Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

We present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin-lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis, however discontinuing the skin-lightening creams halted the progression of the patient's skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. We summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.  J Drugs Dermatol. 2024;23(7):567-568.     doi:10.36849/JDD.8248.

Efficacy and tolerability of a depigmenting gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that targets the biological processes regulating skin melanogenesis.

BACKGROUND: The diverse causes of hyperpigmentation and complex nature of melanogenesis make it a challenge to manage. Current approaches either fail to deliver effective pigmentation control or have undesirable safety profiles that preclude their long-term use. AIMS: To evaluate the capacity of a cosmetic gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that was designed to target the biological processes regulating skin melanogenesis to attenuate melanin production in vitro and reduce hyperpigmentation clinically. METHODS: Capacity to reduce melanin production in vitro was determined in melanocyte-containing reconstructed human epidermis (RHEm). Clinical efficacy and skin tolerability following twice daily application were assessed in 35 subjects with slight to moderate facial hyperpigmentation by instrumental (VISIA®-CR, Mexameter®) and clinical (mMASI, clinical score, IGA for hyperpigmentation) evaluation on D14, D28, D56, and D84. Maintenance of pigmentation control was followed up 1 month after cessation of treatment on D112. RESULTS: In RHEm in vitro, melanin production was reduced by 50.0% from baseline (D0) on D14 (p < 0.001) and by 67.0% on D21 (p < 0.001). Clinical reductions from baseline in brown spots count (-9.0%; p < 0.05), brown spots area (-16.7%; p < 0.001), and the melanin index (-11.4%; p < 0.001) were observed within 14 days of use. Statistically significant improvements in all clinical parameters were achieved by D28. By the end of treatment on D84, the number and surface area of brown spots were reduced by 28.4% and 40.3% compared to D0, respectively (p < 0.001, both), the melanin index was reduced by 31.1% (p < 0.001), mMASI was reduced by 63.0% (p < 0.001), and skin luminosity was increased by 79.0% (p < 0.001). IGA was reduced from 2.3 on D0 to 1.3 on D84 (p < 0.001). Improvements to all these parameters were maintained until D112, 1 month after termination of treatment. The product also demonstrated very good skin tolerability. CONCLUSION: A gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, and hydroxy acids, designed to target the biological processes regulating skin melanogenesis, demonstrates rapid, robust, and sustained pigmentation control in this cohort.

Skin lightening properties of zerumbone cream: A placebo-controlled study.

OBJECTIVE: Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) in vitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. METHODS: Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. RESULTS: Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. CONCLUSION: ZER demonstrated significant potential as a skin-lightening agent.

The effect of emulgel preparation on the stability of Kojic acid in the topical anti-hyperpigmentation products.

BACKGROUND: The emulgel, a novel drug delivery system, merges emulsion and gel, offering advantages like enhanced stability, precise control over drug release kinetics, and increased drug absorption compared to emulsions alone. Kojic acid (KA) demonstrates potent inhibition of the tyrosinase enzyme, a crucial player in the melanin synthesis pathway. AIMS: The main objective of this experimental study is to formulate KA within an emulgel framework and assess its stability under various environmental conditions. METHODS: One percent of KA emulgel and 1% simple gel, serving as the control product, were supplemented with varying concentrations of sodium metabisulfite (SMBS) for its antioxidant properties. The formulations were segregated into four groups and subjected to diverse maintenance and stress conditions over a three-month period. Monthly evaluations of physicochemical alterations were conducted, initially employing digital photography, followed by the extraction of KA and subsequent quantification of its concentration through high performance liquid chromatography (HPLC). RESULTS: The best formulations for retaining KA among the prepared ones were the 0.25% SMBS KA emulgel and the 0.1% SMBS KA simple gel, capable of retaining 86% and 76% of the initial KA content under stress conditions, respectively (p < 0.0001). CONCLUSIONS: Regarding to this study, ideal storage condition for KA emulgel and simple gel is in the refrigerator temperatures. Moreover, optimal SMBS concentrations for stability enhancement are 0.25% for emulgel and 0.1% for the simple gel. A significant statistical difference was observed between refrigerated emulgel and simple gel in the retention of KA in the presence of optimum concentration of antioxidants (p < 0.0001).

Efficacy and safety of novel topical pigment-correcting regimen with biweekly diamond tip microdermabrasion procedures on facial hyperpigmentation.

BACKGROUND: Facial hyperpigmentation can negatively affect an individual's emotional and psychosocial well-being. AIMS: Assess safety and tolerability of a combination of microdermabrasion (DG) procedures using a novel brightening pro-infusion serum (EC-DG) with a targeted at-home treatment regimen in subjects with mild to severe facial hyperpigmentation, including melasma, post-inflammatory hyperpigmentation, and dark spots. PATIENTS/METHODS: This 12-week, open-label study enrolled 18 subjects (Fitzpatrick skin types I-IV) who underwent 6 in-office DG procedures with EC-DG (one procedure administered biweekly), along with daily topical application of a brightening treatment serum and dark spot cream. End points included change from baseline across multiple skin quality attributes and the Melasma Area and Severity Index (MASI), self-assessment questionnaires, and tolerability assessments. RESULTS: The combination treatment was well tolerated and resulted in significant (p ≤ 0.05) improvements from baseline in radiance, tactile roughness, and moisturization/hydration immediately after the first treatment, in MASI score at day 3, and in overall hyperpigmentation at week 4. Most (94.1%) subjects were satisfied with treatment. CONCLUSIONS: DG procedures using EC-DG combined with a targeted at-home skincare regimen are effective and tolerable for treating facial hyperpigmentation across a broad range of skin types.

Hispanic/Latinos and Skincare: Disparities in Product Development, Marketing, and Toxicity.

“Hispanic” and “Latino” (also known as Mestizo) describe a diverse racial and ethnic group, with a range of cultures, languages, and biological ancestry. It includes individuals of Mexican, Central-to-South American, and Spanish-Caribbean (eg, Cuban, Puerto Rican, and Dominican) descent.1 Individuals of Hispanic/Latino race and ethnicity represent a heterogenous group of people with different skin tones and Fitzpatrick phototypes. Hispanic/Latinos are the fastest growing population in the United States (US) - projected to increase from 55 million in 2014 to 119 million in 2060, an increase of 115%.2 By 2060, more than one-quarter (29%) of the US is projected to be Hispanic/Latino.2.

Randomized, Double-Blinded, Split-Face Study Comparing the Efficacy and Tolerability of Two Topical Products for Melasma.

BACKGROUND: Melasma is a common disorder of hyperpigmentation that disproportionately affects individuals with skin of color. There is a paucity of studies evaluating non-hydroquinone (HQ) topical therapies for the treatment of melasma in darker skin types. OBJECTIVE: To compare the safety, efficacy, and tolerability of a HQ-free, retinol-free cosmetic topical brightener (CTB) and HQ 4% in the treatment of moderate symmetric facial melasma in patients with Fitzpatrick skin types (FST) III–VI. Methods & Materials: This was a randomized, double-blinded, split-face clinical trial. Eighteen adult patients with facial melasma were treated with CTB and HQ 4%, each to a different side of the face, twice daily for 12 weeks. Clinical assessments included half-face Melasma Area Severity Index (MASI), Overall Hyperpigmentation scale, and Melasma Severity Rating Scale (MSRS). Patients completed a Melasma Quality of Life (MelasQoL) questionnaire and clinical photographs were taken at each visit. RESULTS: CTB and HQ 4% demonstrated statistically significant improvements in half-face MASI, Overall Hyperpigmentation, MSRS and MelasQol compared to baseline. HQ 4% showed statistically significant improvements in MSRS at week 12 compared to CTB, but was non-superior for all other clinical endpoints. CONCLUSION: HQ-free, retinol-free CTB and HQ 4% both are effective and well-tolerated in the treatment of moderate facial melasma in FST III–VI. J Drugs Dermatol. 2020;19(9):822-827. doi:10.36849/JDD.2020.5353.

Post-Inflammatory Hyperpigmentation: A Review of Treatment Strategies.

Post-inflammatory hyperpigmentation (PIH) is a reactive process resulting from increased melanin or abnormal distribution of melanin secondary to inflammatory skin conditions, dermatologic therapies, and external stimuli. Because PIH is a common condition that has a substantial effect on the quality of life, an understanding of its treatment modalities is essential. Though there are many therapeutic strategies for hyperpigmentary conditions such as melasma that are described in the literature, fewer studies focus on PIH. This article aims to provide a comprehensive literature review of therapies specifically used to treat PIH, such as topical combinations, chemical peels, and lasers. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4887.

The Therapeutic Use of Antioxidants for Melasma.

Melasma is a chronic dermatologic condition with an incompletely understood pathogenesis and well-demonstrated impact on patient quality of life. Melasma is a common cause for seeking dermatologic care, and with no universally efficacious therapy or cure, com-bination treatment is the best approach for many cases. Numerous studies have demonstrated the role of oxidative stress in patients with melasma, prompting investigation into several antioxidants for melasma therapy. In this review, we discuss the well-defined role of oxidative stress in melasma and the therapeutic efficacy of various antioxidants for patients suffering from melasma. We focus our discussion on studies investigating the role of vitamin C, azelaic acid, cysteamine, glutathione, carotenoids, and numerous other antioxidants in disorders of hyperpigmentation. There is promising evidence for the use of these antioxidants, as topical, oral, and intra-venous preparations, both in isolation and in conjunction with other melasma therapies. J Drugs Dermatol. 2020;19(8):788-792. doi:10.36849/JDD.2020.5079.

Advances in the Design of Genuine Human Tyrosinase Inhibitors for Targeting Melanogenesis and Related Pigmentations.

Human tyrosinase (hsTYR) is the key enzyme ensuring the conversion of l-tyrosine to dopaquinone, thereby initiating melanin synthesis, i.e., melanogenesis. Although the protein has long been familiar, knowledge about its three-dimensional structure and efficient overexpression protocols emerged only recently. Consequently, for decades medicinal chemistry studies aiming at developing skin depigmenting agents relied almost exclusively on biological assays performed using mushroom tyrosinase (abTYR), producing a plethoric literature, often of little useful purpose. Indeed, several recent reports have pointed out spectacular differences in terms of interaction patterns and inhibition values between hsTYR and abTYR, including for widely used standard tyrosinase inhibitors. In this review, we summarize the last developments regarding the potential role of hsTYR in human pathologies, the advances in recombinant expression systems and structural data retrieving, and the pioneer generation of true hsTYR inhibitors. Finally, we present suggestions for the design of future inhibitors of this highly attractive target in pharmacology and dermocosmetics.

Development, Characterization and Pharmacological Evaluation of Antiblemish Cream Containing Herbal Oils.

BACKGROUND: Many topical agents are available in the market, which interfere with the pigmentation process at different levels. They are often known to cause side effects ranging from irritation to tumor over chronic use. OBJECTIVE: The present study was designed to develop and characterize an anti blemish cream containing herbal oils. METHODS: A herbal cream was formulated using dill, nagarmotha and black cumin oil and subjected to evaluation of its anti blemish potential against stress augmented UV-B rays-induced hyperpigmentation. Topical oil in water type of creams containing 2%, 4% and 6% of each oil was formulated using herbal oils. The formulated cream was characterized for solubility, pH, particle size, grittiness, viscosity, stability, phase separation, shelf life and spreadability, and found to be stable. Acute dermal toxicity was carried out individually for dill, nagarmotha and black cumin oil according to the OECD guidelines 402. Hyperpigmentation was induced in all the experimental animals by stress-augmented UV-B irradiation method. The animals were treated for 30 days (twice daily) with standard and test formulations by topical administration, whereas the disease group was left untreated. The skin of the animals was subjected to photographical study as well as grading for pigmentation and irritation before and after treatment. After the treatment period, the serum antioxidant levels were estimated and histopathology, histochemical studies of skin were performed. RESULTS: The animals treated with test formulations containing 2%, 4%, and 6% of herbal oil showed significant improvement in pigmentation compared to disease control as it is evident in photographic biochemical, histopathological and histochemical studies. CONCLUSION: Thus, it was concluded that the developed anti-blemish cream containing herbal oils possesses significant anti-blemish potential. This study necessitates further evaluations in human subjects as it could have a high positive therapeutic value in the treatment of hyperpigmentation.

Fabrication, characterization and comparison of α-arbutin loaded dissolving and hydrogel forming microneedles.

In this study, polyacrylic acid-co-maleic acid (PAMA) and polyvinyl alcohol (PVA) (1:4) were used to fabricate dissolving microneedles (DMNs) and hydrogel forming microneedles (HMNs) which incorporated α-arbutin. Αlpha-arbutin is commonly used as a skin lightening agent. However, it has poor penetration ability due to its hydrophilic properties. The purpose of this study was to compare the permeation of α-arbutin into the skin using DMNs and HMNs. Both types of microneedles (MNs) were sharp, strong with elegant appearance and approximately 100% penetrated the neonatal porcine skin. All needles of α-arbutin loaded DMNs were completely dissolved within 45 min, whereas maximum swelling of HMNs was observed at 4 h. In vitro permeation studies showed that α-arbutin loaded DMNs and HMNs provided significantly about 4.5 and 2.8 times, respectively, greater α-arbutin permeability than gel and commercial cream (P < 0.05). In vivo study also showed high intradermal delivery of α-arbutin levels using DMNs (5.33 µg/mL) and HMNs (1.47 µg/mL) when compared to that of commercial cream 0.15 µg/mL. Moreover, the micro-holes caused by applying MNs can reseal within 1 h. MNs were also stable at 25 °C for 3 months. The results suggested that DMNs and HMNs developed have a promising platform for transdermal delivery.

Study of efficacy of microneedling and mesoneedling in the treatment of epidermal melasma: A pilot trial.

BACKGROUND: Melasma is a difficult to treat pigmentation disorder. However, some successes have been attained by microneedling. The aim of the present study was to evaluate the efficacy of microneedling using meso-depigmentation solution (mesoneedling) in comparison with standard microneedling, over a 4-month treatment period. METHODS: As a part of this pilot study, 20 patients received microneedling on one side and mesoneedling on another side of their face. Treatment was repeated on a monthly basis for 4 months. Treatment efficacy was defined through Dermacatch® colorimetry, modified Melasma Area and Severity (mMASI) score determination, Investigator's Global Assessment (IGA), and patient questionnaires, whereby all assessments were conducted at the baseline, as well after 2 and 4 months of treatment. RESULTS: Before treatments, mean difference between pigmented and normal skin calculated by Dermacatch® was 43.7 ± 20.12 and 44.6 ± 20.72 in microneedling sides and mesoneedling sides, respectively. After two and four sessions, these values declined to 34.5 ± 16.26 and 28.05 ± 13.79 on the side subjected to microneedling, while 29.75 ± 15.07 and 20.45 ± 10.58 were measured on the mesoneedling side. Statistically significant differences have been observed between microneedling and mesoneedling treatments at both time points (P = .0001, P = .0001). The mMASI scores obtained upon treatment completion were significantly lower on both the microneedling and the mesoneedling side. The IGA and patients' self-assessment scores further confirmed that both treatments were effective in treating melasma, without producing any notable side-effects or complications. CONCLUSION: In sum, both microneedling and mesoneedling are effective in decreasing melanin content in the epidermal melasma lesions.

Randomised, controlled, double-blind study of combination therapy of oral tranexamic acid and topical hydroquinone in the treatment of melasma.

BACKGROUND/OBJECTIVES: Melasma is a common pigmentary disorder for which oral tranexamic acid has shown some efficacy in previous studies. The aim of this study was to assess the effectiveness of oral tranexamic acid in combination with hydroquinone cream in the treatment of melasma. METHODS: Subjects with moderate-to-severe melasma were enrolled. Group A received hydroquinone 4% cream, sunscreen and oral tranexamic acid, while Group B received hydroquinone 4% cream, sunscreen and placebo capsules for 3 months. All subjects had an additional 3-month follow-up visit on sunscreen alone. The primary outcome measure was change in modified Melasma Area and Severity Index (mMASI) score. In addition, the melanin index was measured using a mexameter. RESULTS: Fifty subjects were enrolled, and all completed the study. There was a 55% reduction in mMASI after 3 months from mean 8.96 (SD 2.45) to 4.0 (SD 1.6) in Group A compared to 10.9% from mean 8.53 (SD 2.04) to 7.6 (SD 2.0) in Group B. Three months after oral and topical therapy was discontinued, there was a 42% decrease in mMASI compared to baseline in Group A (mean 5.1 SD 1.7) vs. 4.7% in Group B (mean 8.1 SD 2.0). No serious adverse events were observed. CONCLUSIONS: A combination of oral tranexamic acid and topical hydroquinone is more effective than hydroquinone alone in the treatment of melasma.

Effects of oligomeric proanthocyanidins (OPCs) of red wine to improve skin whitening and moisturizing in healthy women - a placebo-controlled randomized double-blind parallel group comparative study.

OBJECTIVE: This study was undertaken to evaluate the effects of red wine from grapes oligomeric procyanidins (OPCs) intake on skin color and skin moisture in Japanese healthy women. The purpose of this study was to improve skin condition, with the primary endpoint set to improve sunburn by ultraviolet (UV) and the secondary endpoint set to improve dryness. PATIENTS AND METHODS: A randomized, placebo-controlled, double-blind, parallel-group study was conducted on 100 subjects (30 to 59 years of age). They were administered a test beverage, including 200 mg of the red wine OPCs (the test beverage group) or a placebo beverage (the control beverage group) once a day for 12 weeks. The properties of facial skin were measured at 0 (start value), 4th, 8th, and 12th week of the test period. RESULTS: After 12 weeks of administration, the pigmentation scores and melanin index values of the OPC group were significantly reduced from the start value and were lower than the control group (p<0.05). In addition, the OPC group showed a significant increase in water content of the stratum corneum compared to the start value, while that of the control group significantly decreased. CONCLUSIONS: The red wine OPCs showed the effects of skin whitening and moisturizing, and it is suggested that OPCs may improve the skin condition of healthy women.

Anti-aging and brightening effects of a topical treatment containing vitamin C, vitamin E, and raspberry leaf cell culture extract: A split-face, randomized controlled trial.

BACKGROUND: Skin aging has many manifestations such as wrinkles, uneven skin tone, and dryness. Both intrinsic and extrinsic factors, especially ultraviolet light-induced oxidative radicals, contribute to the etiology of aging. Human skin requires both water- and lipid-soluble nutrient components, including hydrophilic and lipophilic antioxidants. Vitamins C and E have important protective effects in the aging process and require exogenous supply. Raspberry leaf extracts contain botanical actives that have the potential to hydrating and moisturizing skin. Topical products with these ingredients may therefore combine to provide improved anti-aging effects over single ingredients. OBJECTIVES: To evaluate the anti-aging and brightening effects of an encapsulated serum containing vitamin C (20% w/w), vitamin E, and European raspberry (Rubus idaeus) leaf cell culture extract. METHODS: Fifty female volunteers aged 30-65 years were allocated one capsule of serum for topical application on one side of the face for 2 months, in addition to self-use of facial skin products. Both test (treated) and contralateral (untreated) sides were dermatologically assessed after 4 and 8 weeks. Skin color (melanin index), elasticity, radiance, moisture, and water evaporation were measured by Mexameter MX18® , Cutometer® , Glossymeter GL200® , Corneometer CM825® , and Tewameter TM300® instruments, respectively (Courage + Khazaka Electronic GmbH). Skin microtopography parameters, smoothness (SEsm), roughness (SEr), scaliness (SEsc), and wrinkles (SEw), were measured by Visioscan® VC98 USB (Courage + Khazaka Electronic GmbH), and gross lifting effects were measured by VECTRA® H1 (Canfield Scientific), and adverse reactions and satisfaction were also assessed. RESULTS: Skin color, elasticity, and radiance were significantly improved. The smoothness, scaliness, and wrinkles were also revealed significant improvement. Mild adverse reactions were tingling and tightness. CONCLUSIONS: The vitamin C, vitamin E, and raspberry leaf cell culture extract serum has anti-aging and brightening effects of skin.

Skin-lightening practices behind the veil: An epidemiological study among Saudi women.

BACKGROUND: Women are adopting skin-lightening practices worldwide in an attempt to enhance their skin tone. The reasons and beliefs behind such practices vary from culture to culture. Scarce data are available for this phenomenon among Saudi women. We carried out this study to determine the practices, reasons, and correlates of skin-lightening practices among women in the northern region of Saudi Arabia. METHOD: Using nonprobability convenient sampling, an analytical cross-sectional study was carried out among women attending two multispecialty hospitals in the Al-Jouf region. A prevalidated, self-administered questionnaire containing 35 items about demographic characteristics, skin-lightening practices, knowledge of skin-lightening products (SLPs), reasons, and perceptions about lighter skin tone was used to collect data. RESULTS: Among 605 sampled women, usage of skin-lightening practices was found in 382 participants (63.1%). All participants had relatively lighter skin. Skin type and education affected skin-lightening practices significantly (P values = 0.002 and 0.012, respectively). The prevalent reason for using SLPs was cosmetic (66%). One-third of users faced side effects from these products. The SLP users believed that lighter skin tone plays a role in self-esteem, perception of beauty, social class, marriage, and employment opportunities (P values < 0.01) as compared to nonusers. Media was found to influence the use of SLPs (P values < 0.001). CONCLUSION: Skin-lightening practices are prevalent among Saudi women. Such practices are reinforced by a belief that fairer skin is associated with beauty, self-esteem, and financial and social advantages. A public health educational campaign is needed to decrease the usage of SLPs.

Topical metformin in the treatment of melasma: A preliminary clinical trial.

BACKGROUND: Melasma is a common acquired pigmentary disorder characterized by symmetric hyperpigmented macules on the face. Triple combination cream (TCC) remains the gold standard treatment but its prolonged use often causes adverse effects. Recently, studies have shown that topical metformin has melanopenic action. AIMS: To evaluate the safety and efficacy of topical metformin in the treatment of melasma and to compare its efficacy with TCC (hydroquinone 2% + tretinoin 0.025% + fluocinolone acetonide 0.01%). METHODS: This was a randomized controlled study conducted on 40 patients with melasma aged more than 18 years. Patients in group 1 (n = 20) were treated with 30% metformin lotion, whereas group 2 patients (n = 20) were treated with TCC for 8 weeks. Pigmentation was assessed using Melasma Area and Severity Index (MASI) at baseline and after 8 weeks. Outcome measures included global improvement scale (grades 1-4) and patient satisfaction. Safety was assessed according to adverse events and patch testing. RESULTS: All 40 patients completed the study. Out of 20 patients in group 1, 11 showed grade 1 improvement (1% to <25%) and grade 2 (25%-50%) and grade 3 (>50%-75%) improvements were seen in one patient each. In group 2, grades 1, 2, 3, and 4 improvements were seen in 14, 2, 1, and 1 patients, respectively. However, the difference was not statistically significant. Adverse events were noted in three patients in group 2 and none in group 1. CONCLUSION: Topical metformin is a novel, safe, and almost as effective modality as TCC to treat melasma.

Melasma: A critical analysis of clinical trials investigating treatment modalities published in the past 10 years.

BACKGROUND: Melasma is an acquired disorder of facial pigmentation which is a treatment challenge. AIMS: The aim of this article is to critically appraise the clinical trial evidence for different treatment modalities for melasma, published in peer-reviewed journals in the past 10 years. PATIENTS/METHODS: The literature review was conducted using PubMed and MEDLINE. The search was performed in July 2019, and search parameters were limited to all English language articles published in the past 10 years only. RESULTS: Eighty-nine clinical trials were found. Four clinical trials investigated topical hydroquinone, supporting its safety and efficacy as first-line treatment. Twelve studies showed tranexamic acid as very promising. Nineteen studies assessed various novel oral, injectable, and topical treatments and highlight some new potential future treatments. Forty-two studies investigated laser and light treatment in melasma: LFQS laser is still one of the best options, especially in darker skin types. However, the picosecond laser has shown excellent results. Finally, 11 studies looked at peels. Overall, peels have not been shown to be superior to the use of topical therapy alone. CONCLUSION: Topical therapy with a HQ and retinoid-based product should be first line for a minimum of 3 months with the addition of oral tranexamic acid at 250 mg BD if no contraindication. Second-line treatment with lasers includes the LFQS Nd:YAG, picosecond laser, and the pulsed dye laser in lighter skin types. Third-line therapy would be the addition of chemical peels to the above treatments, with GA or TCA peels having the most evidence for effectiveness.