Prime Journal Case study by Leonardo Marini, MD, PhD Reducing Stubborn Pigmentation With Cysteamine Cream

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Leonardo Marini, MD, PhD, discusses a recent case of treating melasma in a female patient with a new 5% cysteamine topical formulation


Stubborn pigmentation has long been a common problem that patients present to their dermatologists and aesthetic practitioners.

Over the years, a number of topical formulations have been used to reduce stubborn pigmentation with mixed results in terms of efficacy and side-effects. In the following case, we had a female customer presenting with pigment reduction across her face with a new topical formulation consisting of 5% cysteamine with positive results and no observable side-effects

LEONARDO MARINI, MD, PHD,  Medical Director of SDC — The Skin Doctors’ Center of Trieste, Italy

LEONARDO MARINI, MD, PHD, Medical Director of
SDC — The Skin Doctors’ Center of Trieste, Italy

A FORTUNATE WOMAN CRAVES NOTHING BUT A GOOD anti‑depressant cream, said a customer with long-lasting, unpleasant to be seen, skin pigmentation, desperate to find an effective and durable solution to the frustrating skin concern she faced reflected in the mirror every single day of her life. Stubborn pigmentation is a well-known reactive skin pigmentation concern that is difficult to reduce and control. In some cases, it can even variably affect mental health, social life, and emotional well-being of less fortunate customers. Stubborn pigmentation typically presents with irregular patches, dark yellow to variable hues of brown in colour, mostly distributed on sun-exposed facial skin regions1-3. Retrospectively, various natural and synthetic formulations have been proposed to reduce unpleasant skin pigmentations. Centuries ago, topical formulations containing ammonia salts of mercury and potassium hydroxide were used but their highly toxic behaviour, once discovered, made them less popular4,5. In the recent past, intensive research was devoted to finding a safe and reliable resolution to reduce unwanted skin pigmentations. Since the 1960s, some other agents has been considered as the gold standard topical anti- Stubborn pigmentation agent in the United States. After some time, several studies revealed that other agent-containing formulations, in spite of their significant degree of success, have a low safety profile. The increased risk of renal carcinoma noted in rodent models taking oral other agents as well as exogenous ochronosis induced by prolonged use of topical formulations containing this agent led to the release of a warning report from the World Health Organization in 1997. After that, the agent was banned and/or its use strictly regulated in several countries around the World7. In 1975, Albert Kligman introduced his triple-main-ingredient topical formula (KF). It contained other agents, retinoic acid, and dexamethasone synergistically acting together to produce an effective skin bleaching effect. After it was made available on the market, it proved to be the most effective topical solution to reduce Stubborn pigmentation 8,9. Despite its high degree of efficacy, variable levels of side-effects were observed, such as skin hypotrophy related to prolonged contact with topical corticosteroids contained in the formulation, ochronosis, irrigative skin alterations. These side-effects were observed more intensively as topical care progressed in time thus preventing long-term use of KF as maintenance therapy 10,11.

While other agents was having its golden time as a successful skin bleaching agent, research focusing on alternative, effective solutions still progressed, and in 1966, Chavin et al. introduced cysteamine. As a naturally synthesised anti-oxidant agent derived from L-cysteine, cysteamine showed excellent pigment suppressing properties when injected subcutaneously in black goldfish. Further studies were made and, in 2000, Qui et al. confirmed that cysteamine was to able to reduce melanin synthesis by 80% in cultured B16 melanocytes12,13.

Other independent studies also confirmed cysteamine’s stronger pigment correction effect when compared with other agents

Other independent studies also confirmed cysteamine’s stronger pigment reduction effect when compared with other agents14,15. In spite of its excellent pigment-suppressing properties, cysteamine had a major problem; its rapid oxidation was associated with the liberation of an extremely unpleasant odour preventing its use in any topical preparations. The solution to this seemingly unsolvable problem came, as it is often the case, after an accidental ‘error’ during a laboratory experiment. Behrooz Kasraee, an Iranian born dermatologist researcher, discovered how to neutralise cysteamine’s foul odour while preserving its pigment suppressing properties. In recent years, these important innovations led to the introduction of cysteamine in the highly competitive world of skin depigmenting agents and a 5% topical formulation was made available on the market. As it always happens when the medical devices market proposes new skin pigmentation suppressants, cautious optimism and investigative scepticism are the rule. We introduced this innovative topical formulation to two extremely cooperative customers affected by stubborn pigmentation. They were extremely frustrated by their unresponsive, long-lasting skin depigmenting concern. After discussing the rationale of this innovative topical care, along with its potential benefits and side effects, written informed consent was obtained. The first case was a 34-year-old female customer suffering from progressively worsening stubborn pigmentation for 2 years prior.

Her irregularly shaped pigmented brownish patches were most evident on her fronto-glabellar region, upper-lip and cheeks. Minimal spontaneous improvement was noted during winter months consistently followed by intense worsening associated with UV exposure during spring and summer, in spite of ‘religious’ use of high SPF (50+) balanced sunscreens.

Figure 1 (A) Prior to  treatment and (B) After 4  weeks of treatment

Figure 1 (A) Prior to

treatment and (B) After 4

weeks of treatment

Stubborn pigmentation onset was reported after one year of oral contraceptive medication. The customer reported two 6-month cycles of modified topical KF with a minimal depigmenting effect on her brown patches in spite of evident, disturbing skin irritation. The second case was a 54-year-old female customer who reported to be affected by hyperpigmentation for 6 years. Her pigmented patches were mostly distributed on the lateral thirds of her frontal region. As usually seen in this kind of reactive pigmentation concern, the clinical situation was reported to worsen after intense UV exposure. She tried three 6 month cycles of topical modified KF, which revealed progressively less effective skin pigmentation control with time. Both customers had a positive history of insufficiently protected, intense UV exposure during their younger years, followed by relatively recent, properly balanced high SPF sunscreens. Neither user reported irregularities associated with their menstrual cycles during the last 5 years.

Treatment plan

We always like to prepare the skin to improve and optimise trans-epidermal penetration of topical agent. Our protocol consists of four full face low-pressure microdermabrasion sessions (MegaPeel — Dermamed Solutions, USA), scheduled every 15 days. In addition, a twenty-minute contact 5% other agent peel-off mask (LEM— Laboratorio Ecoceutico Magistrale, Italy) was applied immediately after the first and last microdermabrasion sessions. As a second step, customers were instructed to apply Cysteamine - Intensive 5% cysteamine pigment corrector cream – 15-min skin contact time - at bedtime for 4 weeks followed by one application always at bedtime, two non-consecutive nights per week as maintenance therapy according to the producer suggested protocol. Morning topical skin care routine consisted of 15% azelaic acid gel (Finacea – Bayer, Germany) to be applied immediately after gentle facial miniaturization with spring thermal water (La Roche Posay Laboratories, France). This step was immediately followed by topical application of Hyalu B5 hyaluronic acid serum (La Roche Posay Laboratoires, France) and a soothing/hydrating cream (Cream for Intolerant Skin - Avene Laboratoires, France). Topical sun protection (Fotoprotector 100+ Spot-prevent ISDN-Spain) was recommended daily during the course of care.

Figure 2 (A) Prior to  treatment and (B) After 4  weeks of treatment

Figure 2 (A) Prior to

treatment and (B) After 4

weeks of treatment



Clinical exam and standard clinical photography (Canon digital camera with a 50 mm macro lens and dedicated TTL flashlight) revealed a drastic, almost uniform pigment correction of in the first case and a significant intensity decrease of localised pigmentation in the second customer. No side-effects or complications were reported or observed during the course of the correction. Customers’ clinical perception of Cysteamine Intensive Pigment Corrector Cream solution was reported good and effective (Figure 1). They both expressed a strong sense of positive confidence in the topical solution recommended.Our case report, even if stubborn pigmentation considering two customers only, showed that Cysteamine (5% cysteamine cream) was an extremely effective, well accepted, complication-free depigmenting formulation particularly considering that both cases have been previously reduced with multiple modified KF cycles. We can happily confirm that we are entirely in line with the results produced by other much more extensive studies recently published16–18. If we consider that cysteamine is a non-cytotoxic, non-mutagenic, and non-carcinogenic depigmenting agent compared with other agents containing formulations, there is little doubt about what to choose when planning stubborn pigmentation corrector. Very possibly the long-awaited anti-depressant skin bleaching cream might have been found after all.

LEONARDO MARINI, MD, PHD, Medical Director of SDC — The Skin Doctors’ Center of Trieste, Italy

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