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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.

Xanthohumol (XN), representing the group of chalcones, is a hydroxyl and superoxide free radical scavenger. It also has antimicrobial properties, showing antibacterial activity against Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus epidermidis and Propionibacterium acnes. XN exerts an inhibitory effect on tyrosinase (it hinders the oxidation of l-tyrosine and l-DOPA). However, it also affects the transport of pigment (through a reduction in the number and length of dendrites) and its degradation (through damage to melanosomes). Additionally, it has been shown to inhibit the different activation pathways of the premeditated response in macrophages and reduce the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Xanthohumol also improves skin elasticity by reducing the activity of elastase and MMP 1, 2 and 9, and it increases the expression of type I, III and V collagen, as well as elastin and fibrillins in skin fibroblasts. It acts against the main factors contributing to the pathogenesis of acne by inhibiting pro-inflammatory mediators (e.g., COX-2, PGE2, IL-1β and TNF-α). Moreover, it shows antibacterial activity against P. acnes and S. aureus, as well as seboregulatory and antioxidant properties. It has also been recognized that XN intake could affect diabetic wound healing. XN shows antitumoral activity, e.g., in the case of skin melanoma, which is associated with the antioxidant, pro-apoptotic, anti-angiogenic and immunostimulating effects of this compound. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no standard treatment for relapsed/refractory NK/T-cell lymphoma (NKTCL). Liposomal mitoxantrone (Lipo-MIT) showed good anti-tumor effect in patients with NKTCL, breaking the limitation of natural resistance of NKTCL to anthracyclines. To further improve the efficacy, we tried a combination therapy based on Lipo-MIT in patients with relapsed/refractory NKTCL. Methods: 12 patients with relapsed/refractory NKTCL were enrolled in this retrospective study, all of whom had previously received pegaspargase-based treatments. The salvage treatment was a combination regimen based on Lipo-MIT. The efficacy was evaluated after every two cycles. Results: 11 patients had stage IV NKTCL, and all but one patients had an NRI score of ≥3. The median previous lines of treatment was two (range, 1-4), and five patients were refractory to their last line of treatment. The best response rates were as follows: complete response (CR) in five (41.7%) patients, partial response in five (41.7%) patients, stable disease in one (8.3%) patient, and progressive disease in one (8.3%) patient. At a median follow-up of four months (range, 2-14), seven patients died, with a median PFS of five months and a median OS of seven months. The six-month PFS and OS rate was 44.4% and 52.1%, respectively. All patients had suffered from side effects, among which myelosuppression was most reported. Nine patients had grade three or more myelosuppression, and the median recovery time from myelosuppression was 14 days (2-35 days). Five patients had obvious skin hyperpigmentation, and the CR rate was significantly higher compared with those without skin hyperpigmentation (80% vs. 14.3%, p=0.023). Other side effects included liver insufficiency (N=4), coagulation dysfunction (N=4), acute pancreatitis (N=2), and immunotherapy-related adverse effects (irAEs, N=2). Conclusion: Combination therapy based on Lipo-MIT has a high remission rate for relapsed/refractory NKTCL, but the duration of remission needs to be further extended. Lipo-MIT has obvious myelosuppression toxicity, and active supportive therapy should be given when combined with other cytotoxic drugs. [ABSTRACT FROM AUTHOR]

Hyperpigmentation skin disorders are marked by an abnormal accumulation or export of melanin pigment synthesized within melanocytes and pose a significant aesthetic concern. The search for novel natural compounds that exhibit pharmacological potential for treating pigmentation disorders is growing. In this study, kahweol (KW) and cafestol (CFS), two structural analogs of coffee diterpenes, were evaluated and compared for their effects on melanogenesis using B16F10 mouse melanoma cells and primary human melanocytes derived from Asian and African American skin. To the best of our knowledge, there are no reports of the effects of KW and CFS on melanogenesis yet. We first screened nontoxic concentrations of both compounds using an MTS assay after 72 h incubations and subsequently tested their effects on melanin synthesis and export. Cellular tyrosinase activity and cell-free mushroom tyrosinase activity were assayed to study the mechanisms of melanogenesis suppression. Human melanocytes from a moderately pigmented donor (HEMn-MP cells) and from a darkly pigmented donor (HEMn-DP cells) were next examined, and effects on cellular viability, melanin content, cellular tyrosinase activity, and melanin export (quantitated via dendricity) were similarly examined for both compounds. Our results show that KW and CFS did not significantly affect intracellular melanin content but suppressed extracellular melanin in B16F10 cells and dendritic parameters in human melanocytes, indicating their unique capacity to target extracellular melanogenesis and melanin export. Although KW showed a greater extracellular melanogenesis inhibitory capacity in B16F10 cells, in both primary melanocyte cells, CFS emerged as a potent inhibitor of melanin export compared to KW. Together, these results reveal novel modes of action of both compounds and indicate a promise to use CFS as a novel candidate for treating hyperpigmentation disorders of the human skin for clinical and cosmetic use. Additional research is necessary to shed light on the molecular pathways and the efficacy of melanogenesis inhibition by CFS in 3D human skin equivalents and in vivo studies.

Hyperpigmentation skin disorders are marked by an abnormal accumulation or export of melanin pigment synthesized within melanocytes and pose a significant aesthetic concern. The search for novel natural compounds that exhibit pharmacological potential for treating pigmentation disorders is growing. In this study, kahweol (KW) and cafestol (CFS), two structural analogs of coffee diterpenes, were evaluated and compared for their effects on melanogenesis using B16F10 mouse melanoma cells and primary human melanocytes derived from Asian and African American skin. To the best of our knowledge, there are no reports of the effects of KW and CFS on melanogenesis yet. We first screened nontoxic concentrations of both compounds using an MTS assay after 72 h incubations and subsequently tested their effects on melanin synthesis and export. Cellular tyrosinase activity and cell-free mushroom tyrosinase activity were assayed to study the mechanisms of melanogenesis suppression. Human melanocytes from a moderately pigmented donor (HEMn-MP cells) and from a darkly pigmented donor (HEMn-DP cells) were next examined, and effects on cellular viability, melanin content, cellular tyrosinase activity, and melanin export (quantitated via dendricity) were similarly examined for both compounds. Our results show that KW and CFS did not significantly affect intracellular melanin content but suppressed extracellular melanin in B16F10 cells and dendritic parameters in human melanocytes, indicating their unique capacity to target extracellular melanogenesis and melanin export. Although KW showed a greater extracellular melanogenesis inhibitory capacity in B16F10 cells, in both primary melanocyte cells, CFS emerged as a potent inhibitor of melanin export compared to KW. Together, these results reveal novel modes of action of both compounds and indicate a promise to use CFS as a novel candidate for treating hyperpigmentation disorders of the human skin for clinical and cosmetic use. Additional research is necessary to shed light on the molecular pathways and the efficacy of melanogenesis inhibition by CFS in 3D human skin equivalents and in vivo studies. [ABSTRACT FROM AUTHOR]

BackgroundCronkhite-Canada syndrome (CCS) is extremely rare in children, presenting with complex clinical manifestations often leading to misdiagnosis.Case presentationWe reported a description of a 13-year-old boy with CSS presenting with persistent diarrhea, vomiting, abdominal pain, along with symptoms of weight loss, alopecia, and skin hyperpigmentation. The patient had ectodermal manifestations such as alopecia and skin hyperpigmentation. Laboratory tests revealed hypoalbuminemia, normal inflammatory indicators, positive anti-dsDNA antibodies, anti-centromere antibodies, and anti-nuclear antibodies. Gastrointestinal endoscopy identified polypoid changes in the stomach, duodenum, and colon, with pathology indicating glandular dilation, cryptitis, and crypt abscesses. Treatment with prednisone led to significant improvement in symptoms, including normalization of stool consistency, hair regrowth, and disappearance of skin hyperpigmentation.ConclusionThis study emphasizes the importance of comprehensive assessment, endoscopic examination, histological biopsy, and the effectiveness of steroid therapy in the diagnosis and management of CCS in children. In children presenting with diarrhea, abdominal pain, weight loss, polyposis, and ectodermal manifestations, CCS should be considered.

Skin hyperpigmentation is a dermatological condition characterized by darkening of the skin due to increased melanin production. Various factors such as excessive sun exposure, skin inflammation, hormonal imbalance, and genetic predisposition can contribute to the development of these conditions, significantly affecting quality of life. This work aims to explore the efficacy of cosmeceuticals in the treatment of hyperpigmentation, focusing on products available in tropical regions like Brazil. To achieve this, a narrative literature review with a qualitative approach based on scientific articles, dissertations, and journals obtained through the Google Scholar, PubMed, and Science Direct platforms using the following search keywords: cosmeceuticals, cosmetics, skin lightening, skin regeneration, published between 2003 and 2023, in Portuguese and English languages, was conducted. The different types of hyperpigmentation, such as melasma, post-inflammatory hyperpigmentation, and solar lentigines, were discussed, addressing their clinical characteristics and pathophysiologies, presenting the main mechanisms involved in the formation of skin hyperpigmentation. Subsequently, the main active ingredients used in the treatment of hyperpigmentation were highlighted, such as niacinamide, retinol, vitamin C, kojic acid, arbutin, and hydroquinone. The mechanisms of action of each active ingredient and their scientific evidence of efficacy are discussed. Through a literature analysis, recommendations were provided for the appropriate and safe use of cosmetics in the treatment of skin hyperpigmentation, considering factors such as skin type, dermatological conditions, and sun protection measures. The work aims to contribute to advancing knowledge about the treatment of skin hyperpigmentation, providing updated information on the role of cosmeticals in this context.

There is growing evidence that oxidative stress plays a role in melasma and disrupts primary cilia formation. Additionally, primary cilia have been suggested to have an inhibitory role in melanogenesis. This study examined the potential link between oxidative stress, skin hyperpigmentation, and primary cilia. We compared the expression levels of the nuclear factor E2-related factor 2 (NRF2), intraflagellar transport 88 (IFT88), and glioma-associated oncogene homologs (GLIs) in skin samples from patients with melasma, both in affected and unaffected areas. We also explored the roles of NRF2, IFT88, and GLIs in ciliogenesis and pigmentation using cultured adult human keratinocytes, with or without melanocytes. Our findings revealed decreased levels of NRF2, heme oxygenase-1, IFT88, and GLIs in lesional skin from melasma patients. The knockdown of NRF2 resulted in reduced expressions of IFT88 and GLI1, along with fewer ciliated cells. Furthermore, NRF2, IFT88, or GLI1 knockdown led to increased expressions in protease-activated receptor-2 (PAR2), K10, involucrin, tyrosinase, and/or melanin. These effects were reversed by the smoothened agonist 1.1. Calcium also upregulated these proteins, but not NRF2. The upregulation of involucrin and PAR2 after NRF2 knockdown was mitigated with a calcium chelator. In summary, our study suggests that oxidative stress in NRF2-downregulated melasma keratinocytes impedes ciliogenesis and related molecular processes. This inhibition stimulates keratinocyte differentiation, resulting in melanin synthesis and melanosome transfer, ultimately leading to skin hyperpigmentation. [ABSTRACT FROM AUTHOR]

Background: Noninvasive skin rejuvenation treatment is growing in recognition to aesthetic medicine. Aim: The objective of the study was to assess the efficacy and the safety of the 675‐nm laser source treatment of photodamaged hands. Materials and methods: The study included 21 patients (6 males and 15 females) with a mean age of 63 (± 9) years. Patients were treated with —two to three sessions of the 675‐nm laser with a 1‐month interval between sessions. Photos of each patient were collected at baseline, and 3 months after the last laser session. The 5‐point Global Aesthetic Improvement Scale (GAIS) was recorded with their final assessment session (3 months). Results: The total GAIS scores showed satisfactory results: 15 patients (71%) experienced 4 score (excellent improvement) changes and 6 patients (29%) experienced 3 score (good improvement) changes. Clinical images showed good efficacy and visible aesthetic results for the management of photodamaged skin. No serious adverse effects were recorded. Conclusion: This study demonstrates the safety and efficacy of for the aesthetic improvement of skin pigmentation and texture for photodamaged hands. [ABSTRACT FROM AUTHOR]

Background. Understanding the connection between skin lesions and the pathology of internal organs and body systems that may have caused them is a prerequisite for successful cosmetic therapy. Aim. The aim of this study was to analyze the influence of a patient’s somatic pathology on the manifestation of skin abnormalities. Materials and methods. The study was conducted according to a “case-control” design and was accompanied by a retrospective study of outpatient records of patients with the disease (group 1) and patients without it (control group). It is aimed at revealing the connection between a patient’s skin manifestations and somatic pathology, as well as the effectiveness of therapeutic measures for the correction of such a condition. Results. Patients with acne and rosacea have a statistically significantly higher incidence of gastrointestinal diseases (in particular, gastritis caused by Helicobacter), diabetes mellitus, vitamin and micronutrient deficiencies, which significantly affects the effectiveness of their treatment and quality of life. In such chronic dermatoses, disruption of intestinal microbiocenosis can be considered as a comorbid condition. Hyperpigmentation of patients’ skin was caused by hormonal dysfunction (hyperestrogenism) and was accompanied by vitamin D deficiency. Conclusions. In cosmetology practice, therapy of dermatoses should be individualized and based on the analysis of the course of the disease, considering the diagnosed dysfunctions of certain organs or systems that cause skin pathological changes, as well as the prevalence and severity of dermatosis, presence of comorbid background and mental disorders. A holistic approach in the therapy of dermatoses involving a dermatologist, a psychologist, a cosmetologist, and specialized clinicians will ensure their effective treatment. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to quantitatively assess the effectiveness of microneedle mesotherapy in reducing skin discoloration. The results were analyzed using the gray-level co-occurrence matrix (GLCM) method. Material and methods: The skin of the forearm (7 × 7 cm) of 12 women aged 29 to 68 was examined. Microneedle mesotherapy was performed using a dermapen with a preparation containing 12% ascorbic acid. Each of the volunteers underwent a series of four microneedle mesotherapy treatments. The effectiveness of the treatment was quantified using the methods of image analysis and processing. A series of clinical images were taken in cross-polarized light before and after a series of cosmetic procedures. Then, the treated areas were analyzed by determining the parameters of the gray-level co-occurrence matrix (GLCM) algorithm: contrast and homogeneity. Results: During image pre-processing, the volunteers' clinical images were separated into red (R), green (G) and blue (B) channels. The photos taken after the procedure show an increase in skin brightness compared to the photos taken before the procedure. The average increase in skin brightness after the treatment was 10.6%, the average decrease in GLCM contrast was 10.7%, and the average homogeneity increased by 14.5%. Based on the analysis, the greatest differences in the GLCM contrast were observed during tests performed in the B channel of the RGB scale. With a decrease in GLCM contrast, an increase in postoperative homogeneity of 0.1 was noted, which is 14.5%. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to demonstrate the effects of using a preparation containing kojic acid on skin hyperpigmentation using hyperspectral imaging, which enables a quantitative assessment of the effect of the preparation used on the reduction of skin discoloration. Materials and methods: Preliminary studies were carried out on 12 patients with post-acne skin. A hyperspectral camera with a spectral range of 400–1000 nm was used to image skin hyperpigmentation before and after the application of 3% kojic acid. Hyperspectral profiles were analyzed, and image analysis and processing methods were applied. Results: Studies performed using a hyperspectral camera have shown that kojic acid reduces skin discoloration by increasing skin brightness in 75% of patients tested, reducing skin contrast in approximately 83% and increasing skin homogeneity in approximately 67% of patients. [ABSTRACT FROM AUTHOR]

Polymyxin B is a reserve drug for resistant gram-negative bacterial infections. A rare side effect of polymyxin B is cutaneous hyperpigmentation, which characteristically involves face and neck. This is commonly reported in pediatric population. We report a case of polymyxin B-induced skin and nail hyperpigmentation and acute kidney injury in an adult patient of malignant otitis externa.

Abnormal skin pigmentation commonly occurs during the wound healing process due to the overproduction of melanin. Chicken egg white (CEW) has long been used to improve skin health. Previous published works had found CEW proteins house bioactive peptides that inhibit tyrosinase, the key enzyme of melanogenesis. The current study aimed to evaluate the anti-pigmentation potential and mechanism of the CEW-derived peptide (GYSLGNWVCAAK) and hydrolysates (CEWHmono and CEWHdi), using a cell-based model. All of these peptide and hydrolysates inhibited intracellular tyrosinase activity and melanin level up to 45.39 ± 1.31 and 70.01 ± 1.00%, respectively. GYSLGNWVCAAK and CEWHdi reduced intracellular cAMP levels by 13.38 ± 3.65 and 14.55 ± 2.82%, respectively; however, CEWHmono did not affect cAMP level. Moreover, the hydrolysates downregulated the mRNA expression of melanogenesis-related genes, such as Mitf, Tyr, Trp-1 and Trp-2, but GYSLGNWVCAAK only suppressed Tyr gene expression. Downregulation of the genes may lower the catalytic activities and/or affect the structural stability of TYR, TRP-1 and TRP-2; thus, impeding melanogenesis to cause an anti-pigmentation effect in the cell. Outcomes from the current study could serve as the starting point to understand the underlying complex, multifaceted melanogenesis regulatory mechanism at the cellular level. [ABSTRACT FROM AUTHOR]

There is growing evidence that oxidative stress plays a role in melasma and disrupts primary cilia formation. Additionally, primary cilia have been suggested to have an inhibitory role in melanogenesis. This study examined the potential link between oxidative stress, skin hyperpigmentation, and primary cilia. We compared the expression levels of the nuclear factor E2-related factor 2 (NRF2), intraflagellar transport 88 (IFT88), and glioma-associated oncogene homologs (GLIs) in skin samples from patients with melasma, both in affected and unaffected areas. We also explored the roles of NRF2, IFT88, and GLIs in ciliogenesis and pigmentation using cultured adult human keratinocytes, with or without melanocytes. Our findings revealed decreased levels of NRF2, heme oxygenase-1, IFT88, and GLIs in lesional skin from melasma patients. The knockdown of NRF2 resulted in reduced expressions of IFT88 and GLI1, along with fewer ciliated cells. Furthermore, NRF2, IFT88, or GLI1 knockdown led to increased expressions in protease-activated receptor-2 (PAR2), K10, involucrin, tyrosinase, and/or melanin. These effects were reversed by the smoothened agonist 1.1. Calcium also upregulated these proteins, but not NRF2. The upregulation of involucrin and PAR2 after NRF2 knockdown was mitigated with a calcium chelator. In summary, our study suggests that oxidative stress in NRF2-downregulated melasma keratinocytes impedes ciliogenesis and related molecular processes. This inhibition stimulates keratinocyte differentiation, resulting in melanin synthesis and melanosome transfer, ultimately leading to skin hyperpigmentation.

Polymyxin B is a reserve drug for resistant gram-negative bacterial infections. A rare side effect of polymyxin B is cutaneous hyperpigmentation, which characteristically involves face and neck. This is commonly reported in pediatric population. We report a case of polymyxin B-induced skin and nail hyperpigmentation and acute kidney injury in an adult patient of malignant otitis externa. [ABSTRACT FROM AUTHOR]

Background: Toxicity is a major concern related to the clinical use of polymyxin B, and available safety data for renal transplant patients are limited. Aims: We investigated the safety of polymyxin B and toxicity risk factors in renal transplant patients. Methods: A prospective study was performed on a group of renal transplant patients who received intravenous polymyxin B between January 2018 and August 2021. Polymyxin B treatment was monitored to evaluate toxicity and risk factors. Results: A total of 235 courses of polymyxin B were administered to 213 patients. Of these, 121 (51.5%) developed skin hyperpigmentation (SH), 149 (63.4%) developed neurotoxicity and 10 (5.5%) developed acute kidney injury of which 80% was reversible. Risk factors for developing SH included a high total dose by weight (odds ration [OR] 1.31, 95% confidence interval [CI] 1.08–1.60, P =.008) and the presence of neurotoxicity (OR 2.86, 95% CI 1.56–5.26, P =.001). Neurotoxicity manifested during the first 2 days of treatment. Neurotoxicity occurred most commonly in women (OR 3.84, 95% CI 1.82–8.10, P <.0001), and the presence of SH (OR 1.98, 95% CI 1.13–3.46, P =.016) was also an independent risk factor. Conclusions: Neurotoxicity and SH are the two major adverse effects of polymyxin B in renal transplant patients, which may limit its clinical use. [ABSTRACT FROM AUTHOR]

Polymyxin B is a polypeptide antimicrobial with bactericidal activity against aerobic gramnegative bacteria, including multidrug-resistant bacteria. Neurotoxicity and nephrotoxicity are consecrated side effects, but brown-brown cutaneous hyperpigmentation was observed on the face, neck, posterior region of the trunk, buttocks and posterior and proximal regions of the lower limbs five days after the beginning of the administration of this antibiotic in a patient hospitalized in the Internal Medicine Infirmary of a hospital in the interior of the State of Ceará. Polymyxin B-induced cutaneous hyperpigmentation is a side effect considered to be poorly described in the medical literature. The etiopathogenic mechanisms that cause this rare alteration remain unknown, but they may involve oxidative stress reactions, causing a release of histamine, which has a melanogenic effect, culminating in the deposition of melanin in the dermis. Although not a life-threatening adverse effect, cutaneous hyperpigmentation can cause significant aesthetic damage, in addition to psychological disorders, but several questions regarding this reaction remain unclear, such as possible therapies that could be used and prognosis. Therefore, the objective of this work was to report a case of cutaneous hyperpigmentation induced by Polymyxin B in a patient admitted to the Internal Medicine Infirmary in a hospital in the interior of the State of Ceará, in addition to reviewing the literature on the same subject. For this, an active search was carried out for the clinical-epidemiological and socioenvironmental data present in the files of the hospital in question, in the patient's chart, in addition to searching and reading journals in the PubMed and SciELO databases in the year 2022. [ABSTRACT FROM AUTHOR]

Yoichi Fukushima,1 Yoshinari Takahashi,2 Yoshimi Kishimoto,3 Chie Taguchi,3 Norie Suzuki,3 Mihoko Yokoyama,4 Kazuo Kondo3,5 1Wellness Communications Section, Nestlé Japan Ltd., Tokyo, Japan; 2Inary Corp., Tokyo, Japan; 3Endowed Research Department “Food for Health”, Ochanomizu University, Tokyo, Japan; 4Yokoyama Skin Clinic, Tokyo, Japan; 5Institute of Life Innovations Studies, Toyo University, Gunma, JapanCorrespondence: Yoichi FukushimaWellness Communications Section, Nestlé Japan Ltd., Tennoz Square, 2-2-20 Higashi-Shinagawa, Shinagawa-ku, Tokyo 140-0002, JapanTel +81 3 5769 6299Fax +81 3 5769 6291Email yoichi.fukushima@jp.nestle.comPurpose: Hyperpigmentation of the skin can occur at any age depending on etiological factors but its intensity increases during adolescence in Japanese females and gradually develops further in adults. The purpose of this study was to characterize factors that influence skin hyperpigmentation, including age, skin type and dietary polyphenol sources.Patients and Methods: A cross-sectional survey of healthy Japanese women aged from 30 to 60 years (n=244) was conducted using food and environmental questionnaires and a VISIA™ facial photoimage analyzer.Results: UV Pigmented Spot (PS) scores correlated negatively with the consumption of total polyphenols (TPs) (R=− 0.224, p< 0.001) and the rate of hyperpigmented spot development (PS score/age after 18 years of age) was suppressed by the consumption of TPs. This trend was independent of the melanin index and the skin type, which indicates the ability of the skin to tan after sun exposure. Consumption of coffee, the largest source of TPs, suppressed the PS score (p< 0.001). Consumption of green tea, the second largest source of TPs, also suppressed the PS score, which was weaker than coffee but was statistically significant (p=0.029). The PS score was suppressed the most in subjects with both a high consumption of coffee and green tea.Conclusion: Higher consumption of TPs may be beneficial to alleviate photoaging of the skin, and coffee as well as green tea contribute to suppress skin hyperpigmentation through adding large amounts of TPs in the diet.Keywords: coffee, green tea, polyphenol, photoaging, skin hyperpigmentation

Background: Cronkhite-Canada syndrome (CCS) is extremely rare in children, presenting with complex clinical manifestations often leading to misdiagnosis., Case Presentation: We reported a description of a 13-year-old boy with CSS presenting with persistent diarrhea, vomiting, abdominal pain, along with symptoms of weight loss, alopecia, and skin hyperpigmentation. The patient had ectodermal manifestations such as alopecia and skin hyperpigmentation. Laboratory tests revealed hypoalbuminemia, normal inflammatory indicators, positive anti-dsDNA antibodies, anti-centromere antibodies, and anti-nuclear antibodies. Gastrointestinal endoscopy identified polypoid changes in the stomach, duodenum, and colon, with pathology indicating glandular dilation, cryptitis, and crypt abscesses. Treatment with prednisone led to significant improvement in symptoms, including normalization of stool consistency, hair regrowth, and disappearance of skin hyperpigmentation., Conclusion: This study emphasizes the importance of comprehensive assessment, endoscopic examination, histological biopsy, and the effectiveness of steroid therapy in the diagnosis and management of CCS in children. In children presenting with diarrhea, abdominal pain, weight loss, polyposis, and ectodermal manifestations, CCS should be considered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Shi, Fu, Zhao, Cheng, Hou and Zhao.)

Objective： To analyze the clinical characteristics of skin hyperpigmentation induced by polymyxin B and possible mechanism involved. Methods: Case reports of skin hyperpigmentation induced by polymyxin B were retrieved from PubMed, EmBase, Cochrane Library, China Nat io nal Knowledge Infrasructure (CNKI) and W anfang Data Digitalization Journals. The obtained data combined with a case encountered in clinical work were summarized and analyzed. Results： 14 case reports involving 18 patients were retrieved, and there was another case encountered in clinical work, totalling 19 patients, of whom 12 (63.2%) were male patients, 4 (21.1%) were female patients and 3 (15.8%) were of unknown gender. Elderly patients ($65 years old) accounted for 26.3% • 3-29 days after medication, there occurred cases of polymyxin B-related skin hyperpigmentation, of which 14 (73.7%) occurred 14 days after medication. There were 9 patients with reported clinical outcomes, and the skin color of the 4 patients returned to normal 45 days to 3 months after cessation of the drug. The mechanism of skin hyperpigmentation induced by polymyxin B might be associated with histamine release, Langerhans cell proliferation, oxidative stress response and increased melanin synthesis by phenylalanine. Conclusion: Skin hyperpigmentation induced by polymyxin B is commonly seen in clinical practice, and the symptoms usually develop in the early stage after medication, mostly affecting the face and neck. The adverse drug reactions are reversible and the original skin color could return to normal several months after drug withdrawal. However, the possible mechanism involved remains unknown, which demands further research. [ABSTRACT FROM AUTHOR]

Abnormal skin pigmentation commonly occurs during the wound healing process due to the overproduction of melanin. Chicken egg white (CEW) has long been used to improve skin health. Previous published works had found CEW proteins house bioactive peptides that inhibit tyrosinase, the key enzyme of melanogenesis. The current study aimed to evaluate the anti-pigmentation potential and mechanism of the CEW-derived peptide (GYSLGNWVCAAK) and hydrolysates (CEWHmono and CEWHdi), using a cell-based model. All of these peptide and hydrolysates inhibited intracellular tyrosinase activity and melanin level up to 45.39 ± 1.31 and 70.01 ± 1.00%, respectively. GYSLGNWVCAAK and CEWHdi reduced intracellular cAMP levels by 13.38 ± 3.65 and 14.55 ± 2.82%, respectively; however, CEWHmono did not affect cAMP level. Moreover, the hydrolysates downregulated the mRNA expression of melanogenesis-related genes, such as Mitf, Tyr, Trp-1 and Trp-2, but GYSLGNWVCAAK only suppressed Tyr gene expression. Downregulation of the genes may lower the catalytic activities and/or affect the structural stability of TYR, TRP-1 and TRP-2; thus, impeding melanogenesis to cause an anti-pigmentation effect in the cell. Outcomes from the current study could serve as the starting point to understand the underlying complex, multifaceted melanogenesis regulatory mechanism at the cellular level.

Background: Some in vitro studies have reported the potential of antioxidants for the reduction of melanogenesis. However, it is important to assess the clinical efficacy of these substances in reducing skin hyperpigmentation. Thus, the aim of this study was to evaluate the clinical efficacy of dermocosmetic formulations based on antioxidants using Reflectance confocal microscopy (RCM). Methods: Thirty‐two healthy females aged 39‐55 years were enrolled and divided into four groups: Vehicle (V), V with ascorbyl tetraisopalmitate (ATIP), V with Spirulina sp., and V with hydroxytyrosol‐titrated olive extract. Imaging analyses by high‐resolution methods and RCM were performed in the malar region of the face before and after a 42‐day period of application of the studied formulations. Results: Reflectance confocal microscopy imaging analyses showed a significant reduction of number of hyperreflective pixels and basal layer brightness after 42 days of application of formulations containing the antioxidants compared to vehicle and baseline values, suggesting an improvement of the skin pigmentation pattern. Conclusion: Reflectance confocal microscopy permitted the identification of skin hyperpigmentation and the assessment of the clinical efficacy of dermocosmetic formulations based on antioxidants in a noninvasive way. All formulations containing antioxidants significantly reduced skin hyperpigmentation after the period of application. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no standard treatment for relapsed/refractory NK/T-cell lymphoma (NKTCL). Liposomal mitoxantrone (Lipo-MIT) showed good anti-tumor effect in patients with NKTCL, breaking the limitation of natural resistance of NKTCL to anthracyclines. To further improve the efficacy, we tried a combination therapy based on Lipo-MIT in patients with relapsed/refractory NKTCL., Methods: 12 patients with relapsed/refractory NKTCL were enrolled in this retrospective study, all of whom had previously received pegaspargase-based treatments. The salvage treatment was a combination regimen based on Lipo-MIT. The efficacy was evaluated after every two cycles., Results: 11 patients had stage IV NKTCL, and all but one patients had an NRI score of ≥3. The median previous lines of treatment was two (range, 1-4), and five patients were refractory to their last line of treatment. The best response rates were as follows: complete response (CR) in five (41.7%) patients, partial response in five (41.7%) patients, stable disease in one (8.3%) patient, and progressive disease in one (8.3%) patient. At a median follow-up of four months (range, 2-14), seven patients died, with a median PFS of five months and a median OS of seven months. The six-month PFS and OS rate was 44.4% and 52.1%, respectively. All patients had suffered from side effects, among which myelosuppression was most reported. Nine patients had grade three or more myelosuppression, and the median recovery time from myelosuppression was 14 days (2-35 days). Five patients had obvious skin hyperpigmentation, and the CR rate was significantly higher compared with those without skin hyperpigmentation (80% vs. 14.3%, p=0.023). Other side effects included liver insufficiency (N=4), coagulation dysfunction (N=4), acute pancreatitis (N=2), and immunotherapy-related adverse effects (irAEs, N=2)., Conclusion: Combination therapy based on Lipo-MIT has a high remission rate for relapsed/refractory NKTCL, but the duration of remission needs to be further extended. Lipo-MIT has obvious myelosuppression toxicity, and active supportive therapy should be given when combined with other cytotoxic drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Yang, Yang, Cong, Song and Wang.)

Abstract Background Polymyxin B (PMB), which is regarded as the ultimate antibacterial treatment against some intractable gram-negative bacteria with its outstanding anti-bacterial activities, inflicts several adverse effects on patients. However, skin hyperpigmentaion (SH) induced by PMB is very rare. Here, we report a case of polymyxin B-induced skin hyperpigmentation (PMB-iSH) in a 21-year-old female. To the best of our knowledge, this is the first case of PMB-iSH in China. Case presentation A 21-year-old female patient with sepsis received the administration of PMB by intravenous injection for the treatment of multi-drug resistant Klebsiella pneumoniae (MDR-KP) infection. She later suffered from a rare adverse drug reaction (ADR), namely PMB-iSH, after 5-day PMB administration during her treatment. There were multiple red rashes spread on the whole body skin at first. With the rashes fading away, SH with dark round spots appeared, associated with no pain or pruritus. The skin of the head and neck was darkened evidently, and dark brown spots were spread on the skin of trunk and limbs. About a month after her admission, urged by the relatives, the patient was transferred back to the local hospital for further treatment in the end, and her skin color didn’t recover to the previous state at that time. Conclusion Both our case and the literature review highlight that PMB can give rise to SH indeed. Clinicians and pharmacists should attach great importance to this rare pigmentary disorder and further investigation is warranted.

Context: Recreational nitrogen oxide (N2O) abuse can cause nervous system damage. There was a sharp increase in the number of patients with neurological disorders associated with recreational N2O use in China, as recreational N2O use became popular in young people nationwide. Among cases with neurological disorders caused by N2O abuse, a few showed skin hyperpigmentation, which has rarely been reported. We explored the characteristics of hyperpigmentation in N2O abusers to draw the attention of clinicians to this rare cutaneous symptom related to N2O abuse. Methods: We retrospectively collected data of patients with neurological disorders related to recreational N2O abuse in Shengjing Hospital of China Medical University from January 2014 to June 2019. Detailed clinical data were gathered from patients who manifested skin pigmentation, including the history of N2O abuse and characteristics of neurological lesions and skin pigmentation. Results: In total, 66 patients (average age: 22.7 ± 4.5 years, 36 males) with neurological disorders due to N2O abuse were included; four of them (17–23 years old, 1 male) manifested skin hyperpigmentation. The duration of N2O abuse of the four patients ranged from 2 to 24 months, and they all had peripheral neuropathy; the two patients also had subacute combined degeneration of the spinal cord. One patient exhibited significant hyperpigmentation throughout the body (trunk, limbs, and face), with no abnormalities in cortisol and other biochemical tests. One patient presented with punctuate pigmentation throughout the trunk. Two patients presented with finger skin pigmentation, especially in the distal phalanxes. Pigmentation after N2O use remitted slowly with vitamin B12 supplementation. Conclusion: Skin hyperpigmentation is a rare symptom in N2O abusers, which can distribute locally in hands or diffusely throughout the body. Therefore, attention should be paid to a history of N2O abuse and serum vitamin B12 level should be tested. [ABSTRACT FROM AUTHOR]

Familial glucocorticoid deficiency type 1 (FGD1) is an autosomal recessive disorder caused by mutations in the melanocortin 2 receptor (MC2R) gene, characterized by a low or undetectable serum cortisol level and a high adrenocorticotropic hormone (ACTH) level. Clinical manifestations include hypoglycemia, seizure, skin hyperpigmentation, hyperbilirubinemia, cholestasis, and a tall stature. Some dysmorphic features such as, a prominent forehead, hypertelorism, a broad nasal bridge, and small tapering fingers, have been reported. Children with FGD1 may have other isolated endocrine abnormalities. To date, no patient with FGD1 has been reported in mainland China. Here we report on a Chinese patient with FGD1 having a novel MC2R gene variant, a mild transverse palm crease, hypertelorism, and subtle/transient endocrine abnormalities relating to all three zones of the adrenal cortex and thyroid gland. We also reviewed cases with dysmorphic features or additional endocrine abnormalities.

Summary: Parry‐Romberg syndrome is a hemifacial atrophy which can be complicated by melasma. We present two cases of Parry‐Romberg syndrome, treated by fat transfer and bleaching of the skin using a modified "Kligman's formula." The atrophy, as well as the skin dyschromia, improved, and the results were stable. [ABSTRACT FROM AUTHOR]

Familial glucocorticoid deficiency type 1 (FGD1) is an autosomal recessive disorder caused by mutations in the melanocortin 2 receptor (MC2R) gene, characterized by a low or undetectable serum cortisol level and a high adrenocorticotropic hormone (ACTH) level. Clinical manifestations include hypoglycemia, seizure, skin hyperpigmentation, hyperbilirubinemia, cholestasis, and a tall stature. Some dysmorphic features such as, a prominent forehead, hypertelorism, a broad nasal bridge, and small tapering fingers, have been reported. Children with FGD1 may have other isolated endocrine abnormalities. To date, no patient with FGD1 has been reported in mainland China. Here we report on a Chinese patient with FGD1 having a novel MC2R gene variant, a mild transverse palm crease, hypertelorism, and subtle/transient endocrine abnormalities relating to all three zones of the adrenal cortex and thyroid gland. We also reviewed cases with dysmorphic features or additional endocrine abnormalities. [ABSTRACT FROM AUTHOR]

In addition, the hyperpigmentation of skin can also be a cutaneous manifestation of systemic diseases or conditions, which raises the need for a proper quantification of skin hyperpigmentation to monitor disease progression [[1] [3]]. Keywords: Skin hyperpigmentation; Skin hyperpigmentation index; Quantification EN Skin hyperpigmentation Skin hyperpigmentation index Quantification 486 488 3 05/08/21 20210501 NES 210501 Dear Editor Hyperpigmentation is a darkening of the skin, mostly caused by increased production of melanin due to melanocyte activation or hemosiderin deposits in the skin [[1]]. As a result, we recently presented an advanced digital image processing system called the "skin hyperpigmentation index" (SHI) for the automated quantification of skin hyperpigmentation. [Extracted from the article]

Skin hyperpigmentation disorders arise due to aberrant regulation of melanin synthesis and export. Current treatments include natural compounds like kojic acid and hydroquinone, which suffer from limitations due to adverse reactions. Thermorubin (TR) is a secondary metabolite derived from the fungus Thermoactinomyces antibioticus and has previously demonstrated to possess anti-inflammatory properties by inhibition of matrix metalloproteinases (MMPs), as well as antimicrobial activity. In the current study, we explored whether TR might be a used as a candidate for the treatment of skin hyperpigmentation disorders by studying its effects on melanin synthesis and melanin export in B16F10 mouse melanoma cells and primary human melanocytes derived from darkly-pigmented (DP) skin. Non-toxic doses of TR were first identified in B16F10 mouse melanoma cells. These doses were subsequently tested for their effects on both extracellular and intracellular melanin levels under conditions of basal and hormone-stimulated melanogenesis. Our results demonstrated that TR at 25 µM inhibited total melanin levels with selective inhibition of extracellular melanin in B16F10 cells under both basal and hormone-stimulated conditions. The mechanisms of inhibition did not include tyrosinase inhibition, either in cellular lysates or cell-free system. However, TR potently inhibited activity of α-glucosidase enzyme in vitro and exhibited antioxidant activity. Furthermore, our results with primary human melanocytes from DP skin showed that TR at 10 µM significantly suppressed dendricity along with an increase in accumulation of intracellular melanin. These findings point to a mechanism of action of TR as an exclusive inhibitor of melanosome export. Taken together, our preliminary results demonstrate that TR might offer a novel ingredient as a skin depigmenting agent for inclusion in cosmetic formulations. Further studies delineating molecular mechanisms of hypopigmentation of TR and testing in human skin tissue-equivalents are warranted.