Topical Stabilized Cysteamine as a New Treatment for Hyperpigmentation Disorders: Melasma, Post-Inflammatory Hyperpigmentation, and Lentigines

Cysteamine is an aminothiol naturally present in cells of the human body as an antioxidant resulting from the degradation of Coenzyme A.¹ Physiological levels are well distributed in mammalian tissues. Highly concentrated in human milk, cysteamine acts as an intrinsic antioxidant and is known for its protective role.² It was originally evaluated in the 1950s for its protection properties against ionizing radiation and in the 1970s for the treatment of cystinosis.^3,4 Today it is still the first and only drug approved by the FDA for this orphan disease.⁵ As a potent antioxidant, cysteamine is known to be one of the most potent depigmenting agents available. This has been confirmed through several in vivo animal studies over the past few decades.^6,7 Other animal studies have verified it to have significantly higher efficacy as a depigmenting agent when compared to hydroquinone in vivo.^8,9 However, due to a very offensive odor and rapid oxidation, the use of cysteamine as a topical treatment was postponed until recent years, when its stabilization was achieved leading to an acceptable formulation for topical application (stabilized-cysteamine-5% Cream).¹⁰ In 2015 this formulation was proven to be effective for the treatment of melasma.¹¹ Since then, new hyper-pigmentary uses for topical stabilized cysteamine (st.Cys) have emerged following its demonstrated efficacy in multiples clinical studies and case reports. In this review, we will discuss clinical efficacy, safety and tolerability of st.Cys in the treatment of different skin hyperpigmentation disorders such as melasma, post-inflammatory hyperpigmentation, and lentigines.

Depigmenting Mechanism of Action of Thiols
Cysteamine is an aminothiol and its method of depigmenting action is not yet fully understood.

Some thiol molecules are known to inhibit tyrosinase and peroxidase, essential enzymes in the melanogenesis pathway leading to the conversion of tyrosine into dopaquinone, and the polymerization of indoles into melanin, respectively (Figure 1).¹²

As a copper and iron ion chelating agent, it is suggested that cysteamine could slow down the conversion of Tyrosine into dopaquinone, by preventing Fenton-type reactions.^13,14

Thiols, can also increase levels of intracellular glutathione, amplifying natural depigmenting effects.^14,15

As a known antioxidant, cysteamine quenches hydroxy free radicals.16 Antioxidant agents play a key role in the inhibition