Persistent pigmentation and erythema in acne patients are common problems that can cause distress to patients for much longer than acne itself. Lighter skinned patients frequently develop erythema (and pigmentation to a lesser degree) in areas where they once had acne lesions, while dark skinned patients typically present with dyschromia (erythema is likely present, but difficult to appreciate due to the color of the skin).¹

Surveying Available Treatments

Facial acne has a significant psychological impact and is itself associated with depression.² Moreover, facial erythema, scars, and dyschromia have their own psychosocial effects in social situations and the work environment. Research suggests that facial lesions, including scars and birthmarks, negatively impact individuals' performance in job interviews.³ Early, effective acne therapy to prevent the development of post-inflammatory hyperpigmentation (PIH), erythema, and scarring is imperative. The most common prescription medications to treat acne-related PIH include hydroquinones, retinoids, and azelaic acid.^4-7

Retinoids. Topical retinoids serve several functions in the skin, including normalizing follicular hyperkeratosis and reducing inflammation through their influence on toll-like receptors.⁸ First, topical retinoids help accelerate cell turnover and consequently reduce melanin content in the stratum corneum. They also may interfere with melanosome transfer of melanin to keratinocytes.4 Finally, thinning the stratum corneum can lead to enhanced penetration of other, concurrent topical lightening agents. Tretinoin 0.1% cream has been demonstrated to be effective for hyperpigmentation as monotherapy and in combination with hydroquinone.^4,5 Other topical retinoids, including tazarotene and adapalane, likely help pigmentation by the similar mechanisms as tretinoin.

Azelaic acid. Azelaic acid is a dicarboxylic acid found in nature in wheat, rye, or barley. Used commonly for the treatment of rosacea (or in some cases of acne), it possesses cytotoxic and anti-proliferate effects, in addition to anti-tyrosinase effects.6 Available as a 15% gel (Finacea, Bayer) or 20% cream (Azelex, Allergan), its use for hyperpigmentation is off-label. Azelaic acid may be used as monotherapy or in combination with other agents such as topical retinoids. Skin irritation is a concern when using azelaic acid, but it usually resolves with continued use.

Hydroquinone. Hydroquinone inhibits the activity of tyrosinase and may be considered the gold standard of skin lightening drugs.⁹ Irritation potential and the risk of developing exogenous ochronosis limit long-term use. While used effectively as monotherapy, hydroquinone is commonly combined with other agents such as topical retinoids.

Educate and Communicate

Topical lightening creams are only effective if patients adhere to the regimen. For that reason, perhaps the most important element to attaining success is patient education. Most of the bleaching agents have the potential to cause cutaneous irritation, which patients must be aware of. Overirritation itself can lead to additional PIH. Moreover, ideally only hyperpigmented lesions should be treated to prevent lightening of normal skin from hydroquinone. This may be challenging, depending on the extent of pigmentation of the skin. Application of a small amount of medication should be used to reduce the risk of irritation. (Usually a pea-sized amount is enough to cover the entire face.) While in some cases, the goal of therapy is twice-daily application, this may not be possible from the outset of treatment. Initially, evening or every-other-evening regimens should be employed and gradually advanced as tolerated.

Strict sunscreen use is critical to avoid UV-induced pigmentation of the skin. Finally, setting appropriate expectations, as with any therapy, is essential for success in the topical treatment of PIH. Improvement may not be obvious until after several months of continuous topical therapy.

Conclusion

Post-inflammatory hyperpigmentation is a significant source of morbidity in acne patients and can last longer than actual acne lesions themselves. Topical retinoids, azelaic acid, and hydroquinone can be used as monotherapy or in varying combinations to improve the appearance of pigmentation. Proper patient education, and continued treatment of underlying acne, is extremely important to ensure optimal outcomes.

Dr. Zeichner has served as a consultant or investigator for Allergan, Beiersdorf, Galderma, Medicis, Onset, Pharmaderm, Promius, and Valeant.

Joshua Zeichner, MD, FAAD is an Assistant Professor and Director of Cosmetic and Clinical Research in the Department of Dermatology at Mount Sinai Medical Center in New York.

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