ROSACEA Dialogue with a Mentor Albert Kligman, M.D., Ph.D., is a pioneer who continues to break new ground in dermatology.
knowledge remains so poor. Consider that rosacea
his career to challenging the status quo,
and acne vulgaris are related disorders, and while
Aand to this day continues to play an active we have a good understanding about the causes of
role in the ever-changing arena of dermatology.
acne and how to treat it, we remain as ignorant
Even as he celebrates his 88th birthday this
today about rosacea as we were about acne 50
month, Dr. Kligman remains a strong example
of the power behind research and continues toshed light on some of the more perplexing der-
Q What have been some of the major mile- stones in treatment of rosacea?
In this, the first installment in a sponsored
There are many different treatments that have
series entitled, “Dialogue with a Mentor,” where
been introduced and talked about as helpful for
long-time veterans of dermatology share their
rosacea, but I believe there are only a few med-
experience, insights, and what they believe will
ications that offer unassailable efficacy. Among
have the most impact on future practice, Dr.
oral agents, I think nobody will deny antibiotics
Kligman sets his sights on what he views as still
are important therapy, particularly the tetracy-
uncharted territory — the diagnosis and treat-
clines, but they must be given in full doses. In
addition, there is no question that isotretinoin,
even at moderate doses, is very effective for more
noted for the development of tretinoin, ground-
severe cases. At the topical treatment level,
breaking work in the advancement of acne man-
metronidazole has become a mainstay, but there
agement, and is the physician who coined the
are a number of other topical agents being used
term “cosmeceutical” when referring to his use
according to prescriber personal preference. I
of retinoids in anti-aging. Dr. Kligman has a
don’t believe there is sufficient good science
wealth of experience, and in this interview out-
backing the purported activity of some of the
lines some of his opinions and findings as they
topical drugs for reducing the features of rosacea
Q What are your thoughts about the Q What impact do you believe the National pathogenesis of rosacea? Rosacea Society classification system will
It appears the answer to that question is not a
have on the understanding, recognition, and
simple one because rather than having a single
diagnosis of rosacea?
cause, rosacea probably develops as a result of
It’s an excellent start, but I think it is too simplified
multiple interacting factors, some of which
because I believe there are many more varieties of
include genetic determination and perhaps the
rosacea in addition to the four subtypes listed in
presence of demodectic mites in some individu-
that system. However, the goal of developing a
als. The pathogenesis of rosacea is a subject that
standard classification for enabling research and
has been debated and disagreed on for many
communication is a good one, and the system was
years, and I consider it a real scandal that our
have not seen good supporting evidence for those
Q For 10 years,an oral antibiotic plus topi- claims. Through my own limited experience, I cal metronidazole has been the foundation
have been unimpressed with the benefits of the
for treating rosacea. Do you agree that it is the “ideal regimen?” For most patients, it is a good idea to initiate Q A recent report suggests topical metron-
therapy with such a combination systemic and
idazole has an antioxidant effect. Do you think
topical treatment. However, the treatment has to
that might encourage patient compliance?
be tailored to the manifestations of the individual
“Antioxidant” has become an important buzz-
patient. For example, there is an under-recog-
word in the popular lexicon and is a term that is
nized form of rosacea with hard edema, and in
being widely used for marketing purposes.
that situation I add massage as a physical therapy,
Therefore, the idea that use of metronidazole
while I prescribe isotretinoin if I see a patient with
provides antioxidant benefits might motivate
some patients to adhere better to treatment. However, we still haven’t the faintest idea about
Q Are there situations where you would
the real mechanism of metronidazole’s efficacy
prescribe monotherapy instead of combina- tion treatment? Probably 95 percent of the time, I initiate treat- Q Some information suggests that only 10
ment with the combination of an oral antibiot-
percent of patients with rosacea are receiv-
ic and a topical agent. I might consider topical
ing treatment. Does that surprise you and
metronidazole treatment as monotherapy for a
what can be done to improve the situation?
patient presenting with very early, mild rosacea.
I think that statistic may understate the situa-
In general, however, medical management of
tion, but certainly more than 50 percent of
rosacea should be multimodal. Rosacea is a seri-
affected persons are not receiving care because
ous disease with potentially significant psy-
they have not been properly diagnosed. That is
chosocial consequences, and there are many
another piece of the scandal about rosacea I
patients who are finally receiving treatment after
referred to earlier. However, the National
suffering for 20 years without a diagnosis.
Rosacea Society (NRS) is doing an invaluableand effective job in spreading the word to raise
Q To reduce the development of drug-
awareness and bring forward better treatment. resistant bacterial strains, the FDA has man- dated new statements appear on the physi- Q Do you foresee any new developments cian labeling for all systemic antibacterial in treatment occurring over the next five to drugs. Do you think that will affect prescrib- 10 years? ing patterns for rosacea?
We have begun to do some research on the use of
I don’t think those concerns are particularly rele-
topical retinoids, and I think as we collect more
vant to rosacea and I don’t expect them to have
information, they will emerge as a first order
much impact on our reliance on oral antibiotics.
treatment. There is a good rationale for using
In theory, use of antibiotics for the treatment of
topical retinoids recognizing that patients with
rosacea could contribute to the emergence of
rosacea have severely photodamaged skin even at
resistant bacteria. However, there does not appear
the time of disease onset. Therefore, I think top-
to be an important bacterial cause of rosacea that
ical retinoids are indicated and effective because
we need to be concerned about, and we’ve been
of their benefits for restoring the dermal matrix.
using oral antibiotics for 35 years with a great safe-
Otherwise, more basic research is needed to
elucidate the pathogenesis of rosacea because
Dialogue
only with that information will we be able to
with a Mentor Q What experience do you have with some identify targeted therapies. We can continue to of the more recently introduced therapies for rosacea?
about avoiding triggers and our current empiri-
My own impression of azelaic acid is that its effi-
cal approaches to drug treatment. However, we
cacy is being overstated. Similarly, while there are
need to support some serious basic research
some people who think the topical immunomod-
because that will provide a foundation for devel-
ulators tacrolimus and pimecrolimus work, I
Learning & Behavior2003, 31 (2), 185-191 Changes in stimulus salience as a result ofstimulus preexposure: Evidence from aversiveIn two experiments, rats received preexposure to three compound flavor stimuli, AX, BX, and CX,where X represents a saline solution. AX and BX were presented in alternation; CX, on a separate blockof trials. The value of X was then modified, being devalued by av
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