Reliability Assessment and Validation of the Skin Hyperpigmentation Index Compared to the Physician Global Assessment Score

<b><i>Background:</i></b> The skin hyperpigmentation index (SHI), a new objective method for measuring skin hyperpigmentation, needs validation. <b><i>Objective:</i></b> To gain evidence of the reliability and validity of the SHI. <b><i>Methods:</i></b> Fifteen raters were divided into 3 groups (5 dermatologists, 5 nondermatologist physicians, and 5 nonphysician clinicians). Each rated 5 pigmented mole lesions with mild-to-severe hyperpigmentation to determine intra- and interrater reliability. All raters photographed the lesions and rated them using the subjective Physician Global Assessment (PGA) score. The same photographs were then assessed based on automatic computer measurement software using the online SHI tool (https://shi.skinimageanalysis.com). <b><i>Results:</i></b> The SHI reliability was excellent for all intra- and interrater assessments, while most PGA assessments showed good intra- and interrater agreement. Between-group reliability was excellent for SHI, while moderate-to-good for PGA evaluations. Concordance between the SHI and PGA assessments was strong across all groups of assessors. <b><i>Conclusion:</i></b> There is evidence that the SHI is a reliable instrument for measuring skin hyperpigmentation, and can be used by nonexperienced clinicians.

α-Amyrin and β-Amyrin Isolated from Celastrus hindsii Leaves and Their Antioxidant, Anti-Xanthine Oxidase, and Anti-Tyrosinase Potentials

Celastrus hindsii is a popular medicinal plant in Vietnam and Southeast Asian countries as well as in South America. In this study, an amount of 12.05 g of an α-amyrin and β-amyrin mixture was isolated from C. hindsii (10.75 g/kg dry weight) by column chromatography applying different solvent systems to obtain maximum efficiency. α-Amyrin and β-amyrin were then confirmed by gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS), and nuclear magnetic resonance (NMR). The antioxidant activities of the α-amyrin and β-amyrin mixture were determined via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays with IC50 of 125.55 and 155.28 µg/mL, respectively. The mixture exhibited a high potential for preventing gout by inhibiting a relevant key enzyme, xanthine oxidase (XO) (IC50 = 258.22 µg/mL). Additionally, an important enzyme in skin hyperpigmentation, tyrosinase, was suppressed by the α-amyrin and β-amyrin mixture (IC50 = 178.85 µg/mL). This study showed that C. hindsii is an abundant source for the isolation of α-amyrin and β-amyrin. Furthermore, this was the first study indicating that α-amyrin and β-amyrin mixture are promising in future therapies for gout and skin hyperpigmentation.

Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (GDA) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA-overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging.

Minocycline-induced blue sclera and skin hyperpigmentation

A 73-year-old man presented to the emergency department with lethargy and influenza-like symptoms. Incidentally, prominent blue sclera and blue-grey skin discolouration to the periorbital skin, pinnae, neck, upper and lower limbs, hands, feet, fingernails and toenails were noted. His general practitioner (GP) had previously ceased amiodarone, believing it to be the causative agent. A literature search confirms the side effects were likely due to minocycline, which the patient had been taking for 10 years. Long-term minocycline use is associated with scleral and skin hyperpigmentation, with no apparent adverse effect on ocular structure or function. The pigmentation may reverse with cessation of minocycline, or it may be permanent. Amiodarone may also cause skin hyperpigmentation, but scleral pigmentation is not a known association. This case report explores the side effect profiles of these two drugs, and highlights the potential for confusion regarding causative agents when used concurrently.

A Review of Oral Therapies for the Treatment of Skin Hyperpigmentation

This review article examines evidence supporting the use of oral therapies in treating idiopathic, actinic, and metabolically induced skin hyperpigmentation. A thorough review of the literature regarding oral treatments for hyperpigmentation was systematically conducted through PubMed. Keywords used in the primary search include “Hyperpigmentation,” “Melanosis” or “Melasma,” “Lightening,” “Oral,” and “Therapeutics.” The search was limited to the English language, and no timeframe restrictions were implemented. Numerous orally administered therapies have been proposed for the treatment of skin hyperpigmentation. There is an abundant body of literature demonstrating the efficacy of orally administered tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. It is reasonable to expect that the most effective oral therapies will address known underlying causes of hyperpigmentation such as thyroid disease, diabetes, and hormonal imbalance. Improvement due to oral therapy of otherwise unresponsive skin hyperpigmentation or hyperpigmentation of unknown cause is less predictable. This review is limited by the strength of evidence contained within the available studies. Clinical studies investigating the treatments discussed within this article are limited in number, at times lack blinding in the study design, and are based on small sample sizes. Based on existing research, the most promising oral remedies for hyperpigmentation appear to be tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. Additional studies to better establish safety and efficacy are necessary.

Human amniotic stem cells-derived exosmal miR-181a-5p and miR-199a inhibit melanogenesis and promote melanosome degradation in skin hyperpigmentation, respectively

Background Hyperpigmentation of skin is caused by an imbalance between the melanosome/melanin synthesis in melanocytes and the melanosome/melanin degradation in keratinocytes. Although studies showed that stem cells play a role in hypopigmentation, the underlying mechanisms are far not elucidated. Human amniotic stem cells (hASCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) were considered to be a promising cell source for stem cells-based therapy of many diseases clinically due to their pluripotent potential, no tumorigenesis and immunogenicity, no ethical issues, and potent paracrine effects. Here, we reported that both hASCs and their conditional medium (CM) had a potent anti-hyperpigmentation in skin in vivo and in vitro. Methods hAESCs and hAMSCs were identified by RT-PCR, flow cytometric analysis and immunofluorescence. Effects of hASCs and hASC-CM on pigmentation were evaluated in B16F10 cells stimulated with α-melanocyte-stimulating hormone (α-MSH), and mouse ears or human skin substitutes treated with ultraviolet radiation B (UVB). Expressions of the key proteins related with melanogenesis and autophagic flux were detected by western blot in B16F10 cells for further exploring the effects and the underlying mechanisms of hAESC-CM and hAMSC-CM on melanogenesis and melanosome degradation. The hAMSCs exosomes-derived miRNAs were determined by sequencing. RT-PCR, western blot, melanin content analysis and luciferase activity assay were used to determine the hypopigmentation of miR-181a-5p and miR-199a. Results In our study, we observed that both hASCs and their CM significantly alleviated the α-MSH in B16F10 cells or UVB-induced hyperpigmentation in mouse ears or human skin substitutes by suppressing melanin synthesis and promoting melanosome degradation in vivo and in vitro. Furthermore, we demonstrated that miR-181a-5p and miR-199a derived from hASCs exosomes remarkably inhibited melanogenesis by suppressing MITF (microphthalmia-associated transcription factor) which is a master regulator for governing melanogenesis and promoting melanosome degradation through activating autophagy, respectively. Conclusions Our studies provided strong evidence that the conditional medium and exosomes derived from hAMSCs inhibit skin hyperpigmentation by suppressing melanogenesis and promoting melanosome degradation, indicating that the hASCs exosomes or their released microRNAs might be as reagents for cell-free therapy in hyperpigmented disorders clinically.

Skin hyperpigmentation and its treatment with herbs: an alternative method

Background With an increasing number of patients, those who are facing a lot of skin-related complaints, often referred to as skin of pigmentation patients, are on the rise. Among all the most common complaints in patients with skin of color is hyperpigmentation. So, there is need of herbal formulation for treatment of hyperpigmentation. Main body This review article addresses the different types of hyperpigmentation, causes, and its treatment with herbs for the management of the skin hyperpigmentation. As uneven pigmentation of skin or hyperpigmentation is a common skin condition, which occurs when the skin produces more melanin. This can make spots or patches of skin appear darker than surrounding areas. Some forms of hyperpigmentation with post-inflammatory, melasma, and sun spots are more likely to affect areas of face, arms, and legs due to sun exposure and injury. Although the availability of multiple treatments for the condition which leads to some adverse effects, hyperpigmentation continues to present skin care management challenges for dermatologists. Conclusion Some plants and phytoconstituents, e.g., Azadirachta indica, Glycyrrhiza glabra, Panax ginseng and genistein, ellagic acids, quercetin, are very useful in herbal cosmetic as anti-hyperpigmentry agents in cosmetic industries. Some of flavonoids and triterpenoids present in plants also show their effect as antioxidant and skin whitening agents. It is expected that this review will compile and improve the existing knowledge on the potential utilization of herbs for the treatment of skin hyperpigmentation.