Reducing Carbon Dioxide Laser-Induced Postinflammatory Hyperpigmentation with Prophylactic Photobiomodulation: A Case Study.

Objective: This study aimed to investigate the effectiveness of prophylactic photobiomodulation (PBM) in reducing postinflammatory hyperpigmentation (PIH) induced by carbon dioxide (CO2) laser resurfacing in a patient with periorbital syringomas. Background: PIH is a common condition characterized by abnormal skin pigmentation after an inflammatory process occurring in up to 20-30% of patients undergoing CO2 laser resurfacing. Methods: The patient was treated with PBM using a pulsed home-use device at 630 nm before and after CO2 laser treatment. The patient was asked to treat the right periorbital area before and after the CO2 laser treatment, which was continued once a day for 2 consecutive weeks. Results: At 12 weeks, PIH was significantly reduced on the treated side compared with the contralateral untreated side (leading to persistent erythema at 6 months). Conclusions: This is the first report of prophylactic treatment of CO2 laser-induced dyschromia using PBM.

Pycnogenol® prevents skin hyperpigmentation following sclerotherapy.

BACKGROUND: The aim of this registry supplement study was to evaluate the effects of the oral supplement Pycnogenol® on possible skin discolorations or other minor skin changes after varicose vein sclerotherapy in comparison with a standard management (SM). METHODS: One hundred sixty-one subjects completed the study. 84 took Pycnogenol® from the day before sclerotherapy for 12 weeks and followed SM. 77 followed SM only and served as controls. 420 injection sites were followed-up in the Pycnogenol® group and 431 in the control group. The number of injected veins (using only Aetoxysklerol) was on average 4-8 veins/patient. No side effects were observed for the SM or for supplementation. Pycnogenol® supplementation showed a good tolerability. The two management groups were comparable for age, sex and veins distribution at inclusion. RESULTS: After 12 weeks, skin discoloration assessed by a skin staining score was generally significantly lower and less frequent (P<0.05) with Pycnogenol® with a score of 0.4±0.2 compared to controls (with a score of 2.1±0.4). In addition, the number of stains per treated vein was significantly lower in the Pycnogenol® group than the control group. CONCLUSIONS: Varicose vein sclerotherapy is a minimally invasive procedure almost without complications. Pycnogenol® intake appears to improve healing and prevent skin discolorations after injection of the sclerosing agent. To verify this effect of Pycnogenol®, more studies for a longer period are needed.

Importance of treating acne sequelae in skin of color: 6-month phase IV study of trifarotene with an appropriate skincare routine including UV protection in acne-induced post-inflammatory hyperpigmentation.

BACKGROUND: Acne-induced hyperpigmentation (AIH) may accompany acne vulgaris (AV) inflammation in all skin phototypes. Trifarotene has shown depigmenting properties in vivo. This study evaluated trifarotene plus skincare because it is increasingly recognized that holistic AV management should include skincare and treatments. METHODS: This is a phase IV double-blind, parallel-group study of patients (13-35 years) with moderate AV and AIH treated with trifarotene (N = 60) or vehicle (N = 63) plus skincare regimen (moisturizer, cleanser, and sunscreen) for 24 weeks. Assessments included the AIH overall disease severity (ODS) score, post-AV hyperpigmentation index (PAHPI), exit interviews, photography, and acne assessments. Standard safety assessments were included. RESULTS: Trifarotene 50 µg/g cream improved significantly from baseline in ODS score versus vehicle (-1.6 vs. -1.1, P = 0.03) at Week 12, but scores were comparable between groups at Week 24 (primary endpoint). Trifarotene had a better reduction in PAHPI score at Week 24 (-18.9% vs. -11.3% vehicle, P < 0.01). Lesion count reductions were higher with trifarotene at Week 12 versus vehicle (P < 0.001) and at Week 24 (P < 0.05), as were IGA success rates versus vehicle at Weeks 12 (P < 0.05) and 24 (P < 0.05). Patients agreed that the skincare regimen contributed to less irritation, making treatment adherence easier. Photography showed improvements in pigmentation and erythema across all skin types. AEs were more common in the vehicle group versus trifarotene (30.2 vs. 16.7%, respectively). CONCLUSIONS: In all skin phototypes, there was more rapid improvement in the ODS and PAHPI scores with trifarotene by Weeks 12 and 24, respectively. The combination of trifarotene and skincare correlated with high patient satisfaction and adherence to the treatment protocol.

Guide to tinted sunscreens in skin of color.

Disorders of hyperpigmentation, such as melasma and post-inflammatory hyperpigmentation, disproportionately affect skin of color and have a profound impact on quality of life. Exposure to ultraviolet light (UVL) is a well-documented factor in these disorders. However, recent studies show that visible light (VL) is a significant and underrecognized contributor to hyperpigmentation, especially in skin of color. Our objective is to review the role of VL in disorders of hyperpigmentation and that of tinted sunscreens in protecting against VL. Tinted sunscreens containing iron oxides should be recommended over nontinted sunscreens for patients prone to disorders of hyperpigmentation, as iron oxides protect against VL in addition to UVL. Tinted sunscreens are more effective than nontinted sunscreens in preventing melasma relapses and reducing hyperpigmentation, and they may also enhance the depigmenting efficacy of topical hydroquinone. In the search for an ideal tinted sunscreen for a particular patient, several factors must be considered, including a broad spectrum with adequate coverage of both UVL and VL, tint, formulation texture, active ingredients, and cost. VL is increasingly recognized as a major contributor of hyperpigmentation, and adequate treatment for disorders of hyperpigmentation should include protection against VL. Tinted sunscreens are ideal but require consideration of cosmesis, efficacy, and affordability.

The role of epidermal growth factor-containing topical products on recovery and post-inflammatory hyperpigmentation prevention after laser surgeries: A systematic review and meta-analysis.

BACKGROUND: Post-inflammatory hyperpigmentation (PIH) is a common complication after laser surgeries. Recent studies applied epidermal growth factor (EGF) on the lasered area after laser surgery to decrease the incidence of PIH with controversial results. Therefore, a comprehensive literature review of randomized controlled trials (RCTs) was conducted to investigate the issue. METHODS: Two reviewers independently searched the literatures, extracted, and analyzed the data. A total of seven RCTs involving 169 patients were included to evaluate the efficacy of EGF on recovery and PIH prevention after laser surgery. RESULTS: The results show that the incidence of PIH in the EGF group was relatively lower than that in the control group, although the difference was not statistically significant (OR 0.64, 95% CI 0.33 ~ 1.25, p = 0.19). However, the EGF groups had a significant decrease in melanin index (MI) scores at the 1st month after the laser surgery when compared to the control groups (SMD -1.57, 95% CI -2.83 ~ -0.31, p = 0.01). In addition, the patients on the EGF side rated significantly higher satisfactory scores (SMD 0.49, 95% CI 0.22 ~ 0.76, p = 0.0004). There was no significant difference as regard to changes in MI at the 2nd week and 2nd month, erythema index (EI), and trans-epidermal water loss (TEWL) at days 3 and 7 after laser therapy, respectively. CONCLUSION: The current meta-analysis found a limited temporary inhibitory effect of EGF-containing topical products on PIH with no significant effect on reducing post-laser erythema or promoting epidermal barrier repair. More studies are needed in the future due to the small sample size and marked intergroup heterogeneities.

Suture Selection to Minimize Postoperative Postinflammatory Hyperpigmentation in Patients With Skin of Color During Mohs Micrographic Surgery.

The effects of suture selection on postinflammatory hyperpigmentation (PIH) in patients with skin of color who have had Mohs micrographic surgery (MMS) are limited. During the COVID-19 pandemic, fast-absorbing gut sutures reduced the need for in-person follow-up visits without increasing the frequency of postoperative complications. Although absorbable gut sutures are popular, they are highly reactive and can induce inflammation in patients with skin of color. Choosing less inflammatory, nonabsorbable sutures can improve the cosmetic outcome for patients with skin of color who undergo MMS.

Aloe vera gel for prevention of chemotherapy-induced hyperpigmentation: Four case reports.

RATIONALE: This study aimed to evaluate the efficacy of topical application of Aloe vera gel in preventing chemotherapy-induced hyperpigmentation (CIH). CIH is a common side effect of chemotherapy that causes skin irritation, redness, and itching. Aloe vera has been studied for its potential use in treating radiation-induced dermatitis, which may help alleviate some of the symptoms associated with this condition. PATIENT CONCERNS: In this study, 4 children requiring curative chemotherapy were prospectively enrolled and treated with Aloe vera gel. DIAGNOSIS: Acute skin reactions were monitored and classified according to the Common Terminology Criteria for Adverse Events Grading Scale. INTERVENTIONS: Patients were asked to use the gel on one-half of the body field twice daily from the beginning of treatment until 4 weeks after the completion of chemotherapy, with no medication to be used on the other half. OUTCOMES: The results indicate that applying Aloe vera gel may reduce the visibility of hyperpigmentation at subsequent time points. The most important observation was that the continued application of Aloe vera gel 4 weeks after the completion of chemotherapy was effective in reducing the grading of CIH. LESSONS: These effects highlight the potential of Aloe vera gel as a topical onconutraceutical treatment for CIH.

The effect of low-intensity cold atmospheric plasma jet on photoaging-induced hyperpigmentation in mouse model.

BACKGROUND: Cold atmospheric plasma (CAP) produces reactive oxygen/nitrogen species (RONS) in the target and can induce cytoprotective effects by activating hormesis-related pathways when its intensity is in the low range. OBJECTIVES: The aim of this study is to evaluate the effect of low-intensified CAP (LICAP) on skin with photoaging-induced hyperpigmentation in an animal model. METHODS: Changes in cell viability and RONS production following LICAP treatment were measured. For the in vivo study, 30 hairless mice underwent antecedent photoaging induction followed by the allocated therapy (i.e., LICAP, topical ascorbic acid (AA), or both). During the first 4 weeks of the treatment period (8 weeks), ultraviolet (UV)-B irradiation was concurrently administered. Visual inspection and measurement of the melanin index (MI) were performed to assess the change in skin pigmentation at Weeks 0, 2, 4, 6, and 8. RESULTS: RONS production increased linearly until the saturation point. Cell viability was not significantly affected by LICAP treatment. At Week 8, MI was significantly decreased in every treatment group compared with the values at Week 0 and Week 4. The treatment effect of the concurrent therapy group was superior to that of the LICAP and AA groups. CONCLUSION: LICAP appears to be a novel modality for photoprotection and pigment reduction in photodamaged skin. LICAP treatment and topical AA application seem to exert a synergistic effect.

Sun exposure, a relevant exposome factor in acne patients and how photoprotection can improve outcomes.

BACKGROUND: Acne pathophysiology includes a complex interaction among inflammatory mediators, hyperseborrhea, alteration of keratinization and follicular colonization by Propionibacterium acnes. AIMS: To describe the impact of the exposome on acne and how photoprotection can improve outcomes. METHODS: A narrative review of the literature was carried out; searches with Google Scholar and Pubmed from January 1992 to November 2022 were performed. The keywords used were "acne," "sunscreens," "photoprotection," "cosmetics," "cosmeceuticals," "pathogenesis," "etiology," "exposome," "sunlight," "stress," "lack of sleep," "diet," "postinflammatory hyperpigmentation," "pollution," "exposome," "ultraviolet radiation," and "visible light." RESULTS: Environmental factors such as solar radiation, air pollution, tobacco consumption, psychological stress, diverse microorganisms, nutrition, among others, can trigger or worsen acne. Solar radiation can temporarily improve lesions. However, it can induce proinflammatory and profibrotic responses, and produce post-inflammatory hyperpigmentation and/or post-inflammatory erythema. While photoprotection is widely recommended to acne patients, only four relevant studies were found. Sunscreens can significantly improve symptomatology or enhance treatment and can prevent post-inflammatory hyperpigmentation. Furthermore, they can provide camouflage and improve quality of life. Based on acne pathogenesis, optimal sunscreens should have emollient, antioxidant and sebum controlling properties. CONCLUSIONS: The exposome and solar radiation can trigger or worsen acne. UV light can induce post-inflammatory hyperpigmentation/erythema, and can initiate flares. The use of specifically formulated sunscreens could enhance adherence to topical or systemic therapy, camouflage lesions (tinted sunscreens), decrease inflammation, and reduce the incidence of post-inflammatory hyperpigmentation/erythema.

Human dermal fibroblast-derived extracellular matrix reduces postinflammatory hyperpigmentation after fractional carbon dioxide laser facial resurfacing in Asians.

BACKGROUND: Extracellular matrix (ECM) components promote the development of skin wounds by providing biological scaffolds and regenerative microenvironments. AIMS: To evaluate the beneficial effects of human dermal fibroblast-derived ECM after fractional carbon dioxide laser resurfacing in Asians. PATIENTS/METHODS: In this double-blind, randomized, vehicle-controlled, split-face study, 15 participants with features of facial skin aging were treated with a single session of fractional carbon dioxide laser, followed by the application of either ECM (ECM group) or placebo (control group). In vivo skin parameters were measured at baseline and after 4 and 12 weeks of treatment using the Antera 3D®, Cutometer® MPA580, Dermascan®, and Tewameter®. RESULTS: A total of 14 participants (mean age 45.1 ± 9.7 years) completed the study. The change in melanin level was significantly lower in the ECM group than in the control group at week 12 (p < 0.05). Transient increase in erythema level was observed at week 4 in the control group, and the change in the erythema level was greater in the control group than in the ECM group (p = 0.014). Though the ECM group showed improvements in the dermal density, texture, transepidermal water loss, marionette lines (volume, maximum depth, and average depth), and nasolabial folds (volume, maximum depth, and length), no significant differences were found between the two groups. Treatment-related adverse events were not reported. CONCLUSIONS: We suggest that human dermal fibroblast-derived ECM may be used as adjunctive therapy after fractional carbon dioxide resurfacing to prevent postinflammatory hyperpigmentation in Asians.

Disorders of hyperpigmentation. Part II. Review of management and treatment options for hyperpigmentation.

Key challenges in the management of pigmentary disorders such as melasma and postinflammatory hyperpigmentation are their resistance to treatment, tendency to recur after treatment, and the risk of exacerbating hyperpigmentation with many treatment modalities. The second article in this 2-part continuing medical education series on pigmentary disorders focuses on the evidence behind medical and procedural treatments of dyschromias, including photoprotection, topical lightening agents, oral agents, chemical peels, and laser therapy.

Incobotulinum Toxin Type A for Treatment of Ultraviolet-B-Induced Hyperpigmentation: A Prospective, Randomized, Controlled Trial.

Incobotulinum toxin A (IncoBoNT-A) is effective in preventing ultraviolet B (UVB)-induced hyperpigmentation. This prospective, randomized, controlled study aimed to evaluate the effect of IncoBoNT-A on the treatment of UVB-induced hyperpigmentation in 15 volunteers. Five hyperpigmentation squares (2 × 2 cm) were induced by local UVB on the abdomen at baseline. At Day 7, each site was randomized to receive no treatment (control), normal saline, or intradermal IncoBoNT-A injection with 1:2.5, 1:5, and 1:7.5 dilutions (12, 6, and 4 units, respectively). The mean lightness index (L*), hyperpigmentation improvement score evaluated by blinded dermatologists, and participant satisfaction scores were obtained at Days 21, 28, and 35. At Day 21, improvements in mean L* of 1:2.5, 1:5, and 1:7.5 IncoBoNT-A-treated, saline-treated, and control sites were 14.30%, 12.28%, 6.62%, 0.32%, and 4.98%, respectively (p = 0.86). At Day 28, the improvement in mean L* in IncoBoNT-A-treated groups was superior to that in the other groups. In terms of the hyperpigmentation improvement score, 12 participants (80%) experienced better outcomes with the IncoBoNT-A-injected site compared with the other sites. IncoBoNT-A, especially at higher concentrations, showed some positive effects on the treatment of UVB-induced hyperpigmentation. This may serve as an adjuvant treatment for hyperpigmentary conditions that are aggravated by UVB.

A new in vitro method to predict in vivo photoprotection of skin hyperpigmentation induced by visible light.

BACKGROUND: Ultraviolet radiation is the main cause of skin pigmentation, but more recently visible light has been shown to be an important contributor especially in melano-competent subjects. Photoprotection from visible light can improve several hyperpigmentation disorders. Recently, a visible light photoprotection assessment method has been proposed based on in vivo pigmentation; the visible light photoprotection factor (VL-PF) is determined by assessment of the change in colorimetry parameter ITA over several days measured using a chromameter. Although in vivo methods remain the most representative of real life, in vitro methods are more suited to screening sunscreen formulations. OBJECTIVE: The aim of this study was to evaluate the correlation between in vivo and in vitro methods in assessing protection against visible light induced pigmentation. METHODS: We first analysed the in vitro protective properties of the 10 commercially available sunscreens using transmission measurements in the visible spectrum. Then, we performed a monocentric, double-blind, randomized controlled study with intra-individual comparisons in 20 healthy subjects and measure the VL-PF in vivo of those sunscreens. The correlation between the VL-PF and the percentage of blocked light was evaluated using the coefficient of determination R2 . RESULTS: A strong significant correlation was demonstrated between in vivo visible light protection factor and in vitro transmittance measurements, with the highest correlation factor at 420 nm and in the spectrum covering from 400 to 469 nm. CONCLUSION: Transmittance measurements were found to be a good predictive tool to evaluate sunscreen visible light photoprotection efficacy and could be used to select formulations for final in vivo testing.

Effectiveness of an epidermal growth factor-containing cream on postinflammatory hyperpigmentation after 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser treatment of acquired bilateral nevus of Ota-like macules (Hori's nevus) in Asians: A split-face, double-blinded, randomized controlled study.

BACKGROUND: Epidermal growth factor (EGF) may promote wound healing and decrease laser-induced postinflammatory hyperpigmentation (PIH). OBJECTIVES: To evaluate the effectiveness of an EGF-containing cream on PIH, post-laser erythema, and transepidermal water loss (TEWL) after 1,064-nm Q-Switched Nd: YAG laser treatment of Hori's nevus. METHODS: This is a split-face, double-blinded, randomized, controlled study conducted in 30 subjects with bilateral Hori's nevus. After laser treatment, participants were randomized to apply EGF cream on one facial side and placebo on the other side for 8 weeks. The incidence and intensity of PIH were assessed by photographs and melanin indexes (MIs) ratio at baseline, Week 2, Week 4, and Week 8. Post-laser erythema and TEWL were measured at baseline, Day 1, Day 3, and Day 7. Side effects and patient satisfaction score were evaluated. RESULTS: The incidence of PIH was 26.7% in EGF group compared to 20% in placebo. The intensity of PIH was 0.057 (0.033-0.086) and 0.045 (0.027-0.076) in EGF and placebo group, respectively. There was no significant difference in both incidence (p = 0.5) and intensity of PIH (p = 0.145). Post-laser erythema was not statistically different between groups. EGF could alleviate TEWL better than placebo but without statistical significance. Patient satisfaction score was significantly higher in EGF group compared to placebo (p < 0.001). CONCLUSIONS: The EGF-containing cream could not prevent PIH. It may reduce laser-induced skin barrier damage. Future studies in more subjects are needed.

Efficacy and safety of tretinoin 0.05% cream to prevent hyperpigmentation during narrowband UV-B phototherapy in patients with facial vitiligo: a randomized clinical trial.

BACKGROUND: Narrowband UV-B (NBUVB) phototherapy is the mainstay of vitiligo treatment, but hyperpigmentation is one of the limitations. Meanwhile, topical tretinoin is effective against pigmentary disorders. OBJECTIVE: To determine whether tretinoin 0.05% cream would prevent hyperpigmentation when patients with facial vitiligo underwent phototherapy. METHODS: A randomized, controlled, split-face trial was conducted. Adult patients with stable, non-segmental facial vitiligo were enrolled. The left/right sides of the face were randomly allocated to receive either topical tretinoin 0.05% cream or moisturizer twice daily. The entire face was subjected to NBUVB phototherapy twice weekly for 12 weeks. The degree of hyperpigmentation was assessed as the delta L* (brightness) value of the darkest spot in each side of the face at baseline and every 4 weeks. The degree of repigmentation was assessed. RESULTS: Twenty-five patients were enrolled; 21 completed the study. The delta L* value was significantly different between the two groups: -0.5% in the tretinoin group and -8.7% in the control group at 12 weeks (p = .002). Marked repigmentation was achieved in 15 patients of both groups. CONCLUSIONS: Tretinoin 0.05% cream prevented hyperpigmentation during NBUVB phototherapy in patients with facial vitiligo, and did not compromise the overall treatment response. TRIAL REGISTRATION: ClinicalTrials.gov NCT03933774.

An open-label, investigator-initiated, single-center, prospective, pilot clinical study to evaluate the efficacy of a skin whitening serum applied twice daily combined with a spot-preventing SPF50+ sunscreen in healthy female subjects with melasma hyperpigmentation.

BACKGROUND: Melasma is a common skin disorder characterized by alterations in normal skin pigmentation. The objective was to evaluate the efficacy and safety of a skin whitening serum containing niacinamide, hydroxyphenoxy propionic acid, dipotassium glycyrrhizate, glycolic acid, and 4-n-butylresorcinol applied twice daily combined with a spot-preventing SPF50+ sunscreen for treatment of melasma. METHODS: Twelve healthy Caucasian women with melasma (Fitzpatrick skin types II-IV) were enrolled in this pilot clinical study. Efficacy evaluations were performed at baseline and weeks 4, 8, and 12 of treatment and included clinical and instrumental assessments. RESULTS: All endpoints for melasma hyperpigmentation showed a statistically significant improvement from baseline to the end of the study. There was only one dropout. No signs of irritation or discomfort were observed at baseline, w4, w8, or w12. An overall improvement in melasma was observed both clinically and on reflectance confocal microscopy (RCM). CONCLUSION: This topical skin whitening serum had favorable outcomes for the treatment of melasma hyperpigmentation in adult women, as demonstrated on investigator and instrumental assessments. The results of this pilot study need to be confirmed in randomized, controlled studies with a larger sample size.

Misconceptions of photoprotection in skin of color.

Terrestrial sunlight is the portion of electromagnetic radiation that is emitted by the sun and reaches Earth's surface. It encompasses 3 major components: UV radiation (290-400 nm), visible light (400-700 nm), and infrared radiation. The deleterious effects of UV radiation have been appreciated for decades, particularly among those with light skin tones (Fitzpatrick skin types I-II) who primarily manifest with burns of varying degrees of severity with sun exposure. In recent years, studies have increasingly shown the negative impact of visible light on skin health, particularly in individuals with skin of color (Fitzpatrick skin types IV-VI), including the exacerbation of hyperpigmentation disorders such as melasma and post-inflammatory hyperpigmentation, as well as induction of the former. Recommendations from medical societies and the US Food and Drug Administration for photoprotection have been evolving along with the knowledge base. Yet, misconceptions about skin damage related to sunlight and the benefits of photoprotection (particularly among those with Fitzpatrick skin types V-VI) are still prevalent among both clinicians and patients. Among patients with skin of color, disorders of hyperpigmentation and other consequences from sun exposure have been associated with impaired skin health and negative burden on quality of life. This review summarizes currently available evidence of the impact of both UV and visible wavelengths and the low utilization of photoprotection measures among people with skin of color, with the goal of providing recommendations to help educate patients.

Impact of visible light on skin health: The role of antioxidants and free radical quenchers in skin protection.

Until recently, the primary focus of photobiology has centered on the impact of UV radiation on skin health, including DNA damage and oncogenesis; however, the significant effects of visible light (VL) on skin remain grossly underreported. VL has been reported to cause erythema in individuals with light skin (Fitzpatrick skin types [FSTs] I-III) and pigmentary changes in individuals with dark skin types (FSTs IV-VI). These effects have importance in dermatologic diseases and potentially play a role in conditions aggravated by sun exposure, including phototoxicity in patients with FSTs I to III and post-inflammatory hyperpigmentation and melasma in patients with FSTs IV to VI. The induction of free radicals, leading to the generation of reactive species, is one driving mechanism of VL-induced skin pathologies, leading to the induction of melanogenesis and hyperpigmentation. Initial clinical studies have demonstrated the effectiveness of topical sunscreen with antioxidant combinations in inhibiting VL + UV-A1-induced erythema in FSTs I to III and reducing pigmentation in FSTs IV to VI. Antioxidants may help prevent the worsening of pigmentary disorders and can be incorporated into photoprotective strategies. It is essential that dermatologists and the public are aware of the impact of VL on skin, especially in patients with skin of color, and understand the available options for VL protection.

Natural and Synthetic Bioactives for Skin Health, Disease and Management.

The skin is the largest organ of the integumentary system, strategically located at the interface of the body's internal and external environment. [...].

Implementation of design of experiments for optimization of forced degradation conditions and development of a stability-indicating high-performance liquid chromatography method for sepiwhite.

Sepiwhite is a novel anti-pigmenting agent that is derived from fatty acid and phenylalanine and used for hyperpigmentation induced by light exposure or inflammation. In this study, a simple and validated high-performance liquid chromatography method for the quantitation of sepiwhite was developed. Optimized forced degradation of sepiwhite at thermal, acid/base, photolysis, oxidative, and heavy metal ions conditions were evaluated and the effect of each of them on production of specific 10%-30% degradants was studied by the approach of design of experiments. Sepiwhite accelerated study was conducted and toxicity of sepiwhite at each condition was tested. An optimized high-performance liquid chromatography method was validated by a face-centered central composition design. Ten different degradants were identified from sepiwhite and degradation behavior under different conditions was studied. Sepiwhite and its degradant products show no cytotoxicity. This optimized high-performance liquid chromatography method can be applied for quality control assay and sepiwhite degradation behavior may be considered in the manufacturing of sepiwhite products.