Rucinol

We conducted a review of topical agents currently used in melasma, discussing their mechanism of action, efficacy, safety, and tolerability, with an update on newer treatments.

A systematic review from PubMed database was performed, using PRISMA guidelines. The search was limited to English and Spanish studies that were double or single blinded, prospective, controlled or randomized clinical trials, reviews of literature, and meta-analysis studies.

348 studies were analyzed; 80 papers met inclusion criteria. Triple combination (TC) therapy and hydroquinone (HQ) are still the most well-studied agents with strong evidence-based recommendation. TC therapy remains the gold standard of care based on efficacy and patient tolerability. Evidence has shown ascorbic acid, azelaic acid, glycolic acid, kojic acid, salicylic acid, and niacinamide to be effective as adjuvant therapies with minimal side effects. Tranexamic acid (TA) and cysteamine have become recent agents of interest due to their good tolerability, however more trials and studies are warranted. Less evidence exists for other topical agents, such as linoleic acid, mulberry extract oil, rucinol, 2% undecylenoyl phenylalanine, and epidermal growth factors agents.

Some studies discussed represented a low sample size, and there is an overall lack of recent studies with larger populations and long-term follow up.

TC therapy continues to be the gold standard of care. Topical cysteamine and TA are newer options that can be incorporated as adjuvant and maintenance treatments into a patient's regimen. Cysteamine and topical TA have no known severe adverse effects. Evidence comparing other topical adjuvant treatments to HQ, maintains HQ as the gold standard of care.

Numerous medications are used to treat hyperpigmentation. However, several reports have indicated that repeated application of some agents, such as rhododendrol (RD), raspberry ketone (RK) and monobenzone (MB), can be toxic to melanocytes. Although these agents had severe side effects in human trials, no current in vitro methods can predict the safety of such drugs. This study assessed the in vitro effects of five depigmentary compounds including leukoderma‐inducing agents. In particular, we determined the effects of different concentrations and exposure times of different depigmentary agents on cell viability and melanogenesis in the presence and absence of ultraviolet B (UVB) radiation. Concentrations of RD, RK and MB that inhibit melanogenesis are similar to concentrations that are cytotoxic; however, concentrations of rucinol (RC) and AP736 that inhibit melanogenesis are much lower than concentrations that are cytotoxic. Furthermore, the concentrations that cause toxic effects depend on exposure duration, and prolonged exposure to RD, RK and MB had more cytotoxic effects than prolonged exposure to RC and AP736. The cytotoxic effects of RD and RK appear to be mediated by apoptosis due to increased expression of caspase‐3 and caspase‐8; UVB radiation increased the cytotoxicity of these agents and also increased caspase activity. Our results indicate that different leukoderma‐inducing compounds have different effects on the viability of normal epidermal melanocytes and suggest that the in vitro assay used here can be used to predict whether an investigational compound that induces leukoderma may lead to adverse effects in human trials.