1. Clinical Analysis for Today’s Skincare Specialists July 2015 | VOL. 36, NO. 07 |
By Ilya Petrou, M.D. | Staff Correspondent
To sell or not
to sell...that is
the question
Lisette Hilton | Staff Correspondent
In This Issue July 2015 VOL. 36, NO. 07
CLINICAL 14
Pediatric trials for AD systemic
treatments
FDA DODAC supportive of pediatric clinical trials
COSMETIC 26
Hair removal lasers: are they right for
your practice?
Business considerations, safety tips and nuances
ONCOLOGY 30
Personalized melanoma vaccines
debut in humans
First human trial of personalized vaccines
BUSINESS 40
How to start a clinical trial program
Experts share the how-to details
| THE TAKEAWAY | KELLY CORDORO, M.D., discusses differentiating diseases and treatment recommendations for pediatric dermatology. SEE PAGE 44
Although NRAS mutations are fre-
quently found in congenital melanocytic
nevi, new research data has revealed that
BRAFmutationsarealsoassociatedwiththe
development of these nevi as well as with
neurocutaneousmelanocytosis.According
to one expert in the field, these
breakthrough findings could
BRAF gene mutation breakthrough
for targeted therapies
potentially open the door in the future for
BRAF-targeted therapies in select congen-
ital melanocytic nevi and neurocutaneous
melanocytosiscasesthattestpositiveforthe
BRAFmutatedgene,offeringmuchneeded
hope for this patient population.
“Even though dermatologists are some-
CONGENITAL MELANOCYTIC NEVI see page 36
Dermatologypracticesareattracting
privateequitybuyerswhohavethepoten-
tial to swoop in and make problems like
heavy debt vanish. But there are impor-
tant considerations to take into account
before signing away full ownership.
David Wagener, M.B.A., C.P.A., pre-
sented on the variety of options that phy-
sicianshavetoselectfromattheAAD2015
annualmeetinginSanFrancisco. Wagener
is CEO of the Miami, Fla., group practice
Skin and Cancer Associates, and presi-
dent of the practice’s management firm,
Advanced Dermatology Management.
INVESTOR-OWNED GROUP PRACTICE
Being part of an investor-owned group
practice is among the choices open to
practicesandissomethingrelativelynew
to consider, he says.
To accomplish this, private equity
firmspartnerwithdermatologyandother
practices in a transaction that optimizes
alignment between the practice and in-
vestor,maximizesfinancialflexibilityand
positions the newly formed company for
Business
TO SELL OR NOT TO SELL see page 41
A
SHOWN HERE A. Giant Congenital Melanocytic Nevus
(GCMN) with extensive nodularity involving the upper
back and neck. B. Hairy GCMN involving the entire
back. Satellites are evident in the extremities.
Source: Miguel Reyes-Múgica, M.D.
B
CONGENITAL
MELANOCYTICNEVI
DermatologyTimes®
July2015Volume36No.07ClinicalAnalysisforToday’sSkincareSpecialistsDermatologyTimes.com
2. 3JULY 2015 ⁄ DERMATOLOGYTIMES.COM
EDITORIAL ADVISORY BOARD
Insight & Opinion From Our Advisory Board Leaders
A
ccording to Wikipedia, the dif-
ferential approach to diagno-
sis was first suggested a century
ago by a pioneering German psychia-
trist, Emil Kraeplin, but contributions to
the evolution of the differential diagnosis
(Ddx) have been made by countless out-
standing physician-scientist-educators.
The golden age of U.S. medicine nurtured
the great diagnosticians, including Inter-
nal Medicine’s Tinsley Randolph Harrison,
Pediatrics’ Frank Oski and Dermatolo-
gy’s Samuel Moschella and Walter Shelly.
As a medical student, I sat in awe at Dr.
Ralph Feigin’s “Rounds,” a series of case
presentations with comprehensive Ddx.
Since then, nailing the diagnosis has been
my loftiest goal.
Almost 30 years have passed since I
was inspired by Feigin Rounds. I am now
very familiar with a long (and ever-ex-
panding) list of common and rare con-
ditions that apply to complex patients
in search of a diagnosis, especially be-
cause cutaneous signs are readily availa-
ble clues that require a trained eye, rather
than imaging or laboratory testing. So for
me, compiling the Ddx list is now much
less difficult than communicating the pos-
sibility of a life-altering diagnosis, espe-
cially to an unsuspecting patient, family
and referring physician.
One of my most memorable early
challenges was an infant referred for
“eczema.” When I walked in the room,
his other features took precedence: fail-
ure-to-thrive, sparse, brittle hair and verti-
cal nystagmus. Although I had never seen
a case, trichothiodystrophy was at the
top of my Ddx. However, I was much less
sure about the best way to communicate
my concerns to the baby’s medically un-
sophisticated mother. I started by gently
pointing out his unusual features followed
by a phrase that has served me well since
then: “Has your doctor ever mentioned
this to you?”
A year or so later, a more medically so-
phisticated mother brought her 8-month-
old son in for evaluation of “eczema.” She
was convinced that he had food-allergy
triggered atopic dermatitis, and had
restricted his diet to elemental formula,
so I allowed her opinion to sway my inex-
perienced diagnostic skills. Although my
documented impression was incorrect, I
commented on the atypical distribution of
his erythroderma, accentuated at the skin
folds and diaper area. I did not see him
again until almost age 3, when his obvi-
ously brittle hair moved Netherton’s to the
top of the list. A little later, his similarly
affected sister was born.
In the past 2 decades, I have diag-
nosed hundreds of children with uncom-
mon and rare disorders. In many cases,
medical advances have defined stand-
ard evaluation, and even successful treat-
ment: confirmatory gene testing and IL1
receptor antagonists for the cryopyrin-
opathies; MRA/MRV and propranolol for
PHACE; gene sequencing panels for
infants with epidermolysis bullosa or
collodion phenotype, and the miraculous
clinical trial evaluating the impact of neo-
natal protein replacement on the early
development of teeth, sweat glands and
hair follicles in children affected by X-
linked hypohidrotic ectodermal dysplasia.
But more often, establishing a rare diag-
nosis prompts more angst than action.
Furthermore, the value of nailing a di-
agnosis has gradually diminished, espe-
cially relative to the revenue generated by
procedures or patient volume. But diag-
nosis remains my passion and, occasion-
ally, an annoying obsession. Sometimes, I
can’t help but assess friends, distant
relatives and acquaintances, then agonize
about whether to divulge my suspicions.
In a moment of irony, my brother (who has
a touch of oppositional defiant disorder)
diagnosed me with another ODD (obses-
sive diagnosing disorder).
One day last week, my first patient
was a 15 year old with a chief complaint
of acne. The first glimpse prepared me
for a longer-than-expected visit. He was
Nailing the diagnosis
tall and thin, with arachnodactlyly. On closer
exam, he had pectus excavatum, a high
arched palate, crowded teeth, hyperextensi-
ble joints, flat feet, prominent striae and mild
acne. His family history was non-contribu-
tory. The reply to my question about his doc-
tor’s mention of the distinguishing features
was that a genetics consultation years earlier
did not recommend any additional evaluation.
This left me with three no-win choices: rec-
ommend a second opinion, ignore the signs
or explain both options in more detail. I chose
the last and most time-consuming (at the
expense of my patients waiting to be seen).
I face a similar conundrum every time I see
an infant with a low-risk midline sacral birth-
mark or a congenital nevus at with low-likeli-
hood of neurocutaneous melanosis: how to
decide on the relative risk-to-benefit of high-
cost imaging requiring general anesthesia?
Sometimes my tendency to minimize expen-
sive evaluation has failed patients. Just last
year, my negative history and physical exam
did not prompt further evaluation for a patient
who presented with erythema nodosum (EN),
and developed hematochezia a year later. I
learned about the IBD via a smug electronic
message from the pediatric gastroenterolo-
gist who performed the colonoscopy. Rather
than sending a defensive eReply, I called her
to discuss the case. She was unaware of
the possibility of “idiopathic” EN, or the wide
range of possible associated extracutaneous
problems.
Investing the time in direct communica-
tion with colleagues, rather than waging chart
wars, is usually a very worthwhile win-win-
win for me, patients and colleagues. It took
me years to recognize the importance of
these informal discussions in fostering
valuable collaboration, and expanding my
own Ddx. These days, when I receive a
request for a biopsy alone, rather than a
diagnostic evaluation, or a limited impression
like “not a surgical candidate,” I make every
effort to contact the clinician for more valua-
ble information hidden in the sound bite.
In the age of EMR, the value of direct com-
munication should be part of medical school
curriculum. Perhaps the ghosts of golden-
age medicine and the current champions of
accountable care and cost-effective medi-
cine will make it so. DT
Elaine C. Siegfried, M.D.,
is professor of pediatrics
and dermatology,
Saint Louis University Health
Sciences Center, St. Louis, Mo.
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What’s the new FDA Concern
with safety of cosmetics?
What’s your diagnosis?
Blog
A 53-year-old woman is
complaining of this somewhat
tender rash on her legs and
feet that has been present
for many months now.
CHOOSE ONE:
LINCHEN PLANUS
INSECT BITES
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LAST MONTH’S DIAGNOSIS:
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MULTIMEDIA
Eradicating actinic keratosis:
Pros and Cons
Dr.NealBhatiashareshisperspectiveonactinic
keratosisfromhisControversiessessionatthe
23rdWorldCongressforDermatology:prosand
consonroutineeradication,trendingpopulations
andmodalitiesoftreatment.Learnmore:
bit.ly/actinickeratosisprosandcons
Laser devices I
would buy today
vs. throw away
When it comes to
laser devices, what
devices would you buy today and what would
you throw away? Vegas Cosmetic Surgery
2014 Laser Roundtable.
bit.ly/devicesIwouldbuyvsthrowaway
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
6 INTER CTIVE Resource Centers
®
For more information on specialized
areas of dermatology, related articles
and business resources, go to:
modernmedicine.com/ResourceCenters
Best practices in the evaluation and
management of actinic keratoses
DermatologyTimes.com/actinickeratoses
Current and emerging therapies
for psoriatic arthritis
DermatologyTimes.com/psoriatic-arthritis
Fillers and toxins:
Cosmetic and therapeutic options
DermatologyTimes.com/injectables
Insights into managing
atopic dermatitis and acne
DermatologyTimes.com/atopicdermatitis
7. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
8 LEGALEAGLE
D
r. Skin has a large dermatology
practice with an emphasis on
acne. Many of his fellow derma-
tologists refer to him their most diffi-
cult patients. In fact, Dr. Skin prides
himself on his ability to manage these
difficult acne patients. For 20 years,
he has been a strong advocate of
using oral retinoids for treatment-
resistant cystic acne and has suc-
cessfully treated many patients.
As would be expected, many pa-
tients have had some side effects; all
have been manageable. He has seen
dose-related headaches, arthralgias,
dry skin and eye, as well as occa-
sional nausea and vomiting in some
patients. In addition, because of the
rare reports of mood changes from
oral retinoids, he asks all patients
about a psychiatric history.
All of his patients have done well
until one (a married highly success-
ful businessman with three children),
who had virtually no prior difficulty
with other acne treatments, shot him-
self in the head 2 years ago. Although
Dr. Skin is saddened by his patient’s
death, he assumes this was a rare
tragedy that was unrelated to the pa-
tient’s treatment.
Soon thereafter, the deceased pa-
tient’s family brings a lawsuit against
Dr. Skin, alleging he was negligent in
prescribing oral retinoids and that the
medication led to the suicide. Worse
than that, the family files a wrong-
ful death lawsuit against Dr. Skin. Dr.
Skin, of course, is beyond horrified
and hires an attorney to defend him-
self.
After extensive discussions, the at-
torney and defendant physician seek
to have the case thrown out of court.
However, during the mandatory law-
suit required discovery period, it is de-
termined that other patients given oral
retinoids have also committed suicide.
Based on this information, the judge in
the case denies Dr. Skin’s motion for
summary judgment to have the case
thrown out of court. With this informa-
tion, plaintiff’s attorney seeks to settle
the case with Dr. Skin for $6 million.
Dr. Skin becomes very depressed.
His career, practice, reputation and
everything he holds dear are at risk
simply because he tried to be a good
doctor. Should he try to defend him-
self? Will he lose the case at trial?
FOUR ELEMENTS MUST BE PROVED
A medical malpractice case, based on
negligence, can only be won by plain-
tiff’s attorney if four elements can be
proved in a court of law. These ele-
ments are
➧ Duty
➧ Breach of duty
➧ Causation
➧ Damages
A physician is required to perform
his duty as would any reasonable phy-
sician. If he does not do so, he has
breached that duty. Then, if there is
a nexus between the breach of that
duty and damages, the plaintiff may
win her lawsuit. Clearly, the death of
Dr. Skin’s patient has the requisite ele-
ment of damages. Those damages are
measured by the economic value that
would be present if the deceased was
still alive. However, did Dr. Skin per-
form in accordance with a reasonable
duty and, if not, did the breach of that
duty lead to his patient’s death?
If Dr. Skin had prescribed oral reti-
noids and not asked about a history of
depression, then one might argue he
had breached his duty. This, however,
assumes there is scientific evidence
that oral retinoids actually do lead to
an increased incidence of suicide by
patients taking the medication.
Dr. Skin did ask his patient about a
psychiatric history. Although the judge
may not have granted Dr. Skin’s motion
for summary judgement, the plaintiff’s
attorney will need to prove that oral ret-
inoid patients have a higher incidence
of suicide. This will be problematic for
the plaintiff’s attorney. Dr. Skin may
have to defend the lawsuit, but is un-
likely to lose the case. DT
David J. Goldberg, M.D., J.D.
is director of Skin Laser and Surgery
Specialists of New York and New
Jersey; director of laser research, Mount
Sinai School of Medicine; and adjunct
professor of law, Fordham Law School.
My patient with acne committed suicide
His career, practice, reputation and
everything he holds dear are at risk simply
because he tried to be a good doctor.
Should he try to defend himself? Will he
lose the case at trial?
DidDr.Skinperform
inaccordancewitha
reasonabledutyand,
ifnot,didthebreach
ofthatdutyleadto
hispatient’sdeath?
AM I LIABLE FOR WRONGFUL DEATH?
9. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
10 IRREGULARBORDER
P
robiotics, which are helpful bacteria
that protect the body from harm-
ful bacteria, are literally everywhere.
Strolling through the aisles of any grocery
store, we can find yogurts, milks, juices
and other consumables that contain nat-
urally occurring probiotics such as lacto-
bacillus or bifidobacterium, or foodstuffs
that are artificially teeming with these cel-
ebrated organisms. Upon further prob-
ing we even encounter “prebiotics,” or
nondigestible food ingredients (such as
cellulose) that promote the growth of ben-
eficial microorganisms in the intestines —
i.e., sustenance for our symbionts.
In light of increasing antibiotic resis-
tance due to over- and misuse, coupled
with patients’ preferences for more ho-
listic, natural approaches to healing, are
we entering an era of anti-antibiotics and
pro-probiotics? Replacing the drugs with
the bugs, if you will? There is, in fact, in-
teresting literature on the various applica-
tions of probiotics in skin health, and for
integrative practitioners striving to com-
bine the best of allopathy with nature’s
bounty, several of these studies are here
mentioned.
ACNE
In 2014, Bowe et al. reviewed a theory
from 1930 known as the “gut-brain-skin
axis” — essentially, the idea that dis-
turbed emotional states such as stress,
anxiety and depression can reciprocally
contribute to altered gut flora (SIBO: small
intestinal bacterial overgrowth) and GI
leakage, which in turn recruits a systemic
inflammatory response with skin manifes-
tations such as acne.1
While this theory
has not been directly studied with respect
to acne, Parodi and colleagues showed in
2008 that patients with rosacea had a 10-
fold greater incidence of SIBO as com-
pared to healthy controls.2
Additionally,
studies examining the therapeutic bene-
fit of oral and topical probiotic administra-
tion in mild acne patients within the last
decade have been promising, with mech-
anistic theories including decreased re-
lease of inflammatory mediators as well
as increased production of ceramide and
skin barrier restoration.3,4
ATOPIC DERMATITIS
Stapholococcus colonization of skin com-
promised by eczema is a common and
known phenomenon, as is the inflamma-
tory basis of atopic dermatitis. As such,
probiotics theoretically confer a dual ben-
efit of antimicrobial as well as anti-inflam-
matory therapy. In practice, however, the
data is mixed. Initial studies of different
strains of oral lactobacillus for both pre-
vention and treatment of atopic dermatitis
were encouraging,5,6
but follow-up re-
views and meta-analyses have been con-
flicting.7,8,9
Another difficulty in reviewing
the literature is the lack of standardization
in which probiotic strains are tested, in
what dosages, and administered to which
study subject (pregnant/lactating mother
vs. affected child). Overall, the risk of oral
probiotic supplementation appears to be
low (except for a theoretical risk of infec-
tion in immunocompromised patients), so
until more convincing evidence emerges
in either direction, use may be encour-
aged in the interested patient. And, of
further significance, topical probiotics are
another emerging approach to atopic der-
matitis and barrier repair, with the addi-
tional benefit of increasing local ceramide
production.4,10,11
WOUND HEALING / MRSA
Although slightly tongue-in-cheek, the
word “kefir” in the title of this article has a
legitimate place in the wound-healing lit-
erature. Kefirs are natural probiotic com-
pounds (yeast/bacteria fermentation
starters) with anti-inflammatory and anti-
microbial properties, which are typically
packaged into drinkable yogurts and la-
beled as such. Huseini and colleagues re-
searched the application of kefir-based
gels of varying durations of incubation/
potency on mice with cutaneous burns.
The kefir gels were compared to no inter-
vention, gel vehicle alone or silver sulfadi-
azine (conventional therapy). Overall, the
kefir gel with 96 hours of incubation (lon-
gest) yielded superior results in terms of
inflammation, scar formation and wound
re-epithelialization.12
As a purported
mechanism in wound healing, Wong and
colleagues suggested that probiotics may
help to normalize disruptions in human
microbial communities and bacteria-host
interactions that contribute to non-heal-
ing wounds.13
As patients with chronic wounds can
become colonized with MRSA (methicil-
lin-resistant staphylococcus aureus), re-
searchers have also studied what, if any,
role probiotics may play in preventing or
treating MRSA infections. Shu’s group in
2013 found that supplementing mice with
a skin-commensal bacterium (P.Acnes)
resulted in both in vitro / vivo growth sup-
pression of the most prevalent strain of
community-acquired MRSA.14
Another
study looking at species-specific inhibition
of various probiotics and MRSA found in-
hibitory activity of lactobacillus plantarum
both in cell culture and mouse models.15
Dr. Reena Rupani, M.D., FAAD,
Center for Health and Healing
Mount Sinai Beth Israel
Probiotics for healthy skin
A SIDE OF KEFIR WITH YOUR KOMBUCHA?
Probiotics, which
are helpful bacteria
that protect the
body from harmful
bateria, are literally
everywhere.
PROBIOTICS: see page 18
11. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
12 VIGNETTEDERMATOLOGY
But only those close to the dermatolo-
gist knew the depths of his despair.
Patients and colleagues remember him
for his love of people, cosmetic derma-
tology, art, culture and song. They also
remember him as always striving to be
at the cutting edge of his field.
THE DERMATOLOGIST
Roy Geronemus, M.D., a member of
the Dermatology Times Editorial Advi-
sory Board, worked with Dr. Brandt at
their New York City practice for two de-
cades and knew him since 1978, when Dr.
Brandt was a dermatology resident at the
University of Miami School of Medicine,
Miami, Fla.
Dr. Geronemus, who gave a eulogy in
honor of Dr. Brandt in New York, says the
two were as different as two people can
be, but they had a mutual respect and
strong friendship. He said that his col-
league was a creative genius in address-
ing the aging face and was distinguished
as the world’s biggest user of Botox and
fillers.
“He made cosmetic dermatology more
scientific,” Dr. Geronemus says. “He put
a lot of thought and creativity into apply-
ing the science of cosmetic dermatology
to the actual implementation. So, he
understood what he was using. He under-
stood anatomy. He understood how the
injectables would work, appropriately, in
such a way that provided a different way
of looking at things. Other dermatologists
wanted to know his secrets and he freely
shared them — he published widely and
lectured all over the world. But very few, if
any, had Fred’s artistic eye.”
Dr. Brandt’s partner in practice in
Coral Gables and former mentee, derma-
tologist Jeremy B. Green, M.D., says Dr.
Brandt would host journal clubs for their
group, including his other partner Joely
Kaufman, M.D.
“Here’s somebody who is 65 years old
and arguably one of the top dermatolo-
gists for what he did on the planet, striv-
ing to learn more, to get better,” says Dr.
Green. “He was a master, who acted like
he was an apprentice.”
Despite his celebrity, following and
reputation, Dr. Brandt was a man of great
humility, according to Dr. Green.
“When I first started working with him,
he’d introduce me as his colleague — his
partner. He treated me as an equal,” says
Dr. Green, noting that “he was always
in the company of famous dermatolo-
gists, plastic surgeons and heads of in-
dustry. He’d introduce me to all these top
people. And that was so amazing. I didn’t
think I deserved that. That’s the person
he was.”
Patients loved him and that love was
mutual, according to his colleagues.
Vanity Fair1
covered the service at the
Alice Tully Hall at Lincoln Center, where
the stage was adorned with 3,000
orchids. (There was a second funeral for
Dr. Brandt in Miami.) Among the celebri-
ties giving eulogies were television per-
sonalities Joy Behar and Kelly Ripa, who
recalled the time Dr. Brandt rapped, “Oh,
Juvéderm, girl, you’re so firm!”
Bursting into song was something Dr.
Brandt did often. He’d sing to patients
and, sometimes, they’d sing along. He
loved Sinatra and the songs from Car-
ousel. One of his favorites to serenade to
patients, a take-off on Duke Ellington’s
doo-wop classic “It won’t mean a thing
if you don’t get a lift,” according to Dr.
Geronemus.
A fun and caring man, Dr. Brandt could
Fredric S. Brandt, M.D.
one of cosmetic dermatology’s most celebrated,
accomplished and recognized physicians, died April 5, 2015.
His colleagues, still reeling from the loss, remember
the legacy and brilliance of the man who came
to be known as “The Baron of Botox.”
Farewell to Fredric S. Brandt, M.D.
remember minute details about each of
his patients’ lives.
“People would wait for hours to see
him,” Dr. Green says. “Even though this
was not ideal to some in the waiting room,
once they left, they were beaming. Ironi-
cally enough — for how everything turned
out — Dr. Brandt was a counselor. He
was so much more than a doctor to [his
patients]. He enjoyed the limelight but,
ultimately, what he cared about were the
patients and making sure we did every-
thing safely. Everything had to be on the
cutting edge.”
THE MAN; THE FRIEND
Dr. Geronemus says his partner was really
out there. “He would not wear lab coats
to the office. He would wear designer
clothes. About a month ago, we were
leaving the office together. I was wearing
a Zegna suit, carrying an old fashioned
Wall Street briefcase. Fred was wearing
his typical doctor’s garb — a designer
outfit with a Givenchy bag draped over
his shoulder. We looked at each other and
laughed,” Dr. Geronemus says.
His antics often drew laughs, even in
more serious and professional situations.
“We were in Sweden together helping to
launch the filler Restylane, and he broke
into a rap song about me that he con-
cocted on the spot. It was creative and
hysterical,” Dr. Geronemus says. “He even
got me into the act on occasion including
one holiday party, where we dressed up
as Sonny and Cher — wigs and all. I was
Sonny; he was Cher. We sang ‘I Got You
Babe.’”
Inside, he was the kind of man one
wouldn’t expect, given the façade. The
friendships Dr. Brandt made in and out of
dermatology weren’t about the celebrity,
according to Dr. Green.
“It was about him being a human
being. The clothes he wore and his ap-
pearance — that façade would melt away
Lisette Hilton | STAFF CORRESPONDENT
F
redric S. Brandt, M.D. was 65. He had successful practices in Coral
Gables, Fla. and New York City. He branded a lucrative skincare line
and cared for A-list clientele. He also suffered from what friends say
was a long battle with depression.
FREDERIC S. BRANDT see page 25
12.
13. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
CLINICAL DERMATOLOGY14
24SCLERODERMA SKIN ULCERS
Tips for managing this challenging condition
Theexpandingpipelineofdrugsforthe
treatmentofatopicdermatitis(AD)iscre-
atingexcitementamongdermatologists
astheyanticipateeffectivenewtherapies
akintotherecentbreakthroughsthathave
occurredformanagementofmoderate-
to-severe plaque psoriasis. At the same
time,however,pediatricdermatologyex-
pertshavebeenconcernedabouttheex-
clusionofchildrenfromthedrugdevel-
opment process.
Now, after a recent meeting of the
Food and Drug Administration (FDA)
Dermatologic and Ophthalmic Drugs
Advisory Committee (DODAC), there is
good reason to believe that the unmet
medicalneedwillbeaddressedregard-
ing systemic treatments approved spe-
cifically for children with severe AD.
Elaine C. Siegfried, M.D., Dermatol-
ogy Times editorial advisor and pro-
fessor of pediatrics and dermatol-
ogy, Saint Louis University Health Sci-
ences Center, St. Louis, Mo., served as a
temporary DODAC member for the
March 2015 meeting. She tells Derma-
tology Times, “Prior to the meeting, we
anticipated differing opinions about
the importance of including children
in clinical trials. But at the end of the
day there was unanimous agreement
that benefits of including children out-
weighed the risks, and that even young
children should be considered eligible
to participate in trials.”
Dr. Siegfried also paid tribute to cur-
rent leaders at the FDA whose enlight-
ened thinking and collaborative spirit
are paving the way to a better future for
children with severe skin disease.
She says, “I can’t over emphasize how
thrilled the pediatric dermatology com-
munity is to have leaders at the FDA like
Dr. Kendall Marcus (Director, Division
of Dermatology and Dental Products,
DDDP) and Dr. Jill Lindstrom (Clinical
TeamLeader,DDDP)whorecognizethat
childrenwithskindiseasehavebeenther-
apeuticorphansandwhoareinterestedin
movingforwardtocorrectthatomission.”
Predicting infection risk could
lead to more targeted treatment
and prevention, as well as reduce
unnecessary antibiotic use. A study led
by Harvard Medical School researchers
looks at 113 burn patients with burns
on more than 20% of their bodies. They
found that a biomarker model based on
observed differences in gene expression
correctly predicted infection susceptibility
of more than 80% of patients.
SOURCE: BIT.LY/PREDICTINGINFECTIONRISK
PEDIATRIC AD see page 17
Pediatric trials for AD
systemic treatments
CHERYL GUTTMAN KRADER
STAFF CORRESPONDENT
Raynaud’s phenomenon
is usually present ...
That phenomenon may
create digital ulcers that
are horrible in terms of
the impact on quality of
life of patients.”
Alain Brassard, M.D., FRCPC
Canadian Association of Wound Care
Scleroderma skin ulcers
See story page 24
Quotable DTExtra
Dr. Siegfried observes that, histori-
cally, the FDA has always served as a
strong guardian of children’s safety.
More recently, however, there has been
asea-changeinconceptsabouthowbest
to carry out that responsibility.
She notes that a presentation at the
DODAC meeting by Michelle Roth-
Cline, M.D., Ph.D., Pediatric Ethicist in
theFDAOfficeofPediatricTherapeutics,
includedaslidethateloquentlysumma-
rizedtheissue,stating,“Wehaveevolved
from a view that we must protect chil-
dren from research to a view that we
mustprotectchildrenthroughresearch.”
Dr. Siegfried adds, “There has also
been a misperception that many par-
entswouldnotconsentonbehalfoftheir
childrentoparticipateintrialsofinvesti-
gationalagentsbecausetheydon’twant
them to be guinea pigs. However, with-
out the quality of data on the safety and
efficacy of medications possible only
through prospective, multicenter clin-
ical trials, all children treated off-label
are guinea pigs.”
A PRODUCTIVE AFTERNOON
The open session DODAC meeting was
sponsoredbytheDDDP.Itfeaturedsev-
eralformalpresentationsdeliveredbyFDA
officialsandindustryrepresentatives,as
well as testimony from dermatologists,
14. PRESCRIBE
ATOUGH
TOPICAL
SOOLANTRA®
(ivermectin) CREAM,1%—POWERFUL
AND RAPID RESULTS FROM A ONCE-DAILY TOPICAL1,2
*†
. –20.5 (–64.9%) mean inflammatory lesion count reduction at week 122
*†
. Better efficacy from once-daily Soolantra Cream,1% vs twice-daily metronidazole 0.75% cream as early as 3 weeks3‡
. Specifically formulated for patients with inflammatory lesions of rosacea—Cetaphil®
Moisturizing Cream was the basis for the vehicle2
www.soolantra.com/hcp
Important Safety Information
Indication: SOOLANTRA®
(ivermectin) Cream,1% is indicated for the treatment of inflammatory lesions of rosacea. Adverse Events: In clinical trials with SOOLANTRA®
Cream,
the most common adverse reactions (incidence ≤1%) included skin burning sensation and skin irritation. Warnings/Precautions: Not for oral, ophthalmic, or intravaginal use.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see brief summary of Prescribing Information on adjacent page.
*The efficacy and safety of SOOLANTRA®
Cream, 1% once daily was evaluated in subjects aged ≥18 years in 2 identically designed phase 3 clinical trials (N=1371). Final results were comparable between the
2 studies, with the least favorable results presented here.
†
A phase 3, multicenter, randomized, double-blind, 12-week, vehicle-controlled, parallel-group study assessing the efficacy and safety of SOOLANTRA®
Cream, 1% once daily in 683 subjects with moderate to
severe papulopustular rosacea (Investigator Global Assessment [IGA] score of 3 or 4).
‡
An investigator-blinded, multicenter, randomized, parallel-group study comparing the efficacy and safety of SOOLANTRA®
Cream, 1% once daily with metronidazole 0.75% cream twice daily in 962 subjects with
moderate to severe papulopustular rosacea (IGA score of 3 or 4) over a 16-week treatment period.
TREATING INFLAMMATORY LESIONS OF ROSACEA CAN BE TOUGH…
16. 17JULY 2015 ⁄ DERMATOLOGYTIMES.COM
CLINICAL DERMATOLOGY
researchers with expertise in basic sci-
ence, representatives from the National
Eczema Association, parents and pedi-
atric patients suffering with severe AD,
and a series of discussions designed to
address various issues relating to the
conduct of future clinical trials of novel
systemic products for children with AD
that is inadequately responsive to topi-
cal therapy. Questions explored during
the discussions include:
➧ Howmuchevidenceoftreatmentef-
fectandsafetyshouldbeobtainedin
adults prior to conducting studies in
children?
➧ Howmuchuncertaintyaboutthepo-
tential risks and benefits is tolerable
when initiating a pediatric trial?
➧ What are the features of the appro-
priatepediatricpopulationinwhom
to study systemic treatments so that
risks and potential benefits of inves-
tigationalagentscanbecomparedto
the population receiving currently
available alternate treatments?
➧ Should older pediatric subpopula-
tions be studied prior to or concur-
rently with younger pediatric sub-
populations?
Lawrence Eichenfield, M.D., chief of
Pediatric and Adolescent Dermatology,
Rady Children’s Hospital, San Diego,
Calif., spoke as a representative for Re-
generon-Sanofi,butpriortothemeeting
healsoobtainedunanimoussupportfor
including children in AD clinical drug
trials from non-industry stakeholders.
Those groups included the American
Academy of Dermatology (AAD), Soci-
etyforPediatricDermatology,theInter-
nationalSocietyofAtopicDermatitisand
the National Eczema Association.
Heartfelt testimony from young pa-
tients with severe AD was particularly
compellinginbringingforththeimpact
of the disease on affected children and
their families.
“Considering15skinconditionsusing
disability-adjustedlifeyearstomeasure
burden, the 2010 Global Burden of Dis-
ease Study found ‘dermatitis including
eczema’ ranked number one. Yet, until
recently, there has been relatively little
interest in drug development for this
common, often debilitating disease,”
says Dr. Siegfried.
“Although interest is growing, the
factremainsthatADaffectsmanymore
childrenthanadults.Withthatinmind,
pediatricdermatologistshavebeencon-
cernedaboutexclusionofchildrenfrom
investigational research of new drugs
that have the potential to better control
their disease. We have been struggling
for generations to make the best treat-
ment recommendations for children
with severe AD. Finally, we have hope
for the chance to offer them better op-
tions in the foreseeable future.”
THE PATH FORWARD
Seven years ago, as chairman of the En-
vironmentandDrugsCommitteeofthe
AAD,Dr.Siegfriedbegantoexploremech-
anismstofacilitateinclusionofchildren
inthenewdrugdevelopmentprocess.At
thattime,shebecameawareoftheFDA
Code of Federal Regulations on Good
Guidance Practices1
(GGPs), including
theFDA’spoliciesandproceduresforde-
veloping,issuingandusingguidancedoc-
uments.Article10.115oftheFederalReg-
ister2
defines a guidance document as a
tool“preparedforFDAstaff,applicants/
sponsors,andthepublicthatdescribethe
agency’s interpretation of or policy on a
regulatoryissue.Guidancedocumentsin-
clude,butarenotlimitedto,documents
thatrelateto:thedesign,production,la-
beling,promotion,manufacturing,and
testing of regulated products...”
Dr. Siegfried initiated her efforts in
theearlydaysofnewdrugdevelopment
forpsoriasis,afterrecognizingageneral
reluctance to include children in trials,
aswellassuboptimaldesignandlackof
standardization among the few studies
that were enrolling children.
“Overtheyears,wehaveimplemented
several action items to further the proc-
ess of developing a guidance document
that could be adopted by the FDA and
used by industry as a framework for
pediatric drug trial planning. The re-
centDODACmeetinghasbeenthemost
positivesteptowardsacknowledgingour
efforts, and we are looking forward to
working together for the benefit of chil-
dren with severe AD.”
With funding and administrative
support from the National Eczema
Association and the Pediatric Derma-
tology Research Alliance, and encour-
agement from the FDA, Dr. Siegfried
and colleagues are hoping to organ-
ize a group of individuals with wide-
ranging expertise in clinical trial de-
sign relevant to investigation of med-
ications for AD in children. Although
it may be ambitious, she hopes a draft
that can be submitted to the FDA for
review and that revision will be com-
pleted within a year.
“The FDA has final say on the con-
tent of its guidance documents, so FDA
review and acceptance are required,”
saysDr.Siegfried.“However,wearevery
pleased that the FDA DDDP leadership
is receptive to extramural input. Work-
ing together in a positive and coopera-
tivewaywillultimatelyleadtodevelop-
ment of the best products.”
In the meantime, Dr. Siegfried ex-
pects there will be an ongoing dialogue
abouttheissuesofpediatricADdrugde-
velopmentandthatcompaniesinvolved
inthisareaofresearchwillbeapproach-
ingpediatricstudyplanswithincreased
interest and effort. DT
Disclosures: Dr. Siegfried serves as a consultant for
Valeant, Promius, Pierre-Fabre, Boeringer-Ingel-
heim and Celgene, and as a principle investigator for
Pierre-Fabre, Anacor and Amgen.
References:
1. http://www.accessdata.fda.gov/scripts/cdrh/
cfdocs/cfcfr/CFRSearch.cfm?fr=10.115 draft
2. http://www.gpo.gov/fdsys/pkg/FR-2000-09-19/
pdf/00-23887.pdf
PEDIATRIC AD:
DODAC supportive of clinical trials from page 14
“We have evolved from a view that we
must protect children from research
to a view that we must protect children
through research.”
Elaine C. Siegfried, M.D.
St. Louise, Mo.
17. AGING SKIN
Probiotics may also protect the skin
against photoaging. A recent study ex-
amined the impact of orally supple-
menting mice with a bifidobacterium
strain prior to UVB radiation, three times
weekly for 7 weeks. Compared to con-
trols, supplementation significantly sup-
pressed changes in transepidermal
water loss, skin hydration, epidermal
thickening and attenuated the damage
to the tight junction structure and base-
ment membrane induced by chronic
UVB irradiation, possibly via measur-
ably-decreased interleukin-1-beta pro-
duction in the skin.16
This study con-
firmed prior research from 2014, where
mouse supplementation with a bifi-
dobacterium strain attenuated UV-in-
duced barrier perturbation and oxidative
stress of the skin,17
possibly via reduced
generation of reactive oxygen species
(ROS).
GLOW OF HEALTH
As the old adage goes, “You are what
you eat.” So can consuming probiot-
ics induce a “glow of health,” or even a
fountain of youth? Levkovich’s study in
aged mice demonstrated an epithelial
follicular anagen-phase shift with sebo-
cytogenesis, resulting in thick lustrous
fur — all from eating probiotic-supple-
mented yogurt.18
Vegan needs are cov-
ered by kimchi, a fermented Korean cru-
ciferous dish with naturally-occuring
lactobacillus species.19
The fermented
tea beverage known as kombucha con-
fers four main properties: detoxification,
antioxidation, energizing potencies and
promotion of depressed immunity.20
At
every turn, we are confronted with con-
sumables teeming with bacteria, the
Good Guys of the New Frontier.
It thus appears that the potential ap-
plications of probiotics in skin disease
are vast, as evidenced by the sampling
of studies above. Like any popular
“It-Girl,” probiotics are popping up ev-
erywhere, ranging from therapeutics to
cosmetics, foods and beverages. Yet,
also like “old wine in a new bottle,”21
probiotics merit a closer look and fur-
ther study to determine which strains
confer tangible benefits in which ap-
plications, among what patient popula-
tions and at which dosages. While it is
tempting to jump on the bandwagon of
broad utility, such enthusiasm must be
tempered with careful study and con-
sideration. DT
References
1. Bowe W, Patel NB, Logan AC. Acne vulgaris, pro-
biotics and the gut-brain-skin axis: from anec-
dote to translational medicine. Benef Microbes.
2014;5(2):185-99.
2. Parodi A, Paolino S, Greco A, et al. Small intesti-
nal bacterial overgrowth in rosacea: clinical ef-
fectiveness of its eradication. Clin Gastroenterol
Hepatol. 2008;6(7):759-64.
3. Muizzuddin N, Maher W, Sullivan M, Schnittger
S, Mammone T. Physiological effect of a probi-
otic on skin. J Cosmet Sci. 2012;63(6):385-95.
4. Di marzio L, Cinque B, De simone C, Cifone MG.
Effect of the lactic acid bacterium Streptococ-
cus thermophilus on ceramide levels in human
keratinocytes in vitro and stratum corneum in
vivo. J Invest Dermatol. 1999;113(1):98-106.
5. Kalliomäki M, Salminen S, Arvilommi H,
Kero P, Koskinen P, Isolauri E. Probiotics
in primary prevention of atopic disease: a
randomised placebo-controlled trial. Lancet.
2001;357(9262):1076-9.
6. Weston S, Halbert A, Richmond P, Prescott
SL. Effects of probiotics on atopic dermatitis:
a randomised controlled trial. Arch Dis Child.
2005;90(9):892-7.
7. Van der aa LB, Heymans HS, Van aalderen WM,
Sprikkelman AB. Probiotics and prebiotics in
atopic dermatitis: review of the theoretical back-
ground and clinical evidence. Pediatr Allergy
Immunol. 2010;21(2 Pt 2):e355-67.
8. Pelucchi C, Chatenoud L, Turati F, et al. Probi-
otics supplementation during pregnancy or in-
fancy for the prevention of atopic dermatitis:
a meta-analysis. Epidemiology.
2012;23(3):402-14.
9. Boyle RJ, Bath-hextall FJ, Leonardi-bee J,
Murrell DF, Tang ML. Probiotics for treat-
ing eczema. Cochrane Database Syst Rev.
2008;(4):CD006135.
10. Di marzio L, Centi C, Cinque B, et al. Effect of
the lactic acid bacterium Streptococcus ther-
mophilus on stratum corneum ceramide levels
and signs and symptoms of atopic dermatitis
patients. Exp Dermatol. 2003;12(5):615-20.
11. Di marzio L, Cinque B, Cupelli F, De simone C, Ci-
fone MG, Giuliani M. Increase of skin-ceramide
levels in aged subjects following a short-term
topical application of bacterial sphingomyelin-
ase from Streptococcus thermophilus. Int J Im-
munopathol Pharmacol. 2008;21(1):137-43.
12. Huseini HF, Rahimzadeh G, Fazeli MR, Meh-
razma M, Salehi M. Evaluation of wound
healing activities of kefir products. Burns.
2012;38(5):719-23.
13. Wong VW, Martindale RG, Longaker MT, Gurtner
GC. From germ theory to germ therapy: skin mi-
crobiota, chronic wounds, and probiotics. Plast
Reconstr Surg. 2013;132(5):854e-861e.
14. Shu M, Wang Y, Yu J, et al. Fermentation of Pro-
pionibacterium acnes, a commensal bacterium
in the human skin microbiome, as skin probiot-
ics against methicillin-resistant Staphylococcus
aureus. PLoS ONE. 2013;8(2):e55380.
15. Sikorska H, Smoragiewicz W. Role of probiotics
in the prevention and treatment of meticillin-
resistant Staphylococcus aureus infections. Int J
Antimicrob Agents. 2013;42(6):475-81.
16. Satoh T, Murata M, Iwabuchi N, et al. Effect of
Bifidobacterium breve B-3 on skin photoaging
induced by chronic UV irradiation in mice. Benef
Microbes. 2015;:1-8.
17. Ishii Y, Sugimoto S, Izawa N, Sone T, Chiba K,
Miyazaki K. Oral administration of Bifidobacte-
rium breve attenuates UV-induced barrier per-
turbation and oxidative stress in hairless mice
skin. Arch Dermatol Res. 2014;306(5):467-73.
18. Levkovich T, Poutahidis T, Smillie C, et al. Pro-
biotic bacteria induce a ‘glow of health’. PLoS
ONE. 2013;8(1):e53867.
19. Park KY, Jeong JK, Lee YE, Daily JW. Health
benefits of kimchi (Korean fermented veg-
etables) as a probiotic food. J Med Food.
2014;17(1):6-20.
20. Vina I, Semjonovs P, Linde R, Denina I. Current
evidence on physiological activity and expected
health effects of kombucha fermented bever-
age. J Med Food. 2014;17(2):179-88.
21. Kumar S, Mahajan BB, Kamra N. Future
perspective of probiotics in dermatology: an
old wine in new bottle. Dermatol Online J.
2014;20(9).
®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
18 IRREGULARBORDER
PROBIOTICS:
Kefir gels from page 10
Probioticsmayhelptonormalize
disruptionsinhumanmicrobial
communitiesandbacteria-hostinteractions
thatcontributetonon-healingwounds.
18. 24 CLINICAL DERMATOLOGY
Scleroderma skin ulcers are challenging to manage and can be ap-
proachedwithavarietyoftherapiesandtreatments,accordingto Alain
Brassard,M.D.,FRCPC,professorof dermatologyandmedicineinthe
DepartmentofMedicineattheUniversityofAlbertainEdmonton,speak-
ing at the annual meeting of the Canadian Association of Wound Care
(CAWC).
Inthecaseofsclerodermaoftheskin,approximately35%ofpatients
will eventually get cutaneous ulcers, according to Dr. Brassard.
“Sclerodermaisadiseasethatissystemicandneedstobetreatedsys-
temicallytohealtheulcers,”saysDr.Brassard,inaninterviewwithDer-
matologyTimes.“Theulcersarerelatedtoendothelialcellsthataredriv-
ingthescleroderma.Raynaud’sphenomenonisusuallypresentinmany
patientswithscleroderma.Thatphenomenonmaycreatedigitalulcers
that are horrible in terms of the impact on quality of life of patients.”
PHARMACOLOGIC APPROACHES
Pharmacologicapproachesincludevasodilators,whichtargetRaynaud’s
phenomenon, and agents aimed at endothelial cell protection such as
Phosphodiesterase-5 inhibitors (sildenafil and tadalafil). Secondary
Raynaud’s phenomenon linked with scleroderma can be more severe
than primary Raynaud’s phenomenon.
Calcium-channel blockers have been shown to offer a significant
benefit in managing Raynaud’s phenomenon because of the improve-
ment in the frequency and severity of ischemic attacks.1
Another study has found that infusions of iloprost was a preferred
therapy for acute necrosis. Scleroderma ulcers may herald pulmonary
hypertension. Bosentan monohydrate, an endothelial cell protector,
avoidsvasoconstrictionandhasdemonstratedthatitiseffectiveinpre-
venting the formation of new digital ulcers as well as reduce the devel-
opment of pulmonary arterial hypertension.2
Statins are agents that are immunomodulatory, vasodilatory and
antifibrotic.3
The evidence, however, for their use in managing scle-
roderma and systemic sclerosis is weak, as they have not been studied
in large trials but could be considered and should be studied further.4
NEUROMODULATOR APPROACH
Anotheremergingmedicaltherapyinthetreatmentofdigitalulcersin
patients with systemic sclerosis is botulinum toxin type A, which de-
creases swelling, decreases pain and enhances perfusion of fingers by
opening up the vasculature and permitting better oxygenation.
Cliniciansshouldbecautiousaboutinjectingbotulinumtoxinsoas
nottocauseexcessiverelaxationofthehandmuscles.Injectionsshould
beinitiallylimitedtothefingers,withsuccessiveinjectionstothehand
if necessary at subsequent visits.
Injection of botulinum toxin is a less invasive alternative to surgical
sympathectomy, producing a chemical sympathectomy that will have
a duration of several months.
Non-pharmacological management avenues include avoidance
of cold, stress and trauma, as well as smoking cessation. On the
horizonliefuturetreatmentsforsclerodermalskinulcers,suchasstem
cell therapy. DT
Disclosures: Dr. Brassard has no relevant disclosures.
Sclerodermaskin ulcers
LOUISE GAGNON | STAFF CORRESPONDENT
WHICH APPROACH IS BEST?
See references and read the full article at: bit.ly/Sclerodermaskinulcers
19. 25JULY 2015 ⁄ DERMATOLOGYTIMES.COM
VIGNETTEDERMATOLOGY
as soon as you met him. He was the most
gentle, sweet, loving guy,” Dr. Green says.
THE END
As jovial, prominent and successful as he
was, Dr. Brandt suffered from a darkness
those who were close to him could feel
but not fix.
Going forward hasn’t been easy, says
Dr. Geronemus. “We have a lot of very
distraught patients. We have people call-
ing the office in tears. Patients coming in
in tears. “He had a very high level of cli-
entele and people who weren’t high level.
He treated them all well. And they were
truly his friends. The staff were very close
to him.”
Dr. Geronemus says Dr. Brandt
seemed bothered by a few things in the
weeks before his death, but Dr. Gerone-
mus didn’t sense the seriousness of his
business partner’s depression.
MEMORIALFUNDS
In tribute to Dr. Brandt, the American
Society for Dermatologic Surgery (ASDS)
has set up two memorial funds.
The Allergan Foundation has commit-
ted $300,000 for the ASDS to administer
The Fredric S. Brandt, M.D., Innovations
in Aesthetics Fellowship Fund in col-
laboration with the Society’s accredited
cosmetic dermatologic surgery fellowship
training programs. The fund supports the
career development of junior dermato-
logic surgeon-scientists focused on cos-
metic treatments and patient care.
ASDS also has established the Fredric
S. Brandt, M.D., Memorial Research Fund
to support well-conceived clinical re-
search projects in cosmetic dermatologic
surgery or board-directed research relat-
ing to the safety of cosmetic procedures,
according to an ASDS press release.
“This Memorial Research Fund gives
Dr. Brandt’s friends, colleagues and in-
dustry partners a mechanism to honor his
memory in a way that is consistent with
who he was as a person and physician —
innovative, giving and collaborative — for
the benefit of the entire specialty,” says
ASDS President George J. Hruza, M.D.,
M.B.A.
For information about donating to
either fund, contact Tara Azzano at taz-
zano@asds.net or 847-956-9128. DT
Reference:
1. Grinnell, Sunhee. In Loving Memory of Dr. Fredric
Brandt (1949-2015). Vanity Fair. April 17, 2015.
Available online at: http://www.vanityfair.com/
style/2015/04/in-loving-memory-of-dr-fredric-
brandt-1949-2015
FREDERIC S. BRANDT:
Farewell to the Baron of Botox from page 12
Read the full article:
bit.ly/Farewellfredericbrandt
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COSMETIC DERMATOLOGY26
Dermatologistsconsideringlaser
hairremovaltechnologyfortheirlaser
practicesshouldgointoitknowingthe
level of competition, their patients’
needs and that there are plenty of op-
tions —some more effective than oth-
ers, says Landon Pryor, M.D., plastic
surgeon, Rockford, Ill., and clinical
assistant professor of plastic surgery
at University of Illinois.
“Beforeinvestinginanydevice,lookat
multiple vendors and find out… specif-
ics, as far as what kind of clearance [to]
expect. Is it 50% hair reduction, 100%,
90%?Howmanytreatmentsareneeded?
What are the skin types [for treatment
with the laser]?” Dr. Pryor says.
HAIR REMOVAL NUANCES FOR
THE DERMATOLOGIST
TerrenceKeaney,M.D.,clinicalprofessor
of dermatology and urology at George
Washington University Medical Cen-
ter, and director of the men’s cosmetic
center, W for MEN, at the Washington
InstituteofDermatologicLaserSurgery,
saysdermatologistsneedtopayspecial
attention to patient skin type when of-
fering hair removal laser services.
“Typically, with hair removal, we
prefer a little longer wavelength that
is a little less specific to pigment to
avoid any burning or scarring. For
lighter skin types, using a more pig-
ment-specific laser hair removal de-
vice is nice,” Dr. Keaney says. “So,
having a laser platform that can treat
bothisdefinitelyanadvantage,instead
of having to buy a different device for
Using a lidocaine mix with
hyaluronic acid (HA) fillers to help
mitigate pain is not an uncommon practice.
But can adding epinephrine to lidocaine
further offset bruising and pain? A research
team investigated the severity of bruising and
pain in patients treated with the cohesive
polydensified matrix HA in three different
preparations: CPMHA (BEL), CPMHA
with lidocaine (BEL-L) and CPMHA with
lidocaine and epinephrine (BEL-LE).
SOURCE: BIT.LY/HAFILLERS
28
29ENERGY TECHNOLOGY 411
When it comes to energy devices,
Dr. E. Victor Ross shares what does what
LASER SAFETY TIPS
Experts offer these laser safety tips
HAIR REMOVAL DEVICES see page 28
Hair removal lasers: are they
right for your practice?
LISETTE HILTON | STAFF CORRESPONDENT
If I were to grade the
three, I’d give non-abla-
tive lasers an A-plus,
ablative lasers an A and
conventional resurfacing
a B, due mainly to
relatively long down-
time for the patient.”
E. Victor Ross, M.D.
San Diego, Calif.
Energy devices: what does what
See story page 29
Several factors come into play
when considering whether
to add laser hair removal to
the dermatologist’s practice.
Industry experts offer their
insights and advice.
QUICK READ
Quotable DTExtra
“With hair removal, we prefer a little
longer wavelength that is a little less
specific to pigment to avoid any burning
or scarring. For lighter skin types,
using a more pigment-specific
laser hair removal device is nice.”
Landon Pryor, M.D.
Rockford, Ill.
22. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
28 COSMETIC DERMATOLOGY
darker skin types and a different de-
vice for lighter skin types.”
Michael H. Gold,
M.D., medical direc-
tor, Gold Skin Care
Center and Tennessee
ClinicalResearchCen-
ter, Nashville, Tenn.,
says hair removal is
his laser practice’s do-
mainandasourceforreferralforother
procedures. Dr. Gold’s practice has
more than 40 devices.
“For hair reduction, I recommend
theSopranoICE810nmDiodewithIn-
Motiontechnology(AlmaLasers).Itisa
very efficacious way to treat hair for all
skin types,” says Dr. Gold. “The system
has a 2.0 cm spot handpiece with con-
tactcoolingfortreatinglargeareas.The
patients tolerate the virtually painless
treatment very well, and my staff can
treatabackinlessthan20minutes.This
systemhasnoconsumablesandhasin-
creasedthevolumeinmylasercenter.”
Other laser hair removal diode sys-
tems also work with vacuum technol-
ogy to reduce pain and bring the tar-
get closer to the light source, accord-
ing to Dr. Gold.
“Thesetechnologiesworkgreatinmy
practice, as do some of the other wave-
lengths for specific patients, including
theNd:YAGsystemsforsomeofmyskin
type VI individuals,” Dr. Gold says.
Being able to treat larger surface
areas is a trend in hair removal, ac-
cording to Dr. Keaney.
“In men, for example, we’re treating
backs. In women we’re treating legs or
bikiniareas,”Dr.Keaneysays.“Withtra-
ditionalspotsizesthatwe’vehadinthe
past, that can take a long time. I think
a lot of companies are [offering] newer
technologies where they’re able to de-
liver laser hair removal in much larger
areas,dramaticallydecreasingthetime
in treatment, which is a big complaint
with some hair removal cases.”
SAFETY, TREATMENT TIPS
Don’ttakethesafetyofperforminghair
removallaserservicesforgranted,says
Dr. Pryor, who points out that this is a
medicaltreatmentandshouldbetreated
as such. “If the physician is not doing
thetreatment,…itneedstobedelegated
to a laser technician that is appropri-
ately trained in that device,” he says.
According to Dr. Pryor, he consults
with patients before they begin hair
removal treatment at his practice.
It’salsoimportanttohaveclearstaff
rulesonhowtheyshouldproceedwith
large surface areas, says Dr. Keaney.
“Sometimes when you’re treating for
a long period of time, you can forget
whereyou’vepreviouslytreated,so[it’s
important to carefully mark] certain
areas where you’ve treated and have
a very systematic approach,” he says.
IS LASER HAIR REMOVAL
RIGHT FOR YOUR PRACTICE?
Hair removal is popular and highly
competitive.
Vic Narurkar, M.D., chairman of der-
matology at California Pacific Medical
Center, San Francisco, who has a cos-
metic-onlydermatologypracticefeatur-
ing16lasers,saysdermatologistsshould
think twice about investing in hair re-
moval technology if they’re just getting
started in lasers. With spas and non-
derm practices in the mix of competi-
torsprovidingtheservice,pricewarsare
common.So,whilehavinghairremoval
lasers makes sense in a comprehensive
laserpractice,dermatologistsmightfirst
focus on less competitive areas, such as
thetreatmentofvascularconditions,ac-
cording to Dr. Narurkar. DT
HAIR REMOVAL LASERS:
Device nuances from page 26
While having hair
removal lasers
makes sense in a
comprehensive
laser practice,
dermatologists
might first
focus on less
competitive areas.
For more articles like this:
bit.ly/Nonsurgicaltreatments
SAFE LASER operation practices protect not only patients but also
staff. Experts offer these as their top safety tips:
▶ Take a Course
Bruce Katz, M.D., director of the Juva Skin and Laser Center in
Midtown Manhattan, recommends dermatologists follow strict laser
safety guidelines.
“People can learn those in a laser safety course. It’s like learning to
drive a boat or driving a car. You have to take a course and make sure
exactly what precautions to take,” Dr. Katz says.
▶ Train Staff Adequately
Terrence Keaney, M.D., director of men’s cosmetic center at the
Washington Institute of Dermatologic Laser Surgery, in Washington, DC,
says dermatologists need to oversee proper training of the staff.
“It’s not see one; do one. [Staff] should log a significant amount of
cases,” Dr. Keaney says.
▶ Have a Dedicated Safety Officer
Vic Narurkar, M.D., who has 16 lasers at his cosmetic-only
dermatology practice in San Francisco, says dermatologists who
offer lasers should have a dedicated laser safety officer.
“You need to train your staff on optic… safety and that is all
done through the laser safety officer,” Dr. Narurkar says. “We have
one in our office — that’s me. And I trained all my staff.”
Dr. Narurkar also recommends dermatologists capitalize
on the in-services and training that most of the manufacturers
provide.
▶ Pay Attention to Details
Seemingly small precautions can make a big difference in the safety
of a laser practice, Dr. Katz says. One example: Patients should
never wear paper gowns. Why? They can catch fire. Cloth gowns are
recommended for safety, according to Dr. Katz. DT
Laser
safety
tips
Michael H. Gold
23. 29JULY 2015 ⁄ DERMATOLOGYTIMES.COM
COSMETIC DERMATOLOGY
Giventhenumberofconditionstotreat
as well as the ever-increasing variety of
devices with which to treat them, even
seasonedpractitionersmightneedare-
freshercourseonwhatdevicesdowhat.
That’saccordingtoE.VictorRoss,M.D.,
of Scripps Clinic, San Diego, who pre-
sented “Energy Devices A to Z: What
Does What,” at the inaugural Aesthetic
+MedicalDermatologySymposia,held
in Coeur d’Alene, Idaho, in May 2015.
Dr.Rossreviewedwhatdeviceswork
best for specific conditions, including
facial rejuvenation (especially acne
scars), red and brown spots, tattoo re-
moval and skin tightening.
ENERGY FOR ACNE SCARS
For ease of use by the practitioner and
littledowntimeinvolvedforthepatient,
Dr. Ross gives his highest grade to non-
ablative fractional lasers.
“Ablativelasersofferbetterresults,but
there’s more downtime involved,” says
Dr. Ross. “Conventional resurfacing is
still widely used, but if I were to grade
thethree,I’dgivenon-ablativelasersan
A-plus,ablativelasersanAandconven-
tionalresurfacingaB,duemainlytothe
relativelylongdowntimeforthepatient.”
A new technology for treating acne
scars is radio frequency (RF) needling,
which uses a combination of radio fre-
quencyandneedlingtoinducecollagen
production in the deeper skin layers.
He notes that vascular lesions bene-
fit from pulsed dye, potassium titanyl
phosphate (KTP) and intense pulsed
light (IPL) lasers.
TATTOO REMOVAL
There’s new technology for removing
tattoos,”Dr.Rosssays.“Thehottestnew
thing is the picosecond laser, which is
a step up from the nanosecond laser
in that it’s capable of removing tattoos
withfewertreatmentsessions.Still,some
tattoos just don’t respond — to any de-
vice we use — but it looks like picosec-
ond lasers are trending for the future.”
Fractionallasersremainachoicefor
removing some resistant tattoos.
BROWNSPOTS,SCARSSKINTIGHTENING
Forbrownspots,“There’sacollageofdif-
ferent things you can do,” Dr. Ross says,
citing fractional (especially thulium),
Q-switchedlasers,IPLandKTPlasersas
thepreferredtoolsfortheseindications.
Whenitcomestoscars,fractional,Q-
switchedandvascularlasersremainthe
devicesofchoice,accordingtoDr.Ross.
“In this area, you
basically find the par-
ticular characteristic
of the scar that differ-
entiates it from normal
surrounding skin, and
then choose the most
appropriate device to
treat it with.”
The idea of replac-
ing surgical proce-
dures with energy de-
vices for skin tighten-
ing is appealing for pa-
tientswhowanttowant
to turn back the clock
without the expense of
significant downtime.
“In reality, though,
non-surgical ‘facelifts’
using energy devices
only help temporar-
ily or can defer a face-
liftuntillater,”Dr.Ross
explains.
COSMETIC VS MEDICAL
Inkeepingwiththetitle
ofthemeetingDr.Ross
made sure to differen-
tiate.
“When we think of
cosmetic versus med-
ical application for
RF, ultrasound and
laser devices, there are
areas that can be clas-
sified as medical, such
as port wine stains, se-
vere scars and birth-
marks,” he says. “With
these and other such
conditions,weareoften
treating psychological
as well as medical is-
sues.”
As for the future of
energy devices, Dr.
Ross had this predic-
tion: “They will be
smaller, easier to use
and more ergonomi-
cally friendly, and feature more sophis-
ticated ‘navigational’ features to help in
their use. They will provide more feed-
backtothepractitionerregardingproper
settings by scanning — or even photo-
graphing — the area being treated.” DT
Energy devices: what does what?
BILL GILLETTE | STAFF CORRESPONDENT
24. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
CUTANEOUSONCOLOGY30
Identifying specific neo-antigens
inmelanoma,acancerknownforhav-
inghighnumbersofgeneticmutations
causedbyexposuretoultravioletlight,
isnoeasytask.Amelanomabiopsytypi-
callycarries500ormoremutatedgenes.
Todate,vaccineshavetargetednon-
mutated shared proteins expressed
in normal and cancer cells. This has
made it difficult to stimulate a robust
immune response because the im-
mune system does not see these pro-
teins as foreign, says Gerald Linette,
M.D., Ph.D., a Washington University
medical oncologist.
Researchers recently published re-
sults on the first human study1
look-
ing at personalized vaccines designed
to activate T-cells aimed at individual
cancer patient’s mutations. The study,
including three advanced melanoma
patients, suggests these tailor-made
vaccines boost T-cell number and di-
versity, resulting in a tumor response.
The vaccines in this study are engi-
neered based on which of the tumor-
specific proteins altered due to DNA
mutations are most likely to elicit a
strong individual immune response,
accordingtoco-authorElaineMardis,
Ph.D., co-director of the McDonnell
Genome Institute at Washington Uni-
versity.
“Inparticular,ourvaccineapproach
seeks to remind the patient’s immune
systemthatthesemutatedproteinsare
truly non-self…,” Dr. Mardis says.
METHODOLOGY
Researcherssequencedthegenomesof
the patients’ tumors. They used mass
spectrometrytoidentifyneo-antigens
on the tumors’ surfaces that were en-
codedbyspecificmutantgenes.There-
searchersselectedasetofsevenunique
neo-antigenstoengineereachvaccine,
andusedpatient-deriveddendriticcells
to deliver the neo-antigens to the im-
munesystem.Eachpatientreceivedthree
vaccine doses during about 18 weeks.
FINDINGS
Blood analyses revealed that each
patient’s immune system responded
to specific neo-antigens in the vac-
cines. The vaccines stimulated di-
verse clones of T-cells against neo-
antigens, suggesting this approach
also could be used to activate T-cells
in other cancers with high mutation
rates, such as lung cancer, bladder
cancer and certain colorectal can-
cers, according to a press release
by Washington University School
of Medicine.
After receiving the individualized
vaccines, the one patient who began
the study in remission remains in re-
mission, with no evidence of cancer.
Regarding the other two patients, one
patient had a transient two-month re-
gression of lung metastasis while the
other patient had stable disease, ac-
cording to Dr. Linette’s comments at
anewsconference withthestudy’sre-
searchers.
Total global spending on
oncology medicines –
including therapeutic treatments
and supportive care – reached the
$100 billion threshold in 2014, while
spending on oncology drugs in
the United States increased 5.3%
compounded annual growth rate
(CAGR) in 2014 to reach $42.4
billion, according to a new report.
SOURCE: BIT.LY/ONCOLOGYSPENDING
33
34FDA ABOUT-FACE ON T-VEC
Approval comes days after accelerated
schedule denied
‘ADDICTION’ MAY FUEL TANNING,
RISK TAKING
Indoor tanning linked with risky behaviors
PERSONALIZED VACCINE see page 39
Personalized melanoma
vaccines debut in humans
LISETTE HILTON | STAFF CORRESPONDENT
There’s a chance
that patients who
routinely tan also
regularly engage in
unprotected sex, binge
drinking and illicit
drug use.”
Hensin Tsao, M.D., Ph.D.
MauiDerm 2015
‘Addiction’ may fuel tanning,
risk taking
See story page 33
Quotable DTExtra
25.
26.
27. 33JULY 2015 ⁄ DERMATOLOGYTIMES.COM
CUTANEOUSONCOLOGY
Maui – Taken together, two new stud-
iessuggestthatamongteens,indoortan-
ningislinkedwithotherriskybehaviors,
andthattannersmaybeseekingasortof
naturalhigh.Thisinformationmayhelp
dermatologistsdiscusshealthylivingin
general with patients.
Recent data reflect a slight down-
turn in tanning among teenagers, says
HensinTsao,M.D.,Ph.D.,atMauiDerm.
He is clinical director of the Massa-
chusetts General Hospital Melanoma
Pigmented Lesion Center, director
of the MGH Melanoma Genetics Pro-
gram, and professor of dermatology at
Harvard Medical School.
A national survey shows that the
proportion of teens who had tanned
indoors fell from 25.45% to 20.9% be-
tween2009and2011.1
Amongtheheavi-
est users, non-Hispanic white females
aged 16 years and up, the correspond-
ing figures are 37% and 29%.
Perhaps more surprising are statisti-
cally significant associations that sur-
facedbetweenindoortanningandother
risky behaviors, such as binge drinking
(reportedby31.2%offemaletannersand
6.2%ofmaletanners),unhealthydieting
(27.8%versus9.3%,respectively)andsex-
ual intercourse (29.6% versus 6.5%). For
girls, the data also revealed statistically
significant associations between tan-
ning and sunscreen avoidance (24.9%),
illegaldruguse(28.4%),andhavingfour
or more sexual partners (26.6%).
Frequent tanners exhibit even more
willingness to take risks, says Dr. Tsao.
Amonggirlswhotanmorethan10times
yearly,55%to65.5%reportedsunscreen
avoidance, binge drinking and steroid
use without prescriptions.
Overall, Dr. Tsao says that by age 18,
“Roughlyone-thirdofallAmericanhigh
schoolgirlsprobablyhavetanned.More
importantly, there’s a chance that pa-
tients who routinely tan also regularly
engageinunprotectedsex,bingedrink-
ing and illicit drug use.” And a similar
biochemicalbuzzmaydrivealltheseill-
advised behaviors, he surmises.
In this regard, a mouse study has
shown that, with respect to tanning,
β-endorphins in the skin may drive ad-
dictivebehavior.2
UVdamagetokeratino-
cytesproduceshormoneproductsinthe
skinincludingthepro-opiomelanocortin
(POMC)gene,saysDr.Tsao.Components
thatsplitoffthispeptideincludemelano-
cyte-stimulating hormone, which stim-
ulates tanning. “The other component
people don’t think about is a natural en-
dogenous opiate, β-endorphin. Maybe
this secondary product has some more
central behavioral influence” than pre-
viously recognized.
In the study, UVB-irradiated mice
had higher serum β-endorphin levels
versus unirradiated mice. Additionally,
threshold pressure testing of the skin
showed that irradiated mice could tol-
eratemorepressureandheat,suggesting
thattheirskinhadbeenanesthetized—
an effect that the opiate antagonist nal-
oxone reversed.
Givingirradiatedmicenaloxonepro-
duced opiate withdrawal symptoms.
And, when given a choice, irradiated
mice avoided water infused with nalox-
one in favor of pure water. “That’s addi-
tional evidence that they’re somewhat
behaviorally addicted,” says Dr. Tsao.
Although tanning beds provide
largely UVA rather than UVB, he says,
“The study is intriguing. UVB creates
mutations in the skin. Perhaps the gen-
esis of this pathway is sunburn pain.”
If tanning is truly a component of
global risk-taking behavior, “That has
much less to do with mutations in the
skin than with the brain’s pleasure cen-
ter.” Ultimately, he’d like to see studies
showingconvincinglythattannershave
higherβ-endorphinandopiatelevels—
and then investigating whether opiate
antagonists could curb humans’ urge
to tan.
For now, he says that, when counsel-
ing patients who tan, dermatologists
can consider it an opening to discuss
whether they’re engaging in other risky
behaviors. “Tanning may be an oppor-
tunity to open a dialogue about risk be-
haviorsandhealthylivingoverall.”That
includes eating five servings of fruit or
vegetablesdaily—anotherhealthyhabit
that tanners in the survey shunned. DT
Disclosures: Dr. Tsao serves on the editorial boards
of several dermatology journals and has received re-
search funding from the National Institutes of Health
and the American Skin Association.
References
1. Guy GP Jr, Berkowitz Z, Tai E, Holman DM, Ever-
ett Jones S, Richardson LC. Indoor tanning among
high school students in the United States, 2009
and 2011. JAMA Dermatol. 2014;150(5):501-11.
2. Fell GL, Robinson KC, Mao J, Woolf CJ, Fisher DE.
Skin β-endorphin mediates addiction to UV light.
Cell. 2014;157(7):1527-34.
‘Addiction’ may fuel tanning, risk-taking
JOHN JESITUS | STAFF CORRESPONDENT
yvoice of the dermatologist
“We have been struggling for generations to make the
best treatment recommendations for children with
severe AD. Finally, we have hope for the chance to
offer them better options in the foreseeable future.”
Elaine Siegfried, M.D.
See Pediatric trials for AD systemic treatments, page 14
28. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
34 CUTANEOUSONCOLOGY
TwodaysafteritreportedthattheFood
and Drug Administration had denied
accelerated approval to Amgen exper-
imental melanoma drug talimogene
laherparepvec(T-Vec),Reutersreported
that an FDA advisory panel voted to
approve the drug for marketing.
Dermatology Times discussed the
approval with Wm. Philip Werschler,
M.D., FAAD, FAACS, Associate Clin-
ical Professor at University of Wash-
ington School of Medicine in Seat-
tle, Wash.
“Globally, the treatment of mela-
nomahasadvancedgreatlyinthepast
5 years. It appears that we are on the
cuspofsignificantsuccessinthemed-
icalmanagementofmelanoma,some-
thing that heretofore was the domain
of surgical management.
“Because of the culmination of
many decades of dedicated research
on the genetics and biological be-
havior of melanoma, and tumor re-
sponse to various medical interven-
tions, today there exists a variety of
anti-tumor drug options of various
types and classes. The medical on-
cologist, in consultation with derma-
tologists, internists and surgeons is at
the same time fortunate and bewil-
dered in terms of selecting the best
and most efficacious and most appro-
priate drug therapy options for the in-
dividual melanomapatient.Truly,the
era of personalized medicine is upon
us with regard to melanoma therapy.
“The seemingly confusing about-
faceoftheFDAwithregardtoAmgen’s
T-Vec investigational drug perhaps is
better examined in the perspective
of a very rapidly changing landscape
of melanoma therapy. I applaud the
FDA for having the insight and cour-
age to face criticism and be willing to
reexamine facts to arrive at a differ-
ent conclusion from one reached just
days earlier.”
Reuters reported April 27 that
FDA staff reviewers said they could
not consider an accelerated review of
T-Vec—anengineeredvirusthatkills
cancer cells when injected into tu-
mors and primes the immune system
to attack the disease — due to con-
cerns over the design and results of
a key study. Specifically, an indepen-
dent panel said it questioned whether
the immunotherapy improved over-
all survival of patients.
Also on April 27, Medical Marketing
Media reported that the recent ap-
proval of drugs such as Merck’s Key-
truda and Bristol-Myers Squibb’s Op-
divo—unavailablewhenAmgenstarted
testing in 2009 — reduced the urgency
of an accelerated-approval designation
for T-Vec. According to MMM, Amgen
and Merck signed a deal last year to ex-
plore how T-Vec worked with PD-1 in-
hibitor Keytruda.
Then, on April 29, Reuters reported
the FDA’s ruling that T-Vec had shown
enough efficacy to earn marketing
approval. According to another re-
port by Medscape Medical News, the
recommendation for approval came
from two advisory panels: the Onco-
logic Drugs Advisory Committee and
the Cellular, Tissue and Gene Thera-
piesAdvisoryCommittee,membersof
which voted 22-1 to approve.
T-Vec contains a genetically mod-
ified version of the herpes simplex
virus, engineered to replicate in the
tumor and destroy cancer cells.
Thedrugalsoisbeingconsideredfor
approval in the European Union. DT
Researchersconductingafirst-of-
its-kindstudycombiningthecheckpoint
inhibitor tremelimumab with an anti-
CD40monoclonalantibodydrugreport
the dual treatments are safe and pro-
duce a clinical response in metastatic
melanoma patients.
Researchers presented the abstract
for the Phase I trial during the Amer-
ican Association for Cancer Research
(AACR) 2015 meeting in Philadelphia.
“… New treatment protocols com-
bining immunotherapies are coming.
This is the first combination of an im-
munostimulatory agent with check-
point blockade,” says lead author
David Bajor, M.D., instructor in the
hematology/oncology division in the
Perelman School of Medicine, Univer-
sity of Pennsylvania. “When they are
thoughtfullycombinedwithimmune-
stimulating compounds like CD40 or
drugs targeting other facets of the im-
mune system, we hope to be able to in-
crease the response rate to previously
approved therapies.”
While researchers were concerned
thatthecombinationcouldincreaseside
effects, that didn’t happen in this study.
“Generally, the adverse event pro-
file seen in this particular combination
(agonistic CD40 and tremelimumab) is
similar to that of each drug alone,” Dr.
Bajor says. “The most significant der-
matologic toxicity we saw was pruritus.
Notably, several of our patients who did
very well and, thus, were on the com-
bination for many months had grade
2 pruritus with or without a macu-
lar/papular rash. Identifying non-cor-
ticosteroid based treatments for this
side effect could greatly improve the
comfort and quality of life for patients
receiving this type of treatment, while
allaying the oncologists’ fears of damp-
ening the immune response.”
Dr. Bajor has no relevant disclo-
sures. DT
FDA OKs melanoma drug after
denying it accelerated approval
Immunotherapy combo appears safe,
shrinks metastatic melanoma tumors
BILL GILLETTE | STAFF CORRESPONDENT
LISETTE HILTON | STAFF CORRESPONDENT
Read the full article at:
bit.ly/melanomacombosafe
29. Bio-Oil®
is a skincare oil that helps improve the appearance of scars, stretch marks
and uneven skin tone. It contains natural oils, vitamins and the breakthrough
ingredient PurCellin Oil™
. For comprehensive product information and results of
clinical trials, please visit bio-oil.com. Bio-Oil is the No.1 selling scar and stretch
mark product in 18 countries. $11.99 (2fl.oz).
30. ®
JULY 2015 ⁄ DERMATOLOGYTIMES.COM
36 CUTANEOUSONCOLOGY
although it may not be the most impor-
tant one or the most frequent problem
you see, is malignant transformation of
the nevi. However, another significant
concernisthestigmatizationofthesepa-
tients, as well as the limited treatment
options of these lesions, which can be
difficult to manage because surgeries
canbequitechallengingtoperformand
are typically multiple,” says Dr. Reyes-
Múgica.
AccordingtoDr.Reyes-Múgica,these
typically complex and staged surgeries
can also sometimes be disfiguring. The
success of treatment often depends on
the location of the nevus and its unique
pattern or thickness, as well as the indi-
vidual patient’s idiosyncratic ability to
repair tissues.
“There are several different factors
that need to be taken into considera-
tion when deciding on the appropriate
treatment approach for CMN lesions.
Each case must be approached individ-
ually, as no one treatment strategy fits
all,” says Dr. Reyes-Múgica.
Dr. Reyes-Múgica and colleagues re-
cently published their results of a pro-
spectivestudythatinvestigatedtheasso-
ciation between the standardized clin-
ical features of CMN and large/giant
CMN in a large patient cohort, with
the mutational status of NRAS Q61 and
BRAF V600 in nevi lesions.1
The ongoing study included 66
CONGENITAL MELANOCYTIC NEVI see page 39
CONGENITAL MELANOCYTIC NEVI:
BRAF gene mutation breakthrough from page 1
Not only could
an association
between BRAF
mutations and
large/giant CMN
be identified, but
there is also a
clear association
with the BRAF-
mutated gene
and NCM.
Proliferative nodule arising in a GCMN.
Note the upper portion with scattered
nevus cells surrounding a hair follicle
in the upper center. The lower
portion of the image shows a highly
cellular lesion with small nevus cells
(proliferative nodule) (HE, 10X).
Photo credit: Miguel Reyes-Múgica, M.D.
Brain cortex of a patient with
neurocutaneous melanocytosis (NCM)
showing pigmented NCM cells in the
leptomeninges and infiltrating through
the perivascular Virchow-Robin spaces
(HE, 4X).
Photo credit: Miguel Reyes-Múgica, M.D.
Classic low power histological view of
a GCMN. Note the impressive thickness
of the lesion, involving subcutaneous
tissue and replacing dermal
components (HE, 4X).
Photo credit: Miguel Reyes-Múgica, M.D.
GCMN stained with HMB45
immunohistochemistry. The lesion
involves fascial plane and replaces
the subcutaneous tissue and dermis
(HMB45, 4X).
Photo credit: Miguel Reyes-Múgica, M.D.
what familiar with CMN (congenital
melanocytic nevi) and NCM (neurocu-
taneousmelanocytosis),theaveragecli-
nicianmaybeoverwhelmedwhencon-
fronted with such a patient regarding
therapy and management. Therefore,
it is important that clinicians not only
recognize this significant issue but also
become more familiar with the current
treatmentapproachesaswellasthosein
thepipeline,”saysMiguelReyes-Múgica,
M.D., Chief of Pathology and Director
of Laboratories, Children’s Hospital of
Pittsburgh of UPMC, Pittsburgh, Penn.
CMNarebenignproliferationsofmu-
tant melanocytes (nevomelanocytes)
that are typically present at birth or de-
velopshortlyafterbirth,andcanloosely
be categorized into small ( 1.5 cm di-
ameter),medium(1.5-10cm),large(11-20
cm),andgiant(20cmdiameter)lesions.
LargeandgiantCMNlesionsarepar-
ticularlyassociatedwithasetofcompli-
cationsthatincludedecreasedsweating,
xerosis, pruritus and skin fragility. Pa-
tients also experience altered or dimin-
ished tissue growth due to the hamar-
tomatous and infiltrative nature of the
lesions; a higher complexity of surgical
removal; and childhood psychological
problems secondary to cosmetic issues
and social stigmatization.
CMN are also associated with an in-
creasedlifetimeriskofmalignanttrans-
formationtomelanomaaswellastherisk
forNCM,aproliferationofnevomelano-
cytesintheleptomeningesandbrainpa-
renchyma,furtherunderscoringtheur-
gencytoaddresstheselesionsappropri-
ately and in a timely manner.
“The biggest worry with CMN,
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38 TRADETOOLS
Neossance squalane
skin solution
AMYRIS introduces Neossance squalane skin solution, which, according to
the company, is derived from plant sugar and is a high-purity, high-quality,
sustainable replacement for squalane. Neossance is a fully saturated, non-polar
hydrocarbon. Squalene is naturally present in the skin’s lipid barrier, preventing
moisture loss while restoring the skin’s suppleness and flexibility. Squalane’s
exceptional moisturizing properties and ability to penetrate the skin have made
squalane a long time favorite amongst cosmetic formulators. According to the
company, Neossance offers a silky, smooth and elegant texture without a greasy,
heavy after feel.
AMYRIS
w w w . a m y r i s . c o m
OVER-THE-COUNTER ACNE REGIMEN
GALDERMA LABORATORIES announces
the launch of Benzac Acne Solutions, an
over-the-counter acne regimen. The new
3-step regimen includes the Benzac Skin
Balancing Foaming Cleanser, Benzac
Intensive Spot Treatment and Benzac
Blemish Clearing Hydrator. According
to the company, Benzac treats stubborn
acne and prevents new breakouts from
forming with the use of salicylic acid,
while pharmaceutical-grade East Indian
sandalwood oil calms and soothes the
skin. Benzac also contains the mineral
zinc, which helps to prevent skin moisture
loss. According to the company, this
acene regimen is safe for sensitive skin,
dermatologist tested, non-comedogenic
and free of artificial fragrances and dyes.
GALDERMA
w w w . g a l d e r m a U S A . c o m
MOISTURIZER TREATS
SYMPTOMS OF
PHOTOAGING
SKINCEUTICALS
launches Metacell
Renewal B3
, a
comprehensive daily
corrective moisturizer
that the company says
visibly corrects early
symptoms of
photoaging to
reduce wrinkles,
re-tighten surface
elasticity and even
skin tone. The
company says that
Metacell Renewal B3
utilizes an inverse
aqueous emulsion
to deliver a high
concentration of
5% niacinamide
combined with 2.5%
tightening tri-peptide
concentrate and 15% glycerin
to correct early symptoms of
photoaging.
SKINCEUTICALS
w w w . s k i n c e u t i c a l s . c o m
NEW NAIL
STRENGTHENING
TREATMENT
DERMELECT
COSMECEUTICALS has
launched its Dermelect
Nail Strengthener Duo,
which includes two
treatments. According to
the company, Launchpad
Nail Strengthener Base
Coat helps to encourage
stubborn nails to grow
and improves strength;
Rejuvenail Fortifying Nail Cuticle
treatment hydrates and strengthens
nails. The company says that these
products utilize protein-peptide
technology to hydrate, protect and
strengthen nails.
DERMELECT
w w w . d e r m e l e c t . c o m
