The History and Current Status of Platelet-Rich Plasma Therapy in Dermatology.

Since the 1800s, platelet-rich plasma (PRP) has been used as a treatment for a wide range of medical conditions with a concomitant effect of tending to reduce the need for some invasive procedures. The aim of this narrative review was to concisely document the history and current usage of PRP specifically in the field of dermatology. Four databases (PubMed, Google Scholar, CINAHL, and Web of Science) were searched for primary articles written in English that evaluated human subjects and focused on PRP use in dermatology. Initial search terms included "platelet rich plasma," "alopecia," "androgenic alopecia," "dermatology," "PDGF," "aging," "skin rejuvenation," "diabetic ulcers," "venous leg ulcers," "acne," "acne scars," "scars," "hyperpigmentation," "melasma," "hypopigmentation," "vitiligo," and "PRP." After review, articles were excluded if they were commentaries, editorials, animal studies, review articles, or were unrelated to dermatology. The bibliography of retrieved articles was also searched for relevant articles. The present review results describe the function of PRP from its first usage for thrombocytopenia to its usage for melasma. In this time frame, its use in dermatology has gone through many evolutions from using its healing factors for treating wounds to using it as the treatment for wrinkles, hair loss, scars, ulcers, and skin pigmentation disorders. Its anti-inflammatory and growth factors have been shown to initiate a healing cascade that promotes the growth and regeneration of tissues. It is hoped that this review will help educate patients and physicians about the efficacy of PRP therapy and thereby help avoid unnecessary invasive procedures for certain conditions.

Efficacy and Safety of Nicotinamide 10%, Associated with Magnesium Ascorbyl Phosphate 5% and Hyaluronic Acid 5%, Compared to Hydroquinone 4% in Women with Facial Melasma: A Randomized, Double-Blind, Controlled Clinical Trial.

Background: Nicotinamide has demonstrated efficacy in the treatment of melasma. Topical antioxidants and humectants may enhance its performance. Currently, there is no controlled trial on the combination of 10% nicotinamide, 5% magnesium ascorbyl phosphate, and 5% hyaluronic acid, a dermo-cosmetic compound, in comparison to 4% hydroquinone for the treatment of melasma. This study aimed to explore the tolerability and efficacy of the association of the combined product versus hydroquinone. Methods: A randomized, double-blind trial involving women with facial melasma was conducted. Participants were instructed to apply the combined product (NIC group) twice daily or 4% hydroquinone for 60 days (HQ group) at night and placebo in the morning. Evaluations were performed at inclusion, after 14 and 60 days of treatment, measuring the modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life Scale (MELASQoL), and colorimetric luminosity. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. Results: Both interventions led to a progressive improvement in mMASI, MELASQoL, and GAIS, without a difference between them on D14 and D60 (p>0.2). For NIC, the mean reduction (95% CI) in mMASI was 16% (8-24%) on D14 and 32% (23-41%) on D60, while for HQ, it was 10% (7-24%) on D14 and 43% (34-52%) on D60. Reduction in colorimetric luminosity was greater in the HQ group at D60 (p=0.01). No serious side effects were identified. Of the initially included 50 patients, one was lost to follow-up in the HQ group on D60, and one withdrew consent from the NIC group, both unrelated to treatment. Conclusion: The association of 10% nicotinamide, 5% magnesium ascorbyl phosphate, and 5% hyaluronic acid was safe and well-tolerated, although its overall clinical efficacy was numerically inferior to 4% hydroquinone. This regimen can be considered for patients with poor tolerability to hydroquinone. Clinical Trial Registration: #RBR-4mkfmr8.

Glutathione as a skin-lightening agent and in melasma: a systematic review.

Hyperpigmentary disorders, including melasma, are challenging to treat. Glutathione has anti-melanogenic and antioxidant properties, which led to its use as a skin-lightening agent. Our objective was to review the published evidence and literature on the efficacy and safety of glutathione as a skin-lightening agent and in the treatment of melasma. A literature search was done in the PubMed, Embase, and Cochrane library databases using the search terms "glutathione as a skin-lightening agent" and "glutathione in melasma" for the past 10 years. The level of evidence, strength of recommendation, and risk of bias assessment were evaluated. Among various forms of topical glutathione, glutathione 0.5% was significantly more effective compared to glutathione 0.1% and placebo. For glutathione alone versus glutathione plus microneedling, more improvement was seen. Five randomized controlled trials and a single open-arm clinical study on oral glutathione at doses of 250 mg once a day, 250 mg twice a day, and 500 mg once a day showed a significant reduction in the melanin index compared to placebo. The combination of topical 2% glutathione plus oral glutathione was superior to monotherapy alone. There was only one placebo-controlled study on intravenous (IV) glutathione [6/16 (37.5%) vs. 3 (18.7%), (p0.054)]. The risk of bias assessment showed that almost an equal number of studies have low and high risk of bias. Topical versus oral glutathione both provide moderately efficacious skin-lightening outcomes that are localized versus generalized and have minimal versus substantial adverse effects, but they are unsustainable, with variable costs. IV glutathione is contraindicated due to lack of efficacy and side effects. It may work more as an antioxidant in melasma.

Evaluation the efficacy of microneedling with topical metformin solution compared with microneedling with topical vitamin C solution in treatment of melasma.

Several treatment modalities have been used for the treatment of melasma. Topical metformin is an anti-diabetic drug, which has melanopenic action. Vitamin C acts on melanin by inhibiting the tyrosinase enzyme, thus inhibiting melanogenesis. To compare the efficacy and safety of microneedling combined with topical metformin solution versus microneedling combined with topical vitamin C in the treatment of melasma. A spitted-face interventional comparative on 30 female patients suffering from melasma. The right side of the face was treated with microneedling and topical metformin, while the left side was treated with microneedling and topical vitamin C solution. Hemi-MASI score decreased significantly after treatment from before treatment in both groups P-value < 0.001. The percentage of improvement of Hemi-MASI score metformin group was 48.29%, While with vitamin C group was 37.19%. There was a significant improvement in dermoscopic findings in microneedling with topical metformin than with topical vitamin C group. Microneedling with topical metformin or topical vitamin C solution can be an effective and safe therapeutic option for treating melasma with no significant side effects.

Prevention of Melasma During Pregnancy: Risk Factors and Photoprotection-Focused Strategies.

Melasma is a benign but emotionally distressing skin condition that reduces patients' quality of life, with prevalence rates during pregnancy ranging from 36.4% to 75%. Troublingly, up to 30% of cases are reported to persist after delivery, even ten years later. And recurrence and aggravation are common in subsequent pregnancies. This review examines the risk factors and mechanisms associated with melasma during pregnancy and summarized corresponding preventive strategies. We emphasize the critical role of photoprotection, including the use of sunscreens from the first trimester, in reducing the incidence of melasma.

Efficacy of Subdermal Poly-d,l-Lactic Acid Injections for the Treatment of Melasma.

BACKGROUND: Melasma is a chronic, recurrent skin disorder with limited long-term treatment success using conventional therapies like hydroquinone and laser treatments, which primarily target epidermal components while leaving dermal aspects untreated. OBJECTIVE: To evaluate the efficacy and safety of poly-d,l lactic acid (PDLLA) subdermal injections for treating moderate melasma. METHODS: Three female patients (age range: 45-59 years) with Fitzpatrick skin types III and IV received three PDLLA injection sessions at 3-week intervals. Treatment outcomes were assessed using the Melasma Area and Severity Index (MASI) and patient satisfaction scores at 12-week follow-up. RESULTS: All patients showed significant MASI score improvements (reduction range: 3.60-6.30 points). Patient satisfaction ratings ranged from 3 to 4 out of 4. Temporary side effects included mild edema and bruising, resolving within 72 h. CONCLUSIONS: PDLLA subdermal injections showed promising results in melasma treatment, potentially due to its biostimulatory effects on collagen production and dermal remodeling. Further research, including histopathological analysis, is needed to confirm long-term efficacy and safety, and understand underlying mechanisms.

Azelaic Acid: Mechanisms of Action and Clinical Applications.

AZA is a non-phenolic, saturated dicarboxylic acid with nine carbon atoms, naturally produced by the yeast Malassezia. It has diverse physiological activities, including antibacterial, anti-keratinizing, antimelanogenic, antioxidant and anti-inflammatory effects. AZA is widely used in dermatology and is FDA-approved for treating papulopustular rosacea. It also shows significant efficacy in acne vulgaris and melasma. This review summarizes the mechanisms of action and clinical applications of AZA, aiming to provide theoretical support for its clinical and cosmetic use and to facilitate further research.

Melasma Revisited: National Survey Reveals How Dermatologists Diagnose and Treat This Complex Skin Condition.

BACKGROUND: Melasma is a chronic condition characterized by dark patches on the facial skin. It has a known female gender dominancy, and women usually think of melasma as being a serious cosmetic problem. Treatment of melasma can be seriously challenging, thus, dermatologists may employ different approaches for melasma. This study aimed to investigate how dermatologists diagnose and treat patients with melasma and to present the general characteristics of patients with melasma. METHODS: A survey was conducted using Google Forms targeting dermatologists in Turkiye. A total of 199 dermatologists (142 females/57 males) participated in the study. RESULTS: Most of the participants (52.3%) were residents. Majority gender of the patients was female and most common age range of patients with melasma was 30-40 years. Mixed melasma was the most common type (57.4%). Malar region was the most frequent location (58.6%). Wood's lamp examination was used by 25.6% of the participants. Topical treatment was the first-line choice for melasma therapy (95%), with Kligman's formula being the most used topical agent (69.8%). Oral therapy was not used by 70.8% of the participants. Tranexamic acid was the first choice for oral treatment (23.4%). Only 24.9% of the dermatologists used laser/light therapy, and Q-switched Nd-YAG laser was the most preferred device (58%). The most common recurrence rate was 41%-60% (45.9%). CONCLUSIONS: The findings of the current study investigating the melasma management in Turkiye revealed a female predominance and peak prevalence in the 30-40 years age group. Kligman's formula is the preferred topical treatment, whereas oral tranexamic acid remains underutilized. Recurrence rates are high, highlighting the need for preventative strategies. This study emphasizes the importance of personalized approaches and ongoing research for effective melasma management.

A Randomized Study to Evaluate the Efficacy of Oral Tranexamic Acid, Modified Kligman's Formula, and Placebo Cream in Melasma.

Background: Despite the availability of various treatment modalities, the treatment of melasma is often incomplete, with a high recurrence rate. The present study was undertaken to assess the efficacy and safety of oral tranexamic acid (TXA), modified Kligman's formula (MKF), and a placebo cream in melasma. Materials and Methods: Ninety cases of melasma of both sexes were enrolled, and divided into three groups of 30 patients each. The baseline severity of melasma was graded by Melasma Area Severity Index (MASI) score. Group A, B, and C patients were treated with oral TXA 250 mg twice daily, daily MKF cream at night, and daily placebo cream at night, respectively, for 12 weeks. Improvement in MASI score was calculated after 4, 8, and 12 weeks. At each visit, adverse effects, if any, were noted. Statistical analysis was done using Chi-square test. Results: Based on intention to treat analysis, at the end of 12 weeks, the reduction in MASI score in oral TXA, MKF, and placebo groups was 9.94(65.91%), 6.12(54.78%), and 2.07(17.22%), respectively (P = 0.00). The difference in reduction of mean MASI scores after 12 weeks between oral TXA group and MKF group was not significant (P = 0.29). The efficacy of oral TXA and MKB was significantly higher than that of the placebo group (P = 0.01 and P = 0.03, respectively). Adverse effects in all groups were mild and self-limiting. Limitations: A limited sample size, non-blinded design, and absence of dermoscopic evaluation were the study limitations. Conclusion: In view of its excellent safety profile, oral TXA may be considered as a better option for moderate to severe melasma.

Efficacy of Microneedle as an Assisted Therapy for Melasma: A Meta-analysis and Systematic Review of Randomized Controlled Trials.

BACKGROUND: Melasma is a common hyperpigmentary disorder, it has variety of treatment options, but it usually has a poor curative effect and high recurrence rate. Microneedles have shown certain prospects in the treatment of melasma as an assisted therapy, but there is no consensus on its efficacy and safety. To evaluate the efficacy and safety of microneedles as an adjuvant treatment for melasma. METHODS: Statistical tools were used to adjust the improvement of MASI scores in all studies to obtain standardized mean differences (SMD), and then, meta-analysis were performed. Risk ratio (RR) was utilized to assess adverse reactions, clinical effectiveness, and patient satisfaction. RESULTS: The effects of microneedle-assisted treatment for melasma begin to manifest at the 4th week, with optimal results observed at the 24th week, and with a high patient satisfaction. Compared with oral medication alone, microneedle-assisted therapy began to be more effective at week 12 and continued by 24 weeks. Compared with laser therapy alone, microneedle-assisted therapy also showed stronger efficacy, at the 8th week, microneedle-assisted treatment was significantly more effective, reaching its peak at the 12th week. Finally, in the comparison of microneedle and microinjection therapy, microneedle has always been more significant than micro-injection. CONCLUSIONS: Microneedle is a valuable adjunctive therapy for melasma treatment. It enhances long-term clinical outcomes compared to monotherapy and is associated with high patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Latin American consensus on the treatment of melasma.

Melasma is a chronic, relapsing hyperpigmentation disorder that primarily affects photoexposed areas, occurring most frequently in adult women with darker skin phototypes. The primary factors contributing to its development include sun exposure, sex hormones (e.g., pregnancy), and genetic predisposition. Melasma is highly prevalent in Latin America, where many countries lie in intertropical zones and exhibit significant ethnic diversity because of centuries of intermixing among Native Americans, Europeans, and Sub-Saharan Africans. Nine Latin American experts formulated a DELPHI-based consensus to develop a valuable approach for treating melasma in this diverse population. After establishing an accurate diagnosis, assessing the impact on quality of life, and determining disease severity, the consensus recommends mitigating known triggers and promoting rigorous photoprotection. Active therapy should be tailored based on individual characteristics (e.g., pregnancy status, previous treatments, skin sensitivity). Treatment options include topical depigmenting agents, systemic therapies, and procedural interventions such as laser therapy, microneedling, and chemical peels. Periodic reassessment of the treatment is essential, with strategies adjusted if targeted outcomes are not achieved. Once clinical remission is attained, patients should continue using topical depigmenting agents and maintain strict photoprotection measures to prevent recurrence.

Diffuse Facial Leukoderma Secondary to Localized Use of Hydroquinone.

Disorders of hyperpigmentation are extremely common, and hydroquinone remains one of the most common treatments for hyperpigmentation. Adverse events reported with hydroquinone use include acneiform eruptions, ochronosis, and irritant dermatitis; leukoderma has been reported in rare instances. Largely, these cases report leukoderma localized to the site of application. However, we report a case of diffuse facial leukoderma with only localized use of hydroquinone. With appropriate and prompt treatment, this leukoderma can respond to vitiligo treatment algorithms.

Safety and efficacy of a picosecond 755-nm alexandrite laser combined with topical tranexamic acid in the treatment of melasma.

BACKGROUND: The picosecond 755-nm alexandrite laser and topical tranexamic acid (TA) have shown promise in treating melasma. AIM: This aim of this study was to evaluate the efficacy and safety of combining to a picosecond 755-nm alexandrite laser combined with topical TA for melasma treatment. PATIENTS AND METHODS: Forty-eight patients' facial halves with bilateral symmetrical melasma were randomized to receive either topical TA and picosecond laser treatment or laser monotherapy. All patients received three consecutive picosecond laser treatment sessions at 4-week intervals, and additional one side facial received topical TA treatment twice daily until 4 weeks after the third treatments. Efficacy was assessed using the Modified Melasma Area and Severity Index (mMASI) score, VISIA (Canfield, USA) red area feature counts, and average pore volume as measured by Antera 3D®. Patient satisfaction was evaluated through questionnaires. RESULTS: Thirty-five patients completed the study. Post-treatment, mMASI scores and VISIA red area feature counts were lower in combination therapy halves and laser monotherapy halves, and average melanin level was lower in the combination therapy halves (p < 0.05). Comparisons between the combination therapy halves and laser monotherapy halves after the third treatment revealed significant differences in mMASI scores, melanin levels, and VISIA red area feature counts (p < 0.05). After treatment, patient satisfaction rates in the combination therapy halves and monotherapy halves was 71.4% and 54.3%, respectively (p < 0.05). No obvious adverse effects were observed in the combination therapy halves; whereas, 10.42% (5/48) of participants in the laser monotherapy halves experienced temporary pigmentation, which resolved within 3 months. CONCLUSION: The picosecond 755-nm alexandrite laser, when used independently and in combination with topical TA, has been proven to be effective in the improvement of melasma. However, the combined treatment approach showed a more pronounced improvement in melasma symptoms, with higher patient satisfaction, and was associated with a lower incidence of adverse effects. These findings strongly support that integrating topical TA with picosecond laser therapy as a superior therapeutic strategy for melasma management. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200057771.

Modulation of Melanocyte in Melasma Patients After Picosecond Laser Treatment.

BACKGROUND: Melasma is a therapeutically challenging hyperpigmented skin condition. Currently, there is a lack of in vivo observation regarding changes in melanin and dendritic melanocytes after laser treatment. OBJECTIVE: To investigate alterations in melanin and melanocytes in melasma before and after laser treatment using optical coherence tomography (OCT). METHODS: Eight female melasma patients were enrolled in Taiwan. Based on the baseline OCT scans, the patients were categorized into either epidermal-type or mixed-type melasma and were assigned different treatment protocols accordingly. Sequential OCT images were collected from melasma lesions and normal skin at baseline, Week 4 and Week 8. RESULTS: After 8 weeks of laser treatment, the mean Melasma Area Severity Index (MASI) score improved from 10.92 to 6.30. Results from OCT showed no significant changes in the normalized density, area, or intensity of melanin in both lesional and normal skin. At baseline, the mean length of dendritic melanocytes in the affected skin was 15% longer than those in normal skin; at Week 8, the mean length of lesional dendritic melanocytes became the same as those in normal skin. Additionally, the mean width of dendritic melanocytes decreased from being 4% wider to only 2% wider than those in normal skin. CONCLUSION: After 8 weeks of treatment, an improvement of MASI score was noted, mainly attributable to a reduction in lesional area. OCT showed no notable change regarding melanin, but a decrease in length and width of dendritic melanocytes was noted in the lesional skin of melasma patients.

Plasma Metabolomics Indicates Potential Biomarkers and Abnormal Metabolic Pathways in Female Melasma Patients.

BACKGROUND: Melasma is a common and chronic pigmentary disorder with complex pathogenesis, and the relationship between melasma and metabolic syndrome remains elusive. Thus, metabolomics might contribute to the early detection of potential metabolic abnormalities in individuals with melasma. OBJECTIVE: The present study aims to analyze changes in plasma metabolites of female melasma patients and identify disease markers as well as explore potential therapeutic targets. METHODS: Plasma samples from 20 female patients with melasma and 21 healthy female controls that were comparable in terms of age and body mass index were collected for untargeted metabolomics investigations. Ultra-high performance liquid chromatography-mass spectrometry was used to analyze metabolites in the plasma. Metabolic pathway analyses were employed to identify significantly differentially expressed metabolites in melasma patients. Receiver operating characteristic curves were constructed, and correlation analyses were performed using the modified Melasma Area and Severity Index and oxidative stress levels. RESULTS: In contrast to healthy subjects, melasma patients showed significant alterations in 125 plasma metabolites, including amino acids, lipids, and carbohydrate-related metabolites. KEGG pathway analysis suggested that primary pathways associated with the development of melasma include tryptophan metabolism, as well as the biosynthesis of phenylalanine, tyrosine, and tryptophan. Importantly, based on receiver operating characteristic curves and correlation analyses, several metabolites were identified as robust biomarkers for melasma. CONCLUSION: Collectively, this study identified significant changes in plasma metabolites in melasma patients, providing new insights into the pathogenesis of melasma and opening novel therapeutic avenues.

Nano-vesicular systems for melanocytes targeting and melasma treatment: In-vitro characterization, ex-vivo skin retention, and preliminary clinical appraisal.

Melasma represents an acquired melanogenesis disorder resulting in skin's hyperpigmentation effect. Although several approaches are adopted for melasma treatment, nanotechnology presents the most convenient one. Therefore, the present work aimed to formulate and characterize three nano-vesicular systems namely, liposomes, penetration enhancer containing vesicles (PEVs) and invasomes to enhance the topical delivery of the skin whitening agent; alpha arbutin (α-arbutin) for the treatment of melasma. Liposomes were prepared according to a 23 full factorial design and the selected formula was further employed for the preparation of PEVs and invasomes. Results showed that the three vesicular systems exhibited nano-sizes ranging from 151.95 to 672.5 nm, negative charges ranging from -12.50 to -28.20 mV, high entrapment efficiencies ranging from 80.59 to 99.53 %, good stability and prolonged-release of α-arbutin for 24 h after dispersion in hydrogel form. The deposition study from the vesicular hydrogel confirmed their effectiveness for the drug's accumulation in the skin reaching an average of 1.6-fold higher in the stratum corneum, 1.6-1.8-fold higher in the epidermis, and 1.6-1.8-fold higher in the dermis compared to the free drug dispersion in hydrogel. A preliminary clinical split-face study on patients suffering from melasma revealed that α-arbutin-loaded liposomes and PEVs in hydrogel forms showed better clinical outcomes compared to the free α-arbutin hydrogel as well as to the previously published α-arbutin encapsulated in chitosan nanoparticles and dispersed in hydrogel form. This delineates the aforementioned nano-vesicular systems as effective and clinically superior delivery means for melasma management.

Safety and Efficacy of Trichloroacetic Acid Peels in the Treatment of Melasma: A Split-face, Randomized, Prospective Trial in Latin American Women.

Background: There is controversy on the efficacy and safety of chemical peels used to treat Hispanic women with melasma. Studies evaluating superficial peels for melasma are limited due to lack of controls, blinding or objective assessment tools, poor inclusion of darker phototypes, and small sample number. Objectives: We sought to evaluate the safety and efficacy of trichloroacetic acid (TCA) peels when added to hydroquinone and tretinoin in the treatment of melasma in Hispanic women. Methods: A single blinded, prospective, split-face trial of superficial TCA peels was performed on Hispanic women with melasma. Topical hydroquinone and tretinoin were used on both sides. A total of four monthly peels were performed on one side. The relative reduction of melasma severity was evaluated using narrowband reflectance spectrophotometry (NRS), Modified Melasma Area and Severity Index (mMASI), and Global Melasma Severity Assessment (GMSA). Adverse events were monitored. Results: Thirty-three patients completed the study. Pigment intensity was reduced on both sides based on all measures. A greater improvement of mMASI and GMSA was achieved on the peeled side. Limitations: Limitations include the single-center study design with one blinded investigator. Conclusion: Based on our results, TCA peels appear to be safe and effective in augmenting treatment response on melasma patients with phototypes III and IV treated with hydroquinone and tretinoin.

What lies behind melasma: a review of the related skin microenvironment.

Melasma is an acquired chronic pigmentary disorder affecting millions of individuals worldwide. However, the pathogenesis of melasma remains unclear. This article provides a comprehensive review of the pathophysiological changes occurring in the skin microenvironment of melasma lesions, which can be summarized as follows: (1) skin barrier dysfunction and abnormal synthesis, transport, and intracellular distribution of melanin in the epidermis; (2) basement membrane damage; (3) solar elastosis, vascular changes, senescent fibroblasts, mast cell infiltration, and sebocyte participation in the dermis; and (4) systemic factors such as sex hormones and oxidative stress. Furthermore, potential therapeutic strategies are introduced to provide novel perspectives for fundamental and clinical research related to melasma.

Tyrosinase Inhibition and Antimelanogenic Effects of Resorcinol-Containing Compounds.

Tyrosinases (TYRs) are copper-containing metalloenzymes present in a large diversity of species. In human, hTYR is responsible for pivotal steps in melanogenesis, catalysing the oxidation of l-tyrosine to l-DOPA and further to dopaquinone. While numerous TYR inhibitors have been reported, polyphenolic compounds tend to dominate the literature. However, many of these compounds, particularly monophenols and catechols, have been identified as alternative substrates rather than true inhibitors, given their structural similarity to natural substrates. Resorcinol-containing compounds have emerged as promising candidates to address this challenge, as the meta-dihydroxy moiety in resorcinol demonstrates resistance to TYR-mediated oxidation, while retaining the favourable interactions with copper ions provided by the hydroxy groups. Although their precise mechanism of action remains debated, resorcinol derivatives have yielded some of the most active compounds against isolated mushroom and human TYRs, as well as clinically used dermocosmetic agents like rucinol and thiamidol, which exhibited very promising effects in patients with facial melasma. This review outlines the development of resorcinol-containing TYR inhibitors, categorized by scaffold type, ranging from simple alkyl analogues to intricate synthetic derivatives. Mechanistic insights about the resorcinol-TYR interaction are also presented and debated.