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S u n Prot e c t i o n : C u r re n t

Management Strategies
A d d re s s i n g UV E x p o s u re
Leslie E. Cohen, MD*, Robert T. Grant, MD, MSc
KEYWORDS
 Sun protection  Skin cancer prevention  Photoaging  Sunscreen regulation  UV filters

KEY POINTS
 Sunscreen use can prevent the effects of photoaging and reduce the risk of skin cancer that is
associated with ultraviolet exposure.
 All forms of sun protection in addition to sunscreen, including avoidance of exposure, physical protection, and seeking shade, should be emphasized to patients.
 A sunscreen should have a sun protection factor greater than 15 for ultraviolet B protection and for
ultraviolet A protection should have a critical wavelength of 370 nm or greater in order to be considered broad-spectrum in the United States.

It is well established that ultraviolet (UV) exposure


plays a role in photoaging and certain types of skin
cancer. It is important to understand what forms of
protection exist against UV radiation and to be
able to evaluate which sunscreens, when used as
directed, can provide the most benefit to patients.

PHOTOAGING FROM SUN EXPOSURE


UV light can severely damage the skin and cause
premature aging. Photoaging can be characterized
by visible wrinkles, hyperpigmentation and uneven
pigmentation of the skin, coarseness, laxity, telangiectasias, lentigines, and atrophy.13 In 2013,
Hughes and colleagues4 published a randomized
controlled trial to evaluate whether sunscreen
could prevent the use of photoaging in adults
younger than 55 years of age. Nine-hundred and
three adults were randomized into 4 groups: daily
use of broad-spectrum sunscreen and 30 mg of
beta carotene, daily use of sunscreen and placebo,
discretionary use of sunscreen and 30 mg of beta

carotene, and discretionary use of sunscreen and


placebo. Using skin surface replicas of the patients dorsal hands, the study assessed changes
in microtopography over 4 years in the sunscreen
and beta carotene groups compared with control
groups in a blinded fashion. Increases in microtopography are known to significantly correlate with
risk for actinic keratosis and skin cancer.5,6 Hughes
and colleagues4 reported that skin aging from
baseline to the end of the trial was 24% less in
the daily sunscreen group than in the discretionary
sunscreen group (odds ratio, 0.76; 95% confidence interval, 0.590.98). It is important to understand the topical options available to patients for
protection against photoaging in addition to counseling patients to avoid exposure altogether.

CANCERS ASSOCIATED WITH SUN EXPOSURE


It is also well known that UV radiation increases
the risk for benign, premalignant, and malignant
neoplasms on the face, neck, hands, and other
areas of the body chronically exposed to the sun.
Sun protection and the use of sunscreen are key

Conflicts of interest: The authors have no conflict of interest to disclose.


Division of Plastic Surgery, New York-Presbyterian Hospital, 525 East 68th Street, New York, NY 10065, USA
* Corresponding author.
E-mail address: LeslieECohen@gmail.com
Clin Plastic Surg - (2016) -http://dx.doi.org/10.1016/j.cps.2016.03.006
0094-1298/16/$ see front matter 2016 Elsevier Inc. All rights reserved.

plasticsurgery.theclinics.com

INTRODUCTION

Cohen & Grant


to skin cancer prevention. According to the Skin
Cancer Foundation, 90% of nonmelanoma skin
cancers and 86% of melanomas are related to
sun exposure and UV radiation.
This finding has been validated by many studies
linking UV radiation with the molecular changes
associated with skin cancer. p53 Mutations have
been detected in nonmelanoma skin cancers
from white patients in much higher frequencies
(50%90%) compared with internal malignancies.
These mutations are predominated by the C:G /
T:A mutation at dipyrimidine sites, namely the UV
signature mutations.7 There are other types of
mutations seen in human skin cancers that are
located in sun-exposed body sites that imply that
oxidative DNA damage may also be implicated in
photocarinogenesis.8,9
Almost all cases are preventable by avoiding
exposure to UV radiation from sunlight and artificial sources.

DAMAGE FROM ULTRAVIOLET RADIATION


Although UV radiation can have positive effects on
the skin, such an improvement of mood, increased
vitamin D3 synthesis, and improvement in skin conditions such as psoriasis, UV radiation is mostly
responsible for skin damage.10 There are 3 different
types of UV radiation that are classified by wavelength: UVA (315400 nm), UVB (280315 nm)
and UVC (100 to 280 nm). UVC is germicidal, but
does not reach human skin and is absorbed by oxygen and ozone in the atmosphere. UVA and UVB
reach human skin and cause photodamage.
UVB is medium wavelength (280320 nm) and
cannot penetrate the skin as deeply as UVA rays
can. Although most UVB radiation is filtered by
the atmosphere, it is more energetic than UVA
photons and contributes more to aging and cancer
than UVA light does. It is more common in the
summertime, and peak hours are between 10 AM
and 4 PM depending on the location. UVB radiation
mostly injures the epidermis and contributes to
most acute sunburns. UVA radiation is present
throughout the day regardless of season or the
weather. UVA is therefore the longer wavelength
(315400 nm) and makes up 95% of the radiation
that reaches humans and penetrates deeper into
the dermis of the skin.1113
UV radiation causes intracellular damage in multiple ways. UV light leads to the buildup of reactive
oxygen species and inflammatory mediators, and
inhibits the mitochondrial genome of cells and
the ability of cells to repair themselves.1 More specifically, UVA light is carcinogenic because it produces reactive oxygen species and induces the
inflammatory signaling pathways.9 UVA radiation

can increase the presence of collagen-degrading


matrix metalloproteinases, which can result in
deeper wrinkles and loss of overall collagen.14
UVB light damages DNA by forming covalent
bonds between pyrimidine bases that have a
high mutagenic risk.15,16
Overall, UV light cumulatively increases damage
on a cellular level, increases melanin synthesis, decreases cell immunity, and is photocarcinogenic.

SUNSCREEN
History
Creams to protect the skin against sunburn first
emerged in the 1940s. In 1944, Benjamin Green
invented red veterinary petrolatum, a greasy material, in order to protect soldiers and himself against
UV light in World War II. This substance mixed with
cocoa butter and coconut oil as eventually developed into Coppertone suntan cream. In 1988, the
US Food and Drug Administration (FDA) approved
a sunscreen product called avobenzone, which is
a UVA-only filter. Until that point, the only
approved filters were UVB filters that incidentally
had UVA protection.17 The industry has now
evolved; there are more than 30 different UV filters
approved worldwide to protect against exposure
to sunlight.18 The FDA regulates the chemicals
used in sunscreens and, as of 2012, has limited
the claims for sun protection factor (SPF), how
waterproof a product is, and the length of time it
remains effective.19 Thus, the United States still
has far fewer protects approved by the FDA for
market than the European countries do. For
example, Tinosorb M and Tinosorb S (Bemotrizinol) are ingredients used for UVA protection, with
peak absorption at 310 nm and 340 nm, that are
not yet approved in the United States.20,21

Mechanism
Sunscreens should have certain basic features.
They should be water resistant, hypoallergenic,
photostable, and should not penetrate the skin.
They should also have the ability to dissipate
absorbed light energy without forming reactive intermediates or harmful byproducts.22,23 Typically
sunscreens contain both organic and inorganic
UV filters that combined are broad-spectrum and
protect against the entirety of the UVA and UVB
range. UV filters are classified in 2 groups and
many sunscreens today combine both types of filters in their formulations.

Organic Filters
The first group is chemical or organic filters that
usually come in a liquid form. It is commonly

Sun Protection
found in a liquid formulation or as a water-based
medium. Most organic filters have aromatic compounds conjugated with carbonyl groups. Organic
filters absorb high-energy photons. Electrons in
their benzene rings get excited and absorb in the
UV range. This energy becomes dissipated as
heat or light in a longer wavelength.24
At present there are 15 organic filters approved in
the United States but, as previously mentioned,
many more are used worldwide. There are only 2
organic filters, oxybenzone and avobenzone, that
protect against UVA rays in the United States. Oxybenzone is one of the most widely used UVA
organic filters; it can absorb UV radiation from 270
to 350 nm with absorption peaks at 288 and
350 nm. Although it is an effective filter, there are
a few controversies surrounding its use.25 There
are some in vitro and in vivo studies that have highlighted potential effects of oxybenzone as a hormone modulator. In 2004, Janua and colleagues26
performed a single-blinded human study in which
15 men and 17 postmenopausal women applied a
cream containing 10% oxybenzone(weight/weight)
to their entire bodies at a dose of 2 mg/cm2. After
4 hours of sunscreen application with oxybenzone,
male patients had lower levels of estradiol and
testosterone, whereas inhibin B was slightly
increased. Female patients showed a decrease in
testosterone within the first 24 hours. However, in
both male and female patients, after 4 days of daily
topical application, the investigators found no significant differences in the measured serum hormone levels between the treatment and control
groups among either men or women. The study
concluded that the differences in hormone levels
were not related to the sunscreens containing oxybenzone.25,26 Despite such controversy, up to 6%
oxybenzone is still approved for use in cosmetic
products in the United States.27 Avobenzone is an
organic filter that protects from 310 to 400 nm. It
is the only UVA long-range filter approved by the
FDA but is extremely unstable, meaning it degrades
after 1 hour of exposure. Thus, it must be stabilized
in the final formulation.28,29 There are many classes
of organic filters, including dibenzoylmethane,
benzophenone, p-aminobenzoate, salicylate,
camphor, and cinnamate derivatives. Two of the
new UV filter classes being used worldwide are triazones and benzotriazoles. With triazones, the molecular weight is greater than 500 Da, which
reduces skin penetration. This group has higher absorption coefficients, better antiinflammatory effects, and is highly photostable.24 One such filter,
Tinosorb S, has been able to improve the photostability of other UV filters in a sunscreen.30 Tinosorb A2B, approved in Europe, is a new filter that
protects in the range from 290 to 340 nm, which is

unique because it covers the gap between pure


UVA or UVB filters.24

Inorganic Filters
The second group is inorganic filters, previously
classed as physical filters. Inorganic filters are
minerals that reflect and scatter UV light, and
have a small amount of absorption as well. These
sunscreens have insoluble particles.18 The most
well-known inorganic filters are titanium dioxide
and zinc oxide. Historically, these mineral filters
had poor particle dispersion and were thick and
difficult to apply. They created an opaque film on
the skin and were comedogenic, which decreased
their appeal. Now these materials can be micronized to less than 100 nm and have broader refractive abilities and better protection in the UVB
range. They are easier to apply and spread over
the skin. However, these materials are not
approved in a spray form because of potential
toxicity to the lungs.31 The penetration ability of
nanoparticles in the skin is still a particular focus
of research, especially to skin that is already sun
damaged. There remains a need for further
research on the safety profiles of these specific
products.
In addition, Tinosorb M (already approved in
Europe) is under development. It is created as
organic microparticles that can be dispersed in
water, and it has good photostability and broadspectrum action. It is able to reflect, absorb, and
scatter UV radiation, giving it the properties of
both organic and inorganic filters.32
One warning for patients is that many sunscreens are labeled as natural. This term
commonly refers to aforementioned sunscreens
that contain only the minerals zinc oxide or titanium dioxide as active agents. These mineral sunscreens in general are less likely to have chemicals
such as avobenzone that may induce allergic reactions or skin irritation. It is important again to be
aware that these products may not offer complete
sun protection.

Regulation
Sunscreen labels can be confusing. In 1956,
Rudolf Schulze used the term protection factor,
now called SPF.33 SPF is the quotient of the minimal erythema dose with applied sunscreen and
the minimal erythema dose without sunscreen. It
is an indication of protection against UVB radiation only. It is a faulty system because a sunscreens effectiveness varies with skin type,
amount applied, frequency of reapplication,
formulation of the product, and activities such
as swimming.34

Cohen & Grant


Although the FDA does not support that any
sunscreen less than an SPF of 15 can help prevent
skin cancer, it also states that there is no evidence
to support any increased efficacy in a sunscreen
product with an SPF greater than 50. Thus, the
FDA does not allow any sunscreen to advertise
an SPF greater than 50. All such high-SPF sunscreens can only note on the label that the SPF
is 501. According to the FDA, a high SPF does
not correlate with any UVA protection. SPFs
greater than 50 may inflate peoples sense of protection, which can lead to prolonged exposure.12
In 2006, the European Commission gave a recommendation on the effectiveness of sunscreen that
included a UVA protection factor/SPF ratio of at
least 1:3.35
There is no UVA rating system in the United
States.12 However, the FDA has certain labeling
requirements. It has mandated that any sunscreens with a label broad-spectrum must protect against from UVB and UVA rays. In 2011,
the FDA ruled that, in order to define a product
as broad-spectrum, the products critical wavelength had to be greater than or equal to 370 nm.
The critical wavelength describes the range of
protection over the entire UV spectrum (290
400 nm) and is the wavelength at which 90% of
the cumulative area under the total absorbance
curve occurs. The longer the critical wavelength
is, the broader the UVA protection of the product.36 This label is only a pass/fail test.
Water resistance has a large effect on the quality
of a sunscreen. The FDA states that a product can
be labeled water resistant only if there is no decrease
in SPF level after 2 baths of 20 minutes. In addition,
the FDA does not allow sunscreens to be labeled
sunblock, sweat-proof, waterproof, or all-day.36

New Products
There may be a few new products under development that attempt to protect against sun damage
via new mechanisms. There have been a few
studies recently of the effect of the DNA repair enzymes photolyase and endonuclease. In a recent
randomized clinical study, the clinical and molecular effects of sunscreens that included DNA repair
enzymes were compared with traditional sunscreens in 28 patients with diagnosed actinic keratosis, a precursor of squamous cell carcinoma. The
main outcome measures included hyperkeratosis,
field cancerization (as measured by fluorescence
diagnostics), and levels of cyclobutane pyrimidine
dimers (CPDs) in skin biopsies. A similar effect on
hyperkeratosis was found, but the addition of
DNA repair enzymes to sunscreens was more
effective in reducing field cancerization and CPDs

than sunscreens alone.37 DNA repair enzymes


may therefore be added to sunscreens in the future.
The FDA has not approved many new products
in the last 10 years. Most sunscreens that are
advertised as broad-spectrum in the United States
contain the chemical oxybenzone or avobenzone
to block UVA radiation. The most recent chemical
approved for blocking UVA radiation is ecamsule,
an organic compound.
Unlike avobenzone, which is not intrinsically
photostable and requires photostabilizers to prevent degradation, ecamsule is a photostable
organic UVA absorber, so it does not significantly
break down when exposed to UV light.30,38,39
The UVB range is 290 to 320 nm, and the UVA
range is 320 to 400 nm. Ecamsule is stated to provide protection in the 290-nm to 400-nm range,
with peak protection at 345 nm. Ecamsule should
be combined with a UVB-blocking agent because
it does not provide coverage for the entire UV
spectrum.40

Awareness
In 2012, the FDA officially announced that only a
sunscreen with an SPF of 15 or higher may
permitted to be marketed as able to reduce the
risk of skin cancer. There are many sunscreens
on the market that are labeled with an SPF less
than 15 and that are still permitted to be sold. Patients should be aware that there is no evidence
that an SPF less than 15 has any preventive role
against cancer. Per the FDA, it is recommended
to use a water-resistant, broad-spectrum sunscreen with an SPF of 30 or more for an extended
outdoor activity.
It is not only important to advise patients on their
risk of skin cancer from UV exposure but also key
to counsel them on risk of cancer recurrence once
they have had a cancer resected. A recent study
from Ireland interviewed 250 patients who underwent excision of basal cell carcinomas. Only
28.8% of patients acknowledged that they understood that the pathology of the lesion removed
was basal cell carcinoma and that there was an
increased risk of recurrence of a similar lesion in
the next 3 years. Women and patients less than 65
years of age were significantly better informed about
their diagnosis than men (P<.021 and P<.001
respectively). Of note, although 76.8% of patients
undertook some form of outdoor activity every
day, only 22.8% wore sunscreen every day.41 It is
key to communicate not only the patients final
pathology after a skin cancer is resected but what
their recurrence risk is and the benefits of sun protection; possibly even more in male patients in order
to increase earlier rates of detection.

Sun Protection
Limitations of Sunscreen
Although routine use of sunscreen is of utmost
importance, finding shade, wearing widebrimmed hats and clothing to cover exposed
areas, and wearing UV-blocking sunglasses
should be emphasized as well. It is important to
counsel patients that, if they are using a higherSPF sunscreen, not to be enticed into staying in
the sun longer. Patients should be advised to
apply sunscreen everywhere that is exposed and
to apply at least 30 mL (1 oz) of sunscreen 15 minutes before going outside. Patients should also
be educated that they need to reapply at least
every 2 hours regardless of what the SPF of their
sunscreen is so that they avoid overexposure to
UVA and UVB rays.

SUMMARY
The use of sunscreen is essential for protection
against photoaging and skin cancer. There is no
global consensus on rating systems for sunscreens
but it is essential to understand what makes a product broad-spectrum. In addition, physicians should
have a general understanding that high-quality,
successful sunscreens should not only provide
broad-spectrum protection with UVA and UVB protection but also be formulated so that they are easy
to apply, are water resistant, and are photostable in
order to increase user compliance.

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