Psoriasis is an autoimmune, inflammatory and often chronic skin disorder that affects 3% of the general population.1
There is a growing body of evidence supporting the link between psoriasis and cardiometabolic risk including obesity, metabolic syndrome, diabetes, hyperlipidemia and myocardial infarction.2,3 The mechanisms underlying this link are currently being investigated, but it is thought to be related with psoriasis triggering systemic inflammation, leading to an increase in inflammatory adipokines, endothelial dysfunction and insulin resistance.1-4
Although one-third to one-half of psoriasis cases begin during childhood, it is unclear whether childhood psoriasis is similarly associated with a cardiometabolic risk profile.5,6 There is conflicting evidence in the literature.
A recent systematic review concluded that psoriasis in children was not associated with metabolic or cardiovascular comorbidities, except overweight and obesity.7 Other studies have supported that all children with psoriasis should be screened for cardiovascular and metabolic comorbidities given their predisposition to such conditions.5,8-11 There are currently limited screening guidelines for metabolic and cardiovascular disorders in pediatric psoriasis.
Given the limitations of the current evidence, the authors performed a systematic review and meta-analysis to determine the association between pediatric psoriasis and metabolic comorbidities, association between pediatric psoriasis and cardiovascular comorbidities, and association between pediatric psoriasis and lipid profile abnormalities and anthropomorphic parameters such as the waist/height ratio .
| Methods |
> Literature search
The present study was carried out in accordance with the recommendations of the PRISMA guidelines. Electronic searches were performed using Ovid Medline, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club and Database of Review Abstracts of Effectiveness (DARE). ) from their start dates to May 2019. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies. All identified articles were systematically evaluated using the inclusion and exclusion criteria.
> Selection criteria
Eligible retrospective or prospective studies comparing cases (pediatric psoriasis) and controls and meta-analyses were included in the present review. Studies must have reported proportion of cardiovascular or metabolic comorbidity in each study arm, or the average metabolic or lipid laboratory profile for each arm, in cases/controls under 18 years of age. Studies that did not include any of the above outcomes were excluded.
When institutions published duplicate studies with increasing numbers of patients or longer durations of follow-up, only the most complete reports were included for quantitative evaluation at each time interval.
All publications were limited to those involving human subjects and in the English language. Abstracts, case reports, conference presentations, editorials, and expert opinions were excluded. Review articles were omitted due to potential publication bias and duplication of results.
> Data extraction
All data were extracted from the texts, tables and figures of the articles (KP). Data were confirmed and verified by a second reviewer (GL), discussing differences to reach consensus.
Dichotomous key outcomes recorded included the proportion of patients with overweight BMI, obese BMI, metabolic syndrome, diabetes, hypertension, hyperlipidemia, ischemic heart disease, or heart failure.
Continuous outcomes recorded include BMI, systolic blood pressure, diastolic blood pressure, HDL, LDL, triglycerides, and total cholesterol. The final results were reviewed by the principal investigator (GF).
> Statistical analysis
The odds ratio (OR) or weighted mean difference (WMD) was used as a summary statistic. In the present meta-analysis, we presented the results using the random effects model to account for possible clinical diversity and methodological variation between studies.
Chi square tests were used to study heterogeneity between trials. The I2 statistic was used to estimate the percentage of total variation between studies due to heterogeneity rather than chance, with values greater than 50% considered substantial heterogeneity.
The I2 can be calculated as: I2 = 100% × (Q - df ) / Q, with Q defined as Cochrane heterogeneity statistics and df defined as degree of freedom. Specific analyzes considering confounders were not possible because raw data were not available. All P values were 2-sided. All statistical analysis was performed using Review Manager version 5.3 (Cochrane Collaboration, Software Update, Oxford, United Kingdom).
| Results |
> Search strategy and patient characteristics
A total of 1259 references were identified through electronic database searches. After exclusion of duplicates or irrelevant references, 65 potentially relevant articles were retrieved. After a detailed evaluation of these articles, a final 17 studies were selected for the present meta-analysis.5,8-10,12-24
There were a total of 43,808 cases of pediatric psoriasis, compared with 5,384,057 controls. The weighted mean age of psoriasis cases was 11.4 years (95% CI: 10.9-12) compared to controls with an age of 11.2 years (95% CI: 10.7-11.7). without significant differences (P = 0.270). The proportion of women in the psoriasis group was 54%, compared to 45.1% of controls; however, this difference was not significant (P = 0.150).
> Association with obesity
Of 1560 pediatric psoriasis cases compared with 1003 controls, a significant association was found between pediatric psoriasis and overweight BMI class (OR 1.58, 95% CI 1.14-2.19, P = 0.006, I2 = 41%) without significant heterogeneity.
Of 43,162 cases compared with 5,251,036 controls, pediatric psoriasis was significantly associated with obesity (OR 2.45; 95% CI 1.73-3.48, p < 0.001, I2 = 93%), however, with significant heterogeneity.
A subgroup analysis was performed to determine whether the severity of pediatric psoriasis affected the odds of obesity. The authors determined that moderate-severe childhood psoriasis was significantly associated with higher odds of obesity compared with mild childhood psoriasis (OR 1.66; 95% CI 1.16-2.37; P = 0.005; I2 = 0% ).
> Association with diabetes
Of 41,979 cases and 5,250,421 controls, childhood psoriasis was significantly associated with diabetes (OR 2.32, 95% CI 1.34-4.03, P = 0.003, I2 = 93%).
> Association with hypertension
Compared with controls, pediatric psoriasis was significantly associated with hypertension (OR 2.19; 95% CI: 1.62-2.95; P < 0.001; I2 = 74%). There is significant heterogeneity.
> Association with hyperlipidemia
Compared with controls, pediatric psoriasis was significantly associated with hyperlipidemia (OR 2.01; 95% CI: 1.66-2.42; P < 0.001, I2 = 30%), without significant heterogeneity.
> Association with metabolic syndrome
Compared with controls, pediatric psoriasis was significantly associated with metabolic syndrome (OR 1.75, 95% CI 1.75 to 7.14, P < 0.001, I2 = 38%), without significant heterogeneity.
> Association with cardiovascular disease
Compared with controls, pediatric psoriasis was significantly associated with ischemic heart disease or heart failure (OR 3.15; 95% CI 1.06-9.42, P = 0.040, I2 = 85%). There was significant heterogeneity.
> Waist-height ratio
The odds of increasing waist-to-height ratio above a threshold level were pooled across included studies. This threshold was 0.5 for Lee et al., Mahe et al., Torres et al., and 0.539 for Paller et al. In the meta-analysis, childhood psoriasis was significantly associated with increased waist-to-height ratio compared with controls (OR 1.87, 95% CI 1.12-3.13, P = 0.020, I2 = 53%).
> Metabolic and lipid profile
There was no significant difference in the levels of HDL (WMD −0.01, 95% CI: -0.06, 0.03; P = 0.56; I2 = 78%), LDL (WMD 0.07, 95% CI % −0.10, 0.24, P = 0.450, I2 = 96%), triglycerides (WMD 0.08, 95% CI −0.01, 0.17, P = 0.100, I2 = 87%), or total cholesterol (WMD 0.15, 95% CI 0.14, 0.16, P < 0.001; I2 = 0%).
| Discussion |
Although the relationship between psoriasis and cardiometabolic comorbidities is well established in adults, the situation in children is less clear, and although there is increasing research, the evidence remains contradictory. This has implications for the advice offered to parents.
The authors performed an updated systematic review and meta-analysis, with extensive and comprehensive search terms used to capture many reportable cardiovascular and metabolic pathologies in pediatric psoriasis.
| The study demonstrates that there is a statistically significant association between pediatric psoriasis and overweight/obesity and waist:height ratio >0.5, in addition to metabolic syndrome, diabetes, hyperlipidemia, hypertension and ischemia and heart failure. |
They showed that the association with obesity depends on the severity of the disease, where patients with moderate-severe psoriasis have higher odds of obesity compared to mild psoriasis.
The authors’ findings differ from recent reviews and pooled analyses. A recent systematic review by Badaoui and colleagues concluded that in addition to overweight/obesity, there is no confirmed link with other cardiovascular or metabolic comorbidities, and does not recommend systematic screening.7 However, this study did not extract data and did not statistically group the cohorts. available, but evaluated studies based on their individual results and conclusions.
In the authors’ meta-analysis, they were able to statistically pool all data from available studies and demonstrated significant associations with a number of cardiometabolic comorbidities. Pietrazak and colleagues conducted a meta-analysis to evaluate the link between children with psoriasis and metabolic disorder.25
Of their 7 included studies comprising 965 children, 3 studies included data that could be analyzed and were suggestive of a significant association with metabolic syndrome. The authors also showed lower levels of HDL cholesterol in children with psoriasis, but similar levels of triglycerides and blood pressure.
The authors were able to update this analysis with considerably more studies and 43,808 cases of pediatric psoriasis, compared with 5,384,057 controls, allowing for greater statistical power. This study looked at a larger number of endpoints, including separating obese and overweight BMI groups, evaluated additional cardiometabolic disorders such as diabetes, hypertension, heart disease, and ischemic failure, and demonstrated a link with waist:height ratio.
The authors’ pooled meta-analysis demonstrating a higher prevalence of waist-to-height ratio ≥0.50 in children with psoriasis suggests that children with psoriasis, even if not clinically overweight or obese, are at increased risk for central adiposity compared with controls without psoriasis.
The waist-to-height ratio provides an objective and convenient way to quantify central adiposity in children with psoriasis and has been reported to predict risk in adolescence.26
The degree to which this association is influenced by psoriasis severity is unclear. Lee et al conducted a multicenter cross-sectional case-control study comparing 135 children with psoriasis versus 73 control children.18
They did not show a significant difference in the proportion of cases with an elevated waist-to-height ratio in patients with moderate-severe psoriasis versus mild psoriasis (P = 0.400).
In contrast, Paller and colleagues analyzed 614 children from nine countries and demonstrated an elevated waist-to-height ratio in psoriasis overall, as well as for the severe psoriasis subgroup but not in the mild psoriasis subgroup.10
For children with psoriasis with an abnormal waist-to-height ratio indicating abdominal adiposity, this may be an opportunity for the treating physician to perform further cardiometabolic screening as well as provide counseling and intervention to mitigate future risks of comorbidities.
The authors’ results have clinical implications.
Children with psoriasis may benefit from early and frequent monitoring of metabolic risk.
In this meta-analysis, they found no difference in subgroup analysis in terms of the strength of the association between pediatric psoriasis and comorbidities, with ORs ranging from 2.01-3.15. Kwa et al performed a nationwide population analysis of 4,884,448 hospitalized children in the United States.
In their analysis, they showed that the odds of obesity, diabetes, and hypertension were approximately twice as high in the 0-9 year old group versus the 10-17 year old group. The odds of arrhythmias were similar, while the odds of valvular heart disease were higher in the 10- to 17-year-old cohort compared with the 0- to 19-year-old cohort. Pediatric patients with psoriasis appear to have a higher risk of metabolic cardiovascular comorbidities compared to valvular heart disease and arrhythmias, and this risk is higher in those under 9 years of age.
Therefore, the authors recommend monitoring comorbidities in pediatric psoriasis. According to current guidelines, physicians should evaluate obesity annually using BMI starting at age 2 years, screen for type 2 diabetes using fasting serum glucose starting at age 10 if overweight or multiple risk factors are present, detect dyslipidemia through lipid panels from the age of 9, and monitor hypertension annually from the age of 3.11
Closer monitoring can lead to lifestyle modifications, educational interventions for both children and their parents in terms of diet, physical activity and behavioral changes in terms of smoking and alcohol consumption.
There are also implications in terms of treatment options; However, more prospective data and trials are required to determine whether medication side effects increase cardiometabolic risk in patients with psoriasis.27
The present study has several limitations .
First, this is a meta-analysis of predominantly retrospective observational studies, which are susceptible to selection bias. There is considerable heterogeneity among the cohorts, including institutional clinic data as well as administrative claims data. The latter is susceptible to coding error and omission error. Data extracted from retrospective chart review are also limited by assessment and recall biases.
The data collected were prevalence data and, as such, do not provide information on the incidence or new cases of cardiometabolic comorbidities in a childhood psoriasis cohort over time. The reported results are a diverse track of events during childhood and early adulthood, adding further heterogeneity.
The present analysis is an unadjusted pooled meta-analysis and, as such, does not take into account potential confounders. In particular, there is evidence supporting an increased cardiometabolic risk in African American and Hispanic groups for childhood psoriasis, which may bias the results presented.17
The studies did not report results in psoriasis subgroups such as chronic plaque versus guttate and, as such, subgroup analysis according to psoriasis type was not possible. Previous treatments as well as lifestyle habits, physical activity and diet are parameters that have the potential to confound the results presented, but were not addressed in the included studies.
In summary , in this systematic review and pooled meta-analysis the authors demonstrated a significant association between childhood psoriasis and obesity, central adiposity, and other cardiometabolic comorbidities.
It is important to consider this relationship when proposing treatment medications such as acitretin and cyclosporine, which may have a direct impact on these comorbidities. Clinicians should consider evaluating comorbidities in children with psoriasis, which may allow for early lifestyle and educational interventions.
