SUNLIGHT 1) UV induced neoplasia 2) UVA and sunscreens 3) Melanin and sun protection 4) "Safe tan" and thimine dimers 5) Sunscreen and sweat 6) Recommended SPF number --------------------------------------------------------- -------------------- UV-INDUCED NEOPLASIA -------------------- You can think of the tumorigenic effects of the sun as occuring in two basic modes. One is the induction of mutations and the other is tumor promotion. The induction of mutations probably occurs most intensely during sunburns (which is probably why sunburns are so tightly linked to long-term tumor risk). Mutations may not be immediately expressed as tumors, since it takes several mutations to make a tumor, and these mutations may take years to accumulate in a given skin stem cell. We begin to accumulate mutations from the first time we walk (or are taken out) in the sun. The effects from mutations may have a long latency, in other words it may be years before a tumor shows up from sunburns in childhood. The other effect from the sun is tumor promotion. This effect is immediate over a time span of days and weeks. If you have skin which has acquired a large number of mutations from a lifetime of sun exposure, precancerous areas (and cancers) can begin to show up in these areas of skin after a few days or weeks of additional sun exposure (all sun exposure probably contributes to this promoting effect, not just sunburn exposures). What is happening is that the sunlight is stimulating the clonal expansion of cells which have already acquired one or more mutations, and are thus predisposed to grow more rapidly with sun stimulation than the surrounding normal skin cells. For a number of reasons, this may also lead to more rapid accumulation of additional mutations and ultimately, fully malignant cells (basal cell carcinomas, squamous carcinomas, melanomas). This tumor promotion effect is obviously most important in elderly individuals who have already acquired a large number of mutations, and is something which can be (and has been) readily observed in trials of sunscreens in the elderly ^A[1]^A. The difference in the number of actinic keratoses in sunscreen treated elderly patients and placebo treated elderly patients diverge almost immediately (within the first month), althought unless you are doing a study and keeping careful records, you might not even notice it (certainly the patients are not likely to notice). Over a year or two, though, there will be a fairly dramatic drop in how often you will see them if they are doing a good job of sun protection, particular in more equatorial lattitudes, where sun effects are more intense. In other words, the elderly may actually benefit the most from sunscreen use, and the old thought that it is "too late" for them is just not so. Skin malignancies probably follow similar trends, but this is harder to see in short term studies due to the greater latency in the development of malignant lesions. It would probably take a 3-5 year sunscreen study to see this effect convincingly, and as far as I know, no one wants to foot the bill for such an undertaking. The bottom line is sunscreens for the elderly--YOU BET!! Mark Naylor, M.D. University of Oklahoma Health Sciences Center --------------------------------------------- Mark - how can I "feel good" if I wear sunscreen? Less UV to my skin means less release of beta-endorfun from my skin to my bloodstream to my brain, and less fun for me! Seriously, I wonder if beta-endorphins from the skin are the reason some people get "tanorexia nervosa", and maybe why some others (eg. those with severe eczema and psoriasis) prefer not to get 100% cleared up, and perhaps why some patients, on the other hand, persist with UV light treatment. Kevin C. Smith MD FRCPC ----------------------- Mark, thanks for the very informative posting based on your research. Two rather simplistic questions remain in my brain (I haven't found your journal article yet). (1) What is this photoreactive mutation ? (2) We were trained to believe that UV actually slows down epidermal growth rates and that was one of the reasons it was able to smash psoriasis. I still regurgitate this to patients. Is there any basis for this old idea? Thanks, Diane oThanks for this interesting discourse. As far as you know, is there any evidence that any of the topical agents we use, i.e., the retinoids, glycolics, etc. have any effect on the " first hit ", that is, can we normalize the skin before the tumor is induced via the "second hit ". I know about the putative effects of the retinoids in head and neck cancers, and some hematopoietic problems. I'm aware of the speculation about retinoids normalizing the sun damaged areas, that is, the actinics may appear better. Are we really doing anything to change the situation in the long run? Elliot Puritz ------------- I just had to respond to the phenomenon of dermatologists extolling the virtues of sunlight. I have observed over the years that our personal affection for sitting in the warm sunshine sometimes makes physicians (and derms too) blind to the hard facts about sunlight. As far as the physiology of the skin per se, there is no beneficial effect from sunlight, zero, naught, nada, none. If it's vitamin D you want, go drink a glass of milk, or take a multivitamin. We can get all of that we want from our diets and/or dietary supplements. Vitamin D supplementation is never a good reason to accumulate UV damage. If you want to go out and enjoy the sunlight, fine. Just remember to put on the sunscreen and wear a hat. You can still get the "feel good" effect while minimizing UV-induced mutations. The Australians have recently reported a plateau in melanoma incidence that (I believe) is largely due to concerted efforts by physicians and other health care providers as well as governmental programs promoting sunscreen use and sun avoidance behavior (yes, governments sometimes actually do good things) [1]. The rest of the world would do well to emulate their example. 1. Giles GG, Armstrong BK, Burton RC, et al.: Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994. Br Med J 312:1121-1125, 1996. Mark Naylor, M.D. ----------------- >Have you ever had a patient complain of "feeling hotter" with sunscreens. >I have had several, in people highly motivated to use sunscreens. Can you >explain this phenomenon? Thanks, Diane Thaler Yes, I think sunscreens do make you feel a little hotter. Being a marathon runner and an avid cyclist myself, I can tell you that it is not a problem that keeps you from doing what you want though. Just drink more water or run a little slower if you really think you are overheating. I don't think I have heard of a case of heat stroke where sunscreen was the proximate cause. Mark Naylor, M.D. ----------------- On 10/29/96 Barbara Reed posed the classic question about how much sun exposure is safe exposure. I apologize if I sound a bit like a zealot; I guess I'll have to plead guilty on that count. If I can't convince a majority of this group though, I won't have a chance with the FDA. The real answer is that no one knows for sure (but I don't say that to patients because it sounds like I am giving carte blache for what my gut tells me is unsafe behavior). My own feeling is that the question of a safe UV dose is analogous to ionizing radiation where the question is how much radiation exposure is safe? The answer with ionizing radiation (and probably UV in an analogous way) is that there appears to be no threshold below which there is zero response. In other words you can get DNA mutations and chromosome damage from UV doses which do not cause sunburn, but the frequency of this damage may be low and difficult to measure (but not necessarily zero or insignificant, given enough low intensity exposure). There is good scientific evidence that suberythemal UV exposures cause DNA damage. For example, at least three studies in experimental mice showed that tumors can be induced with suberythemal UV [1-3]. Pyrimidine dimer formation, a major precursor lesion of ultraviolet-induced DNA damage, also occurs following suberythemal exposure [4-6] as do sunburn cells (cells which have undergone apoptosis as a result of DNA damage [7]. There is probably an assymtotic curve describing mutation rate which gets very steep when the erythema threshold is reached. My own feeling is that the DNA mutation rate is fairly low with non-erythema provoking exposures, and the major effect in this range is tumor promotion, which does not require DNA mutations to produce tumors (because it works with mutations which are already present). So you can think of the main effect of suberythemal UV exposure as mainly a tumor promoting influence and erythemal UV exposure as mainly a mutating influence. This is an oversimplification though, because in truth both mutation and promotion are going on simultaneously at any UV dose, and it is just the relative significance of each which changes with the UV intensity. What is taught in radiation safety courses nowdays is the concept of "ALARA" which stands for "As Low As Reasonably Achievable" which is a reasonably self-explanatory idea. In other words, because there is no threshold below which no effect occurs, we should try to keep our radiation exposure to the lowest level which is reasonably achievable consistent with accepted practices with radioisotopes. I think that we should follow exactly the same priniciple with UV exposure, namely go out and do what you want to do, just use the ALARA principle. For me that means a high SPF sunscreen (greater than or equal to 30 SPF), and a hat if I am going to be outside for more than 15-30 minutes between 10 AM and 2 PM. (and of course try to schedule outdoor activity for early or late in the day when possible). 1. Gallagher CH, Greenoak GE, Reeve VE, et al.: Ultraviolet carcinogenesis in the hairless mouse skin. Influence of the sunscreen 2-ethylhexyl-p-methoxycinnamate. Australian Journal of Experimental Biology & Medical Science 62(( Pt 5)):577-588, 1984. 2. van Weelden H, van der Putte SC, Toonstra J, et al.: UVA-induced tumours in pigmented hairless mice and the carcinogenic risks of tanning with UVA. Arch Dermatol Res 282(5):289-294, 1990. 3. Gallagher CH, Canfield PJ, Greenoak GE, et al.: Characterization and histogenesis of tumors in the hairless mouse produced by low-dosage incremental ultraviolet radiation. J Invest Dermatol 83(3):169-174, 1984. 4. Kinley JS, Brunborg G, Moan J, et al.: Detection of UVR-induced DNA damage in mouse epidermis in vivo using alkaline elution. Photochemistry & Photobiology 61(2):149-158, 1995. 5. Harber LC, Kochevar IE: Pyrimidine dimer formation and repair in human skin. Cancer Res 40(9):3181-3185, 1980. 6. Leipold B, Remy W: Use of avidin-biotin-peroxidase complex for measurement of UV lesions in human DNA by microELISA. Journal of Immunological Methods 66(2):227-234, 1984. 7. Ziegler A, Jonason AS, Leffell DJ, et al.: Sunburn and p53 in the onset of skin cancer. Nature 372(6508):773-776, 1994.^A Mark Naylor, M.D. ----------------- No one would argue with the idea that sunburning is bad, and everyone seems to agree that "too much" sunlight is harmful. But I have never seen the definition of what is too much, and also: Where is the proof that even a little sunlight is "bad"? Barbara R. Reed, MD ------------------- I find these questions from Diane, Kevin, Walter and others concerning the phycological effects of sunlight thought-provoking, even if I can't buy into it personally. I should preface this by saying that I enjoy outdoor activity whenever I get the chance, and that I would (almost) never discourage anyone from doing fun things outdoors. I do think it should be done intelligently. I tend to agree that telling everyone not to go outdoors between 10 AM and 2 PM is a little unrealistic, but if outdoor activity can be scheduled at others times, why not. Sunscreens and protective clothing (especially hats) are a more practical solution for most people in most situations. I will stipulate that there are real psychological benefits associated with outdoor activity and sunlight. Also, as far as I know, most of the CNS effects of sunlight, such as affects on sleep patterns, circadian rhythms and that kind of thing are thought to be due to visible wavelengths, not UV wavelengths, so chemical UV screens (sunscreens) should have no effect on them. As far as serotonin goes, what little is produced and released by either keratinocytes or melanocytes in the skin, probably has its primary role in paracrine response to noxious stimuli (such as UV burns). It seems speculative to me to link serotonin produced as a local inflammatory mediator in skin to CNS effects. Peripheral serotonin production as far as I am aware has nothing to do with the complex neural pathways that involve serotonin as a neurotransmitter. One speculative paper published in 1994 theorized a link between UV-induced serotonin from melanocytes in vitro and circadian rhythms, but presented no evidence of such a link [1]. The bulk of the literature on circadian rhythms indicates that visible or multichromatic (white) light, probably acting via the visual system and the pineal gland is/are responsible for circadian rhythms, not UV effects on melanocytes. While there is some evidence that keratinocytes can produce measurable amounts of beta endorphin [2], whether this tiny quantity of peripherally-produced endorphin has any central nervous system effect is speculative at best. Whether any of this has anything to do with the psychological effects of sunlight is even more speculative still. What we do know is that (as far as I am aware) all of the local effects of UV on skin are adverse ones. In the case of phototherapy, we are willing to accept these adverse effects to obtain a therapeutic benefit, but in any other situation, it seems to me that the best course is to minimize UV exposure. My own hypothesis is that the psychological effects of sunlight are just that, e.g., psychologic rather than physiologic, so they will occur whether an individual uses a chemical UV blocker or not. To put it another way, I would predict that if you did a double-blind, placebo-controlled trial between sunscreen and placebo lotion to evaluate any particular CNS parameter you care to measure, there would be no difference between the two groups. Food for thought, for sure! 1. Iyengar B: Indoleamines and the UV-light-sensitive photoperiodic responses of the melanocyte network: a biological calendar? Experientia 50(8):733-6, 1994. 2. Wintzen M, Yaar M, Burbach JP, et al.: Proopiomelanocortin gene product regulation in keratinocytes. J Invest Dermatol 106(4):673-8, 1996. Mark Naylor, M.D. University of Oklahoma ---------------------- On 10/29/96 Diane Thaler and Elliot Puritz took the risk of inviting me to expound more about UV effects on skin: This is obviously my favorite subject, but I'll try to restrain myself. To answer Diane's question directly, UV exposure can cause skin cells to grow faster or slower depending on how you do the experiment. There is actually a biphasic response in normal mouse skin to a single big dose of UV with early growth suppression and later proliferation of cells. I think the situation with psoriasis is more complicated because these are not normal cells and the immune system is also involved. Obviously there is a net suppression of keratinocyte proliferation in psoriatic plaques during chronic phototherapy. I don't think that this is a very helpful way of thinking about how UV causes skin cancer, though. Elliot asked about how retinoids or alpha hydroxy acids might impact the process of UV tumor formation. My guess would be that if they have a beneficial effect, it would be on the process of tumor promotion, since I don't think it likely that anything is going to repair a DNA mutation once it has formed and been replicated (the DNA excision repair machinery actually causes the mutation when it mis-repairs a cyclobutane dimer or a pyrimidine (6-4) pyrimidone photoproduct). If retinoids help suppress the tumor promotion process, they may be clinically useful in suppressing skin cancer. In my mind, whether retinoids actually do this is still an open question, but maybe the answer is yes, assuming they are used in conjunction with adequate sun protection. You can think of two general types of direct UV effects that impact skin cancer. The first is the phenomenon of tumor initiation (mutations and damage to chromosomes) and the second is tumor promotion (immediate effects related to stimulation of growth factor and signalling pathways). UV not only causes mutations in DNA, but also chromosome damage such as deletions and translocations which are probably just as important if not more important than the mutations. These effects on DNA and chromosomes are what underlies the long term effects of UV on skin cancer such as the increased melanoma risk due to sunburns (mutations and chromosome damage probably accumulate at an increased rate during a UV burn). This is what a basic scientist would call tumor initiation, and its ultimate effects may not be seen for many years (until tumor promotion speeds things up later in life). The other important (and immediate) effect of UV is the activation of so-called signal transduction pathways including prostaglandins, IL-1, IL-2, IL-6, IL-10, interferon-gamma, and TNF-alpha (to name some of the pathways that are known to be involved). The proximate mechanisms for these signal transduction pathway activations are not well understood, but involve direct photochemical damage to target molecules such as lipids and indirect effects through the generation of reactive oxygen species (hydroxyl radicals and the like). The net result of these (and probably other) pathway activations is the stimulation of skin cells containing mutations and chromosome damage to grow faster than the surrounding normal skin cells. This is what tumor promotion is all about, and as you see, it does not directly involve DNA mutations. Sun protection can prevent tumor promotion, and in doing so, lowers the risk that an abnormal cell or foci of cells will develop into a clinically evident lesion (e.g., an actinic keratosis or an atypical solar lentigo) with a concomitantly increased chance of acquiring additional DNA damage that will cause it to become a fully malignant skin cancer. Retinoids might have a role in the suppression of tumor promotion and I think definitely for helping to repair the effects of photoaging, but that is getting into a different topic. The bottom line as far as sun protection is that it helps prevent skin cancer in at least two ways. In young people (and older people too, really) it prevents the mutations and chromosome damage that will in the long term lead to tumors. In older people it prevents the mutated cells **that are already present** from developing into clinically evident lesions. The underlying assumption here is that most mutated cells will not give rise to cancer if tumor promotion is avoided. So everyone benefits from sun protection, but in different ways. There are also very important effects from the immune system that impact these processes, but I have already gone on too long. Mark Naylor, M.D. Mark, I've tried to get our local schools and city/community teams to schedule games away from peak UV periods to avoid heat exhaustion and dehydration. No go. Maybe they would respond more to the UV issue. Certainly sunscreens sweat off on these soccer, baseball, and football players if they apply them at all. Have you ever had a patient complain of "feeling hotter" with sunscreens. I have had several, in people highly motivated to use sunscreens. Can you explain this phenomenon? Thanks, Diane Thaler ------------------ UVA AND SUNSCREENS ------------------ I am concerned that by using sunscreen many patients will stay out in the sun much longer than they otherwise would, ie, high SPF sunscreen may give many patients a false sense of safety. I seem to recall the the UVA flux at the earth's surface is about ten times as much as UVB. If patients are not burning due to the high UVB protective effect of sunscreen, they may be getting a much higher dose of UVA than they otherwise would get. Don't we need to break SPF down into UVA protective factor, and UVB protective factor? Walter H. Wood, M.D. --------------------- I agree with Walter - it would be handy if we could have numbers for UV-A and UV-B protection, perhaps some sort of "area under the curve" type thing. One item with commercial potential would be a sunscreen with a "window" that let through 311-313 nm UV -- this wavelength is very useful for psoriasis and a number of other condtions. Kevin C. Smith MD FRCPC ----------------------- Do you know what wavelengths it covers? I have the same issues as Dr. Wood, and attempt to recommend broad spectrum for wrinkles, drugs, ple etc. Diane Thaler ------------ Walter Wood was commenting about UVA and sunscreens vis-a-vis how this might impact recommendations for sunscreeens. I think this is an excellent subject for a discussion among experts on RXDERM-L. Here are some of my thoughts along these lines: The UVA (320 nm) "irradiance" (roughly the number of photons hitting the earth's surface per unit area, usually expressed as Watts/square meter) is about 1 x 10-1 W/m2. This is approximately 100-1000 times greater than the UVB irradiance at 295 nm (about 1 x 10-4 W/m2 to 1 x 10-5 W/m2) at the earth's surface at noon on a cloudless summer day in North America^A[1]^A (A good review of this can be had on the world wide web at http://www.ciesin.org/docs/001-503/001-503.html for those with web access). Because UVB (300 nm) is 100-1000 times more efficient at causing erythema than UVA (>320 nm), these factors almost cancel each other out, although the erythema effect from from sunlight ends up being mostly due to UVB (about 85%) vs. UVA (about 15%) [see chapter on UVR in the Fourth edition of Fitzpatrick's "Dermatology in General Medicine"]. One problem with this comparison is that you can't necessarily say that the erythemal effectiveness of UVB and UVA directly correlate with their ability to produce tumors. It is clear to me from reviewing a lot of animal and human data on this recently that the portion of the UVA spectrum that is most carcinogenic is the "shortwave UVA" region, (roughly 320-335 nm). Therefore, in my opinion, as long as our sunscreens cover UVB and the short UVA wavebands, we are covering more than 90% of the carcinogenic spectrum of sunlight, and any effect of sunscreens "encouraging people stay out longer" (or however you want to put that) is probably negligible. It is important to note that most broad spectrum, high SPF sunscreen preparations on the American market today do just that (that is cover against UVB and short-wave UVA). I have yet to see any evidence to support the idea that sunscreens "cause" people to get substantially more UVA exposure than they would otherwise, and that this additional UVA is clinically significant, especially given that sunscreens (broad spectrum, high SPF ones anyway) have coverage against shortwave UVA. It is, in short, a purely theoretical argument. Without proof, I am certainly not going to forgo recommending sunscreen use to people, especially when my own personal experience is that I pretty much go out and do what I am going to do regardless of any sun protection/sunburn considerations. Because of that, I am without any doubt better off with a high SPF sunscreen on (and a hat too, of course) and I imagine that I am like most people in this regard. These concerns vis-a-vis UVA and sunscreens are very interesting to think about, and further study is certainly needed, given that much is at stake. However, as clinical dermatologists who have to make practical decisions regarding real-world problems we should not forget that UVB is the major action spectrum for sunburn and skin cancer (including melanoma) and that sunscreens (which in general do protect better against UVB) have been shown in clinical trials to reduce sun-induced neoplasia (e.g., actinic keratoses) [2, 3]. Let's also not forget that the Australians, who make a big point of recommending sunscreens to everyone, have apparently plateaued their melanoma incidence (e.g., the melanoma incidence in Australia is no longer increasing as it is in the U.S. and everywhere else as far as I know) [4]. This is a remarkable achievment when one considers the epidemic incidence of melanoma in recent decades! Given the evidence at hand, to not recommend sunscreens to susceptible individuals is taking a much greater chance of doing harm than vice versa in my opinion. How we come down on this question is important because we are (appropriately) the pacesetters of professional opinion on such subjects, and how we think (and therefore act) will be magnified many-fold because of this. 1. Diffey BL: Solar ultraviolet radiation effects on biological systems. Physics in Medicine and Biology 36(3):299-328, 1991. 2. Naylor MF, Boyd A, Smith DW, et al.: High Sun Protection Factor (SPF) Sunscreens in the Suppression of Actinic Neoplasia. Arch Dermatol 131(2):170-175, 1995. 3. Thompson SC, Jolley D, Marks R: Reduction of solar keratoses by regular sunscreen use. N Engl J Med 329(16):1147-1151, 1993. 4. Giles GG, Armstrong BK, Burton RC, et al.: Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994. Br Med J 312:1121-1125, 1996. Mark Naylor, M.D ---------------- -------------------------- MELANIN AND SUM PROTECTION -------------------------- Melanin is great protection against sun damage to UVL. I believe that it is safer to tan gradually than to use high SPF sunscreen every day, except once in a while when you forget it and get burned and thus risk inducing melanoma. Yelva Lynfield MD ----------------- This is matter that I have thought a lot about, so I will express an informed opinion, although I admit I don't have data yet to back this up. I agree that melanin is a great UV protector. Sunscreens, because they are not complete blocks, work best when there is some melanin pigment in the skin. In practice (years of personal experience) I can tell you that people (me in particular) will definitely tan somewhat through even the strongest sunscreen (especially a weak one of SPF 15 or less) given enough exposure. To some degree this incidental tanning is protective, because on subsequent exposures the same sunscreen works better because of the small amount of tan you got from previous exposures. Therefore in my opinion, the safest way to get some protective melanin is through continuous use of an SPF 45 or 50 sunscreen, e.g., the inevitable incidental tanning you pick up in spite of your best efforts to prevent it. I think you will get the least DNA damage over time following a continuous use strategy. There is always the danger of forgetting the screen and getting the UV burn, but I would say learn to make sunscreen application second nature and do it all the time if you are really worried about that (and I am). Mark Naylor, M.D. ----------------- --------------------------- SAFE TAN AND THIMINE DIMERS --------------------------- I'll go out on a limb here. I think I recall from a recent "throw-away" that I threw away, that there will potentially be such a thing as a safe tan. Seems that UVB causes thimine dimers that stimulate melanosome release from melanocytes. In guinea pigs, the thimine dimers themselves caused the formation of a nice tan, but without the adverse effects on DNA. I suspect this will eventually will be a gold mine for the cosmetic industry. Dan Mitchell, MD ---------------- I think Dan is probably referring to the "Dermatology Focus", volume 15(1), Spring 1996 [a publication of the Dermatology Foundation] which had a write-up about thymine dimers and tanning [1] . This is work being done by Mark Eller, Mina Yaar, and Barbara Gilchrest at Boston University, and Dan is absolutely right about its potential for being the holy grail of the "safe" tan. This work dovetails from the basic observation that UV induces tanning by first causing DNA damage in the form of thymine dimers, and that (presumably) during the DNA repair process these excised thymine dimers somehow act as a signalling molecule to induce at least some of the cutaneous tanning machinery. These folks showed that topically applied thymine dimers can induce tanning in guinea pigs, a most remarkable achievement. If topically applied thymine dimers can be turned into a practical commercial product that can induce tanning without UV exposure it will be a tremendous innovation. I suspect that we are several years away from being able to recommend such a product, however, and I have no idea if this is even practical in humans. Does anyone know of anything in human trials or are we still at the guinea pig stage on this? Mark Naylor, M.D. ----------------- ------------------- SUNSCREEN AND SWEAT ------------------- Which ones don't sweat off? " Lyphazome 30" ( from Fountain Pharmaceutical in Largo, Florida) is absorbed into the stratum corneum within 60 seconds. Doesn't even get into your eyes while scuba diving! Philip Hughes, M.D. ------------------- Suggestion for "heavy duty" athletes using sunscreen...Use a gel/alcohol based product. Studies in the sports medicine literature show that these preparations are best in that environment.. Darrell Rigel ------------- Which ones don't sweat off? I remember the sales pitch on Solbar 50, besides being UVB/UVA (as high as they came at that time), was that the base was the same as DML-Forte hand cream, and stayed on for four washings. Have their been studies done on duration of screening ability in marathon runners, for example-the ones that sweat anyway? Diane Thaler ------------ ---------------------- RECOMMENDED SPF NUMBER ---------------------- Mark, how do you respond when patients comment that they have been told that an SPF over l5 in inconsequential. Where did this story originate? Diane Thaler ------------ I explain to patients that IF people slathered on sunscreen the way it is used in the lab when SPFs are being determined, an SPF of 15 would be perfectly adequate, BUT in the real world people don't usually put sunscreen on thick enough, then some rubs or washes off; SO as a practical matter it most people use a 30 or 40 they will actually GET about 15 worth of protection. This is why the FDA eventually broke down and allowed advertising of SPFs greater than 15 -- because in the REAL world higher SPFs are useful. Kevin C. Smith MD FRCPC ----------------------- The question was raised as to where patients got the idea that one need not exceed an SPF of 15 for appropriate skin protection: There was a review of sunscreens 8 to ten years ago (I am 53 so my memory may be faulty as to the exact time) in Consumer's Report and their dermatological consultant averred that there was no value to a sunscreen greater than 15. That consultant seemed unconcerned with the possibility that some of the shorter wavelengths of UVA might have some importance in the production of human cutaneous disorders and that some of the higher SPF sunscreens actually offered protection in that range. That article may have been the source of that impression. Pat Condry ---------- It takes about 10 minutes for a fair-skinned person tanning in June at a latitude equal to Philadelphia at midday to reach one MED. It should take roughly 200-250 minutes to be exposed to 15 MEDs--it's more than 15X10 because of the waning of irradiance away from noon. So being conservative in the calculations, if someone applies SPF 15 perfectly (big assumption), they can only stay out from 10:00AM to 2:00 PM--longer than that, they will reach MED. But I would argue that DNA damage is occurring at suberythmogenic doses of UVB--turning red is the physiological response to damage that has occurred. So certainly if people plan to be out for >4 hours at peak summertime, and justifiably even if they plan to be out less--its SPF 30 for me!! My argument does not address the issue raised by Mark Naylor regarding UVA protection in sunscreens. On another note, I would like to address the misconception of the "melanoma epidemic". It is indisputibly true that the mortality rate from malignant melanome is rising--several percent per year in the U.S., I believe. However, if the mortality rate is broken down by age group in the U.S., the numbers are stable or falling. THe reason that the overall mortality rate from melanoma is rising is that our population is aging. For example, the highest melanoma mortality rate by age group is 85 and older--not surprising, given that this cohort has had eighty-odd years to be burned. Because this is the most rapidly growing segment of our population, they are pulling up the overall melanoma mortality rate. So we don't have a melanoma epidemic, we have an aging epidemic. I don't have a ready reference for this, but it is based on recent NCI SEER data. Marty Okun ----------- The lifetime risk for melanoma among Americans rose from 1 in 1,500 in 1930 to 1 in 150 in 1985, and is now projected to reach 1 in 75 in the next four years [1] . If current trends continue, young adults in the 15-34 age group will be dying faster from melanoma after the turn of the century than from the combination of breast cancer and leukemia, the current leading cancer causes of death in this age group [2] . This highlights the particularly insidious effect of this tumor since it definitely affects the most productive group in the population, not just the elderly. No offense Marty, but I think those who argue that there is no melanoma epidemic have a "tough row to hoe" (as we say in the Southern US) given these kind of figures. My own feeling is that the rise we are seeing in the melanoma incidence is real and not due to better case identification (earlier diagnosis) as some have suggested. For one thing you have to realize that earlier diagnosis only give a temporary rise in the incidence statistics, since all those people would eventually be diagnosed whether they were diagnosed early or not. Death by melanoma is the kind of thing that gets noticed one way or another. Many people have used the rising death rate from melanoma as evidence that the incidence increase is real, which is, I think, the point that Marty was commenting on. Older people do die at a higher rate of melanoma, but I am skeptical that this can explain the entire death rate increase for melanoma. Perhaps Darryl Rigel could comment on this for us, since he is a recognized authority in this area. At the very least the melanoma incidence is not decreasing although it may be levelling off a bit even in the US (the population is getting more sophisticated about sun protection). The recent experience of the Australians in seeing a plateauing of melanoma incidence is clearly a milestone if it holds up [3] . This is certainly where we would like to go in the US, and I encourage everyone to keep hammering your patients about sun protection since this is something that we can do that will eventually have a big impact. 1. Rigel DS: Malignant melanoma: perspectives on incidence and its effects on awareness, diagnosis and treatment. CA 46(4):195-198, 1996. 2. Boring CC, Squires TS, Tong T: Cancer statistics, 1993. CA 43(1):7-26, 1993. 3. Giles GG, Armstrong BK, Burton RC, et al.: Has mortality from melanoma stopped rising in Australia? Analysis of trends between 1931 and 1994. Br Med J 312:1121-1125, 1996. Mark Naylor, M.D. ----------------- My personal bias is that a 15 SPF is the lowest SPF rating that ought to even be called a "sunscreen". I think lesser SPF preparation should be thought of mainly as tanning aids. On a more scientific note, there is good evidence that a 15 SPF and 30 SPF are significantly different. The first thing that comes to mind is Kays Kaidbey's study that showed significantly higher numbers of sunburn cells (mean 7.45 vs. 2.96) in human skin protected with SPF 15 sunscreen vs. skin protected with an SPF 30 sunscreen [1] Sunburn cells are thought to be keratinocytes that have received so much UV DNA damage that the DNA cannot be repaired and have subsequently undergone p53-induced apoptosis. It is worthy of note that in Kaidbey's study even the SPF 30 preparation did not completely stop the formation of sunburn cells. I agree entirely with Marty Okun's point that DNA damage can occur even without the development of erythema, which is precisely why I disagree so strongly with the premise that a 15 SPF is a sufficient sunscreen for most people since it usually prevents the development of frank erythema. Even if a 15 SPF sunscreen can prevent erythema, it clearly does not provide the same degree of protection as a 30 SPF sunscreen. I think a more interesting question is whether there is a difference between a 30 and a 45 SPF sunscreen. Until we have some kind of definitive answer to this last question, the FDA should back off its proposed labelling ban for high SPF sunscreens (in vitro studies that measure how "completely" sunscreens stop UV in a spectrometer have no relevance in the real world and do not impress me in the slightest). Personally, I use an SPF 45 preparation. Another point about the higher SPF sunscreens that does not often get much mention is that they tend to give better protection against shortwave UVA (the portion of the UVA spectrum that probably contributes most to carcinogenesis), since they have higher concentrations of more agents, including ones that give coverage in this range, e.g., benzophenones and to a lesser degree, cinnamates. 1. Kaidbey KH: The photoprotective potential of the new superpotent sunscreens. J Amer Acad Dermatol 22(3):449-452, 1990. Mark Naylor, M.D. ----------------- Careful study of residual sun protection of sunscreens following rubbing, sweating, swimming, etc., has not been done. To tell patients to use higher SPF sunscreens so that they do not have to reapply them is misleading. The May 1995 Consumer Reports evaluated 37 different sunscreens (SPF 15 - 35) and found the products "water-proofness" or "rub-proofness" claims to be overstated or outright wrong. I agree with Mark Naylor, further study must be done regarding true UVB/UVA SPF. Furthermore, until manufacturer's claims are substantiated by independent labs, I recommend to my patients the, "reapply sunscreen every two hours rule" - I agree, tough to follow, but it's the best we've got for now. Joseph Yohn ----------- Any comments on the sunscreens I recommend? Solbar 50, Shade 45, Durascreen 30, Neutrogena 17 (titanium microsized). I thought these provided the broadest UVA protection. I like good UVA protection for LE, Drug, PLE (some) etc. Diane Thaler ------------ I agree there's no good evidence, but the best advice I can give is that: "As a practical matter, if you use higher number SPF, all other things being equal you will get better protection. Remember that the way sunscreen is ACTUALLY used, the protection you get will probably be less that that on the label. If you use a "waterproof" sunscreen you will probably get better protection." When there is better evidence available, I will refine my advice, but for today, that's the advice I follow myself, and that's the advice I give my patients. Consumer Reports does not have a lot of credibility with me, in particular with regard to medical matters. Kevin C. Smith MD FRCPC ----------------------- On a more practical side, try a #15 on one arm and a #30 on ther other arm. Go in the sun for 1 hour (I stayed out for 4-5 hours actually, working in my garden) Then assess which arm has erythema. My personal favorite sunscreen spreads very nicely, doesn't sting my eyes, and, in addition to a UVB and UVA block, has titanium dioxide in it. It is Johnson and Johnson's Baby #30. I've been using it daily for a good fifteen years. It works some the next day also but not as well as the first day (some erythema) Patients tend to listen better when I explain my personal "testing". Maida L. Burrow --------------- Maida, I thought that I checked out ingredients once and the Johnsons regular sunscreen had the same ingredients as the Baby-or it might have been another brand. We have found the only solution to stinging eyes from simming or sweating with sunscreen is to use the waxy lip stuff on the lids or the neutrogena waxy stick on the forehead. We will try Johnsons again though on your advice. Diane Thaler ------------ I agree with Maida - I always tell people: "Find a sunscreen you LIKE, because if you don't like it you won't use it, and if you don't use it you'll get no sun protection at all." Kevin C. Smith MD FRCPC ----------------------- I think Photoplex is no longer made. The only suscreen on the market in the U S that contains Parsol 1789 is Shade UVAGard, to the best of my knowledge. Gene Sienkiewicz, M. D. ----------------------- My expertise is tumor biology and clinical dermatology, so I don't want to misrepresent myself as an expert on sunscreen formulations. With that caveat, I do have opinions. I like Solbar 50 and Shade 45, both good products that I have used personally. Most of the high SPF preparations have reasonably good protection in the shortwave UVA region because they are high concentration mixtures of several sunscreening agents, some of which have pretty good coverage there (e.g., benzophenones, cinnamates). We don't have good yardsticks for measuring exactly how good this UVA protection is in the U.S. as has been mentioned by several on the list. Neutrogena's product probably has reasonably good UVA coverage for its SPF rating if for no other reason that it contains an occlusive agent (e.g. titanium dioxide particles) which block all wavelengths including the visible ones (>400 nm) and is therefore an excellent sunscreen, although many people don't like the "clown paint" look unless they have fairly pale complexion to start with. I have no personal or professional experience with with Durascreen 30. Another good sunscreen to mention in regard to UVA is Photoplex, marketed in the U.S. by Allergan (I think). This is one I recommend most often in UVA sensitivity disorders. Mark Naylor, M.D. ----------------- I get upset when people try and justify the position that SPF 15 sunscreens are all we need to protect people by using an in vitro test such as UV spectrometry to show that 95% of incident UV can be blocked by an SPF 15 preparation as opposed to 97.5% of incident (these are not accurate figures, but they are ballpark) UV being blocked by the SPF 30 sunscreen. This comparison makes it look as if the difference between the two is inconsequential, but in the real world, e.g. on real skin under real sunlight, the difference is extremely important. Walter of all people should understand how a "bean counter" (like the ones that are running the health care system in the U.S. now) would be impressed by such in vitro tests and procede to tell the physcians who work for them that they can't recommend high SPF preparations because they are not cost-effective or some such nonsense. My real point was that studies have to be done on real skin to be convincing to me, preferrably human skin. Kays Kaidbey's study that I cited earlier is a good example of an experiment that was done on human skin that clearly shows the difference between an SPF 15 and an SPF 30 preparation, and is a far better measure of the biologic importance of the SPF difference [1] . 1. Kaidbey KH: The photoprotective potential of the new superpotent sunscreens. J Amer Acad Dermatol 22(3):449-452, 1990. Mark Naylor, M.D. ----------------- I use UVAGuard when I want UVA protection. It is well tolerated, water resistant, and even the spf 15 form of it seems to work better than some other 30's and 40's. We have very intense sun here in Missouri and I have gone on float trips down local rivers with a single application (10am) of UVAGuard and gotten merely pink while friends around me were burning through their 30's. John Uhlemann ------------- REMARKS ON BIOLOGIC EVALUATION OF PROTECTION FACTOR FOR SUN PRODUCTS I shall just give some information on how to measure the filtering power of a compound through biologic methods based on the results of "in vivo" studies on human or laboratory animal skin.= The methods employed measure the erythema-threshold rise. Erythema-threshold means the skin inflammatory reaction characterized by erythema, with or without edema, hardly noticeable yet clearly defined, which is obtained through consistent experimental conditions (same radiation source and incidence) and assessed by the same observer.=20 Under constant radiation intensity, the erythema-threshold and therefore the minimal erythematogenic dose (MED) is defined by radiation time. Radiation time corresponding to MED clearly depends on the type of skin and radiation source. The Sun Protection Factor (SPF) of a solar filter is obtained by calculating the ratio between MED on sun protected and unprotected skin. In other words, it indicates the prolongation rate of the solar filter under examination with respect to the radiation time necessary to provoke the erythema-threshold. A more accurate SPF value is obtained by taking into account also the quantity of product applied per surface unit. This is obtained by multiplying SPF by the following ratio (ml of applied product/cm2 of treated skin). The SPF of a UV filter can be determined according to: 1) the USA method proposed by the OTC group of FDA, 2) the German method proposed by the Deutches Institut f=FCr Normung (DIN). In both cases, the method is the following: on the back of a volunteer a series of generally square surfaces of limited size arranged along horizontal lines is marked. The product under examination and a reference standard product are then applied on the surfaces of different lines. The remaining, untreated surface is the unprotected control skin. These areas then undergo radiation for different periods of time and, at a 16-24 hours interval, the different erythema degrees are recorded.=20 The ratio between the time necessary to obtain the erythema-threshold with the tested product (namely its MED) and the time necessary to induce the same degree of erythema on unprotected skin corresponds to the individual SPF. Since this test is conducted on a population of individuals, it is more appropriate to define the effectiveness of a UV filter as average protection rate (Q). The average protection rate: Q (log) is the average of individual protection rates (Qi). Therefore it is sufficient to know the number of protected areas in which no erythema has occurred (delta i) Qi(log) =3D delta i / 2 Then, the average of the sum of these individual values (delta/2) is converted by means of an appropriate table into the average protection rate, with the following mathematic formula: Q=3D2^delta/2 The compound has no effect if Q=3D1, it has screening properties if Q>1 and it is phototoxic if Q<1. The USA (FDA) and the German (DIN) methods differ from each other on several points indicated here below: Type of UV radiation source: - the FDA method employs a filtered Xenon arc lamp producing a continuous emission spectrum without peaks in UV.B and UV.A regions; - the DIN method employs an Osram Ultravitalux lamp (or a Philips MLU 300-WE) having a spectrum with two peaks at 312 and 365 nm which virtually does not produce UVA, apart from the second peak. There is no common agreement on the most suitable type of lamp when the SPF is less than 15. Conversely, when SPF is >15 the Xenon arc lamp should be used, since it produces a higher quantity of UVA. Quantity of product applied: FDA method: 2.0 mg/cm2; DIN method: 1.5=B10.15 mg/cm2. The quantity of product applied corresponds to a filter of about 20lm and 15lm in the FDA and DIN method respectively. Radiation time increase on different skin areas: FDA method: 25%; DIN method: 40%. SPF calculation: FDA method: it is based on arithmetic average; DIN method: it is based on geometric average. Standard Reference Product: FDA method: 8% homosalate, SPF=3D4.1; DIN method: 2.7% p-methoxy-2-ethylhexyl-cinnamate, SPF=3D3.7. MED Evaluation Time: FDA method: unprotected skin MED is measured 24 hours before evaluating the MED value of the skin protected with the tested product. Type of Skin: FDA method: 20 subjects with light skin who, after a 30-60 minute sun exposure after the winter season get easily or relatively easily sunburnt (Skin type I-III according to a classification distinguishing 6 types of skin with progressively decreasing sun sensitivity); DIN method: 20 subjects. Washing-Away Resistance: Unlike the DIN method, the FDA standard requires product resistance examination after water immersion. Each immersion lasts 20 minutes followed by a 20 minute interval before radiation exposure. If the product is still effective after two immersions, it can be defined as water-resistant. If it is still effective after four immersions, it can be declared as waterproof. Variations of the Australian Standards Association Within the FDA method there is also a variation approved by the Australian Standards Association in which the major change refers to the number of persons employed for the test, namely 10 instead of 20. Therefore, the standard error in the individual SPF average must not exceed =B110%, instead of =B15% as required by the FDA. Because of all these differences, different values are obtained with these two methods, which result to be definitely better in the FDA procedure. For example, regarding the same W/O emulsion containing 1.5% 2-ethylhexyl-4-dimethylaminobenzoate - with the DIN method (FRG) a 5-6 SPF value is obtained; - with the FDA method (USA) a 10-12 SPF value is obtained. This difference creates confusion in the consumer as well as wrong interpretations about the screening power of any advertised product. It mainly derives from a different quantity of product applied and therefore a different film thickness on the skin. As a matter of fact, if a 20lm film corresponds to a 10 SPF, theoretically a 15lm film of the same sunscreen shall have a 7.5 SPF. Obviously enough, the SPF value also depends on the carrier with which it is combined. The higher its skin adhesion and its capability to form a compact film, the better its final filtering result and, at equal dose, the higher its SPF value. Very good results are obtained with ointments and W/O creams (see non-sensitizing Seboside based W/O creams). Yet skin adherence and water-repellent properties can also be effectively obtained with PME-1 containing O/W emulsions, with the advantage, over W/O ones, of a better and more uniform filter adsorption - if lipid soluble - into the corneous layer. TABLE OF CONVERSION SPF DIN SPF OTC (German Method) (USA Method) 2 - 3 4 - 6 3 - 4 6 - 8 4 - 5 8 - 10 5 - 6 10 - 12 6 - 7 12 - 14 7 - 8 14 - 16 8 - 9 16 - 18 Giorgio Rialdi -------------- The following is taken from an article about Nanophase Materials in this month's Scientific American: In contrast, radiation having shorter wavelengths, such as damaging ultraviolet light, cannot pass easily through dispersed nanophase ceramic particles, such as titania, zinc oxide and iron oxide. In this case, the tiny grains readily absorb or scatter the short ultraviolet rays. Consequently, nanophase powders are being tested for use in sunscreens. Also, because of quantum confinement effects, the observed color of certain nanophase clusters can vary depending on their sizes. Louis Brus, formerly at AT&T Bell Laboratories and now at Columbia University, has produced in solution several nanophase versions of cadmium selenide, each of which appears to be a different color. In fact, cadmium selenide can be made almost any color in the spectrum simply by changing its cluster size. As such, nanophase powders are making rapid inroads into the cosmetics industry. ***I wonder if we'll be seeing cadmium as an allergen (or causing other problems, like toxicity) in cosmetics? Zinc oxide, in its conventional polycrystalline form and doped with a number of selected impurities, is the basic material from which voltage-dependent resistors, or varistors, are made. In these simple and widely used devices, the electrical resistance effectively drops as the current through them rises over very wide ranges, keeping the voltage across them constant at some value, called a threshold voltage. This nonlinear behavior of these varistors arises from the electrical properties of their grain boundaries. Hence, I conjectured that nanophase zinc oxide--having a much larger number of grain boundaries than the normal variety--might prove to be an even better varistor material, if we could make it. With the help of my Argonne colleagues, we were able to produce pure nanophase zinc oxide. In collaboration with University of Notre Dame student Jongtae Lee, Thomas Mason of Northwestern and others, we recently demonstrated that even pure nanophase zinc oxide exhibits varistor behavior. Its threshold voltage is small--about 40 times smaller than that for conventional, heavily doped varistor material--but usable just the same. And investigations led by our former colleague Ramasamy, now back at the University of Madras, show that if nanophase zinc oxide is doped similarly to commercial varistors, it may be even more useful. Indeed, it should be possible to produce zinc oxide varistors with threshold voltages that range over a factor of more than 300. The key engineering parameter will be the grain size and hence the number of grain boundaries loaded into the material, as well as the amount and type of dopants loaded into those grain boundaries. Much work is needed to turn these results into final products, but the potential is enormous. *** I wonder if nanophase zinc oxide would have useful properties at the electrical current levels seen in living tissue, eg. to affect wound healing, or maybe keloids? Kevin C. Smith MD FRCPC -----------------------