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Vancouver,
B.C.— A large void of successful treatments exists for
the very common disorders of hyperpigmentation, Rebat M. Halder,
MD, director of The Ethnic Skin Research Institute, Howard University,
Washington, D.C., told physicians at Dermatology Update.
Dark skins are especially prone to hyperpigmentation, and disorders
are expected to become more prevalent due to demographics. “Half
the population in North America in the mid part of this century
will be nonwhite,” said Dr. Halder, professor and chair, department
of dermatology, Howard University.
Current therapies are lengthy, some produce skin irritation, and
sun exposure reverses many of the benefits seen from treatment,
he said. But new therapies are in the pipeline, and Dr. Halder reviewed
these along with current therapies that act to inhibit tyrosinase,
remove melanin, or destroy melanin granules in the epidermis.
The first line of treatment is to reduce sun exposure, then follow
with monotherapy or combination therapy using phenolic and/or nonphenolic
agents. An SPF greater than 30 is recommended for the prevention
of melasma, solar lentigines, postinflammatory hyperpigmentation,
and the kind of photodamage seen particularly in Asians, where dark
macules and lentigines occur.
“UVA affects hyperpigmentation the most, and the effect of
UVA is present all year long,” he said. “Particularly
when treating melasma, a physical block may be better than a chemical
block.”
Current treatments in Canada
Hydroquinone, the gold standard for more than 50 years, interrupts
the tyrosine-tyrosinase pathway of melanin synthesis. Efficacy is
related to concentration. The over-the-counter concentration is
2%; 3% and 4% are typical prescription formulations and these have
a shorter onset of action. Higher concentrations can produce exogenous
ochronosis. Antioxidants and alpha hydroxy acids can be added to
increase penetration and enhance efficacy, Dr. Halder said.
“We still consider hydroquinone to be a good drug for hyperpigmentation,”
he said.
Topical corticosteroids affect the secretory function of melanocytes,
and also affect the enzyme tyrosinase.
Tretinoin has
a mild peeling effect that gets rid of melanin in keratinocytes.
A 1994 study at the University of Michigan showed good results when
tretinoin was used as a monotherapy for postinflammatory hyperpigmentation
in African-Americans. However, duration of treatment required was
20 to 40 weeks. Tretinoin can also be used in combination therapy.
Azelaic acid is a naturally occuring dicarboxylic acid. A 20% concentration
has been found to be as effective as 4% hydroquinone in treating
melasma, Dr. Halder said. “I use it in acne patients who have
postinflammatory hyperpigmentation to be applied once or twice a
day, all over the face. Azelaic acid selectively inhibits active
melanocytes so you won’t get a lightening of the whole facial
colour, you’ll get a selected lightening just on the hyperpigmented
macules.”
New treatments
Indication: Solar lentigines
2% 4-hydroxyanisole (Mequinol, Galderma) and 0.01% tretinoin is
a new, topical, combination treatment expected to arrive in the
U.S. and Canada this year.
Indication: Final depigmentation of very disfiguring vitiligo
Monobenzyl ether of hydroquinone (Benoquin) destroys melanocytes.
If used on normal skin, patients can develop a chemical type of
vitiligo. It is not indicated for treatment of hyperpigmentation.
It is available in the U.S., but not in Canada.
Indication: Melasma
Tri-Luma™ Cream (Galderma) is a triple-combination therapy
containing 0.01% fluocinolone acetonide, 4% hydroquinone, and 0.05%
tretinoin. It is available in the U.S., but not in Canada.
N-acetyl-4-cysteaminylphenol (NCAP) is being developed in Japan,
where hydroquinones are banned. In a study by Jimbow et al (Dermatol
Ther, Vol 14;2001:35-45) 4% NCAP produced moderate-to-marked improvement
of melasma in two to four weeks. The study also found that NCAP
is less irritating and more stable than hydroquinone. NCAP increases
intracellular glutathione by stimulating theomelanin rather than
new melanin. Tyrosinase activity is inhibited.
Kojic acid, 3%, is derived from Aspergillus oryzae. It also inhibits
tyrosinase, but does so indirectly by chelating copper. Its efficacy
is as good as hydroquinone. Long-term studies in Japan have found
there is potential for erythema and contact dermatitis.
Arbutin is the naturally occurring D-isomer of hydroquinone, found
as a natural plant product. Developed in Japan, it is used there
for postinflammatory pigmentation and melasma. It is not available
in North America. “Its action is concentration dependent, but
you can get a paradoxical hyperpigmentation with higher concentrations.
It is different from ochronosis,” Dr. Halder said.
Licorice extract, used widely in Egypt, chelates copper to inhibit
tyrosinase, as does Kojic acid. It also has corticosteroid effects,
making it a good drug to develop, Dr. Halder said. It is not available
in North America.
Niacinamide, studied in Japan for melasma treatment, has a different
mechanism of action: it inhibits transfer of melanosomes from the
melanocyte to the keratinocyte.
Mechanical therapies
Laser therapy, microdermabrasion and chemical peels are not effective
in treating melasma, Dr. Halder said, adding that some lasers have
been shown to destroy melanin granules in the epidermis.
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