Efficacy and safety of a novel triple combination cream compared to Kligman's trio for melasma: A 24-week double-blind prospective randomized controlled trial.

BACKGROUND: Kligman's trio (KT), combining hydroquinone, retinoic acid and corticosteroid, is considered as the gold standard treatment of melasma. Its efficacy has never been matched before, but it is tempered by frequent adverse effects. OBJECTIVE: To assess the efficacy and tolerance of a New Trio (NT) combination with isobutylamido-thiazolyl-resorcinol, retinoic acid and cortosteroid compared to KT. METHODS: We conducted a 24-week monocentric trial, randomized, double-blind, controlled versus KT, with 40 melasma patients. NT and KT were applied for 12 weeks and associated with the same sunscreen applied for 24 weeks. The primary endpoint was the modified Melasma Area Severity Index (mMASI) at 12 weeks. Patient quality of life was investigated using MelasQoL. RESULTS: After 12 weeks, KT and NT groups both demonstrated a significant improvement in mMASI, respectively -2.84 (SE 0.69, p < 0.0002) and -4.33 (SE 0.71, p < 0.0001). The mean difference between the two groups was -1.49 (IC 95% -3.52 to 0.54, p = 0.14). MelasQoL improvement was -6.66 (SE 3.29, p = 0.0515) with KT and -12.57 (SE 3.29, p = 0.0006) with NT. CONCLUSION: The NT combination appears to be an effective treatment option for treating melasma and could be considered as a well-tolerated alternative to KT.

Split-face comparison of hydroquinone 4% plus nitrogen plasma vs. hydroquinone 4% alone in the treatment of melasma.

Treatment of skin diseases is important yet challenging. One of the most common skin diseases in women is melasma, which features acquired facial hyperpigmentation. We studied the effect of cold atmospheric nitrogen plasma on this disease. To characterize the nitrogen plasma, we obtained the relative intensity of the species and the plasma temperature and skin temperature during processing at different input powers and gas flows. Patients complaining of melasma were treated with hydroquinone on both sides of the face, and one side was randomly selected for additional nitrogen plasma therapy. Eight treatment sessions of plasma processing were provided 1 week apart, and one follow-up session was scheduled 1 month after the end of treatment. The rate of improvement was scored by a dermatologist in the eighth session and 1 month following the last session using the modified Melasma Area Severity Index (mMASI). Skin biomechanical characteristics such as melanin, cutaneous resonance running time (CRRT), transepidermal water loss (TEWL), and hydration were measured at baseline and during the fourth, eighth, and follow-up sessions. On both sides, we observed a significant decrease in both CRRT and melanin (P < 0.05). TEWL did not change on both sides, while hydration decreased significantly only on the side to which hydroquinone was applied in isolation (P < 0.05). According to clinical scores, on both sides, we had significant improvement. On the side that plasma was not applied, the percentage reduction of pigmentation (mMASI) in the eighth and follow-up sessions in comparison with the baseline was 5.49 ± 8.50% and 33.04 ± 9.17%, respectively, while on the other side, these figures were 20.57 ± 6.64% and 48.11 ± 11%. For melanin, these figures were 13.84 ± 4.84% and 18.23 ± 7.10% on the hydroquinone side and 21.56 ± 3.13% and 23.93 ± 3.02% on the other side. According to these results, nitrogen plasma can safely complement topical hydroquinone to improve clinical outcomes when treating melasma without causing stratum corneum damage or skin discomfort, though confirmatory studies are needed.

Mechanisms of action of Lycium barbarum polysaccharide in protecting against vitiligo mice through modulation of the STAT3-Hsp70-CXCL9/CXCL10 pathway.

CONTEXT: Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress. OBJECTIVE: This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway. RESULTS: LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1ß (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively. CONCLUSION: These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.

Tranexamic acid in melasma: A focused review on drug administration routes.

BACKGROUND: Melasma is a disorder of hyperpigmentation and vascularization often found in women between the ages of 20 and 40. The pathogenesis is unknown, but melasma often occurs in sun-exposed areas of the face, forearms, and back. Risk factors include family history, increased estrogen/progesterone, certain medications, and UV exposure. Melasma is typically treated with topical hydroquinone (HQ); however, it is often refractory to treatment. Tranexamic acid (TXA) is a plasmin inhibitor used off-label in the treatment of melasma. TXA can be administered orally, topically, or intralesionally. AIMS: The purpose of this review is to characterize the wide variety of TXA delivery methods for melasma treatment and the efficacy of these methods compared with traditional treatments. PATIENTS/METHODS: A comprehensive PubMed and Embase search was conducted in May 2022 using the phrases tranexamic acid and melasma. Forty-six articles were included in this review. RESULTS: Oral, intralesional, and topical TXA is safe and effective treatments for melasma. They have been studied in a variety of randomized controlled trials and have been compared with several traditional treatments. Overall, MASI scores in patients using TXA in any form improved. CONCLUSIONS: Oral TXA was found to be the most effective, especially in cases of refractory melasma; however, it caused GI upset and menstrual irregularities in many patients. The pro-thrombotic nature of this drug must be considered before safely prescribing to patients. Intralesional injections and microneedling with topical TXA were found to be effective alternatives to oral treatment. Lastly, topical TXA alone was found to be the least effective method but can be combined with other cosmeceuticals to improve outcomes. Topical TXA was also found to be better tolerated than hydroquinone, a traditional topical melasma treatment.

Prospective, randomized, double-blind clinical study of split-body comparison of topical hydroquinone and hexylresorcinol for skin pigment appearance.

Dyspigmentation is a common cosmetic concern in dermatology. Currently, the first line topical medication in the United States is hydroquinone. Hydroquinone use is associated with potential safety concerns including cytotoxicity to melanocytes, systemic absorption, metabolism in distant organs, and production of potentially carcinogenic metabolites. Hexylresorcinol is an ingredient that has been used in food preservation and as antiseptic has been shown to inhibit tyrosinase in vitro and has been studied as a novel skin-lightening agent. To perform a double-blind randomized split-body investigation of comparison on topical hexylresorcinol and hydroquinone on face and hands to assess for change in the appearance of skin tone and pigmentation. Thirty-two healthy female participants ages 35-65 (50.93 ± 7.37) years old with skin type I-IV were randomized to using either topical 1% hexylresorcinol or 2% hydroquinone on the left or right side of the face and corresponding hand over 12 weeks. The topical preparation was applied twice a day to assigned areas. Standardized photos were taken of the face and colorimetric measurements were taken of both sides of the forehead, cheeks and each hand at baseline (Day 0), week 4, and week 12. Of the 32 participants, 3 were lost to follow-up and the remaining were included in the final analysis. Pigmentation measured by colorimeter and clinical grading were significantly decreased at 4 and 12 weeks relative to baseline with no difference between the HR and HQ groups. No adverse effects were noted with either intervention. Hexylresorcinol 1% is well-tolerated and equivalent to hydroquinone 2% in reducing the appearance of facial and hand pigment. Further studies with an expanded population and longer time course are warranted.Registration No.: NCT04345094.

Hydroquinone-induced skin irritant reaction could be achieved by activating mast cells via mas-related G protein-coupled receptor X2.

Hydroquinone (HQ) is one of the most effective drugs to treat hyperpigmentary disorders, but often causes skin irritation in clinic. Mast cell plays an important role in contact dermatitis and triggering pseudo-allergic reactions via MRGPRX2. Whether HQ-induced skin irritant reaction through activating mast cells via MRGPRX2 remains unknown. To investigate the role of mast cells in HQ-induced skin irritant reaction and verify whether MRGPRX2 participated in the HQ effect on mast cells which contributed to the pathogenesis of skin irritant reaction, a mouse model of HQ-induced skin irritation was established to observe the local and systemic inflammation associated with mast cell receptor MrgprB2. Human mast cell LAD2 was used to verify the effect of HQ on mast cells via MRGPRX2 by knocking down with siRNA. As a result, mast cells were involved in the development of HQ-induced irritant reaction, and local inflammation is closely related to mast cell receptor MrgprB2. HQ could activate mast cells via MRGPRX2, causing changes in calcium concentration, degranulation and release of inflammatory cytokines which lead to skin irritant reaction. In conclusion, HQ-induced skin irritant reaction could be skin pseudo-allergic reactions achieved by activating mast cells via MRGPRX2.

The antioxidant, tert-butylhydroquinone: a new cause of asthma.

The antioxidant, tert-butylhydroquinone (TBHQ), a common additive in food and cosmetics can cause allergic contact dermatitis. A 49-year-old non-atopic male factory worker developed asthma in connection with cleaning mixing drums containing TBHQ. Due to the suspicion that TBHQ might be the cause of asthma, a specific inhalation challenge was carried out. Lactose was used as a control agent. The following day he developed asthma symptoms with a 41% drop in FEV1 after 30-min exposure to small amounts of TBHQ and water. Methacholine reactivity increased 5-fold after TBHQ exposure compared to pre-exposure reactivity. This suggests that TBHQ may be the cause of asthma in this case. Due to this case respirators were introduced in the factory to reduce TBHQ exposure. TBHQ has not previously been shown to cause asthma.

Combination of autologous platelet rich plasma and hydroquinone 4% is more effective than hydroquinone alone in treatment of melasma: A split-face comparative study.

Melasma is a common acquired circumscribed hyper-pigmentary disorder involving sun-exposed areas, particularly face. The high frequency of recurrence renders the management more challenging. Autologous platelet rich plasma (PRP) has promising potential in the treatment of melasma. This study evaluates the efficacy of combination of autologous PRP and Hydroquinone and compares it with the gold standard molecule 4% Hydroquinone. Thirty patients with melasma were enrolled in this split-face study conducted between 2018 and 2020. All the patients were prescribed Hydroquinone cream 4% to be applied on the affected area at night. Microneedling was performed once a month (total four sessions) on both sides of face, followed by application of autologous platelet rich plasma on right side and normal saline as control on left side of affected area. Modified Melasma Area and Severity Index (MASI) score, Patient satisfaction score and Physician's Global Assessment score were calculated at baseline and after each session and improvement was assessed. Improvement in mean modified MASI score was significant on both sides of face. Mean percentage improvement in modified MASI score on study side and control side was 82% and 69% respectively. The difference between the two sides was statistically significant in terms of modified MASI, patient satisfaction and physician global assessment scores. Adverse effects were mild and transient. Autologous platelet rich plasma is an effective and safe therapy for treatment of melasma. Combination of autologous PRP and 4% Hydroquinone showed greater improvement than hydroquinone alone.

Pigmentation control in pregnancy-induced melasma: Clinical assessment of a non-hydroquinone, non-retinol pigment-correcting serum.

BACKGROUND: Melasma is an acquired disorder that results in irregular brown patches on the skin that can occur due to hormonal changes. Although pregnancy-induced melasma is usually temporary, it can become a chronic condition, with significant negative impact on quality of life (QoL). AIMS: Determine the efficacy and tolerability of a topical, non-hydroquinone, non-retinol pigment-correcting serum (LYT2) for the treatment of pregnancy-induced melasma. METHODS: This 12-week, single-center clinical trial enrolled 34 non-pregnant women who developed mild to severe facial melasma following a previous pregnancy (mean age, 42 years). LYT2 was applied twice daily to facial skin for 12 weeks in addition to a basic skincare regimen. Outcomes included changes from baseline in skin physiology parameters, such as brightness (L*), using objective digital image analysis, investigator-rated Overall Hyperpigmentation scale, Global Improvement, and Melasma Area and Severity Index (MASI), as well as subject-assessed Melasma Quality of Life Scale. Subjects also completed a questionnaire on self-perceived efficacy and attributes of the study product. Tolerability was assessed by the investigators (erythema, scaling, and edema) and subjects (burning/stinging and itching). Clinical assessments were conducted at baseline and Weeks 4, 8, and 12. RESULTS: LYT2 provided statistically significant reductions in overall hyperpigmentation scores as early as Week 4 (-5.8% change from baseline) and continued through Week 12 (-14.6% change from baseline; all p < 0.001). Significant improvements in MASI scores and QoL were also achieved following LYT2 treatment, which was well tolerated. CONCLUSIONS: LYT2 represents a new efficacious alternative to hydroquinone-based treatments for pregnancy-induced melasma.

Comparison of the efficacy of cysteamine 5% cream and hydroquinone 4%/ascorbic acid 3% combination cream in the treatment of epidermal melasma.

BACKGROUND: Few safe and effective treatments are available for melasma. Cysteamine, a non-melanocytotoxic molecule is a safer alternative to hydroquinone and usable for long-term use. AIM: To evaluate the effect of cysteamine 5% cream in the treatment of melasma. METHODS: Sixty-five of 80 patients completed this single-blind, randomized, controlled trial. The patients received cysteamine 5% or hydroquinone 4%/ascorbic acid 3% (HC) cream. The therapeutic response was evaluated by modified MASI (mMASI) and melanin index (SkinColorCatch) after 2 and 4 months of treatment. The effect of treatment on the quality of life was also assessed. RESULTS: The decrease in mMASI score was from 6.69 ± 2.96 to 4.47 ± 2.16 in the cysteamine group and from 6.26 ± 3.25 to 3.87 ± 2.00 in the HC group after 4 months (p values < 0.001). The melanin index decreased from 37.72 ± 10.17 to 31.47 ± 11.90 in the cysteamine group and from 36.37 ± 10.80 to 23.16 ± 8.83 in the HC group after 4 months (p-value = 0.003 and <0.001, respectively). The difference between mMASI score at baseline and month 4 was not significant between both groups (p-value > 0.05). The difference between the melanin index at baseline and month 4 was significantly more pronounced in the HC group (p-value = 0.002). Quality of life improved in both groups (p-value < 0.05), but was not significantly different between groups (p-value > 0.05). CONCLUSION: Cysteamine was confirmed to be an effective treatment for melasma, with equivalent results to HC in reducing mMASI score and improving quality of life, despite lesser melanin index reduction observed. Cysteamine and HC efficacy was confirmed in patients recalcitrant to previous treatments, by a significant reduction of mMASI and melanin index.

Hyperpigmentation: Looking beyond hydroquinone.

Hyperpigmentation is the most common complaint in the age group 40-45 years, seeking consultation for skin disorders. Hydroquinone is a commonly used depigmenting agent in clinical practice for treating hyperpigmentation. Prolonged use of hydroquinone has been associated with cancer risk and exogenous ochronosis. The CARES (The Coronavirus Aid, Relief, and Economic Security Act) Act of 2020 has instituted significant changes to hydroquinone containing OTC (over the counter) products, and consequently, many hydroquinone-based OTC products had to be withdrawn from the market. Henceforth, products containing hydroquinone would need US Food and Drug Administration approval via new drug application pathways for commercialization. Alternative treatment options to hydroquinone in clinical practice are reviewed in this paper with regard to their safety and efficacy vis a vis hydroquinone. Also, new potential treatment options such as thiamidol, Polypodium leucotomos, and glutathione are discussed. The review shows that these alternative depigmenting agents can be rationally combined to achieve desired treatment goals in the management of hyperpigmentation.

Exogenous ochronosis associated with hydroquinone: a systematic review.

Exogenous ochronosis is a potential side effect associated with hydroquinone, and treatment is often unsatisfactory. Our study objectives were to review data on hydroquinone-associated ochronosis to determine risk factors for patients experiencing this adverse event. On September 27, 2020 (MEDLINE/PubMed), and October 30, 2020 (Scopus and Web of Science), databases were searched for "ochronosis + hydroquinone" by both authors to reduce risk basis. PRISMA reporting guidelines were used to select 56 articles with a total of 126 patients with hydroquinone-associated ochronosis. Included articles described hydroquinone-associated ochronosis. Articles were excluded if they had irrelevant content, were non-English language text, and were non-case studies. Full text articles were assessed and recorded. Cross-tabulation analysis was performed on categorical data, and Fisher exact test was performed. Ochronosis was most often reported in middle-aged women (53.2%), of African descent (45.2%), Black races (55.5%), and Fitzpatrick skin types V-VI (52.4%). It was most frequently reported with unknown and hydroquinone concentrations greater than 4% (32.5 and 35.7% cases, respectively). Median duration of use was 5 years, with only four cases reported with courses 3 months or shorter and eight cases reported with use 1 year or less. All patients presented with facial blue-black or gray-blue macules in a reticulate, lace-like fashion. Histopathology consistently showed solar elastosis and brownish-yellow, 'banana-shaped' fibers between degenerated collagen fibers of the papillary dermis. Based on these findings, we conclude that hydroquinone in concentrations above 4% and in treatment courses longer than 3 months may be associated with new-onset ochronosis.

Oral tranexamic acid, hydroquinone 4% and low-fluence 1064 nm Q-switched Nd:YAG laser for mixed melasma: Clinical and dermoscopic evaluation.

BACKGROUND: Tranexamic acid (TA) can prevent melanocyte activation by various stimuli. Combining TA with either hydroquinone 4% or Q-switched Nd:YAG laser may be associated with greater improvement of melasma. OBJECTIVES: We aimed to evaluate the efficacy and safety of oral TA alone and combined with either topical hydroquinone 4% or low-fluence 1064 nm Q-switched Nd:YAG laser in treatment of mixed melasma. PATIENTS & METHODS: Patients were randomly divided into three groups of 20 patients each. Group A were treated with oral TA 250 mg twice daily for three months; group B were treated with TA similarly combined with topical hydroquinone 4% cream; group C were treated with TA combined with two sessions of 1064 nm low-fluence Q-switched ND:YAG laser (850-1200 mJ/cm2 , 4-5 Hz,spot size 4 mm) spaced 4 weeks apart. Patients were followed monthly for 9 months. RESULTS: After cessation of therapy, the mean mMASI score was lowest in group B (2.34 ± 2.37) followed by groups A (6.38 ± 4.04) and C (7.24 ± 4.95).Mean percentage of mMASI score improvement was 35.91 ± 24.13, 77.47 ± 19.07, and 24.94 ± 27.79 in groups A, B, and C (p < 0.001). There was a significant reduction of telangiectasia in the three groups. Reported side effects were itching & irritation, post-inflammatory hyperpigmentation, and gastritis. CONCLUSION: Oral TA is a tolerable effective treatment modality for melasma. Combining hydroquinone 4% with oral TA is associated with a relatively earlier and better cosmetic outcome.

Repigmentation by combined narrow­band ultraviolet B/adipose­derived stem cell transplantation in the mouse model: Role of Nrf2/HO­1­mediated Ca2+ homeostasis.

Vitiligo is a depigmentation disease commonly seen in clinical practice, mainly involving loss of functional epidermal pigment cells and hair follicle melanocytes. Narrow­band ultraviolet B (NB­UVB) has emerged as the first choice of treatment for vitiligo, but long­term exposure may have serious consequences. Recently, it was reported that adipose­derived stem cells (ADSCs) improve melanocyte growth and the efficacy of melanocyte transplantation. The present study aimed to examine the efficacy of NB­UVB/ADSC­transplantation combined therapy on a mouse vitiligo model and explore the underlying mechanisms by focusing on endoplasmic reticulum stress and cellular calcium (Ca2+) homeostasis. Vitiligo mice models were established by applying 40% monobenzone (MBZ) cream twice daily and treated with NB­UVB/ADSC combination therapy. Some treated mice were also given ML385, a nuclear factor erythroid 2 like 2 (Nr2) inhibitor. Histopathological changes were evaluated using a depigmentation evaluation score and observed with hematoxylin and eosin staining on skin tissues. ELISA was used to measure diagnostic markers in plasma. Flow cytometric assay was performed to quantify CD3+, CD4+ and CD8+ levels. Expression levels of associated proteins were detected with western blot and immunofluorescence. Treatment of mice with MBZ­induced depigmentation patches on the skin was accompanied with loss of redox balance and disruption of cellular Ca2+ homeostasis. Oxidative stress and Ca2+ unbalancing were improved after the mice were treated by NB­UVB/ADSCs transplantation combination therapy. ML385, strongly negated the protective effect of NB­UVB/ADSC transplantation combination therapy, indicating the critical role of Nr2 signaling. The findings improved the understanding of the pathogenesis of vitiligo and will guide future development of therapeutic strategies against it.

Machine learning-driven identification of early-life air toxic combinations associated with childhood asthma outcomes.

Air pollution is a well-known contributor to asthma. Air toxics are hazardous air pollutants that cause or may cause serious health effects. Although individual air toxics have been associated with asthma, only a limited number of studies have specifically examined combinations of air toxics associated with the disease. We geocoded air toxic levels from the US National Air Toxics Assessment (NATA) to residential locations for participants of our AiRway in Asthma (ARIA) study. We then applied Data-driven ExposurE Profile extraction (DEEP), a machine learning-based method, to discover combinations of early-life air toxics associated with current use of daily asthma controller medication, lifetime emergency department visit for asthma, and lifetime overnight hospitalization for asthma. We discovered 20 multi-air toxic combinations and 18 single air toxics associated with at least 1 outcome. The multi-air toxic combinations included those containing acrylic acid, ethylidene dichloride, and hydroquinone, and they were significantly associated with asthma outcomes. Several air toxic members of the combinations would not have been identified by single air toxic analyses, supporting the use of machine learning-based methods designed to detect combinatorial effects. Our findings provide knowledge about air toxic combinations associated with childhood asthma.

Efficacy and safety of topical isobutylamido thiazolyl resorcinol (Thiamidol) vs. 4% hydroquinone cream for facial melasma: an evaluator-blinded, randomized controlled trial.

BACKGROUND: Melasma can be refractory to treatment, and relapses are frequent. Thiamidol is a new potent tyrosinase inhibitor that has been found effective as a cosmeceutical for the depigmenting of melasma. OBJECTIVE: This study compared the efficacy and tolerability of topical 0.2% Thiamidol vs. 4% hydroquinone for facial melasma. METHODS: Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomly assigned to apply a double layer of 0.2% Thiamidol twice a day or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Seve:rity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life [Melasma Quality of Life Index (MELASQoL)], colourimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation. RESULTS: One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III-IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35-50%) for Thiamidol and 33% (23-42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colourimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67-97%) for participants in the Thiamidol group and 74% (CI: 95% 61-93%) for those in the hydroquinone group. There were only mild adverse effects in the Thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. CONCLUSION: The melasma improvement achieved using 0.2% Thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone.