Differential diagnosis and management of hyperpigmentation.

There is an increasing recognition of ethnic dermatology to reflect the increase in skin of colour (SOC) populations in the UK. Hyperpigmentary disorder is one of the commonest skin concerns in SOC but there has been limited training available in this field of dermatology. Variations in skin colour are genetically determined by the amount of melanin content, the eumelanin/pheomelanin ratio and the size of melanosomes, but is also influenced by other factors such as hormones and extrinsic factors such as ultraviolet radiation. Hyperpigmentation is a broad term to describe increased pigmentation in the skin, and making a correct diagnosis is an important first step in the successful management of hyperpigmentary disorders. A systematic approach based on the disease pathogenesis (e.g. reactive vs. nonreactive, increased melanin vs. increased number of cells or epidermal vs. dermal pigmentation) aided by a detailed history and clinical examination is the best way to diagnose a hyperpigmentary disorder. Based on its pathogenesis, management can be planned. For epidermal hyperpigmentation caused by increased melanin, topical skin-lightening agents targeting inhibition of tyrosinase or melanosome transfer and promotion of keratinocyte turnover can be used. Hydroquinone-containing cream is the gold-standard treatment for epidermal hyperpigmentation. Alternative treatments include laser toning or chemical peels. However, increased dermal pigmentation is more challenging to target with topical treatments. If hyperpigmentation is due to increased numbers of melanocytes or keratinocytes, high-fluence laser is the most appropriate treatment method.

Inhibition of melanogenesis by Aster yomena callus pellet extract in melanoma cells and patients with skin pigmentation.

Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena. This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. Excessive melanogenesis was induced in B16F10 melanoma cells using α-melanocyte stimulating hormone (α-MSH). The effects of AYC-P-E treatment on melanin biosynthesis inducers and melanin synthesis inhibition were assessed. Based on the results, a clinical study was conducted in subjects with skin pigmentation. AYC-P-E inhibited melanogenesis in α-MSH-treated B16F10 cells, accompanied by decreased mRNA and protein expression of melanin biosynthesis inducers, including cyclic AMP response element-binding protein (CREB), tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), and TRP-2. This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment.

A Clinical Anti-Ageing Comparative Study of 0.3 and 0.5% Retinol Serums: A Clinically Controlled Trial.

BACKGROUND: Retinol influences the process of keratinization of the epidermis, which improves stratum corneum structure and reduces transepidermal water loss. It also significantly enhances mature skin by brightening hyperpigmentation and reducing the signs of photoageing. Cosmeceuticals are intended to both provide aesthetic effects for the skin and allow dermatological treatment. The aim of the study was to assess the rejuvenating effect of retinol serum on facial skin at concentrations of 0.3 and 0.5%, as well as any improvements in skin brightening and elasticity. MATERIALS AND METHODS: Thirty-seven volunteers were included in the study, after confirming tolerance. The novel formula was applied once daily to the face for a period of 12 weeks: one retinol concentration on the left side and the other on the right. The initial study with liquid crystal formula (study vehicle) was carried out for 8 weeks on 28 volunteers. Treatment efficiency was evaluated at baseline, and 56 and 84 days following treatment using the multi probe adapter and Fotomedicus imaging system. PRIMOS was used to measure skin surface roughness. The visual analogue scale method enabled the results to be determined by 3 independent specialists. RESULTS: Skin hyperpigmentation, unevenness, and wrinkles gradually decreased over the course of treatment, both on the left and right parts of the face. Adverse events were predominantly mild or moderate skin irritation. More frequent and more intense symptoms were observed on the left side (0.5%). CONCLUSION: Retinol in liquid crystal formulation is safe and provides significant clinical benefits associated with unification of skin colour, overall skin tone, skin elasticity, and moisture. Regular use of retinol typically results in brightening of the skin and reduced signs of ageing. The objective findings confirmed the effectiveness of the procedures.

Hyperpigmentation after Foamed Bleomycin Sclerotherapy for Vascular Malformations.

The present report documents 6 patients who developed distinctive hyperpigmented skin lesions after bleomycin sclerotherapy for vascular malformations of the face, neck, and extremities. The patients ranged in age from 2 to 65 years and included both black and white and male and female patients. The bleomycin treatment dose varied from 15 to 45 U, with 5 of the 6 patients receiving foamed bleomycin. The hyperpigmented lesions were near the patient's vascular anomaly and attributable to postprocedural cutaneous pressure (eg, electrocardiographic [ECG] leads or tape). Hyperpigmentation faded slowly over time but was visible up to 3 years after the procedure.

Reliability assessment and validation of the dermal pigmentation area and severity index: a new scoring method for acquired dermal macular hyperpigmentation.

BACKGROUND: Dermal pigmentation area and severity score (DPASI) is a recently proposed scoring system for acquired dermal macular hyperpigmentation (ADMH). OBJECTIVE: To determine the reliability and validity of DPASI. METHODS: After standardized training, three researchers independently rated 55 patients with ADMH on two consecutive days within 1 week, to determine intra-rater and inter-rater reliability. Validation was performed by comparing DPASI with the physician global assessment score. RESULTS: Test-retest reliability of individual raters tested by Pearson's r showed good correlation for all three raters (r = 0.984, P < 0.0001; r = 0.983, P < 0.000 and r = 0.970, P < 0.0001). Inter-rater agreement computed by intra-class correlation coefficient also showed good correlation (ICC = 0.997, P < 0.0001). Internal consistency as measured by Cronbach's alpha was 0.997. The score faired well in face and content validity (I-CVI of 0.87). On usability assessment, the scale had a median score of 4 on a scale from 1 to 5. The meantime taken to score the patients were 307.2 ± 83, 308.9 ± 84.4, 350.15 ± 91.8 s by three observers, respectively. CONCLUSION: The DPASI is a reliable measure of ADMH severity. The use of dermoscopy decreases inter and intra-observer variation resulting in a more objective score.

Effect of the Stromal Vascular Fraction on Changes in Melanin Formation in B16 Cells Treated by IBMX.

OBJECTIVE: To investigate the effect of the stromal vascular fraction (SVF) on changes in melanin formation and tyrosinase activity in B16 cells treated by 3-isobutyl-1 methylxanthine (IBMX) and to explore the mechanism of SVF-mediated inhibition of pigmentation. METHODS: We co-cultured extracted SVFs and B16 cells treated with IBMX in a certain proportion, and the marker molecule HMB-45 was detected by immunochemistry. Melanin content was determined by NaOH lysis. Activity of tyrosinase was measured by the DOPA oxidation method. RESULTS: HMB-45 was commonly expressed in B16 cells induced by IBMX. After the addition of SVFs, the expression of HMB-45 decreased significantly and positively correlated with increases in SVFs. After the induction of B16 cells by IBMX, melanin content increased significantly. However, melanin decreased after SVF and B16 co-culturing; the effect was more substantial with the increase and decrease in SVFs, and the activity of tyrosinase decreased. CONCLUSION: SVFs inhibit the production of melanin and reduce the activity of tyrosinase, possibly providing a new breakthrough for the treatment of pigment disorders. NO LEVEL ASSIGNED: 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 .

Ashy dermatosis: a review.

Ashy dermatosis is characterized by asymptomatic, symmetrically-distributed, gray-colored macules located on the trunk, neck, face, and upper extremities. The condition occurs most commonly in patients with Fitzpatrick phototype III-V skin. The etiology is unknown, but drug ingestion, infection, and genetic factors have been suggested to elicit ashy dermatosis. No gold standard treatments have been established yet. The most successful treatment to date has been clofazimine, although topical tacrolimus, oral dapsone, narrowband ultraviolet light B phototherapy, and isotretinoin have shown treatment success. Ashy dermatosis is primarily a cosmetic concern, but can be a very distressing condition, especially for dark skinned individuals. Therefore, an increase in clinician awareness and more studies are needed to further understand the etiology and treatment options for this disease. This review serves as a single source for clinicians to stay up-to-date regarding the history, clinical presentation, histology, pathogenesis, differential diagnosis, and management options for ashy dermatosis. It also suggests an alternative name that more appropriately encompasses the clinical and histopathologic features, while acknowledging our lack of understanding of its etiology: macular hyperpigmentation of indeterminate etiology.

A Gunpowder Tattoo in a 6-Year-Old Girl.

Gunpowder tattoos result from explosion and subsequent traumatic implantation of pigmented granules into varying layers of the skin. This report details the case of a 6-year-old with a gunpowder tattoo on the face.

[Post-inflammatory hyperpigmentation occuring after cosmetic procedures]. / Les hyperpigmentations post-inflammatoires succédant à des actes esthétiques.

A post-inflammatory hyperpigmentation (PIHP) can occur after cosmetic procedures such as chemical peels and lasers. Patients must be informed about this risk. Precautionary measures before, during and after the procedure can prevent or reduce the risk of PIHP. These procedures should not be done in summer on suntanned skin and patients have to be aware of the importance of an effective photoprotection. The PIHP occurs more frequently on dark-skinned patients, in Asians as well as in women with melasma history. In these cases, risk/benefit assessment of the cosmetic procedure is required: no risky procedure in patients at risk! PIHP can also be related to technical errors such as too high concentration or too long exposure time during peel procedure as well as excessive threshold fluences during laser procedure. If many therapies for PIHP damages can be proposed, patients feel frequently that they are not as quickly effective as they would like. Patients must be reassured as many PIHP resolve spontaneously. If photoprotection is always required, it is also possible to accelerate the pigmentation's clearing using the Kligman trio or the numerous topical lightening agents targeting several steps of the hyperpigmentation process. More invasive and expensive therapies such as peels, lasers, IPL or radiofrequency might be used for refractory cases. As a pigmentary relapse might occur after these procedures, the traditional Kligman trio should be always considered.

[Post-inflammatory hyperpigmentation]. / L'hyperpigmentation post-inflammatoire.

Post-inflammatory hyperpigmentation (PIH) is a hyperpigmentation of the skin occurring after and sometimes during an inflammatory process. Although more frequent in dark skinned individuals, PIH can be observed in any type of skin and at all ages. In most case a strong impact on the quality of life of affected individuals is observed. The pathophysiology of PIH remains largely unknown. The activation of the melanocytes occurs in the first week following the inflammation emphasizing the crucial role of early preventive measures. Photoprotection with balanced UVA and UVB protection is required. Visible light could also play a role in PIH but this remains to be demonstrated. Healing topics with anti-inflammatory properties are of interest after a skin procedure. When the risk of PIH is high or when PIH occurs, topical steroids remains the gold standard approach.

[How to optimize scarring in dermatologic surgery?] / Optimisation de la cicatrisation en chirurgie dermatologique et gestions des aléas.

Scarring is the response elicited by the skin surface to injury and loss of tissue material. Wound healing takes place through a complex natural repair system consisting of vascular, inflammatory and proliferative phenomena, followed by a remodelling and cell apoptosis phase. This incredible repair system is inevitable, but sometimes unpredictable due to individual differences based on multiple factors. The scar is the objective criterion of a skin surgery, both for the patient and the dermsurgeon. It is therefore crucial to establish with the patient during the preoperative consultation, the size and positioning of the expected scar, taking into account the oncologic, anatomic and surgical constraints. Scars can ideally blend into normal skin, but may also give rise to various abnormalities. We can manage and prevent these abnormalities by mastering initial inflammation, that may induce hyperpigmentation and hypertrophy. Early massage using cortocosteroid topic or anti-inflammatory moisturizers may be effective. Random individual scarring may be minimized by a dynamic personalized accompanying scarring.

Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease.

Reticulate acropigmentation of Kitamura (RAK) is a rare genetic disorder of cutaneous pigmentation with an autosomal dominant pattern of inheritance and a high penetration rate. The characteristic skin lesions are reticulate, slightly depressed pigmented macules mainly affecting the dorsa of the hands and feet, which first appear before puberty and subsequently expand to the proximal limb and the trunk. To identify mutations that cause RAK, we performed exome sequencing of four family members in a pedigree with RAK. Fifty-three SNV/Indels were considered as candidate mutations after some condition narrowing. We confirmed the mutation status in each candidate gene of four other members in the same pedigree to find the gene that matched the mutation status and phenotype of each member. A mutation in ADAM10 encoding a zinc metalloprotease, a disintegrin and metalloprotease domain-containing protein 10 (ADAM10), was identified in the RAK family. ADAM10 is known to be involved in the ectodomain shedding of various substrates in the skin. Sanger sequencing of four additional unrelated RAK patients revealed four additional ADAM10 mutations. We identified a total of three truncating mutations, a splice site mutation and a missense mutation in ADAM10. We searched for mutations in the KRT5 gene, a causative gene for the similar pigmentation disorder Dowling-Degos disease (DDD), in all the patients and found no KRT5 mutation. These results reveal that mutations in ADAM10 are a cause of RAK and that RAK is an independent clinical entity distinct from DDD.

Influence of density and background color to stress response, appetite, growth, and blind-side hypermelanosis of flounder, Paralichthys olivaceus.

To study the relevance of density and background color to stress response, appetite, and growth in olive flounder, Paralichthys olivaceus, we reared two duplicate groups of juveniles (total length 4.46 ± 0.06 cm, body weight 0.77 ± 0.03 g) in flat-bottom aquaria with dark-green (control) and white backgrounds for 120 days. We measured cortisol and glucose levels in blood and calculated the daily food intake, food conversion efficiency, survival rate, and growth rate. To study the relevance of density and background color to malpigmentation (hypermelanosis) on the blind side, we also compared malpigmented ratios and prepro-melanin-concentrating hormone mRNA activities in the brain between the dark-green and white background groups, as well as between a relatively lower density (60 days) and higher density (120 days). Although we measured relatively higher levels of cortisol and glucose in the white background group and over 200 % of coverage area [PCA]), the bright background failed to induce an acute stress response of more than 20 ng/ml cortisol and 40 mg/dl glucose both in 60 days and 120 days, but did enhance appetite and growth. Also, a bright background color delayed hyperpigmentation only at a low density below 200 % PCA, but did not inhibit malpigmentation at a high density of more than 200 % PCA. In addition, below 200 % PCA, expression of MCH mRNA was significantly higher in the white group, but the level was reversed and was lower in the white group at more than 200 % PCA. In conclusion, although did not induce a high stress response over 200 % PCA, the bright background color resulted in a moderate increasing of cortisol level in blood below 20 ng/ml and enhanced appetite and growth. Moreover, at a density below 200 % PCA, the bright color inhibited hypermelanosis with high MCH mRNA activity, but at more than 200 % PCA did not inhibit malpigmentation, and the fish showed low MCH mRNA activity, indicating that the inhibitory effect of a bright background color on hypermelanosis is density dependent.

[Pigmentary disorders induced by anticancer agents. part I: chemotherapy]. / Anomalies pigmentaires induites par les traitements anticancéreux. Première partie : les chimiothérapies.

The occurrence of hyperpigmentation during chemotherapy is one of the most frequent dermatological adverse events observed with these drugs. It may arise with numerous anticancer agents, and can be either localized or diffuse, occurring either immediately or after inflammatory dermatological lesions. Nails, mucosa and skin may all be affected. Though the incidence is high in clinical practice, such drug-induced hyperpigmentation has been only rarely individualized and characterized. Herein we describe the main clinical, histological and pathophysiological characteristics of these lesions and the most frequently incriminated chemotherapeutic agents, as well as the anatomical areas involved and the most specific clinical patterns such as flagellate dermatitis, reticulate or serpentine supravenous hyperpigmentation and eruptive naevi.