J. Cosmet. Sci., 71, 385–397 (November/December 2020) 385 A Topical Depigmentation Program Against Hyperpigmentation Enhances the Benefi ts of Previously Performed Chemical Peeling Procedures of the Face MAURIZIO CAVALLINI, FABIO MONTANARO, and MARCO PAPAGNI , Unit of Dermatology and Dermatosurgery, CDI Hospital, Milan 20124, Italy (M.C., M.P.), Statistics and Data Management Unit, Latis S.r.l., Genova 16121, Italy (F.M.) Accepted for publication June 16, 2020. Synopsis Chemical peeling can reduce skin hyperpigmentation however, once exhausted its thinning action, the depigmentation process does not continue further. We carried out a monocentric, prospective, noncontrolled study aimed at the evaluation of the effi cacy, safety, ease of use, pleasantness, and tolerability of a depigmentation topical treatment program in women submitted to a previous chemical peeling. The topical treatment has been administered daily for 30 days to 16 women submitted to a chemical peeling containing a fi xed-dose combination of salicylic acid, pyruvic acid, and retinoic acid within 7 days before study inclusion. Target skin areas have been evaluated for melanin concentration and skin texture before peeling and at study visits 1 (after peeling) and 2 (after the 30-day treatment). The topical treatment program induced a decrease in melanin concentration between study visits 1 and 2 (-4.74% p = 0.0008). It reduced melanin concentration even further between the prepeeling period and visit 2 (-7.8% p 0.0001). Patients rated the depigmentation topical treatment program as “very simple” (87.5%) and “simple” (12.5%) to use and as “pleasant” (56.25%) and “very pleasant” (43.75%). Results support the use of the home-based depigmentation topical treatment program to potentiate the effectiveness of a previous chemical peeling in hyperpigmentation reduction. I N TRODUCTION C utaneous pigment disorders can affect both genders, with prevalence among female subjects, and with different etiology. Pigment disorders can cause an aesthetic discomfort that, in many cases, is quite relevant, representing a persistent psychosocial burden for the patient (1). Hyperpigmentation consists of localized dark skin patches caused by qualitative and quantitative alterations in pigment distribution. Cutaneous pigment dis- orders can be classifi ed as hypermelanosis, that is, an increased or altered distribution of the pigment melanin in the epidermis and/or dermis, and as endogenous or exogenous hyperchromia (e.g., due to accumulation of nonmelanin pigments, such as hemosiderin, a granular pigment derived from ferritin bilirubin, an orange–yellow pigment normally Address all correspondence to Marco Papagni at dottmarcopapagni@gmail.com.

JOURNAL OF COSMETIC SCIENCE 386 occurring during heme catabolism drugs etc.). Acquired forms of hypermelanosis can have several different causes (e.g., metabolic or endocrine disorders, defi ciencies, cutaneous injuries, infl ammatory dermatoses, and systemic and neurological diseases) (2,3). Melasma is the most frequent form of acquired hypermelanosis, occurring most commonly on the face and also in extrafacial areas (4), and is characterized by an increased deposition of melanin (5). Various epidemiological studies estimated the prevalence of melasma at 1% in the general population and 9–50% in higher risk populations (6,7). Morphologically, melasma presents as symmetric reticulated hyperpigmented patches with irregular bor- ders on the centrofacial region, malar cheeks, mandible, and rarely upper chest and ex- tremities (4). Melasma, rather than a rigid linear epidermal problem, is now considered a heterogeneous pathology derived from a complex interplay among melanocytes, kerati- nocytes, dermal fi broblasts, and vascular endothelial cells (8). Melanin is produced by melanocytes in the basal layer of the epidermis from the amino acid tyrosine, within organ- elles known as melanosomes, through a reaction catalyzed by the tyrosinase enzyme. Melanocytes then export mature melanosomes to nearby keratinocytes through their dendrites to induce pigmentation (9). Immunohistochemical studies on skin biopsies confi rmed a signifi cant increase in melanin in melasma but no quantitative increase in melanocytes in the hyperpigmented areas of skin that, however, resulted in larger and very prominent dendrites (10). The factors that can cause an increase in melanin concentra- tion are numerous and include, among others, hormonal and genetic factors, high exposure to ultraviolet rays, darker skin types, some drugs, infections, or infl ammatory processes (6,7). However, the pathogenesis of melasma is not yet fully understood. Increased ex- pression of the stem cell factor in the dermis and of the tyrosine kinase receptor c-kit in the epidermis has been suggested to play an important role in the mechanism of hyper- pigmentation in melasma (11). A relevant role in melasma has also been suggested for increased microcirculation, triggered by a signifi cantly increased level of the vascular endothelial growth factor (VEGF), a major angiogenic factor of the skin constitutively produced by keratinocytes and whose receptors are expressed both in melanocytes and vascular endothelial cells (12,13). The VEGF could have a direct infl uence on melanocyte behavior and melanogenesis through its receptors. Interestingly, the VEGF is known to stimulate the arachidonic acid release and the phosphorylation and activation of the cyto- solic phospholipase A2 (14). It is possible that the resulting metabolites from this path- way affect melanogenesis as well. T he result of increased melanin concentration is an uneven skin tone. Although common, the management of this disorder remains challenging, given the incomplete understanding of its pathogenesis, chronicity, and recurrence rates. Moreover, melasma treatment is quite challenging because of the presence of melanin deposits at varying depths in the epidermis and dermis (15), with dermal and mixed melasma (a combination of the epider- mal and dermal types) having the worse prognosis because many topical therapies are not able to target dermal melanophages (16). Several methods and strategies have been re- ported so far in the literature to address skin hyperpigmentation. The goal of melasma treatment is to decrease melanin production and increase its elimination. In addition to traditional treatments, there are also new p romising strategies, including oral, topical, and procedural therapies (5). Among them, the chemical peeling, also called “chemical resurfacing,” that consists in the application of one or more substances, in immediate or delayed sequence, which causes a chemical ablation of defi ned skin layers. This treatment leads to a uniform and taut skin, through the regeneration and repair mechanisms of the