AGENTS AFFECTING PIGMENTATION

HYDROQUINONE, MONOBENZONE, MEQUINOL

Hydroquinone, monobenzone (Benoquin, the monobenzyl ether of hydroquinone), and mequinol (the monomethyl
ether of hydroquinone) are used to reduce hyperpigmentation of the skin. Topical hydroquinone and mequinol
usually result in temporary lightening, whereas monobenzone causes irreversible depigmentation.
The mechanism of action of these compounds appears to involve inhibition of the enzyme tyrosinase, thus
interfering with the biosynthesis of melanin. In addition, monobenzone may be toxic to melanocytes, resulting in
permanent depigmentation. Some percutaneous absorption of these compounds takes place, because monobenzone
may cause hypopigmentation at sites distant from the area of application. Both hydroquinone and monobenzone
may cause local irritation. Allergic sensitization to these compounds can occur. Prescription combinations of
hydroquinone, fluocinolone acetonide, and retinoic acid (Tri-Luma) and mequinol and retinoic acid (Solage) are
more effective than their individual components.
TRIOXSALEN METHOXSALEN
Trioxsalen and methoxsalen are psoralens used for the repigmentation of depigmented macules of vitiligo. With the
recent development of high-intensity long-wave ultraviolet fluorescent lamps, photochemotherapy with oral
methoxsalen for psoriasis and with oral trioxsalen for vitiligo has been under intensive investigation.
Psoralens must be photoactivated by long-wave-length ultraviolet light in the range of 320-400 nm (UVA) to
produce a beneficial effect. Psoralens intercalate with DNA and, with subsequent UVA irradiation, cyclobutane
adducts are formed with pyrimidine bases. Both monofunctional and bifunctional adducts may be formed, the latter
causing interstrand cross-links. These DNA photoproducts may inhibit DNA synthesis. The major long-term risks
of psoralen photochemotherapy are cataracts and skin cancer.
SUNSCREENS
Topical medications useful in protecting against sunlight contain either chemical compounds that absorb ultraviolet
light, called sunscreens, or opaque materials such as titanium dioxide that reflect light, called sunshades. The three
classes of chemical compounds most commonly used in sunscreens are p-aminobenzoic acid (PABA) and its esters,
the benzophenones, and the dibenzoylmethanes.
Most sunscreen preparations are designed to absorb ultraviolet light in the ultraviolet B (UVB) wavelength range
from 280 to 320 nm, which is the range responsible for most of the erythema and tanning associated with sun
exposure. Chronic exposure to light in this range induces aging of the skin and photocarcinogenesis. Paraaminobenzoic acid and its esters are the most effective available absorbers in the B region.
The benzophenones include oxybenzone, dioxybenzone, and sulisobenzone. These compounds provide a broader
spectrum of absorption from 250 to 360 nm, but their effectiveness in the UVB erythema range is less than that of
p-aminobenzoic acid. The dibenzoylmethanes include Parasol and Eusolex. These compounds absorb wavelengths
throughout the longer ultraviolet A range, 320 nm to 400 nm, with maximum absorption at 360 nm. Patients
particularly sensitive to UVA wavelengths include individuals with polymorphous light eruption, cutaneous lupus
erythematosus, and drug-induced photosensitivity. In these patients, dibenzoylmethane-containing sunscreen may
provide improved photoprotection. Although not approved by the FDA at this time, terephthalylidene
dicamphorsulfuric acid (Mexoryl) appears to provide greater UVA protection than the dibenzoylmethanes.
The sun protection factor (SPF) of a given sunscreen is a measure of its effectiveness in absorbing erythrogenic
ultraviolet light. It is determined by measuring the minimal erythema dose with and without the sunscreen in a

group of normal people. The ratio of the minimal erythema dose with sunscreen to the minimal erythema dose
without sunscreen is the SPF. Fair-skinned individuals who sunburn easily are advised to use a product with an SPF
of 15 or greater.
GG
SUNSCREENS
Introduction
Photoprotection from the acute and chronic effects of sun exposure is readily available with sunscreens. The major
active ingredients of available sunscreens include chemical agents that absorb incident solar radiation in the UVB
and/or UVA ranges and physical agents that contain particulate materials that can block or reflect incident energy
and reduce its transmission to the skin. Many of the sunscreens available are mixtures of organic chemical
absorbers and particulate physical substances. Ideal sunscreens provide a broad spectrum of protection and are
formulations that are photostable and remain intact for sustained periods on the skin. They also should be
nonirritating, invisible, and nonstaining to clothing. No single sunscreen ingredient possesses all these desirable
properties, but many are quite effective nonetheless.
UVA Sunscreen Agents
Currently available UVA filters in the United States include (1) avobenzone, also known as Parsol 1789; (2)
oxybenzone (2-hydroxy-4-methoxy-benzophenone); (3) titanium dioxide; and (4) zinc oxide. Additional UVA
sunscreens, including ecamsule (MEXORYLSX and XL), bisethylhexyloxyphenol methoxyphenyl triazine
(TINOSORBS), and methylene bisbenzotriazolyl tetramethylbutylphenol (TINSORB M), are available in Europe
and elsewhere but not in the United States.
UVB Sunscreen Agents
There are numerous UVB filters, including (1) PABA esters (e.g., padimate O); (2) cinnamates (octinoxate); (3)
octocrylene (2-ethylhexyl-2-cyano-3,3 diphenylacrylate); and (4) salicylates (octisalate).
The major measurement of sunscreen photoprotection is the sun protection factor (SPF), which defines a ratio of
the minimal dose of incident sunlight that will produce erythema or redness (sunburn) on skin with the sunscreen in
place (protected) and the dose that evokes the same reaction on skin without the sunscreen (unprotected). The SPF
provides valuable information regarding UVB protection but is useless in documenting UVA efficacy because no
standard systems have been developed to measure UVA protection. Such protocols are needed because more than
85% of solar ultraviolet radiation reaching earth's surface is UVA, which penetrates more deeply into human skin
than does UVB and appears to play an important role in photoaging and photocarcinogenesis. Despite their
universal availability, a major problem with sunscreens is the fact that people do not use them on a regular basis. In
a population study evaluating the use of sunscreens in northern England, it was reported that only 35% of females
and 8% of males regularly used sunscreens (Ling et al., 2003). Furthermore, 22% of those surveyed used no
sunscreen at all, and 34% recalled at least one sunburn reaction in the previous 2 years.
There is evidence that the regular use of sunscreens can reduce the risk of actinic keratoses (Thompson et al.,
1993) and squamous cell carcinomas (SCCs) of the skin. One study noted a 46% decrease in the incidence of SCCs
in people who used sunscreen regularly for 4.5 years (Green et al., 1999).
Except for total sun avoidance, sunscreens are the best single method of protection from UV-induced damage to the
skin. There is a need for more definitive answers to questions related to the efficacy of sunscreens in reducing skin
cancer risk. Prospects for more effective photoprotection are excellent as better sunscreen components are
developed and as more careful evaluations are performed (Rigel, 2002).