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Acta Dermato-venereologica Feb 2018Treatment of vitiligo is challenging and requires a multidisciplinary approach. Fractional carbon dioxide (CO2) laser as an add-on to conventional treatment has been... (Meta-Analysis)
Meta-Analysis Review
Treatment of vitiligo is challenging and requires a multidisciplinary approach. Fractional carbon dioxide (CO2) laser as an add-on to conventional treatment has been reported to be effective, but there is no consensus on its use. A systematic review was performed by searching major databases for relevant publications to February 2017. Six studies with 85 participants were included. For those with refractory vitiligo, the addition of fractional CO2 laser to routine treatment modalities was superior to conventional treatment alone in terms of > 50% re-pigmentation (risk ratio (RR) 4.90, 95% confidence interval (95% CI), 1.15-20.93; p = 0.03), physician improvement score (mean difference (MD) 0.81, 95% CI 0.33-1.29; p < 0.001), < 25% re-pigmentation (RR 0.64, 95% CI, 0.49-0.85; p=0.002) and patient satisfaction (MD 1.61, 95% CI 0.73-2.49; p< 0.001). Side-effects were minor. These results provide evidence supporting that fractional CO2 laser is a valuable treatment modality for patients with vitiligo, especially for those with refractory vitiligo.
Topics: Chi-Square Distribution; Combined Modality Therapy; Humans; Lasers, Gas; Low-Level Light Therapy; Odds Ratio; Risk Factors; Skin; Skin Pigmentation; Treatment Outcome; Vitiligo
PubMed: 29110015
DOI: 10.2340/00015555-2836 -
The British Journal of Dermatology Apr 2018Vitiligo is a chronic disorder causing skin depigmentation with global prevalence varying from 0·2% to 1·8%. U.K. guidelines recommend assessment of psychological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitiligo is a chronic disorder causing skin depigmentation with global prevalence varying from 0·2% to 1·8%. U.K. guidelines recommend assessment of psychological state during clinical evaluation of vitiligo. However, the prevalence of psychological comorbidity in people with vitiligo has not been described.
OBJECTIVES
To establish the prevalence of psychological symptoms or disorders in people with vitiligo and describe the outcome measures used.
METHODS
We performed a comprehensive search of MEDLINE, Embase, CINAHL and PsycINFO to identify observational studies assessing the prevalence of psychological symptoms or disorders (December 2016). DerSimonian and Lard random-effects models were used to estimate the overall pooled prevalence.
RESULTS
We identified 29 studies with 2530 people with vitiligo. Most studies included a measure of either depression (n = 25) or anxiety (n = 13). The commonest tools were the Hospital Anxiety and Depression Scale and the Centre for Epidemiology Studies Depression Scale. Ten studies provided information on 13 other psychological outcomes. Pooled prevalence using depression-specific and anxiety-specific questionnaires was 0·29 [95% confidence interval (CI) 0·21-0·38] and 0·33 (95% CI 0·18-0·49), respectively. Prevalence was lower for clinically diagnosed depression (0·21, 95% CI 0·15-0·28) and anxiety (0·15, 95% CI 0·06-0·24). When nonspecific tools were used the prevalence remained similar for depression (0·27, 95% CI 0·08-0·46) but increased for anxiety (0·46, 95% CI 0·39-0·52). High heterogeneity was observed.
CONCLUSIONS
A range of psychological outcomes are common in people with vitiligo. The prevalence of anxiety was influenced by type of screening tool, suggesting the need for validation of psychological outcome screening tools in the field of dermatology.
Topics: Anxiety Disorders; Depressive Disorder; Female; Humans; Male; Observational Studies as Topic; Prevalence; Psychiatric Status Rating Scales; Research Design; Vitiligo
PubMed: 28991357
DOI: 10.1111/bjd.16049 -
Annals of Oncology : Official Journal... Oct 2017Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand... (Review)
Review
BACKGROUND
Immune checkpoint inhibitor (ICI) monoclonal antibodies (mAbs) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1) produce unique toxicity profiles. The objective of this review was to identify patterns and incidence of immune-related adverse events (irAE) based on tumour type and ICI class.
METHODS
Medline, EMBASE and COCHRANE databases were searched to identify prospective monotherapy trials of ICIs from 2003 to November 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR), χ2 tests and multivariable regression models were used to analyse for effect size and associations.
RESULTS
We identified 48 trials (6938 patients), including 26 CTLA-4, 17 PD-1, 2 PD-L1 trials, and 3 studies tested both CTLA-4 and PD-1. Grade 3/4 irAE were more common with CTLA-4 mAbs compared with PD-1 (31% versus 10%). All grades colitis (OR 8.7, 95% CI 5.8-12.9), hypophysitis (OR 6.5, 95% CI 3.0-14.3) and rash (OR 2.0, 95% CI 1.8-2.3) were more frequent with CTLA-4 mAbs; whereas pneumonitis (OR 6.4, 95% CI 3.2-12.7), hypothyroidism (OR 4.3, 95% CI 2.9-6.3), arthralgia (OR 3.5, 95% CI 2.6-4.8) and vitiligo (OR 3.5, 95% CI 2.3-5.3) were more common with PD-1 mAbs. Comparison of irAE from the three most studied tumour types in PD-1 mAbs trials [melanoma (n = 2048), non-small-cell lung cancer (n = 1030) and renal cell carcinoma (n = 573)] showed melanoma patients had a higher frequency of gastrointestinal and skin irAE and lower frequency of pneumonitis.
DISCUSSION
CTLA-4 and PD-1 mAbs have distinct irAE profiles. Different immune microenvironments may drive histology-specific irAE patterns. Other tumour-dependent irAE profiles may be identified as data emerge from ICI trials.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; CTLA-4 Antigen; Clinical Trials as Topic; Humans; Immune System Diseases; Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 28945858
DOI: 10.1093/annonc/mdx286 -
Journal of the American Academy of... Nov 2017The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from these drugs is unknown.
OBJECTIVE
To conduct a systematic review and meta-analysis of published clinical trials and determine the incidence and risk of development of targeted therapy-induced pigmentary changes.
METHODS
A comprehensive search was conducted to identify studies reporting targeted therapy-induced pigmentary changes. The incidence and relative risk were calculated. Case reports and series were reviewed to understand clinical characteristics.
RESULTS
A total of 8052 patients from 36 clinical trials were included. The calculated overall incidences of targeted cancer therapy-induced all-grade pigmentary changes in the skin and hair were 17.7% (95% confidence interval [CI], 11.9-25.4) and 21.5% (95% CI, 14.9-30.1), respectively. The relative risk of all-grade pigmentary changes of skin and hair were 93.7 (95% CI, 5.86-1497.164) and 20.1 (95% CI, 8.35-48.248). Across 53 case reports/series (N = 75 patients), epidermal growth factor receptor and breakpoint cluster region-abelson inhibitors were the most common offending agents.
LIMITATIONS
Potential under-reporting and variability in oncologists reporting these events.
CONCLUSION
There is a significant risk of development of pigmentary changes during treatment with targeted anticancer therapies. Appropriate counseling and management are critical to minimize psychosocial impairment and deterioration in quality of life.
Topics: Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Molecular Targeted Therapy; Neoplasms; Pigmentation Disorders; Prevalence; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 28918974
DOI: 10.1016/j.jaad.2017.06.044 -
JAMA Dermatology Jul 2017References to the expected treatment response to phototherapy would be helpful in the management of vitiligo because phototherapy requires long treatment durations over... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
References to the expected treatment response to phototherapy would be helpful in the management of vitiligo because phototherapy requires long treatment durations over several months.
OBJECTIVE
To estimate the treatment response of vitiligo to phototherapy.
DATA SOURCES
A comprehensive database search of MEDLINE, EMBASE, and the Cochrane library from inception to January 26, 2016, was performed for all prospective studies. The main keywords used were vitiligo, phototherapy, psoralen, PUVA, ultraviolet, NBUVB, and narrowband.
STUDY SELECTION
All prospective studies reporting phototherapy outcome for at least 10 participants with generalized vitiligo were included. Of 319 studies initially identified, the full texts of 141 studies were assessed for eligibility, and 35 were finally included in the analysis. Of these, 29 studies included 1201 patients undergoing narrowband UV-B (NBUVB) phototherapy, and 9 included 227 patients undergoing psoralen-UV-A (PUVA) phototherapy.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted the following data: study design, number and characteristics of the participants, phototherapy protocol, and rate of repigmentation based on the quartile scale. Single-arm meta-analyses were performed for the NBUVB and PUVA groups. Sample size-weighted means were calculated using a random-effects model for the repigmentation rates of the included studies.
MAIN OUTCOMES AND MEASURES
The primary outcomes were at least mild (≥25%), at least moderate (≥50%), and marked (≥75%) responses on a quartile scale. Response rates were calculated as the number of participants who showed the corresponding repigmentation divided by the number of all participants enrolled in the individual studies.
RESULTS
The meta-analysis included 35 unique studies (1428 unique patients). For NBUVB phototherapy, an at least mild response occurred in 62.1% (95% CI, 46.9%-77.3%) of 130 patients in 3 studies at 3 months, 74.2% (95% CI, 68.5%-79.8%) of 232 patients in 11 studies at 6 months, and 75.0% (95% CI, 60.9%-89.2%) of 512 patients in 8 studies at 12 months. A marked response was achieved in 13.0% (95% CI, 2.1%-23.9%) of 106 patients in 2 studies at 3 months, 19.2% (95% CI, 11.4%-27.0%) of 266 patients in 13 studies at 6 months, and 35.7% (95% CI, 21.5%-49.9%) of 540 patients in 9 studies at 12 months. For PUVA phototherapy, an at least mild response occurred in 51.4% (95% CI, 28.1%-74.7%) of 103 patients in 4 studies at 6 months and 61.6% (95% CI, 20.2%-100%) of 72 patients in 3 studies at 12 months. In the subgroup analyses, marked responses were achieved on the face and neck in 44.2% (95% CI, 24.2%-64.2%), on the trunk in 26.1% (95% CI, 8.7%-43.5%), on the extremities in 17.3% (95% CI, 8.2%-26.5%), and on the hands and feet in none after at least 6 months of NBUVB phototherapy.
CONCLUSIONS AND RELEVANCE
Long-duration phototherapy should be encouraged to enhance the treatment response in vitiligo. The greatest response is anticipated on the face and neck.
Topics: Humans; PUVA Therapy; Photosensitizing Agents; Phototherapy; Skin Pigmentation; Time Factors; Treatment Outcome; Ultraviolet Therapy; Vitiligo
PubMed: 28355423
DOI: 10.1001/jamadermatol.2017.0002 -
Indian Journal of Dermatology,... 2017Protein tyrosine phosphatase, non-receptor type 22 gene, which translates to lymphoid tyrosine phosphatase, is considered to be a susceptibility gene marker associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Protein tyrosine phosphatase, non-receptor type 22 gene, which translates to lymphoid tyrosine phosphatase, is considered to be a susceptibility gene marker associated with several autoimmune diseases. Several studies have demonstrated the association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism with vitiligo. However, these studies showed conflicting results. Meta-analysis of the same was conducted earlier that included fewer number of publications in their study.
AIM
We performed a meta-analysis of a total of seven studies consisting of 2094 cases and 3613 controls to evaluate the possible association of protein tyrosine phosphatase, non-receptor type 22 +1858C>T polymorphism with vitiligo susceptibility.
METHODS
We conducted a literature search in PubMed, Google Scholar and Dogpile for all published paper on protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and vitiligo risk till June 2016. Data analysis was performed by RevMan 5.3 and comprehensive meta-analysis v3.0 software.
RESULTS
Meta-analysis showed an overall significant association of protein tyrosine phosphatase, non- receptor type 22 +1858C→T polymorphism with vitiligo in all models (allelic model [T vs. C]: odds ratio = 1.50, 95% confidence interval [1.32-1.71], P< 0.001; dominant model [TT + CT vs. CC]: odds ratio = 1.61, 95% confidence interval [1.16-2.24], P = 0.004; recessive model [TT vs. CT + CC]: odds ratio = 4.82, 95% confidence interval [1.11-20.92], P = 0.04; homozygous model [TT vs. CC]: odds ratio = 5.34, 95% confidence interval [1.23-23.24], P = 0.03; co-dominant model [CT vs. CC]: odds ratio = 1.52, 95% confidence interval [1.09-2.13], P = 0.01). No publication bias was detected in the funnel plot study.
LIMITATIONS
Limited ethnic-based studies, unable to satisfy data by gender or vitiligo-type are some limitations of the present meta-analysis.
CONCLUSION
Stratifying data by ethnicity showed an association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T with vitiligo in European population (odds ratio = 1.53, 95% confidence interval [1.34-1.75], P< 0.001) but not in Asian population (odds ratio = 0.59, 95% confidence interval [0.26-1.32], P = 0.2). In conclusion, protein tyrosine phosphatase, non-receptor type 22 +1858 T allele predisposes European individuals to vitiligo.
Topics: Alleles; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Vitiligo; White People
PubMed: 28164884
DOI: 10.4103/0378-6323.199422 -
Oncotarget Jan 2017Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents.
METHODS
PubMed search was conducted in February of 2016. The randomized trials needed to have at least one of the study arms consisting of nivolumab or pembrolizumab monotherapy and a control arm containing no anti-PD-1 therapy. Data were analyzed using random effects meta-analysis for risk ratios. Heterogeneity across studies was analyzed using Q and I2 statistics.
RESULTS
Nine randomized trials and 5,353 patients were included in our meta-analysis. There was evidence of significant heterogeneity between studies. The pooled relative risk (RR) for treatment-related all grade AEs and grade 3/4 AEs was 0.88 (95% CI 0.81-0.95;P=0.002) and 0.39 (95% CI 0.29-0.53; P<0.001) respectively favoring anti-PD-1 therapy versus standard of care approach. The RR of treatment-related death was 0.45 (95% CI 0.19-1.09; P=0.076). Patients treated with PD-1 inhibitors had an increased risk of hyperthyroidism [RR of 3.44 (95% CI 1.98-5.99; P<0.001)] and hypothyroidism [RR of 6.79 (95% CI 3.10-14.84; P<0.001)]. All grade pruritus and vitiligo were also more common among these patients. The pooled absolute risks of pneumonitis and hypophysitis were 2.65% and 0.47% respectively.
CONCLUSION
Approved PD-1 inhibitors are well tolerated, associated with significant low risk of severe treatment-related AEs and increased risk of thyroid dysfunction, pruritus, and vitiligo.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Drug Approval; Humans; Neoplasms; Nivolumab; Odds Ratio; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 27852042
DOI: 10.18632/oncotarget.13315 -
European Journal of Cancer (Oxford,... Jun 2016Dermatologic adverse events (AEs) are some of the most frequently observed toxicities of immune-checkpoint inhibitor therapy, but they have received little attention.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dermatologic adverse events (AEs) are some of the most frequently observed toxicities of immune-checkpoint inhibitor therapy, but they have received little attention. The drugs, pembrolizumab and nivolumab are recently approved inhibitors of the programmed death (PD)-1 receptor that have overlapping AE profiles however, the incidence, relative risk (RR), and clinico-morphological pattern of the associated dermatologic AEs are not known.
METHODS
We conducted a systematic review of the literature, and performed a meta-analysis of dermatologic AEs observed with the use of pembrolizumab and nivolumab in cancer patients. An electronic search was conducted using the PubMed, and Web of Science, and on the American Society of Clinical Oncology and European Society for Medical Oncology meeting abstracts' libraries for potentially relevant oncology trials, that employed the drugs at Food and Drug Administration-approved doses and reported dermatologic AEs. The incidence, RR and 95% confidence intervals were calculated using either random- or fixed-effects models based on the heterogeneity of included studies. The clinical presentation, histology of affected skin areas, and management strategies (based on institutional experience), are also presented.
RESULTS
Rash, pruritus and vitiligo were found to be the most frequently reported dermatologic AEs. The calculated incidence of all-grade rash with pembrolizumab and nivolumab was 16.7% (RR = 2.6) and 14.3% (RR = 2.5), respectively. Other significant all-grade AEs included pruritus (pembrolizumab: incidence, 20.2% [RR = 49.9]; nivolumab: incidence, 13.2% [RR = 34.5]) and vitiligo (pembrolizumab: incidence, 8.3% [RR = 17.5]; nivolumab: 7.5% [RR = 14.6]). Interestingly, all the vitiligo events were reported in trials investigating melanoma. The RR for developing dermatologic AEs in general, was 2.95 with pembrolizumab, and 2.3 with nivolumab.
CONCLUSION
We found that pembrolizumab and nivolumab are both associated with dermatologic AEs, primarily low-grade rash, pruritus, and vitiligo, which are reminiscent of those seen with ipilimumab. Knowledge of these findings is critical for optimal care, maintaining dose intensity, and health-related quality of life in cancer patients receiving PD-1 inhibitors.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cell Cycle Checkpoints; Clinical Trials as Topic; Drug Eruptions; Exanthema; Female; Humans; Male; Middle Aged; Neoplasms; Nivolumab; Programmed Cell Death 1 Receptor; Pruritus; Vitiligo; Young Adult
PubMed: 27043866
DOI: 10.1016/j.ejca.2016.02.010 -
BMC Medicine Sep 2015Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a tolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was to assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and tremelimumab).
METHODS
A systematic search of literature up to February 2014 was performed in MEDLINE, EMBASE, and Cochrane databases to identify relevant articles. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using R(©), package meta.
RESULTS
Overall, 81 articles were included in the study, with a total of 1265 patients from 22 clinical trials included in the meta-analysis. Described irAEs consisted of skin lesions (rash, pruritus, and vitiligo), colitis, and less frequently hepatitis, hypophysitis, thyroiditis, and some rare events such as sarcoidosis, uveitis, Guillain-Barré syndrome, immune-mediated cytopenia and polymyalgia rheumatic/Horton. The overall incidence of all-grade irAEs was 72 % (95 % CI, 65-79 %). The overall incidence of high-grade irAEs was 24 % (95 % CI, 18-30 %). The risk of developing irAEs was dependent of dosage, with incidence of all-grade irAEs being evaluated to 61 % (95 % CI, 56-66 %) for ipilimumab 3 mg/kg and 79 % (95 % CI, 69-89 %) for ipilimumab 10 mg/kg. Death due to irAEs occurred in 0.86 % of patients. The median time of onset of irAEs was about 10 weeks (IQR, 6-12) after the onset of treatment, corresponding with the first three cycles but varied according to the organ system involved. Such immune activation could also be indicative for tumor-specific T-cell activation and irAE occurrence was associated with clinical response to CTLA-4 blocking in 60 % of patients.
CONCLUSION
The price of potential long-term survival to metastatic tumors is an atypical immune toxicity, reflecting the mechanism of action of anti-CTLA-4 antibodies. A better knowledge of these irAEs and its management in a multidisciplinary approach will help to reduce morbidity and therapy interruptions.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; CTLA-4 Antigen; Humans; Immunologic Factors; Immunotherapy; Ipilimumab; Neoplasms
PubMed: 26337719
DOI: 10.1186/s12916-015-0455-8 -
Clinical, Cosmetic and Investigational... 2015Alopecia areata (AA) is an autoimmune disorder characterized by patches of non-scarring alopecia affecting scalp and body hair that can be psychologically devastating.... (Review)
Review
BACKGROUND
Alopecia areata (AA) is an autoimmune disorder characterized by patches of non-scarring alopecia affecting scalp and body hair that can be psychologically devastating. AA is clinically heterogenous, and its natural history is unpredictable. There is no preventative therapy or cure.
OBJECTIVE
The objective of this study is to provide an evidence-based systematic review on the epidemiology and the burden of AA.
METHODS AND SELECTION CRITERIA
A search was conducted of the published, peer-reviewed literature via PubMed, Embase, and Web of Science. Studies published in English within the last 51 years that measured AA's incidence, prevalence, distribution, disability-adjusted life years (DALYs), quality of life, and associated psychiatric and medical comorbidities were included. Two authors assessed studies and extracted the data.
RESULTS
The lifetime incidence of AA is approximately 2% worldwide. Both formal population studies found no sex predominance. First onset is most common in the third and fourth decades of life but may occur at any age. An earlier age of first onset corresponds with an increased lifetime risk of extensive disease. Global DALYs for AA were calculated at 1,332,800 in 2010. AA patients are at risk for depression and anxiety, atopy, vitiligo, thyroid disease, and other autoimmune conditions.
CONCLUSION
AA is the most prevalent autoimmune disorder and the second most prevalent hair loss disorder after androgenetic alopecia, and the lifetime risk in the global population is approximately 2%. AA is associated with psychiatric and medical comorbidities including depression, anxiety, and several autoimmune disorders, and an increased global burden of disease.
PubMed: 26244028
DOI: 10.2147/CCID.S53985