Prevention and Treatment of the Aging Skin with Cosmeceuticals: Phenolic Skin Lightening Agents

Hyperpigmentation disorders are among the most common findings in dermatology practices. The majority of these pigmentation disorders are:

• Melasma
• Chloasma (Melasma affecting pregnant women)
• Solar Lentigines
• Post-Inflammatory Hyperpigmentation

While individuals of all ages and skin hues can be affected, some groups have an increased incidence of such diseases, like women of reproductive age and darker skin tones who are the most affected by melasma.

The key causes of hyperpigmentation are sun (UV) exposure, hormonal therapies or changes (pregnancy and contraceptives included), some medications, inflammatory diseases (such as acne) and genetic predisposition.

What are melasma and post-inflammatory hyperpigmentation?

• Melasma is a common acquired and localized disorder characterized by irregular light to dark brown macules and patches with well-demarcated borders, often symmetrically distributed on the areas affected. Face, neck and upper extremities are the most common affected regions.
• Post-Inflammatory hyperpigmentation (PIH) is another common condition that occurs as a consequence of cutaneous inflammation: this can be due to inflammatory dermatoses (such as acne), infections, traumas and reactions to medications or medical procedures. In the case of PIH the lesions have the same pattern and distribution as the causing condition, but the intensity of the hyperpigmentation is not related to the degree of the previous inflammation.

The main medical indications of the undermentioned phenolic compounds are the treatment of melasma and post-inflammatory hyperpigmentation, although they might as well be used as alternative and adjuvant therapies for the treatment of other disorders.

Hydroquinone (HQ)

Hydroquinone has been the treatment of choice for hyperpigmentation since 1961. Its therapeutic effects are limited to the area of application and are reversible. They become visible after four weeks of daily use.

HQ works by inhibiting tyrosinase, an enzyme that controls the production of melanin, which is the pigment responsible for our skin tone.

Hydroquinone is available in topical formulations usually ranging from 2% (OTC) to 4-10% (prescription only) concentration and might be combined with other agents like tretinoin, glycolic acid and corticosteroids. Higher concentrations, although more effective, are linked with augmented side effects. It is generally used in two to four months cycles.

Monobenzyl Ether of Hydroquinone (MBEH)

Also known as monobenzone, MBEH works similarly to HQ, but is metabolized by melanocytes (cells that produce melanin) into free radicals which are capable of permanently destroying the melanocytes. For this reason, the effects of MBEH are not reversible even after discontinuation of the topical therapy. Furthermore, its therapeutic effect is observed also on distant sites from the application area, thus is primarly used as a generalized depigmentation agent.

It usually takes 9-12 months of daily application to achieve the desired depigmentation.

N-Acetyl-4-S-Cysteaminylphenol (NCAP)

NCAP is a more stable and less irritating agent when compared to HQ. It works by tying to tyrosinase and therefore preventing it from binding to its target substrate in the melanocytes and producing melanin.

Its action is visible after two to four weeks of treatment.

Arbutin

Arbutin is a precursor form of hydroquinone present at high concentration in certain plants like bearberry, blueberry and cranberry.

It acts similarly to hydroquinone and suppresses the maturation of melanocytes as well, but there are fewer reports of irritation and other side effects.

Warnings and Advices

• Erythema, stinging, irritation and allergic contact dermatitis, nail discoloration, paradoxical post-inflammatory hyper-melanosis and ochronosis (blue-greyish pigmentation of the skin) are some of the reported possible side effects. For this reason, it is greatly advised to consult a dermatologist before using these products both for the OTC and for the prescription only formulations.
• No studies have been conducted to endorse the use of these topical formulations during pregnancy or while breastfeeding. Consult your physician for more information and before use.
• In 2006 the FDA and other regulatory agencies reported some evidence that hydroquinone might be carcinogenic and might cause ochronosis. However, those studies were conducted on animals only and were involving very high doses of HQ taken orally. Further studies mitigated those concerns and no human studies show such links. Nevertheless, it is still banned from sale in some countries.
• Melanin is the pigment responsible for our skin tone, but it is also the chemical that absorbs the majority of the UV rays that hit our skin, protecting it from sun damage and cancer. Hence, the use of a broad-spectrum SPF 50 sunscreen is strongly advised during and after treatment.

Last edit: 23/05/2018