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The Journal of Dermatological Treatment Dec 2024This study aimed to evaluate the efficacy of tranexamic acid (TXA) in treating melasma through a meta-analysis and systematic review of randomized controlled trials... (Meta-Analysis)
Meta-Analysis Review
This study aimed to evaluate the efficacy of tranexamic acid (TXA) in treating melasma through a meta-analysis and systematic review of randomized controlled trials (RCTs). The study focused on identifying associated adverse effects and comparing TXA's effectiveness with other melasma treatments. Following PROSPERO and PRISMA guidelines, an extensive electronic search was conducted across four databases for RCTs on TXA use in melasma. Inclusion criteria encompassed full-text English articles with specific outcome measures, while studies with high bias risk or non-English publications were excluded. Data were extracted from 22 relevant studies and analyzed using the RevMan software, with heterogeneity identified using I² statistics and forest plots. A total of 22 studies with 1280 patients were included. TXA was administered orally, topically, or via injection, with treatment durations ranging from 8 weeks to nearly 2 years. TXA significantly reduced melasma severity, evidenced by reductions in MASI, mMASI, MI, and hemi-MASI scores. Oral TXA showed the most substantial decrease in MASI scores, followed by injections and topical applications. However, studies exhibited high heterogeneity, particularly in combined treatments. Adverse effects included gastrointestinal discomfort, skin irritation, and menstrual irregularities. TXA is effective in treating melasma, either alone or combined with other treatments. Despite significant reductions in melasma severity, further research is necessary to standardize TXA administration methods and address long-term effects. The high heterogeneity observed suggests a need for more consistent treatment protocols.
Topics: Melanosis; Humans; Tranexamic Acid; Randomized Controlled Trials as Topic; Treatment Outcome; Administration, Oral; Antifibrinolytic Agents; Severity of Illness Index; Administration, Cutaneous
PubMed: 38843906
DOI: 10.1080/09546634.2024.2361106 -
Osteoporosis International : a Journal... Jun 2024Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are...
Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.
PubMed: 38836946
DOI: 10.1007/s00198-024-07127-z -
Peptides Jun 2024The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions...
The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.
PubMed: 38834138
DOI: 10.1016/j.peptides.2024.171255 -
Cureus May 2024Terra firma-forme dermatosis is an acquired and idiopathic disorder with an underestimated incidence. It is characterized by brownish skin pigmentation, forming...
Terra firma-forme dermatosis is an acquired and idiopathic disorder with an underestimated incidence. It is characterized by brownish skin pigmentation, forming asymptomatic plaques that give a soiled skin appearance. Soap and water have a minor effect; however, friction with 70% ethyl or isopropyl alcohol immediately eliminates plaques to a normal skin appearance, thus being the ideal method for diagnosis and treatment. The lack of familiarity with this disease possibly contributes to an alarming underdiagnosis. In this report, the authors present a case of terra firma-forme occurring in a 14-year-old Mexican patient who presented with a heart-shaped pigmented lesion in the pubic area.
PubMed: 38826967
DOI: 10.7759/cureus.59565 -
Journal of Surgical Case Reports May 2024Peutz-Jeghers syndrome (PJS) is a rare genetic disorder causing gastrointestinal polyps and skin pigmentation. Our case report highlights a unique instance of...
Peutz-Jeghers syndrome (PJS) is a rare genetic disorder causing gastrointestinal polyps and skin pigmentation. Our case report highlights a unique instance of jejuno-jejunal intussusception associated with PJS in a 28-year-old female patient who presented to the emergency department with colicky abdominal pain, tachycardia, and gastrointestinal symptoms. Physical examination revealed mucocutaneous hyperpigmentation. Imaging studies showed a U-shaped distension in the jejunum with thickening and pneumatosis. Laparotomy revealed a jejuno-jejunal volvulus with intussusception. Surgical resection successfully addressed gangrenous jejunal tissue and ileal polyps. Histopathology confirmed PJS polyps. Postoperatively, the patient recovered well and was discharged. Family history revealed similar skin lesions in her uncle. Our case highlights the need for prompt surgical intervention to address complications associated with PJS and elucidates a unique presentation of PJS involving jejuno-jejunal intussusception and volvulus leading to complete small bowel obstruction. We aim to deepen understanding and prompt discussions on optimal therapeutic strategies.
PubMed: 38812577
DOI: 10.1093/jscr/rjae335 -
Skin Research and Technology : Official... Jun 2024Vitiligo is an acquired autoimmune depigmented disorder characterized by the presence of white and well-defined patches on the skin, mucous membrane, or both. It is...
BACKGROUND
Vitiligo is an acquired autoimmune depigmented disorder characterized by the presence of white and well-defined patches on the skin, mucous membrane, or both. It is associated with a significant disease burden and has a profoundly impacts patients' quality of life. Autoimmune thyroid diseases (AITDs) result from an autoimmune system dysregulation, leading to an erroneous immune attack on the thyroid gland. Previous observational and epidemiological studies have suggested the association between vitiligo and AITDs. However, the bidirectional cause-effect relationship between vitiligo and AITDs has not been formally assessed.
METHOD
Two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore potential causal relationships between genetically increased risk of vitiligo and AITDs, using summary statistics from genome-wide association studies in European populations. Causal effects were primarily estimated using the inverse variance weighted method, and additional quality control was performed using the MR-Egger, weighted median, simple mode, and weight mode methods. Sensitivity analysis was conducted to assess the robustness of the results.
RESULTS
The forward MR analysis showed a positive causal relationship between vitiligo and autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves' disease (GD). The odds ratio (OR) were 1.17 (95% CI, 1.01-1.35; p = 0.04), 1.12 (95% CI, 1.03-1.22; p = 0.01), and 1.13 (95% CI, 1.06-1.20; p < 0.01), respectively. In the reverse MR analysis, a positive causal relationship was found between AIT and vitiligo, with an OR of 1.10 (95% CI, 1.01-1.35; p = 0.04). However, no causal relationship was observed between AIH (p = 0.10) or GD (p = 0.61) and vitiligo. Sensitivity analysis revealed no evidence of horizontal pleiotropy or heterogeneity.
CONCLUSIONS
The genetic-level investigation provides evidence of a genetic causal association between susceptibility to vitiligo and an increased risk of AITDs. Additionally, the results demonstrate a genetic causal association between susceptibility to AIT and an increased risk of vitiligo, while not indicating a similar association with susceptibility to AIH or GD.
Topics: Vitiligo; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Genetic Predisposition to Disease; Thyroiditis, Autoimmune; Autoimmune Diseases; Thyroid Diseases; Polymorphism, Single Nucleotide
PubMed: 38807429
DOI: 10.1111/srt.13742 -
Cell Reports Jun 2024Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin...
Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We show substantially increased levels of 5',8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents insights with intervention potential.
Topics: Xeroderma Pigmentosum; Induced Pluripotent Stem Cells; Humans; Neurons; Oxidative Stress; Endoplasmic Reticulum Stress; Proteasome Endopeptidase Complex; Cell Differentiation; DNA Damage; Models, Biological; Multiomics
PubMed: 38805398
DOI: 10.1016/j.celrep.2024.114243 -
Advances in Therapy Jul 2024Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological...
INTRODUCTION
Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological conditions. Our current understanding of vitiligo burden and management in the real world is limited. This real-world analysis presents data on vitiligo epidemiology, comorbidities, and treatment of patients in Israel.
METHODS
This retrospective study analyzed data from the Maccabi Health Services database. Prevalent patients with vitiligo in 2021 were matched to patients in the general population on the basis of age group, gender, and socioeconomic status. Patient demographics, vitiligo incidence and prevalence, comorbidities, and treatment patterns are reported. Data are presented as percentages, mean, median, P values, and standard mean differences (SMD).
RESULTS
In this analysis, 11,412 patients with vitiligo were matched to patients from the general population. Incidence and prevalence rates increased over time from 2005 to 2021. Compared to the general population, patients with vitiligo were more likely to have an immune-mediated comorbidity (29.7% vs 18.4% [P < 0.001; SMD 0.27]) or psychological comorbidity (18.7% vs 15.9% [P < 0.001; SMD 0.07]). Comorbidities included atopic dermatitis (patients with vitiligo vs general population 12.5% vs 8.4%), psoriasis (5.8% vs 3.6%), Hashimoto's thyroiditis (2.9% vs 1.1%), alopecia areata (2.2% vs 0.9%), depression (10.8% vs 9.5%), and sleep disorder/insomnia (5.9% vs 4.4%). Only 74.8% of all patients with vitiligo had ever received treatment, with topical corticosteroids (51.5%) and calcineurin inhibitors (36.5%) most commonly prescribed. At the end of 2021, 83.7% of patients were untreated.
CONCLUSION
Patients with vitiligo are more likely to have various immune-related and psychological comorbidities, highlighting the significant impact of the condition on well-being. Nearly a quarter of patients had never received treatment, with many receiving only topical treatments, and medication persistence was low. This highlights the lack of adequate treatment in this population and the need for more effective management options.
Topics: Humans; Vitiligo; Male; Female; Retrospective Studies; Adult; Israel; Middle Aged; Prevalence; Comorbidity; Incidence; Young Adult; Adolescent; Child; Aged; Child, Preschool
PubMed: 38802636
DOI: 10.1007/s12325-024-02875-0 -
Journal of Cutaneous and Aesthetic... 2024Facial pigmentation is a common presentation of patients attending dermatology out patient department (OPD) and is of great concern to patients. Facial pigmentation may...
INTRODUCTION
Facial pigmentation is a common presentation of patients attending dermatology out patient department (OPD) and is of great concern to patients. Facial pigmentation may be multifactorial and is only rarely diagnosed accurately by a detailed history and clinical examination. Pigmentary disorders cause psychological distress and negatively impact the quality of life of an individual.
AIMS AND OBJECTIVES
(1) To study different dermoscopic patterns in facial melanosis. (2) To estimate the frequency of different dermoscopic patterns.
MATERIALS AND METHODS
Patients with facial hyperpigmentation attending the dermatology OPD were recruited after taking their written consent. A detailed history was taken to collect demographic data. Clinical examination and dermoscopy were done in all patients. Biopsy was done as and when required. Descriptive statistics has been used to describe the quantitative data. Qualitative data were presented as frequency and percentage for clinical and dermoscopic patterns.
RESULTS
The study included 100 patients with 15 different facial melanoses. The most common age group affected was 21-40 years in 53 (53%) cases. The female-to-male ratio was 1.63:1. Melasma was reported as the most common cause of facial melanosis constituting 49 (49%) of the total cases. Out of the total melasma cases, epidermal melasma constituted 22 (45%) cases, dermal melasma constituted four (4%) cases and mixed melasma constituted 23 (47%) cases. Other cases included were lichen planus pigmentosus (14; 14%), facial acanthosis nigricans (14; 14%), periorbital hyperpigmentation (7; 7%), post-inflammatory hyperpigmentation (4; 4%), exogenous ochronosis (2; 2%), lentigines (2; 2%), frictional melanosis (2;2%), and one case each of Becker's nevus, nevus of Ota, olanzapine-induced hyperpigmentation, Riehl's melanosis, macular amyloidosis, and tanning.
CONCLUSIONS
Melasma was reported as the most common cause of facial melanosis. The most common dermoscopic feature was accentuated pseudopigment network. The study is beneficial in understanding the different clinical and dermoscopic patterns of facial melanosis, thus helping the physician to effectively manage the conditions and reduce the need of biopsy.
LIMITATIONS
(1) A small sample size. (2) Histopathological correlation was not done in all cases.
PubMed: 38800811
DOI: 10.4103/JCAS.JCAS_48_23 -
International Journal of Molecular... May 2024Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis...
Epidermal melanin synthesis determines an individual's skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable.
Topics: Humans; Melanins; Melanocytes; Plasma Gases; Epidermis; Ultraviolet Rays; Skin Pigmentation; Cells, Cultured; Reactive Oxygen Species; Biopsy; Melanogenesis
PubMed: 38791225
DOI: 10.3390/ijms25105186