and by new synthesis in the troposphere. The increased UVB penetrance is easily measured at the earth’s surface in Antarctica because of its pristine troposphere, which thus provides little additional UVB filtration by pollutants. The excess of ozone destruction over formation for the past two decades has also depleted stratospheric ozone over heavily populated areas. As the stratospheric ozone layer is depleted, the quantity of harmful UV reaching the earth’s surface increases. A study published in the Aug 1, 1996 issue of Geophysical Research Letters confirms that harmful radiation from the sun has been hitting populated areas in increasing amounts over the past 15 years, as the ozone layer has been depleted.1 A commonly used measure designed to capture this effect is the radiation amplification factor (RAF). The RAF is defined

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approximately as the percentage increase in biologically active UV striking the earth’s surface that results from a 1% decrease in the ozone layer at that location. RAF values vary between 0.7 and 1.2 for the erythema action spectrum, 1.1 to 1.6 for the skin cancer action spectrum, and 1.5 to 2.3 for DNA damage spectrum.2 To put the potential increase in UV radiation striking the United States caused by ozone depletion in perspective, it is instructive to examine ozone depletion over the past decade. It has been estimated that total ozone over the United States decreased by between 4.8% and 7.4% during the period 19791992.2 Given these decreases, the total increase in biologically active UV radiation striking the United States should have increased by 5.0% to 7.2% for the erythema action spectrum, by 8.2% to 12.9% for the DNA damage spectrum, and 6.1% to 9.5% for the skin cancer action spectrum.2 Issues in need of further study Although increased ground-based measurements of UVB have been recorded in Antarctica and Australia in proportion to overlying decreases in stratospheric ozone, ground-based UVB measurements in the United States, albeit elevated, have not shown the expected magnitude of increases. This disparity has been used by some as evidence that the risk of ozone depletion has been exaggerated. It is very likely that the disparity is attributable to lower tropospheric pollutants that can absorb UVB (ie, ozone from cars and industrial oxides) or particulate pollutants, which can reflect and scatter UVB in Antarctica and Australia. The use of monthly averaged values also may minimize the ability to determine UVB trends because this removes the ability to assess the frequency of high irradiance days that occur when local pollutants diminish after rains and specific weather conditions. Another issue needing further clarification is whether an increment in UVB intensity would ever be of sufficient magnitude to result in increased risk to health. It has been argued that the magnitude of increased UVB intensity in Canada, even at the nadir of ozone in 2010-2020, would represent only a fraction of the increase in UVB irradiance that would occur by vacationing in the tropics or visiting tanning parlors. This argument becomes particularly cogent if the most important risk for melanoma is intermittent high-intensity exposure rather than accumulated long-term exposure. Although public education to modify behavior is clearly of great importance, in view of the overwhelming evidence of known harmful effects of UVB, and the documented increase in UVB associated with ozone depletion, it is highly likely that this

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increase, albeit proportionately small, may further contribute to the increase in risk to health. A third issue is whether increasing the UVB intensity in the presence of the already high intensity and biologically active UVA wavelengths will have any discernible effect on health outcomes because the actual wavelengths most responsible for melanoma and immunosuppression have not been completely elucidated. Latitudinal variations in UVB intensity are accompanied by variations in intensity of UVA and visible wavelengths, so latitudinal data ascribing increased incidences of skin cancer solely to the increased UVB irradiance actually cannot rule out that the risk is due to increased total UV irradiance (a spectrum of active wavelengths). This uncertainty, along with the fact that natural processes also can degrade stratospheric ozone (eg, the Mount Pinatubo eruption), has been used by some to argue that regulatory controls on CFCs are unnecessary and costly to our economy. Experience with patients with xeroderma pigmentosum supports the role of UVB in cutaneous carcinomas. These patients are highly susceptible to melanoma and keratinocytic skin cancer, and they accumulate DNA mutations caused by thymidine dimers that they are unable to repair; these dimers are highly specific for UVB.3 Whether UVA-induced oxidative DNA lesions are also unrepaired in these patients is an area of active investigation. The presence of characteristic UVB-induced DNA mutations in lesions of squamous cell carcinomas and actinic keratosis of normal individuals also constitute strong evidence for UVB as an important element of the adverse health impact of solar radiation. The presence of thymidine dimer–induced DNA mutations in skin cancers that resulted in inability to produce functional proteins critical for controlling cell growth (ie, p53) constitutes additional hard evidence that UVB is playing a critical role in the formation of skin cancer. The degree to which other wavelengths may also play a role is at this time unclear. Skin cancers: Nonmelanoma and melanoma Evidence indicates that cumulative lifetime exposure to solar radiation (UVB) is the most important cause of nonmelanoma skin cancer in human beings.4-6 Given that there is a lengthy latency period between exposure to UVB radiation and the onset of nonmelanoma skin cancer, there is no evidence that such cancers occurring in the United States today are related to increases in UVB exposure associated with the onset of ozone depletion in the Northern Hemisphere. A commonly used measure to capture the potential increase in nonmelanoma skin cancer incidence

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associated with ozone depletion is the amplification factor (AF). The AF is defined as the percentage increase in nonmelanoma skin cancer that would result from a 1% decrease in ozone. The AFs for basal cell carcinoma and squamous cell carcinoma are about 1.7 and 3.0, respectively.4 In other words, for each 1% sustained decrease in ozone, the incidence of basal cell and squamous cell skin cancers among fair-skinned persons will increase by 1.7% and 3.0% annually, respectively. Given these estimates, and the fact that ozone depletion is expected to continue to occur into the next century, it appears likely that rates of nonmelanoma skin cancer will increase over time. Studies indicate that exposure to solar radiation is an important risk factor in the onset of melanoma and that incidence of severe intermittent exposure (ie, sunburn) during childhood and adolescence may be particularly relevant to the later onset of the disease.7,8 Like nonmelanoma skin cancer, and as supported by the observation of PUVA-induced melanoma, there is a long delay between exposure to solar radiation and the onset of melanoma. As a result, there is no evidence that the melanoma incidence observed to date is related to recent increased UV levels associated with ozone depletion. As depletion continues to occur, future rates of melanoma incidence and fatalities should increase. For example, one study has estimated that the rate of incidence of melanoma-related deaths in 3 U.S. cities (Minneapolis, Minn; San Francisco, Calif; and El Paso, Tex) will increase by a total of 1.43% to 1.94% per year for the male population and 0.91% to 1.27% per year for the female population for each 1% decrease in ozone.9 Summary The above projections, to some degree, assume that UVB is the critical wavelength for carcinogenesis. If longer wavelengths are also involved, the AF of increased UVB will have to be reduced. If tropospheric UVB-absorbing/scattering pollutants also

B. Tanning, tanning booths, and melanoma: Risky or protective?*1 Martin A. Weinstock, MD, PhD, Henry W. Lim, MD, Vincent A. DeLeo, MD, Rex Amonette, MD, and James M. Spencer, MD Does a tan protect against melanoma? It has been argued that all tanning is a manifestation of injury, and that there is no “safe tan.”2 However, having a tan does offer some protection *An earlier version of this article has been published (see reference 1).

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increase, the AF may also have to be reduced. However, despite these caveats, it has been calculated that, even if melanoma is removed from the projections, the economic models still clearly indicate a net economic benefit in minimizing ozone depletion because of reduction in nonmelanoma incidence and morbidity.10 REFERENCES 1. Herman JR, Bhatia PK, Ziemke J, Ahmad Z, Larko D. UV-B increases (1979-1992) from decreases in total ozone. Geophysical Res Lett 1996;23:2117-120. 2. Madronich S, de Gruijl FR. Stratospheric ozone depletion between 1979 and 1992: implications for biologically active ultraviolet-B radiation and non-melanoma skin cancer incidence. Photochem Photobiol 1994;59:541-6. 3. Mahler VM, Dorney DJ, Mendrala AL, Konz-Thomas B, McCormick JJ. DNA excision-repair process in human cells can eliminate the cytotoxic and mutagenetic consequences of ultraviolet irradiation. Mutat Res 1979;62:311-23. 4. Scotto J, Fears TR, Fraumeni JF Jr. Incidence of nonmelanoma skin cancer in the United States. National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health and Human Services, Bethesda, MD. NIH Publication No. 83-2433. April 1983. 5. Slaper H, Velders GJM, Daniel JS, de Gruijl FR, van der Leun JC. Estimates of ozone depletion and skin cancer incidence to examine the Vienna Convention achievements. Nature 1996;384:256-8. 6. Longstreth JD, de Gruijl FR, Kripke ML, Takizawa Y, van der Leun JC. Effects of increased solar ultraviolet radiation on human health. Environmental Effects of Ozone Depletion: 1994 Assessment. United Nations Environment Programme; 1994. p. 23-48. 7. Khlat M, Vail A, Parkin M, Green A. Mortality from melanoma in migrants to Australia: variation by age at arrival and duration of stay. Am J Epidemiol 1992;135:1103-13. 8. Cooke KR, Fraser J. Migration and death from malignant melanoma. Int J Cancer 1985;36:175-8. 9. Pitcher HM, Longstreth JD. Melanoma mortality and exposure to ultraviolet radiation: an empirical relationship. Environ Int 1991;17:7-21. 10. US Environmental Protection Agency Air Docket (AD) #A-91-50, US EPA, Regulatory Impact Analysis. Compliance With Section 604 of the Clean Air Act for the Phaseout of Ozone Depleting Chemicals. Washington (DC): Office of Air and Radiation; July 1, 1992.

from subsequent acute sunburn. So what about melanoma? The relation of cumulative sun exposure to melanoma incidence is not a simple linear one. Indeed, the observation from many studies led to the hypothesis that intermittent sun exposure is more closely linked to melanoma than more constant exposure patterns.3 It has also been observed in several studies that recreational exposure is more closely associated with melanoma than occupational exposure. One explanation of these observations is that a tan fades in the absence of repeat-

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ed exposure, so when exposures are infrequent, they will typically occur on untanned (therefore arguably unprotected) skin and hence cause more damage. One aspect of this hypothesis is that individuals differ substantially in their ability to tan. If a tan is protective, that protection should apply primarily to persons who tan readily, and to a lesser extent or not at all among those who are “sun sensitive” and therefore cannot develop a substantially photoprotective tan. Several published reports describe this sort of complex association between melanoma risk and sun sensitivity,4-8 although other investigators were not able to confirm this form of association.3 Some of these data have been reviewed elsewhere.1 The evidence does not clearly prove the hypothesis true or false. If the hypothesis is true, we must be careful not to translate it into a recommendation for the general population to seek a tan because, under this hypothesis, those who must exert the most effort in obtaining a tan are precisely those who are most damaged by doing so. Hence the key issue for individuals would become whether they obtain a sufficiently deep tan easily enough that the damage incurred in obtaining a tan outweighs the still controversial potential benefit of having one. The idea that burns, and not long-term exposure, cause melanoma is a hypothesis based on epidemiologic studies. There are a paucity of animal studies to address this issue. However, there is one study utilizing the South American opossum Monodelphis domestica in which multiple low-dose exposures to UV radiation were more effective in inducing melanocytic tumors than a few high-dose exposures,9 which is at variance with the “burns only” hypothesis. Three times weekly of UVB radiation for up to 12 months has also been shown to induce melanocytic hyperplasia in human skin transplanted to recombinase activating gene-1 (RAG-1) knockout mice,10 further implicating the role of long-term UV exposure in this process. Do tanning booths cause melanoma? It seemed that we had effectively maximized our UV exposures by developing within our society the proclivity to sunbathe at the beach, that is to lie horizontally surrounded by reflective surfaces when the sun is at its maximal elevation, and to do so essentially without protection from clothing. Yet, just at this moment a new means of supplemental UV exposure has become popular, despite the risk and expense: the tanning parlor. The many adverse health affects associated with tanning parlor use have been reviewed.11 Among the adverse effects (other than cancer) that have been

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attributed to tanning booth exposure are atypical melanocytic proliferations, lentigines, phototoxic and photoallergic medication reactions, and immunosuppression. A recent study on 22 subjects receiving suntan parlor exposure showed localized suppression of contact hypersensitivity, sensitization and elicitation, and an increase in circulating T suppressor cells when compared with the controlled group.12 It must be noted that UVA radiation sources sometimes used in tanning parlors produce a tan that is not as protective against subsequent sunburn as a UVB-induced tan.13,14 Indeed, there is published evidence to suggest that tanning with UVA may be more hazardous than tanning with UVB.15 It also should be noted, however, that the bulbs used in tanning parlors may emit substantial doses of UVB radiation and that patrons of these facilities are unlikely to be able to determine the content of the radiation to which they are exposed. There are 3 points about a “protective” indoor tan. First, burns can and do occur rather frequently at tanning parlors. Of course this is not the operator’s objective, but surveys in tanning parlors report such burns are, in fact, quite common. Second, persons with skin types I and II, thought to be at greatest risk for melanoma, are by definition poor tanners and will not get much tan at a tanning parlor. Third, the tan acquired at tanning parlors has been shown to provide litte protection against subsequent sunburn.13,14 Issues in need of further study Unfortunately, the action spectrum for human melanoma is unknown. The only sun-related malignancy or cutaneous malignancy with a welldescribed action spectrum (based on a mammalian model) is squamous cell carcinoma. With respect to the wavelengths of solar irradiation at the earth’s surface, this action spectrum is essentially identical to the erythema action spectrum.16 However, an alternate action spectrum that is more heavily weighted to the longer wavelengths, including UVA and visible light, has been found in the platyfishswordtail hybrid model of melanoma, which suggests that UVA is a much more potent inducer of melanoma, relative to UVB, than it is of tanning.17 In human skin transplanted to RAG-1 mice, melanocytic hyperplasia was induced by long-term UVB radiation.10 The limited human evidence relies in large part on the genetic DNA repair disorder xeroderma pigmentosum, in which UVB-induced DNA alterations are poorly repaired. Patients with this disorder are sun sensitive and have an extraordinarily high incidence of squamous cell carcinoma and melanoma, among others.18

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Case-control studies have evaluated the association between artificial UV exposure and subsequent melanoma. Some of these were unable to associate these exposures with melanoma risk, or others noted an association that was not statistically significant. Although many aspects of the studies were not described in detail, the above observations may have been due to the inadequate latent period after exposure, little actual exposure of the subjects, and the inadequate power to detect an association.4,19-28 However, several studies did note a significant elevation in risk among users of UV lamps.29-34 In the 4 studies with more rigorous designs in which the analysis was described in detail, a dose-response relationship was observed.31-34 These 4 studies were conducted in relatively cold northern climates (Scotland, Ontario, northern continental Europe, and Sweden) where natural sun exposure is relatively low, so the relative contribution of artificial sources of UV exposure is greater than in the United States, southern Europe, and Australia. The results of these studies are limited by the inability to characterize the emission spectra of the artificial UV light sources to which the participants were exposed. Because of the increasing popularity of these sources of exposure in recent years, the longer term effects of their use may not fully manifest for some time, so our ability to study these effects epidemiologically is limited. The evidence relevant to the association of melanoma with tanning lamp exposure has recently been reviewed in detail.35

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Summary The evidence of harm from tanning parlors, particularly their potential link to melanoma, has been sufficiently compelling to generate a recommendation from the American Medical Association that interstate commerce in tanning booths be banned in the United States. The political as well as public health aspects of this issue will undoubtedly continue while we seek additional scientific data relevant to this issue.

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21. REFERENCES 1. Weinstock MA. Controversies in the role of sunlight in the pathogenesis of cutaneous melanoma. Photochem Photobiol 1996;63:406-10. 2. Bargoil SC, Erdman LK. Safe tan: an oxymoron. Cancer Nursing 1993;16:139-44. 3. Elwood JM. Melanoma and sun exposure: contrasts between intermittent and chronic exposure. World J Surg 1992;16:15766. 4. Dubin N, Mosseson M, Pasternack BS. Sun exposure and malignant melanoma among susceptible individuals. Environ Health Perspect 1989;81:139-51. 5. Holman CDJ, Armstrong BK, Heenan PJ. Relationship of cuta-

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neous malignant melanoma to individual sunlight-exposure habits. J Natl Cancer Inst 1986;76:403-14. Weinstock MA, Colditz GA, Willett WC, Stampfer MJ, Bronstein BR, Mihm MC, et al. Melanoma and the sun: the effect of swim suits and a “healthy” tan on the risk of nonfamilial malignant melanoma in women. Am J Epidemiol 1991;134:462-70. White E, Kirkpatrick CS, Lee JAH. Case-control study of malignant melanoma in Washington State. I. Constitutional factors and sun exposure. Am J Epidemiol 1994;139:857-68. Nelemans PJ, Groenendal H, Kiemeney LALM, Rampen FHJ, Ruiter DJ, Verbeek ALM. Effect of intermittent exposure to sunlight on melanoma risk among indoor workers and sun-sensitive individuals. Environ Health Perspect 1993;101:252-5. Ley RD. Animal models for melanoma. In: Mukhtar H, editor. Skin cancer: mechanisms and human relevance. Boca Raton (FL): CRC Press; 1995. p. 9-11. Atillasoy ES, Seykora JT, Soballe PW, Elenitsas R, Nesbit M, Elder DE, et al. UVB induces atypical melanocytic lesions and melanoma in human skin. Am J Pathol 1998;152:1179-86. Spencer JM, Amonette RA. Indoor tanning: risks, benefits, and future trends. J Am Acad Dermatol 1995;33:288-98. Whitmore SE, Morison WL. Suntan parlor exposure and immunosuppression [abstract]. Photodermatol Photoimmunol Photomed 1998;14:41. Gange RW, Blackett AD, Matzinger EA, Sutherland BM, Kochevar IE. Comparative protection efficacy of UVA- and UVB-induced tans against erythema and formation of endonuclease-sensitive sites in DNA by UVB in human skin. J Invest Dermatol 1985;85:362-4. Kaidbey KH, Kligman AM. sunburn protection by longwave ultraviolet radiation-induced pigmentation. Arch Dermatol 1978;114:46-8. Diffey BL, Farr PM. Tanning with UVB or UVA: an appraisal of risks. J Photochem Photobiol B 1991;8:219-23. de Gruijl FR, Sterenborg HJCM, Forbes PD, Davies RE, Cole C, Kelfkens G, et al. Wavelength dependence of skin cancer induction by ultraviolet irradiation of albino hairless mice. Cancer Res 1993;53:53-60. Setlow RB, Grist E, Thompson K, Woodhead AD. Wavelengths effective in induction of malignant melanoma. Proc Natl Acad Sci U S A 1993;90:6666-70. Kraemer KH, Lee M-M, Andrews AD, Lambert WC. The role of sunlight and DNA repair in melanoma and nonmelanoma akin cancer: the xeroderma pigmentosum paradigm. Arch Dermatol 1994;130:1018-21. Osterlind A, Tucher MA, Stone BJ, Jansen OM. The Danish case control study of cutaneous malignant melanoma: II: importance of UV-light exposure. Int J Cancer 1988;42:319-24. Gallagher RP, Elwood JM, Hill GB. Risk factors for cutaneous malignant melanoma: the western Canada Melanoma Study. Recent Results Cancer Res 1985;102:38-55. Elwood JM,Williamson C, Stapleton PH. Malignant melanoma in relation to moles, pigmentation, and exposure to fluorescent and other lighting sources. Br J Cancer 1986;53:65-74. Dunn-Lane J, Herity B, Moriarty MJ, Conroy R. A case control study of malignant melanoma. Ir Med J 1993;86:57-9. Beitner H, Norell SE, Ringborg U, Wennersten G, Mattson B. Malignant melanoma: aetiological importance of individual pigmentation and sun exposure. Br J Dermatol 1990;122:43-51. Klepp O, Magnus K. Some environmental and bodily characteristics of melanoma patients: a case-control study. Int J Cancer 1979;23:482-6. MacKie RM, Freudenberger T, Aitchison TC. Personal risk-factor chart for cutaneous melanoma. Lancet 1989;2:487-90. Garbe C, Weiß J, Kruger S, Garbe E, Buttner P, Bertz J, et al. The

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German melanoma registry and environmental risk factors implied. Recent Results Cancer Res 1993;128:69-89. Holly EA, Kelly JW, Shpall SN, Chiu SH. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol 1987;17:459-68. Holly EA, Aston DA, Cress RD, Ahn DK, Kristiansin JJ. Cutaneous melanoma in women: I. Exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light. Am J Epidemiol 1995;141:923-33. Adam SA, Sheaves JK, Wright NH, Mosser G, Harris RW, Vessey MP. A case-control study of the possible association between oral contraceptives and malignant melanomas. Br J Cancer 1981;44:45-50. Autier P, Joarlette M, Lejeune F, Lienard D, Andre J, Achten G. Cutaneous malignant melanoma and exposure to sunlamps and sunbeds: a descriptive study in Belgium. Melanoma Res 1991;1:69-74. Swerdlow AJ, English JSC, MacKie RM, O’Dougherty CJ, Hunter JAA, Clark J, et al. Fluorescent lights, ultraviolet lamps, and risk of cutaneous melanoma. Br Med J 1988;297:647-50.

C. Unanswered questions on the use of sunscreen Cheryl Rosen, MD, FRCPC The ability of sunscreens to reduce sunburn is well established, confirmed by “extensive human experience.”1 It is important, particularly for public education, that although erythema is the end point used in the most standard evaluation of sunscreens, the prevention of sunburn does not equal prevention of all UV radiation–induced effects. It should be remembered that sunscreens are recommended for use as part of a “package” of sun protection strategies, including wearing tightly woven clothing, a hat, seeking shade, and avoiding peak exposure times. Sunscreens should not be used as a means of extending the duration of sun exposure. There are unanswered questions which remain concerning sunscreens. The following will be examined in this section: 1. Prevention/causation of skin cancer 2. Recommendations regarding use in children younger than 6 months of age 3. Actual use of sunscreens 4. Safety of sunscreen compounds 5. Sunscreens and vitamin D metabolism 6. UVA protection 7. Sunscreen protection against immunosuppression 1. Prevention/causation of skin cancer Sunscreens have been shown to prevent the development of actinic keratoses.2,3 Because actinic keratoses are precursors of squamous cell carcinomas, sunscreen use may decrease the risk of developing a squamous cell carcinoma. Certainly, in ani-

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32. Walter SD, Marrett LD, From L, Hertzman C, Shannon HS, Roy P. The association of cutaneous malignant melanoma with the use of sunbeds and sunlamps. Am J Epidemiol 1990;131:23243. 33. Autier P, Dore J-F, Lejeune F, Koelmel KF, Feffeler O, Hille P, et al. Cutaneous malignant melanoma and exposure to sunlamps or sunbeds: an EORTC multicenter case-control study in Belgium, France and Germany. EORTC Melanoma Cooperative Group. Int J Cancer 1994;58:809-13. 34. Westerdahl J, Olsson H, Måsbäck A, Ingvar C, Jonsson N, Brandt L, et al. Use of sunbeds or sunlamps and malignant melanoma in southern Sweden. Am J Epidemiol 1994;140:691-9. 35. Swerdlow AJ, Weinstock MA. Do tanning lamps cause melanoma? An epidemiologic assessment. J Am Acad Dermatol 1998;38:89-98.

mal models, sunscreens have been shown to prevent photocarcinogenesis.4 However, there are no conclusive experimental data in humans that sunscreens have an effect on the development of melanoma or basal cell carcinoma. The relation between sunscreen use and the development of melanoma is difficult to establish in epidemiologic studies for several reasons: 1. Recall of sunscreen use 2.Negative confounding: people who are most sun sensitive are more likely to avoid sun exposure, but to wear sunscreen when they are out in the sun. Excessive sun exposure resulting in repeated sunburns in the past may lead to increased sunscreen use in the present, that is, current sunscreen use may not represent earlier usage [M. Berwick, presentation at the meeting of the American Association for the Advancement of Science, Philadelphia, Pa, February 1998].5,6 3. The question asked: If the study compares people who have never used a sunscreen to “ever having used a sunscreen,” the group of people who have “ever” used a sunscreen will have great variability, including people who have used the product once in a lifetime and those who use it daily. This question does not account for the chronology of sunscreen use (ie, the time at which the person began wearing a sunscreen and the duration of use). 4. Individual sunscreen products vary greatly, with respect to active sunscreening ingredients, sun protection factor (SPF), and substantivity. In Europe, psoralens may have been present in the sunscreen products people had used. People may confuse the names of products and may have been using products to enhance tanning.

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5. These studies were all conducted from 1974 through 1993. The long latency period before the development of melanoma must be considered. Highly effective sunscreens were not available 15 years before diagnosis. Childhood use of sunscreens in the people involved in these studies is unlikely. Vigorous discussions have been held concerning the use of sunscreens as a risk factor for melanoma. In a matched case-control study in Sweden, the authors found a relation between sunscreen use and risk of melanoma, with an odds ratio of 1.8 for “almost always vs never wearing sunscreens.”6 This study did not address sunscreen use in a detailed fashion, asking only “When you spend time out in the sunshine, do you use sunscreens?” This would seem to reflect current sunscreen use, and not past usage. A group of epidemiologic studies has examined this question.6-14 Several have found an increased risk of melanoma associated with the use of sunscreens,6,7,9,10,12 others found a decreased risk,13,14 and others no alteration of risk.8,11 Many of these studies were reviewed in an excellent paper which found that the results were heterogeneous and that it was not possible to derive a conclusion based on metaanalysis.15 In summary, various population-based studies have compared groups of people with melanoma to control groups with respect to sunscreen use, with inconclusive results. It has been stated that the rising incidence of melanoma has paralleled the increased use of sunscreens.16 However, the incidence of melanoma began to increase before the widespread availability of sunscreens. According to the latest report of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, the incidence of cutaneous melanoma in the United States rose by 6% in 1997. One possible explanation for the dramatic increase of melanoma incidence in the United States is to be found in the results of the 1996 survey from the American Academy of Dermatology. The survey showed that of persons who have an average or above average risk of development of melanoma, 30% did not wear sunscreen regularly. Only 19% of the respondents said they actively limit exposure, compared with 23% of people interviewed in 1986. Thirty-nine percent of persons surveyed in 1996, compared with 30% of those surveyed in 1986, reported at least one sunburn the previous summer. In addition, in a National Canadian Survey on Sun Exposure and Protective Behaviours, 47% of people surveyed did not wear sunscreens on the face and 48% did not use sunscreen on the rest of their body.

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To explain the association of sunscreen use and melanoma observed in some studies, several authors have suggested that using a sunscreen allows a person to stay out in the sun for a longer period without burning.16,17 During this period, because sunscreens provide better protection against UVB, there is greater exposure to UVA. However, it should be noted that the action spectrum for induction of human melanoma is not known. In the Xiphophorus fish melanoma model, UVA is highly effective in inducing melanoma.18 In a South American opossum model (Monodelphis domestica), primarily UVBinduced DNA damage was found to be key in melanoma development.19 In human skin transplanted to immunodeficient (RAG-1) mice, melanocytic hyperplasia was induced by long-term UVB radiation.20 Furthermore, recent evidence suggests that the incidence of melanoma in Australia may be decelerating (Australian Institute of Health and Welfare), which does not support an association between sunscreen use and melanoma, because sunscreen use continues to be widely advocated.21 The relation between sunscreen use and melanoma has received substantial coverage in the popular press. A study by Wolf, Donawho, and Kripke22 received significant attention at the time of its publication. This study used a murine model in which melanoma cells are injected into mouse ears after the completion of a series of UVB radiation, and the ability of these melanoma cells to develop into a tumor in the mouse is measured. The group exposed to UV radiation had an enhanced outgrowth of the melanoma cells. Sunscreens were unable to prevent this UV-enhanced outgrowth of melanoma cells.22 This cannot be interpreted to suggest that sunscreens are unable to prevent the occurrence of melanoma, although it was reported as such in the lay press because the model begins with the injection of malignant cells. There was widespread coverage after the presentation by Dr Marianne Berwick at the 1998 meeting of the American Association for the Advancement of Science, where Dr Berwick reviewed the epidemiologic studies that examined the relation between sunscreen use and melanoma (see above). As reviewed earlier in this article, there are significant limitations with epidemiologic studies, which, taken together, showed inconclusive results. In a study investigating the development of nevi in children, children with poor sun tolerance had significantly more nevi, and sunscreen use appeared to be associated with an increased number of nevi.23 However, it should be noted that sunscreen use was not found to be a factor on multivariate analysis. A more recent study has also examined this question.24

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2. Recommendations regarding use in children younger than 6 months of age Recommendations at the present time suggest that sunscreens should not be used on infants younger than 6 months of age. There does not appear to be scientific evidence to support this recommendation, apart from a concern that babies may not be able to properly metabolize these compounds. However, until children can move independently, it seems prudent to keep them out of the sun and to rely on clothing and sun avoidance. 3. Actual use of sunscreens The actual use of sunscreens has been studied. The protection provided by a sunscreen depends greatly on the ways in which they are applied and on the activities pursued after application.25 It appears that people do not apply as much sunscreen as is used in most testing protocols and thus may not be receiving as much protection as the SPF value would indicate.26,27 In a study of 808 persons at a beach in Denmark, 46% wore sunscreen; 0.5 mg/cm2 was applied, far less than the amount recommended by the Food and Drug Administration (2 mg/cm2, or 2 µL/cm2).27 With the use of a thinner layer of sunscreen, the calculated SPF was lower than the SPF on the product label. In an in vitro model using excised human skin, the thickness of application of a titanium dioxide–based sunscreen also affected the value of the SPF.28 For a product labeled SPF 25, with the application of 1.3 mg/cm2, the mean SPF was 9.6 ± 1.1, compared with 22.6 ± 3.3 with a thickness of 2 mg/cm2.28 The amount of sunscreen applied to the skin appears to be related to the type of sunscreen used.25 Persons apply two thirds the quantity of a physical sunscreen compared with a chemical sunscreen with the same SPF.25 It has been recommended by some authors that SPF testing use the amount of sunscreen that has been found to be used by the general public, to obtain a realistic SPF value.27 In a letter to the editor, Diffey29 reports that to apply 2 µl/cm2 of sunscreen to the entire skin surface of an adult with a typical surface area of 1.73 m2, 35 mL of sunscreen would be required. This is approximately one third to one fourth of the volume of a typical sunscreen container. In a study of 10 “fair-skinned” human volunteers, PABA provided greater protection against erythema 2 hours after application than when UV exposure occurred immediately after application.30 With o-PABA (2-ethylhexyl p-dimethyl aminobenzoate), there was no difference in protection whether the o-PABA was applied immediately or 2 hours before UV exposure.30 It is often stated that sunscreens should be applied 20 minutes before outdoor exposure, so

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there would be sufficient time for absorption into the skin. This recommendation is often part of consumer education regarding sunscreen use, although there is no evidence to suggest that newer sunscreen formulations are not as protective against erythema if applied immediately or 5 to 10 minutes before sun exposure. 4. Safety of sunscreen compounds: Mutagenicity, photochemistry There is no study to date showing that sunscreens are carcinogenic. However, chemical sunscreen compounds (also known as organic sunscreens) do absorb UV radiation. They then are in an excited state and must reenter the ground state by dissipating the absorbed energy by one of several processes. This energy is probably mostly dissipated harmlessly, but it is possible that the energy may be be involved in chemical reactions in the skin. The energy may be dissipated by fluorescence, phosphorescence, selfquenching, or heat.31 The compounds may also undergo photofragmentation and photoisomerization or may transfer the energy to other molecules, including oxygen. Reactive oxygen species and other photoproducts may be formed. These highly reactive species could possibly react with a variety of cellular components, including DNA. The photochemistry of sunscreening compounds has been well reviewed.31-33 The physical blockers (also referred to as inorganic sunscreens) titanium dioxide and zinc oxide are semiconductors and for this reason are able to absorb UV radiation as well as act as scattering agents. They have been demonstrated to improve the survival of organic sunscreens in vitro after UV exposure.33 However, as illustrated below, it is clear that further work is required to learn more about the photochemistry of sunscreen compounds, particularily concerning their interaction with human skin. There is a concern that Parsol 1789 is photolabile. Deflandre and Lang34 reported a 36% reduction in the absorbance capacity of Parsol 1789 within 15 minutes of UV radiation exposure. More recently, in work published to date in abstract form, photodegradation of Parsol 1789 was documented in an in vitro assay, with some sunscreen formulations losing up to 50% of their UV blocking ability.35,36 Oxybenzone was found to undergo photooxidation in an in vitro model and on human skin.37 It was also found to be systemically absorbed in a study that measured oxybenzone and its metabolites in the urine of human volunteers.38 The volunteers were exposed to 12.4 mg/cm2 of a commercial sunscreen on both forearms. This amount is 6 times the amount used in standard SPF assessment. Over a 12-

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hour period of exposure, 1% to 2% of the applied oxybenzone was absorbed and excreted in urine. In a study of excised human skin, significant absorption (approximately 39%) of PABA into the epidermis was detected, whereas very little octyl dimethyl PABA was absorbed (approximately 3%).30 In vitro mutagenicity assays have shown that octyl dimethyl PABA is photomutagenic in a yeast system.39 In this same assay, dibenzoylmethane was also toxic. Parsol 1789, although chemically related to dibenzoylmethane, was not tested. Knowland et al39 make a distinction between a film of sunscreen on the surface of the skin and the effect of sunscreen compounds which might penetrate into the skin and have contact with viable keratinocytes. 2-Ethylhexylp-methoxycinnamate (EHMC) has been found to be weakly mutagenic in Ames testing.40 The relevance of these in vitro studies to human use is unclear. The structural and biochemical features, particularly the multilayered nature of the epidermis, are reviewed by Naylor and Farmer,40 who suggest that the genotoxic species, including reactive oxygen species, would be at a distance from the basal cell layer, the important target for mutagenesis and carcinogenesis. 5. Sunscreens and vitamin D metabolism Questions have been raised concerning the ability of vitamin D to prevent melanoma. In an attempt to answer this, a case-control study examined dietary vitamin D intake and melanoma risk.41 There was no association of melanoma risk with vitamin D intake. Several studies have examined the vitamin D metabolism in patients using sunscreens on an ongoing basis. In one study in the United States, long-term PABA-treated patients had a lower mean level of 25-hydroxyvitamin D (25-OHD); however, it was still within normal limits.42 Two persons in the sunscreen group did have 25-OHD levels below the normal limit. In an Australian randomized doubleblind control trial, in which patients wore sunscreen or placebo for 7 months, the mean levels of 25-OHD were the same in both placebo and sunscreen users.43 No person was found to have abnormal vitamin D levels. In a study of 8 patients with xeroderma pigmentosum who practiced intensive sun protection, low normal levels of serum 25-OHD, with normal levels of the active metabolite, 1,25-(OH)2D3, calcium and parathyroid hormone were found.44 Thus, by diet alone, which was not noted to contain vitamin D supplements, normal vitamin D levels were maintained over a 6-year period. 6. UVA protection Sunscreens were initially developed with UVB-

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absorbing compounds. Over time, substances that can absorb UVA have been added; sunscreens with SPF 8 or higher do contain UVA absorbers. Sunscreens are generally better at absorbing UVB radiation. Although the newer formulations do have compounds that absorb further in the UVA spectrum, such as Parsol 1789, the entire UVA spectrum is not absorbed. There is much concern that people, protected against sunburning, will stay out longer in the sun and be exposed to far greater amounts of UVA. This concern is particularly relevant in the context of the photocarcinogenicity of UVA. To measure the effectiveness of sunscreen products to protect skin from the effects of UVA, a variety of testing methods have been developed. As the lower erythemogenic ability of UVA leads to practical problems such as length of exposure time required, alternatives to UVA-induced erythema have been developed. Protocols have chosen a variety of end points, including erythema, immediate pigment darkening, delayed tanning, inhibition of tritiated thymidine incorporation to evaluate sunscreen efficacy in blocking UVA effects.45-47 In some studies, the skin is pretreated with UVA photosensitizers (psoralen, anthracene) to lower the threshold of UVA to produce erythema.48,49 It may be problematic to use photosensitizers because an exaggerated protection factor may be obtained when the absorption spectrum of the sunscreen coincides with the action spectrum of the sensitizer.50 In other studies, nonsensitized erythema and pigmentation has been used as the endpoint in an animal model and in human volunteers.45,46,49,51 One study has used a population of photosensitive patients, with erythropoietic protoporphyria and chronic actinic dermatitis, to evaluate sunscreen efficacy against UVB, UVA, and visible light.52 Currently, there is no standard method for assessing the protection provided against UVA. The consumer must look for the words “broad spectrum” or “UVB and UVA protection” or check the list of ingredients for the presence of both UVB and UVA protective compounds. 7. Sunscreen protection against immunosuppression The extent to which sunscreeens protect against UV-induced immunosuppression remains unresolved. It is important to remember that the action spectra for different UV-induced end points may differ and in many cases are not known. Sunscreen products may have different absorption spectra because of their particular combination of active sunscreeening compounds and the composition of the vehicle. This will alter the spectral characteristics of the radiation entering the skin and may result in a

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particular sunscreen product being better able to attenuate one, but not another, end point.53 In hairless albino mice, a sunscreen containing octyldimethyl PABA and a benzophenone, with an SPF 15, was not able to prevent suppression of contact hypersensitivity and the induction of susceptibility to transplanted UV-induced tumor cells, whereas a product containing EHMC and benzophenone with the same SPF did provide protection against these effects.54 In another study, neither combination prevented the UV-induced inhibition of contact sensitization, although both prevented UVB-induced decrease in the number of Langerhans cells.55 Although sunscreens containing PABA-ester and a benzophenone were able to inhibit the immediate histologic changes after UVB exposure, they were not able to block the induction of tolerance to UV-induced tumors.56 Sunscreens containing octyldimethyl PABA, EHMC, and benzophenone provided greater protection against UV-induced edema and cyclobutane pyrimidine dimer formation than immunosuppression, as studied in a murine model using delayed-type hypersensitivity against Candida albicans and contact hypersensitivity to dinitrofluorobenzene (DNFB).57,58 Again in a murine model, using FS20 sunlamps with a Kodacel filter to remove UVC, commercial sunscreen products were able to prevent UVB-induced immune suppression of DNFB contact hypersensitivity.59 Sunscreens containing 7.5% EHMC and 8% octylPABA or 6% benzophenone-3 were able to substantially diminish the depletion of dendritic cells in the epidermis and prevented the UV-induced suppression of contact hypersensitivity to DNFB in a murine model.60 In a study using human volunteers, an SPF 29 sunscreen containing octyl methoxycinnamate, oxybenzone, and octyl salicylate was able to prevent UVB-induced suppression of contact hypersensitivity to dinitrochlorobenzene.61 In humans, sunscreen preparations containing EHMC and oxybenzone were able to prevent the UV inhibition of contact hypersensitivity to nickel.62 Summary Sunscreens are an important component of sun protection strategies, which should also include wearing tightly woven clothing, a hat, seeking shade, and avoiding peak exposure time. This was reviewed in a recent editorial.63 Sunscreen should not be used to prolong duration of sun exposure. Further studies are clearly required to resolve the many unanswered questions in the use of sunscreens. REFERENCES 1. International Agency for Research on Cancer. World Health Organization. Solar and ultraviolet radiation. IARC Monographs

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on the Evaluation of Carcinogenic Risks to Humans. 1992;55(Appendix 1):285-90. Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by regular sunscreen use. N Engl J Med 1993;329:1147-51. Naylor MF, Boyd A, Smith DW, Cameron GS, Hubbard D, Neldner KH. High sun protection factor sunscreens in the suppression of actinic neoplasia. Arch Dermatol 1995;131:170-5. Kligman LH, Akin FJ, Kligman AM. Sunscreens prevent ultraviolet photocarcinogenesis. J Am Acad Dermatol 1980;3:30-5. Berwick M. UV and melanoma: the sunscreen perspective [abstract]. Photochem Photobiol 1998;68:2s. Westerdahl J, Olsson H, Masback A, Ingvar C, Jonsson N. Is the use of sunscreens a risk factor for malignant melanoma? Melanoma Res 1995;5:59-65. Beitner H, Norell SE, Ringborg U, Wennersten G, Mattson B. Malignant melanoma: aetiological importance of individual pigmentation and sun exposure. Br J Dermatol 1990;122:43-51. Osterlind A, Tucker MA, Stone BJ, Jensen OM. The Danish casecontrol study of cutaneous melanoma. II. Importance of UVlight exposure. Int J Cancer 1988;42:319-24. Klepp O, Magnus K. Some environmental and bodily characteristics of melanoma patients: a case-control study. Int J Cancer 1979;23:482-6. Autier P, Dore J-F, Schifflers E, Cesarini JP, Bollaerts A, Koelmel KF, et al. Melanoma and use of sunscreens: an EORTC case-control study in Germany, Belgium and France. The EORTC Melanoma Cooperative Group. Int J Cancer 1995;61:749-55. Holman CDJ, Armstrong BK, Heenan PJ. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. J Natl Cancer Inst 1986;76:403-14. Graham S, Marshall J, Haughey B, Stoll H, Zielezny M, Brasure J, et al. An inquiry into the epidemiology of melanoma. Am J Epidemiol 1985;122:606-19. Holly EA, Aston DA, Cress RD, Ahn DK, Kristiansen JJ. Cutaneous melanoma in women. 1. Exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light. Am J Epidemiol 1995;141:923-33. Rodenas JM, Delgado-Rodriguez M, Herranz M, Tercedor J, Serrano S. Sun exposure, pigmentary traits, and risk of cutaneous malignant melanoma: a case-control study in a Mediterranean population. Cancer Causes Control 1996;7:27583. Wille L, Gefeller O, Kolmel KF. Sunscreens in melanoma protection: pros and cons. In: Altmeyer P, Hoffman K, Stucker M, editors. Skin cancer and UV radiation. Berlin: Springer-Verlag; 1997. p. 343-56. Garland CF, Garland FC, Gorham ED. Could sunscreens increase melanoma risk? Am J Public Health 1992;82:614-5. Autier P, Dore J-F, Renard F, Luther H, Cattaruzza MS, Gefeller O, et al. Melanoma and sunscreen use: need for studies representative of actual behaviours. Melanoma Res 1997;7(suppl 2):S115-S120. Setlow RB, Grist E, Thompson K, Woodhead AD. Wavelengths effective in induction of malignant melanoma. Proc Natl Acad Sci U S A 1993;90:6666-70. Ley RD, Applegate LA, Padilla RS, Stuart TD. Ultraviolet radiationinduced malignant melanoma in Monodelphis domestica. Photochem Photobiol 1989;50:1-5. Atillasoy ES, Seykora JT, Soballe PW, Elenitsas R, Nesbit M, Elder DE, et al. UVB induces atypical melanocytic lesions and melanoma in human skin. Am J Pathol 1998; 152:1179-86. Naylor M, Farmer K. In reply: the case for sunscreen revisited. Arch Dermatol 1998;134:510-1. Wolf P, Donawho CK, Kripke ML. Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in mice. J Natl Cancer Inst 1994;86:99-105.

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23. Autier P, Dore J-F, Luther H. The case for sunscreens revisited. Arch Dermatol 1998;134:509-19. 24. Autier P, Dore J-F, Cattaruzza MS, Renard F, Luther H, GentiloniSilverj F, et al. Sunscreen use, wearing clothes, and number of nevi in 6- to 7-year-old European children. J Natl Cancer Inst 1998;90:1873-80. 25. Diffey BL, Grice J.The influence of sunscreen type on photoprotection. Br J Dermatol 1997;137:103-5. 26. Stenberg C, Larko O. Sunscreen application and its importance for the Sun Protection Factor. Arch Dermatol 1985;121:1400-2. 27. Wulf H-C, Stender I-M, Lock-Andersen J. Sunscreens used at the beach do not protect against erythema: a new definition of SPF is proposed. Photoderm Photoimmunol Photomed 1997;13: 129-32. 28. Stokes R, Diffey B. How well are sunscreen users protected? Photoderm Photoimmunol Photomed 1997;13:186-8. 29. Diffey BL. Sunscreens, suntans and skin cancer: people do not apply enough sunscreen for protection [letter]. Br Med J 1996;313:942. 30. Blank IH, Cohen JH, Anderson RR, Jaenicke KF, Parrish JA. Observations on the mechanism of the protective action of sunscreens. J Invest Dermatol 1982;78:381-5. 31. Martincigh BS, Allen JM, Allen SK. Sunscreens: the molecules and their photochemistry. In: Gasparro FP, editor. Sunscreen photobiology. Berlin: Springer-Verlag; 1997. p. 11-45. 32. Knowland J, McHugh PJ, Dunford R. The photochemical potential of some sunscreens to damage DNA. In: Gasparro, FP, editor. Sunscreen photobiology. Berlin: Springer-Verlag; 1997. p. 47-61. 33. Gasparro FP, Mitchnick M, Nash JF. A review of sunscreen safety and efficacy. Photochem Photobiol 1998;68:243-56. 34. Deflandre A, Lang G. Photostability assessment of sunscreens: benzylidene camphor and dibenzoylmethane derivatives. Int J Cosmet Sci 1988;10:53-62. 35. Sayre RM, Dowdy J. Avobenzone and the photostability of sunscreen products [abstract]. Photoderm Photoimmunol Photomed 1998;14:38. 36. Sayre RM, Dowdy JC, Sayre DL. Photoinstability of avobenzone containing sunscreen products [abstract]. Photochem Photobiol 1998;67:20s-1s. 37. Schallreuter KU, Wood JM, Farwell DW, Moore J, Edwards HGM. Oxybenzone oxidation following solar irradiation of skin: photoprotection versus antioxidant inactivation. J Invest Dermatol 1996;106:583-6. 38. Hayden CGJ, Roberts MS, Benson HAE. Systemic absorption of sunscreen after topical application. Lancet 1997;350:863-4. 39. Knowland J, McKenzie EA, McHugh PJ, Cridland NA. Sunlightinduced mutagenicity of a common sunscreen ingredient. FEBS Lett 1993;324:309-13. 40. Naylor MF, Farmer KC. The case for sunscreens. Arch Dermatol 1997;133:1146-54. 41. Weinstock MA, Stampfer MJ, Lew RA,Willett WC, Sober AJ. Casecontrol study of melanoma and dietary vitamin D: implications for advocacy of sun protection. J Invest Dermatol 1992;98:80911. 42. Matsuoka LY, Wortsman J, Hanifan N, Holick MF. Chronic sunscreen use decreases circulating concentrations of 25-hydroxyvitamin D. Arch Dermatol 1988;124:1802-4. 43. Marks R, Foley PA, Jolley D, Knight KR, Harrison J, Thompson SC. The effect of regular sunscreen use on vitamin D levels in an Australian population. Arch Dermatol 1995;131:415-21. 44. Sollitto RB, Kraemer KH, DiGiovanna JJ. Normal vitamin D levels can be maintained despite rigorous photoprotection: six years’ experience with xeroderma pigmentosum. J Am Acad Dermatol 1997;37:942-7.

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45. Chew S, DeLeo VA, Harber LC. An animal model for evaluation of topical photoprotection against ultraviolet A (320380 nm) radiation. J Invest Dermatol 1987;89:410-4. 46. Cole C, van Fossen R. Measurement of sunscreen UVA protection: an unsensitized human model. J Am Acad Dermatol 1992;26:178-84. 47. Kaidbey KH, Barnes A. Determination of UVA protection factors by means of immediate pigment darkening in normal skin. J Am Acad Dermatol 1991;25:262-6. 48. Jarratt M, Hill M, Smiles K. Topical protection against long-wave ultraviolet A. J Am Acad Dermatol 1983;9:354-60. 49. Roelandts R.Which components in broad-spectrum sunscreens are most necessary for adequate UVA protection? J Am Acad Dermatol 1991;25:999-1004. 50. Urbach F, Cole CA. Effects of light source and photosensitizer on predicted protection factors of UVA sunscreens [abstract]. Photochem Photobiol 1986;43(suppl):86s. 51. Kaidbey K, Gange RW. Comparison of methods for assessing photoprotection against ultraviolet A in vivo. J Am Acad Dermatol 1987;16:346-53. 52. Diffey BL, Farr PM. Sunscreen protection against UVB, UVA and blue light: an in vivo and in vitro comparison. Br J Dermatol 1991;124:258-63. 53. Walker SL,Young AR. Sunscreens offer the same UVB protection factors for inflammation and immunosuppression in the mouse. J Invest Dermatol 1997;108:133-8. 54. Reeve VE, Bosnic M, Boehm-Wilcox C, Ley RD. Differential protection by two sunscreens from UV radiation-induced immunosuppression. J Invest Dermatol 1981;97:624-8. 55. Ho KK-L, Halliday GM, Barnetson RStC. Sunscreens protect epidermal Langerhans cells and Thy- 1+ cells but not local contact sensitization from the effects of ultraviolet light. J Invest Dermatol 1992;98:720-4. 56. Gurish MF, Roberts LK, Krueger GG, Daynes RA.The effect of various sunscreen agents on skin damage and the induction of tumor susceptibility in mice subjected to ultraviolet irradiation. J Invest Dermatol 1981;76:246-51. 57. Wolf P, Yarosh DB, Kripke ML. Effects of sunscreens and a DNA excision repair enzyme on ultraviolet radiation-induced inflammation, immune suppression, and cyclobutane pyrimidine dimer formation in mice. J Invest Dermatol 1993;101:523-7. 58. Wolf P, Donawho CK, Kripke ML. Analysis of the protective effect of different sunscreens on ultraviolet radiation-induced local and systemic suppression of contact hypersensitivity and inflammatory responses in mice. J Invest Dermatol 1993;100: 254-9. 59. Roberts LK, Beasley DG. Commercial sunscreen lotions prevent ultraviolet-radiation-induced immune suppression of contact hypersensitivity. J Invest Dermatol 1995;105:339-44. 60. Wolf P, Cox P, Yarosh DB, Kripke ML. Sunscreens and T4N5 liposomes differ in their ability to protect against ultravioletinduced sunburn cell formation, alterations of dendritic epidermal cells and local suppression of contact hypersensitivity. J Invest Dermatol 1995;104:287-92. 61. Whitmore SE, Morison WL. Prevention of UVB-induced immunosuppression in humans by a high Sun Protection Factor sunscreen. Arch Dermatol 1995;131:1128-33. 62. Damian DL, Halliday GM, Barnetson RStC. Broad-spectrum sunscreens provide greater protection against ultraviolet-radiation-induced suppression of contact hypersensitivity to a recall antigen in humans. J Invest Dermatol 1997; 109:146-151 63. Turner M. Sun safety: avoiding noonday sun, wearing protective clothing, and the use of sunscreen. J Natl Cancer Inst 1998;90: 1854-5.

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D. Increased incidence of melanoma: Real or epiphenomenon? Jason K. Rivers, MD, FRCPC In many countries the incidence rate for melanoma has increased steadily for several decades.1-5 Moreover, there is some suggestion that melanoma may be the most rapidly increasing cancer in white populations.1 Because of this, melanoma has become a major public health problem. As such, awareness of melanoma has increased in recent years because of the concerted efforts of public health campaigns in several countries.6-8 However, there is concern being voiced that the apparent increased incidence of melanoma may be due in part to aggressive screening itself and that more screening may lead to a further artifactual increase in incidence rates.9 There are other concerns, too. Although the incidence of melanoma appears to be increasing at an alarming rate, melanoma-specific mortality has risen at a lesser pace, which suggests that other factors may be at play to explain the current increase in incidence of melanoma. These issues are discussed in order below. Issues to be answered 1. Increasing incidence rate without an accompanying increase in mortality rate There is little doubt that the reported incidence of melanoma has increased at a steady rate in many countries around the globe for several years. However, the incidence of melanoma has now stopped rising in many populations of European origin and in some has even begun to fall.1,10 One of the major concerns in evaluating melanoma incidence trends is whether the increases may be a consequence of greater public awareness. If this were the case, then the increase should be reflected in thin melanomas exclusively. However, both North American and Australian data have shown an increased incidence of thicker lesions, especially in men, suggesting that the increased incidence of melanoma is real.3,11,12 Recent trends in mortality indicate that death rates from melanoma may be approaching their zenith. In the United States, birth cohort analyses indicate that mortality rates have declined for women born since the early 1930s and in men born since 1950.13 Because the effective treatment of advanced melanoma has not changed over the past few decades, this flattening of the mortality curve is thought to be related to the earlier detection of melanomas with consequent effective surgery. It has been suggested that the lifetime risk of development of invasive melanoma is 1 in 105 for

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Americans born in 1993, and that with current incidence rates, 1 of every 75 people in the United States will be at risk of the development of melanoma during their lifetime.5 However, this projection may be an overestimation given that the incidence of melanoma may be leveling off in younger birth cohorts.14 Further confirmation of this is required, particularly because several investigators have in the past revealed an underascertainment of melanoma.15,16 2. Improved registration of diagnosed melanoma In the United States, cancer registry data has been shown to under-report melanoma between 2% and more than 20% of cases,15,16 and in many places, in situ melanoma is not recorded at all. The underreporting is partly because the diagnosis and management of melanomas are mostly done in outpatient facilities, which are not included in many cancer registry data. Furthermore, although melanoma incidence was increasing, no change in ascertainment of melanoma was observed in a populationbased cancer registry in Australia, both during and after a period when intense incidence ascertainment efforts were in place.3 Therefore it is unlikely that improved melanoma registration explains the increased melanoma incidence that has been observed worldwide. 3. Changes in the criteria used to diagnose melanoma The histologic criteria used to diagnose melanoma have probably not changed significantly over the past several decades, as determined by a review of pathologic material by van der Esch et al.17 Other findings in populations with increasing incidence rates support the same conclusions.3,18 However, others9 point out that although diagnostic criteria may not have changed, pathologists may have more recently augmented the sensitivity of their histologic examination to diagnose melanomas at an earlier stage, thereby potentially compromising diagnostic specificity. 4. An increase in the number of melanocytic nevi being submitted for histology with ensuing earlier diagnosis In one population with an increasing melanoma incidence, there was no evidence of a change in medical practice over a 4-year period in the number of skin lesions being submitted for histologic examination.3 However, during the year after an Australian television program on melanoma aired, the incidence of melanoma increased by more than 150% and the number of skin biopsies performed tripled.9 Similar findings have been observed in other countries where public health campaigns have been initiated.9,19 If, overall, the increased excision of pig-

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mented lesions has been responsible for the rise in melanoma incidence, then we should be observing a rise in the diagnosis of thin melanoma with a corresponding decrease in the proportion of thick lesions being diagnosed. This does not appear to be happening. Studies that have analyzed incidence and tumor thickness have shown the number of thick lesions has not decreased significantly.9,20 Furthermore, Burton et al20 have clearly pointed out that, in a stable population from New South Wales Australia, if early diagnosis as a result of a public education campaign held in 1987 and 1988 was the only reason for the increase in melanoma incidence in that population, then the incidence would have fallen to zero for the 5 years between 1993 and 1997. Because the total incidence has not been observed to fall in that population, it is unlikely that a “harvesting effect” completely explains the observed increase in incidence in that group. 5. The detection of a low-risk, nonmetastasizing form of melanoma It has been proposed that another explanation for the sharp rise in melanoma incidence is due to the detection of a form of the disease that is slow growing and has little or no propensity to metastasize.3,20 However, up to 5% of thin melanomas (< 0.75 mm in Breslow thickness) may metastasize; therefore this hypothesis is not able to be tested for obvious ethical reasons. Summary After consideration of the factors that could influence the incidence of melanoma, the observed increase in melanoma incidence rates is real and not just an epiphenomenon. Sunlight has been implicated as the major environmental factor for the development of melanoma.21 If, as noted above, the melanoma increase is real, and other possible explanations have been dismissed, a change in the prevalence of the major risk factor is the likely explanation for the increase. If sunlight-related behavior changed markedly in cohorts reaching adolescence and adulthood around World War II, with increasing exposure to high intensity solar UV radiation, this might account for much of the increased incidence. It is hoped that with the widespread adoption of “sunsafe” behavior in recent birth cohorts, the most recent trends of decreasing melanoma incidence and mortality will continue. REFERENCES 1. Armstrong BK, Kricker A. Cutaneous melanoma. Cancer Surveys 1994;19:219-39.

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2. Armstrong BK. Epidemiology of malignant melanoma: Intermittent or total accumulated exposure to the sun? J Dermatol Surg Oncol 1988;14:835-49. 3. Burton RC, Coates MS, Hersey P, Roberts C, Chetty MP, Chen S, et al. An analysis of a melanoma epidemic. Int J Cancer 1993;55:765-70. 4. Franceschi S, La Vecchia C, Lucchini F, Cristofolini M. The epidemiology of cutaneous malignant melanoma: aetiology and European data. Eur J Cancer Prev 1991;1:9-22. 5. Gloster HM Jr, Brodland DG. The epidemiology of skin cancer. Dermatol Surg 1996;22:217-26. 6. Marks R. Skin cancer control in Australia: the balance between primary prevention and early detection. Arch Dermatol 1995;131:474-8. 7. MacKie RM, Hole D. Audit of public education campaign to encourage earlier detection of malignant melanoma. BMJ 1992;304:1012-5. 8. Rivers JK, Gallagher RP. Public education projects in skin cancer: experience of the Canadian Dermatology Association. Cancer 1995;75:661-6. 9. Swerlick RA, Chen S. The melanoma epidemic: More apparent than real? Mayo Clin Proc 1997;72:559-64. 10. Armstrong BK. The epidemiology of melanoma worldwide. Melanoma Res 1997;7(supp 1):S1. 11. Gallagher RP, Elwood M. Recent programs in the epidemiology of malignant melanoma. In: Gallagher RP, Elwood JM, editors. Epidemiological aspects of cutaneous malignant melanoma. Boston: Kluwer Academic Publications; 1994. p. 3-12. 12. MacLennan R, Green AC, McLeod GRC, Martin NG. Increasing incidence of cutaneous melanoma in Queensland, Australia. J Natl Cancer Inst 1992;84:1427-32. 13. Roush GC, McKay L, Holford T. A reversal in the long-term increase in deaths attributable to malignant melanoma. Cancer 1992;69:1714-20. 14. Gallagher RP, Phillips N, Coldman AJ, McLean, DI. In: Altmeyer P, Hoffman K, Sturker M, editors. Skin cancer and UV radiation. New York: Springer-Verlag; 1997. p. 501-6. 15. Karagas MR, Thomas DB, Roth GJ, Johnson LK, Weiss NS. The effects of changes in health care delivery on the reported incidence of cutaneous melanoma in western Washington State. Am J Epidemiol 1991;133:58-62. 16. Koh HK, Geller A, Miller DR, Clapp RW, Lew RA. Underreporting of cutaneous melanoma in cancer registries nationwide. J Am Acad Dermatol 1992;27:1035-6. 17. van der Esch EP, Muir CS, Nectoux J, Macfarlane G, Maisonneuve P, Bharucha H, et al. Temporal change in diagnostic criteria as a cause of the increase of malignant melanoma over time is unlikely. Int J Cancer 1991;47:483-90. 18. MacKie R, Hunter JAA, Aitchison TC, Hole D, Mclaren K, Rankin R, et al. Cutaneous malignant melanoma, Scotland, 1979-89. Lancet 1992;338:971-5. 19. Melia J, Cooper EJ, Frost T, Graham-Brown R, Hunter J, Marsden A, et al. Cancer Research Campaign health education programme to promote the early detection of cutaneous melanoma I: work-load and referral patterns. Br J Dermatol 1995;132:405-13. 20. Burton RC, Armstrong BK. Current melanoma epidemic: A nonmetastasizing form of melanoma? World J Surg 1995;19:330-3. 21. Armstrong BK, Kricker A. How much melanoma is caused by sun exposure? Melanoma Res 1993;3:395-401.

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II. PREVENTION A. Prevention strategies Henry W. Lim, MD, and Wilma Bergfeld, MD Sun and skin cancer It is well established that nonmelanoma skin cancer is associated with cumulative sun exposure.1-3 The correlation between sun exposure and melanoma is not a linear one.4 Skin color, tendency to burn rather than tan,5-7 number of weeks spent on holiday at the beach,8 and increased number of melanocytic nevi (which are associated with increased sun exposure)9-11 are known risk factors for melanoma. However, persons who work indoors have a higher incidence of melanoma as compared with those who work outdoors, suggesting that intermittent rather than long-term sun exposure is closely linked with melanoma development.4 Childhood sun exposure is strongly associated with increased numbers of melanocytic nevi, a known risk factor for melanoma.9,12,13 History of sunburns during childhood is associated with an increased risk of melanoma.8,14,15 Therefore any prevention strategies msut address the issue of sun exposure in adults as well as in children. Prevention strategies Primary prevention consists of reduction of sun exposure.16 At the American Academy of Dermatology and Centers for Disease Control and Prevention Consensus Conference,17 the following recommendations were developed: A. Limit exposure to UV radiation, especially between 10 AM and 4 PM; B. Wear protective clothing and sunglasses; C. Use sunscreens (SPF-15 or higher) including SPF lip balms; D. Avoid artificial tanning devices; E. For children younger than 6 months of age, use of hats, clothing, and shading, rather than sunscreen; F. Encourage children to practice the shadow rule: Seek shade when your shadow is shorter than you are tall. Provision of shady areas and preservation of the ozone layer should contribute to primary prevention of skin cancer.16 Education of children should begin as early as 3 years of age; parental behavior is one of the earliest “teachers.”18 Education messages should be tailored to account for culture, ethnicity, gender, and age; partnership with media is essential as TV and movies are the single most powerful communicator for children. Secondary prevention consists of early detection of skin cancer.16 A critical component of the educa-

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tional message is that skin cancer is the most prevalent cancer, and it is curable if detected early.18 Skin awareness and self-examination allow the detection of early, easily treatable skin cancers with very high rates of cure. The public needs to be educated on the warning signs of melanoma and nonmelanoma skin cancer, which include the ABCD rule of melanoma (asymmetry, border irregularity, varied color, and diameter greater than 6 mm), and the need to have physicians evaluate any new and persistent skin marks or changes in a skin mark.18-20 Partnership with media, physician-based education of patients, other health professionals, and health and beauty service providers are integral components of secondary prevention.18 REFERENCES 1. Giles G, Marks R, Foley P. Incidence of non-melanocytic skin cancer treated in Australia. Br Med J 1988;296:13-7. 2. Vitasa BC, Taylor HR, Strickland PT, Rosenthal FS, West S, Abbey H, et al. Association of nonmelanoma skin cancer and actinic keratosis with cumulative solar ultraviolet exposure in Maryland watermen. Cancer 1990;65:2811-7. 3. Miller SJ. Biology of basal cell carcinoma (Part I). J Am Acad Dermatol 1991;24:1-13. 4. Weinstock MA. Controversies in the role of sunlight in the pathogenesis of cutaneous melanoma. Photochem Photobiol 1996;63:406-10. 5. Dubin N, Mosseson M, Pasternack BS. Sun exposure and malignant melanoma among susceptible individuals. Environ Health Perspect 1989;81:139-51. 6. Weinstock MA, Colditz GA, Gillett WC, Stampfer MJ, Bronstein BR, Mihm MC, et al. Melanoma and the sun: the effect of swim suits and a “healthy” tan on the risk of nonfamilial malignant melanoma in women. Am J Epidemiol 1991;134:462-70. 7. Nelemans PJ, Gronendal H, Kiemeney LA, Rampen FH, Ruiter DJ, Verbeek AL. Effect of intermittent exposure to sunlight on melanoma risk among indoor workers and sun-sensitive individuals. Environ Health Perspect 1993;101:252-5. 8. Zanetti R, Franceschi S, Rosso S, Colonna S, Bidoli E. Cutaneous melanoma and sunburns in childhood in a southern European population. Eur J Cancer 1992;28A:1172-6. 9. Harrison SL, MacLennan R, Speare R, Wronski I. Sun exposure and melanocytic nevi in young Australian children. Lancet 1994;344:1529-32. 10. Grob JJ, Gouvernet J, Aymar D, Mostaque A, Romano MH, Collet AM, et al. Count of benign melanocytic nevi as a major indicator of risk for nonfamilial nodular and superficial spreading melanoma. Cancer 1990;66:387-95. 11. Augustsson A, Stierner R, Rosdahl I, Suukkulla M. Common and dysplastic nevi as risk factor for cutaneous malignant melanoma in a Swedish population. Acta Derm Venereol (Stockh) 1991;71:518-24. 12. Green A, Siskind V, Hansen ME, Hanson L, Leech P. Melanocytic nevi in schoolchildren in Queensland. J Am Acad Dermatol 1989;20:1054-60. 13. Fritschi L, McHenry P, Green A, MacKie R, Green L, Siskind V. Nevi in shcoolchildren in Scotland and Australia. Br J Dermatol 1994;130:599-603. 14. Cress RD, Holly EA, Ahn DK. Cutaneous melanoma in women. V. Characteristics of those who tan and those who burn when exposed to summer sun. Epidemiology 1995;6:538-43.

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15. Holly EA, Aston DA, Cross RD, Ahn DK, Kristiansen JJ. Cutaneous melanoma in women. I. Exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light. Am J Epidemiol 1995;141:923-33. 16. Koh HK, Geller AC, Miller DR, Grossbart TA, Lew RA. Prevention and early detection strategies for melanoma and skin cancer: current status. Arch Dermatol 1996;132:436-33. 17. Goldsmith L, Koh HK, Bewerse B, Reilley B, Wyatt S, Bergfeld W, et al. Proceedings from the national conference to develop a national skin cancer agenda: American Academy of Dermatology and Centers for Disease Control and Prevention, April 8-10, 1995. J Am Acad Dermatol 1996;34:822-3.

18. Bergfeld WF, Farris PK, Wyatt SW, Reilley B, Bewerse BA, Koh HK. Executive summary of the national Partners in Prevention Skin Cancer Conference: American Academy of Dermatology and Centers for Disease Control and Prevention. J Am Acad Dermatol 1997;36:798-801. 19. Koh HK. Cutaneous melanoma. N Engl J Med 1991;325:171-82. 20. Friedman RJ, Rigel DS, Silverman MK, Kopf AW, Vossaert KA. Malignant melanoma in the 1990’s: the continued importance of early detection and the role of physician examination and self-examination of the skin. CA Cancer J Clin 1991;41:201-26.

B. Public messages Alvin James Miller, Sandra Gordon, Paul Gross, Kevin Cooper, MD, Allan Eustis, Thomas Downham, MD, Howard Koh, MD and Drusilla Hufford, MBA

ozone/index.html). In addition to the daily UV Index forecast, an archive of UV Index bulletins and annual (1996-1997) time series of UV Index forecasts plus other information for the general public are also available on other Web pages.

UV Index In the summer of 1994, the National Weather Service (NWS) in cooperation with the US Environmental Protection Agency (EPA) and the Centers for Disease Control and Prevention (CDC) initiated the UV Index for 58 cities as 1-day forecasts of the level of erythemally weighted (skin-damaging) UV radiation (UVR) to reach the earth’s surface during noon (local standard time).1 The UV Index forecast informs the public of the intensity level of UVR reaching the surface. Knowing this, the public can take sun protection steps to avoid overexposure to UVR. The UV Index includes the effects of clouds and elevation of UVR. The UV Index uses satellite measurements of total ozone from either the TIROS Operational Vertical Sounder (TOVS) or Solar Backscatter Ultraviolet Ozone Sensor/2 (SBUV/2) instruments. From these measurements a 2-day forecast of the total ozone field covering the earth is generated. The Frederick-Lubin radiative transfer model is used to compute the irradiances for the UV wavelengths between 290 and 400 nm. The irradiances are weighted by the human erythemal action spectrum and integrated over a range of wavelengths to determine a dose rate (in milliwatts per square meter). The World Meteorological Organization (WMO) standard of one UV Index unit per 25 mW/m2 is then used to convert the dose rate to the unitless UV Index. This value is adjusted to include the effect of elevation (about 6% increase per kilometer).2 The final UV Index is corrected for clear sky-elevation and attenuated for cloud cover using model output statistics to forecast; it appears in text bulletin and national map form on the US EPA Ozone Depletion Home Page (http://www.epa.gov/docs/

UV Index update The American Academy of Dermatology has called the rise in skin cancer caused by overexposure to solar radiation in the United States an undeclared epidemic, for the following reasons: • Since the 1930s there has been an 1800% rise in malignant melanoma, the deadliest form of skin cancer. • More than 1 million cases of skin cancer are expected to occur in the United States this year alone. • One in 5 Americans can expect to develop skin cancer in their lifetime. • One American dies of skin cancer every hour. The American Academy of Ophthalmology has also cautioned that excess exposure of the eyes to UV radiation can cause a painful burn of the cornea, and long-term eye exposure to UV radiation may increase the incidence of cataracts, pterygium, and possibly macular degeneration. To address these serious public health issues, the EPA and the NWS introduced in 1994 a daily report on levels of UV radiation that the public might experience. The UV Index can help the public be aware of and plan for the level of UV radiation exposure expected on a given day. Armed with this information, the public can use simple sun-protective behaviors to reduce their lifetime risk of developing skin cancer and cataracts. This article contains health messages that may be helpful to broadcast meteorologists when they deliver the UV Index report. These messages are the product of close cooperation between EPA, NWS, the American Academy of Dermatology, the American Academy of Ophthalmology, the American Meteorological Society, and representatives of the broadcast meteorology community

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who actively broadcast weather information to the public. Composite health messages for 5 UV Index exposure categories Very high: A UV Index reading of 10+ means you are at very high risk of harm from unprotected sun exposure. Fair-skinned persons may burn in less than 5 minutes. Outdoor workers are especially at risk, as are vacationers who can receive very intense sun exposure on holiday which they are not accustomed to. Minimize sun exposure during mid day hours, from 10:00 AM to 4:00 PM. Apply sunscreen liberally about 20 minutes before sun exposure. Use a broad-spectrum sunscreen with a SPF of at least 15 every 2 hours. Wear a hat with a wide brim and protective clothing with a tight weave, and sunglasses to protect the eyes. High: A UV Index reading of 7-9 means you are at high risk of harm from unprotected sun exposure. Fair-skinned persons may burn in less than 10 minutes. Minimize sun exposure during midday hours, from 10:00 AM to 4:00 PM. Protect yourself by liberally applying a broad-spectrum sunscreen with an SPF of at least 15 about 20 minutes before sun exposure. Wear protective clothing including a hat with a wide brim, other protective clothing, and sunglasses to protect the eyes. Moderate: A UV Index reading of 5-6 means you are at moderate risk of harm from unprotected sun exposure. Fair-skinned persons may burn in less than 15 minutes. Apply a broad-spectrum sunscreen with SPF of at least 15 about 20 minutes before sun exposure. Wear a wide-brimmed hat and sunglasses to protect your eyes. Low: A UV Index reading of 3-4 means you are at low risk of harm from unprotected sun exposure. However, fair-skinned persons may burn in less than 20 minutes. Wearing a hat with a wide brim and sunglasses will protect your eyes. Use of a broad-spectrum sunscreen and protective clothing will reduce any long-term risks from outdoor activity. Minimal: A UV Index reading of 0-2 means minimal danger from the sun’s UV rays for the average person. Most people can stay in the sun for up to 1 hour during the hours of peak sun strength, 10:00 AM to 4:00 PM, without burning. People with very sensitive skin and infants should always be protected from prolonged sun exposure. It should be recognized that the daily UV Index is calculated for specific sites and may be different for nearby locations. UV reflected from water or snow may raise UV exposure above levels predicted in the UV Index. At high altitudes, there is less atmosphere to screen out UV rays, meaning that exposure will also be higher than at lower altitudes nearby.

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Precautions such as minimizing sun exposure, liberally applying broad-spectrum sunscreen about 20 minutes before sun exposure, and wearing protective clothing and sunglasses are important under these conditions. Using shadow to estimate UV intensity When it is not too cloudy, shadow can help to estimate UV intensity. Because UV intensity changes during the day, and the UV Index is calculated to represent the daily maximum, using one’s shadow can supplement information available through weather services. In addition, providing broadcast listeners with a simple rule-of-thumb for UV intensity may encourage people to be careful when their exposure may be greatest. For children, whose lifetime risk of skin cancer and cataracts can be reduced through simple behavior changes, the shadow rule is especially easy to learn and use. However, some caution in using this rule is needed because people can experience significant UV exposure on a cloudy day, when they cannot see their shadow. Public health messages for broadcasters Everyone enjoys being outdoors. You cannot— and would not want to—totally avoid exposure to the sun, but you can take steps to reduce sun exposure. A prudent preventive program consists of a combination of effective actions to reduce or prevent exposure to UV radiation. Preventive actions include minimizing sun exposure when the sun is highest, from 10:00 AM to 4:00 PM, applying broadspectrum sunscreen with an SPF of at least 15, and wearing protective clothing and sunglasses. People get about 80% of their lifetime sun exposure by 18 years of age; therefore the best prevention programs should focus on children, building healthy sun habits to prevent future skin cancers. Minimize sun exposure • Seeking shade is a good idea but don’t forget that water, sand, pavement, and grass reflect UV rays even under a tree, near a building or a shady umbrella. (For UV Index 7 and above) • Take a tip from the Victorians: use an umbrella as portable, personal shade. (For UV Index 7 and above) • Our society is very active year round. Take precautions during routine outdoor activities such as gardening or playing sports, including golf, cycling, or tennis. Taking precautions is especially important when the activity is being performed over several hours, particularly if those hours fall during the peak sun hours of 10:00 AM to 4:00 PM. At sporting events, sun protection may be needed for both participants and spectators. (For UV Index 7 and above)

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Protective clothing • Tightly woven fabrics afford the most protection against UV rays. UV rays can pass through the holes and spaces of loosely -knit fabrics. (F or UV Index 7 and above) • Hats with wide brims offer protection for the face, ears, neck, and eyes. Hats may be easier than sunglasses for tots to wear . (F or UV Index 3 and above) Broad-spectr um sunscreen and other protective measures • Broad-spectr um sunscreen with an SPF of at least 15 offers substantial protection against sunbur ning, especially for fair -skinned people. All skin types need protection from solar UV rays. P ersons with lighter skin types are at the greatest risk of developing skin cancer , but all people are at some risk. W rinkling, toughening, and aging of the skin will happen faster to sunbathers and others who spend time outdoors. Broad-spectr um sunFig 1. The shadow r ule. If your shadow is taller than you screens are recommended for ever yone. (F or UV are, your UV exposure is lik ely to be low . If your shadow is Index 7 and above) shor ter than you, you are being exposed to high levels of • A sunblock usually reflects or scatters all UV rays. UV radiation. A sunblock is a good choice for outdoor work ers. Sunblock is also a good choice for outdoor workers. Sunblock is also a good choice for protecting the nose and the rims of the ears. (F or UV Index • Minimize exposure to the sun during the hours 5 and above) when exposure could be most damaging, from • Apply sunscreen liberally about 20 minutes before 10:00 AM to 4:00 PM. Typically , exposure at 8:00AM or 4:00 PM is only one third that at midday . Try get- sun exposure. F or an average adult, the recomting outdoor activities accomplished during these mended dose is 1 oz, or a quar ter of a 4-oz bottle, hours. Remember , however , you can still get a per application. Reapply ever y 2 hours, af ter sunbur n even in the midaf ter noon. (F or UV Index being in the water , or af ter exercising and sweat5 and above) ing. (F or UV Index 5 and above) • Skiers need to know that snow is a par ticularly • Broad-spectr um sunscreens contain active ingregood reflector of UV rays. W ear UV -protective sundients that absorb at least 85% of the UV A rays and glasses or goggles and broad-spectr um sunUVB rays of the sun. Read labels carefully and screeen on exposed skin. Because the sun is choose a broad-spectr um sunscreen of at least being reflected up at you, in addition to coming SPF 15 which filters out both UV A and UVB radiafrom above, remember to protect areas that ordition. (F or UV Index 3 and above) narily don’t get sun, including under the chin and • Applying broad-spectr um sunscreen should be nose. (F or winter and early spring) par t of the daily routine, lik e br ushing teeth. The shadow ule r Cosmetics companies now facilitate this routine • One way to judge how much UV exposure you are for women; in many cases, foundations and moisgetting is to look for your shadow . If your shadow turizers have been refor mulated to include sunis taller than you are (in the early mor ning and screens. (F or UV Index 3 and above) late af ter noon), your UV exposure is lik ely to be • Apply sunscreen about 20 minutes before expolow. If your shadow is shor ter than you (around sure to all exposed skin, including easily overmidday), you are being exposed to high levels of look ed areas lik e the rims of the ears, the back of 3 When your shadow is shor UV radiation (F ig 1). t, the neck, and the tops of the feet. (F or UV Index seek shade, and tak e precautions to protect your 3 and above) skin and eyes (F ig 1). • Use broad-spectr um sunscreens of at least SPF 15 • If you can see your shadow , you are being that are specially for mulated to protect the lips exposed to UV radiation. T ake precautions to probecause regular sunscreens can taste bitter . (For tect your skin and eyes. UV Index 3 or above)

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• Incidental time in the sun can add up to longterm sun damage. Don’t forget the time spent walking the dog, window shopping, performing outdoor chores, or jogging at lunch. Even on overcast days, 30% to 60% of the sun’s rays can penetrate to the earth’s surface. (For UV Index 3 and above) Eye protection • The American Academy of Ophthalmology recommends sunglasses that block 99% to 100% of all UV rays (both UVA and UVB). Some reduction in blue light may also be beneficial, but colors should not be severely distorted. • Wearing sunglasses protects the lids of our eyes as well as the lens. (For UV Index 5 and above) • Read sunglass labels carefully. There is no adequate standard of labeling at present. Glasses that simply block UV or meet American National Standards Institute standards may not block 99% to 100% of UVA and UVB. Seek products that explicitly state they provide the degree of protection you want. • A cap or a hat with a wide brim will block roughly 50% of UV radiation from reaching the eyes. Wearing sunglasses as well can block the remainder of the UV rays. • Sunglasses alone do not provide full protection because light comes in over and around the rims. Curved glasses give added protection to the sides of the eyes. Immune system effects • Use of a lip balm or lip cream containing a sunscreen protects some people from getting cold sores (painful lip sores caused by herpes simplex types 1 and 2). (For UV Index 5 and above) • Use of a sunscreen can prevent sunburn and some of the sun’s damaging effects on the immune system. (For UV Index 5 and above) Tips for kids: Be sun wise! • Remember: —Short shadow, seek shade. —Big hat, shady face! • Encourage your parents and your schools to plant trees. • Try to stay out of the sun when possible. • Use sunscreen every day.

REFERENCES 1. Long CS, Miller AJ, Lee HT, Wild JD, Przywarty RC, Hufford D. Ultraviolet Index forecast issued by the National Weather Service. Bull Am Meteorol Soc 1996;64:792-9. 2. Long CS. Ultraviolet Index verification report. Washington (DC): National Oceanic and Atmospheric Administration, National Weather Service, National Centers for Environmental Prediction and Climate Prediction Center; 1996. p. 1-9. 3. Downham TF II. The shadow rule: a simple method for sun protection. South Med J 1998;91:619-23.

**** Affiliations: Henry W. Lim, MD, Department of Dermatology, Henry Ford Hospital, Detroit, Mich; Kevin D. Cooper, MD, Department of Dermatology, Case Western Reserve University, Cleveland, Ohio; Reva Rubenstein, PhD, Science Advisor, EPA, Washington, DC; Drusilla Hufford, MBA, Director, Stratospheric Protection Division, US Environmental Protection Agency, Washington, DC; Thomas Downham II, MD, Department of Dermatology, Henry Ford Hospital, Detroit, Mich; Ron Trancik, PhD, Pharmacia-Upjohn Co, Kalamazoo, Mich; Robert Swerlick, MD, Department of Dermatology, Emory University School of Medicine, Atlanta, Ga; Martin A. Weinstock, MD, PhD, Dermatoepidemiology Unit, Veterans Affairs Medical Center, and Brown University, Providence, RI; Vincent A. DeLeo, MD, Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY; Rex Amonette, MD, Division of Dermatology, University of Tennessee, Memphis; James M. Spencer, MD, MS, Department of Dermatology, The Mount Sinai School of Medicine, New York, NY; Cheryl Rosen, MD, FRCPC, Division of Dermatology, Toronto Hospital-Western Division, University of Toronto, Ontario, Canada; Jason K. Rivers, MD, Division of Dermatology, University of British Columbia, Vancouver, BC, Canada; Wilma Bergfeld, MD, Departments of Dermatology and Pathology, Cleveland Clinic Foundation, Cleveland, Ohio; Alvin James Miller, National Weather Service, Camp Spring, Md; Sandra Gordon, Director, Communications, American Academy of Dermatology, Schaumburg, Ill; Paul Gross, Weather Department, WDIV-TV, Detroit, Mich; Allan Eustis, National Weather Service, Camp Spring, Md; Howard Koh, MD, Commissioner, Massachusetts Department of Public Health, Boston, Mass.