Dermatology Times May 2015 ezine

Clinical Analysis for Today’s Skincare Specialists May 2015 | VOL. 36, NO. 05 |
Louise Gagnon | Staff Correspondent
Targeting your
melanoma therapy
Figure A. Melanoma site. B. Markings for
impending surgery Photos: Charles M. Balch, M.D.
Fast, in-offce photodynamic
therapy with no patient pain
Karen Donley-Hayes | Staff Correspondent
InThis Issue May 2015 VOL. 36, NO. 05
CLINICAL 16
Chikungunya and Coxsackievirus A6
Viruses making waves in the U.S.
COSMETIC 22
The non-surgical eye lift
Combining fllers and neuromodulators can yield
excellent results and high patient satisfaction
ONCOLOGY 30
Mutations infuence
CTLA-4 blockade response
Exome sequencing helps predict survival
BUSINESS 46
Narrowing networks create
harrowing choices
Paring of plans impacts patient choice
| THE TAKEAWAY | SEEMAL DESAI, M.D., Insights into managing vitiligo, part 2 of dyspigmentation discussion SEE PAGE 52
Personalizedtherapyinthemanagement
ofsomecancersisatrendthatwilllikelycon-
tinue, as more clues about the genetic and
molecular signature of melanoma are re-
vealed,accordingtoCharlesM.BalchM.D.,
F.A.C.S.,aprofessorofsurgery,Universityof
TexasSouthwesternMedicalCenter,Dallas.
ÒBreastcancerandlungcanceraremod-
elsofwhatwewilldowithmelanomainthe
future,ÓDr.Balchsays.ÒWewillusegenetic
andmolecularbiomarkerstoselectpatients
fortargetedtherapy,includingpatientswho
may benefit from immunotherapy.Ó
With the availability of targeted thera-
pies, the development of treatment algo-
rithms continues to evolve in melanoma,
Surrogate measures test efficacy of agents
a disease that is very heterogeneous genet-
ically, but that has been treated clinically
in a homogeneous fashion, Dr. Balch says.
ÒIf patients have stage IV disease, and
they go into remission, one question to ask
ishowlongtokeeptreatingthem,ÓDr.Balch
says.ÒTherewillbemanysubsetsofpatients.
BRAFandanumberofotherreceptors[have]
yettobeemployedataclinicallevel.Forex-
ample,acrallentiginousmelanomaisdiffer-
entthansun-inducedskinmelanoma.
BIOMARKERSANDNEO-ADJUVANTTHERAPY
ÒTherewillbemorebiomarkersthanBRAF
that will be identified in the future to help
A
B
TARGETING see page 45
For nearly two decades, dermatol-
ogists have been able to offer their pa-
tientsahighlyeffectivetreatmentforAKs
thanks to Levulan, a liquid containing 5
aminolevulinic acid (5-ALA), to treat ac-
tinickeratosesusingphotodynamicther-
apy(PDT).TheFDAapprovedLevulan(5-
ALA) based on a 14- to 18-hour incuba-
tion after application to the face or scalp.
However, two significant factors
clouded an otherwise bright advance-
ment with this therapy: time and pain,
and too much of both. These issues
havebeenaprimaryfocusforMaui-
based dermatologist George Mar-
tin, M.D., a practicing clinician,
clinical investigator, and interna-
tional lecturer. He is founder and
program chairman of MauiDerm,
theinternationallyrecognizedder-
matology meeting. Along with Dr.
Ted Rosen, Dr. Martin discussed
PDT at MauiDerm 2015.
PAINLESS PDT
ONCOLOGY
PAINLESS PDT see page 42
DermatologyTimes®
May2015Volume36No.05ClinicalAnalysisforToday’sSkincareSpecialistsDermatologyTimes.com
ES603013_DT0515_CV1.pgs 04.22.2015 20:35 ADVblackyellowmagentacyan

For patients with moderate to severe plaque psoriasis who are
candidates for phototherapy or systemic therapy
◆ Otezla was evaluated in 2 multicenter, double-blind, placebo-
controlled trials of similar design. Patients with moderate to severe
plaque psoriasis (N = 1257) were randomized 2:1 to Otezla 30 mg or
placebo twice dailyfor 16 weeks, after a 5-daytitration1,2
◆ Inclusion criteria: Age ≥18 years, BSA involvement ≥10%, sPGA ≥3,
PASI score ≥12, candidates for phototherapy or systemic therapy1
◆ PASI-75 response at week 16 (primary endpoint)1,2
– Study 1: Otezla 33% vs placebo 5% (P < 0.0001)
– Similar PASI-75 response was achieved in Study 2
BSA, body surface area; PASI, Psoriasis Area and Severity Index; sPGA, static
Physician Global Assessment.
IMPORTANT SAFETY INFORMATION
Contraindications
◆ Otezla® (apremilast) is contraindicated in patients with a
known hypersensitivityto apremilast orto any ofthe
excipients in the formulation
Warnings and Precautions
◆ Depression: Treatment with Otezla is associated with an
increase in adverse reactions of depression. During clinical
trials, 1.3% (12/920) of patients treated with Otezla reported
depression compared to 0.4% (2/506) on placebo; 0.1%
(1/1308) of Otezla patients discontinued treatment due to
depression compared with none on placebo (0/506).
Depression was reported as serious in 0.1% (1/1308) of
patients exposed to Otezla, compared to none in
placebo-treated patients (0/506). Suicidal behavior was
observed in 0.1% (1/1308) of patients on Otezla, compared to
0.2% (1/506) on placebo. One patient treated with Otezla
attempted suicide; one patient on placebo committed
suicide
— Carefullyweighthe risks and benefits oftreatmentwith
Otezla for patients with a history of depression and/or
suicidal thoughts/behavior, or in patients who develop
such symptoms while on Otezla. Patients, caregivers, and
families should be advised ofthe need to be alert forthe
emergence orworsening of depression, suicidal thoughts
orothermoodchanges,andthey should contact their
healthcare provider if such changes occur
◆ Weight Decrease: Body weight loss of 5-10% occurred in 12%
(96/784) of patients treated with Otezla and in 5% (19/382)
of patients treated with placebo. Body weight loss of ≥10%
occurred in 2% (16/784) of patients treated with Otezla
compared to 1% (3/382) of patients treated with placebo.
Monitor body weight regularly; evaluate unexplained or
clinically significant weight loss, and consider
discontinuation of Otezla
◆ Drug Interactions: Apremilast exposure was decreased
when Otezla was co-administered with rifampin, a strong
CYP450 enzyme inducer; loss of Otezla efficacy may occur.
Concomitant use of Otezla with CYP450 enzyme inducers
(eg, rifampin, phenobarbital, carbamazepine, phenytoin) is
not recommended
Adverse Reactions
◆ Adverse reactions reported in ≥5% of patients were
(Otezla%, placebo%): diarrhea (17, 6), nausea (17, 7), upper
respiratorytractinfection(9,6),tensionheadache (8, 4), and
headache (6, 4)
Use in Specific Populations
◆ Pregnancy and Nursing Mothers: Otezla is Pregnancy
Category C; it has not been studied in pregnant women. Use
during pregnancy only if the potential benefit justifies the
potential risk to the fetus. It is not known whether
apremilast or its metabolites are present in human milk.
Caution should be exercised when Otezla is administered to
a nursing woman
◆ Renal Impairment: Otezla dosage should be reduced in
patients with severe renal impairment (creatinine clearance
less than 30 mL/min); for details, see Dosage and
Administration, Section 2, in the Full Prescribing Information
Please turn the page for Brief Summary of
Full Prescribing Information.
References: 1. Otezla [package insert]. Summit, NJ: Celgene Corporation; 2014.
2. Data on file, Celgene Corporation.
Get the latest news at otezlapro.com
Otezla® is a registered trademark
of Celgene Corporation.
© 2015 Celgene Corporation 04/15
USII-APR150063b
1
ES605612_DT0515_CV2_FP.pgs 04.25.2015 00:13 ADVblackyellowmagentacyan

OTEZLA® (apremilast) tablets, for oral use
The following is a Brief Summary; refer to Full Prescribing Information for
complete product information.
INDICATIONS AND USAGE
OTEZLA® (apremilast) is indicated for the treatment of patients with moderate
to severe plaque psoriasis who are candidates for phototherapy or systemic
therapy.
CONTRAINDICATIONS
OTEZLA is contraindicated in patients with a known hypersensitivity to
apremilast or to any of the excipients in the formulation [see Adverse Reactions
(6.1)].
WARNINGS AND PRECAUTIONS
Depression: Treatment with OTEZLA is associated with an increase in adverse
reactions of depression. Before using OTEZLA in patients with a history of
depression and/or suicidal thoughts or behavior prescribers should carefully
weigh the risks and benefits of treatment with OTEZLA in such patients.
Patients, their caregivers, and families should be advised of the need to be
alert for the emergence or worsening of depression, suicidal thoughts or other
mood changes, and if such changes occur to contact their healthcare provider.
Prescribers should carefully evaluate the risks and benefits of continuing
treatment with OTEZLA if such events occur. During the 0 to 16 week placebo-
controlled period of the 3 controlled clinical trials, 1.3% (12/920) of patients
treated with OTEZLA reported depression compared to 0.4% (2/506) treated
with placebo. During the clinical trials, 0.1% (1/1308) of patients treated with
OTEZLA discontinued treatment due to depression compared with none in
placebo-treated patients (0/506). Depression was reported as serious in 0.1%
(1/1308) of patients exposed to OTEZLA, compared to none in placebo-treated
patients (0/506). Instances of suicidal behavior have been observed in 0.1%
(1/1308) of patients while receiving OTEZLA, compared to 0.2% (1/506) in
placebo-treated patients. In the clinical trials, one patient treated with OTEZLA
attempted suicide while one who received placebo committed suicide.
Weight Decrease: During the controlled period of the trials in psoriasis, weight
decrease between 5%-10% of body weight occurred in 12% (96/784) of patients
treated with OTEZLA compared to 5% (19/382) treated with placebo. Weight
decrease of ≥ 10% of body weight occurred in 2% (16/784) of patients treated
with OTEZLA 30 mg twice daily compared to 1% (3/382) patients treated with
placebo. Patients treated with OTEZLA should have their weight monitored
regularly. If unexplained or clinically significant weight loss occurs, weight loss
should be evaluated, and discontinuation of OTEZLA should be considered.
Drug Interactions: Co-administration of strong cytochrome P450 enzyme
inducer, rifampin, resulted in a reduction of systemic exposure of apremilast,
which may result in a loss of efficacy of OTEZLA. Therefore, the use of
cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital,
carbamazepine, phenytoin) with OTEZLA is not recommended [see Drug
Interactions (7.1) and Clinical Pharmacology (12.3)].
ADVERSE REACTIONS
Clinical Trials Experience in Psoriasis: Because clinical trials are conducted
under widely varying conditions, adverse reaction rates observed in the clinical
trial of a drug cannot be directly compared to rates in the clinical trials of
another drug and may not reflect the rates observed in clinical practice. Diarrhea,
nausea, and upper respiratory tract infection were the most commonly
reported adverse reactions. The most common adverse reactions leading to
discontinuation for patients taking OTEZLA were nausea (1.6%), diarrhea
(1.0%), and headache (0.8%). The proportion of patients with psoriasis who
discontinued treatment due to any adverse reaction was 6.1% for patients
treated with OTEZLA 30 mg twice daily and 4.1% for placebo-treated patients.
Table 3: Adverse Reactions Reported in ≥1% of Patients on OTEZLA and With
Greater Frequency Than in Patients on Placebo; up to Day 112 (Week 16)
Placebo OTEZLA 30 mg BID
Preferred Term (N=506) (N=920)
n (%) n (%)
Diarrhea 32 (6) 160 (17)
Nausea 35 (7) 155 (17)
Upper respiratory tract infection 31 (6) 84 (9)
Tension headache 21 (4) 75 (8)
Headache 19 (4) 55 (6)
Abdominal pain* 11 (2) 39 (4)
Vomiting 8 (2) 35 (4)
Fatigue 9 (2) 29 (3)
(continued)
Table 3: Adverse Reactions Reported in ≥1% of Patients on OTEZLA and With
Greater Frequency Than in Patients on Placebo; up to Day 112 (Week 16)
Placebo OTEZLA 30 mg BID
Preferred Term (N=506) (N=920)
n (%) n (%)
Dyspepsia 6 (1) 29 (3)
Decrease appetite 5 (1) 26 (3)
Insomnia 4 (1) 21 (2)
Back pain 4 (1) 20 (2)
Migraine 5 (1) 19 (2)
Frequent bowel movements 1 (0) 17 (2)
Depression 2 (0) 12 (1)
Bronchitis 2 (0) 12 (1)
Tooth abscess 0 (0) 10 (1)
Folliculitis 0 (0) 9 (1)
Sinus headache 0 (0) 9 (1)
*Two subjects treated with OTEZLA experienced serious adverse reaction of
abdominal pain.
Severe worsening of psoriasis (rebound) occurred in 0.3% (4/1184) patients
following discontinuation of treatment with OTEZLA (apremilast).
DRUG INTERACTIONS
Strong CYP 450 Inducers: Apremilast exposure is decreased when OTEZLA is
co-administered with strong CYP450 inducers (such as rifampin) and may
result in loss of efficacy [see Warnings and Precautions (5.3) and Clinical
Pharmacology (12.3)].
USE IN SPECIFIC POPULATIONS
Pregnancy: Pregnancy Category C: OTEZLA should be used during pregnancy
only if the potential benefit justifies the potential risk to the fetus. Pregnancy
Exposure Registry: There is a pregnancy exposure registry that monitors
pregnancy outcomes in women exposed to OTEZLA during pregnancy.
Information about the registry can be obtained by calling 1-877-311-8972.
Nursing Mothers: It is not known whether OTEZLA or its metabolites are present
in human milk. Because many drugs are present in human milk, caution should
be exercised when OTEZLA is administered to a nursing woman. Pediatric use:
The safety and effectiveness of OTEZLA in pediatric patients less than 18 years
of age have not been established. Geriatric use: Of the 1257 patients who
enrolled in two placebo-controlled psoriasis trials (PSOR 1 and PSOR 2), a total
of 108 psoriasis patients were 65 years of age and older, including 9 patients
who were 75 years of age and older. No overall differences were observed in
the efficacy and safety in elderly patients ≥ 65 years of age and younger adult
patients <65 years of age in the clinical trials. Renal Impairment: OTEZLA
pharmacokinetics were not characterized in patients with mild (creatinine
clearance of 60-89 mL per minute estimated by the Cockcroft–Gault equation)
or moderate (creatinine clearance of 30-59 mL per minute estimated by the
Cockroft–Gault equation) renal impairment. The dose of OTEZLA should be
reduced to 30 mg once daily in patients with severe renal impairment (creatinine
clearance of less than 30 mL per minute estimated by the Cockroft–Gault
equation) [see Dosage and Administration (2.2) and Clinical Pharmacology
(12.3)]. Hepatic Impairment: Apremilast pharmacokinetics were characterized
in patients with moderate (Child Pugh B) and severe (Child Pugh C) hepatic
impairment. No dose adjustment is necessary in these patients.
OVERDOSAGE
In case of overdose, patients should seek immediate medical help. Patients
should be managed by symptomatic and supportive care should there be an
overdose.
Manufactured for: Celgene Corporation, Summit, NJ 07901
OTEZLA® is a registered trademark of Celgene Corporation.
Pat. http://www.celgene.com/therapies
©2014 Celgene Corporation, All Rights Reserved.
Based on APRPI.003 OTZ_PsO_HCP_BSv.003 09_2014
Rx Only
ES605611_DT0515_003_FP.pgs 04.25.2015 00:13 ADVblack

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5MAY 2015 ∕ DERMATOLOGYTIMES.COM
EDITORIAL ADVISORY BOARD
Insight & Opinion From Our Advisory Board Leaders
R
adiotherapy has been a part of
the dermatologist’s therapeu-
tic armamentarium for over 70
years. With the emergence of excel-
lent surgical options and the logistic
problems of administering radiation
therapy (RT) in the office, this form of
treatment has almost completely dis-
appeared over the past 30 years.
Now there is a new technology
which has been designed to be a
practical alternative to the old-
fashioned RT, namely electronic sur-
face brachytherapy (EBT). Unlike its
predecessor, which used radioactive
isotopes, EBT delivers low-energy ra-
diation at a high dose rate through an
applicator placed directly on the skin.
Thus, there is less shielding needed
and no requirement for a dedicated
lead-lined room.
There is one major drawback of EBT
from the point of view of the dermatol-
ogist: A radiation oncologist must be
the person to actually administer the
treatment, which is given twice weekly
for 4 weeks to non-melanoma skin
cancers.
The dermatologist becomes the
“middle man” between his patients
and the radiation therapist. In spite of
the fact that he is not actually giving
the treatments, he is taking a substan-
tial percentage of the reimbursement
from third-party payers. Apparently
this can be quite lucrative. There is an
“urban legend” that one dermatologist
in a large city near where I practice
has billed over one million dollars in
one year from this procedure alone.
Maybe I am being ultra-sensitive,
but this procedure as performed in the
dermatologist’s office has the distinct
scent of a major conflict of interest.
The proponents of EBT argue that this
is a part of offering “a comprehensive
spectrum of skin cancer care.” It
gives the patient an additional choice
of therapy, and most importantly, it
protects the dermatologist’s turf from
interlopers like free-standing radiation
oncologists and others.
I have a much different take on this
situation. In my view, this is all about the
money. With EBT, an office can find a
new source of revenue without so much
as touching the patient. It begins to look
very attractive. From the purely medi-
cal standpoint, we routinely collaborate
with other physicians without concern
about “losing our turf.” When I refer a
patient to the excellent head and neck
surgeon in our community for the exci-
sion of a squamous cell carcinoma of
the lip, I never feel as if I have lost any-
thing, and I know the patient is better
served by him than by me. Likewise, if I
think that a patient would benefit from
EBT, there would be no problem with re-
ferring directly to a radiation oncologist,
thus eliminating any taint of a conflict of
interest.
IS EBT MORE EFFECTIVE THAN SURGERY?
This brings us to the issue of the useful-
ness or need for EBT. In my 35 years of
practice in both an academic and pri-
vate practice environment, I have cared
for many thousands of patients with
skin cancer. I can count on one hand
the number of those patients who would
benefit from EBT rather than surgery. In
fact, in a recent review of the subject,
the authors suggested that EBT was re-
ally best for tumors less than 2 mm in
depth and less than 2 cm in diameter.
These would be the exact tumors which
are well treated by electrodessica-
tion and curettage, surgical excision or
Mohs micrographic surgery.
Is this technology more effective
than surgery? There is scant pub-
lished data to address this question.
The only study that I could find, re-
ported by a paid consultant to the
manufacturer of the EBT equipment,
showed that in 46 lesions treated,
there were no recurrences after one
year. If someone out there knows of
any controlled trials conducted by
disinterested parties with data which
extends to five years, please let me
know; otherwise EBT appears to be
in the early investigational stages of
development. There is at least one
major health insurance carrier that has
decided that it will not cover the cost
of the procedure because of the de-
termination that the procedure should
be classified as investigational/experi-
mental.
In conclusion, I can safely predict
that, if reimbursement for EBT evolves
to be the same as that of other skin
cancer treatment modalities, it would
soon be gone from the face of the
earth. Furthermore, I would like to
ask the users of this form of therapy
whether they would continue to rec-
ommend this modality if only the radi-
ation oncologists in their communities
owned the machines. Our patients do
not need this as a treatment option.
We dermatologists will continue to be
the major providers of care for those
with skin cancer, with or without this
technology.
What are your thoughts on EBT?
To continue the discussion, go to
http://bit.ly/dermsofferebt. DT
Should dermatologists offer EBT?
Norman Levine, M.D.,
is a private practitioner
in Tucson, Ariz.
Dermatologists will continue to be
the major providers of care for those
with skin cancer, with or without this
technology.

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6 EDITORIAL ADVISORY BOARD
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The Dermatology Times Editorial Advisory Board
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Members review meeting programs; suggest story
topics, special reports and sources; evaluate
manuscripts; conduct interviews and roundtables;
and counsel editors as questions arise.
Dr. Joel
Schlessinger
Omaha, Neb.
Dr. James
Spencer
St. Petersburg, Fla.
Dr. Helen
Torok
Medina, Ohio
Dr. Philip
Werschler
Spokane, Wash.
Dr. Albert
Yan
Philadelphia, Pa.
Dr. Tina
Alster
WashingtonD.C.
Dr. Seth
Matarasso
San Francisco, Calif.
Dr. Patti
Farris
New Orleans, La.
Dr. Roy
Geronemus
New York, N.Y.
Dr. David
Goldberg
New York, N.Y.
Dr. Ranella
Hirsch
Boston, Mass.
Zoe Diana Draelos, M.D.,
is consulting professor
of dermatology,
Duke University School
of Medicine, Durham, N.C.
Norman Levine, M.D.,
in Tucson, Ariz.
Ronald G. Wheeland, M.D.,
in Tucson, Ariz.
Elaine Siegfried, M.D.,
is professor of pediatrics &
dermatology, Saint Louis
University Health Sciences
Center, St. Louis, Mo.
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®
8 LEGALEAGLE
D
r. Joe wants to begin to use
a new dermal filler. Because
he has always tried to treat
patients in a most conscientious man-
ner, he reached out to the company
selling the filler and asked Dr. Al, a
world-renowned injector, to come to
Dr. Joe’s office to help him with his
first day of treatments. Dr. Joe had
three patients scheduled on the first
day. He had told all three patients that
Dr. Al, the world-renowned physician,
would be assisting in the treatments.
One of the three patients was very
anxious and scheduled the treatment
only because Dr. Al would be assist-
ing. All patients signed a general con-
sent form that simply stipulated their
agreement to undergo the procedure
by Dr. Joe.
Unfortunately, on the actual day of
treatment, Dr. Al had to cancel his visit
at the last moment. All three patients
were treated by Dr. Joe. There were
no complications. However, soon after
the procedure date, the anxious pa-
tient became increasingly distraught
because he had so much swelling
from the injection. He was certain
this occurred because the treatment
was performed solely by Dr. Joe. The
swelling resolved over several weeks.
He sued Dr. Joe for battery. The basis
of the suit was that, although no un-
toward event happened during the
procedure (malpractice), a procedure
was performed on him for which he
never provided consent. The plaintiff
expected Dr. Al to be present during
the procedure.
Dr. Joe has now determined that
a lawsuit based in battery will not be
covered by his medical malpractice
insurance. He has conceded that the
patient had been told that the proce-
dure would be performed by both he
and Dr. Al. However, he cannot under-
stand how a battery cause of action
could proceed against him. He knows
that such a lawsuit, if successful
against him, could cause him to lose
his medical license even though no
untoward event occurred.
A New Jersey case examined the
issue of whether a plaintiff can recover
for the substitution of a heath care
provider absent actual harm. In that
case, a patient consented to undergo
spinal fusion by his physician know-
ing that the procedure would be per-
formed by both his doctor and another
world-renowned surgeon who would
be spending the day with his doctor.
On the day of the procedure, the fa-
mous physician was not available. His
physician substituted an associate to
help him with the surgery. The signed
consent form never stipulated that the
procedure was to take place under
the guidance of the famous surgeon.
Unfortunately, there were numerous
post-operative complications, but
none of them led to any permanent
injury. The patient chose to sue on a
theory of battery and not medical mal-
practice based on negligence. Neg-
ligence would have required proving
damages. The battery cause of action
could be brought absent any injury.
It was based solely on a procedure
being performed without the patient’s
consent.
The New Jersey court looked at
cases based on a lack of informed
consent and noted that, in order
to be successful, the patient must
prove that the doctor withheld per-
tinent medical information concern-
ing the risks of the procedure and al-
ternatives. The suing plaintiff must
also prove causation, which requires a
showing by the plaintiff that a reason-
ably prudent person in the plaintiff’s
position would have declined to un-
dergo the treatment if informed of the
risks that the defendant doctor failed
to disclose. Thus, the court required
damages for informed consent law-
suits, much like it did for negligence
lawsuits.
True battery, based on a lack of in-
formed consent, was reserved solely
for those instances where the patient
consented to one type of operation
but the physician performed a sub-
stantially different one from that for
which authorization was obtained, or
for instances where no consent was
obtained.
The New Jersey court assumed that
the surgeon had made the promise of
having the expert surgeon present—
even though this was not contained
in the signed consent form. The suing
plaintiff in fact had consented to the
surgery and to his physician perform-
ing that surgery. The court found that
there was no evidence that the sur-
geon had deviated from the standard
of care. The plaintiff had also suffered
no long-term harm. Since this claim
was based on informed consent, and
not on medical battery, the plaintiff
was entitled to nothing.
Similarly, Dr. Joe had obtained
consent from his patients for the new
filler. The procedure was performed
without long-term complication. There
is no basis for a medical malpractice
claim based on informed consent.
There was also no basis for a suit
based on battery. DT
David 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.
Did I commit battery?
I did nothing wrong...

LEO, the LEO Lion Design, and Enstilar are registered trademarks of LEO Pharma A/S.
Copyright 2015 LEO Pharma Inc. 3428-EN-15-314 March 2015 Printed in USA
Go to enstilarcomingsoon.com
ES603502_DT0515_009_FP.pgs 04.23.2015 00:38 ADVblackyellowmagentacyan

®
10 IRREGULARBORDER
T
his year’s AAD Annual meet-
ing took place in San Francisco,
home of Levi Strauss, the jeans
manufacturer. How appropriate, as the
jeans were originally dyed with indigo.1
OLD WORLD PLANT
A well-known group of Old World plants
are the source for the blue powder2
the
Chinese call qing dai, including Baphi-
cacavthus cusia, Polygonum tinctorium,
Isatis indigotica and
Indigofera tinctoria. Known best as a dye
in the Western world, indigo naturalis
has been used in China for the treatment
of many ailments.3
This “indigo” should
not be confused with Wrightia tinctoria,
also known as Sweet Indrajao, Pala in-
digo plant, or Dyers’s oleander, which is
also used medicinally, more so in the Ay-
urvedic approach to health.4
Commercial
preparations of W. tinctoria are available
in the U.S.5
Over the past few years, indigo natura-
lis has been finding a role in the treatment
of psoriasis. A Medline search for “indigo
psoria*” reveals 26 articles with all but
one having been published in this century
and over two-thirds published since 2009,
the earliest being in 1982.6
Dr. Lin and col-
leagues have been the movers and shak-
ers in this field, publishing about the use
of indigo for treating plaque psoriasis in
both children7
and adults.8
MECHANISM OF ACTION
In addition to clinical observations, Dr.
Lin’s team performed studies that might
point to a mechanism of action: The ex-
pression of proliferating marker Ki-67
and inflammatory marker CD3 were de-
creased, while the differentiation marker
filaggrin was increased in the epidermis
after topical application of indigo nat-
uralis ointment. Further studies on in-
digo extract looked at the anti-inflamma-
tory effects of an extract of indigo nat-
uralis and its main components indiru-
bin, indigo, and tryptanthrin in human
neutrophils. Superoxide anion genera-
tion and elastase release were inhibited
in a concentration dependent fashion in
formyl-L-methionyl-L-leucyl-L-phenylal-
anine (FMLP)-activated human neutro-
phils. The extract attenuated the FMLP-
induced phosphorylation of extracel-
lular regulated kinase, p38 MAPK and
c-Jun N-terminal kinase, and also in-
hibited calcium mobilization caused by
FMLP. The indigo extract did not affect
cellular cAMP levels. The main compo-
nents alone (indirubin, indigo and trypt-
anthrin) did not produce similar changes
in human neutrophils.9
Not only neutrophils are responsive
to indigo: primary cultured human um-
bilical vein endothelial cells (HUVECs)
pretreated with an indigo naturalis ex-
tract attenuated TNF-α-induced in-
Dr. Daniel Mark Siegel, M.D., M.S.
(Management and Policy), is a clinical professor
of dermatology, SUNY Downstate, and is a
practicing physician at Long Island Skin Cancer
and Dermatologic Surgery, N.Y. cyberderm@
dermsurg.org http://www.liskincancer.com/
Indigo naturalis
creases in T cell adhesion to HUVECs
as well as decreased the protein and
messenger (m)RNA expression levels
of vascular cell adhesion molecule-1
(VCAM-1) in these cells.
Indigo naturalis extract also inhibited
the protein expression of activator pro-
tein-1 (AP-1)/c-Jun, a critical transcrip-
tion factor for the activation of VCAM-1
gene expression. The authors believe
that the reduction of lymphocyte adhe-
sion to vascular cells by indigo naturalis
extract could reduce the inflammatory
reactions caused by lymphocyte infiltra-
tion in the epidermal layer and help to
improve psoriasis.10
MULTIPLE STUDIES AND USES
Many other small studies have been per-
formed on this plant extract and a meta-
analysis in 2013 reported limited sup-
port for clinical efficacy but no significant
side effects.11
The most recent addition
to the clinical literature showed that a de-
colorized indigo in an oil vehicle was ef-
ficacious in treating nail psoriasis,12
likely
adding a useful new treatment to our ar-
mamentarium for a disease that is diffi-
cult to manage.
Commercially, there are a number of
indigo-containing products on the mar-
ket. One group I find especially intriguing
is a line produced by Kamedis, an Israeli
company that uses sustainably grown
and harvested plants from China. Their
PSO Medis line uses indigo naturalis as
one of its active ingredients and the clini-
cal results they report are impressive.13
Why should you, the practicing der-
matologist care? Very simple. Your
patients are learning about alternative
treatments on the Internet and you can
stay credible by knowing these novel op-
tions. As indigo naturalis is very safe and
not at all painful like an injection into the
nail matrix, it might even be a first-line
treatment for patients for whom local as
opposed to systemic therapy would be a
good option. DT
Disclosures: Dr. Seigel has a consulting agreement
with Kamedis.
Studieson
indigonaturalis
lookedattheanti-
inflammatoryeffects
ofanextractofindigo
naturalisandits
maincomponents
indirubin,indigo,
andtryptanthrinin
humanneutrophils.
INDIGO see page 29
Indigo naturalis is an Old World
plant with multiple uses. Used in
China for centuries as a traditional
medicine, current clinical studies are
showing its effectiveness as well as
identifying mechanisms of action.
QUICK READ

Where size and cosmetic
elegance meet
• 430g size, great for patients with
widespread inflammatory dermatoses
• Nongreasy, cream-like formulation
(Triamcinolone Acetonide Ointment, USP)
Trianex
®
0.05%
BIG for Widespread
Inflammatory Dermatoses
INDICATION AND IMPORTANT SAFETY INFORMATION
Trianex®
0.05% (Triamcinolone Acetonide Ointment, USP) is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
The most common adverse events with Trianex Ointment include burning, itching, irritation, dryness, and folliculitis. Trianex Ointment is contraindicated in patients who are
hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can produce reversible HPA-axis suppression.
Please See Full Prescribing Information on reverse side.
Trianex is a registered trademark of CMP Pharma, Inc. ©2015 Promius Pharma, LLC. All rights reserved.

Trianex®
0.05%
(Triamcinolone Acetonide Ointment, USP)
Proprietary Hydrous Emulsified Base
Rx Only
DESCRIPTION
Topical corticosteroids, such as Trianex®
0.05% (Triamcinolone Acetonide Ointment, USP),
constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic
agents.
Each gram of Trianex®
0.05% (Triamcinolone Acetonide Ointment, USP) contains 0.5 mg of
Triamcinolone Acetonide USP in a water-in-oil emulsion composed of Light Mineral Oil NF,
Purified Water USP, White Petrolatum USP, Heavy Mineral Oil USP, Mineral Wax, and Lanolin
Alcohols NF. The white ointment is for topical use only.
Triamcinolone Acetonide has the molecular
formula of C24
H31
FO6
and is designated chemically
as Pregna- 1, 4-diene-3, 20-dione,
9-fluoro-11, 21- dihydroxy - 16, 17-
[(1-methylethylidene)bis (oxy)]-, (11ß, 16α)-.
It has a molecular weight of 434.50 and the
following structural formula:
CLINICAL PHARMACOLOGY
Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions.
The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various
laboratory methods, including vasoconstrictor assays, are used to compare and predict
potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence
to suggest that a recognizable correlation exists between vasoconstrictor potency and
therapeutic efficacy in man.
Pharmacokinetics
The extent of percutaneous absorption of topical corticosteroids is determined by many
factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive
dressings.
Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or
other disease processes in the skin increase percutaneous absorption. Occlusive dressings
substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive
dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses (see
DOSAGE AND ADMINISTRATION). Once absorbed through the skin, topical corticosteroids
are handled through pharmacokinetic pathways similar to systemically administered
corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees.
Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys.
Some of the topical corticosteroids and their metabolites are also excreted into the bile.
Trianex®
0.05% (Triamcinolone Acetonide Ointment, USP) is indicated for the relief of the
inflammatory and pruritic manifestations of corticosteroid responsive dermatoses.
CONTRAINDICATIONS
Trianex®
0.05% (Triamcinolone Acetonide Ointment, USP) is contraindicated in those
patients with a history of hypersensitivity to any of the components of the preparation.
PRECAUTIONS
General
Systemic absorption of topical corticosteroids has produced reversible hypothalamic-
pituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s syndrome,
hyperglycemia, and glucosuria in some patients.
Conditions which augment systemic absorption include the application of the more
potent steroids, use over large surface areas, prolonged use, and the addition of occlusive
dressings.
Therefore, patients receiving a large dose of a potent topical steroid applied to a large
surface area or under an occlusive dressing should be evaluated periodically for evidence of
HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. If HPA
axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the
frequency of application, or to substitute a less potent steroid.
Recovery of HPA axis function is generally prompt and complete upon discontinuation
of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring
supplemental systemic corticosteroids.
Children may absorb proportionally larger amounts of topical corticosteroids and thus
be more susceptible to systemic toxicity (see PRECAUTIONS-Pediatric Use).
If irritation develops, topical corticosteroids should be discontinued and appropriate
therapy instituted.
In the presence of dermatological infections, the use of an appropriate antifungal or
antibacterial agent should be instituted. If a favorable response does not occur promptly,
the corticosteroid should be discontinued until the infection has been adequately controlled.
Information for the Patient
Patients using topical corticosteroids should receive the following information and
instructions:
1. This medication is to be used as directed by the physician. It is for external use only.
Avoid contact with the eyes.
2. Patients should be advised not to use this medication for any disorder other than that
for which it was prescribed.
3. The treated skin area should not be bandaged or otherwise covered or wrapped so as
to be occlusive unless directed by the physician.
4. Patients should report any signs of local adverse reactions especially under occlusive
dressing.
5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic
pants on a child being treated in the diaper area, as these garments may constitute
occlusive dressings.
Laboratory Tests
The following tests may be helpful in evaluating the HPA axis suppression:
Urinary free cortisol test
ACTH stimulation test
Carcinogenesis, Mutagenesis and Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential
or the effect on fertility of topical corticosteroids.
Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed
negative results.
Pregnancy Category C
Corticosteroids are generally teratogenic in laboratory animals when administered
systemically at relatively low dosage levels. The more potent corticosteroids have been
shown to be teratogenic after dermal application in laboratory animals. There are no
adequate and well-controlled studies in pregnant women on teratogenic effects from
topically applied corticosteroids. Therefore, topical corticosteroids should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of
this class should not be used extensively on pregnant patients, in large amounts, or for
prolonged periods of time.
Nursing Mothers
It is not known whether topical administration of corticosteroids could result in sufficient
systemic absorption to produce detectable quantities in breast milk. Systemically
administered corticosteroids are secreted into breast milk in quantities not likely to have
a deleterious effect on the infant. Nevertheless, caution should be exercised when topical
corticosteroids are administered to a nursing woman.
Pediatric Use
Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-
induced HPA axis suppression and Cushing’s syndrome than mature patients because of
a larger skin surface area to body weight ratio.
Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome and intracranial
hypertension have been reported in children receiving topical corticosteroids. Manifestations
of adrenal suppression in children include linear growth retardation, delayed weight gain,
low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of
intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
Administration of topical corticosteroids to children should be limited to the least amount
compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may
interfere with the growth and development of children.
ADVERSE REACTIONS
The following local adverse reactions are reported infrequently with topical corticosteroids,
but may occur more frequently with the use of occlusive dressings. These reactions are
listed in an approximate decreasing order of occurrence:
Burning, Itching, Irritation, Dryness, Folliculitis, Hypertrichosis, Acneiform eruptions,
Hypopigmentation, Perioral dermatitis, Allergic contact dermatitis, Maceration of the skin,
Secondary infection, Skin atrophy, Striae, and Miliaria
OVERDOSAGE
Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic
effects (see PRECAUTIONS).
DOSAGE AND ADMINISTRATION
Trianex®
0.05% (Triamcinolone Acetonide Ointment, USP) is generally applied to the affected
area as a thin film from two to four times daily depending on the severity of the condition.
Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions.
If an infection develops, the use of occlusive dressings should be discontinued and
appropriate antimicrobial therapy instituted.
HOW SUPPLIED
Trianex®
0.05% (Triamcinolone Acetonide Ointment, USP) is supplied in 430 g jars
(NDC 67857-806-19).
KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.
You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects
to Promius Pharma, LLC at 1-888-966-8766.
STORE AT CONTROLLED ROOM TEMPERATURE 15°– 30° C (59°– 86° F).
DISPENSE IN A WELL-CLOSED CONTAINER.
CAUTION: Federal law prohibits dispensing without prescription
For external use only. Not for ophthalmic use.
Distributed by:
Promius Pharma, LLC
Princeton, NJ 08540
Manufactured by:
CMP Pharma, Inc.
Farmville, NC 27828
Trianex is a registered trademark of CMP Pharma, Inc.
006735
Revised 0115

CLINICAL DERMATOLOGY
QuotableDTExtra
MauiDerm 2015 - Hidradenitis sup-
purativa (HS) is a debilitating chronic
inflammatorydiseasethathashistori-
callybeenverychallengingtotreat,with
truly effective therapeutic modalities
few and far between. Recent research
with TNF inhibitors has shown prom-
iseforthetreatmentandmanagement
of HS, offering effective systemic ther-
apy for moderate to severe cases.
Also known as acne inversa, HS is
characterized by the development of
painfulabscesses,nodulesandfistulas
in apocrine gland-bearing skin such
as in the inguinal, sub-mammary and
axillaryregions. Keloids,contractures
and immobility commonly develop in
the affected areas. In severe cases, HS
canbeassociatedwithanumberofco-
morbidities including metabolic syn-
drome, follicular occlusion disorders,
spondylarthropathy, inflammatory
bowel diseases such as Crohn’s dis-
ease and others. HS and its co-mor-
bidities can have a significant nega-
tive impact on patient quality of life,
begging the need for effective thera-
pies that can address this notoriously
difficult-to-treat disease.
“It is very important to remember
that HS is an inflammatory disease
akin to psoriasis, psoriatic arthritis
and Crohn’s disease. As such, evolv-
ing agents such as the TNF inhibitors
that can reduce the inflammation in
the patient could be an ideal treat-
ment option for HS patients, particu-
larlythosewithmoderatetoseveredis-
easeorinrefractorycases,”saysBruce
E. Strober, M.D., Ph.D., associate pro-
fessor and vice chair, Department of
Dermatology, University of Connect-
icut School of Medicine, Farmington,
Conn.
AccordingtoDr.Strober,severaldif-
ferentTNFinhibitingagentshavebeen
tried and researched in clinical trials
for the treatment and improvement of
the symptoms of HS including etan-
ercept (Enbrel, Amgen), infliximab
(Remicade, Janssen), and most re-
centlyadalimumab(Humira,AbbVie).
AbbVie recently announced phase
3 data of the PIONEER I study, a 36-
week, multicenter, randomized, dou-
ble-blinded, two-period clinical trial
that evaluated the efficacy and safety
of adalimumab in 307 patients with
moderate to severe HS.1
In the first 12-
14
16CHIKUNGUNYA AND COXSACKIE
Viruses making waves in U.S.
DERMATOLOGISTS SHOULD
RECOGNIZE BDD
Body dysmorphic disorder under-recognized
TNF INHIBITORS see page 21
TNF Inhibitors Prove Effective
ILYA PETROU, M.D. | STAFF CORRESPONDENT
TNF inhibitors are effective in
improving the clinical symptoms
of moderate to severe hidradenitis
suppurativa, representing an
exciting therapeutic option for
this challenging disease.
QUICK READ
“In my opinion, TNF inhibition will be
the gold standard therapy for HS,
particularly in more severe and
refractory cases.”
Bruce Strober, M.D., Ph.D.,
Farmington, Conn.
[BDD] is present in up to
2.4% of the general
population, but in
dermatology clinics it
is [present in] anywhere
from 9% to 14%Ó of
patients in the U.S.
Neelam Vashi, M.D.
Boston, Mass.
on the importance of dermatologists
recognizing body dysmorphic disorder
See story page 14
Researchers have identified gene variants
that suggest a genetic component for
rosacea, which could lead to new treatment
targets and a better understanding of
this incurable skin disease. Researchers
identified two rosacea-associated single
nucleotide polymorphisms (SNPs), one of
which replicated in another group of 29,481
people, including 3,205 rosacea cases. The
confirmed SNP, rs763035, is inter-genic
between HLA-DRA and BTNL2.
SOURCE: BIT.LY/COLLAGENFILLERS

®
14 CLINICAL DERMATOLOGY
Body dysmorphic disorder (BDD)
is a relatively recent diagnosis and is
under-recognized, according to a der-
matologistspeakingatthe73rdannual
meeting of the American Academy of
Dermatology (San Francisco, 2015).
“[BDD] is present in up to 2.4% of
the general population, but in der-
matology clinics it is [present in]
anywhere from 9 - 14% [of patients],”
says Neelam Vashi, M.D., assistant
professor of dermatology,
director, Boston Univer-
sity Center for Ethnic Skin,
Cosmetic and Laser Center,
Boston University School of
Medicine, Boston Medical
Center in Boston, Mass. “It is
important to recognize this
disorder, so we can screen
these patients because they
will not be happy with cos-
metic treatments.”
Researchsuggeststhat90%
of patients with BDD report
their symptoms unchanged or wors-
ened after a dermatologic procedure,
Dr. Vashi says.
The suicide rate for BDD patients
is much higher than in the general
population, Dr. Vashi stresses. “A
total of 0.3% of patients with BDD
die annually due to suicide, a rate
which is 37 times higher than in the
general population,” she says.
Screening questionnaires such
as the Body Dysmorphic Disorder
Questionnaire-Dermatology Ver-
sion, the Dysmorphic Con-
cern Questionnaire and the
Body Image Concern Inven-
tory, which have all been
validated by psychiatrists,
can be employed to iden-
tify patients in dermatology
practices suspected of hav-
ing BDD, but posing some
key questions to patients
might reveal whether a pa-
tient has BDD, according to
Dr. Vashi.
“Asking patients why they
are requesting a specific procedure,
how much distress the [perceived]
condition is causing them, and how
much they think about this condi-
tion on a daily basis [are fundamen-
tal questions],” she says. “Answers
to those questions will give you a lot
of insight and you don’t necessarily
need to [use a screening tool].”
One “red flag” that a patient may
have BDD is when a patient has been
“doctor shopping” and has visited nu-
merous dermatologists, requesting a
particular procedure, Dr. Vashi says.
“They may tell you that they have
been to a dozen physicians and that
they have not been helped,” she says.
Some examples of what patients
with BDD may request include a
hair transplant when no thinning
of hair is present or laser treatment
to treat a scar that is non-existent,
she says.
Dermatologists may consider re-
ferring patients with BDD to mental
health professionals for cognitive-
behavioral therapy. DT
National Institutes of Health re-
searchers found that clindamycin
and trimethoprim–sulfamethoxazole
(TMP-SMX) work equally well to treat
uncomplicatedskininfections,includ-
ing cellulitis and abscesses.
There is no standard treatment
for community-associated methicil-
lin-resistant Staphylococcus aureus
(MRSA) skin infections. Clindamycin
and TMP-SMX are older antibiotics,
no longer under patent. Both are rec-
ommended to treat community-as-
sociated MRSA, but it was unclear if
they were equally effective.
Researchers tested the two anti-
biotics in 466 adults and children
with uncomplicated skin infections.
All those with abscesses underwent
incision and drainage, and patients
were randomly assigned to receive
either clindamycin or TMP-SMX for
10 days.
They report in a study in the New
England Journal of Medicine that the
cure rate, determined 7 to 10 days
after treatment, was 89.5% for clin-
damycin and 88.2% for TMP-SMX.
Side effects from the drugs were
comparable, suggesting that either
of the antibiotics offers an inexpen-
sive and effective treatment for un-
complicated skin infectious acquired
outside of hospitals.
“These drugs have a proven safety
record, they are inexpensive, and
they are effective. The results show
that there are now many choices to
treat these infections. What was lack-
ing were data about efficacy. Now
that this is in hand, clinicians can be
confidentinusingthesedrugs,”study
author Henry F. Chambers, M.D.,
professor of medicine, University
of California San Francisco School
of Medicine, San Francisco, Calif.,
writes in an email to Dermatology
Times.
“Case series, observational data
and limited clinical trial data sug-
gested these drugs should be effec-
tive. And, now, with this large, well-
designed, high quality study, there is
confirmation of this.” DT
Dermatologists should recognize BDD
Of-patent antibiotics fght
community-associated MRSA
LOUISE GAGNON | STAFF CORRESPONDENT
BY LISETTE HILTON
14PERCENT
of dermatology
patients have
BDD
Up to

®
Chikungunya, a tropical virus, “had
never infected anyone in the Western
Hemisphere until December 20, 2013,”
whenitappearedintheCaribbean,says
StephenK.Tyring,M.D.,Ph.D.Sincethen,
thanks to international travel and the
spreadoftheAedesaegyptimosquitothat
carrieschikungunya,“Thisdiseasehas
spreadextremelyrapidlythroughoutthe
CaribbeanandsouthernUnitedStates,”
where it has already infected approxi-
mately1millionpeopletotal.Dr.Tyringis
clinicalprofessorofdermatology,micro-
biology/molecular genetics, and inter-
nal medicine at the University of Texas
and director of the Center for Clinical
Studies in Houston, Texas.
Skin signs of chikungunya can re-
semble those of dengue — islands of
white in a sea of red rash. “The differ-
ence is that only one strain of chikun-
gunya is known to cause problems,
whereas dengue has four strains” that
do. This means that if a person is in-
fected with chikungunya a second
time, says Dr. Tyring, the infection
likely will be milder than the first; the
opposite is true with dengue, which
can lead to dengue hemorrhagic fever.
Becausebothchikungunyaandden-
gue cause skin symptoms, he says, pa-
tients with these diseases may present
to dermatologists. However, derma-
tologists more likely will see these ill-
nesses when consulting with primary
care physicians who have hospital-
ized patients due to severe fever and
other systemic manifestations. The
only ways to tell the two apart for cer-
tain include checking serology for an-
tibodiesorusingpolymerasechainre-
action(PCR)assaystocheckfortheac-
tual virus, he says.
Patients who present with acute
onset of fever, rash and polyarthralgia
should be evaluated for chikungunya,
particularlypatientswhohaveexisting
dermatosessuchaspsoriasis,acne,at-
opicdermatitisortuberculoidleprosy,
astheseconditionscanbeexacerbated
by chikungunya.
As with dengue, says Dr. Tyring,
VIRUSES see page 18
Chikungunya and Coxsackievirus A6
JOHN JESITUS | STAFF CORRESPONDENT
Infectious-disease challenges
include atypical and once-exotic
threats. Chikungunya is a tropical,
mosquito-borne disease which
keeps advancing westward, experts
say. Coxsackievirus A6 affects
adults more severely than children
and has atypical symptoms.
QUICK READ
A
Viruses making waves in the U.S.
B
C
Mucocutaneous manifestations of
the chikungunya virus
A. Purpuric macules
B. Nasal hyperpigmentation
C. Vesiculobullous lesions
Photos: Stephen K. Tyring, M.D.

Barrier Protection
for the Ages
Rx Only
The TwinPack offers a supply of 2 tubes as an
added convenience and for greater coverage of
affected areas during the seasons when atopic
dermatitis tends to flare most. With one prescription,
patients can receive twice as much therapy for
the same pharmacy co-pay as with the single tube.
TwinPack
ELETONE®
CREAM NOW AVAILABLE IN
Contains two100-gram tubesof Eletone®
Cream
Copyright © 2014 Mission Pharmacal Company. All rights reserved. ELE-14109
ELETONE®
CREAM
Nonsteroidal Atopic Dermatitis Therapy
PRODUCT DESCRIPTION: Eletone®
Cream is a non-steroidal, lipid-rich,
fragrance free emulsion formulated with Hydrolipid Technology™ for the
management and relief of burning, itching, and redness associated with various
types of dermatoses. There are no restrictions on age or duration of use and the
product has a low potential for irritation.
INDICATIONS FOR USE: Eletone®
Cream is indicated for the management and
relief of burning, itching, and redness associated with various types of dermatoses,
including atopic dermatitis, allergic contact dermatitis, and radiation dermatitis
(post-radiation treatment).
CONTRAINDICATIONS: THIS PRODUCT SHOULD NOT BE USED DURING THE
PERIOD OF TIME WHEN RADIATION TREATMENT IS OCCURRING BECAUSE OF THE
INCREASED RISK OF SKIN TOXICITY WHEN RADIATING THROUGH PETROLATUM AND
OIL. Eletone®
Cream is contraindicated in patients with a known hypersensitivity
to any of the components of the formulation.
PRECAUTIONS: Eletone®
Cream is for external use only. Eletone®
Cream
does not contain a sunscreen and should always be used in conjunction with
a sunscreen in sun exposed areas.
INSTRUCTIONS FOR USE: Apply liberally to the affected areas three
times daily or as needed. If skin is broken, cover Eletone®
Cream with a
dressing of choice.
INGREDIENTS: Eletone®
Cream contains petrolatum, purified water,
mineral oil, cetostearyl alcohol, ceteth-20, citric acid, sodium citrate,
propylparaben, and butylparaben.
HOW SUPPLIED: Eletone®
Cream is available in a 100 gram tube
NHRIC 0178-0368-01.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
[see USP Controlled Room Temperature].
CAUTION: Rx only. Federal law restricts this device
to sale by or on the order of a physician.
For illustrative purposes
only. Individual dose
will vary by patient.

®
the only treatment for chikungunya is
supportivecare,typicallywithanti-in-
flammatory agents, pain medications
andhydration.“Usually,theacutesigns
andsymptoms(fever,muscleandjoint
aches) will pass within a week or so.
The big problem with chikungunya is
thejointproblems,”whichmayrequire
a rheumatology referral. Although far
less lethal than dengue, chikungunya
causesexcruciatingjointpainthatcan
last from weeks to, rarely, years. “Peo-
ple say it feels like their arms and legs
are being pulled out of the socket.”
ATYPICAL COXSACKIEVIRUS
Closer to home, Dr. Tyring warns of a
newwrinkleappearingwiththeatypical
strain of hand, foot and mouth (HFM)
diseasedermatologistsincreasinglyen-
counter.1
Inthelast2years,saysDr.Ty-
ring, his clinic has seen 20 to 30 adults
with HFM disease caused by Coxsack-
ievirus A6 (CVA6). Less common than
other strains of Coxsackievirus, this
strainseemstomakeadultssickerthan
children.
Along with blisters on the palms,
soles, mouth and elsewhere, Dr. Ty-
ring explains, adults get quite sys-
temically ill, with muscle aches and
fever whose origins emergency-room
personnel cannot identify, so these
patients are commonly hospitalized.
Sheila Fallon Friedlander,
M.D., professor of clinical
pediatrics and medicine
(dermatology) at the Uni-
versity of California, San
Diego, adds, “Kids may
have significant hemor-
rhagic and blistering le-
sions, but they usually do
quite well.”
As with chikungunya and dengue,
says Dr. Tyring, “There’s no specific
treatment. But what’s unique about
the adults we’ve seen over the past 2
years with HFM disease is that, when
the signs and symptoms are improv-
ing, patients start shedding their toe-
nails and fingernails.”
Dr. FriedlanderhasalsoseenCVA6-
associatedonychomadesisinchildren,
appearingthreetoeightweeksafterin-
fection onset. “It’s important to warn
families about this possibility, and re-
assure them when it develops.”
In some cases, she adds, a patient
may present with nail shedding only.
Whenquestioned,themotherremem-
bers that the child had an illness that
VIRUSES see page 21
VIRUSES:
Atypical Coxsackievirus A6 from page 16
A
B
C
Chikungunya can
cause excruciating
joint pain that can
last from weeks to,
rarely, years.
CHIKUNGUNYA
manifestations and
spread A. Scrotal erythema,
aphthous-like ulcers
B. Countries and territories
reported with cases as of
July 2014 C. Morbilliform
rash
Photos: Stephen K. Tyring, M.D.

Levulan®
, Kerastick®
, and BLU-U®
are registered
trademarks of DUSA Pharmaceuticals, Inc.®
,
a Sun Pharma company.
© 2015, DUSA Pharmaceuticals, Inc.
All Rights Reserved
IMPORTANT RISK INFORMATION
Contraindicated in patients with
cutaneous photosensitivity at
wavelengths of 400-450 nm, porphyria,
or known allergies to porphyrins,
and in patients with known sensitivity
to any of the components of the
LEVULAN KERASTICK for Topical
Solution.
The most common adverse events
include scaling/crusting, hypo/
hyperpigmentation, itching, stinging
and/or burning, erythema and
edema. Severe stinging and/or
burning at one or more lesions being
treated was reported by at least
50% of patients at some time during
treatment. However, these efects are
temporary and should completely
resolve by 4 weeks after treatment.
*At 8 weeks, 77% of patients treated with
LEVULAN KERASTICK PDT experienced
75% clearance of AK lesions vs 23% of
the control group. 83% of the patients
treated with LEVULAN KERASTICK PDT
had 75% clearance of face lesions and
60% of the patients had 75% clearance
of scalp lesions. 66% of patients
treated with LEVULAN KERASTICK PDT
experienced 100% clearance of AK
lesions vs 13% of the control group. 70%
of the patients treated with LEVULAN
KERASTICK PDT had 100% clearance
of face lesions and 55% of the patients
had 100% clearance of scalp lesions.
*Results from two identical, randomized,
multi-center, two-arm Phase 3 studies
with a total of 243 patients. Patients who
were not complete responders at week 8
had a retreatment of the persistent target
lesions. All patients returned at week 12
after initial treatment.
†
Patients treated with LEVULAN KERASTICK
PDT should avoid exposure of the
photosensitized lesions to sunlight or
prolonged or intense light for at least 40
hours. Most common adverse events
are temporary and should completely
** LEVULAN KERASTICK PDT is a 2-part
treatment procedure that can be
completed within a 24 hour period.
LEVULAN KERASTICK must be applied
by a qualifed healthcare professional.
Please see full prescribing
information on adjacent page.
Levulan®
Kerastick®
(aminolevulinic acid HCl) for Topical Solution, 20% plus blue light illumination
using the BLU-U®
Blue Light Photodynamic Therapy Illuminator is indicated for the treatment of
minimally to moderately thick actinic keratoses of the face or scalp.
A CLEAR PATH FOR TREATING AK LESIONS…
LEVULAN KERASTICK + BLU-U
®
HIGH CLEARANCE* LOW DOWNTIME
†
PHYSICIAN CONTROLLED**
MKT-1769AW Rev A

Levulan® Kerastick® (aminolevulinic acid HCl)
for Topical Solution, 20%
CONTRAINDICATIONS
The LEVULAN KERASTICK
Photosensitivity

ala

oval:
INDICAI NSAND

US
9
AG
99

The LEVULAN KERASTICK for Topical Solution, a porphyrin
precursor, plus blue light illumination using the BLU-U®
Blue Light Photodynamic Therapy Illuminator is indicated
for the treatment of minimally to moderately thick actinic
keratoses of the face or scalp.
for Topical Solution plus blue
light illumination using the BLU-U Blue Light
Photodynamic Therapy Illuminator is contraindicated in
patients with cutaneous photosensitivity at wavelengths of
400-450 nm, porphyria or known allergies to porphyrins,
and in patients with known sensitivity to any of the
components of the LEVULAN KERASTICK for Topical
Solution.
During the time period between the application of
LEVULAN KERASTICK Topical Solution and exposure to
activating light from the BLU-U Blue Light Photodynamic
Therapy Illuminator, the treatment site will become
photosensitive. After LEVULAN KERASTICK Topical Solution
application, patients should avoid exposure of the
photosensitive treatment sites to sunlight or bright indoor
light (e.g., examination lamps, operating room lamps,
tanning beds, or lights at close proximity) during the
period prior to blue light treatment. Exposure may result in
a stinging and/or burning sensation and may cause
erythema and/or edema of the lesions. Before exposure to
sunlight, patients should, therefore, protect treated lesions
from the sun by wearing a wide-brimmed hat or similar
head covering of light-opaque material. Sunscreens will
not protect against photosensitivity reactions caused by
visible light. It has not been determined if perspiration can
spread the LEVULAN KERASTICK Topical Solution outside
the treatment site to eye or surrounding skin.
Application of LEVULAN KERASTICK Topical Solution to
perilesional areas of photodamaged skin of the face or
scalp may result in photosensitization. Upon exposure to
activating light from the BLU-U Blue Light Photodynamic
Therapy Illuminator, such photosensitized skin may
produce a stinging and/or burning sensation and may
become erythematous and/or edematous in a manner
similar to that of actinic keratoses treated with LEVULAN
KERASTICK Photodynamic Therapy. Because of the
potential for skin to become photosensitized, the LEVULAN
KERASTICK should be used by a qualified health
professional to apply drug only to actinic keratoses and
not perilesional skin. If for any reason the patient cannot
return for blue light treatment during the prescribed period
after application of LEVULAN KERASTICK Topical Solution
(14 to 18 hours), the patient should call the doctor. The
patient should also continue to avoid exposure of the
photosensitized lesions to sunlight or prolonged or
intense light for at least 40 hours. If stinging and/or
burning is noted, exposure to light should be reduced.
Irritation
The LEVULAN KERASTICK Topical Solution contains
alcohol and is intended for topical use only. Do not apply
to the eyes or to mucous membranes. Excessive irritation
may be experienced if this product is applied under
occlusion.
Coagulation Defects
The LEVULAN KERASTICK for Topical Solution has not
been tested on patients with inherited or acquired
coagulation defects.
ADVERSE REACTIONS
In Phase 3 studies, no non-cutaneous adverse events
were found to be consistently associated with LEVULAN
KERASTICK Topical Solution application followed by blue
light exposure.
Photodynamic Therapy Response: The constellation
of transient local symptoms of stinging and/or burning,
itching, erythema and edema as a result of LEVULAN
KERASTICK Topical Solution plus BLU-U treatment was
observed in all clinical studies of LEVULAN KERASTICK for
Topical Solution Photodynamic Therapy for actinic
keratoses treatment. Stinging and/or burning subsided • After LEVULAN KERASTICK Topical Solution is applied
between 1 minute and 24 hours after the to the actinic keratoses in the doctor’s office, the
BLU-U Blue Light Photodynamic Therapy Illuminator was patient will be told to return the next day. During this
turned off, and appeared qualitatively similar to that time the actinic keratoses will become sensitive to light
perceived by patients with erythropoietic protoporphyria (photosensitive). Care should be taken to keep the
upon exposure to sunlight. There was no clear drug dose treated actinic keratoses dry and out of bright light.
or light dose dependent change in the incidence or After LEVULAN KERASTICK Topical Solution is applied,
severity of stinging and/or burning. it is important for the patient to wear light-protective
clothing, such as a wide-brimmed hat, when exposed
In two Phase 3 trials, the sensation of stinging and/or to sunlight or sources of light.
burning appeared to reach a plateau at 6 minutes into the
treatment. Severe stinging and/or burning at one or more • Fourteen to eighteen hours after application of
lesions being treated was reported by at least 50% of the LEVULAN KERASTICK Topical Solution the patient will
patients at some time during treatment. The majority of return to the doctor’s office to receive blue light
patients reported that all lesions treated exhibited at least treatment, which is the second and final step in the
slight stinging and/or burning. Less than 3% of patients treatment. Prior to blue light treatment, the actinic
discontinued light treatment due to stinging keratoses will be rinsed with tap water. The patient will
and/or burning. be given goggles to wear as eye protection during the
blue light treatment.
In the Phase 3 trials, the most common changes in lesion
appearance after LEVULAN KERASTICK for • The blue light is of low intensity and will not heat the
Topical Solution Photodynamic Therapy were erythema skin. However, during the light treatment, which lasts
and edema. In 99% of active treatment patients, some or for approximately 17 minutes, the patient will
all lesions were erythematous shortly after treatment, experience sensations of tingling, stinging, prickling or
while in 79% of vehicle treatment patients, some or all burning of the treated lesions. These feelings of
lesions were erythematous. In 35% of active treatment discomfort should improve at the end of the light
patients, some or all lesions were edematous, while no treatment.
vehicle-treated patients had edematous lesions. Both
erythema and edema resolved to baseline or improved by • Following treatment, the actinic keratoses and, to
4 weeks after therapy. LEVULAN KERASTICK Topical some degree, the surrounding skin, will redden, and
Solution application to photodamaged perilesional skin swelling and scaling may also occur. However, these
resulted in photosensitization of photodamaged skin and
in a photodynamic response (see Warnings and
Precautions).
LEVUL
Other Localized Cutaneous Adverse Experiences: Inc.®
Table 1 depicts the incidence and severity of cutaneous Pharm
adverse events in Phase 3 studies, stratified by anatomic
site treated. US
Manuf
25 Upt
For mo
1-978
www.
Adverse Experiences Reported by Body System:
LAB-1
In the Phase 3 studies, 7 patients experienced a serious
adverse event. All were deemed remotely or not related to
treatment. No clinically significant patterns of clinical
laboratory changes were observed for standard serum
chemical or hematologic parameters in any of the
controlled clinical trials.
OVERDOSAGE
LEVULAN KERASTICK Topical Solution Overdose
LEVULAN KERASTICK Topical Solution overdose has not
been reported. In the unlikely event that the
drug is ingested, monitoring and supportive care are
recommended. The patient should be advised to avoid
incidental exposure to intense light sources for at least 40
hours after ingestion. The consequences of exceeding the
recommended topical dosage are unknown.
BLU-U Light Overdose
There is no information on overdose of blue light from the
BLU-U Blue Light Photodynamic Therapy
Illuminator following LEVULAN KERASTICK Topical Solution
application.
Information for Patients:
LEVULAN KERASTICK Photodynamic Therapy for Actinic
Keratoses.
• The first step in LEVULAN KERASTICK Photodynamic
Therapy (PDT) for actinic keratoses is application of
the LEVULAN KERASTICK Topical Solution to actinic
keratoses located on the patient’s face or scalp.
lesion changes are temporary and should completely
AN®
, KERASTIC
and DUSA®
ar
aceuticals, Inc.,
Patents: 5,07
actured for: DU
on Drive, Wilmi
re information
-657-7500
dusapharma.co
442AW Rev B
K®
, BLU-U®
, DUSA Pharmaceuticals,
e registered trademarks of DUSA
a Sun Pharma company.
9,262 5,211,938 5,954,703,
SA Pharmaceuticals, Inc.®
ngton, MA 01887
please contact: 1-877-533-3872 or
m

CLINICAL DERMATOLOGY
included a rash, fever and cough 1 to 2
months previously. Similarly, “Some-
timestheparentsdeveloponychomad-
esisastheironlypresentingsymptom.”
Theonlywaytodetermineabsolutelyif
patientshavetheA6strain,saysDr.Ty-
ring, is sending swabs from deep buc-
cal mucosa to the Centers for Disease
Control Prevention.
Drs. Friedlander and Tyring report
norelevantfinancialinterests.Thisarti-
clewasassembledfrompresentationsat
MauiDerm 2015 and supplemental in-
terviews. DT
References
1. Downing C, Ramirez-fort MK, Doan HQ, et al.
Coxsackievirus A6 associated hand, foot and
mouth disease in adults: clinical presenta-
tion and review of the literature. J Clin Virol.
2014;60(4):381-6.
week study period (Period A), patients
were randomized to receive adalim-
umab 160 mg at week 0, 80mg at week
2and40mgonceweekly(n=153)start-
ing at week 4, or placebo (n = 154). Fol-
lowing Period A, eligible patients were
re-randomizedina24-weektreatment
period (Period B) in which they re-
ceived adalimumab 40 mg weekly, 40
mg every other week or placebo. The
results of Period B have not yet been
released. Using the Hidradenitis Sup-
purativa Clinical Response (HiSCR)
measure, investigators assessed treat-
ment response, which was defined as
atleast50%reductionfrombaselinein
total abscess and inflammatory nod-
ule count at week 12 with no increase
for abscess or draining fistula count.
The results from Period A were very
positive, with those patients who re-
ceived adalimumab 40 mg weekly
showing significant improvement in
theirHS-relatedabscessesandinflam-
matory nodules compared to those in
the placebo arm at week 12 (41.8% vs
26%, respectively). Less than 5% of all
patients experienced adverse events
in this study: the most common were
exacerbation of HS (9.2% vs 13.2%),
nasopharyngitis (5.9% vs 10.5%) and
headache (9.2% vs 9.9%).
“One of the central goals of HS ther-
apy is to reduce the inflammatory re-
sponse. The nice thing about the im-
plementation of systemic therapies
like adalimumab is that we can treat
the disease on a whole and not just the
symptoms. TNF inhibitors can effec-
tively address the inflammatory com-
ponent and can potentially maintain
a long-term improvement and relief in
patients’ HS related symptoms,” says
Neal Bhatia, M.D., director of clinical
dermatology, Therapeutics Clinical
Research in San Diego, Calif.
For milder cases of HS, Dr. Strober
says that patients can be treated suc-
cessfully with topical agents such as
clindamycinandbenzoylperoxide.For
moderatecases,theadditionoforalan-
tibiotics of the tetracycline class (dox-
ycycline or minocycline) would be the
next therapeutic step Dr. Strober says,
or even the use of oral clindamycin in
combination with rifampin.
“In truth, however, there are very
few good therapies for moderate to se-
vereHSuntilwetalkabouttheTNFin-
hibitors. Adalimumab and infliximab
are two drugs that have shown a very
goodefficacyinmoderatetosevereHS
andinmyopinion,TNFinhibitionwill
be the gold standard therapy for HS,
particularlyinmoresevereandrefrac-
tory cases,” Dr. Strober says.
AccordingtoDr.Strober,bothadali-
mumab and infliximab have been
shown to work well in over half the pa-
tients who take it and can benefit from
thosedrugs.InadditiontoTNFinhibi-
tion, Dr. Strober recommends that pa-
tients concomitantly take methotrex-
ate because it augments response by
raisingdruglevelsandreducesimmu-
nogenicity of the biologic.
“I think physicians should not shy
away from more aggressive therapy in
HSpatientsbecausetheirqualityoflife
without treatment is miserable. These
patients are suffering and this is not a
condition where we want to be timid
and hold back because of the concern
of side effects such as nasopharyngi-
tis or headaches, which in the big pic-
turearetrulyminimalcomparedtothe
devastating consequences of HS dis-
ease when not treated effectively,” Dr.
Bhatia says. DT
Disclosures: Dr. Bhatia has no relevant disclosures.
Dr. Strober is an Advisory Board member and consul-
tant at AbbVie and receives an honoraria from AbbVie.
References:
1. Clinical research, clinical trials and therapeutics. J
Invest Dermatol. 2014;134 Suppl 2:S30-8.
TNF INHIBITORS:
reducing infammatory response from page 13
VIRUSES:
CVA6 diagnosis from page 18
“The nice thing about the implementation
of systemic therapies like adalimumab
is that we can treat the disease on a
whole and not just the symptoms. TNF
inhibitors can effectively address the
inflammatory component and can
potentially maintain a long-
term improvement and relief in
patients’ HS related symptoms.”
Neal Bhatia, M.D.,
San Diego, Calif.
1MILLION
Approx.1million
infectedwith
chikungunya

®
COSMETIC DERMATOLOGY22
25BELOTERO RULES
This HA filler requires injection know-how to
get the most for patient results.
Althoughrelativelyfewphysicians
perform nonsurgical eye lifts, combin-
ing fillers and neuromodulators in this
areacanyieldexcellentresultsandhigh
patientsatisfaction,accordingtoonein-
ternationalexpertwhopresentedatlast
year’sCosmeticBootcampinAspen,Colo.
Age-related changes that impact the
periorbital area include skin laxity, vol-
ume loss, and bone resorption, all of
which lead to deflation and a combi-
nation of apparent descent of the upper
eyelid and brow (pseudoptosis) and in
some cases true descent, says Steven
Liew, FRACS. He is a Sydney, Australia-
basedplasticsurgeoninprivatepractice.
THE UPPER PERIORBIT
Theagingprocessoftheupperperiorbit
is a complex and dynamic process. The
signsofagingrangefromtissuedeflation
andsignificantvolumelossthatrequires
volumereplacement,totissuedeflation
andsofttissueptosis,whichrequiressur-
gical excision and lifting.
“An attractive upper periorbit in-
cludes an eyebrow of
appropriate height and
shape, eyebrow tissue
that is firm, taught and
full, a smooth upper
eyelid and eyebrow-lid
junction and a smooth
ogee curve transition-
ing from the forehead down to the in-
fra-brow region,” Dr. Liew says.
Because the eyebrow can descend in
many places, creating optimal results
often requires filling the entire length
of the eyebrow, according to Dr. Liew.
Doing so improves the eyebrow’s verti-
A team of Korean researchers has developed
a composite filler made of cross-linked
hyaluronic acid (HA) and human collagen
(COL) derived from the umbilical cord. The
researchers, from CHA University in Pocheon,
South Korea, write that their goal was to
improve the kind of biocompatibility and
durability found in commercially available
fillers. The authors write that the composites
showed improved or similar physical
properties over the commercial fillers.
SOURCE: BIT.LY/COLLAGENFILLERS
The nonsurgical eye lift
JOHN JESITUS | STAFF CORRESPONDENT
Since we’re using very
small aliquots, high up
in the skin and superf-
cially, [Belotero] longev-
ity may not be as great as
with some other types of
volumizing fllers.”
Derek H. Jones, M.D.
Beverly Hills, Calif.
on the “rules” for Belotero use
See story page 25
Specifc techniques with injectable
HAs can buy some patients years
before requiring eyelid surgery.
QUICK READ
Quotable DTExtra
Dr. Steven Liew
46-year-old female patient shown
before (left) and 3 months after (right)
0.3 cc Juvéderm Ultraplus injected
with a 25-guage needle deep at the
supraperiosteal level.
Photos: Dr. Steven Liew
calpositionwhilealso creating forward
projectionthatrecruitslaxskinsuchthat
patients can buy a few years before they
require eyelid surgery.
Instead of performing surgery on a
58-year-old Asian female patient with
periorbitalhollowing,Dr.Liewdescribes
filling the patient’s entire upper perior-
bital rim on both sides with a total of 0.4
mLJuvédermUltraXC(hyaluronicacid/
HA, Allergan) per side for volume, eye-
browcontourandprojectionthatlasted
around 15 months.
“That’s why I like to inject all filler
productsdeepontothebonehere.Stud-
ies1
have shown the potential for perio-
steal thickening in this area,” he says,
adding thatthebody’snaturalhyaluro-
nidaseislessplentifulatthebonylayer.
“Itypicallyusea25-gaugecannulain
this region, constantly feeling the bone.
Once I get to the right position, I do an
anterograde and a retrograde injection,
putting my index finger along the su-
praorbital rim sulcus, feeling the can-
nula and moving across where the su-
praorbital neurovascular bundles are
located.”
However, there’s one area Dr. Liew
NONSURGICAL EYE LIFT see page 29

ACZONE®
(dapsone) Gel 5%
BRIEF SUMMARY—PLEASE SEE THE ACZONE®
PACKAGE INSERT FOR FULL
PRESCRIBING INFORMATION.
ACZONE®
Gel, 5%, is indicated for the topical treatment of acne vulgaris.
DOSAGE AND ADMINISTRATION
For topical use only. Not for oral, ophthalmic, or intravaginal use. After the
skin is gently washed and patted dry, apply approximately a pea-sized
amount of ACZONE®
Gel, 5%, in a thin layer to the acne affected areas
twice daily. Rub in ACZONE®
Gel, 5%, gently and completely. ACZONE®
Gel, 5%, is gritty with visible drug substance particles. Wash hands after
application of ACZONE®
Gel, 5%.
If there is no improvement after 12 weeks, treatment with ACZONE®
Gel,
5%, should be reassessed.
CONTRAINDICATIONS
None.
Hematological Effects
Oral dapsone treatment has produced dose-related hemolysis and
hemolytic anemia. Individuals with glucose-6-phosphate dehydrogenase
(G6PD) deficiency are more prone to hemolysis with the use of certain
drugs. G6PD deficiency is most prevalent in populations of African, South
Asian, Middle Eastern, and Mediterranean ancestry.
There was no evidence of clinically relevant hemolysis or anemia in
patients treated with ACZONE®
Gel, 5%, including patients who were
G6PD deficient. Some subjects with G6PD deficiency using ACZONE®
Gel developed laboratory changes suggestive of mild hemolysis.
If signs and symptoms suggestive of hemolytic anemia occur, ACZONE®
Gel, 5% should be discontinued. ACZONE®
Gel, 5% should not be
used in patients who are taking oral dapsone or antimalarial medications
because of the potential for hemolytic reactions. Combination of
ACZONE®
Gel, 5%, with trimethoprim/sulfamethoxazole (TMP/SMX) may
increase the likelihood of hemolysis in patients with G6PD deficiency.
Peripheral Neuropathy
Peripheral neuropathy (motor loss and muscle weakness) has been
reported with oral dapsone treatment. No events of peripheral neuropathy
were observed in clinical trials with topical ACZONE®
Gel, 5% treatment.
Skin
Skin reactions (toxic epidermal necrolysis, erythema multiforme, morbil-
liform and scarlatiniform reactions, bullous and exfoliative dermatitis,
erythema nodosum, and urticaria) have been reported with oral dapsone
treatment. These types of skin reactions were not observed in clinical
trials with topical ACZONE®
Gel, 5% treatment.
ADVERSE REACTIONS
Clinical Studies Experience
Because clinical trials are conducted under prescribed conditions,
adverse reaction rates observed in the clinical trials of a drug cannot be
directly compared to rates in the clinical trials of another drug and may
not reflect the rates observed in practice.
Serious adverse reactions reported in patients treated with ACZONE®
Gel, 5%, during clinical trials included but were not limited to
the following:
• Nervous system/Psychiatric – Suicide attempt, tonic clonic movements.
• Gastrointestinal – Abdominal pain, severe vomiting, pancreatitis.
• Other – Severe pharyngitis.
In the clinical trials, a total of 12 out of 4032 patients were reported to
have depression (3 of 1660 treated with vehicle and 9 of 2372 treated with
ACZONE®
Gel, 5%). Psychosis was reported in 2 of 2372 patients treated
with ACZONE®
Gel, 5%, and in 0 of 1660 patients treated with vehicle.
Combined contact sensitization/irritation studies with ACZONE®
Gel, 5%, in 253 healthy subjects resulted in at least 3 subjects with
moderate erythema. ACZONE®
Gel, 5%, did not induce phototoxicity or
photoallergy in human dermal safety studies.
ACZONE®
Gel, 5%, was evaluated for 12 weeks in four controlled studies
for local cutaneous events in 1819 patients. The most common events
reported from these studies include oiliness/peeling, dryness, and erythema.
One patient treated with ACZONE®
Gel in the clinical trials had facial
swelling which led to discontinuation of medication.
In addition, 486 patients were evaluated in a 12 month safety study. The
adverse event profile in this study was consistent with that observed in the
vehicle-controlled studies.
Experience with Oral Use of Dapsone
Although not observed in the clinical trials with ACZONE®
Gel (topical
dapsone) serious adverse reactions have been reported with oral use of
dapsone,includingagranulocytosis,hemolyticanemia,peripheralneuropathy
(motor loss and muscle weakness), and skin reactions (toxic epidermal
necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions,
bullous and exfoliative dermatitis, erythema nodosum, and urticaria).
DRUG INTERACTIONS
Trimethoprim-Sulfamethoxazole
A drug-drug interaction study evaluated the effect of the use of ACZONE®
Gel, 5%, in combination with double strength (160 mg/800 mg)
trimethoprim-sulfamethoxazole (TMP/SMX). During co-administration,
systemic levels of TMP and SMX were essentially unchanged. However,
levels of dapsone and its metabolites increased in the presence of TMP/
SMX. Systemic exposure (AUC0-12
) of dapsone and N-acetyl-dapsone
(NAD) were increased by about 40% and 20% respectively in the
presence of TMP/SMX. Notably, systemic exposure (AUC0-12
) of dapsone
hydroxylamine (DHA) was more than doubled in the presence of TMP/
SMX. Exposure from the proposed topical dose is about 1% of that from
the 100 mg oral dose, even when co-administered with TMP/SMX.
Topical Benzoyl Peroxide
Topical application of ACZONE®
Gel followed by benzoyl peroxide in
subjects with acne vulgaris resulted in a temporary local yellow or orange
discoloration of the skin and facial hair (reported by 7 out of 95 subjects
in a clinical study) with resolution in 4 to 57 days.
Drug Interactions with Oral Dapsone
Certain concomitant medications (such as rifampin, anticonvulsants,
St. John’s wort) may increase the formation of dapsone hydroxylamine,
a metabolite of dapsone associated with hemolysis. With oral dapsone
treatment, folic acid antagonists such as pyrimethamine have been noted
to possibly increase the likelihood of hematologic reactions.
USE IN SPECIFIC POPULATIONS
Pregnancy
Teratogenic Effects: Pregnancy Category C
There are no adequate and well controlled studies in pregnant women.
Dapsone has been shown to have an embryocidal effect in rats and rabbits
when administered orally in doses of 75 mg/kg/day and 150 mg/kg/day
(approximately 800 and 500 times the systemic exposure observed in
human females as a result of use of the maximum recommended topical
dose, based on AUC comparisons), respectively. These effects were
probably secondary to maternal toxicity. ACZONE®
Gel, 5%, should be
used during pregnancy only if the potential benefit justifies the potential
risk to the fetus.
Nursing Mothers
Although systemic absorption of dapsone following topical application of
ACZONE®
Gel, 5%, is minimal relative to oral dapsone administration, it is
known that dapsone is excreted in human milk. Because of the potential for
oral dapsone to cause adverse reactions in nursing infants, a decision should
be made whether to discontinue nursing or to discontinue ACZONE®
Gel,
5%, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and efficacy was evaluated in 1169 children aged 12-17 years
old treated with ACZONE®
Gel, 5%, in the clinical studies. The adverse
event rate for ACZONE®
Gel, 5%, was similar to the vehicle control group.
Safety and efficacy was not studied in pediatric patients less than 12 years
of age, therefore ACZONE®
Gel, 5%, is not recommended for use in this
age group.
Geriatric Use
Clinical studies of ACZONE®
Gel, 5%, did not include sufficient number of
patients aged 65 and over to determine whether they respond differently
from younger patients.
G6PD Deficiency
ACZONE®
Gel, 5% and vehicle were evaluated in a randomized,
double-blind, cross-over design clinical study of 64 patients with G6PD
deficiency and acne vulgaris. Subjects were Black (88%), Asian (6%),
Hispanic (2%) or of other racial origin (5%). Blood samples were taken
at Baseline, Week 2, and Week 12 during both vehicle and ACZONE®
Gel, 5% treatment periods. There were 56 out of 64 subjects who had a
Week 2 blood draw and applied at least 50% of treatment applications.
ACZONE®
Gel was associated with a 0.32 g/dL drop in hemoglobin
after two weeks of treatment, but hemoglobin levels generally returned
to baseline levels at Week 12.
There were no changes from baseline in haptoglobin or lactate dehydro-
genase during ACZONE®
or vehicle treatment at either the 2-week or
12-week time point.
The proportion of subjects who experienced decreases in hemoglobin
≥1 g/dL was similar between ACZONE®
Gel, 5% and vehicle treatment (8
of 58 subjects had such decreases during ACZONE®
treatment compared
to 7 of 56 subjects during vehicle treatment among subjects with at
least one on-treatment hemoglobin assessment). Subgroups based on
gender, race, or G6PD enzyme activity did not display any differences in
laboratory results from the overall study group. There was no evidence of
clinically significant hemolytic anemia in this study. Some of these subjects
developed laboratory changes suggestive of mild hemolysis.
OVERDOSAGE
ACZONE®
Gel, 5%, is not for oral use. If oral ingestion occurs,
medical advice should be sought.
Rx ONLY
© 2014 Allergan, Inc.
Irvine, CA 92612, U.S.A.
®
marks owned by Allergan, Inc.
Patented. See www.allergan.com/products/patent_notices
Based on 72205US13
144098 APC14LG14

COSMETIC DERMATOLOGY
Belotero(Merz)hasbecomethetreat-
ment of choice and standard of care for
thecosmetictreatmentoffine,etched-in
faciallines,accordingtoadermatologist
Dermatology Times interviewed on the
topic in 2012.1
DerekH.Jones,M.D.,
clinicalassociateprofes-
sorofdermatology,Uni-
versityofCalifornia,Los
Angeles, and founder
and director, Skin Care
and Laser Physicians
of Beverly Hills, says he
uses the highly cross-linked hyaluronic
acidfillertotreatvertical,etched-inperi-
oralandfine,superficialetched-inradial
cheek lines.
Butthereisacaveat:Beloterorequires
injection know-how.
“Itdoestakesomeexperiencebecause
itisinjecteddifferently[thanotherhyal-
uronic acid fillers],” he says.
TECHNIQUE TIPS
Dr.Jonessayshetransfersalloftheprod-
uct into a 1 cc BD syringe. This particu-
larsyringehasaLuerlock,whichallows
thedermatologisttouseafine32-gauge
needle without concern that the needle
adapterwillflyoffunderhigherpressure
with injection.
He injects with the 32-gauge needle,
using a serial puncture, superficial der-
mis technique.
An advantage of using Belotero is its
Cohesive Polydensified Matrix (CPM)
technology feature. The technology al-
lows the material to smoothly and ho-
mogeneously integrate into the dermis
a day or two after superficial injection,
according to Dr. Jones, an investigator
and consultant for Merz and an inves-
tigatorinthe118-patienttrialthatledto
Belotero’s FDA approval.
“We have seen that with histologic
studies. It has been confirmed by ultra-
sound studies, and we see it clinically,”
Dr. Jones says.
AccordingtoDr.Jones,wheninjected
correctly, Belotero does not form the
pools and lakes that can result after Re-
stylane(Galderma)andJuvéderm(Aller-
gan) injections. Injecting too much su-
perficially, however, can result in some
beading of material, he says.
A CLOSER LOOK AT THE DATA
TworecentstudiessuggestBelotero’stech-
nology makes a difference.2, 3
UCLA re-
searchersreportedinMay2014intheAes-
theticSurgeryJournalthathigh-resolution
ultrasoundshowshyaluronicacidgelfill-
ers with differing production technolo-
gies show distinct spread and distribu-
tion patterns in the periocular tissues.2
“Restylane-L formed a localized hy-
poechoic image within the tissue, with
some spread into bubbles or pearl-like
configuration. Belotero Balance spread
more widely into the tissue plane and
diffused into an elongated or spindle-
shaped hypoechoic image,” according
to the study’s published abstract.2
Researcherspublishedastudy3
inOc-
tober 2013 in Plastic and Reconstructive
SurgerysuggestingthatBeloteroresulted
in greater evenness than Restylane at 4
weeks. A 5-year retrospective review of
317 patients treated with Belotero Bal-
anceshowednoadverseevents,includ-
ingnopersistentnodulesorgranulomas.
A study performed in 2012 compar-
ingBeloteroBalancewithJuvédermand
Restylane showed the fillers perform
Belotero rules for etched lines
This highly cross-linked hyaluronic
acid fller may have become the
treatment of choice for vertical,
etched-in perioral and fne,
superfcial etched-in radial cheek
lines, but there is a caveat: Belotero
requires injection know-how.
QUICK READLISETTE HILTON | STAFF CORRESPONDENT
Derek H. Jones
equally well when used traditionally in
usual volumes, according to Dr. Jones.4
One downside of Belotero, however,
is its longevity.
“Since we’re using very small ali-
quots, high up in the skin and super-
ficially, longevity may not be as great
as with some other types of volumiz-
ing fillers. Generally, I tell patients 6
to 12 months, and that holds true in
my clinical practice,” Dr. Jones says.
TAKE CAUTION: BELOTERO BRUISES
Becausecliniciansuseasuperficialserial
puncturetechnique,Beloteropatientsare
likely to have swelling and bruising for
thefirstcoupleofdays.Dr.Jonessayshe
avoids using Belotero or any other filler
a day or two before a patient has a big
social event.
It’stooearlytotellwhetherRestylane
Silk(Galderma)mightbeabetteroption
in these cases, according to Dr. Jones.
“There has been some burgeoning
interest in Restylane Silk. It’s new on
the market,” Dr. Jones says. “Some of
mycolleagueslikeRestylaneSilkquite
a bit, but I think we need to develop
our experience a bit more in terms of
fine line treatment compared to Be-
lotero.” DT
Disclosures: Dr. Jones is an investigator and
consultant for Merz.
References
1. Petrou, I. Belotero Balance appears to rival
leading dermal fillers. Dermatology Times. Pub-
lished November 1, 2012. Available at: http://
dermatologytimes.modernmedicine.com/der-
matology-times/news/modernmedicine/mod-
ern-medicine-feature-articles/belotero-bal-
ance-appears-riva
2. Goh AS, Kohn JC, Rootman DB, Lin JL, Gold-
berg RA. Hyaluronic acid gel distribution pat-
tern in periocular area with high-resolu-
tion ultrasound imaging. Aesthet Surg J.
2014;34(4):510-5.
3. Lorenc ZP, Fagien S, Flynn TC, Waldorf HA. Re-
view of key Belotero Balance safety and efficacy
trials. Plast Reconstr Surg. 2013;132(4 Suppl
2):33S-40S.
4. Prager W, Wissmueller E, Havermann I, et al. A
prospective, split-face, randomized, compara-
tive study of safety and 12-month longevity of
three formulations of hyaluronic acid dermal
filler for treatment of nasolabial folds. Dermatol
Surg. 2012;38(7 Pt 2):1143-50.
Cohesive
Polydensified
Matrix (CPM)
technology…
allows Belotero
to smoothly and
homogeneously
integrate into the
dermis a day or two
after superficial
injection.

Dermatology Times May 2015 ezine

Dermatology Times May 2015 ezine

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