Supplement to Aesthetic Buyers Guide® • July/August 2004
Levulan Photodynamic Therapy Offers Effective Acne Treatment Alternative
The rapidly increasing interest in Levulan Dr.Anderson’s original exposure to the novel com-
pound was as an investigator for skin cancer. “When
Pharmaceuticals, Inc. (Wilmington, Mass.) to
ALA enters the skin, it becomes metabolized. The skin
treat acne and other medical conditions can largely be
cells turn it into a photosensitizer called porphyrin.
traced back to the efforts of Rox Anderson, M.D.,
Earlier, we had conducted a study showing that seba-
research director of photomedicine at the Wellman
ceous glands were the most active part of the skin for
Center, Massachusetts General Hospital, Boston. “I
producing porphyrins. Sebaceous glands are the root
think light-activated drugs are extremely powerful,” Dr.
Anderson said. “The use of topical 5-aminolevulinic acid
“Although there are many different treatments for
(ALA) is one of the early examples of what I expect to
acne, we have no cures,” observed Dr. Anderson. “We real-
become a growing number of diverse drugs in the near
ly need a cure, something that has a very long-term effect
future. I believe we are near the beginning of this cycle
and treats the activity of the sebaceous gland. Drugs
It was four years ago, at “This is great news because it has a long lasting effect. There was a strong effectiveness against even severe acne.” - Rox Anderson, M.D.
different doses. In the study, we were able to demon-
Yoshiyasu Itoh, M.D., Ph.D. “Those results were similar
strate that treatment inactivates the bacteria in the
to ours,” Dr. Anderson conveyed. “However, back in
hair follicles that is part of the reason people develop
2000, ALA was not approved for anything. It was an
acne. But much more exciting is that we were able to
experimental drug. Since then, the drug is on its way to
show that at high doses, treatment actually shuts down
being embraced by the aesthetic community. ALA is now
the sebaceous gland in the skin. This is great news
FDA approved for the treatment of actinic keratoses.
because it has a long lasting effect. There was a strong
Because the drug is approved, physicians can actually
effectiveness against even severe acne.”
order it and many have begun off-label use to treat
Medical Insight, Inc.® • 27796 Soller Mission Viejo, CA 92692 • (949) 830-5409 • Facsimile: (949) 830-8944 • www.miinews.com
acne. I’m also optimistic about the recent work of look-
There is a kind of clinical creativity going on. ALA PDT
ing at different light sources to activate ALA. The poten-
actually treats a number of aspects of chronic sunlight
tial to use flashlamps, which are very fast treatment
injury to the skin. But I don’t ever expect ALA to be able
sources, with ALA to treat acne is certainly exciting.”
to remove blood vessels. PDT therapy really is meant to
As a physician, Dr. Anderson considers himself
be used synergistically with lasers and other modalities
somewhere in the middle when it comes to implement-
ing a wide range of applications for new technologies. “I
Overall, Dr. Anderson believes that the use of Levulan PDT will continue to grow. “I think it will be “Because Levulan PDT has shown that it
useful for acne and other follicular disorders of the skin. My guess is that it will be used in two different modes. can be very effective in treating acne,
One is a low dose maintenance mode. I can even imag-
physicians are now starting to incorporate
ine combining ALA with sunscreens and letting the sundo the work for you. This would be a totally different
this therapy creatively into their practices.”
approach. The other mode would be a high dose, office-
like to undertake experiments and come up with new
based procedure. I predict this approach will someday
approaches to things. But it takes awhile before we real-
be used for severe acne. I also believe ALA has the
ly understand where it fits into the whole picture.
potential to be as effective as oral retinoids. So ALA will
Because Levulan PDT has shown that it can be very
likely become a very popular approach. But I don’t think
effective in treating acne, physicians are now starting to
we will see ALA replacing our use of creams, topical
incorporate this therapy creatively into their practices.
retinoids, antibiotics and benzoyl peroxide.”
Clinical Roundtable: Levulan PDT Acne Tx Editors Note: For this news article, we inter- “We needed an aggressive treatment
viewed a select group of leading researchers to
for acne patients who
elicit their views and clinical experience regard-
did not feel comfort-
ing the use of Levulan PDT to treat acne. able taking antibiotics or Accutane.” Why did you add Levulan to your - Dore Gilbert, M.D. practice for the treatment of acne? Macrene Alexiades-Armenakas, M.D. – Following Gerald Bock, M.D. – We had the BLU-U lamp (from
the discovery that ALA in combination with the long
DUSA) available and wanted alternative options for our
pulsed pulsed dye laser (LP PDL) was safe and effective
in the treatment of actinic keratoses (Alexiades-Armenakas and Geronemus, Arch Derm, October 2003),
Dore Gilbert, M.D. – We needed an aggressive treat-
we noted improvement in sebaceous hyperplasia and
ment for acne patients who did not feel comfortable tak-
acne rosacea as well. We followed this up with the first
ing antibiotics or Accutane. Many patients don’t want to
study on the treatment of acne using ALA with the LP
take Accutane due to the numerous systemic side effects
PDL vs. ALA PDL, which was published in abstract form
– dryness, scaling, achy joints, the birth control pill
and which I presented at ASLMS in 2003 (Alexiades-
issue for women, and so on. If patients are given an
Armenakas, et al, American Society for Laser Medicine
option, they will usually choose a less complicated route. and Surgery Abstracts, Anaheim, April 2003). It has
In addition, a recent report in the Journal of the
reproducibly shown to be effective in the treatment of
American Medical Association (JAMA) implicates pro-
both comedonal and inflammatory and cystic acne.
longed use of antibiotics with invasive breast cancer.
Until that study is proven to be a faulty study, I have anobligation to my patients, particularly my female
“Studies seem to suggest that PDT
patients, to make them aware and allow them to choosewhich course of treatment they are most comfortable
may hold the key. In my
with. Frankly, anytime there is an alternative to an
experience, I’ve had
existing treatment that is riddled with as many side
some wonderful results
effects as the current traditional acne regimens, I feelobligated to investigate it. As it turns out, Levulan and
treating cystic acne
PDT are proving to be exceptional alternatives for treat-
with Levulan PDT along with either the pulsed dye laser or Flor Mayoral, M.D. – There have been several reports the BLU-U lamp.” - Mark Nestor, M.D., Ph.D.
that show ALA PDT to be effective. Even thoughAccutane has been the gold standard for the treatmentof severe acne, its cost, potential teratogenicity and theside effect of depression in rare patients have made
gland. Also, when I heard that it was increasing the pro-
some parents unwilling to allow their teenagers to take
toporphyrin destruction of the bacteria, I realized that
this medication Levulan provides me a viable treatment
it had a dual effect. We initially began Levulan as a sec-
ondary treatment in our practice. This was for peoplewho had already had two or three treatments of
Mark Nestor, M.D., Ph.D. – Some standard treat-
Accutane and were frustrated. They did not want to deal
ments for acne have significant limitations. For cystic
with the side effects of the drug. We felt that the
acne, in particular, the two treatments that are some-
Levulan worked in a similar fashion to Accutane. We
what effective are long-term oral antibiotics and
also have a number of people in our practice who are
Accutane. However, as mentioned, a recently published
holistically committed and refuse any type of oral med-
study indicates that long-term oral antibiotics may be
ication, including antibiotics or Accutane. Yet, they have
associated with breast cancer in women. Similarly,
severe cystic scarring acne, and need advanced treat-
Accutane is becoming harder and harder to prescribe.
ment beyond the traditional topical treatments.
So we have limited ability to treat cystic acne patients.
We also find that Levulan is a wonderful treatment
Studies seem to suggest that PDT may hold the key. In
for adult acne. Many of these patients have tried every
my experience, I’ve had some wonderful results treating
topical and oral medication, but remain frustrated. We
cystic acne with Levulan PDT along with either the
are now beginning to use Levulan as a frontline treat-
ment for acne when anticipating prolonged treatmentwith either systemic antibiotics and/or Accutane. The
Donald F. Richey, M.D. – I became very interested in
Levulan when I realized that its primary function wasto reduce the size and activity of the sebaceous oil
How does Levulan fit into your acne treatment regimens? “We are now beginning to use Dr. Alexiades-Armenakas – For patients who have Levulan as a frontline
failed systemic antibiotics, topical treatments, and are
treatment for acne
not candidates or are unwilling to take Accutane, laseroptions are recommended, including PDT. when anticipating pro- longed treatment with Dr. Bock – We are still evaluating ALA PDT, but it appears that the BLU-U lamp with Levulan is much either systemic antibi-
more effective than the blue light alone. otics and/or Accutane.” - Donald F. Richey, M.D. Dr. Gilbert – Levulan PDT has become the primary treatment modality of choice for pustular or cystic acne.
If patients have mild acne, then I am inclined to use theBLU-U lamp by itself. Dr. Mayoral – Levulan is a great alternative for those who have failed Accutane and also for those patients
who fail treatments because of non-compliance. It is
simple, effective and has minimal side effects. Dr. Nestor – We use Levulan to treat moderate-to- severe nodular papular and papular cystic acne, typi- cally three sessions. We can use Levulan in combination with BLU-U light alone or in combination with topicals. Dr. Richey – Levulan is increasingly becoming the pri-
mary a line of defense in our practice for treating acne.
dermabrasion, then the Levulan Kerastick is applied. What light sources and treatment pro-
We allow the Levulan to incubate for approximately 45
tocol do you typically use?
minutes. The patients that are receiving the BLU-U willbe exposed to this light source for 12 minutes. For
Dr. Alexiades-Armenakas – The
patients receiving treatment with the Vbeam, we use
the following settings: two passes with 50% overlap, a
10 mm spot size, and a 6 ms pulse duration at 7 J/cm2.
inflammatory acne and the BLU-Ulamp for comedonal, each following
Dr. Nestor – The most common treatment protocol is
about three sessions, roughly three weeks apart, usingLevulan anywhere from 30 minute to 60 minutes after
Macrene Alexiades- Dr. Bock – We do an acetone
microdermabrasion. This is followed by pulsed dye laser
Armenakas, M.D.
at low fluence and nonpurpuric doses. We especially use
on for at least one hour. The BLU-U light exposure is
the BLU-U lamp in darker skinned individuals because
between 8 and 20 minutes. Most of the time we use 15
the pulsed dye laser may have more of a problem get-
minutes of BLU-U light with Levulan.
ting through to the pigment. We can also substitute anIPL device, again at fairly low fluence, 24 to 26 J/cm2. Dr. Gilbert – The light sources that we typically use for Levulan PDT are the BLU-U and intense pulsed light “The most common treatment protocol
(IPL). The blue light treatment begins with a very mild
is about three sessions, roughly three
scrub with acetone. We then evenly apply the Levulan tothe affected areas of the face, neck or back. We allow
weeks apart, using Levulan anywhere
approximately 30 minutes for incubation, and then
from 30 minute to 60 minutes after
expose the patient to the BLU-U for eight minutes.
The IPL protocol is the same, except of course for
microdermabrasion.”
the light source. We use 3.0, 6.0 IPL treatment with anenergy setting of 30 J/cm2. After we perform one pass
Dr. Richey – For acne, we also use the BLU-U with
with the IPL, the patient sits for two to four minutes in
Levulan. We start with a 30 minute incubation after
the BLU-U in order to expose the area or areas to an
an acetone scrub. We typically give the patient 12 min-
additional wavelength of light. This also ensures cover-
utes of actual light exposure. We plan on four sessions
age of any areas that may have been missed by the IPL
at one week intervals. We sometimes increase the drug
incubation period, depending on the erythema thatdevelops after the treatments. We also sometimes use
Dr. Mayoral – I use the BLU-U or the Vbeam laser for
IPL, but that is only for our patients undergoing pho-
my acne patients. The patients will first have a micro-
How do your patients respond? Please
have followed some patients close to two years who have
summarize your clinical results and
remained clear. With three treatments, results are sim-
observations.
ilar with Accutane. About 20% to 30% of patientsrequire more than three sessions. Dr. Alexiades-Armenakas – Typically, they are all cleared in two to four treatments, spaced three weeks Dr. Richey – Our acne patients have responded very
satisfactorily. We have had a few minimal responders,and we have had some almost miraculous responders. Dr. Bock – We have only treated a limited number of
Some of our patients are absolutely thrilled that they
patients. But we have seen a spectacular result in one
have been able to clear their cystic scarring acne
adult male who was on continuous Accutane, antibiotics
without having to take any type of systemic medica-
and anti-inflammatory agents for two and a half years,
tion or spend months and months using topical
without clearing. He cleared dramatically after a single
BLU-U lamp and Levulan treatment. He also remainedclear for a month, when he had a second treatment, andstill remains clear several weeks later. “Levulan PDT could Dr. Gilbert – Most of our patients have an immediate, become a first line
minimal, erythematous reaction. Within two to twelve
modality in the
hours, most patients will develop more erythema. However, the amount of erythema is not predictable. treatment of acne.”
Some patients may have only a mild degree of erythe-
- Gerald Bock, M.D.
ma, while others will have erythema followed by scalingfor another three to four days.
Our clinical results have been very encouraging
with about an 80% success rate. After two to four treat-
What role will Levulan PDT fill in the
ments, most patients are acne free, or have a significant
treatment of acne versus systemic phar-
improvement in their acne condition for six months to
maceuticals and topicals?
one year. However, some patients require maintenancetreatments after about six months. Maintenance treat-
Dr. Bock – If our initial experience is borne out,
ments follow the same protocol as the initial treat-
Levulan PDT could become a first line modality in the
ments, but they are only done on an ‘as needed’ basis.
treatment of acne. Its low side effect profile combinedwith significant effectiveness could be very attractive. Dr. Mayoral – My patients toler- ate the BLU-U lamp and Levulan Dr. Gilbert – In the future Levulan PDT will become
one of the mainstay treatments for pustular and cystic
acne. I’m very excited about adding Levulan PDT to my
practice. It is proving to be a great option for my
patients who don’t wish to, or cannot, take Accutane or
In addition, the process of Levulan PDT has numer-
Flor Mayoral, M.D.
ous ancillary cosmetic benefits. For older patients,
Levulan PDT therapy also treats actinic keratoses. The
The Vbeam also renders a great response, although
procedure can also diminish, if not eliminate, brown
some patients complain of pain. I have seen a couple of
spots and even overall pigmentation. It can tighten
patients that became a little edematous for a couple of
pores, prevent further acne scaring, and smooth existing
days when I combine this laser with the ALA. This
resolves quickly without any problem. Dr. Mayoral – The use of Levulan PDT for the treat- Dr. Nestor – Overall, about 60% of our patients realize
ment of acne has the potential for being very effective
greater than 80% long-term reduction in their acne. We
with less incidence of side effects than oral medications.
It could also be more economical for insurance compa-nies and patients. Dr. Nestor – Topicals can be used with Levulan PDT
without a problem. The idea is to stay away from sys-
temic medications when necessary. Levulan can alsobe used as augmentation for patients who are on sys-temic agents, but no responding well. Levulan PDTcan fit in anywhere because there are no systemic
Almost everything we do as physicians is really
combination therapy. Whether it is PDT or merelyBLU-U light, I have found that combination therapy
with Accutane are multiple, and with further restric-
works the best. For instance, the vitamin A related top-
tions from the FDA, this is going to be a difficult treat-
ical drug adapalene (Differin) is truly great for come-
ment program to orchestrate. We also feel that for the
donal acne, and can help enhance all treatments. In
patient who takes oral antibiotics, the inherent prob-
fact, we’re preparing to start a half-face study compar-
lems of photosensitivity, yeast infections and the con-
ing Differin and BLU-U together versus the BLU-U
troversy over breast cancer must all be carefully
lamp alone for mild to moderate acne.
weighed. I am thrilled that we can now offer an alter-native topical treatment for treating mild through
Dr. Richey – I feel Levulan will be a very important
severe acne. Our patients have more choices, and we can
part of acne treatment, and will be a very competitive
customize our Levulan PDT treatments to their partic-
product to systemic pharmaceuticals. The problems
R O U N D T A B L E P A R T I C I P A N T S : Macrene Alexiades-Armenakas, M.D., Ph.D. Flor Mayoral, M.D. A dermatologist in private practice in New York City A dermatologist in private practice in Miami, Fla. and a clinical instructor of dermatology at the voice (305) 665-6166 Yale University School of Medicine. fax (305) 662-4649 voice (212) 570-2067 email: flormayoral@aol.com fax (212) 861-7964 email: dralexiades@nyderm.org Mark Nestor, M.D., Ph.D. A clinical associate professor of dermatology and Gerald Bock, M.D. dermatologic surgery at the University of Miami A dermatologist in private practice in Stockton, Calif. School of Medicine in Florida. voice (209) 957-0720 voice (305) 933-6716 fax (209) 957-0801 fax (305) 933-3853 email: gnbock@deltaderm.com email: nestormd@admcorp.com Dore Gilbert, M.D. Donald F. Richey, M.D. An associate clinical professor of dermatology at the A cosmetic dermatologist in private practice in University of California, Irvine. For the past 12 years, Chico, Calif. he has also served as chief of dermatology at voice (530) 342-3686 HOAG Memorial Hospital in Newport Beach, Calif. fax (530) 342-4199 voice (949) 718 1222 email: drichey132@aol.com fax (949) 718 1220 email: drgilbert@oco.net
1. Avoid any sun tanning for at least three to four weeks before treatment. 2. Do not treat area (by waxing, tweezing or having electrolysis done) for 2 - 3 weeks prior to procedure. 3. Shave area on the morning of or the night before your treatment day. For a closer shave, let hair grow 3 days before shaving. Depilatory creams can be used in place of shaving. 4. Remove make-up and wash area
Analysis of Susanna Roxman’s poem “Cornelia” Introduction An Example of Roman Virtues Cornelia was a highly educated Roman woman who lived in the second century B.C. She was the daughter of a Roman hero, Publius Cornelius Scipio Africanus Major, who defeated Hannibal in the second Punic War. She married a young, most honourable plebeian, Tiberius Sempronius Gracchus an