Successful Treatment of Recalcitrant Melasma with Picolaser and Isobionicamide-Cysteamine Combination

J Clin Aesthet Dermatol. 2025;18(2):30–32.

by Corey L. Hartman, MD; Michaela Crawford, BS; Cheri Frey, MD; Rawn Bosley, MD; Riccardo Sfriso, PhD; Laure Dirlewanger, MS; and Behrooz Kasraee, MD

Dr. Hartman is with Skin Wellness Dermatology in Birmingham, Alabama, and the Department of Dermatology at the University of Alabama Heersink School of Medicine in Birmingham, Alabama. Ms. Crawford is with the Meharry Medical College School of Medicine in Nashville, Tennessee. Dr. Frey is with the Department of Dermatology at Howard University in Washington, District of Columbia. Dr. Bosley is with Signature Dermatology and Aesthetics in Grapevine, Texas. Dr. Sfriso and Ms. Dirlewanger are with Scientis SA in Geneva, Switzerland. Dr. Kasraee is with Scientis SA in Geneva, Switzerland and Centre de Dermatologie de Cornavin in Geneva, Switzerland.

FUNDING: No funding was provided for this article. 

DISCLOSURES: Dr. Kasraee is a shareholder and the chief scientific officer of Scientis SA. Ms. Dirlewanger and Dr. Sfriso are employees of Scientis SA. Drs. Kasraee, Sfriso, and Dirlewanger did not have a role in data collection and analysis. The remaining authors have no conflicts of interest to declare.

ABSTRACT: Melasma is a highly recurrent disorder that is challenging to treat and significantly affects the quality of life of patients. Cysteamine is an endogenous antioxidant produced during the coenzyme A metabolism cycle and is naturally present in all mammalian cells. The depigmenting efficacy of topical cysteamine has been shown in several double-blind, randomized, placebo-controlled clinical trials. Isobionicamide is a derivative of vitamin B3 and a new depigmenting agent that inhibits melanosomal transfer and was found to potentiate cysteamine’s inhibitory effect on tyrosinase. Picosecond lasers have been shown to be effective in treating melasma in dark-skinned individuals. Herein, we report the case of a 50-year-old patient (phototype V) with recalcitrant melasma who significantly responded to picosecond laser associated with the topical application of isobionicamide-cysteamine. 

Keywords: Melasma, hyperpigmentation, combination treatment, laser, cysteamine, isobionicamide

Melasma is a symmetrical hypermelanosis characterized by well-defined light-to-dark brown macules and patches on sun-exposed areas. The etiology of melasma is still unknown. Sun exposure, hormonal changes, genetic predisposition, pregnancy, and cosmetics are some of the etiological factors of melasma.¹ 

Topical products are the first-line treatment for melasma, but their efficacy can be limited. Kligman’s formula, a triple combination cream containing a combination of hydroquinone, retinoic acid, and a corticosteroid, is the most effective first-line topical treatment for melasma. However, there are concerns regarding its long-term safety due to potential side effects, such as ochronosis, skin atrophy, and irritation.^1,2 

A novel topical treatment containing the isobionicamide-cysteamine complex (Cyspera Intensive System™; Scientis SA, Switzerland) has been shown to be as effective for melasma as Kligman’s formula, but without the risks associated with hydroquinone and corticosteroids.³ Additionally, isobionicamide has been shown to exert anti-inflammatory activity, suggesting possible, but unevaluated, efficacy in preventing post-inflammatory hyperpigmentation.⁴

Laser treatment can be employed in combination with topical therapy to significantly enhance depigmentation of the lesional skin. When lasers are used to treat melasma, various adverse reactions may occur, such as edema, erythema, scaling, and burning. These normally resolve rapidly after treatment. Nevertheless, there are risks of post-inflammatory hyperpigmentation and hypopigmentation associated with laser treatment of melasma, especially in patients with darker skin.⁵ These risks are less present with picosecond lasers, but might still occur in a minority of patients, depending on their phototype, skin sensitivity, and the laser parameters utilized.^6,7

Case presentation. A 50-year-old female patient with phototype V consulted our clinic in December 2021. She presented pronounced skin discoloration on the inferior forehead, left lip, and upper lip. The discoloration was darker than surrounding normally pigmented skin and moderate in severity. Discoloration was present for two years. The patient had no history of birth control pill use, itching, new medication, pregnancy, prior rashes, sunlight exposure, or trauma. In an attempt to treat the skin discoloration, the patient tried specific beauty care regimens and topical vitamin C capsules. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

The patient was diagnosed with melasma with defined hyperpigmented patched in the periorbital/malar distribution. The patient was prescribed mineral sunscreen (Eryfotona Actinica; Isdin), Complexion Blending Lotion 8% (Skin Wellness Dermatology; Birmingham, Alabama) which included the following skin depigmenting agents: kojic acid, arbutin, vitamin C, curcuminoids, and hexylresorcinol, and a cream containing a retinoid combined with an alpha hydroxy acid (SB AlphaRet Cream; Skinbetter Science). Clinical images were acquired before the beginning of treatment using an artificial light source. Follow-up was scheduled at three months.

In March 2022, the patient’s melasma was found to be inadequately controlled. The patient was prescribed to continue treatment with Eryfotona Actinica and retinoid/AHA cream, but discontinued the Complexion Blending Lotion. Instead, Cyspera Intensive System™ (Scientis SA, Switzerland) was recommended. Cyspera Intensive™ was applied daily to the face and washed off after 15 minutes using Cyspera Neutralize™ (Scientis SA, Switzerland). Then, after tapping the skin dry, Cyspera Boost™ (Scientis SA, Switzerland) was applied as a leave-on. 

A session of picosecond laser (PicoSure®, Cynosure) was performed. The patient was made aware of the risks associated with the procedure, including but not limited to crusting, scabbing, blistering, scarring, darker or lighter pigmentary changes, paradoxical hair regrowth, incomplete removal of hair, and infection. 

Four months later, in July 2022, the patient returned to the clinic for a follow-up visit. The patient followed the treatment plan as directed and demonstrated visible improvement in her condition. Clinical images were acquired and compared with those obtained at the first visit (Figure 1). 

Discussion

The management of melasma is challenging. Extreme caution should be taken, especially in patients with darker skin tones, as they are more prone to develop post-inflammatory hyperpigmentation following procedural treatments, with consequent aggravation of the melasma condition.⁸

Isobionicamide is a novel depigmenting molecule from the pyridine family that occurs naturally in common bean (Phaseolus vulgaris L.) root exudates.⁹ Certain molecules from the pyridines are known to be potent inhibitors of melanosomal transfer.¹⁰ Isobionicamide has recently been combined with cysteamine, a known skin-depigmenting compound, to obtain a more potent depigmenting formula.^3,11–13 Isobionicamide also exerts an anti-inflammatory action that helps reduce the irritant effect of cysteamine observed in some patients.

This synergistic isobionicamide-cysteamine complex has recently been tested and compared with Kligman’s formula for the treatment of melasma in a clinical trial. The trial showed that isobionicamide-cysteamine provided the same efficacy and onset of action as the gold-standard treatment for melasma while being well tolerated by the patients during the 16 weeks of the study.³

The case reported herein provides evidence that combination treatment with picosecond laser procedure plus topical isobionicamide-cysteamine treatment can lead to satisfactory results, even in a patient resistant to multiple combination topical therapies. The clinical response to the combination of picolaser and isobionicamide-cysteamine was evident in the follow-up visit, suggesting that the combination treatment was successful. The skin displayed a more even tone, increased luminosity, radiance, and improved texture. Importantly, no adverse events were reported or observed during treatment. The patient reported high satisfaction with the treatment. 

Conclusion

Considering the safety of cysteamine, even as long-term maintenance therapy, the increased depigmentation efficacy when combined with isobionicamide, and the possibility of combining it with in-office procedures, there is hope that melasma treatment could become a more manageable condition in the near future. Randomized clinical studies that include a larger sample size of participants are required to support and confirm the initial promising results observed in this case report.  

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