UVA: GRASPING A BETTER UNDERSTANDING - La Roche

Transcription

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UVA: GRASPING A BETTER
UNDERSTANDING OF THIS
FORMIDABLE OPPONENT
Leading dermatologists discuss what is now known about the harmful effects of UVA,
and they highlight recent clinical advancements in photoprotection technology.
BY HENRY W. LIM, M.D., AND DARRELL S. RIGEL, M.D.
Back when the very first sunscreen was
introduced in 1928, it was believed that
the short-term harmful effects of ultraviolet (UV) radiation exposure, specifically
sunburn, were all we had to fear from the
sun.1,2 In the succeeding decades, however, it has become clear that sunburn is
only the beginning of the pathologic
effects produced by solar exposure.1
Recent years have brought a much
fuller understanding of the effects of photoexposure, their causes, and ways to protect against them.And, after more than 20
years without the introduction of a single
significant new active sunscreen agent,
new photoprotective agents and more
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JULY 2007 SKIN & AGING
substantive formulations have recently
become available in the United States.3
This article will review recent developments in photoprotection. The content is
based on the Clinical Council on Photoprotection, a roundtable meeting of experts
in photoprotection held on Jan. 20, 2007, in
NewYork,NY,and sponsored by La RochePosay Laboratoire Pharmaceutique.
UVA: A CURRENT FOCUS IN
PHOTODAMAGE
Ultraviolet A (UVA) rays have long
been thought to have minimal harmful
effects, while only UVB rays were
believed to have significant deleterious
effects.4 Erythema (sunburn) and the
delayed effect of suntanning are the most
familiar symptoms associated with UVB
overexposure, and its association with
photocarcinogenesis is well established.
Ultraviolet C poses virtually no threat
because it is absorbed by the ozone layer
of the earth’s atmosphere.
However, research is increasingly demonstrating that UVA is a threat, and a far
greater one than has generally been believed.4
UVA radiation is much more abundant
than UVB in natural sunlight; it accounts
for up to 95% of all UV radiation that
reaches Earth.4 Furthermore, whereas the
amount of UVB in sunlight varies accord-
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UVA: A BETTER UNDERSTANDING OF THIS FORMIDABLE OPPONENT
ing to the season, location on the earth,
and time of day, the intensity of UVA
radiation is more uniform and is present
all year round during all daylight hours.4
In addition, while UVB is blocked by
window and automobile glass, UVA is not.5
Furthermore, UVA, which has a longer
wavelength than UVB, penetrates more
deeply into the skin. (See Figure 1, at
right.)6 With UVB radiation, it penetrates
only into the stratum corneum and is
almost fully absorbed before reaching the
upper dermis. On the other hand, UVA
readily penetrates into the mid-dermis.7
The many negative effects of UV radiation on the skin, including erythema, photoaging, carcinogenicity, and immunosuppression, are exhibited in both UVB and
UVA by damage to DNA. Until recently,
the genotoxic damage caused by UVA
radiation has been thought to be less than
that caused by UVB.7 But new research has
called this thinking into question.
In a recent study using a highly accurate
quantitative assay based on high-performance liquid chromatography combined with
mass spectrometry, investigators examined
the type and yield of DNA damage in
human skin samples exposed to UVA and
UVB radiation.8 Cyclobutane pyrimidine
dimers, commonly associated with UVBinduced DNA damage, were found in substantial numbers in UVA-exposed skin as
well. In addition, UVA-generated dimers
were removed at a much lower rate than
were UVB-induced dimers.
The researchers also demonstrated that
while human skin protects itself very effectively against UVB-induced DNA damage,
it protects itself only weakly against UVAinduced injury.8
The Role of UVA in Photoaging
Repeated skin exposure to UV radiation produces a phototrauma referred to as
“dermatoheliosis, or photoaging.Although
photoaging and intrinsic aging can occur
simultaneously, the two processes differ
significantly, and photoaged skin appears
different from intrinsically aged skin, both
macro- and microscopically.
Macroscopically, photoaged skin is
characterized by fine and coarse wrinkling; dyspigmentation or hyperpigmentation spots, including freckles or lentigines; laxity; sallowness; telangiectasias;
and actinic keratoses.7,2
Figure 1. Penetration of various wavelengths of light into human skin.
Microscopically, in normally aging
skin, the dermis becomes hypocellular;
the epidermis atrophies; collagen forms
a stable, cross-linked matrix; and the
vasculature remains intact. In photoaged
skin, by contrast, the epidermis thickens,
the dermis becomes hypercellular (as a
result of mast cell and fibroblast propagation), and the vasculature becomes
dilated and twisted.2
All portions of the solar spectrum,
including UVA, UVB, and infrared
radiation, contribute to photoaging.2
However, UVA is now recognized as
the single most important wavelength
in causing photoaging.4,2 The ability of
UVA to deeply penetrate the dermis
may account for the primacy of its role
in photoaging, as may the fact that
UVA exposure does not produce an
erythemal “warning signal,” so that
higher cumulative doses of UVA radia-
tion may be unknowingly obtained.
The ability of UVA to penetrate glass is
also a factor. Figure 2, next page,
illustrates the result of long-term
indoor exposure to UVA radiation.9
The Role of UVA in
Immunosuppression
Photoimmunosuppression, a well-documented phenomenon, may play an important role in the genesis of skin cancer; it
increases the likelihood and severity of
infectious diseases, and reduces the effectiveness of vaccines.7 Immunosuppression
induced by UV appears to start with DNA
damage and trans to cis-urocanic acid isomerization in the stratum corneum, which
is associated with the production of
cytokines, histamine, and neuropeptides.7
Recent research has shown that UVA
plays a key role in immunosuppression.
Ultraviolet A has been shown to supJULY 2007 SKIN & AGING
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Figure 2. Unilateral cutaneous elastosis, one of the best-known manifestations of helioderma, caused by UVA radiation. The patient
had worked for 15 years in the same room with the same orientation to a window, so that the left side of her face had been continuously exposed to UVA radiation, while the right side had not.
Reprinted with permission from Moulin G et al. Ann Dermatol Venereol. 1994;121:721-723.
press induction and elicitation of the contact and delayed-type hypersensitivity
responses to recall antigens.7 So important
is the impact of UVA on immunosuppression that a new sunscreen measure —
immune protection factor — has been proposed for use along with the current sun
protection factor (SPF) measure because the
latter is not an indicator of degree of protection from UVA.10
The Role of UVA in Carcinogenesis
Strong evidence supports the role of
UV exposure in the development of skin
cancers, including not only nonmelanoma skin cancers such as squamous
cell and basal cell carcinomas,7 but also
malignant melanoma.11
In the case of melanoma, several lines
of epidemiologic evidence, in addition to
other sources of evidence, point particularly to high, intermittent exposure to
solar UV radiation as a significant risk
factor. These data include findings that
the incidence of the disease generally
increases with decreasing latitude and the
heightened intensity of the sun’s rays.
The highest recorded rate of
melanoma in the world occurs in
Australia, where the annual incidence is
up to 20 times the incidence in Europe.11
64
It was long thought that UVB was primarily responsible for melanoma.12
However, increasing evidence indicates
that UVA may also play a significant role.4
Based on an analysis of World Health
Organization data from 45 countries,
Garland and colleagues found that UVA
was associated with melanoma mortality
rates after controlling for UVB and average skin pigmentation.12
Limited but consistent data from studies of
tanning salon users also show UVA exposure
in these beds to be a risk factor for
melanoma. A recent meta-analysis of casecontrol studies and one cohort study conducted between 1984 and 2004 demonstrated a significantly increased risk of cutaneous
melanoma following the use of sunbeds and
sunlamps.13 These results are supported by a
prospective cohort study of 106,379 Swedish
and Norwegian women demonstrating that
the use of tanning devices once a month or
more is statistically significantly associated
with melanoma risk.14
In consideration of findings such as these,
the American Academy of Dermatology has
supported regulations prohibiting minors
from using tanning devices, preventing facilities from advertising such devices as safe, and
urging the placement of a Surgeon General’s
warning on all such devices.15
CONTEMPORARY
CONSIDERATIONS IN
SUNSCREEN USE: BROADENING
OUR PATIENTS’ PROTECTION
In view of the magnitude of the sun’s
negative impact on the skin, we might be
tempted to advise our patients to entirely
avoid UV exposure, both outdoor and
indoor. However, given the impracticality
of such advice, sunscreens are vital in providing protection from the photodamaging effects of UV rays.16
Since their inception, sunscreens have
been known to protect against erythema,
the acute effect of UV exposure. But they
are now understood to protect against many
of the long-term effects of UV exposure as
well,including photoaging,actinic keratoses,
and some skin cancers.17
Because UVA rays, especially the
long-wavelength UVA-1, can pass
through clouds and automobile and
window glass, incidental exposure to
UVA radiation is a daily risk. In view of
research findings implicating UVA in the
most severe consequences of sun exposure, many groups currently recommend
universal, year-round, daily use of a
broad-spectrum sunscreen — one that
protects against both UVB and UVA —
with an SPF of at least 15.18-20
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We need to continue to educate patients
about the need for daily sunscreen use,
about proper sunscreen application, and
about the other steps they need to take to
protect themselves from UV exposure.
(See the patient education handout
titled, “Are You Really Protecting
Yourself from the Sun’s Dangerous
Rays?” and feel free to photocopy it to
distribute to your patients.)
A Look at Common Sunscreen
Ingredients
To provide broad-spectrum photoprotection, a sunscreen must include a combination of organic and inorganic filters.
Advances in sunscreen technology have
mimicked and built upon the body’s natural cutaneous defenses against UV radiation, which include the following:
Among the body’s endogenous defenses
is the ability of the epidermis to scatter the
majority of visible light rays, which is what
inorganic UV filters in sunscreens do.17
A second endogenous defense mechanism is that urocanic acid in the skin undergoes UV-initiated isomerization, which is
what organic filters cause to happen.17
A third endogenous defense shield is
melanin, which protects the skin by filtering and scattering UV rays and
changing the absorbed energy into heat
energy rather than chemical energy —
the same mechanism by which organic
filters protect the skin.17 It is this mechanism that causes a sensation of warmth
in sunscreen wearers, something about
which many patients complain.21
In addition to having light filtering
and scattering capabilities, as well as the
others mentioned above, photostability is
another important characteristic of an
effective sunscreen. UV filters that are
photolabile will be rapidly inactivated
after exposure to UV rays, thus losing
their effectiveness. Several factors contribute to photostability, including the
filter, the presence of other filters in the
product, and the vehicle or solvent. Most
UV filters, including avobenzone, octinoxate, and octyl dimethyl para-amino
benzoic acid (PABA), are photolabile.
Thus, other filters, including zinc oxide,
titanium dioxide, octocrylene, methylbenzylidene camphor, and the salicylates,
are frequently used in sunscreen preparations to increase their photostability.17
Figure 3. Full broad-spectrum UVA and UVB protection provided by octocrylene,
ecamsule, and avobenzone. Data on file. L’Oreal USA. Clark, NJ; 2006.
Constructing the Ideal
Broad-Spectrum Filter
The ideal broad-spectrum filter must be
composed of compatible and complementary filters that can provide effective protection over the entire UVA and UVB spectrum.The aesthetics of the product also need
to be optimized to increase the likelihood of
adherence.17 The ideal sunscreen should also
THE IDEAL BROAD-SPECTRUM
FILTER MUST BE COMPOSED
OF COMPATIBLE AND
COMPLEMENTARY FILTERS
THAT CAN PROVIDE
EFFECTIVE PROTECTION
OVER THE ENTIRE UVA AND
UVB SPECTRUM.
be photostable in order to ensure functional
longevity on the skin. Finally, its vehicle
should be resistant to shedding with rubbing, sweating, or water immersion.17
All UV filters have a particular absorption
spectrum, which can be extended by combining complementary agents. The ideal
sunscreen would combine UVA organic
absorbers, UVB organic absorbers, and an
inorganic filter. UVA organic absorbers
include benzophenones (320 nm to 350
nm),2 avobenzone (357 nm), and, most
recently,ecamsule (Mexoryl SX) (344 nm).22
UVB organic absorbers include salicylates
(~300 nm) and cinnamates (310 nm to 311
nm).2 Inorganic filters, which act to reflect
or scatter UVA and UVB, include titanium
dioxide and zinc oxide.2
Both titanium dioxide and zinc oxide are
inorganic white particulates, so they must be
reformulated for aesthetic purposes for use
in sunscreens, but there is an unfortunate
trade-off involved: Smaller particles yield less
white residue on the skin but poorer photoprotection, while larger particles offer more
protection but more white residue, and
hence the possibility of poor adherence.16,2
New Products Offering
Broad-Spectrum Protection
After two decades without a significant
breakthrough in sunscreen ingredients in
the United States,3 two new options that
promise to improve broad-spectrum,
photostable UV protection have recently
been introduced.
One is a new technology trade-named
Helioplex. Several products are available
using the Helioplex technology, which
combines photostable UVB filters, and
UVA filters avobenzone and oxybenzone in
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a formulation that slows the degradation of
avobenzone to increase its photostability.23,3
Another new introduction features
Mexoryl SX. Mexoryl SX was developed
for use in combination with avobenzone
and octocrylene for broad-spectrum protection. (See Figure 3, previous page.)
In this formulation, octocrylene acts to
stabilize avobenzone. Available in Europe
and Canada since 1993, Mexoryl SX is the
first new photostable short-UVA filter in a
sunscreen formula to be approved by the
U.S. Food and Drug Administration and is
now available in the United States in the
new sunscreen product Anthelios SX.
Anthelios SX is an SPF15 lightweight
moisturizing cream that is intended for
daily use. The product protects against
both UVB and UVA. Fragrance-free and
allergy tested, it is suitable for sensitive skin
and is oil-free and noncomedogenic.
Translating New Knowledge of
UVA into Protection for Patients
A large and growing body of research has
identified UVA as a key contributor to
photoaging, immunosuppression, and carcinogenesis. Because UVA is present all year
round and UVA-1 can pass through window glass, patients need to be advised to
protect themselves every day from UVA.
Growing awareness of the importance
of daily UV protection has led
researchers and manufacturers to focus
on the development of an ideal sunscreen, which would combine photostability with broad-spectrum, well-balanced UV protection. Recent advances
in this regard have led to the introduction of important new photoprotective
ingredients and products. It is hoped
that advances will continue in the
devolvement of new filters, improved photostability, and new application methods. ■
Dr. Lim is Chairman and
C. S. Livingood Chair of the
Department of Dermatology at
Henry Ford Hospital in
Detroit, MI.
Dr.Rigel is Clinical Professor
of Dermatology at New York
University Medical Center in
New York, NY.
66
*Acknowledgments
Clinical Council on Photoprotection:
Alicia Barba, M.D., Miami, FL; Diane
Berson,M.D.,NewYork,NY;David A.Colbert,
M.D., NewYork, NY; Coyle S. Connolly, D.O.,
Philadelphia, PA; Zoe Diana Draelos, M.D.,
Winston-Salem, NC; Cheryl L. Effron, M.D.,
Anaheim, CA; Patricia K. Farris, M.D., New
Orleans, LA; Brad Katchen, M.D., New York,
NY; Amy B. Lewis, M.D., New Haven, CT;
Mary P. Lupo, M.D., New Orleans, LA; Marta
Rendon, M.D., Boca Raton, FL; James M.
Spencer, M.D., New York, NY; and Jessica Wu,
M.D., Los Angeles, CA.
References
1. American Academy of Dermatology. New formulations improve sunscreen effectiveness. Available at:
http://www.aad.org/aad/Newsroom/New+Formul
ations+Improve+Sunscreen+Effectiveness.htm.
Accessed February 11, 2007.
2. Lowe NJ, Friedlander J. Prevention of photodamage with sunprotection and sunscreens. In:
Gilchrest BA, ed. Photodamage. Cambridge, Mass:
Blackwell Science; 1995:201-220.
3. Rundle RL. New sunscreens promised advances
in protection. Wall Street Journal. December 27,
2005. Available at: www.ascdas.org/news/sunscreens.htm. Accessed February 9, 2007.
4. Skin Cancer Foundation.The dangers of tanning. Available at: http://www.skincancer.org.
Accessed February 12, 2007.
5.Tuchinda C, Srivannaboon S, Lim HW.
Photoprotection by window glass, automobile
glass, and sunglasses. J Am Acad Dermatol.
2006;54:845-854.
6. American Academy of Dermatology.
Overexposure to sun can happen indoors and outdoors. Available at:
http://www.aad.org/aad/Newsroom/Photoprotect
ion.htm. Accessed February 11, 2007.
7. Moyal D, Fourtanier A. Acute and chronic effects
of UV on skin: what are they and how to study
them? In: Rigel DS,Weiss R, Lim HW, Dover JS,
eds. Photoaging. New York, NY: Marcel Dekker, Inc;
2004:15-32.
8. Mouret S, Baudouin C, Charveron M, Favier A,
Cadet J, Douki T. Cyclobutane pyrimidine dimers
are predominant DNA lesions in whole human
skin exposed to UVA radiation. Proc Nat Acad Sci.
2006;103:13765-13770. Available at:
http://www.pnas.org/cgi/content/short/103/37/1
3765. Accessed February 12, 2007.
9. Moulin G,Thomas L,Vigneau M, Fiere A. A case
of unilateral elastosis with cysts and comedones.
Favre-Racouchot syndrome. Ann Dermatol Venereol.
1994;121:721-723.
10. American Academy of Dermatology. New
research in sun protection shines the light on sunscreen and importance of sun-safe behaviors
beyond adolescence to lower skin cancer risk.
Available at:
http://www.aad.org/public/News/NewsReleases/
Press+Release+Archives/Skin+Cancer+and+Sun+
Safety/NewPhotoProtectionDeLeo.htm. Accessed
February 11, 2007.
11.World Health Organization. Health effects of
UV radiation. Available at:
http://www.who.int/uv/health/uv_health2/en/pri
nt.html. Accessed February 13, 2007.
12. Garland CF, Garland FC, Gorham EC.
Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality
rates. Ann Epidemiol. 2003;13:395-404.
13. Gallagher RP, Spinelli JJ, Lee TK.Tanning beds,
sunlamps, and risk of cutaneous malignant
melanoma. Cancer Epidem Biomark Preven.
2005;14:562-566.
14.Veierod MB,Weiderpass E,Thorn M, et al. A
prospective study of pigmentation, sun exposure,
and risk of cutaneous malignant melanoma in
women. J Natl Cancer Inst. 2003;95:1530-1538.
15. American Academy of Dermatology. American
Academy of Dermatology issues statement endorsing the World Health Organization’s recommendation to restrict tanning bed use. Available at:
http://www.aad.org/aad/Newsroom/who_endors
ement.htm. Accessed February 14, 2007.
16. Levy SB. Sunscreens and photoprotection.
Available at:
http://www.emedicine.com/derm/topic510.htm.
Accessed December 1, 2006.
17. Kullavanijaya P, Lim HW. Photoprotection. J
Am Acad Dermatol. 2005;52:937-958.
18. American Academy of Dermatology.The future
of sunscreens. Available at:
http://www.aad.org/public/News/NewsReleases/
Press+Release+Archives/Skin+Cancer+and+Sun+
Safety/The+Future+of+Sunscreens.htm. Accessed
February 11, 2007.
19. Lim HW, Draelos ZD, Rigel DS, Ruenger TM.
Shedding light on complete UV protection. Cosmet
Dermatol. 2006;19:1-8.
20. American Academy of Dermatology. 2006 facts
about sunscreen. Available at:
http://www.aad.org/NR/rdonlyres/4D8AD6D2AE9B-42FE-B204FB55C48C7E4E/0/2006FactsAboutSunscreens.do
c. Accessed February 9, 2007.
21. Draelos ZD. Cosmetics. Available at:
www.emedicine.com/derm/topic502.htm.
Accessed December 1, 2006.
22. Moyal D, Chardon A, Kolias N. UVA protection efficacy of sunscreens can be determined by
the persistent pigment darkening (PPD) method
(part 2). Photodermatol Photoimmunol Photomed.
2000;16:250-255.
23. Neutrogena. Suncare FAQs. Available at:
http://www.neutrogena.com/acs/faq.asp. Accessed
February 9, 2007.
DISCLOSURES: Dr. Lim is a consultant for
Johnson & Johnson, La Roche-Posay
Laboratoire
Pharmaceutique,
Orfagen
Laboratories, and Dow Pharmaceutical Sciences.
Dr. Rigel is a consultant and speaker for
Beiersdorf AG, Johnson & Johnson, La RochePosay Laboratoire Pharmaceutique, and
Neutrogena Corporation.
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Page 67
Patient Education Handout
Are You REALLY Protecting Yourself
from the Sun’s Dangerous Rays?
Quiz yourself on whether you are aware of these sun-safe strategies.
Use a Sunscreen Every Day.
• Sun protection is the most important means of preventing skin
cancer and early aging of the skin. Even on the most overcast
days, 80% of the sun’s rays will pass through the clouds. And
UVA rays — the rays that cause early aging, as well as skin cancer
and immune suppression — pass right through window glass.
Thus, daily use of a broad-spectrum sunscreen is recommended
even when you won’t be going outside. When used on a regular
basis, sunscreens actually allow damaged skin to repair itself.
Choose a Sunscreen that Provides
Broad-Spectrum Protection.
• To protect yourself from all of the sun’s dangerous effects,
you need a sunscreen with ingredients that provide protection against UVB and UVA rays. Such ingredients include oxybenzone, octylmethyl cinnamate or cinoxate, sulisobenzone,
salicylates, titanium dioxide, zinc oxide, avobenzone, and
ecamsule (Mexoryl SX).
Choose a Sunscreen with an SPF
(Sun Protection Factor) of at Least 15.
• SPF tells you how much sunburn protection a sunscreen provides. The higher the SPF, the more the sunburn protection.
But remember that the sun’s UVA rays lead to other negative
effects (like early aging and skin cancer), and SPF tells only
about the product’s ability to screen UVB rays. So check for
UVA-protective ingredients as well.
Apply Sunscreen Generously.
• 1 ounce — about enough to fill a shot glass — is the amount needed
to provide enough coverage to exposed areas of the body.
✁
Sources: Moulin G,Thomas L,Vigneau M, Fiere A. A case of unilateral elastosis with cysts and comedones.
Favre-Racouchot syndrome. Ann Dermatol Venereol. 1994;121:721-723. American Academy of Dermatology.
2006 facts about sunscreen. Available at: http://www.aad.org/NR/rdonlyres/4D8AD6D2-AE9B-42FE-B204FB55C48C7E4E/0/2006FactsAboutSunscreens.doc. Accessed February 9, 2007.
67

UVA: GRASPING A BETTER UNDERSTANDING - La Roche

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