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Skin hyperpigmentation represents a common aesthetic and dermatological concern, often resulting from excessive melanin synthesis and oxidative stress. Effective skin-lightening strategies target these processes by inhibiting tyrosinase activity, modulating melanogenic regulators, and enhancing antioxidant defenses. Ursolic acid, a natural triterpene abundant in apple peel, has shown potential as a safe and multifunctional skin-brightening molecule. In this study, an apple oil extract rich in ursolic acid (Annurca Apple Oleolite, AAO) was developed and standardized to 784.40 ± 7.58 µg/mL. The extract demonstrated significant tyrosinase inhibition and a marked reduction in melanin content in A375 melanoma cells, accompanied by downregulation of TYRP-1, TYRP-2, and MITF expression and modulation of oxidative stress markers. These molecular effects were confirmed in a randomized, double-blind, placebo-controlled clinical trial involving 42 subjects with hyperpigmented skin. Topical application of a formulation containing 2.5% AAO for 28 days significantly reduced UV and brown spot scores (–6.4% and − 4.1%, respectively; p  < 0.001), decreased melanin index (–10.2%, p  < 0.001), and improved skin brightness and tone uniformity (ITA° +12.4%; L* +3.1%; both p  < 0.001) compared with placebo. Overall, the results highlight AAO as a promising natural agent for managing skin hyperpigmentation through multiple mechanisms, suggesting its potential utility in both cosmetic and dermatological formulations.

Acanthosis nigricans (AN) is a dermatological condition, marked by hyperpigmentation and skin thickening, frequently affecting body folds like the axillae. Treatment options for axillary hyperpigmentation remain underexplored. This study evaluated the efficacy of 0.025% tretinoin cream in treating axillary hyperpigmentation associated with AN. In a randomized, intra-individual, split-side design study, participants applied 0.025% tretinoin cream on one axilla and a cream-based on the other. The study spanned 12 weeks, with topical application for the first 8 weeks, followed by a 4-week cessation period. Efficacy was measured using the melanin (M) index via narrowband reflectance spectrophotometry. Overall success was evaluated through investigator- and participant-global evaluation (IGE and PGE) scales, with adverse effects monitored. Twenty participants completed the study. The 0.025% tretinoin cream significantly reduced hyperpigmentation compared to the control ( p  < 0.001). By week 8, the mean M index reduction with tretinoin was 28.05%±12.20%, versus 6.55%±12.66% with the control. Hyperpigmentation reappeared partially after treatment cessation. By week 8, 75% of participants in the tretinoin group achieved more than 75% improvement in IGE, compared to 35% in the cream-based group. Similarly, 75% of the tretinoin group reported more than 75% improvement in PGE, whereas only 15% of the cream-based group achieved more than 50% improvement. Adverse effects were mild and included slight erythema, peeling, and itching. The 0.025% tretinoin cream significantly improved AN patients’ axillary hyperpigmentation, demonstrating a safe and effective treatment option with minimal side effects.

Background Periorbital hyperpigmentation (POH) is a common cosmetic problem with a negative impact on the patient's self‐confidence, leading to a decrease in the quality of life. Current treatments include topical agents and mesotherapy, but research remains limited. Aims Due to the undesirable effect of the available treatments, the present study was designed to compare the effectiveness of platelet‐rich plasma (PRP) injection and intradermal injection of tranexamic acid plus vitamin C mesotherapy as a therapeutic method to treat POH. Methods Patients received an intradermal injection of PRP randomly on one side and an intradermal injection of tranexamic acid + vitamin C on the other side of their face, for three sessions with an interval of 3 weeks. Digital photography was taken, and data were assessed based on physician global assessment (PGA) and patient satisfaction. Results Eighteen patients were studied. Among all, 12 patients had a positive family history, 2 had asthma, and 4 had a history of atopic dermatitis. Even though patient satisfaction was higher in the PRP group than in mesotherapy, it was not statistically significant. Both groups showed similar rates of improvement. However, improvement rates did not significantly differ based on various factors including gender, skin type, family history, or medical history. Age and the age of disease onset also did not significantly affect the improvement rates. Conclusion Both methods revealed successful results in the reduction of POH. Comparing the efficacy of these two methods showed that both treatments had similar improvements.

Hyperpigmentation is a common complication in patients with burn injuries during wound healing; however, the mechanisms underlying its occurrence and development remain unclear. Recently, postinflammatory hyperpigmentation (PIH) was found to result from overproduction of melanin. Local or systemic inflammatory responses are often observed in patients who develop hyperpigmentation. However, we lack studies on the relationship between PIH and burn injury. Therefore, we comprehensively reviewed the existing literature on the melanogenesis of the skin, inflammatory mechanisms in pigmentation, and local or systemic alteration in inflammatory cytokines in patients suffering from burn trauma to elucidate the relationship between PIH and burn injury. We believe that this review will guide further research on regulating melanin production in the burn management process.

Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis and sequela of a variety of inflammatory skin conditions. PIH can have a negative impact on a patient’s quality of life, particularly for darker-skinned patients. Studies show that dyschromias, including PIH, are one of the most common presenting complaints of darker-skinned racial ethnic groups when visiting a dermatologist. This is likely due to an increased production or deposition of melanin into the epidermis or dermis by labile melanocytes. A variety of endogenous or exogenous inflammatory conditions can culminate in PIH and typically most epidermal lesions will appear tan, brown, or dark brown while dermal hypermelanosis has a blue-gray discoloration. Depigmenting agents target different steps in the production of melanin, most commonly inhibiting tyrosinase. These agents include hydroquinone, azelaic acid, kojic acid, arbutin, and certain licorice (glycyrrhiza) extracts. Other agents include retinoids, mequinol, ascorbic acid (vitamin C), niacinamide, N -acetyl glucosamine, and soy, and these products depigment by different mechanisms. Certain procedures can also be effective in the treatment of PIH including chemical peeling and laser therapy. It is important to note that these same therapeutic modalities may also play a role in causing PIH. Lastly, those lesions that are not amenable to medical or surgical therapy may experience some improvement with cosmetic camouflage.

Human skin pigmentation and melanin synthesis are incredibly variable, and are impacted by genetics, UV exposure, and some drugs. Patients’ physical appearance, psychological health, and social functioning are all impacted by a sizable number of skin conditions that cause pigmentary abnormalities. Hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced, are the two major classifications of skin pigmentation. Albinism, melasma, vitiligo, Addison’s disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosinase, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, 4 marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.

Background Periorbital hyperpigmentation is a prevalent skin condition that represents a large quantity of cases seen in cosmetic dermatology. Patients tend to be left with pigmentation after Q‐switched ruby laser treatment, especially the perioribital area. Aims The study is conducted to compare the effect of PRP injection combined with laser therapy versus laser alone for periorbital hyperpigmentation treatment. Patients/Methods In this single‐center, case–control study, 30 patients with periorbital hyperpigmentation were allocated to receive PRP injection injection after Q‐switched ruby laser or Q‐switched ruby laser only, followed by a 12‐week and 24‐week follow‐up visit. Visual analogue scale, Sadick tear trough rating scale, and patients' self‐evaluation were used to evaluate the therapeutic effect. Results The combined group achieved a better improvement in long‐term effect and had effect on facial rejuvenation. Patient satisfaction was higher in the combined group. Erythema and mild pain were the most common adverse reactions of both groups. Conclusions Combining with PRP injection can improve the therapeutic effect of Q‐switched ruby laser in treating periorbital hyperpigmentation and lessen the risk of post‐inflammatory hyperpigmentation, indicating a new option for POH treatment.

Most therapeutic approaches for keloids remain clinically unsatisfactory. In the last years, intralesional botulinum toxin-A (IL BTX-A) was proposed for treatment of keloids. Our aim of the study was to compare the clinical efficacy of IL BTX-A and IL 5-Fluorouracil (IL 5-FU) in treatment of keloids. A total of 50 patients with keloids were included in the study, 22 patients (with 26 keloids) were treated with IL BTX-A monthly for up to 6 months and other 22 patients (with 27 keloids) were treated with IL 5-FU weekly for up to 6 weeks, while the remaining 6 patients, each having multiple keloids, were treated with both IL BTX-A for some lesions (8 keloids) and IL 5-FU for their remaining lesions (8 keloids). The clinical improvement was assessed according to flattening of the lesions. Side effects were recorded. A significantly better therapeutic response of keloids was detected after IL BTX-A than IL 5-FU ( P  = 0.041). IL BTX-A achieved excellent and good flattening of the lesions (58.8% and 20.6%) compared to (31.4% and 17.1%) after IL 5-FU, respectively. In BTX-A treated group, there was no statistically significant difference between the clinical response in small lesions compared to medium and large ones ( P  = 0.476). While in 5-FU treated group, small and medium lesions showed significantly better response than larger ones ( P  = 0.009). IL BTX-A caused fewer side effects than IL 5-FU, less pain, itching, no hyperpigmentation and less recurrence. Both IL BTX-A and IL 5-FU showed positive results in treatment of keloids. However, IL BTX-A showed higher clinical efficacy even in large size keloids with less side effects.

Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.