Disorders of hyperpigmentation—melasma, postinflammatory hyperpigmentation, lichen planus pigmentosus, erythema dyschromicum perstans, and pigmented contact dermatitis, among others—are common and challenging to treat. Although they can affect individuals of all skin types, they most commonly are seen in skin of color; in fact, dyspigmentation is one of the most common chief concerns for which individuals of color see a dermatologist.1,2
For many years, hydroquinone (HQ) was one of the main options available for use as a lightening agent. Although effective, it has the risk of causing irritant dermatitis, potentially leading to further dyspigmentation, in addition to the risk of ochronosis with long-term use. It remains an important and useful treatment for pigmentary disorders, but there are numerous other lightening agents that also can be considered in the treatment of disorders of hyperpigmentation.
Herein, we provide recommendations for traditional and newer non-HQ lightening agents that can be considered when treating disorders of hyperpigmentation.
Traditional Non-HQ Lightening Agents
Retinoids—Retinoids are topical vitamin A derivatives that have been used safely and effectively for decades in the treatment of pigmentary disorders. Retinoids have multiple mechanisms of action in improving pigmentation. In addition to impeding tyrosinase induction, they inhibit pigment transfer to keratinocytes and lead to accelerated pigment loss due to epidermal shedding.3 Over-the-counter formulations include retinol, retinaldehyde, and adapalene. Prescription formulations include tretinoin and tazarotene in different strengths and vehicle formulations.4
Glycolic Acid—Glycolic acid is derived from sugarcane and is considered an α-hydroxy acid that leads to rapid desquamation of pigmented keratinocytes.5 Glycolic acid can not only be used in chemical peels but also in topical creams. It is the most common α-hydroxy acid peel and is sometimes paired with HQ and other topical lightening agents for increased penetration. Glycolic acid peels are available in concentrations of 20% to 70% and can be used at various depths. When used incorrectly, it can cause redness, burning, and even skin discoloration; however, when used at the proper concentrations and depth according to Fitzpatrick skin type, there typically are no notable adverse effects, and clinical results are favorable.
Kojic Acid—Kojic acid is a natural metabolite derived from fungi and is widely used in Asian countries. It works by inhibiting the catecholase activity of tyrosinase6 and typically is available in concentrations of 1% to 4%. A study suggested that a concentration of 1% or less typically is safe to use for prolonged periods without adverse effects. Although not more effective than HQ as a monotherapy, kojic acid has been shown to haveimproved efficacy when used in combination with other lightening agents.7
Azelaic Acid—Azelaic acid works by inhibiting tyrosinase, mitochondrial oxidoreductase activation, and DNA synthesis. It preferentially targets heavily pigmented melanocytes and possesses anti-inflammatory and antibacterial properties.8 A 20% concentration of azelaic acid was compared to HQ 4% for the treatment of melasma, and results revealed that the liposomal form of azelaic acid was considerably more tolerable than HQ 4% and also more effective.9