Increased mortality for pregnancy‐associated melanoma: systematic review and meta‐analysis

Among women, pregnancy‐associated melanomas may have a poorer prognosis than other melanomas, but evidence is inconsistent. We conducted a systematic review and meta‐analysis to assess the effect on melanoma outcome of a coinciding pregnancy. The objective of the study was to conduct a systematic review and meta‐analysis of risk of death from, or recurrence of, pregnancy‐associated melanomas compared with other melanomas in women of reproductive age. Cochrane (1996–2013), MEDLINE (1950–2013), EMBASE (1966–2013), CINAHL (1982–2013), and PUBMED (1951–2013) databases were searched for studies assessing the risk of death and recurrence in pregnancy‐associated melanomas. Eligible studies investigated melanoma outcomes in women with pregnancy‐associated melanomas (diagnosed during pregnancy or in 12 months following pregnancy), included a comparison group and reported measures of risk of melanoma death or disease‐free survival. Eligible study designs were cohort studies of women of childbearing age with confirmed diagnoses of cutaneous melanoma. Individual study effect estimates were pooled using the weighted average method. Studies that did not report a quantitative estimate were summarized narratively. Of 304 citations identified, 14 studies met the inclusion criteria, with assessed outcomes being melanoma death (7), recurrence (3), or both (4). Pooled estimates of mortality risk from four studies showed increased risk of melanoma death after adjustment for patient age and stage of melanoma (pHR 1.56, 95% CI 1.23–1.99) for pregnancy‐associated melanoma compared with other melanomas. Based on limited quantitative evidence, pregnancy‐associated melanomas appear to have poorer outcomes than other melanomas.     

Markers of systemic inflammation in psoriasis: a systematic review and meta‐analysis

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)‐1β, IL‐6, IL‐10, C‐reactive protein (CRP), intracellular adhesion molecule (ICAM)‐1, E‐selectin and tumour necrosis factor (TNF)‐α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random‐effects model. Seventy‐eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL‐6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF‐α (d = 1·32, 95% CI 0·86–1·79), E‐selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM‐1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL‐1β and IL‐10 was not significant. Age had a significant effect on the SMD for IL‐6 and TNF‐α. For IL‐6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.     

Alcohol drinking and cutaneous melanoma risk: a systematic review and dose–risk meta‐analysis

It has been suggested that alcohol intake increases sunburn severity, a major risk factor for cutaneous melanoma (CM). Several epidemiological studies have investigated the relationship between alcohol consumption and CM, but the evidence is inconsistent. Therefore, we aimed to quantify this relationship better, using a meta‐analytical approach. The dose–risk relationship was also modelled through a class of flexible nonlinear meta‐regression random effects models. The present meta‐analysis included 16 studies (14 case–control and two cohort investigations) with a total of 6251 cases of CM. The pooled relative risk (RR) for any alcohol drinking compared with no/occasional drinking was 1·20 [95% confidence interval (CI) 1·06–1·37]. The risk estimate was similar in case–control (RR 1·20, 95% CI 1·01–1·44) and cohort studies (RR 1·26, 95% CI 1·19–1·35). The pooled RR was 1·10 (95% CI 0·96–1·26) for light alcohol drinking (≤ 1 drink per day) and 1·18 (95% CI 1·01–1·40) for moderate‐to‐heavy drinking. The pooled RR from 10 studies adjusting for sun exposure was 1·15 (95% CI 0·94–1·41), while the RR from six unadjusted studies was 1·27 (95% CI 1·20–1·35). No evidence of publication bias was detected. This meta‐analysis of published data reveals that alcohol consumption is positively associated with the risk of CM. However, caution in interpreting these results is required, as residual confounding by sun exposure cannot be ruled out.     

Psoriasis and smoking: a systematic review and meta‐analysis

Psoriasis is an inflammatory skin disease associated with increased cardiovascular comorbidity. Smoking is associated with an increased risk of cardiovascular disease, and prior studies have suggested that patients with psoriasis are more likely to be active smokers. Smoking may also be a risk factor in the development of psoriasis. We conducted a systematic review and meta‐analysis to assess the prevalence of smoking among patients with psoriasis, and we reviewed the contribution of smoking to the incidence of psoriasis. A total of 25 prevalence and three incidence studies were identified. The meta‐analysis of prevalence studies included a total of 146 934 patients with psoriasis and 529 111 patients without psoriasis. Random effects meta‐analysis found an association between psoriasis and current smoking [pooled odds ratio (OR) 1·78, 95% confidence interval (CI) 1·52–2·06], as well as between psoriasis and former smoking (pooled OR 1·62, 95% CI 1·33–1·99). Meta‐regression analysis did not reveal any sources of study heterogeneity, but a funnel plot suggested possible publication bias. A subset of studies also examined the association between moderate‐to‐severe psoriasis and smoking, with a pooled OR of 1·72 (95% CI 1·33–2·22) for prevalent smoking. The three incidence studies found an association between smoking and incidence of psoriasis, with a possible dose‐effect of smoking intensity and duration on psoriasis incidence. These findings suggest that smoking is an independent risk factor for the development of psoriasis, and that patients with established psoriasis continue to smoke more than patients without psoriasis.     

Vitiligo and autoantibodies: a systematic review and meta‐analysis

Many studies have reported the prevalence of autoantibodies in patients with vitiligo; however, results were inconsistent for some autoantibodies. This study aimed to conduct a systematic review and meta‐analysis of the prevalence of autoantibodies in vitiligo patients. A systematic review and meta‐analysis of the literature published from inception to Dec 31, 2016 was conducted. Case‐control studies with vitiligo patients and a control group were included. The prevalence of anti‐thyroperoxidase (ATPO) antibodies, anti‐thyroglobulin (ATG) antibodies, antinuclear antibodies (ANA), anti‐gastric parietal cell antibodies (AGPCA), anti‐smooth muscle antibodies (ASMA), anti‐mitochondrial antibodies (AMA), and anti‐adrenal antibodies in vitiligo patients were 15.1 %, 9.7 %, 12.5 %, 11.7 %, 12.6 %, 0.2 %, and 2.5 %, respectively. The prevalence of ATPO antibodies (odds ratio [OR]: 3.975; 95 %; confidence interval [CI]: 3.085–5.122), ATG antibodies (OR: 3.759; 95 % CI: 2.554–5.531), ANA (OR: 1.797, 95 % CI: 1.182–2.731), AGPCA (OR: 2.503; 95 % CI: 1.497–2.896), and anti‐adrenal antibodies (OR: 9.808, 95 % CI: 1.809–53.159) (Figure 2a–e) were significantly higher in vitiligo patients than in the control group. The routine screening of anti‐thyroid antibodies should be performed in vitiligo patients to identify those at high risk of developing autoimmune thyroid disease.     

Mortality in bullous pemphigoid: A systematic review and meta‐analysis of standardized mortality ratios

There are inconsistent data on mortality rates in patients with bullous pemphigoid (BP). Trends in mortality in BP throughout the years are yet to be established. The aim of the present study was to study the mortality in BP patients relative to the general population and to estimate trends in standardized mortality over the past 30 years. We performed a systematic review and meta‐analysis of observational studies in Medline, Embase and Scopus (1823–2017). Reference lists of included studies were also searched for eligible studies. Quality of evidence was assessed using the Newcastle–Ottawa Scale (NOS). A meta‐analysis was performed using random‐effects models to estimate pooled standardized mortality ratios (SMR) with 95% confidence intervals (CI). Meta‐regression models were used to investigate the secular trends in SMR. Ten studies were included covering the period 1960–2015 (1736 patients, 746 deaths). Pooled all‐cause SMR was 3.6 (95% CI, 2.6–5.0). There was no trend in all‐cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04–0.08; P = 0.545). In conclusion, there is a 3.6‐fold increased mortality among patients with BP as compared with the age‐matched general population. The excess mortality in BP has not changed significantly over the past 30 years.     

Zinc and atopic dermatitis: a systematic review and meta‐analysis

Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21–1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non‐significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71–3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High‐quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.     

Psychological stress and psoriasis: a systematic review and meta‐analysis

Psoriasis is a chronic inflammatory skin disease. It is common knowledge among patients with psoriasis and their physicians that psychological stress worsens the disease; however, there is a lack of robust evidence to prove this linkage. This review examined studies evaluating the interaction between preceding psychological stress and psoriasis worsening and onset. The authors reviewed 39 different studies that included 32,537 patients with psoriasis. The first type of studies evaluated psoriasis patients at a specific point in time. They found that approximately half the patients believed that stress worsened their disease and could remember stressful events before the onset or worsening of psoriasis. However, these studies contributed poor evidence for a significant link between stress and psoriasis as the patients were not compared to a control group (people without psoriasis exposed to stressful events), and it was unclear how much time passed between psoriasis worsening/onset and patients’ recall of the events. The second type of studies evaluated the frequency at which patients with psoriasis remembered stressful events before the onset or worsening of their disease compared to people without psoriasis. These studies gave contradictory results ‐ some found that psoriasis patients more frequently recalled stressful events compared to people without psoriasis while other studies found no significant differences. Interestingly, the only study that was not based on patients’ memories but reviewed documented diagnosis of stress disorder, found similar rates between patients with psoriasis and people without psoriasis. The third approach, in one study, evaluated the interaction between stress levels at one point in time and psoriasis severity one month later, finding only a slight link. The authors found no strong evidence to support the belief that preceding psychological stress strongly links with psoriasis worsening and onset. More research, especially studies that record psychological stress and evaluate disease severity over time, are needed to better understand the influence of psychological stress on psoriasis onset and severity.     

Incidence and prevalence of rosacea: a systematic review and meta‐analysis

Rosacea is a common chronic skin condition usually localised in the central part of the face. It is characterised by areas of intermittent or persistent redness, small and superficial dilated blood vessels, small red spots and bumps and some people experience eye symptoms such as dryness, irritation and swollen red eyelids. Rosacea can affect both men and women of all ages, but is most common among fair‐skinned women over the age of 30. The global frequency of rosacea remains unknown, although it is a common condition associated with other diseases outside the skin. The aim of this study was to examine the worldwide frequency of rosacea. The authors did this by examining globally published literature from medical databases reporting the frequency of rosacea. They examined both the frequency in the general population as well as among dermatology outpatients to better understand the absolute burden of this condition. A total of 32 studies were included examining a total of 41 populations with 26 519 836 individuals. Twenty‐two populations were from Europe, 3 from Africa, 4 from Asia, 9 from North America, and 3 from South America. The authors found a frequency of rosacea of 5.46% in the general population and 2.39% among dermatology outpatients. The frequency of rosacea depended on the diagnostic method with higher estimates in questionnaire studies of rosacea symptoms and lower estimates in health registries (i.e. databases). Rosacea was found to affect both women and men equally, and mostly those aged 45–60 years.     

Efficacy and safety of systemic treatments in psoriatic arthritis: a systematic review,meta‐analysis and GRADE evaluation

Twenty per cent of patients with plaque psoriasis also have psoriatic arthritis – a disease affecting joints and entheses. Different treatment options exist but currently no succinct systematic overview exists. A systematic review of approved systemic treatments for psoriatic arthritis was conducted. We systematically searched in three databases (last update September 2017). Data were extracted for ACR20/50, HAQ‐DI, SF‐36 and adverse/serious adverse events after 16–24 weeks. We assessed the quality of evidence using GRADE. Twenty trials were included. Three trials compared two active substances. Results for ACR20 were infliximab + methotrexate vs. methotrexate: RR 1.40 (95% CI 1.07–1.84) very low quality evidence; ixekizumab Q2W vs. adalimumab Q2W: RR 1.08 (95% CI 0.86–1.36) very low quality, leflunomide vs. methotrexate: RR 1.01, (95% CI 0.84–1.21) low quality. Eighteen drug vs. placebo comparisons were included. For ACR20/50, HAQ‐DI and SF‐36, the active treatment was efficacious and the quality of the evidence was mostly moderate to low (15 of 18 comparisons). The quality of evidence for (serious) adverse events was mostly low; differences were rare. In three placebo‐controlled comparisons, leflunomide, MTX and sulfasalazine failed to show statistical superiority for ACR. Besides the established treatment of anti‐TNF antibodies and ustekinumab for psoriatic arthritis, the newer treatment options of IL17 antibodies and apremilast are also effective for the treatment of psoriatic arthritis. Based on just one comparative trial and one drug each, the new class of anti‐IL 17 antibodies appears to be equally effective as the group of anti‐TNF antibodies; for apremilast, this is yet unclear.     

JAK inhibitors for alopecia areata: a systematic review and meta‐analysis

There have been a number of case reports and small clinical trials reporting promising outcomes of Janus Kinase (JAK) inhibitors tofacitinib, ruxolitinib and baricitinib for alopecia areata (AA). The majority of the literature to date is based on small volume data, with a lack of definitive evidence or guidelines. To determine the expected response of AA to JAK inhibitor therapy and factors which influence response and recurrence rates. A systematic review and meta‐analysis was performed according to PRISMA guidelines. From 30 studies and 289 cases, there were 72.4% responders, good responders 45.7% and partial responders 21.4%. Mean time to initial hair growth was 2.2 ± 6.7 months, and time to complete hair regrowth was 6.7 ± 2.2 months. All 37 recurrences occurred when treatment was ceased after 2.7 months. Oral route was significantly associated with response to treatment compared to topical therapy. No difference was found between paediatric and adult cases in proportion of responses. There is promising low‐quality evidence regarding the effectiveness of JAK inhibitors in AA. Future large‐sized randomized studies are required to confirm findings.     

Vitiligo and depression: a systematic review and meta‐analysis of observational studies

Vitiligo is a common depigmenting disorder with profound psychosocial impacts. Previous observational studies have suggested a link between vitiligo and psychiatric morbidity, such as depression. However, variability in study design makes it difficult to quantify accurately the relationship between vitiligo and depression. We aimed to investigate the underlying prevalence and risk of depression among patients with vitiligo. A comprehensive search of MEDLINE, Embase and the Cochrane Library was conducted. Cross‐sectional, case–control or cohort studies that assessed the prevalence of depression among patients with vitiligo or the relationship between vitiligo and depression were included. DerSimonian and Laird random‐effects models were utilized to calculate the pooled prevalence and relative risks. Publication bias was evaluated by funnel plots and Egger's tests. Twenty‐five studies with 2708 cases of vitiligo were included. Based on diagnostic codes, the pooled prevalence of depression among patients with vitiligo was 0·253 [95% confidence interval (CI) 0·16–0·34; P < 0·001)]. Using self‐reported questionnaires, the pooled prevalence of depressive symptoms was 0·336 (95% CI 0·25–0·42; P < 0·001). The pooled odds ratio of depression among patients with vitiligo was 5·05 vs. controls (95% CI 2·21–11·51; P < 0·001). Moderate‐to‐high heterogeneity was observed between the studies. Patients with vitiligo were significantly more likely to suffer from depression. Clinical depression or depressive symptoms can be prevalent, with the actual prevalence differing depending on screening instruments or, possibly, geographical regions. Clinicians should actively evaluate patients with vitiligo for signs/symptoms of depression and provide appropriate referrals to manage their psychiatric symptoms accordingly.     

Alcohol intake and risk of nonmelanoma skin cancer: a systematic review and dose–response meta‐analysis

Nonmelanoma skin cancer (NMSC) comprises mainly basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). The association between alcohol intake and NMSC has been inconclusive; therefore the objective of this study is to quantify the relationship between alcohol intake and NMSC using meta‐analyses. A systematic literature search of PubMed and Embase was performed on 30 October 2016. Eligible articles were case–control or cohort studies that examined alcohol intake and risk of BCC or cSCC and reported relative risks (RRs) with 95% confidence intervals (CIs). Of the 307 articles identified, 13 case–control and cohort studies were included in the systematic review, including 95 241 NMSC cases (91 942 BCC and 3299 cSCC cases). A random‐effects model was used to obtain summary RRs and 95% CIs for dose–response meta‐analyses. For every 10‐gram increase in ethanol intake per day, a positive association was found for both BCC (summary RR of 1·07; 95% CI 1·04–1·09) and cSCC (summary RR of 1·11; 95% CI 1·06–1·16). While there was evidence suggesting a nonlinear association for BCC, it may be due to the sparse data at higher alcohol intake levels. This meta‐analysis found evidence that alcohol drinking is positively associated with both BCC and cSCC risk in a dose‐dependent manner. These results should be interpreted with caution due to potential residual confounding. Nonetheless, because alcohol drinking is a prevalent and modifiable behaviour, it could serve as an important public health target to reduce the global health burden of NMSC.     

Efficacy of systemic therapies for moderate‐to‐severe psoriasis: a systematic review and meta‐analysis of long‐term treatment

Background Despite the chronicity of psoriasis, most systematic reviews focus on short‐term treatment. Methods The systematic search strategy and results from the German Psoriasis Guidelines were adapted. To update the data a literature search in Medline, Embase and the Cochrane Library was conducted. The proportion of participants achieving ≥75% decrease in Psoriasis Area and Severity Index (PASI) as well as Dermatology Life Quality Index (DLQI) reduction at different time points were assessed. Trials were summarized with respect to time periods and study designs. Suitable trials were included in a meta‐analysis. Particular attention was paid to statistical approaches of handling dropouts. Results A total of 33 articles including 27 trials totaling 6575 patients with active treatment were included in the systematic review. Seven randomized controlled trials were eligible for the meta‐analysis. Over a 24 week treatment period infliximab [risk difference (RD) 78%, 95% confidence interval (CI) 72–83%] and ustekinumab 90 mg every 12 weeks (RD 77%, 95% CI 71–83%) were the most efficacious treatments. Adalimumab (RD: 60%, 95% CI 45–74%) showed results within the range of different etanercept dosages (etanercept 50 mg once weekly: RD 62%, 95% CI, 52–72%), (etanercept 25 mg twice weekly: RD 45%, 95% CI 34–56%), (etanercept 50 mg twice weekly: RD 56%, 95% CI 49–62%) and (etanercept 50 mg twice weekly until week 12, then 25 mg twice weekly: RD 50%, 95% CI 42–57%). After 24 weeks a decrease in efficacy for inflximab, adalimumab and etanercept was observed. Conclusions More sufficient data is required to draw reliable conclusions in extended long‐term treatment and head‐to‐head comparisons are necessary.