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  1. Fatin AM, Mathana Sundram TK, Tan SSE, Seghayat MS, Lee CK, Rehman N, et al.
    Skin Res Technol, 2020 Jul;26(4):564-570.
    PMID: 31916334 DOI: 10.1111/srt.12831
    INTRODUCTION: Periorbital hyperpigmentation (POH) is among the commonest esthetic and dermatological complaints. Despite its frequency, there are inadequate information detailing its incidence and prevalence. This subsequently leads to lack of comprehensive POH classification and stratification of impact on an individual's general well'being. Malaysia, a multiracial country with an expansive expatriate population, provides a unique opportunity to identify demographics of POH and subsequently attempts to group this esthetic and dermatological entity.

    OBJECTIVE: This study aims to develop a new and clinically relevant POH classification system and to measure impact on quality of life of POH individuals.

    METHODS: One hundred patients with POH were enrolled, of which all underwent clinical assessment by a clinician. Objective assessment with mexameter and digital analysis were performed. All recruited patients also completed a questionnaire based on dermatology life quality index (DLQI).

    RESULTS: Assessments noted the commonest type of POH among the subjects was vascular (51%) with the least being pigmentary (6%). The location of POH majority involved both the upper and lower eyelids (65%). DLQI scoring shows that a majority (58%) did not disrupt their quality of life.

    CONCLUSION: Vascular type POH was the frequent most form observed, and involvement tends to occur on both eyelids. A majority of noted that POH does not affect they QOL, but the due consideration must be given in those whom are moderately and minimally affected. A thorough and comprehensive holistic approach is required in managing POH despite its focal presentation as it does affect a patient's quality of life.

    Matched MeSH terms: Hyperpigmentation*
  2. Kwan Z, Wong SM, Robinson S, Tan LL, Looi LM, Ismail R
    Ann Acad Med Singap, 2015 Dec;44(12):577-9.
    PMID: 27090079
    Matched MeSH terms: Hyperpigmentation/chemically induced*; Hyperpigmentation/pathology
  3. Abad-Casintahan F, Chow SK, Goh CL, Kubba R, Hayashi N, Noppakun N, et al.
    J Dermatol, 2016 Jul;43(7):826-8.
    PMID: 26813513 DOI: 10.1111/1346-8138.13263
    In patients with darker skin types (Fitzpatrick phototypes III-VI), acne is often accompanied by post-inflammatory hyperpigmentation (PIH). Further, acne-related pigmentation can pose a greater concern for the patient than the acne lesions. There has been little formal study of this acne-related PIH. Recently, the Asian Acne Board - an international group of dermatologists with interest in acne research - made a preliminary evaluation of the frequency and characteristics of PIH in seven Asian countries. A total of 324 sequential acne subjects were evaluated for the presence of PIH. The majority (80.2%) of subjects had mild to moderate acne and there were more females than males (63.0% vs 37.0%). In this population of patients consulting a dermatologist for acne, 58.2% (188/324) had PIH. The results also showed that pigmentation problems are often long lasting: at least 1 year for more than half of subjects and 5 years or longer in 22.3%. In accordance with our clinical experience, patients reported that PIH is quite bothersome, often as bothersome or more so than the acne itself and sometimes more problematic. Excoriation was commonly reported by patients, and may represent a modifiable risk factor that could potentially be improved by patient education.
    Matched MeSH terms: Hyperpigmentation/etiology*; Hyperpigmentation/epidemiology
  4. Mehrabi JN, Bar-Ilan E, Wasim S, Koren A, Zusmanovitch L, Salameh F, et al.
    J Cosmet Dermatol, 2022 Feb;21(2):461-472.
    PMID: 33794033 DOI: 10.1111/jocd.14110
    BACKGROUND: Melasma is an acquired disorder of hyperpigmentation, affecting a million individuals worldwide. Energy-based devices (EBDs) employed to treat melasma include various types of lasers, intense pulsed light (IPL), and radiofrequency (RF). Recent studies have attempted to address recalcitrant and recurring melasma by combining energy-based devices with topical or oral medications.

    OBJECTIVE: This article reviews EBDs-based augmented treatment for melasma and suggests practical pathogenesis-oriented treatment regimens. Treatment algorithms are proposed to address various components of melasma.

    METHODS: A systematic PubMed search was conducted acquiring information from various studies on combination treatments of melasma involving EBDs.

    RESULTS: The 286 retrieved articles were filtered by title to contain at least one type of energy-based modality such as laser, IPL, or RF along with at least one other treatment method. Based on their subject matter, combinations were further categorized into the subheadings: laser plus medication, laser plus laser, and IPL- and RF-containing treatment methods.

    CONCLUSION: There are many energy-based combination treatments that have been explored for mitigation of melasma including laser therapy with medication, multi-laser therapies, IPL, RF, and microneedling devices. Melasma is an exceedingly difficult condition to treat, however, choosing the appropriate tailor-made treatment combination can improve the final outcome.

    Matched MeSH terms: Hyperpigmentation*
  5. Fitzrol DN, Ang SY, Suhaimi A, Yeap TB
    BMJ Case Rep, 2023 Apr 11;16(4).
    PMID: 37041040 DOI: 10.1136/bcr-2022-253959
    Polymyxin B (PB) is a polypeptide bactericidal antibiotic that is commonly used for extensively drug-resistant (XDR) microorganisms such as Acinetobacter baumanii and Klebsiella pneumoniae It can be administered intravenously or intrathecally. Common side effects are nephrotoxicity, neurotoxicity, pruritus and skin hyperpigmentation (SH). The latter is an uncommon adverse reaction of intravenously administered PB. We report a rare occurrence of PB-induced SH secondary to intrathecal administration of PB in a child with A. baumanii XDR ventriculitis. We describe the management of him and a brief review of PB.
    Matched MeSH terms: Hyperpigmentation*
  6. Kwa SK, Gupta ED
    Aust Fam Physician, 2013 Jul;42(7):490-1.
    PMID: 23826603
    An overweight woman, aged 58 years, presented for follow up of hypertension, diabetes and dyslipidaemia. She was noted to have hyperpigmented brown macules on the inner surface of the lower lip and buccal mucosa (Figure 1). She stated that she had first noticed these lesions when aged in her 40s. Her mother died at age 58 years from gastric cancer with extensive metastases, and her brother died at age 45 years from colon cancer with spread to the liver and lungs.
    Matched MeSH terms: Hyperpigmentation/diagnosis*; Hyperpigmentation/genetics
  7. Shah S, Chew SK
    J Cosmet Dermatol, 2018 Oct;17(5):830-839.
    PMID: 29193788 DOI: 10.1111/jocd.12435
    BACKGROUND: Skin hyperpigmentation is the darkening of skin due to the increased production of melanin in the body.

    OBJECTIVES: To evaluate the efficacy and safety of a botanical-based Rosa E pigmentation serum in healthy fair skin female volunteers with wrinkles, skin tone, and pigmentation.

    METHODS: This was a single-arm, open label study conducted in healthy Indian females; 18 subjects aged 30-55, having fair Caucasian-like skin with at least 2 dark skin pigments with facial wrinkles diagnosed by dermatologist were selected. Rosa E pigmentation serum was applied twice a day for 84 days. Effect was evaluated by (i) instrumental technique (spectrophotometer® 2600D), (ii) clinically by dermatologist regarding product efficacy (skin tone, antiwrinkle, pigmentation), and (iii) volunteers self-evaluation.

    RESULTS: The L* value of spectrophotometer reading represents lightness in the skin pigment. Reduction in the pigment was reported from day 14, with significant reductions observed till day 84 compared with baseline. Significant (P < .0001) skin pigmentation lightening was seen on day 14 (1.11) vastly improving on day 84 (1.94) based on photographic assessments. The significant reduction in skin pigment was 76.85%, Felix von Luschan skin color score was 30.24% (P < .0001) with a 7.38-fold reduction in skin tone and 57% reduction in facial wrinkles at day 84 from baseline.

    CONCLUSIONS: Rosa E pigmentation serum was found safe and effective in significant reduction in skin pigments, improvement of skin tone, and antiwrinkle properties instrumentally, clinically, and self-evaluation by volunteers. In these evaluations, best results were seen the longer the Rosa E was used.

    Matched MeSH terms: Hyperpigmentation/drug therapy; Hyperpigmentation/prevention & control*
  8. Goh SW, Adawiyah J, Md Nor N, Yap F, Ch'ng P, Chang CC
    Malays Fam Physician, 2019;14(1):42-46.
    PMID: 31289632
    Prurigo pigmentosa is an inflammatory dermatosis characterized by a pruritic, symmetrically distributed erythematous papular or papulo-vesicular eruption on the trunk arranged in a reticulated pattern that resolves with hyperpigmentation. It is typically non-responsive to topical or systemic steroid therapy. The exact etiology is unknown, but it is more commonly described in the Far East countries. Dietary change is one of the predisposing factors. We report on nine young adult patients with prurigo pigmentosa, among whom five were on ketogenic diets prior to the onset of the eruptions. All cases resolved with oral doxycycline with no recurrence. We hope to improve the awareness of this uncommon skin condition among general practitioners and physicians so that disfiguring hyperpigmentation due to delayed diagnosis and treatment can be avoided.
    Matched MeSH terms: Hyperpigmentation
  9. Patel FB, Newman SA, Norton SA
    Skinmed, 2016 02 01;14(1):53-4.
    PMID: 27072733
    A 20-year-old man of Indo-Malaysian ancestry presented with a complaint of increased facial pigmentation that he first noticed at age 13. He had congenital adrenal hyperplasia (21-hydroxylase deficiency, salt-wasting variant; OMIM 201910), diagnosed during infancy. Glucocorticoid and mineralocorticoid therapy was started at that time, but he had several episodes of salt craving during adolescence. During the past 7 years, the degree of facial pigmentation waxed and waned but never returned to baseline of early adolescence. Progressive skin darkening was also observed in annual family photos, which also showed a vast difference in skin tones between the patient and other members of his immediate family.
    Matched MeSH terms: Hyperpigmentation/etiology*
  10. Lajis AFB
    Medicina (Kaunas), 2018 May 25;54(3).
    PMID: 30344266 DOI: 10.3390/medicina54030035
    For years, clinical studies involving human volunteers and several known pre-clinical in vivo models (i.e., mice, guinea pigs) have demonstrated their reliability in evaluating the effectiveness of a number of depigmenting agents. Although these models have great advantages, they also suffer from several drawbacks, especially involving ethical issues regarding experimentation. At present, a new depigmenting model using zebrafish has been proposed and demonstrated. The application of this model for screening and studying the depigmenting activity of many bioactive compounds has been given great attention in genetics, medicinal chemistry and even the cosmetic industry. Depigmenting studies using this model have been recognized as noteworthy approaches to investigating the antimelanogenic activity of bioactive compounds in vivo. This article details the current knowledge of zebrafish pigmentation and its reliability as a model for the screening and development of depigmenting agents. Several methods to quantify the antimelanogenic activity of bioactive compounds in this model, such as phenotype-based screening, melanin content, tyrosinase inhibitory activity, other related proteins and transcription genes, are reviewed. Depigmenting activity of several bioactive compounds which have been reported towards this model are compared in terms of their molecular structure and possible mode of actions. This includes patented materials with regard to the application of zebrafish as a depigmenting model, in order to give an insight of its intellectual value. At the end of this article, some limitations are highlighted and several recommendations are suggested for improvement of future studies.
    Matched MeSH terms: Hyperpigmentation/drug therapy*
  11. Kumar Dubey S, Pradhan R, Hejmady S, Singhvi G, Choudhury H, Gorain B, et al.
    Int J Pharm, 2021 May 01;600:120499.
    PMID: 33753164 DOI: 10.1016/j.ijpharm.2021.120499
    Age-related macular degeneration (AMD), a degenerative eye disease, is the major cause of irreversible loss of vision among individuals aged 50 and older. Both genetic and environmental factors are responsible for the progressive damage to central vision. It is a multifactorial retinal disease with features such as drusen, hypopigmentation and/or hyperpigmentation of the retinal pigment epithelium, and even choroidal neovascularization in certain patients. AMD is of two major forms: exudative (wet) and atrophic (dry) with changes affecting the macula leading to impaired vision. Although the retina remains an accessible portion for delivering drugs, there are no current options to cure or treat AMD. The existing expensive therapeutics are unable to treat the underlying pathology but display several side effects. However, recent innovations in nanotherapeutics provide an optimal alternative of drug delivery to treat the neovascular condition. These new-age technologies in the nanometer scale would enhance bioactivity and improve the bioavailability of drugs at the site of action to treat AMD. The nanomedicine also provides sustained release of the drug with prolonged retention after penetrating across the ocular tissues. In this review, the insights into the cellular and molecular mechanisms associated with the pathophysiology of AMD are provided. It also serves to review the current progress in nanoparticle-based drug delivery systems that offer feasible treatments in AMD.
    Matched MeSH terms: Hyperpigmentation
  12. Afroze B, Amjad N, Ibrahim SH, Humayun KN, Yakob Y
    Brain Dev, 2014 Nov;36(10):924-7.
    PMID: 24508408 DOI: 10.1016/j.braindev.2013.12.009
    Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) are established subgroups of mitochondrial encephalomyopathy. m.3243A>G a common point mutation is detected in tRNA in majority of patients with MELAS phenotype whereas m.8344A>G point mutation in tRNA is observed, in MERRF phenotype. Adrenal insufficiency has not been reported in mitochondrial disease, except in Kearns-Sayre Syndrome (KSS), which is a mitochondrial deletion syndrome. We report an unusual presentation in a five year old boy who presented with clinical phenotype of MELAS and was found to have m.8344A>G mutation in tRNA. Addison disease was identified due to hyperpigmentation of lips and gums present from early childhood. This is the first report describing adrenal insufficiency in a child with MELAS phenotype.
    Matched MeSH terms: Hyperpigmentation/etiology
  13. Syed Azhar SNA, Ashari SE, Salim N
    Int J Nanomedicine, 2018;13:6465-6479.
    PMID: 30410332 DOI: 10.2147/IJN.S171532
    Introduction: Kojic monooleate (KMO) is an ester derived from a fungal metabolite of kojic acid with monounsaturated fatty acid, oleic acid, which contains tyrosinase inhibitor to treat skin disorders such as hyperpigmentation. In this study, KMO was formulated in an oil-in-water nanoemulsion as a carrier for better penetration into the skin.

    Methods: The nanoemulsion was prepared by using high and low energy emulsification technique. D-optimal mixture experimental design was generated as a tool for optimizing the composition of nanoemulsions suitable for topical delivery systems. Effects of formulation variables including KMO (2.0%-10.0% w/w), mixture of castor oil (CO):lemon essential oil (LO; 9:1) (1.0%-5.0% w/w), Tween 80 (1.0%-4.0% w/w), xanthan gum (0.5%-1.5% w/w), and deionized water (78.8%-94.8% w/w), on droplet size as a response were determined.

    Results: Analysis of variance showed that the fitness of the quadratic polynomial fits the experimental data with F-value (2,479.87), a low P-value (P<0.0001), and a nonsignificant lack of fit. The optimized formulation of KMO-enriched nanoemulsion with desirable criteria was KMO (10.0% w/w), Tween 80 (3.19% w/w), CO:LO (3.74% w/w), xanthan gum (0.70% w/w), and deionized water (81.68% w/w). This optimum formulation showed good agreement between the actual droplet size (110.01 nm) and the predicted droplet size (111.73 nm) with a residual standard error <2.0%. The optimized formulation with pH values (6.28) showed high conductivity (1,492.00 µScm-1) and remained stable under accelerated stability study during storage at 4°C, 25°C, and 45°C for 90 days, centrifugal force as well as freeze-thaw cycles. Rheology measurement justified that the optimized formulation was more elastic (shear thinning and pseudo-plastic properties) rather than demonstrating viscous characteristics. In vitro cytotoxicity of the optimized KMO formulation and KMO oil showed that IC50 (50% inhibition of cell viability) value was >100 µg/mL.

    Conclusion: The survival rate of 3T3 cell on KMO formulation (54.76%) was found to be higher compared to KMO oil (53.37%) without any toxicity sign. This proved that the KMO formulation was less toxic and can be applied for cosmeceutical applications.

    Matched MeSH terms: Hyperpigmentation/drug therapy*
  14. Amini F, Thazin Oo NM, Okechukwu PN, Seghayat MS, Ng ESC
    Australas J Dermatol, 2019 May;60(2):e99-e104.
    PMID: 30215845 DOI: 10.1111/ajd.12918
    BACKGROUND/OBJECTIVES: The unknown pathogenesis of periorbital hyperpigmentation makes its treatment difficult. Existing evidence links p53 and VEGFA genes with skin hyperpigmentation. This study was aimed at (i) identifying the clinical pattern of periorbital hyperpigmentation; and (ii) detecting the presence of VEGFA and P53 single nucleotide polymorphism (SNPs) in different subtypes of periorbital hyperpigmentation in Malaysian Chinese.

    METHODS: A cross-sectional study was conducted among Malaysian Chinese. Clinical assessments were performed, and medical history was collected. Three regions of p53 and two of VEGFA were amplified by PCR followed by direct sequencing using saliva-extracted DNA.

    RESULTS: Eighty-four participants were recruited (average age 22.2 years). In the majority (n = 62), both eyelids were affected. Facial pigmentary, demarcation lines, tear trough and eye bags were not observed. Mixed (pigmented-vascular) was the most common subtype. Thirteen SNPs were found, nine of which are new. Only three out of 13 SNPs showed significant association with periorbital hyperpigmentation presentation. TA genotype in rs1437756379 (p53) was significantly more prevalent among participants with mixed subtype (P = 0.011) while AC genotype in rs1377053612 (VEGFA) was significantly more prevalent among pigmented subtype (P = 0.028). AA genotype in rs1479430148 (VEGFA) was significantly associated with allergic rhinitis in mixed subtype (P = 0.012).

    CONCLUSION: Mixed subtype was the most prevalent type of periorbital hyperpigmentation in the study population. Three polymorphisms in p53 and VEGFA genes were statistically linked with different clinical presentations of periorbital hyperpigmentation.

    Matched MeSH terms: Hyperpigmentation/genetics*
  15. Lajis AFB, Ariff AB
    J Cosmet Dermatol, 2019 Jun;18(3):703-727.
    PMID: 30866156 DOI: 10.1111/jocd.12900
    Human skin pigmentation is a result of constitutive and facultative pigmentation. Facultative pigmentation is frequently stimulated by UV radiation, pharmacologic drugs, and hormones whereby leads to the development of abnormal skin hyperpigmentation. To date, many state-of-art depigmenting compounds have been studied using in vitro model to treat hyperpigmentation problems for cosmetic dermatological applications; little attention has been made to compare the effectiveness of these depigmenting compounds and their mode of actions. In this present article, new and recent depigmenting compounds, their melanogenic pathway targets, and modes of action are reviewed. This article compares the effectiveness of these new depigmenting compounds to modulate several melanogenesis-regulatory enzymes and proteins such as tyrosinase (TYR), TYR-related protein-1 (TRP1), TYR-related protein-2 (TRP2), microphthalmia-associated transcription factor (MITF), extracellular signal-regulated kinase (ERK) and N-terminal kinases (JNK) and mitogen-activated protein kinase p38 (p38 MAPK). Other evidences from in vitro assays such as inhibition on melanosomal transfer, proteasomes, nitric oxide, and inflammation-induced melanogenesis are also highlighted. This article also reviews analytical techniques in different assays performed using in vitro model as well as their advantages and limitations. This article also provides an insight on recent finding and re-examination of some protocols as well as their effectiveness and reliability in the evaluation of depigmenting compounds. Evidence and support from related patents are also incorporated in this present article to give an overview on current patented technology, latest trends, and intellectual values of some depigmenting compounds and protocols, which are rarely highlighted in the literatures.
    Matched MeSH terms: Hyperpigmentation/drug therapy*
  16. Yuniati R, Sihombing NRB, Nauphar D, Tiawarman B, Kartikasari DS, Dewi M, et al.
    Intractable Rare Dis Res, 2021 May;10(2):114-121.
    PMID: 33996357 DOI: 10.5582/irdr.2020.03143
    Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by hypersensitivity of the skin to ultraviolet radiation and other carcinogenic agents. This ailment is characterized by increased photosensitivity, skin xerosis, early skin aging, actinic keratosis, erythematous lesions, and hyperpigmentation macules. In this serial case report, we presented four cases with XP from two families in Indonesia. Both families were referred from rural referral health centers, and each family has two affected siblings. They had freckle-like pigmentation on the face, trunk, and extremities, which progressed since childhood. One patient of family 2 died because of an infectious disease. Histopathological examination using cytokeratine (CK), CD10, and Ber-EP4 staining from available tissue biopsy of one affected case of family 1 identified basal cell carcinoma (BCC) on the cheek and melanoma on the right eye. Mutation analysis found ERCC2, c2047C>T and XPC, c1941T>A in the first and second families, respectively. We suppose that this is the first case report of XP in Indonesia that incorporates clinical examination, genetic analysis, and extensive histopathological examination, including immunohistochemistry staining, and a novel pathogenic variant of XPC was found in the second family.
    Matched MeSH terms: Hyperpigmentation
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