doi: 10.1111/j.1346-8138.2007.00211.x Journal of Dermatology 2007; 34: 25–30 © 2007 Japanese Dermatological Association 25 Blackwell Publishing Asia ORIGINAL ARTICLE Efficacy and safety of serial glycolic acid peels and a topical regimen in the treatment of recalcitrant melasma Hakan ERBIL, Engin SEZER, Bülent TASTAN, Ercan ARCA, Zafer KURUMLU Department of Dermatology, Gülhane Military Medical Academy, School of Medicine, Etlik, Ankara,Turkey ABSTRACT Melasma is a common acquired disorder of facial hyperpigmentation. In this study we investigated the efficacy and safety of a combined treatment regimen including serial glycolic acid peels, topical azelaic acid cream and adapalene gel in the treatment of recalcitrant melasma. Twenty-eight patients with recalcitrant melasma were enrolled in a prospective, randomized, controlled trial lasting 20 weeks. The patients of the group receiving chemical peels underwent serial glycolic acid peels in combination with topical azelaic acid 20% cream (b.i.d.) and adapalene 0.1% gel (q.i.d., applied at night). The control group received only topical treatment including topical azelaic acid and adapalene. The clinical improvement was assessed with the Melasma Area Severity Index (MASI) at baseline and monthly during the 20-week treatment period. The results showed a prominent decrease in MASI scores at the end of the treatment in both groups, although the results were better in the group receiving chemical peels (P = 0.048). All patients tolerated the topical agents well with minimal irritation observed in the first few weeks of the therapy. Three patients in the glycolic acid peel group developed a mild-degree postinflammatory hyperpigmentation with total clearance at the end of the treatment period. Therefore, the present study suggests that combined treatment with serial glycolic acid peels, azelaic acid cream and adapalene gel should be considered as an effective and safe therapy in recalcitrant melasma. Key words: adapalene, azelaic acid, chemical peel, glycolic acid, melasma. INTRODUCTION Melasma is a common, acquired hyperpigmentary disorder characterized by irregular light or dark- brown macules in sun-exposed areas involving the face, neck and less commonly the hand and the forearm. The reported predisposing factors are sunlight exposure, pregnancy, oral contraceptive and hormone replacement therapies, cosmetics and genetic influences. Currently available treatment modalities include chemical peels, laser therapies and topical agents including azelaic acid, hydro- quinone, kojic acid and retinoic acids. 1–4 Unfor- tunately, the results of monotherapies are usually disappointing, especially in dark-skinned individuals. Superficial chemical peels with glycolic acid, trichloroacetic acid (TCA) and Jessner’s solution have been introduced as a treatment option in melasma, primarily acting as removing melanin from the epidermis. 5–7 A recent study indicated an additive inhibitory effect of glycolic acid on melanin synthesis through tyrosinase activity in melanoma cells. 8 Azelaic acid is a depigmenting agent that acts as a tyrosinase inhibitor without resulting in a potentially dangerous side-effect of exogenous ochronosis reported with the use of topical hydroquinone. 9 Ada- palene is a synthetic napthoic acid derivative with potent retinoic acid receptor activity. Adapalene has been documented to be a safe and efficacious monotherapy in the treatment of melasma, with a lower potential for skin-irritation compared with topical tretinoin. 10–12 In recent studies Combined treatment methods such as glycolic acid peels combined with Kligman’s Correspondence: Hakan Erbil, M.D., Assistant Professor, Department of Dermatology, GATA School of Medicine, Etlik, Ankara 06018, Turkey. Email: herbil@gata.edu.tr