Triple Combination Cream Research Articles

A Comparative Study of Efficacy between Oral Tranexamic Acid with Fluocinolone-Based Triple Combination Cream Versus Fluocinolone-Based Triple Combination Cream Alone in Melasma

Introduction: Melasma is an acquired, chronic, recurrent hyper-pigmentary disorder characterized by symmetric light-brown to bluish-gray macules and patches with irregular, sharp borders. The term “melasma” is derived from the Greek word “melas,” meaning black, while “chloasma” refers to its occurrence during pregnancy, derived from “chloazein,” meaning green. Clinically, melasma predominantly affects the face, including the forehead, cheeks, temples, upper lip, chin, and nose. Methods: This cross-sectional study was conducted on 60 clinically diagnosed cases of melasma attending the Skin and VD outpatient department of Combined Military Hospital (CMH), Dhaka, Bangladesh from January 2020 to June 2020. Result: Ages of the patient at onset of melasma, in majority (56.67%) cases were between 20-25 years and 90% study population was female. Most (56.67%) of the patients were housewife. Regarding the distribution of melasma 50% were found malar, 46.67% centro-facial and 3.33% mandibular. By 12 weeks, Group A's mean MASI score further reduced to 6.995 ± 6.056, and Group B's score decreased significantly to 2.19 ± 2.378. The P value of 0.00 confirms a statistically significant difference between the groups at 12 weeks. Conclusion: In conclusion, our study demonstrates that oral tranexamic acid in combination with fluocinolone-based triple combination cream is significantly more effective in treating facial melasma than the cream alone.

BC01 Evaluation of effectiveness of fractional ablative CO2 laser and triple combination cream in the treatment of melasma: a randomized controlled study

BC01 Evaluation of effectiveness of fractional ablative CO2 laser and triple combination cream in the treatment of melasma: a randomized controlled study

Assessing the efficacy of oral tranexamic acid as an adjuvant to triple combination topical treatment in melasma: a meta-analysis of randomized controlled trials

Abstract Melasma is a skin pigmentation disorder that lacks consistent treatment success, despite various methods used. Tranexamic acid (TXA) has shown hypopigmentation properties, but whether its administration should be combined with standard treatment has yet to be clarified. We aimed to perform an investigation of the effectiveness and safety of oral TXA as an adjuvant to triple combination cream (TCC) treatment in melasma. We searched PubMed, Embase and Cochrane (CENTRAL) for studies that compared TCC + adjuvant TXA to TCC treatment alone in patients with melasma. Outcomes of interest included change from the baseline Melasma Area and Severity Index (MASI) score, recurrence of melasma and adverse events. Statistical analysis was performed using R Studio 4.3.2. Four trials involving 490 patients were included. In the pooled analysis, the decrease from baseline in MASI score [mean difference –3.10, 95% confidence interval (CI) –5.85 to –0.35] was significantly higher in patients treated with oral TXA as an adjuvant to TCC compared with TCC alone. Melasma recurrence [risk ratio (RR) 0.28; 95% CI 0.16–0.49] was significantly lower in the group treated with TCC and TXA. Regarding erythema (RR 0.63, 95% CI 0.34–1.17) and burning (RR 0.59, 95% CI 0.30–1.17), no statistically significant difference was found. This meta-analysis demonstrated statistically significant benefits of TCC + TXA combination treatment compared with TCC alone. Furthermore, the results suggest that the addition of TXA to TCC treatment may reduce melasma recurrence.

Topical Steroid Damaged Face - A Dermascopic Analysis

ABSTRACT Background and Objectives: Dermoscopy particularly could be helpful in patients with steroid damaged face to assess and look for the damage caused by the steroid creams as also in cases where the patient provides improper history. Materials and Methods: Patients attending to dermatology OPD with suspected/diagnosed TSDF between the ages of 18 and 60 years were enrolled and assessed on the basis of age, gender, residence, duration, potency, brand of application topical steroid creams, clinical and dermoscopic features. Results: Majority abusing the topical steroid creams were females (n-14) with mean age with SD of 34 ± 11 and were from rural areas (57.8%). Red raised lesions were the most common clinical presentation (n-15) with telangiectasias as the most common dermoscopic feature (n-26). Triple combination creams containing hydroquinone 2%, tretinoin 0.025%, and 0.1% mometasone were on the top of the list (n-20). Conclusion: In this study, the importance of dermoscopy in assessing the features of topical steroid damaged face and preventing further damage is highlighted. Various factors causing topical steroid creams misuse and the easy availability of the creams is to be kept on check.

Targeting the dermis for melasma maintenance treatment

Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma, emphasize the dermal targeting therapy. We investigated maintenance effect of microneedling radiofrequency (RF) for melasma treatment. Subjects with melasma were administered oral tranexamic acid and triple combination cream for 2 months and a randomly assigned half face was treated with RF. After discontinuation of conventional therapy, the half face RF continued monthly over 6 months. Modified melasma area severity index (mMASI) score and L* value by a chromameter were collected monthly. Fifteen subjects were enrolled and eleven completed the 8-month study. At 2nd month of conventional therapy, all subjects showed improvement with a 64% reduction in mMASI score. With continuous RF treatment, the improvement was well maintained; whereas in untreated side, the Δ L* gradually decreased, returning to the baseline after the conventional therapy ended. The continuous microneedling RF therapy is beneficial in maintaining the conventional therapy of melasma suggesting the protective effect of dermal targeting therapy in melasma development.(Clinical Trial registration number: NCT05710068, date of first registration: 02/02/2023).

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.

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. To assess the efficacy and tolerance of a New Trio (NT) combination with isobutylamido-thiazolyl-resorcinol, retinoic acid and cortosteroid compared to KT. 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. 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. The NT combination appears to be an effective treatment option for treating melasma and could be considered as a well-tolerated alternative to KT.

Current updates on melasma treatments

Melasma is a common chronic relapsing pigmentary disorder primarily affecting women. It is highly prevalent in the Indian skin type with a large psychological impact. Treatment is challenging with no cure available yet. Even so, treatment modalities are many and varied-each promising more than the last. We analyzed the understanding of photoprotection, topical and oral treatments, and procedures such as microneedling, laser resurfacing, and peelings that serve as the primary methods for controlling and preventing this illness. While there are a few well established treatments such as hydroquinone and triple combination creams, side effects impede their long-term use. Safer alternatives have now come up which can be used for extended durations such as kojic acid, rucinol, and cysteamine cream. Lasers and light therapies have slowly become an essential component of melasma management. In this manuscript, we attempt to provide a critical and concise review of the current updates in melasma therapy.

Topical and Systemic Therapies in Melasma: A Systematic Review

Introduction: Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It is a chronic and distressing condition, affecting the patients' quality of life, and has been conventionally treated with “first-line” agents including hydroquinone (HQ) alone or as a part of a triple combination cream (TCC), while “second-line” options include chemical peels, and third line options include laser therapy. Materials and Methods: A systematic search was performed for all topical and systemic treatments for melasma up till May 4, 2021, using the PubMed and EMBASE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search terms “melasma” and “treatment” were used to search for the relevant articles on both these databases, and a total of 4020 articles were identified. After removing the duplicate entries and screening the titles, abstracts, and full-text articles, we identified 174 randomized controlled trials (RCTs) or controlled clinical trials. Results: Based on our review, HQ, TCCs, sunscreens, kojic acid (KA), and azelaic acid receive grade A recommendation. Further large-scale studies are required to clearly establish the efficacy of topical vitamin C, resorcinol, and topical tranexamic acid (TXA). Several newer topical agents may play a role only as an add-on or second-line drugs or as maintenance therapy. Oral TXA has a strong recommendation, provided there are no contraindications. Procyanidins, Polypodium leucotomos (PL), and even synbiotics may be taken as adjuncts. Discussion: Several newer topical and systemic agents with multimodal mechanisms of action have now become available, and the balance seems to be tipping in favor of these innovative modalities. However, it is worth mentioning that the choice of agent should be individualized and subject to availability in a particular country.

Evaluating The Efficacy And Safety Of Tranexamic Acid To Hydroquinone And Triple Combination Cream In The Treatment Of Melasma

Background: Melasma is acquired skin condition characterized by sporadic hyperpigmented macules or patches that affects photo-exposed areas which occur chronically. Melasma seriously impairs a patient’s quality of life. Current treatments for melasma include hydroquinone, corticosteroids, retinoids, natural substances, and triple combination creams (TCC), which demonstrate variable efficacy and side-effect profiles. Melasma can now be treated with tranexamic acid (TA), a well-known anti-fibrinolytic drug. Oral, topically applied, and procedural techniques were used to administer TA. Purpose: This review evaluating the efficacy and safety of tranexamic acid to hydroquinone and triple combination cream in the treatment of melasma and suggests steps that need to be taken to mainstream TA use in clinical settings. Review: Among the recent melasma treatments are including hydroquinone (HQ), triple combination topicals, and regular use of broad-spectrum sunscreen. .1 Because plasmin has been shown to have melanogenic properties, tranexamic acid (TA) is an essential therapy option for melasma due to its anti-plasmin (and consequently anti-fibrinolytic) properties. Recent research has shown that melasma-affected skin has enhanced vascularity and VEGF expression in the epidermis, suggesting yet another method by which TA may treat melasma clinically. Conclusion: The review revealed that a combination of tranexamic acid and hydroquinone has better efficacy in treating melasma rather than hydroquinone alone. Oral tranexamic acid combined with TCC can prevent recurrence and sustain the outcome.

Management of Melasma: Emerging Facts

Melasma is a dark or tan discoloration of the skin, whose exact cause is still unclear however sun exposure, hormonal influences, phototoxic drugs, and genetic factors are some of attributing factors. It is more common in females; with an 80% distribution is Centro-facial. Pathophysiologically, melasma shows the surge in dermal and epidermal pigmentation along with melanosomes, perivascular lymphohistiocytic infiltrates, and expansion of melanocytes. The latest treatment regimens include oral, topical, and procedural therapies. Conventional treatment of melasma includes hydroquinone, tretinoin, corticosteroids, and triple combination creams; Tranexamic acid, Polypodium leucotomos, and glutathione are newer drugs that have shown propitious effects. Techniques such as chemical peels, micro-needling, radiofrequency, and laser are also widely used as first-line or complementary treatments for melasma. Combing different treatment modalities have shown better efficacy than monotherapy. The objective of this review is to update the current emerging treatment modalities of melasma.

Melasma hyperpigmentation: An overview of current topical therapeutics

AbstractBackgroundMelasma is a common disorder of hyperpigmentation that affects populations globally and can adversely affect quality of life. Topical therapies—including hydroquinone and nonhydroquinone‐containing formulations—play a central role in the management of melasma.MethodsA literature review was conducted using PubMed and Google Scholar. Search keywords included a combination of the following: “melasma,” “chloasma,” and “topical treatment.” We identified and included seminal and high‐quality peer‐reviewed publications, systematic reviews, randomized controlled trials, case series, case reports, consensus statements, and expert opinions.ResultsTopical therapies are widely used for the treatment of melasma. Triple combination cream containing hydroquinone, fluocinolone, and tretinoin is the most studied formulation with the strongest evidence among treatment options. Numerous other prescription‐based and nonprescription topical agents, including a growing list of cosmeceuticals, have been used in the treatment of melasma, albeit in smaller studies.ConclusionA growing range of topical agents is available for the treatment of melasma. While larger, more robust studies are warranted, nonhydroquinone cosmeceuticals may be useful adjuncts or alternatives to the gold standard of triple‐combination hydroquinone cream.

Oral tranexamic acid with a triple combination cream versus oral tranexamic acid monotherapy in the treatment of severe melasma.

Melasma is an acquired pigmentation disorder with a complex multifactorial etiopathogenesis. Oral tranexamic acid (TA) is a promising drug for its treatment and may enhance outcomes when used in combination. To provide evidence of the efficacy and safety of oral TA as a monotherapy, and in combination with a triple combination cream, for treating melasma in the Hispanic population. Forty-four female Hispanic patients with melasma were randomly assigned to receive 325mg of oral TA every 12h plus f-TCC (fluocinolone-based triple combination cream) every 24h (group A) or 325mg of oral TA every 12h (group B) for 8weeks, after which both groups were crossed-over, and treated for an additional 8weeks. Evaluations of the mMASI score, the melanin index, and the MelasQoL were made at baseline and Weeks 4, 8, 12, and 16. There was a 50.04% and 65.45% improvement in mMASI at Weeks 4 and 8, respectively, in group A, compared to baseline, while for Week 16, an improvement of 76.85% was achieved in group B compared to baseline. Highest scores were consistent with the use of the combined treatment modality in both groups, and were evidenced by the values of the melanin index obtained. There was no significant difference in MelasQoL scores between the 2groups. No serious side effects were observed. The combination of oral TA and f-TCC is more effective than oral TA alone in the treatment of severe melasma in Hispanic patients.

Safety and efficacy of topical metformin 30% cream versus triple combination cream (Kligman's formula) in treating melasma: A randomized controlled study.

Melasma is an acquired common pigmentary condition that mostly presents as pigmented macules on the face. Triple combination creams (TCC), commonly known as kligman's formula, had been regarded as the mainstay of treatment for years. Topical metformin was recently studied for its melanopenic effects and potential use in melasma. This study aimed to evaluate the efficacy and safety of using 30% metformin cream to that of triple combination creams (Kligman's formula) in treating melasma. About 40 patients complaining of melasma were recruited for this controlled randomized trial and were divided into 2 groups. Group 1 (n=20) subjects received 30% metformin cream whereas group 2 (n=20) were treated with TCC for eight consecutive weeks. Pigmentation severity and improvements were assessed using the melasma area severity index (MASI) at baseline and after 8 weeks of using treatment. MASI score decreased dramatically from 12.18±9.33 before treatment to 5.59±4.61 at Week 8 with a mean decrease percentage of 55.97±16.77 for group 1 (p=0.001) and from 16.05±8.73 to 7.54±5.77 with a mean decrease percentage of 56.50±19.44 for group 2 (p=0.001). No significant difference was reported between the two treatment modalities regarding the reduction in melasma throughout the study period (p=0.968). Metformin cream is a safe, potential effective treatment for melasma, which needs to be verified by long-term large scale studies in diffident populations.

Topical Stabilized Cysteamine as a New Treatment for Hyperpigmentation Disorders: Melasma, Post-Inflammatory Hyperpigmentation, and Lentigines.

Cysteamine is an aminothiol naturally present in cells of the human body as an antioxidant resulting from the degradation of Coenzyme A. Physiologically it is well distributed in mammalian tissues. Highly concentrated in human milk, cysteamine acts as an intrinsic antioxidant and is known for its protective role. Multiple studies now document that cysteamine is a potent skin depigmenting agent. Historically, its rapid oxidation and very offensive odor made it difficult for topical use until recently when stabilization of cysteamine was achieved. This has led to an acceptable galenical form for topical application. Since 2015, the efficacy, safety, and tolerability of stabilized cysteamine (st.Cys) has been demonstrated in multiple clinical studies, as well a case reports. Stabilized cysteamine has demonstrated significant effectiveness for the treatment of melasma by two double-blind randomized and vehicle control trials. Stabilized cysteamine (st.Cys) has shown to be as effective as well-known depigmenting therapies, including triple combination cream or tranexamic acid mesotherapy, with higher tolerability. A recent clinical trial has shown considerable efficacy of topical cysteamine for the treatment of senile lentigines, which are usually considered to be resistant to topical depigmenting agents. Topical stabilized cysteamine can be regarded to as one of the most potent treatments available for hyperpigmentation disorders in humans. J Drugs Dermatol. 2021;20(12): 1276-1279. doi:10.36849/JDD.6367.

Efficacy of Intense Pulse Light with Triple Combination Cream Versus Triple Combination Cream alone in the Treatment of Melasma

Introduction: Various studies explored the use of intense pulse light (IPL) therapy in treating melasma, but only a few randomized clinical trials have evaluated the combination of triple combination cream (TCC) with IPL so far. Objective: This study compared the efficacy and safety of the combination of IPL and triple combination cream with triple combination cream alone in treating melasma. Material and Methods: Sixty patients with melasma were enrolled in this assessor-blinded, parallel-group randomized controlled study. Thirty patients were treated with IPL (15J/cm2, two sessions at 2-week intervals) and TCC (Hydroquinone 2%, tretinoin 0.025%, fluocinolone acetonide 0.01%) at night and broad-spectrum sunscreen during day time whereas other groups received only TCC and broad-spectrum sunscreen. The median percentage reduction in melasma area and severity index (MASI) and physician’s global assessment scale was assessed at 12-week to determine the efficacy of the treatment. The incidence of adverse effects at each follow-up and relapse at 16-week were also noted during the study period as the secondary outcome measure. Results: The median reduction in MASI achieved at 12 weeks was 48% in the IPL+TCC group and 13.1% in the TCC group from the baseline. The incidence of relapse was seen in 7.14% and 13.04% patients in the IPL+TCC group and TCC alone group respectively at 16 weeks however, this difference was not statistically significant (p&lt;0.05). Conclusion: Our study supports that IPL and TCC are more effective than TCC therapy alone in treating melasma.

Dermoscopy of topical steroid-dependent or damaged face: A cross-sectional study.

Topical corticosteroid (TCS) abuse is rampant and results in steroid addiction labeled as topical steroid-dependent or damaged face (TSDF). Indian market is replete with triple combination creams containing TCS sold as over-the-counter products at low cost, luring people to use them without prescription. The resultant damage if detected late is irreversible and difficult to treat. Dermoscopy can help in the early identification of features of TSDF at a preclinical stage resulting in better prognosis. However, the literature on the same is limited. This study is undertaken to characterize dermoscopic features of TSDF and to correlate them with potency and duration of application of the TCS. One hundred and thirty-two patients aged 18 years or above, with clinical symptoms and signs suggestive of TSDF and with history of application of TCS on the face for a period of more than one month, were enrolled in the study. Their demographic details, clinical features, and dermoscopy findings were recorded using a predesigned structured format. Comparison of dermoscopic findings with clinical examination, gender, potency of TCS, and duration of TCS use was done using Chi-square test, Fisher's exact test, and one-tailed Z-test. Mean age of the patients was 31.7 ± 8.1 years. Male to female ratio was 2:9. Sixty-nine (52.3%) patients abused TCS for more than one year. Clinical findings noted in the patients were erythema (81.1%), hyperpigmentation (80.3%), and hypertrichosis (68.2%). The most common dermoscopy findings seen were brown globules (96.2%), red diffuse areas (92.4%), vessels (87.1%), white structureless areas (86.4%), and hypertrichosis (80.3%). Red diffuse areas, vessels, brown globules, white structureless areas, and white hair were observed in a statistically higher proportion of cases dermoscopically. Y-shaped vessels and brown globules were seen in significantly higher number of patients, using TCS for more than three months and in those continuing it beyond six months, polygonal vessels were predominant. Lack of histopathological correlation is the limitation of our study. Furthermore, brown globules seen in 96.2% patients of TSDF on dermoscopy may have been over-estimated and not always signify TSDF; instead, it could represent melasma for which patient applied TCS. Dermoscopy in TSDF can help dermatologists in a multitude of ways from confirming the diagnosis to differentiating from other causes of red face and predicting the approximate duration of TCS abuse.

Comparing Efficacy of Intradermal Tranexamic Acid (TA) Verses Fluocinolone-Based Triple Combination (Hydroquinone 4%, Tretinoin 0.05%, Fluocinolone Acetonide 0.01%) Therapy in the Treatment of Melasma

Objective: To evaluate the efficacy of intradermal tranexamic acid (TA) verses fluocinolone-based triple combination (hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%)therapy in the treatment of melasma. Study Design: Randomized comparative trial Place and Duration: Study was conducted at outpatient dermatology department of Sheikh Zayed hospital Rahim Yar Khan for period of six months i.e from September 2020 to February 2021. Methods: Total 110 patients (age 18-40 year) of both genders having melasma on face were enrolled. Patients details demographics, age, sex and body mass index were recorded after taking written consent. Patients were divided into 2-groups. Group I had 55 patients and received intradermal tranexamic acid and group II had 55 patients andwere given topical fluocinolone-based triple combination (hydroquinone 4%, tretinoin 0.05%, fluocinolone acetonide 0.01%) cream. Follow up was taken for 2-months to determine efficacy and safety. Complete data was analyzed usingSPSS 22.0 version. Results: Out of 110 patients 60 (54.54%) were females and 50 (45.46%) were males. Mean age of the patients in group I was 29.15±5.14 years with mean BMI 24.16±7.22 kg/m2 and in group II mean age was 28.17±5.18 years with mean BMI 23.61±2.48 kg/m2. Most of the patients (85 or 77.27%) had mixed melasma followed by dermal (16 patients /14.54%) and epidermal melasma(9 patients/8.18%). We found that malar-type pattern of melasma was most common, found in 66 (60%) of cases. A decrease in MASI score from baseline (15.4) was found 2.4 in group-Iand 5.6 in group-II. In group II erythema, hypertrichosis, hypopigmentation and acneiform lesions were the side effects found but there was no clinically significant side effect found in group I patients. Conclusion: We found in this study that use of intradermal tranexamic acid (TA) in the treatment of melasma was effective and safe because there were no clinically significant side effects found after this treatment and reduction of MASI score was also significant. Keywords: Triple combination, Melasma, MASI, Intradermal tranexamic acid

Trends in Use of Prescription Skin Lightening Creams.

The desire for an even skin tone pervades all cultures and regions of the world. Uniform skin color is considered a sign of beauty and youth. Pigmentation abnormalities can arise idiopathically with genetic predetermination, with injury and environmental exposures, and with advancing age, and can, therefore, be distressing to patients, leading them to seek a variety of treatments with professional assistance. In this short report, we describe the trends in the use of prescription lightening creams, particularly in patients with darker skin types residing in the US. Amongst 404 participants, skin hyperpigmentation had a moderate effect on patients’ quality of life, and the most common diagnosis associated with the use of a prescription product was melasma (60.8%). The most common agent prescribed was hydroquinone (62.9%), followed by triple combination cream (31.4%). It is the dermatologist’s duty to gauge the effect of the pigmentation disease on patients’ life in order to counsel, tailor, and decide on the most appropriate treatment option.

Retrospective Analysis of Combined Treatment with Triple Combination Cream and Hyaluronic Acid Microneedle Patch for Benign Pigmented Skin Lesions

Benign pigmented skin lesions, particularly solar lentigines and seborrheic keratoses, commonly spur visits to a dermatologist...

A comparative study between the efficacy of 35% glycolic acid peel and triple combination cream in the treatment of melasma

A comparative study between the efficacy of 35% glycolic acid peel and triple combination cream in the treatment of melasma - IJCED- Print ISSN No: - 2581-4710 Online ISSN No:- 2581-4729 Article DOI No:- 10.18231/2581-4729.2018.0029, IP Indian Journal of Clinical and Experimental Dermatology-IP Indian J Clin Exp Dermat