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Advanced Drug Delivery Reviews Jan 2020Skin pigmentation is a result of melanin produced by melanocytes in the epidermis. Melanocyte activity, along with the type and distribution of melanins, is the main...
Skin pigmentation is a result of melanin produced by melanocytes in the epidermis. Melanocyte activity, along with the type and distribution of melanins, is the main driver for diversity of skin pigmentation. Dark melanin acts to protect against the deleterious effects of ultraviolet (UV) radiation, including photo-aging and skin cancer formation. In turn, UV radiation activates skin melanocytes to induce further pigmentation (i.e., "tanning pathway"). The well-characterized MSH/MC1R-cAMP-MITF pathway regulates UV-induced melanization. Pharmacologic activation of this pathway ("sunless tanning") represents a potential strategy for skin cancer prevention, particularly in those with light skin or the "red hair" phenotype who tan poorly after UV exposure due to MC1R inactivating polymorphisms. Skin hyperpigmentation can also occur as a result of inflammatory processes and dermatological disorders such as melasma. While primarily of cosmetic concern, these conditions can dramatically impact quality of life of affected patients. Several topical agents are utilized to treat skin pigmentation disorders. Here, we review melanogenesis induced by UV exposure and the agents that target this pathway.
Topics: Administration, Cutaneous; Cyclic AMP; Dermatologic Agents; Drug Delivery Systems; Humans; Melanins; Pigmentation Disorders; Protein Kinases; Skin Pigmentation; Ultraviolet Rays
PubMed: 32092380
DOI: 10.1016/j.addr.2020.02.002 -
Journal of the American Academy of... Sep 2021Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results.
BACKGROUND
Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results.
OBJECTIVE
To systematically review the prevalence of dermoscopic structures in BCC and its subtypes.
METHODS
Databases and reference lists were searched for relevant trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for the relative proportion of BCC dermoscopic features. Random-effects models were used to estimate summary effect sizes.
RESULTS
Included were 31 studies consisting of 5950 BCCs. The most common dermoscopic features seen in BCC were arborizing vessels (59%), shiny white structures (49%), and large blue-grey ovoid nests (34%). Arborizing vessels, ulceration, and blue-grey ovoid nests and globules were most common in nodular BCC; short-fine telangiectasia, multiple small erosions, and leaf-like, spoke wheel and concentric structures in superficial BCC; porcelain white areas and arborizing vessels in morpheaform BCC; and arborizing vessels and ulceration in infiltrative BCC.
LIMITATIONS
Studies had significant heterogeneity. Studies reporting BCC histopathologic subtypes did not provide clinical data on pigmentation of lesions.
CONCLUSION
In addition to arborizing vessels, shiny white structures are a common feature of BCC. A constellation of dermoscopic features may aid in differentiating between BCC histopathologic subtypes.
Topics: Carcinoma, Basal Cell; Dermoscopy; Humans; Pigmentation; Pigmentation Disorders; Skin Neoplasms
PubMed: 31706938
DOI: 10.1016/j.jaad.2019.11.008 -
Frontiers in Medicine 2021Melasma is an acquired pigmentation disorder with challenges in treatment because of its refractory nature and high risk of recurrence. This study aimed to compare the...
Melasma is an acquired pigmentation disorder with challenges in treatment because of its refractory nature and high risk of recurrence. This study aimed to compare the efficacy and side effects of 14 common therapies for melasma using a systematic review and network meta-analysis (NMA). The PubMed, Embase, and Cochrane Library databases were searched till December 2020 using the melasma area and severity index as a therapeutic index. A total of 59 randomized controlled trials (RCTs) met the inclusion criteria and were selected. The ranking of relative efficacy compared with placebo in descending order was Q-switched Nd:Yag 1,064-nm laser (QSND), intense pulsed light, ablative fractional laser (AFL), triple combined cream (TCC), topical vitamin C, oral tranexamic acid (oTA), peeling, azelaic acid, microneedles (MNs), topical tranexamic acid (tTA), tretinoin, picosecond laser, hydroquinone (HQ), and non-AFL. Moreover, QSND was more effective than HQ and tTA against melasma. The ranking of percentage (%) of side effects in ascending order for each of 14 therapies with more than 80 participants was tretinoin (10.1%), oTA (17.6%), HQ (18.2%), AFL (20.0%), QSND (21.5%), TCC (25.7%), tTA (36.75%), peeling (38.0%), and MN (52.3%). Taking both efficacy and safety into consideration, TCC was found to be the most favorable selection among the topical drugs for melasma. QSND and AFL were still the best ways to treat melasma among photoelectric devices. oTA as system administration was a promising way recommended for melasma. Among 31 studies, 87% (27/31) studies showed that the efficacy of combination therapies is superior to that of single therapy. The quality of evidence in this study was generally high because of nearly 50% of split-face RCTs. Based on the published studies, this NMA indicated that QSND, AFL, TCC, and oTA would be the preferred ways to treat melasma for dermatologists. However, more attention should be paid to the efficacy and safety simultaneously during the clinical application. Most of the results were in line with those of the previous studies, but a large number of RCTs should be included for validation or update. identifier: CRD42021239203.
PubMed: 34660626
DOI: 10.3389/fmed.2021.713554 -
The Journal of Dermatological Treatment Feb 2022Vitiligo is an autoimmune disorder characterized by progressive loss of melanocytes, leading to cutaneous depigmentation. Vitiligo has significant psychosocial impacts... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vitiligo is an autoimmune disorder characterized by progressive loss of melanocytes, leading to cutaneous depigmentation. Vitiligo has significant psychosocial impacts on patients and is challenging to manage with limited treatment options. Recent studies have suggested promising results for JAK1/3 inhibitors including tofacitinib and ruxolitinib.
OBJECTIVE
To determine the expected response of vitiligo to JAK inhibitor therapy and factors which influence response rates.
METHODS
A systematic review and meta-analysis was performed according to PRISMA guidelines. Good response was defined as repigmentation >50% or a 'good' or 'excellent' outcome as described by authors. Partial response was defined as some repigmentation <50%.
RESULTS
From the 9 eligible studies, individual patient data from 45 cases were pooled. Good response was achieved in 57.8%, partial response in 22.2%, and none or minimal response in 20% of cases. When subgrouped according to site, facial vitiligo had the highest good response rate (70%), compared to extremities (27.3%) and torso/non-sun exposed areas (13.6%). Concurrent phototherapy was significant associated with higher rates of good overall response ( < .001) and good facial response ( < .001).
CONCLUSIONS
There is promising low-quality evidence regarding the effectiveness of JAK inhibitors in vitiligo. Concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.
Topics: Humans; Janus Kinase Inhibitors; Janus Kinases; Phototherapy; Skin Pigmentation; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 32096671
DOI: 10.1080/09546634.2020.1735615 -
JAMA Dermatology Feb 2021While current evidence supports UV exposure as an important risk factor for cutaneous melanoma in fair-skinned populations, the evidence for this association in skin of...
IMPORTANCE
While current evidence supports UV exposure as an important risk factor for cutaneous melanoma in fair-skinned populations, the evidence for this association in skin of color is less certain.
OBJECTIVE
To critically assess and synthesize the published data regarding the association between UV exposure and the risk of cutaneous melanoma in skin of color.
EVIDENCE REVIEW
A search was conducted including PubMed, Cochrane, and Web of Science databases from database origin to June 3, 2020. Only peer-reviewed original studies were screened in full text. Eligible studies analyzed UV exposure as a risk factor for cutaneous melanoma in people with skin of color, which was defined broadly as any race/ethnicity other than non-Hispanic White, Fitzpatrick skin types IV through VI, or tanning ability of rarely or never burns. Measures of UV exposure included UV index, irradiance, latitude, history of phototherapy, and history of sunburn. Evidence quality was assessed using criteria from the Oxford Centre for Evidence-Based Medicine.
FINDINGS
After duplicate removal, 11 059 database records were screened, 548 full-text articles were assessed, and 13 met inclusion criteria. Study types included 7 ecological studies, 5 cohort studies, and 1 case-control study. All studies used race and/or ethnicity to categorize the participants, and more than 7700 melanomas in skin of color were included. Of the 13 studies that met inclusion criteria, 11 found no association between UV exposure and melanoma in skin of color, 1 study showed a small positive relationship in Black males, and 1 showed a weak association in Hispanic males. All studies were of moderate to low quality (Oxford Centre ratings 2b to 4).
CONCLUSIONS AND RELEVANCE
In this systematic review, the evidence suggests that UV exposure may not be an important risk factor for melanoma development in people with skin of color. Current recommendations promoting UV protection for melanoma prevention in skin of color are not supported by most current studies. However, evidence is of moderate to low quality, and further research is required to fully elucidate this association.
Topics: Humans; Melanoma; Risk Factors; Skin Neoplasms; Skin Pigmentation; Sunburn; Ultraviolet Rays
PubMed: 33325988
DOI: 10.1001/jamadermatol.2020.4616 -
Patient Preference and Adherence 2020Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact... (Review)
Review
BACKGROUND
Medication-induced oral hyperpigmentation is an oral condition that impacts patients' quality of life and has been linked to many systemic therapeutic agents. The exact pathogenesis of tissue pigmentation varies greatly and is not completely known. This systematic review aimed to present data on the causal association between medications and the development of oral/mucosal pigmentation as an adverse drug reaction.
METHODS
A systematic review and analysis of literature were conducted using the following databases: PubMed, Science Direct, ProQuest, Web of Science, and Scopus. The systematic review included original articles written in English and published between January 1982 and June 2020. Following the PRISMA statement, eligible articles were systematically reviewed, and data were extracted from eligible studies and analyzed.
RESULTS
A total of 235 articles were identified, of which 57 met the inclusion criteria and were included in this review. The mean age of included patients was 46.2±16.38 years (range: 10-90 years) with a male to female ratio of 1:1.45. Oral mucosal hyperpigmentation was reported following the use of several classes of medications such as antiviral (eg, zidovudine), antibiotic (eg, minocycline), antimalarial (eg, chloroquine), anti-fungal (eg, ketoconazole), antileprotic (eg, clofazimine), antihypertensive (eg, amlodipine), chemotherapeutic, and antineoplastic drugs. The risk of developing oral pigmentation was significantly higher with antimalarial medications, antibiotics, antineoplastic and chemotherapeutic agents. Medication-induced oral hyperpigmentation was most frequent among women and in the hard palate.
CONCLUSION
Future research is warranted to better understand the pathogenesis and risk factors for medication-induced oral hyperpigmentation in order to reassure patients during prescription and management.
PubMed: 33116439
DOI: 10.2147/PPA.S275783 -
Genes Jan 2023The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly,... (Review)
Review
The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly, this technology can be vital in forensic cases involving human identification from biological traces or human remains, especially when reference samples are not available in the deoxyribose nucleic acid (DNA) database. This review summarizes the currently used methods for predicting human phenotypes such as age, ancestry, pigmentation, and facial features based on genetic variations. To identify the facial features affected by DNA, various two-dimensional (2D)- and three-dimensional (3D)-scanning techniques and analysis tools are reviewed. A comparison between the scanning technologies is also presented in this review. Face-landmarking techniques and face-phenotyping algorithms are discussed in chronological order. Then, the latest approaches in genetic to 3D face shape analysis are emphasized. A systematic review of the current markers that passed the threshold of a genome-wide association (GWAS) of single nucleotide polymorphism (SNP)-face traits from the GWAS Catalog is also provided using the preferred reporting items for systematic reviews and meta-analyses (PRISMA), approach. Finally, the current challenges in forensic DNA phenotyping are analyzed and discussed.
Topics: Humans; Nucleic Acids; Genome-Wide Association Study; Phenotype; Pigmentation; DNA
PubMed: 36672878
DOI: 10.3390/genes14010136 -
American Journal of Ophthalmology Feb 2023To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD).
DESIGN
Systematic review and meta-analysis.
METHODS
The review was performed using the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies and randomized controlled trials were included.
RESULTS
Identification of fibrosis is challenging. Optical coherence tomography angiography and polarization-sensitive optical coherence tomography represent novel options in multimodal imaging. The prevalence of fibrosis at baseline, 12, 24, and 60 months was 13%, 32%, 36%, and 56%, respectively. Approximately 60% of the fibrosis burden in nAMD at 5 years was present in the first year of treatment. Fibrosis development was highest in the first 12 months and slowed down over time. The risk factors of fibrosis included classic choroidal neovascularization (CNV), intra-retinal fluid, hemorrhage, hyperreflective material, CNV lesion size, and retinal thickness. Sub-retinal fluid and pigment epithelial detachment may be protective. Treatment-associated factors included disease activity and time to diagnosis. At baseline, the best corrected visual acuity in eyes with fibrosis was poorer than in eyes without fibrosis (-18.50 letters); this difference became larger at 12 months despite treatment (-26.86 letters).
CONCLUSIONS
There is a need to identify effective treatment strategies for fibrosis and to closely monitor at-risk patients. More studies involving multimodal imaging are required to clarify the definitions and grading criteria for fibrosis.
Topics: Humans; Angiogenesis Inhibitors; Retina; Choroidal Neovascularization; Fibrosis; Tomography, Optical Coherence; Macular Degeneration; Fluorescein Angiography; Intravitreal Injections; Wet Macular Degeneration
PubMed: 36162537
DOI: 10.1016/j.ajo.2022.09.008 -
The Cochrane Database of Systematic... Jan 2023Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by... (Review)
Review
BACKGROUND
Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by valvular incompetence, reflux, venous obstruction or a combination of these symptoms, with consequent distal venous hypertension. Clinical manifestations of CVI include oedema, pain, skin changes, ulcerations and dilated skin veins in the lower limbs. It places a large financial burden on health systems. There is a wide variety of treatment options for CVI, ranging from surgery and medication to compression and physiotherapy. Balneotherapy (treatments involving water) may be a relatively cheap and efficient way to deliver physiotherapy to people with CVI. This is an update of a review first published in 2019.
OBJECTIVES
To assess the effectiveness and safety of balneotherapy for the treatment of people with chronic venous insufficiency.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials comparing balneotherapy to no treatment or other types of treatment for CVI. We also included studies that used a combination of treatments.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. disease severity, 2. health-related quality of life (HRQoL) and 3.
ADVERSE EFFECTS
Our secondary outcomes were 1. pain, 2. oedema, 3. leg ulcer incidence and 4. skin pigmentation changes. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included nine randomised controlled trials involving 1126 participants with CVI. Seven studies evaluated balneotherapy versus no treatment, one study evaluated balneotherapy versus a phlebotonic drug (melilotus officinalis), and one study evaluated balneotherapy versus dryland exercises. We downgraded our certainty in the evidence due to a lack of blinding of participants and investigators, participant-reported outcomes and imprecision. Balneotherapy versus no treatment Balneotherapy compared to no treatment probably results in slightly improved disease severity signs and symptoms scores as assessed by the Venous Clinical Severity Score (VCSS; mean difference (MD) -1.75, 95% confidence interval (CI) -3.02 to -0.49; 3 studies, 671 participants; moderate-certainty evidence). Balneotherapy compared to no treatment may improve HRQoL as assessed by the Chronic Venous Insufficiency Quality of Life Questionnaire 2 (CIVIQ2) at three months, but we are very uncertain about the results (MD -10.46, 95% CI -19.21 to -1.71; 2 studies, 153 participants; very low-certainty evidence). The intervention may improve HRQoL at 12 months (MD -4.48, 95% CI -8.61 to -0.36; 2 studies, 417 participants; low-certainty evidence). It is unclear if the intervention has an effect at six months (MD -2.99, 95% CI -6.53 to 0.56; 2 studies, 436 participants; low-certainty evidence) or nine months (MD -6.40, 95% CI -13.84 to 1.04; 1 study, 59 participants; very low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on the occurrence of adverse effects. The main adverse effects were thromboembolic events (odds radio (OR) 0.35, 95% CI 0.09 to 1.42; 3 studies, 584 participants; low-certainty evidence), erysipelas (OR 2.58, 95% CI 0.65 to 10.22; 2 studies, 519 participants; low-certainty evidence) and palpitations (OR 0.33, 95% CI 0.01 to 8.52; 1 study, 59 participants; low-certainty evidence). No studies reported any serious adverse effects. Balneotherapy compared with no treatment may improve pain scores slightly at three months (MD -1.12, 95% CI -1.35 to -0.88; 2 studies, 354 participants; low-certainty evidence); and six months (MD -1.02, 95% CI -1.25 to -0.78; 2 studies, 352 participants; low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on oedema (measured by leg circumference) at 24 days to three months, but we are very uncertain about the results (standardised mean difference (SMD) 0.32 cm, 95% CI -0.70 to 1.34; 3 studies, 369 participants; very low-certainty evidence). Balneotherapy compared with no treatment may have little or no effect on the incidence of leg ulcers at 12 months, but we are very uncertain about the results (OR 1.06, 95% CI 0.27 to 4.14; 2 studies, 449 participants; very low-certainty evidence). Balneotherapy compared with no treatment may slightly reduce skin pigmentation changes as measured by the pigmentation index at 12 months (MD -3.60, 95% CI -5.95 to -1.25; 1 study, 59 participants; low-certainty evidence). Balneotherapy versus melilotus officinalis For the comparison balneotherapy versus a phlebotonic drug (melilotus officinalis), there was little or no difference in pain symptoms (OR 0.29, 95% CI 0.03 to 2.87; 1 study, 35 participants; very low-certainty evidence) or oedema (OR 0.21, 95% CI 0.02 to 2.27; 1 study, 35 participants; very low-certainty evidence), but we are very uncertain about the results. The study reported no other outcomes of interest. Balneotherapy versus dryland exercise For the comparison balneotherapy versus dryland exercise, evidence from one study showed that balneotherapy may improve HRQoL as assessed by the Varicose Vein Symptom Questionnaire (VVSymQ), but we are very uncertain about the results (MD -3.00, 95% CI -3.80 to -2.20; 34 participants, very low-certainty evidence). Balneotherapy compared with dryland exercises may reduce oedema (leg volume) after five sessions of treatment (right leg: MD -840.70, 95% CI -1053.26 to -628.14; left leg: MD -767.50, 95% CI -910.07 to -624.93; 1 study, 34 participants, low-certainty evidence). The study reported no other outcomes of interest.
AUTHORS' CONCLUSIONS
For the comparison balneotherapy versus no treatment, we identified moderate-certainty evidence that the intervention improves disease severity signs and symptoms scores slightly, low-certainty evidence that it improves pain and skin pigmentation changes, and very low-certainty evidence that it improves HRQoL. Balneotherapy compared with no treatment made little or no difference to adverse effects, oedema or incidence of leg ulcers. Evidence comparing balneotherapy with other interventions was very limited. To ensure adequate comparison between trials, future trials should standardise measurements of outcomes (e.g. disease severity signs and symptoms score, HRQoL, pain and oedema) and follow-up time points.
Topics: Humans; Balneology; Edema; Leg Ulcer; Pain; Quality of Life; Venous Insufficiency; Randomized Controlled Trials as Topic
PubMed: 36622745
DOI: 10.1002/14651858.CD013085.pub3 -
International Ophthalmology Feb 2021To review the basic principles of ultra-widefield fundus autofluorescence (UWF-FAF) and discuss its clinical application for a variety of retinal and choroidal disorders. (Review)
Review
PURPOSE
To review the basic principles of ultra-widefield fundus autofluorescence (UWF-FAF) and discuss its clinical application for a variety of retinal and choroidal disorders.
METHODS
A systematic review of the PubMed database was performed using the search terms "ultra-widefield," "autofluorescence," "retinal disease" and "choroidal disease."
RESULTS
UWF-FAF imaging is a recently developed noninvasive retinal imaging modality with a wide imaging range that can locate peripheral fundus lesions that traditional fundus autofluorescence cannot. Multiple commercially available ultra-widefield imaging systems, including Heidelberg Spectralis and Optomap Ultra-Widefield systems, are available to the clinician. Imaging by UWF-FAF is more comprehensive; it can reflect the content and distribution of the predominant ocular fluorophore in retinal pigment epithelial cells and evaluate the metabolic status of RPE of various retinal and choroidal disorders.
CONCLUSION
UWF-FAF can detect abnormalities that traditional fundus autofluorescence cannot; therefore, it can be used to better elucidate disease pathogenesis, analyze genotype-phenotype correlations, diagnose and monitor disease.
Topics: Fluorescein Angiography; Fundus Oculi; Humans; Optical Imaging; Retina; Retinal Diseases
PubMed: 33040254
DOI: 10.1007/s10792-020-01609-9