-
Dermatology (Basel, Switzerland) 2024Vitiligo is a common depigmentation disorder characterized by defined white patches on the skin and affecting around 0.5% to 2% of the general population. Genetic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitiligo is a common depigmentation disorder characterized by defined white patches on the skin and affecting around 0.5% to 2% of the general population. Genetic association studies have identified several pre-disposing genes and single nucleotide polymorphisms (SNPs) for vitiligo pathogenesis; nonetheless, the reports are often conflicting and rarely conclusive. This comprehensive meta-analysis study was designed to evaluate the effect of the risk variants on vitiligo aetiology and covariate stratified vitiligo risk in the Asian population, considering all the studies published so far.
METHODS
We followed a systematic and comprehensive search to identify the relevant vitiligo-related candidate gene association studies in PubMed using specific keywords. After data extraction, we calculated, for the variants involved, the study-level unadjusted odds ratio, standard errors, and 95% confidence intervals by using logistic regression with additive, dominant effect, and recessive models using R software package (R, 3.4.2) "metafor." Subgroup analysis was performed using logistic regression (generalized linear model; "glm") of disease status on subgroup-specific genotype counts. For a better understanding of the likely biological function of vitiligo-associated variant obtained through the meta-analysis, in silico functional analyses, through standard publicly available web tools, were also conducted.
RESULTS
Thirty-one vitiligo-associated case-control studies on eleven SNPs were analysed in our study. In the fixed-effect meta-analysis, one variant upstream of TNF-α gene: rs1800629 was found to be associated with vitiligo risk in the additive (p = 4.26E-06), dominant (p = 1.65E-7), and recessive (p = 0.000453) models. After Benjamini-Hochberg false discovery rate (FDR) correction, rs1800629/TNF-α was found to be significant at 5% FDR in the dominant (padj = 1.82E-6) and recessive models (padj = 0.0049). In silico characterization revealed the prioritized variant to be regulatory in nature and thus having potential to contribute towards vitiligo pathogenesis.
CONCLUSION
Our study constitutes the first comprehensive meta-analysis of candidate gene-based association studies reported in the whole of the Asian population, followed by an in silico analysis of the vitiligo-associated variant. According to the findings of our study, TNF-α single nucleotide variant rs1800629G>A has a risk association, potentially contributing to vitiligo pathogenesis in the Asian population.
Topics: Vitiligo; Humans; Genetic Predisposition to Disease; Asian People; Tumor Necrosis Factor-alpha; Polymorphism, Single Nucleotide
PubMed: 38377977
DOI: 10.1159/000536480 -
Journal of Cutaneous Medicine and... 2024
Topics: Humans; Hypopigmentation; Mitogen-Activated Protein Kinase Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Vitiligo
PubMed: 38323558
DOI: 10.1177/12034754241230690 -
Cancers Jan 2024Immune checkpoint inhibitors (ICIs) are used to treat many cancers, and cutaneous immune-related adverse events (cirAEs) are among the most frequently encountered toxic... (Review)
Review
Immune checkpoint inhibitors (ICIs) are used to treat many cancers, and cutaneous immune-related adverse events (cirAEs) are among the most frequently encountered toxic effects. Understanding the incidence and prognostic associations of cirAEs is of importance as their uses in different settings, combinations, and tumor types expand. To evaluate the incidence of cirAEs and their association with outcome measures across a variety of ICI regimens and cancers, we performed a systematic review and meta-analysis of published trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) ICIs, both alone and in combination with chemotherapy, antiangiogenic agents, or other ICIs in patients with melanoma, renal cell carcinoma, non-small cell lung cancer, and urothelial carcinoma. Key findings of our study include variable cirAE incidence among tumors and ICI regimens, positive association with increased cirAE incidence and response rate, as well as significant association between increased vitiligo incidence and overall survival. Across 174 studies, rash, pruritis, and vitiligo were the most reported cirAEs, with incidences of 16.7%, 18.0%, and 6.6%, respectively. Higher incidence of cirAEs was associated with ICI combination regimens and with CTLA-4-containing regimens, particularly with higher doses of ipilimumab, as compared to PD-1/L1 monotherapies. Outcome measures including response rate and progression-free survival were positively correlated with incidence of cirAEs. The response rate and incidence of pruritis, vitiligo, and rash were associated with expected rises in incidence of 0.17% ( = 0.0238), 0.40% ( = 0.0010), and 0.18% ( = 0.0413), respectively. Overall survival was positively correlated with the incidence of pruritis, vitiligo, and rash; this association was significant for vitiligo ( = 0.0483). Our analysis provides benchmark incidence rates for cirAEs and links cirAEs with favorable treatment outcomes at a study level across diverse solid tumors and multiple ICI regimens.
PubMed: 38254829
DOI: 10.3390/cancers16020340 -
The Journal of Dermatological Treatment Dec 2024This study aimed to compare the efficacy and safety of excimer laser (EL)-based combination regimens in improving repigmentation. (Meta-Analysis)
Meta-Analysis Review
AIM
This study aimed to compare the efficacy and safety of excimer laser (EL)-based combination regimens in improving repigmentation.
METHODS
A comprehensive search was conducted in PubMed, Web of Science, Cochrane Library, and Embase on July 1, 2023, to include randomized controlled trials of EL combination treatments for vitiligo that met the criteria. The primary outcome measure was a repigmentation rate ≥ 75%, and the secondary outcome measures were a repigmentation rate of ≤ 25% and adverse events.
RESULTS
Eleven studies involving 348 patients were included. Network Meta-Analysis showed that EL combined with antioxidants (SUCRA = 98.8%), EL combined with calcipotriol (SUCRA = 59.8%) and EL combined with tacalcitol (SUCRA = 59.6%) were the three optimal interventions achieving repigmentation rates ≥ 75%. EL alone (SUCRA = 77.6%), EL combined with tacalcitol (SUCRA = 61.7%) and EL combined with antioxidants (SUCRA = 57.2%) were the three interventions with the highest rates of treatment failure. Adverse events in all groups mainly included erythema, burning sensation and hyperpigmentation. Based on the results of the current study, EL combination therapies were safe with mild adverse events.
CONCLUSION
EL combined with antioxidants was the preferred regimen for vitiligo, whereas EL alone was the regimen with the highest rate of treatment failure in vitiligo.
Topics: Humans; Vitiligo; Lasers, Excimer; Network Meta-Analysis; Combined Modality Therapy; Treatment Failure; Treatment Outcome
PubMed: 38230424
DOI: 10.1080/09546634.2024.2302064 -
Journal of Cosmetic Dermatology Jan 2024
Meta-Analysis
Topics: Humans; Nitriles; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Vitiligo; Pyrazoles
PubMed: 38161317
DOI: 10.1111/jocd.15921 -
Archives of Dermatological Research Dec 2023There is increasing demand for natural and sustainable products for the treatment of dermatologic conditions. This systematic review aims to critically analyze published... (Review)
Review
There is increasing demand for natural and sustainable products for the treatment of dermatologic conditions. This systematic review aims to critically analyze published randomized controlled trials (RCTs) and provide evidence-based recommendations on the therapeutic use of curcumin for a variety of dermatological diseases. A systematic search of published literature was performed on July 18, 2023 using PRISMA guidelines for turmeric or curcumin for the treatment of skin diseases. Clinical recommendations were made based on the Oxford Centre for Evidence-Based Medicine guidelines. We identified 18 original randomized controlled trials for use of turmeric or curcumin for psoriasis, radiation dermatitis, oral lichen planus, pruritis, vitiligo, tinea capitis, facial erythema, and scarring. Psoriasis, cesarean section scar, and pruritus received grade of recommendation B. Radiation dermatitis, oral lichen planus, vitiligo, tinea capitis, and facial redness received grade of recommendation C or D. Curcumin was demonstrated to have an excellent safety profile in all clinical trials analyzed. Further research is required to determine optimal dosing and treatment parameters of turmeric. Additional, larger, RCTs and non-RCTs should be conducted to further investigate the safety and efficacy of curcumin as a treatment option for dermatological diseases.
Topics: Humans; Curcumin; Lichen Planus, Oral; Vitiligo; Psoriasis; Tinea Capitis; Dermatitis
PubMed: 38085369
DOI: 10.1007/s00403-023-02754-8 -
Skin Health and Disease Dec 2023Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed... (Review)
Review
Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed death-1 (PD1) and anti-cytotoxic T-lymphocyte-associated protein (anti-CTLA4). However, a significant percentage of patients develop resistance to these immunotherapy drugs. Therefore, novel strategies were developed to target other aspects of the immune response. Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule found on natural killer cells and activated T-cells which negatively regulates T-cell proliferation and function. LAG-3 inhibitors interact with LAG-3 ligands on the surface of T-cells to block T-regulatory (Treg) cell activity, suppress cytokine secretion and restore dysfunctional effector T-cells which subsequently attack and destroy cancer cells. This review reports the dermatologic side effects associated with LAG-3 inhibitors used in the treatment of melanomas. Using PRISMA 2022 guidelines, a comprehensive literature review of PubMed, Google Scholar, Embase, Cochrane, and Web of Science databases was conducted. Three studies were identified that demonstrated that the use of LAG-3 inhibitors, whether as a single agent or in combination with other immune checkpoint inhibitors, resulted in stomatitis, pruritus, rash, dry skin, erythema, and vitiligo. Further research is warranted to assess the cutaneous adverse events observed with LAG-3 inhibitors in treating melanoma and to identify populations most vulnerable to such side effects.
PubMed: 38047262
DOI: 10.1002/ski2.296 -
International Journal of Dermatology Dec 2023Since extracutaneous melanocytes in the eye may also be affected in vitiligo, a systematic review was conducted to explore the ocular manifestations of vitiligo. Studies...
Since extracutaneous melanocytes in the eye may also be affected in vitiligo, a systematic review was conducted to explore the ocular manifestations of vitiligo. Studies point to a higher risk of ocular findings in periorbital vitiligo. Dry eye disease is the most reported ocular abnormality in vitiligo. Additionally, several small studies have found potential links to uveitis and glaucoma. Various other chorioretinal pigmentary changes are also reported, but without accompanying functional consequences or changes in vision. Although there is a need for larger studies to further elucidate these associations, dermatologists should be aware of potential ocular comorbidities in vitiligo and refer to ophthalmology accordingly.
Topics: Humans; Vitiligo; Dermatologists; Pigmentation Disorders; Eye; Glaucoma
PubMed: 37919864
DOI: 10.1111/ijd.16883 -
JAMA Dermatology Jan 2024Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions.
OBJECTIVE
To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions.
DATA SOURCES
PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023.
STUDY SELECTION
This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded.
DATA EXTRACTION AND SYNTHESIS
This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO.
MAIN OUTCOMES AND MEASURES
Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE.
RESULTS
The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.
Topics: Humans; Male; Adult; Janus Kinase Inhibitors; Venous Thromboembolism; Arthritis, Rheumatoid; Dermatitis, Atopic; Treatment Outcome
PubMed: 37910098
DOI: 10.1001/jamadermatol.2023.4090 -
Medicine Oct 2023Vitiligo is an acquired chronic depigmentary disorder affecting approximately 0.5% to 1% of individuals worldwide. The compound glycyrrhizin (CG), a complementary... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of compound glycyrrhizin in combination with conventional therapy in treatment of vitiligo: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Vitiligo is an acquired chronic depigmentary disorder affecting approximately 0.5% to 1% of individuals worldwide. The compound glycyrrhizin (CG), a complementary medicine, has been reported for treatment of vitiligo, but the evidence has not been systematically evaluated. We systematically assessed the efficacy and safety of CG in combination with conventional therapy for the treatment of vitiligo.
METHODS
We searched Embase, Web of Science, PubMed, The Cochrane Library, Chinese BioMedical Literature Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and VIP information from inception to July 2022. Randomized controlled trials comparing CG combined with conventional therapy with conventional therapy alone for vitiligo were included in our analysis. The primary outcome was treatment response, which defined as >50% repigmentation rate of vitiligo after treatment. The secondary outcome was incidence of adverse events. Meta-analysis was performed using the Review Manager 5.4 software. Statistical heterogeneity was evaluated with chi-square and I2 statistics, dichotomous data were expressed as risk ratios (RR) with 95% confidence intervals using the Mantel-Haenszal method.
RESULTS
Thirty-nine studies enrolling with 3994 participants were subjected to this review. The results of our meta-analysis indicated that addition of CG had superior effectiveness on repigmentation rate than phototherapy (RR = 1.28; P < .001), immunosuppressant (RR = 1.76; P < .001), traditional Chinese medicine (RR = 1.38; P < .001), combination of phototherapy and immunosuppressant (RR = 1.42; P < .001), and combination of phototherapy and traditional Chinese medicine (RR = 1.37; P < .001). In addition, CG did not increase the incidence of adverse events for vitiligo (RR = 0.79; P = .05).
CONCLUSIONS
CG as a complementary medicine has a potential benefit in treatment of vitiligo. However, since the methodological flaws in the studies we included, more high-quality randomized controlled trials are warranted.
Topics: Humans; Vitiligo; Drugs, Chinese Herbal; Glycyrrhizic Acid; Randomized Controlled Trials as Topic; Immunosuppressive Agents
PubMed: 37904437
DOI: 10.1097/MD.0000000000035533