a new innovation for the management of hyperpigmentation

NOVEMBER 2013
A NEW INNOVATION
FOR THE MANAGEMENT
OF HYPERPIGMENTATION
A Roundtable Discussion on Novel Management
Strategies for Hyperpigmentation
Published as a promotional supplement to
®
Introduction
Disorders of hyperpigmentation, including melasma,
lentigines, and postinflammatory hyperpigmentation, are
extremely common among patients seen in dermatologists’
offices. While various modalities have been available for
treating these problems, none of the interventions is ideal.
Hydroquinone remains the gold standard as a topical skinlightening agent, but it can cause skin irritation, contact
dermatitis, and exogenous ochronosis, and based on animal
studies, there are theoretical concerns about carcinogenicity
with hydroquinone.1 Arbutin has been introduced as another
topical agent for skin lightening, but it can be hydrolyzed to
hydroquinone by normal skin microflora.2 Chemical peels,
as well as laser and light-based procedures, can also be
used to treat hyperpigmentation, but these procedures may
be associated with downtime and are accompanied by
other risks, including additional hyperpigmentation.3
Lytera was launched in January, 2013, as a nonprescription,
hydroquinone-free topical modality that can be used by
patients of all skin types to reduce the appearance of visible
dark spots while also improving overall skin tone and texture.
It is an innovative product formulated with a combination of
ingredients that target four distinct groups of pathways in the
development of hyperpigmentation (Table 1). The actives in
Lytera inhibit melanocyte activation, reduce melanin synthesis
by limiting tyrosinase availability, decrease melanin transfer
to keratinocytes, and promote keratinocyte turnover.4-10
This supplement summarizes the panel’s discussion of their
experiences encompassing the spectrum of hyperpigmentary
disorders and their variety of approaches, including
combining Lytera with other treatment modalities.
Table 1
Key Ingredients in Lytera
The limitations of existing treatments for hyperpigmentation
have fueled research to develop better alternatives. Recently,
a distinguished panel of dermatologists convened to discuss
their use of Lytera® Skin Brightening Complex (“Lytera”
SkinMedica®, An Allergan Company) in the context of
clinical trials and clinical practice. The discussion was
chaired by Mitchel P. Goldman, MD, San Diego, CA, and the
panel participants included Suzanne Bruce, MD, Houston,
TX; Valerie D. Callender, MD, Glenn Dale, MD; Annie Chiu,
MD, North Redondo Beach, CA; Sabrina Guillen Fabi,
MD, San Diego, CA; Mona Foad, MD, Cincinnati, OH; and
Wendy E. Roberts, MD, Rancho Mirage, CA.
Dr. Goldman: Dr. Bruce, you were involved in a premarketing
clinical trial evaluating the efficacy and safety of Lytera.
Please tell us about your findings.
Dr. Bruce: Our study enrolled patients with Fitzpatrick skin types
I to IV having moderate-to-severe facial hyperpigmentation
who used Lytera twice daily with a standardized skin care
regimen for 12 weeks. In preparation for this discussion, I
reviewed photographs from participants in the trial, and
what struck me was that in addition to the lightening of
brown spots, the patients had improvements in skin texture
and in the background erythema that is seen in significantly
photodamaged skin (Figure 1A and B).
2
Reduce Melanocyte Activation
4-Ethoxybenzaldehyde
Tetrahexyldecyl Ascorbate
Tetrapeptide-30
Reduce Melanin Transfer
4-Ethoxybenzaldehyde
Niacinamide
Tetrapeptide-30
Reduce Melanin Synthesis
Retinol
Linoleic Acid
Glabridine from Glycyrrhiza
Glabra (Licorice) Extract
Hexylresorcinol
Tetrapeptide-30
Remove Epidermal Melanin
Retinol
FIGURE 1A and B: This 56-year-old female was concerned about
facial brown spots, redness, and wrinkles (A). She was started
on Lytera Skin Brightening Complex twice a day and sunscreen.
(B) Note the decrease in her signs of chronic photodamage after
treatment for 3 months.
(A)
(B)
I believe the redness in these patients represents inflammation
from sun damage and that it improved because Lytera
has ingredients with anti-inflammatory activity, including
4-ethoxybenzaldehyde,5 glabiridin from licorice root
extract,8 and niacinamide.4
worth noting that Lytera provided these global improvements
in skin appearance without causing the irritation that can be
seen with hydroquinone and retinoids.
The changes in skin texture, including reduction in fine lines
and pore visibility, were also remarkable. Lytera contains
retinol, but the study participants were prohibited from using
other topical products that can affect skin texture. And, it is
Dr. Goldman:
Certainly,
other
treatments
for
hyperpigmentation can produce inflammation that can
even lead to hyperpigmentation.11 Dr. Roberts, have you
seen similar effects in your patients treated with Lytera?
A NEW INNOVATION FOR THE MANAGEMENT OF HYPERPIGMENTATION
A Roundtable Discussion on Novel Management Strategies for Hyperpigmentation
Dr. Roberts: Absolutely. My experience includes skin of
color (SOC) patients with melasma or postinflammatory
hyperpigmentation (PIH) secondary to acne that I started
on Lytera prior to performing a chemical peel or laser
procedure. In looking at their photographs, I was amazed
at the amount of pigment and textural improvements
they achieved using Lytera alone. I also noticed some
improvement in active acne lesions, which perhaps might
be the result of the anti-inflammatory ingredients in Lytera.
Dr. Goldman: Dr. Fabi was also involved in conducting
premarketing studies with Lytera. What did you notice in
terms of erythema?
Dr. Fabi: Some patients developed more erythema than I
expected, but that is because they were also using a topical
retinol every night along with Lytera twice a day. In clinical
practice, I do not see the erythema when I use Lytera alone,
and when incorporating a topical retinol into the regimen, I
do so slowly to avoid the irritation it can cause.
Focus on Melasma
Dr. Goldman: Melasma is probably the most challenging
hyperpigmentary disorder we treat. What has been your
experience with Lytera for managing melasma?
using it seem to benefit with reduced severity of recurrent
hyperpigmentation.
Dr. Callender: I also like to use Lytera for maintenance
in melasma patients, but a prescription-strength 4%
hydroquinone is indicated for initial treatment. Then, once
the skin is clear or almost clear, I switch to Lytera. Lytera
gives patients a necessary hydroquinone holiday, and I am
finding it works well to mitigate melasma flares.
Dr. Chiu: I also start with prescription hydroquinone when
using a topical agent to treat patients with significant
melasma, and I use a compounded product that contains
8% hydroquinone with ascorbic acid and kojic acid. After
2 months, I switch to azelaic acid 15% gel (Finacea®,
Bayer HealthCare Pharmaceuticals Inc., Wayne, NJ) with
Lytera for maintenance, and I’ve had good success with that
approach. However, I have also used Lytera alone to treat
melasma with good results (Figure 3A and B).
FIGURE 3A and B: (A) This 37-year-old female of Filippino descent
presented for the treatment of melasma. (B) She was started on
Lytera twice daily and already had significant improvement after
6 weeks.
(A)
(B)
Dr. Foad: I especially like using Lytera for melasma, and I
have been impressed over the past few months that it seems
to minimize the severity of recurrences that are inevitable
during the summer (Figure 2A and B).
Dr. Bruce: I have made the same observation. We expect
melasma to get worse in the summer, but Lytera seems to
temper those flares.
Dr. Roberts: I find Lytera a great choice for maintenance
in melasma patients, and agree that patients who are
FIGURE 2A and B: This 38-year-old female with Fitzpatrick skin type III was treated previously for melasma with a Vitalize® peel and 6
weeks later with a 1927-nm nonablative fractional laser procedure. In September, 2012, (A) 3 months after the laser treatment, she
started using the Lytera Skin Brightening System, including Lytera twice daily and topical retinol at night (M and W x 2 weeks, M, W, and
F x 2 weeks, then nightly). After 8 weeks, her melasma was significantly improved (B). She continued using the Lytera Skin Brightening
System, and through the summer of 2013, her melasma is much better than in past summers despite spending a lot of time outdoors
watching her four children play sports.
(A)
(B)
(A)
(B)
(A)
(B)
Published as a promotional supplement to Dermatology Times®
3
FIGURE 4A and B: (A) This 53-year-old Hispanic female with
melasma was treated using IPL in August, 2007, and November,
2010, but without much improvement. Subsequently, she had no
improvement after fractional nonablative laser treatment (Fraxel®
Dual) performed in February, 2011. She was started on Lytera
Skin Brightening Complex, and her follow-up photo (B) shows
significant improvement of her melasma after 12 weeks.
(A)
(B)
Dr. Goldman: I have also used Lytera alone to treat melasma
and achieved good results (Figure 4A and B).
However, I think the combination of Lytera with intense
pulsed light (IPL) is particularly effective, and the explanation
may relate to the ability of each modality to affect both
pigment and the vasculature. Interactions between the
vasculature and melanocytes is a proposed mechanism
in the development of melasma,12 and histological studies
show increased vascularity in the dermis of melasma
lesional skin.13 Consistent with the latter study, our VISIA®
Complexion Analysis (Canfield Scientific, Inc., Fairfield,
NJ) images taken of melasma patients show areas of
hyperpigmentation correspond with sites of increased
vascularity.12
Who else is using Lytera with a procedure to treat melasma?
Dr. Fabi: I agree with you about the beneficial effects of IPL
and Lytera on the vascular component in melasma.
I am using Lytera in patients with melasma as an alternative to
hydroquinone in those who have been using hydroquinone
long term and also as a maintenance regimen after laser
or IPL treatment for patients who have refused to use
hydroquinone. Returning for a procedure every month is
impractical, and by using Lytera, these patients seem to
be maintaining their treatment benefit longer. I think it is
the first topical product we have that works comparably to
hydroquinone and can be used safely long term.
vascularity,14 and I believe that Lytera plus treatment with a
fractional nonablative laser addresses all of these features.
Using the 1927-nm laser with conservative settings, I get
up to 50% clearance after a single treatment. Using Lytera,
I feel more comfortable being sufficiently aggressive with
the laser.
Dr. Foad: I love the 1550/1927 fractional nonablative
laser for treating hyperpigmentation, and we now pretreat
patients with Lytera instead of hydroquinone. For melasma,
I use only the 1927-nm wavelength and do 4 passes. I tell
patients they may need additional treatments, but I’d rather
start conservatively to avoid causing inflammation. I also
use TNS Recovery Complex® (SkinMedica®) pretreatment,
restart it 1 week after the laser procedure, and restart Lytera
2 weeks post laser.
Dr. Bruce: I have combined Lytera with both the 1550-nm
and the 1927-nm fractional nonablative lasers for treating
melasma. I have not seen any patients whose melasma
worsened after their laser treatment, which is a problem that
would occur in an occasional patient before I was using
Lytera. Now, I am trying to be even more conservative,
and I am using the 1440-nm fractional nonablative laser
(Clear+Brilliant®, Solta Medical, Inc.).
Dr. Fabi: I like IPL to treat melasma in patients with
Fitzpatrick skin types I to III, but for patients with recalcitrant
hyperpigmentation or type IV skin, I use the 1927-nm thulium
laser (Figure 5A and B).
FIGURE 5A and B: This 38-year-old female with melasma
and Fitzpatrick skin type IV previously used Epiquin Micro™
(SkinMedica®) and topical retinol every other night, but
experienced irritation and peeling. One month after stopping the
two topical agents (A), she was treated with the 1927-nm thulium
laser. She started Lytera 1 week later and topical retinol after 2
weeks with gradual upward titration of application frequency.
(B) She experienced no peeling or tolerability problems with the
topical agents and had significant improvement in her melasma 1
month after her laser procedure.
(A)
(B)
(A)
(B)
Dr. Goldman: Has anyone used Lytera with a fractional
nonablative laser to treat patients with melasma?
Dr. Roberts: My first-line choice for a procedure to treat
melasma has evolved over time. I first used chemical peels,
then the 1550-nm fractional laser (Fraxel®, Solta Medical,
Inc., Hayward, CA), but now I favor the 1927-nm fractional
thulium laser (Fraxel® Dual, Solta Medical, Inc.) because I
think it is even safer, especially in SOC patients. Histological
studies also show melasma is accompanied by increased
solar elastosis in the dermis in addition to the increased
4
When using a laser, I generally pretreat patients using the
4-component skin brightening system (Lytera Skin Brightening
System, SkinMedica®), but have them stop the retinol and
Lytera 1 week before the procedure. I add clobetasol 2 days
before the laser in darker skinned patients when using the
thulium laser, and add clobetasol for 3 days post treatment in
all patients. I restart Lytera at 1 week and add back the topical
A NEW INNOVATION FOR THE MANAGEMENT OF HYPERPIGMENTATION
A Roundtable Discussion on Novel Management Strategies for Hyperpigmentation
retinol after about 3 weeks. I think this combination approach
provides greater pigment clearance than monotherapy with
Lytera alone and minimizes the risk of PIH, although there are
no studies yet to validate that concept.
Dr. Goldman: We published a study in 2002 in which we
found hydroquinone pretreatment in patients with Fitzpatrick
skin type IV did not prevent PIH after facial resurfacing with
a nonfractional ablative laser.15 The only possible benefit
of pretreatment was that it allowed insight into how much
irritation individuals developed with hydroquinone, which
could help with decisions on post-operative care. To the best
of my knowledge, there has not been a similar study done in
patients undergoing fractional resurfacing. What are your
thoughts about pretreating darker skin type patients with
Lytera to minimize PIH after a fractional laser procedure?
Dr. Fabi: Anecdotally, I believe that use of Lytera is mitigating
the PIH that can definitely occur after treatment with the
1927-nm laser or other lasers and light devices. Since Lytera
contains ingredients with anti-inflammatory activity, it may
decrease the postop redness and secondarily the PIH.
Dr. Roberts: Dr. Goldman, your 2002 paper changed the
landscape in terms of using hydroquinone prior to laser
resurfacing. However, I think some controversy remains. I
still feel more comfortable using a skin-lightening agent prior
to laser to prevent PIH in SOC patients, and before Lytera
was available, I was using hydroquinone. However, not all
people with SOC are recognized as such, and I published
the Roberts Skin Type Classification System that addresses
these individuals who phenotypically appear to be
Fitzpatrick type II or III, but tend to develop postprocedural
hyperpigmentation.16 Often these patients have mixed
ancestry, and using Lytera as a pretreatment for them makes
me feel more comfortable pushing the envelope a little with
the laser procedure.
I start patients on Lytera as soon as we decide to schedule
a procedure, which means they’ll start using it about 2 to 4
weeks before. I ask patients to stop the Lytera 1 week before
the procedure if they are a Fitzpatrick skin type IV or darker
and just 2 days before if they are a lighter skin type, and
I’ve been waiting about 1 week for the skin to normalize
after the procedure before reintroducing Lytera.
Dr. Chiu: I am also using the 1550/1927 laser with Lytera
to treat melasma, and I too am very conservative with the
laser because I have seen patients develop paradoxical
worsening of their melasma. I haven’t done a controlled
study or treated enough patients to make any definitive
statements, and maybe I’ve just been lucky, but I believe
that I am also seeing less rebound hyperpigmentation since
I began using Lytera as a pretreatment.
I especially like using Lytera as pretreatment in Asian and
Native American patients whose skin can look very fair
but who seem prone to develop hyperpigmentation after
fractional nonablative laser treatment. Aside from being
effective, Lytera is well-tolerated in these patients as they are
not developing the irritation and inflammation that I would
see when I was using hydroquinone post or even pre laser.
I allow patients to continue with Lytera immediately after
the laser treatment and have not had problems. There are
occasional patients who develop irritation with Lytera, but
that’s with or without a procedure.
Rejuvenation for Photodamage
Dr. Goldman: Patients who come to the dermatologist with
concerns about hyperpigmentary disorders also include
those with exaggerated freckling and solar lentigos from
sun exposure. What is your experience treating the latter
conditions with Lytera alone or in a combination protocol?
Dr. Foad: I use an analogy of icebergs to describe
hyperpigmented lesions and their treatment to my patients.
Some lesions are like floating icebergs, but with others, there
is much more substance below the surface. Depending on
the depth, patients may need IPL, a peel, fractional laser,
or even an ablative laser treatment to reach the pigment.
Using Lytera helps to “melt” the superficial component and
may be adequate for the “floating icebergs” while allowing
another intervention to be more effective at reaching the
deeper pigment. Nevertheless, no matter what you do,
there can still be some stubborn pigment under the skin
surface, and so I spot treat some of the larger, discrete
lesions with a 755-nm laser.
Dr. Fabi: All of the patients in our premarketing clinical trial
were being treated for lentigines from photodamage and
they did very well. So, now I am using Lytera routinely for
patients who have general dyschromia and a component of
redness from their photodamage (Figure 6A and B). I usually
put them on the 4-component Lytera Skin Brightening System
because I believe the combination of Lytera with the topical
retinol gives enhanced results. However, I instruct patients to
start the topical retinol once a week for 1 week, twice a week
the second week, and then continue to titrate it gradually
upward until they can tolerate nightly application.
Dr. Bruce: I think younger people with photodamage who
typically have just lentigines can be treated with a topical
product alone. Older patients tend to have more macular
seborrheic keratoses (SKs) that can be lightened with a
topical agent, but usually need more aggressive treatment
for better results, either liquid nitrogen, fractional laser, or a
stronger peel.
Dr. Chiu: I have been using Lytera in patients being treated
with IPL for photodamage and find it has been helpful for
improving the results and extending the interval patients can
go between light treatments.
Published as a promotional supplement to Dermatology Times®
5
FIGURE 6A and B: This 56-year-old female with Fitzpatrick skin type IV lives in San Diego and is outside in the sun daily. Having received
no previous treatment for her photodamage (A), she was started on Lytera Skin Brightening Complex and treated with IPL. At 1 month after
IPL (B), her lentigines are much lighter, her skin tone is more even, she has no background erythema or peeling, and her skin texture is
much smoother. Her lentigines did not darken during the following summer months even though she is outside rowing 3 to 4 times a week.
(A)
(B)
(A)
I agree that we have several options that are effective for
treating simple discrete lentigines from photodamage.
However, when the findings are more complex so that
patients also have hazy patchy pigmentation and macular
SKs, I find Lytera is a great product for cleaning up the
diffuse pigmentation after doing a treatment that specifically
targets the lentigines and macular SKs.
Dr. Callender: Photoaging in SOC patients often presents as
generalized facial hyperpigmentation, and sun protection
with a broad-spectrum, SPF30 or higher sunscreen plus
hydroquinone has been the standard treatment. Now, I am
using Lytera instead of hydroquinone and am finding that
Lytera not only works to lighten the skin but also provides
textural improvements to produce better overall cosmetic
results.
However, I want to emphasize that differential diagnosis
is important in SOC patients who present with diffuse
darkening of the face because there are multiple etiologies
for this problem and we want to address any underlying
cause. Aside from being photoaging-induced, the
hyperpigmentation may represent exogenous ochronosis
from long-term use of OTC hydroquinone, and in this
situation there is a particular benefit for switching to Lytera.
Alternatively, diffuse facial hyperpigmentation may be
associated with some systemic diseases, including lupus or
Addison’s disease, or it may develop with use of certain
systemic medications, such as minocycline, chloroquine, or
some diuretics, among others.
Peeling Protocols
Dr. Goldman: Has anyone used Lytera with the Vitalize Peel®
(SkinMedica®)?
Dr. Callender: The Vitalize peel is now my most commonly
used peel, and I do a series of five peels spaced 2 to 4
weeks apart. I use Lytera to both treat hyperpigmentation
and to prevent it in these patients, and a nice thing about
Lytera is that I don’t feel I have to discontinue it between
peels. Patients start using Lytera about 2 weeks before the
6
(B)
(A)
(B)
first peel and are also instructed on daily use of a broadspectrum SPF 30+ sunscreen.
Dr. Foad: We had a pre-spring boot camp where patients
were started on the Lytera Skin Brightening System plus
TNS Essential Serum® (SkinMedica®) and then could
choose to receive a series of peels with the Rejuvenize
Peel™ (SkinMedica®) or IPL treatments. We had a number
of participants, and my aesthetician who was helping with
this program told me it was very effective and the patients
were very happy with their results. While Lytera seems helpful
when treating melasma, as we’ve said before, melasma can
be difficult to treat, and I think Lytera works even better for
hyperpigmentation problems that are not melasma.
Dr. Roberts: I agree with that. There is a lot of photodamage
in our desert-dwelling population and we offered a promotion
combining Lytera with two Vitalize peels. The results were
great, and it was a nice alternative for people who could not
afford a laser procedure.
Future Uses
Dr. Goldman: So, we have discussed using Lytera before
and/or after IPL, fractional nonablative laser resurfacing, and
chemical peels as well as using Lytera for maintenance after
initially treating patients with more aggressive regimens, such
as compounded 8% hydroquinone. We’ve also touched on
the use of Lytera with and without retinol. Now, let’s talk about
other potential uses for Lytera.
We’ve just launched a clinical study to explore whether
treating with the 1565-nm fractional nonablative laser might
improve the clinical results achieved using Lytera based on
the idea that the microzones created with the laser could be
a pathway for enhancing penetration of the topical product.
Dr. Fabi: Approaches to facilitate intraepidermal and even
superficial dermal delivery of Lytera represent an interesting
area of investigation. I have been using the Clear+Brilliant
Perméa™ laser (Solta Medical, Inc.) immediately before
Lytera in some of my patients with recalcitrant pigment,
A NEW INNOVATION FOR THE MANAGEMENT OF HYPERPIGMENTATION
A Roundtable Discussion on Novel Management Strategies for Hyperpigmentation
which takes advantage of the increased Permea™bility of
the epidermis and dermis following the nonablative laser
resurfacing treatment. Given how gentle Lytera is, patients
tolerate the procedure very well, and their results are
enhanced from a single laser treatment. I would also like to
see more research on Lytera for clearing PIH, which can be
very stubborn and even made worse by some of the devices
used for its treatment.
Dr. Roberts: I have had good results incorporating Lytera
as a therapeutic skin lightener in primary and maintenance
peeling regimens for patients with PIH (Figure 7A and
B). I am interested in using Lytera for rejuvenating the
appearance of skin off the face, especially on the chest.
FIGURE 7A and B: This 32-year-old Latina female presented with
postinflammatory hyperpigmentation, superficial scarring, and
uneven skin tone secondary to acne (A). She was treated with
two salicylic acid peels with a between-peel interval of 4 weeks,
chosen based on her scored risk of hyperpigmentation and
scarring using the Roberts Skin Type Classification system.16 Lytera
Skin Brightening Complex was started 1 week after the first peel
and held 2 days prior to the second peel. Her skin appearance is
significantly improved at 4 weeks after the second peel (B).
(A)
(B)
was depigmentation or brightening through some other
mechanism, and unfortunately, this patient did not want any
photographs taken. I am interested to see how Lytera would
work combined with a very conservative fractional laser
procedure to treat these dark circles.
Dr. Foad: I also have patients who feel they benefited with
an overall brightening of their complexion after using Lytera,
and treating under the eye area would be an interesting
topic for a study. I agree that using Lytera off the face is very
appealing because certainly we see a lot of problems with
hyperpigmentation off the face. In addition, I would like to
see research that could provide guidance on how soon we
can safely restart Lytera after different procedures because
now everyone is using their own empirical approaches.
Dr. Chiu: I am wondering if anyone has experience with
Lytera in patients with poikiloderma. That is a tougher
problem because it is a mix of hyper- and hypopigmentation
along with textural changes and telangiectasias.
Dr. Roberts: I treated poikiloderma in a patient using Lytera
combined with three 1550-nm fractional nonablative laser
procedures spaced 1 month apart, and she did very well.
Dr. Bruce: The only thing I would add to the ideas already
mentioned is that I would love to see some formal studies
investigating use of Lytera after fractional laser treatment
for melasma.
Patient Acceptance and Adherence
Dr. Goldman: What are your thoughts about tolerability
when using Lytera or the Lytera Skin Brightening System?
Dr. Callender: I think there is great potential for using Lytera
off the face, and especially for restoring a more youthful
appearance to the hands. I am also interested in using it to
treat hyperpigmented skin in the axillae where women with
SOC often develop darkening as a result of irritation from
shaving and deodorant use.
In addition, I am substituting Lytera for hydroquinone as
a pretreatment when performing laser hair removal for
hirsutism in women with SOC, and it has been working
well. These patients can develop pseudofolliculitis barbae
with secondary PIH, and eliminating the excess pigment
in the skin is helpful to maximize absorption of the laser’s
energy by its intended target.
Dr. Chiu: I had a patient who was using Lytera for melasma
and had dark circles under the eyes. We know there are
a multitude of causes for the latter problem, including
photodamage, and I find it is a tough area to treat because
retinoids and hydroquinone can be especially irritating
on the infraorbital skin. She applied Lytera below the
eyes and had a true brightening effect. I don’t know if it
Dr. Foad: I like to use Lytera plus a topical retinol, because I
think the combination is more efficacious than Lytera alone
whether I am treating melasma or photodamage (Figure
8A and B). However, in order to limit irritation, I have
patients start on the topical retinol Monday and Thursday
only. Then, I have them increase the frequency of topical
retinol use as they are able to tolerate it.
FIGURE 8A and B: (A) This 41-year-old female with Fitzpatrick
skin type I began treatment for her melasma with the Lytera Skin
Brightening System in August 2012. She used SPF 30 Daily Physical
Defense™ every morning, Lytera twice daily, and a topical retinol at
night (M and Th x 2 weeks, M, W, and F x 2 weeks, then nightly).
Her melasma was significantly improved after just 6 weeks (B), and
the patient was exceedingly happy with her results.
(A)
(B)
(A)
(B)
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Dr. Roberts: When I am going to use a topical retinol, I
sometimes start patients on a milder product to mitigate
tolerability issues.
have been several upgrades over the years and the numbers
will differ depending on what software version was used for
the imaging.
Dr. Bruce: I do the same thing because I prefer that patients
follow a routine daily application schedule from the start.
Pre- and post-treatment images are essential. However, it
can be difficult to get the lighting and positioning perfect
with the Visia system or digital photography, and so we
use the 3D imaging system (Vectra® M3, Canfield Scientific,
Inc.) to try to get the best pictures that we can. Does anyone
else have any thoughts on photography?
Dr. Goldman: Does anyone have tips on getting patients to
accept treatment with Lytera and making sure they adhere
to the regimen?
Dr. Fabi: There are pamphlets from the manufacturer that
feature before and after photos, but I like to show photos
from patients we’ve treated and especially from patients
in our study who only used Lytera. A lot of patients are
skeptical that a topical agent can work well on its own,
especially if they had a disappointing experience with other
products previously, and then they are hesitant to buy a new
product or a whole system.
Dr. Goldman: Patients absolutely notice improvements in
texture when looking at their before and after pictures, and
so photography is helpful not only for documenting changes
in hyperpigmentation with use of Lytera but also so that
patients can see how much better they look globally.
Patients also need to understand that they have to use the
product according to the instructions, that it takes 3 to 4
months of treatment to achieve significant results, and that
they can see improvement sooner if the topical product is
used with a laser treatment or some other procedure. I also
think it is important that physicians personally reinforce
the efficacy of the product, and they can do so by citing
published studies in addition to showing pictures from their
own patients.
Dr. Callender: Overall, I’ve seen good patient compliance
with Lytera. The formulation feels very elegant on the skin
and women like using it.
Dr. Bruce: I totally agree about showing a book of before
and after photos from your own patients because then the
physician can speak with authority about efficacy. I also
agree that patients must understand the improvement will be
gradual so that they will not be discouraged by a perceived
lack of benefit and discontinue treatment prematurely.
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Dermatol Venereol 2006;20(7):781-787. 2. Bang SH, Han SJ, Kim DH. Hydrolysis of
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Cosmet Dermatol. 2008;7(3):189-193. 3. Rivas S, Pandya AG. Treatment of melasma
with topical agents, peels and lasers: an evidence-based review. Am J Clin Dermatol 2013;
Jul 24 [Epub ahead of print]. 4. Navarrete-Solís J, Castanedo-Cázares JP, Torres-Álvarez
B, et al. A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone
4% in the treatment of melasma. Dermatol Res Pract. 2011;2011:379173. [Epub 2011
Jul 21]. 5. Sonti S, Holtz R, Mehta R. Mechanistic studies on novel anti-inflammatory
molecule used in the treatment of facial redness. J Invest Dermatol. 2011;131:069.
6. Panich U, Tangsupa-a-nan V, Onkoksoong T, et al. Inhibition of UVA-mediated
melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric
oxide system. Arch Pharm Res. 2011;34(5):811-820. 7. Sato K, Morita M, Ichikawa
C, Takahashi H, Toriyama M. Depigmenting mechanisms of all-trans retinoic acid and
retinol on B16 melanoma cells. Biosci Biotechnol Biochem. 2008;72(10):2589-2597.
8. Yokota T, Nishio H, Kubota Y, Mizoguchi M. The inhibitory effect of glabridin from
licorice extracts on melanogenesis and inflammation. Pigment Cell Res. 1998;11(6):355361. 9. Tasaka K, Kamei C, Nakano S, Takeuchi Y, Yamato M. Effects of certain
resorcinol derivatives on the tyrosinase activity and the growth of melanoma cells.
Methods Find Exp Clin Pharmacol. 1998;20(2):99-109. 10. Bellemère G, Stamatas GN,
Bruère V, Bertin C, Issachar N, Oddos T. Antiaging action of retinol: from molecular to
clinical. Skin Pharmacol Physiol. 2009;22(4):200-209. 11. Ortonne JP, Bissett DL. Latest
insights into skin hyperpigmentation. J Invest Dermatol Symp Proc. 2008;131(1):10-14.
12. Zaleski L, Fabi S, Goldman MP. Treatment of melasma and the use of intense pulsed
light: a review. J Drugs Dermatol 2012;11(11):1316-1320. 13. Kim EH, Kim YC, Lee ES,
Kang HY. The vascular characteristics of melasma. J Dermatol Sci. 2007;46(2):111-116.
14. Hernández-Barrera R, Torres-Alvarez B, Castanedo-Cazares JP, Oros-Ovalie C,
Moncada B. Solar elastosis and presence of mast cells as key features in the pathogenesis
of melasma. Clin Exp Dermatol. 2008;33(3):305-308. 15. Sriprachya-anunt S, Marchell
NL, Fitzpatrick RE, Goldman MP, Rostan EF. Facial resurfacing in patients with Fitzpatrick
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Classification System. J Drugs Dermatol. 2008;7(5):452-456.
Using photography and other imaging to document
personal improvement for individual patients can promote
their adherence. We do a Visia Complexion Analysis at
baseline in all patients and try to get a follow-up. Sometimes,
however, the numerical results on the Visia analysis are
worse at follow-up than at baseline despite obvious clinical
improvement, and then I am reluctant to share the data with
patients. Has anyone else had this experience?
Dr. Goldman: I expect we all have and we noticed that issue
when we did the initial validation studies for the Visia. It is
a matter of having less than exact alignment with the repeat
imaging as the numbers can be dramatically different even
at the same session if the facial positioning is shifted by
even a millimeter. I omit the numbers and show patients
the results for the different scales of pigmentation, redness,
etc. Another factor to consider is whether there has been a
change in software between the two visits, because there
8
Dr. Foad: We like to zoom in with the Visia in order to
capture the textural changes in the skin.
Dr. Goldman: This has been a very informative discussion,
and I think we have all learned a lot from each other’s
insights and experience. I hope that readers will also take
away useful ideas and, if they are not already using Lytera,
be encouraged to incorporate it into their management of
patients with hyperpigmentary disorders.
A NEW INNOVATION FOR THE MANAGEMENT OF HYPERPIGMENTATION
A Roundtable Discussion on Novel Management Strategies for Hyperpigmentation
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