A NEW TREATMENT OPTION IN SKIN HYPERPIGMENTATION TREATMENT: CYSTEAMINE
Melasma is a commonly encountered hyperpigmentation disorder that poses a therapeutic challenge for dermatologists. Melasma is a common, acquired skin disorder mostly affecting sun-exposed areas such as the cheeks, forehead, and upper lip. Melasma is seen in both sexes, but nearly 90 percent of those affected are women. It is particularly more common in darker skin types (Fitzpatrick skin types IV to VI) among Hispanics/Latinos, Asians, and African-Americans. The onset of melasma is during puberty or later, except in darker skin types who tend to develop this issue in the first decade of life. Although there are several triggering factors associated with the onset of melasma, its etiology remains unknown. While sun exposure and genetic factors are the most significant in both sexes, hormonal activity plays a more crucial role in women. Additionally, stress, certain cosmetic products, and medications containing phototoxic substances can cause flare-ups of this condition. Melasma is treated using monotherapies or therapy combinations, mostly fixed triple or dual combinations containing hydroquinone, tretinoin, corticosteroids, or azelaic acid. Modified Kligman’s formula is also quite effective. The aforementioned treatment regimens combined with UVA and UVB blocking sunscreens are mostly effective in epidermal melasma. Discontinuation of oral contraceptives, scented cosmetics, and phototoxic medications, along with UV protection, is beneficial in the treatment of melasma. Chemical peeling and alternative treatments containing glycolic acid are defined as second-line therapies after topical creams used in hyperpigmentation treatment. Laser treatments demonstrate limited efficacy and should be rarely used in melasma treatment. Combining topical agents such as hydroquinone, tretinoin, and corticosteroids along with sun avoidance, regular year-round sunscreen use, and patient education are currently the preferred practices for management.
Recently, cysteamine (mercaptamine) cream has shown promising results compared to placebo. Topical 5% cysteamine is an antioxidant and tyrosinase inhibitor proven to be effective in melasma treatment. However, to date, very few studies have evaluated the efficacy of cysteamine comparing its topical performance to hydroquinone for facial melasma.
Cysteamine is a natural product of L-cysteine metabolism in the human body and is a biological antioxidant produced during the coenzyme A metabolism cycle. It is naturally found in all mammalian cells. It exerts its depigmenting effect by inhibiting melanin synthesis. The exact mechanism of action of cysteamine on melanin synthesis is not yet fully understood. Cysteamine is a thiol compound, and such agents are known to be inhibitors of tyrosinase and peroxidase, two key enzymes involved in melanin biosynthesis. Finally, cysteamine HCl has been shown to increase intracellular glutathione levels. Cysteamine is a natural molecule with an excellent safety profile and known antimutagenic, antimelanoma, and anticarcinogenic effects. Considering the high efficacy of cysteamine HCl, it is likely to replace mutagenic and carcinogenic depigmenting agents such as hydroquinone in the near future. Cysteamine HCl acts not through a melanocytotoxic effect, but by inhibiting melanin synthesis. Treatment can be applied at any time of the year regardless of sunlight intensity. Cysteamine HCl can be used on any phototype and applied to the entire face and neck (including normal skin), avoiding the eye area. Brown spots respond faster than normal skin, and skin pigmentation becomes uniform as treatment progresses. In addition to reducing the pigmentation of spots by up to 77%, it does not exert active toxic effects and is not carcinogenic.
Cysteamine cream can be applied at any time of the year regardless of sunlight intensity. It is suitable for all skin phototypes. Upon contact with air, the rapid oxidation of cysteamine produces a red tint on the tube’s surface and a mild sulfur-like odor. This is normal and harmless. No studies have been conducted on its use in pregnant and breastfeeding mothers, and therefore cysteamine should not be used during pregnancy or while breastfeeding. Although cysteamine is generally very safe, minor undesirable side effects include; skin redness, dryness, or irritation. A burning sensation and mild redness may occur immediately after application, but typically disappear after 30 minutes. This is a normal reaction and may occur during the first few days of application. After 6 weeks of cysteamine application, the risk of skin irritation decreases significantly, and longer exposure durations are generally well tolerated.
Advantages of choosing cysteamine:
- Effective in melasma treatment
- Effective against sun-induced spots
- Effective against post-inflammatory hyperpigmentation
- Active and suitable for all skin tones
- Biocompatible, well-tolerated, and non-photosensitizing
- Safe for sensitive skin types
Adverse reactions:
- Warming sensation
- Redness resolving within 30 minutes
- Irritation and dryness
Theories on how it reduces skin pigment include:
- Inhibition of tyrosinase and peroxidase
- Dopaquinone scavenging
- Chelation of iron and copper ions
- Increased intracellular glutathione
Contraindications:
- Cannot be used by pregnant women, lactating mothers, and vitiligo patients
Use of cysteamine cream:
Cysteamine cream can be applied at any time of the year regardless of sunlight intensity. It is suitable for all skin phototypes. The cream is applied once daily to hyperpigmented facial and neck skin. It is washed off with soap and lukewarm water after 15 minutes. After gently drying the skin, a moisturizing cream is applied. To reduce irritation, it should be applied at least one hour after washing the skin. After 6 weeks of application, if there are no signs of skin irritation such as redness or dryness, the exposure duration can be gradually increased.
Reduction in pigmentation can be observed after 6 weeks. Optimal results can be achieved after 8 to 12 weeks. To maintain its effects, cysteamine cream should be continued indefinitely twice a week. Sunscreen should continue to be used year-round. It can be applied regardless of sun intensity and on any skin phototype.
Local side effects at the cysteamine cream application site may include:
A transient warming or burning sensation and redness that subsides within 30 minutes may be observed. To date (April 2017), no serious adverse events have been reported.
Cysteamine cream should not be preceded or followed immediately by face washing for the 15-minute daily application (the face can be washed at least one hour prior). A burning sensation and mild redness may occur immediately after application, but typically disappear after 30 minutes. This is a normal reaction and can happen in the first few days of application. Cysteamine is generally very safe. Concurrent use with other topical products should be avoided. The cream should be stored at room temperature.
Studies conducted with cysteamine:
A randomized, double-blind, single-center study conducted in Australia administered cysteamine cream and hydroquinone cream to 20 participants for 16 weeks; at week 16, the study was completed with 14 participants, including 5 participants in the cysteamine group and 9 patients in the hydroquinone group. The difference between the cysteamine and hydroquinone intention-to-treat groups was not statistically significant, and hydroquinone cream was generally better tolerated than cysteamine cream. In conclusion, this study suggests that topical cysteamine may have comparable efficacy to topical hydroquinone. Therefore, cysteamine provides a viable alternative for patients and clinicians wishing to avoid topical hydroquinone or seeking a different option. Although adverse effects were more common among participants using cysteamine compared to hydroquinone, these were mild and reversible. Larger studies comparing cysteamine and hydroquinone are needed to substantiate these findings.
In another study conducted to evaluate the efficacy and safety of topical 5% cysteamine and 4% hydroquinone in the treatment of facial melasma in women, a quasi-randomized, multicenter, evaluator-blinded clinical study was carried out on 40 women with facial melasma who applied 5% cysteamine (CYS) or 4% hydroquinone (HQ) nightly to hyperpigmented areas for 120 days. Both groups were required to use tinted sunscreen (SPF 50; PPD 19). Subjects were evaluated at baseline, 60, and 120 days of treatment for colorimetric brightness differences between melasma and adjacent unaffected skin. The Global Aesthetic Improvement Scale was used to assess the difference in skin appearance through standardized photographs; the mean reduction in mMASI scores was 24% for CYS and 41% for HQ at 60 days (P = 0.015), and 38% for CYS and 53% for HQ at 120 days (P = 0.017). Photographic evaluation revealed up to 74% improvement for both groups without a statistically significant difference between them (P = 0.087). MELASQoL scores showed a progressive decrease over time for both groups, despite a greater reduction for HQ after 120 days (P = 0.018). Colorimetric evaluation revealed progressive depigmentation in both groups, with no statistically significant difference between them (P > 0.160). No serious adverse events were detected in either group. Although their frequencies did not differ significantly between groups, the most common local adverse effects with cysteamine were erythema and burning (P > 0.170).
Conclusion: Despite lower performance than hydroquinone in reducing mMASI and MELASQoL in melasma treatment, cysteamine was proven to be safe, well-tolerated, and effective.
In another randomized double-blind clinical trial comparing the efficacy, safety, and tolerability of modified Kligman’s formula (MKF) and cysteamine 5% cream in subjects with epidermal melasma (Maryam Karrabi, Jennifer David, Mohammad Sahebkar ), a total of 50 subjects with epidermal melasma were included. Subjects received either 5% cysteamine cream or an MKF (modified Kligman’s formula: 4% hydroquinone, 0.05% retinoic acid, and 0.1% betamethasone). Cysteamine cream (applied once daily, 15-minute exposure) or MKF (applied once daily, overnight exposure) was used by the subjects for four consecutive months. Treatment efficacy was determined by the modified Melasma Area and Severity Index (mMASI) score, Investigator Global Assessment (IGA), and patient questionnaires.
Findings: The mean (SD) age of the subjects was 34.96 (6.17) and 35.76 (5.23) for the cysteamine and MKF groups, respectively. After 4 months, the mean mMASI score was 7.04 (2.23) in the MKF group and 6.09 (2.01) in the cysteamine group. At both prospective evaluation points (2 months, 4 months), the percentage reduction in the mMASI score was approximately 9% greater with cysteamine cream compared to MKF, and these differences were statistically significant (P = .005 and .001, respectively).
Conclusion: Cysteamine 5% cream demonstrated greater efficacy compared to MKF. Therefore, cysteamine 5% cream has been suggested to be more effective than MKF in the treatment of melasma, with the advantage of being significantly better tolerated. 18.09.2022
References:
1- Evaluation of the efficacy of cysteamine cream compared to hydroquinone in the treatment of melasma: A randomized, double-blind study
Jennifer Nguyen 1, Laura Remyn 2, In Young Chung 3, Anthony Honigman 4, Shima Gourani-Tehrani 5, Ilycia Wutami 2, Celestine Wong 5 6, Eldho Paul 7, Michelle Rodrigues 5 8
25.09.2022
Exp. Pharm. Ahmet Nezihi Pekcan
