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1.  Refractory Postinflammatory Hyperpigmentation Treated Fractional CO2 Laser 
Objective: Postinflammatory hyperpigmentation is a reactive hypermelanosis of the skin that occurs as a consequence of an inflammatory process, such as acne, eczema, drug reactions, burns, chemical peelings, and laser applications. Although topical agents remain to be the first-line treatment of postinflammatory hyperpigmentation, treatment of recalcitrant cases is challenging. The Q-switched ruby laser, the low-dose Q-switched neodymium-doped yttrium aluminum garnet laser, and the fractional 1550nm erbium-doped fiber laser have been reported to improve postinflammatory hyperpigmentation. Design/setting/participants: The authors present a case of refractory postinflammatory hyperpigmentation successfully treated with two sessions of fractional CO2 laser in a 24-year-old woman with Fitzpatrick skin type III. Results: After two treatment sessions with a one-month interval, the lesion totally cleared without any complications. Conclusion: Although many laser systems, including fractional CO2 lasers, can cause postinflammatory hyperpigmentation, they also can be very efficacious tools by using conservative laser settings and by providing appropriate post-treatment care in recalcitrant postinflammatory hyperpigmentation treatment.
PMCID: PMC3970832
2.  Efficacy and Safety of Clindamycin Phosphate 1.2% and Tretinoin 0.025% Gel for the Treatment of Acne and Acne-induced Post-inflammatory Hyperpigmentation in Patients with Skin of Color 
Objective: To assess the efficacy and safety of a topical gel containing clindamycin 1.2% and tretinoin 0.025% for the treatment of acne and acne-induced postinflammatory hyperpigmentation (PIH) in darker skinned patients. Design: Randomized, double-blind, placebo-controlled study. Setting: Two United States clinical sites. Participants: Thirty-three patients 12 years of age or older with skin types IV to VI, mild-to-moderate facial acne, and PIH were enrolled. Measurements: Patients applied clindamycin phosphate/tretinoin gel or a nonmedicated vehicle each evening and a sun protection factor 30 sunscreen daily. Changes in skin erythema and hyperpigmentation were measured using a chromameter and photographic images. Efficacy was assessed using the Evaluators Global Acne Severity Scale, lesion counts, Post-inflammatory Hyperpigmentation Severity Scales and Patient’s Global Assessment Scale. Safety and tolerability were assessed by adverse event reports and a Safety Assessment Scale. Results: The mean (SD) baseline inflammatory lesion count was 11.9 (11.1) in clindamycin/tretinoin-treated patients, decreasing by 5.5 (6.56) after 12 weeks while the mean baseline inflammatory lesion count was 13.6 (11.15) in placebo-treated patients, decreasing by 4.1 (11.36) (p=0.05 for change from baseline, clindamycin/tretinoin vs. placebo). Clindamycin/tretinoin-treated patients generally demonstrated superior efficacy versus placebo treatment. The clindamycin/tretinoin topical gel was well tolerated, causing little or no irritation, although one patient withdrew due to periorbital edema of moderate severity possibly related to clindamycin/tretinoin gel. Conclusion: Although limited by small sample size, the results of this pilot study suggest clindamycin phosphate 1.2% and tretinoin 0.025% topical gel is a safe and effective option for treating mild-to-moderate acne in patients with skin of color.
PMCID: PMC3396458  PMID: 22798973
Indian Journal of Dermatology  2009;54(4):303-309.
Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. In addition to avoidance of aggravating factors like oral pills and ultraviolet exposure, topical therapy has remained the mainstay of treatment. Multiple options for topical treatment are available, of which hydroquinone (HQ) is the most commonly prescribed agent. Besides HQ, other topical agents for which varying degrees of evidence for clinical efficacy exist include azelaic acid, kojic acid, retinoids, topical steroids, glycolic acid, mequinol, and arbutin. Topical medications modify various stages of melanogenesis, the most common mode of action being inhibition of the enzyme, tyrosinase. Combination therapy is the preferred mode of treatment for the synergism and reduction of untoward effects. The most popular combination consists of HQ, a topical steroid, and retinoic acid. Prolonged HQ usage may lead to untoward effects like depigmentation and exogenous ochronosis. The search for safer alternatives has given rise to the development of many newer agents, several of them from natural sources. Well-designed controlled clinical trials are needed to clarify their role in the routine management of melasma.
PMCID: PMC2807702  PMID: 20101327
Melasma; newer agents; topical treatment
4.  Kojic Acid vis-a-vis its Combinations with Hydroquinone and Betamethasone Valerate in Melasma: A Randomized, Single Blind, Comparative Study of Efficacy and Safety 
Indian Journal of Dermatology  2013;58(4):281-285.
Melasma is a relatively common, acquired symmetric hypermelanosis characterized by irregular light to gray-brown macules involving sun-exposed areas. Kojic acid, with its depigmenting potential due to tyrosinase inhibition and suppression of melanogenesis, has become a vital component of the dermatologists’ armamentarium against melasma.
To study and compare the efficacy of kojic acid 1% alone, vis-a-vis its separate combinations with 2% hydroquinone or 0.1% betamethasone valerate and a combination of all these three agents with respect to the duration of symptoms and level of pigmentation in the therapy of melasma.
Materials and Methods:
Eighty patients from a single tertiary care center objectively assessed by calculating the melasma area severity index (MASI) and randomized (simple randomization) into four parallel groups (A, B, C, and D) of 20 each were prescribed once daily local application at night, (participants blinded regarding the difference in identity of interventions), as follows:
Group A – kojic acid 1% cream.
Group B – kojic acid 1% and hydroquinone 2% cream.
Group C – kojic acid 1% and betamethasone valerate 0.1% cream.
Group D – kojic acid 1%, hydroquinone 2%, and betamethasone valerate 0.1% cream.
Strict photoprotection and use of a SPF 15 sunscreen was advised during the day. Patients were evaluated every 2 weeks and a fall in MASI score was calculated at the end of the study period of 12 weeks by the same investigator.
The response was compared according to percentage decrease in MASI score. Efficacy was evaluated among the groups at the end of 3 months using bivariate analysis and calculated by using the paired ‘t’ test. The clinical efficacy of group B was the highest followed closely by group D and group A, that of group C being the lowest.
Kojic acid in synergy with hydroquinone is a superior depigmenting agent as compared with other combinations.
PMCID: PMC3726874  PMID: 23918998
Kojic acid; melasma; MASI score
5.  Glycolic acid peel therapy – a current review 
Chemical peels have been time-tested and are here to stay. Alpha-hydroxy peels are highly popular in the dermatologist’s arsenal of procedures. Glycolic acid peel is the most common alpha-hydroxy acid peel, also known as fruit peel. It is simple, inexpensive, and has no downtime. This review talks about various studies of glycolic acid peels for various indications, such as acne, acne scars, melasma, postinflammatory hyperpigmentation, photoaging, and seborrhea. Combination therapies and treatment procedure are also discussed. Careful review of medical history, examination of the skin, and pre-peel priming of skin are important before every peel. Proper patient selection, peel timing, and neutralization on-time will ensure good results, with no side effects. Depth of the glycolic acid peel depends on the concentration of the acid used, the number of coats applied, and the time for which it is applied. Hence, it can be used as a very superficial peel, or even a medium depth peel. It has been found to be very safe with Fitzpatrick skin types I–IV. All in all, it is a peel that is here to stay.
PMCID: PMC3875240  PMID: 24399880
acne scar; melasma; photoaging; chemical peel; alpha-hydroxy peel
6.  Cosmeceuticals for Hyperpigmentation: What is Available? 
Cosmeceuticals are topical cosmetic-pharmaceutical hybrids that enhance the beauty through constituents that provide additional health-related benefit. Cosmeceuticals are commonly used for hyperpigmentation. These disorders are generally difficult to treat, hence the need for skin lightening agents including, cosmeceuticals. These agents selectively target hyperplastic melanocytes and inhibit key regulatory steps in melanin synthesis. With the recent safety concern regarding use of hydroquinone, the need for alternative natural, safe and efficacious skin lightening agents is becoming all the more necessary and the article attempts to look at other alternative cosmeceuticals available or maybe upcoming in the future. We carried out a PUBMED search using the following terms “cosmeceuticals, hyperpigmentation, skin lightening agents.” We cited the use of various agents used for the treatment of hyperpigmentation, mainly melasma and post-inflammatory hyperpigmentation. We describe the safety and efficacy of these agents and their advantage over the conventional therapy.
PMCID: PMC3663177  PMID: 23723597
Cosmeceuticals; hyperpigmentation; melasma
7.  A Meta-analysis to Investigate the Relation Between Fitzpatrick Skin Types and Tolerability of Adapalene-Benzoyl Peroxide Topical Gel in Subjects with Mild or Moderate Acne 
The overall goal of acne management for all patients is to select treatments that effectively address as many pathogenic factors as possible while minimizing side effects. Acne therapy in darker skin patients presents unique challenges due to differences in the risk of postinflammatory hyperpigmentation, which may develop in response to acne itself or to irritation secondary to treatment. One combination treatment currently available is a gel formulation containing a retinoid (adapalene 0.1%) in fixed combination with an antimicrobial (benzoyl peroxide 2.5%). Results from three randomized, double-blind, vehicle-controlled, clinical trials of adapalene-benzoyl peroxide were combined in a retrospective meta-analysis that included 909 patients treated for 12 weeks and assessed at each visit for erythema, scaling, dryness, and stinging/burning. Only Week 1 results were included in the meta-analysis because the worst severity of cutaneous irritation was found to occur at this timepoint in all three trials. For each study, and for the meta-analysis, comparisons were made using the Cochran-Mantel-Haenszel test. There were no statistically significant differences in dryness, scaling, and stinging/burning with adapalene-benzoyl peroxide treatment when subjects with Fitzpatrick skin types I to III were compared to subjects with Fitzpatrick skin types IV to VI (P=NS). Erythema assessments were statistically different based on skin types, as subjects with Fitzpatrick skin types IV to VI were rated as having “none” more often than those with Fitzpatrick skin types I to III (P<0.001). This could be due to the difficulty in visualizing erythema in patients with darker skin types, mainly Fitzpatrick skin types VI. Acne patients with Fitzpatrick skin types IV to VI were not found to be more susceptible to cutaneous irritation from treatment with the adapalene-benzoyl peroxide gel than patients with Fitzpatrick skin types I to III.
PMCID: PMC2945860  PMID: 20877537
8.  Chemical Peels for Melasma in Dark-Skinned Patients 
Melasma is a common disorder of hyperpigmentation, which has a severe impact on the quality of life. Inspite of tremendous research, the treatment remains frustrating both to the patient and the treating physician. Dark skin types (Fitzpatrick types IV to VI) are especially difficult to treat owing to the increased risk of post-inflammatory hyperpigmentation (PIH). The treatment ranges from a variety of easily applied topical therapies to agents like lasers and chemical peels. Peels are a well-known modality of treatment for melasma, having shown promising results in many clinical trials. However, in darker races, the choice of the peeling agent becomes relatively limited; so, there is the need for priming agents and additional maintenance peels. Although a number of new agents have come up, there is little published evidence supporting their use in day-to -day practice. The traditional glycolic peels prove to be the best both in terms of safety as well as efficacy. Lactic acid peels being relatively inexpensive and having shown equally good results in a few studies, definitely need further experimentation. We also recommend the use of a new peeling agent, the easy phytic solution, which does not require neutralisation unlike the traditional alpha-hydroxy peels. The choice of peeling agent, the peel concentration as well as the frequency and duration of peels are all important to achieve optimum results.
PMCID: PMC3560164  PMID: 23378706
Chemical peels; dark skin; melasma
9.  A Comparative Study of the Efficacy of 4% Hydroquinone vs 0.75% Kojic Acid Cream in the Treatment of Facial Melasma 
Melasma is a common acquired cause of facial hyperpigmentation seen predominantly among females with significant psychological and social impact. It is often recalcitrant to treatment. Several topical hypopigmenting agents have been used to combat melasma. Hydroquinone and Kojic Acid are well established monotherapeutic agents for treating melasma.
This study focuses mainly on the efficacy of once daily application of 4% Hydroquinone and 0.75% Kojic Acid cream (containing 0.75% Kojic acid and 2.5% vitamin C) so as to determine an effective modality of treatment for facial melasma.
Materials and Methods:
A total number of 60 patients with facial melasma attending the Out-patient department of Dermatology, Venerology and Leprosy, Fr. Muller Medical College Hospital, Mangalore from Oct 2008-April 2010 were studied. Patients were allocated alternately to group A and group B. Group A patients received 4% Hydroquinone cream and group B patient received a Kojic Acid cream (which contained 0.75% Kojic acid and 2.5% vitamin C) and were advised to apply topically once daily at night. Patients were followed up on 4th, 8th and 12th week. At each visit side effects were noted and clinical response to treatment was calculated using the MASI score.
Statistical Methods:
Chi square test, student ‘t’ test.
At the 4th week post treatment evaluation, facial hyperpigmentation responded early to 4% Hydroquinone cream than to 0.75% Kojic Acid cream. At the end of 12 week treatment period, 4% Hydroquinone cream had an overall superiority to 0.75% Kojic Acid cream as a topical hypopigmenting agent.
The results of the study show that 4% Hydroquinone cream is a better topical hypopigmenting agent with rapid rate of clinical improvement when compared to 0.75% Kojic Acid cream.
PMCID: PMC3657227  PMID: 23716817
Melasma; 4% Hydroquinone cream; 0.75% Kojic Acid cream
10.  Examining the Impact of Skin Lighteners In Vitro 
Three cosmetically important skin lightening agents, hydroquinone (HQ), kojic acid (KA), and niacinamide (NA), consume the bulk of successful skin lightening ingredients in cosmetic applications. However, the mechanisms by which these ingredients work are still unclear. In this study, melanocytes and keratinocytes were treated with high, nontoxic doses of HQ, KA, and NA and the cells were examined by human microarrays and protein assays for several important targets including cytotoxicity, melanin expression, tyrosinase gene (TYR) and protein expression, melanocortin-1 receptor (MC1R) gene and protein expression, cytochrome c oxidase-1 (COX1) gene and protein expression, and ferritin (FTH1) gene and protein expression. It was found that all the skin lighteners examined showed marked increases in TYR, COX1, and FTH1 gene and protein expression, but not in MC1R expression in melanocytes. Upregulation of COX1 and FTH1 genes and proteins was common across both cell lines, melanocytes and keratinocytes. The results of the tyrosinase expression were somewhat unexpected. The role of iron in the expression of melanin is somewhat unexplored, but common and strong upregulation of ferritin protein in both types of cells due to the treatments suggests that iron plays a more pivotal role in melanin synthesis than previously anticipated.
PMCID: PMC3655678  PMID: 23738040
11.  Synergistic Combination of an In-office Procedure and Home Regimen for the Treatment of Facial Hyperpigmentation 
Hyperpigmentation disorders, such as melasma and solar lentigines, pose a significant treatment challenge for most patients. Combining a series of in-office procedures, such as chemical peels and light- and laser-based treatments, with maintenance therapies have been shown to provide greater efficacy than one treatment alone. However, receiving multiple in-office procedures may be cost prohibitive for patients. A series of eight case studies were conducted to evaluate the efficacy and tolerability of a novel treatment regimen combining one in-office superficial chemical peel procedure followed by a 12-week topical maintenance program consisting of micro-entrapped 4% hydroquinone, tri-retinol, and sunscreen with sun protection factor (SPF) 30+. Patients presented with Fitzpatrick skin types II and III and mild-to-moderate solar lentigines and/or melasma on their facial skin. Physician-graded overall improvement in hyperpigmentation, standardized photography, and patient satisfaction were evaluated at Weeks 4, 8, and 12. At Week 12, all eight patients demonstrated improvements of at least 25 percent in overall facial hyperpigmentation, with six of the patients demonstrating a 50- or 75-percent overall improvement. One hundred percent of the patients rated their experience with the novel treatment regimen as “excellent” or “good” reflecting high patient satisfaction. Standardized photographs also support the physician and patient findings. Results from these case studies demonstrate that this unique treatment regimen combining one in-office procedure followed by 12 weeks of topical maintenance therapy, may provide an effective, simple, and cost-effective option for patients with facial hyperpigmentation.
PMCID: PMC3366447  PMID: 22708006
12.  Cutaneous Pigmentation Following Photosensitivity Induced by Vandetanib (ZD6474) 
Archives of dermatology  2009;145(8):923-925.
Photosensitivity has been reported in patients treated with vandetanib (ZD6474), an inhibitor of epidermal growth factor receptor, vascular endothelial growth factor receptor, and the RET (rearranged during transfection) kinases.
We describe cutaneous hyperpigmentation following photosensitivity in two patients treated with vandetanib. The pigmentation patterns were variable within and between patients. Biopsies from different sites revealed variability in staining patterns with Perls’ and Fontana stains.
These patients highlight the unusual occurrence of cutaneous hyperpigmentation following vandetanib-associated photosensitivity, emphasizing that medications are important causes of acquired photosensitivity and hyperpigmentation. Aggressive photoprotection may facilitate resolution of diffuse hyperpigmentation. Dermatologists should endeavor to identify and report novel cutaneous side effects as new targeted therapies are developed.
PMCID: PMC3521518  PMID: 19687425
13.  Polypodium leucotomos as an Adjunct Treatment of Pigmentary Disorders 
Introduction: Extracts of the tropical fern Polypodium leucotomos appear to possess beneficial properties for the skin attributed to the presence of numerous compounds within the extract that have antioxidant and photoprotective properties. Orally administered Polypodium leucotomos may provide protection against the detrimental photoaging effects of sunlight and can also help reduce the frequency and severity of polymorphous light eruption. Polypodium leucotomos has also been shown to be beneficial for the prevention and potential treatment of several aesthetically relevant conditions. Objective: The purpose of this review is to investigate the beneficial role of Polypodium leucotomos as an adjunct treatment for vitiligo, melasma, and postinflammatory hyperpigmentation. Results: Based on a review of relevant literature including the results of a randomized, placebo-controlled study, the oral administration of Polypodium leucotomos significantly improved the severity of melasma in women after 12 weeks. Three randomized, double-blind, placebo-controlled studies have demonstrated significant improvements in vitiligo when oral Polypodium leucotomos therapy was combined with psoralens plus ultraviolet A and narrowband ultraviolet B. No controlled studies have assessed the efficacy of Polypodium leucotomos for the treatment of postinflammatory hyperpigmentation; however, its known antioxidant and anti-inflammatory properties and demonstrated effectiveness for melasma support its use for treating this condition. No adverse events have been associated with the use of Polypodium leucotomos. Conclusion: In addition to preventing many harmful effects associated with sunlight exposure, orally administered Polypodium leucotomos also appears to provide adjunctive benefits in treating vitiligo, melasma, and may have the potential to help with postinflammatory hyperpigmentation.
PMCID: PMC3970827
14.  The Hunt for Natural Skin Whitening Agents 
Skin whitening products are commercially available for cosmetic purposes in order to obtain a lighter skin appearance. They are also utilized for clinical treatment of pigmentary disorders such as melasma or postinflammatory hyperpigmentation. Whitening agents act at various levels of melanin production in the skin. Many of them are known as competitive inhibitors of tyrosinase, the key enzyme in melanogenesis. Others inhibit the maturation of this enzyme or the transport of pigment granules (melanosomes) from melanocytes to surrounding keratinocytes. In this review we present an overview of (natural) whitening products that may decrease skin pigmentation by their interference with the pigmentary processes.
PMCID: PMC2801997  PMID: 20054473
whitening; tyrosinase inhibitors; natural agents; cosmetics
15.  Epidermal Growth Factor Receptor Inhibitors: A Review of Cutaneous Adverse Events and Management 
Epidermal growth factor inhibitors (EGFRI), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, cutaneous adverse events are common due to the interference of epidermal growth factor receptor (EGFR) signaling in the skin. Cutaneous toxicities lead to poor compliance, drug cessation, and psychosocial discomfort. This paper summarizes the current knowledge concerning the presentation and management of skin toxicity from EGFRI. The common dermatologic adverse events are papulopustules and xerosis. Less common findings are paronychia, regulatory abnormalities of hair growth, maculopapular rash, mucositis, and postinflammatory hyperpigmentation. Radiation enhances EGFRI rash due to synergistic toxicity. There is a positive correlation between the occurrence and severity of cutaneous adverse effects and tumor response. To date, prophylactic systemic tetracycline and tetracycline class antibiotics have proven to be the most effective treatment regime.
PMCID: PMC3958662  PMID: 24723942
16.  Inhibitory Effects of Resveratrol on Melanin Synthesis in Ultraviolet B-Induced Pigmentation in Guinea Pig Skin 
Biomolecules & Therapeutics  2014;22(1):35-40.
Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits α-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging.
PMCID: PMC3936427  PMID: 24596619
Resveratrol; Depigmentation; Hyperpigmentation; Melanogenesis; Guinea pig; Ultraviolet B
17.  Depigmenting Effect of Kojic Acid Esters in Hyperpigmented B16F1 Melanoma Cells 
The depigmenting effect of kojic acid esters synthesized by the esterification of kojic acid using Rhizomucor miehei immobilized lipase was investigated in B16F1 melanoma cells. The depigmenting effect of kojic acid and kojic acid esters was evaluated by the inhibitory effect of melanin formation and tyrosinase activity on alpha-stimulating hormone- (α-MSH-) induced melanin synthesis in B16F1 melanoma cells. The cellular tyrosinase inhibitory effect of kojic acid monooleate, kojic acid monolaurate, and kojic acid monopalmitate was found similar to kojic acid at nontoxic doses ranging from 1.95 to 62.5 μg/mL. However, kojic acid monopalmitate gave slightly higher inhibition to melanin formation compared to other inhibitors at doses ranging from 15.63 to 62.5 μg/mL. Kojic acid and kojic acid esters also show antioxidant activity that will enhance the depigmenting effect. The cytotoxicity of kojic acid esters in B16F1 melanoma cells was significantly lower than kojic acid at high doses, ranging from 125 and 500 μg/mL. Since kojic acid esters have lower cytotoxic effect than kojic acid, it is suggested that kojic acid esters can be used as alternatives for a safe skin whitening agent and potential depigmenting agents to treat hyperpigmentation.
PMCID: PMC3468271  PMID: 23091364
18.  Easy as PIE (Postinflammatory Erythema) 
Background: No term exists to date describing the phenomenon of pink-to-red discoloration after an inflammatory acne lesion. Objectives: To introduce new terminology into the dermatology literature to describe erythema often seen after inflammatory acne vulgaris and to present a treatment option for this type of erythema. Methods: New terminology describing erythema after inflammatory acne is addressed, and a treatment option for postinflammatory erythema is presented. Results: Postinflammatory erythema is a new, accurate descriptor of erythema that occurs after inflammatory acne. Additionally, pulsed dye laser treatment improved postinflammatory erythema in the authors’ patients. Limitations: This paper only presents anecdotal cases. Conclusion: The addition of postinflammatory erythema to the dermatology literature may facilitate accurate communication among providers and direct laser treatment for postinflammatory erythema.
PMCID: PMC3780804  PMID: 24062874
Indian Journal of Dermatology  2009;54(1):41-45.
Melasma is a symmetric progressive hyperpigmentation of the facial skin that occurs in all races but has a predilection for darker skin phenotypes. Depigmenting agents, laser and chemical peeling as classic Jessner's solution, modified Jessner's solution and trichloroacetic acid have been used alone and in combination in the treatment of melasma.
The aim of the study was to compare the therapeutic effect of combined 15% Trichloroacetic acid (TCA) and modified Jessner's solution with 15% TCA on melasma.
Materials and Methods:
Twenty married females with melasma (epidermal type), with a mean age of 38.25 years, were included in this study. All were of skin type III or IV. Fifteen percent TCA was applied to the whole face, with the exception of the left malar area to which combined TCA 15% and modified Jessner's solution was applied.
Our results revealed statistically highly significant difference between MASI Score (Melasma Area and Severity Index) between the right malar area and the left malar area.
Modified Jessner's solution proved to be useful as an adjuvant treatment with TCA in the treatment of melasma, improving the results and minimizing postinflammatory hyperpigmentation.
PMCID: PMC2800869  PMID: 20049268
Classic Jessner's solution; chemical peeling; melasma; modified Jessner's solution; trichloroacetic acid
20.  Effects of trans-4-(aminomethyl) cyclohexanecarboxylic acid/potassium azeloyl diglycinate/niacinamide topical emulsion in Thai adults with melasma: a single-center, randomized, double-blind, controlled study 
Background: Melasma is an acquired hyperpigmentary disorder characterized by dark patches or macules located on the cheeks, forehead, upper lip, chin, and neck. Treatment of melasma involves the use of topical hypopigmenting agents such as hydroquinone, tretinoin, and azelaic acid and its derivatives.
Objective: The purpose of this study was to assess the efficacy of a formulation containing a combination of trans-4-(aminomethyl) cyclohexanecarboxylic acid/potassium azeloyl diglycinate/niacinamide compared with an emulsion-based control in the treatment of melasma in Thai adults.
Methods: In this single-center, randomized, double-blind, controlled study, Thai patients with mild to moderate facial melasma (relative melanin value [RMV] in range of 20–120) were randomized for the application of either the test or the emulsion-based (control) product in the morning and before bedtime for 8 weeks. The supplemental sunscreen product with sun protection factor 30 was distributed to all patients. Subjects were assessed for the intensity of their hyperpigmented skin area by measuring the difference in the absolute melanin value between hyperpigmented skin and normal skin (RMV). This parameter was used as a primary outcome of this study. Additionally, the severity of melasma was determined visually using the Melasma Area and Severity Index (MASI) scored independently by 3 investigators. The assessments of melasma intensity and other skin properties were performed before administration (week 0) and every 2 weeks thereafter for up to 8 weeks. Other skin properties, including moisture content, pH, and redness (erythema value), were measured. Adverse events (AEs), including erythema, scaling, and edema, were also assessed by a dermatologist using the visual grading scale of Frosch and Kligman and COLIPA.
Results: The resulting primary intent-to-treat (ITT) population included 33 patients in the test group and 34 patients in the control group. Sixty patients completed all 8 weeks of the study (on-treatment [OT] population): 91% (30) of the 33 patients in the test group, and 88% (30) of the 34 patients in the control group. Between-group differences in mean RMV were statistically significant at week 6 in both the primary ITT (P = 0.005) and OT (P = 0.006) populations. The significant differences in mean MASI scores between the test and the control groups were initially observed at weeks 4 (P = 0.005) and 8 (P = 0.027) in the OT and primary ITT populations, respectively. Other parameters, including skin pH, erythema, and moisture content did not significantly change from baseline at any time point of study. The incidence of AEs was not different between the test (4/33 [12%]) and control (5/34 [15%]) groups.
Conclusions: The significant differences in RMVs between the test and control groups were observed after 6 weeks of treatment, both in the primary ITT and OT populations. The incidence of patients with AEs was not significantly different between the test and control groups.
PMCID: PMC3969619
trans-4-(aminomethyl) cyclohexanecarboxylic acid/potassium azeloyl diglycinate/niacinamide; melasma; Thai adults
21.  Topical Hypopigmenting Agents for Pigmentary Disorders and Their Mechanisms of Action 
Annals of Dermatology  2012;24(1):1-6.
Melanin is produced in melanocytes and stored in melanosomes. In spite of its beneficial sun-protective effect, abnormal accumulation of melanin results in esthetic problems. Hydroquinone, competing with tyrosine, is a major ingredient in topical pharmacological agents. However, frequent adverse reactions are amongst its major limitation. To solve this problem, several alternatives such as arbutin, kojic acid, aloesin, and 4-n-butyl resorcinol have been developed. Herein, we classify hypopigmenting agents according to their mechanism of action; a) regulation of enzyme, which is subdivided into three categories, i) regulation of transcription and maturation of tyrosinase, ii) inhibition of tyrosinase activity, and iii) post-transcriptional control of tyrosinase; b) inhibition of melanosome transfer, and c) additional mechanisms such as regulation of the melanocyte environment and antioxidant agents.
PMCID: PMC3283838  PMID: 22363147
Hydroquinone; Hypopigmentation; Melanin
22.  Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells 
Journal of Biomedical Science  2010;17(Suppl 1):S45.
Pigmentation in human skin is an important defense mechanism against sunlight or oxidative stress. Despite the protective role of melanin, abnormal hyperpigmentation such as freckles and chloasma sometimes can be serious aesthetic problems. Because of these effects of hyperpigmentation, people have considered the effect of depigmentation. Azelaic acid (AZ) is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we showed that AZ inhibited melanogenesis. In this study, we investigated the antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse melanoma cells.
The mouse melanoma cell line B16F10 was used in the study. We measured melanin contents and tyrosinase activity. To gain the change of protein expression, we carried out western blotting.
We investigated that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes than the treatment of AZ alone. AZ combined with Tau inhibited the melanin production and tyrosinase activity of B16F10 melanoma cells without significant cytotoxicity. Also inhibitory effects after treatment with these combined chemical are stronger than AZ alone on melanogenesis.
These findings indicate that AZ with Tau might play an important role in the regulation of melanin formation and be useful as effective ingredients in antimelanogesis.
PMCID: PMC2994384  PMID: 20804622
23.  Determination of the Thermodegradation of deoxyArbutin in Aqueous Solution by High Performance Liquid Chromatography 
Tyrosinase is the key and rate-limiting enzyme responsible for the conversion of tyrosine into melanin. Competitive inhibition of tyrosinase enzymatic activity results in decreased or absent melanin synthesis by melanocytes in human skin. DeoxyArbutin (4-[(tetrahydro-2H-pyran-2-yl)oxy]phenol), a novel skin whitening agent, was synthesized through the removal of hydroxyl groups from the glucose side-chain of arbutin. DeoxyArbutin not only shows greater inhibition of tyrosinase activity but is also safer than hydroquinone and arbutin. Hence, deoxyArbutin is a potential skin whitening agent for cosmetics and depigmenting drugs; however, stability of this compound under some conditions remains a problem. The lack of stability poses developmental and practical difficulties for the use of deoxyArbutin in cosmetics and medicines. Improving the thermostability of deoxyArbutin is an important issue for its development. In this research, we established an analytical procedure to verify the amount of deoxyArbutin in solutions using a high performance liquid chromatographic (HPLC) method. The results indicate that this novel skin whitening agent is a thermolabile compound in aqueous solutions. Additionally, the rate constant for thermodegradation (k) and the half-life (t1/2) of deoxyArbutin were determined and can be used to understand the thermodegradation kinetics of deoxyArbutin. This information can aid in the application of deoxyArbutin for many future uses.
PMCID: PMC2996804  PMID: 21152314
deoxyArbutin; hydroquinone; skin whitening; thermostability; tyrosinase inhibitor
24.  Plants from Brazilian Cerrado with Potent Tyrosinase Inhibitory Activity 
PLoS ONE  2012;7(11):e48589.
The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC50 value of 11.88 µg/mL, compared to kojic acid (IC50 value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC50 value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations.
PMCID: PMC3500240  PMID: 23173036
25.  A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma 
Background. Multiple modalities have been used in the treatment of melasma with variable success. Niacinamide has anti-inflammatory properties and is able to decrease the transfer of melanosomes. Objective. To evaluate the therapeutic effect of topical niacinamide versus hydroquinone (HQ) in melasma patients. Patients and Methods. Twenty-seven melasma patients were randomized to receive for eight weeks 4% niacinamide cream on one side of the face, and 4% HQ cream on the other. Sunscreen was applied along the observation period. They were assessed by noninvasive techniques for the evaluation of skin color, as well as subjective scales and histological sections initially and after the treatment with niacinamide. Results. All patients showed pigment improvement with both treatments. Colorimetric measures did not show statistical differences between both sides. However, good to excellent improvement was observed with niacinamide in 44% of patients, compared to 55% with HQ. Niacinamide reduced importantly the mast cell infiltrate and showed improvement of solar elastosis in melasma skin. Side effects were present in 18% with niacinamide versus 29% with HQ. Conclusion. Niacinamide induces a decrease in pigmentation, inflammatory infiltrate, and solar elastosis. Niacinamide is a safe and effective therapeutic agent for this condition.
PMCID: PMC3142702  PMID: 21822427

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