The Bidirectional Association Between Psoriatic Disease and Uveitis: An Updated Meta-Analysis

Abstract

Background:

In the past decade, there has been growing research interest in the association between psoriatic diseases and uveitis due to the potential pathogenetic links. However, observational studies have reported inconsistent results.

Methods:

We thoroughly searched PubMed, Embase, and Web of Science for cohort or case-control studies investigating the bidirectional association between psoriatic diseases (psoriasis and psoriatic arthritis) and uveitis. The Newcastle-Ottawa Quality Assessment Scale was used for quality evaluation of included studies. Egger’s test was used for publication bias assessment. We employed a random-effects model to pool individual data, using odds ratios (ORs) with 95% confidence interval (CI) as the effect measure.

Results:

Eleven cohort studies and 1 case-control study with 9,641,856 participants were included. Eleven studies were considered as good quality, and 1 study was considered as fair quality. Egger’s test indicated no significant publication bias. The meta-analysis indicated that patients with psoriatic disease was at higher risk of developing uveitis (OR: 2.14, 95% CI: 1.57-2.90). The result maintained consistent in patients with psoriatic arthritis (OR: 3.13, 95% CI: 2.10-4.67) but not in those with psoriasis without arthritis (OR: 1.40, 95% CI: 0.91-2.14). We also found that uveitis was associated with an increased risk of psoriatic disease (OR: 2.56, 95% CI: 1.66-3.96) including psoriasis without arthritis (OR: 1.99, 95% CI: 1.12-3.53) and psoriatic arthritis (OR: 3.53, 95% CI: 2.08-5.99).

Conclusion:

Our study suggested that uveitis was more likely to be bidirectionally associated with psoriatic arthritis rather than psoriasis without arthritis. More investigations focusing on the mechanisms are needed to better understand these findings from observational studies.

Keywords

psoriasis psoriatic arthritis uveitis meta-analysis systematic review

Introduction

Psoriatic diseases (including psoriasis and psoriatic arthritis) and uveitis are inflammatory disorders, both of which are connected with T-helper 1/T-helper 17 inflammatory reactions.¹ The potential pathogenetic links of psoriatic diseases and uveitis have led to growing research interest in the association between them in the past decade. Two previous meta-analyses of observational studies concluded that psoriasis and psoriatic arthritis were associated with an increased risk of uveitis.^2,3 Notably, these two meta-analyses^2,3 included many cross-sectional studies (5 out of 7 and 11 out of 14, respectively), which had only investigated the coexistence association between psoriatic diseases and uveitis. As a result, the causal evidence remained insufficient. Another meta-analysis published later indicated that uveitis was conversely associated with increased risks of psoriasis and psoriatic arthritis.⁴ Interestingly, a recent Mendelian randomization study revealed that there is no genetic interplay between psoriatic diseases and uveitis.⁵

In brief, the bidirectional association between psoriatic diseases and uveitis need to be further clarified. Considering that several large cohort studies have been published in recent years, which could have provided more evidence, we decided to perform this updated meta-analysis.

Methods

This study has been registered with PROSPERO (http://www.crd.york.ac.uk/PROSPERO), and the registration number is CRD42024600506.

We reported our results and wrote the manuscript in accordance with recommendations of MOOSE guidelines.⁶ Please see the MOOSE checklist in Supplemental Appendix S1.

Literature Search

PubMed, Embase, and Web of Science were thoroughly searched without language restriction for studies published before August 31, 2024. Medical Subject Heading terms together with title and abstract were applied, and the complete search strategy is provided in Supplemental Appendix S2. We also reviewed reference lists of obtained articles to avoid missing any relevant literature.

Inclusion and Exclusion Criteria

Observational studies including case-control or cohort studies were considered. There is no restriction of age, sex, and race on participants. Participants in exposure groups could be patients diagnosed with psoriatic disease (psoriasis and psoriatic arthritis) or uveitis, while the outcome should correspondingly be the incidence of uveitis or psoriatic disease. Control groups should consist of healthy participants. We excluded studies published in the forms of letter or conference abstract.

Two investigators independently reviewed titles, abstracts, and texts and identified eligible studies according to the selection criteria. A third investigator was consulted if the 2 investigators held different opinions.

Data Extraction

Extracted data included authors, study design, study period, sample size, region, exposure, outcome, and covariates adjusted in each study. Data extraction was performed independently by 2 investigators and confirmed by a third investigator.

Risk of Bias Assessment

Risk of bias of included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS), a tool having been widely applied for the method quality evaluation of observational studies in systematic reviews.⁷ NOS assesses the risk of bias in 3 domains including selection, comparability, and exposure/outcome. Details of NOS together with the evaluation criteria (good, fair, or poor quality) based on the NOS score are presented in Supplemental Appendix S3.

Data Synthesis

Odds ratios (ORs) with 95% confidence interval (CI) were used as the effect measure in our meta-analysis. We noticed that included studies have reported different effect measures. Considering that the incidence of outcome of interest was low, all effect measures were considered similar.⁸ The heterogeneity among included studies was assessed using the I-squared (I²) test. A random-effects model was used in consideration of the clinical heterogeneity across studies. Forest plots were used to display individual and pooled results. Egger’s test was used for publication bias evaluation. We analyzed all data using Stata 15.0.

Results

Study Selection

A total of 1288 records were obtained after the initial search in the 3 electronic databases. Then, we removed duplicates and reviewed titles, abstracts, and texts of the remaining publications. According to the selection criteria, 12 studies^9-20 with 9,641,856 participants were finally included in our meta-analysis (Figure 1).

Characteristics of Included Studies and Participants

Eleven cohort studies^9-16,18-20 and 1 case-control study¹⁷ were included. All studies were published between 2015 and 2024, and the sample size ranged from 33,915 to 5,508,878. Three studies^12-14 were from North America, 4 studies^9,11,15,17 were from Europe, and 5 studies^10,16,18-20 were from Asia. Eight studies^{10-12,14,15,18-20} investigated the impact of psoriatic disease on uveitis, 2 studies^16,17 investigated the impact of uveitis on psoriatic disease, and 2 studies^9,13 investigated the bidirectional association between psoriatic disease and uveitis. Detailed characteristics of included studies are provided in Table 1.

Table 1.

Characteristics of Included Studies.

Authors	Study design	Study period	Region	Exposure/outcome	Sample size	Covariates adjusted
Egeberg et al.⁹	Cohort study	1997-2011	Denmark	Cohort 1: Psoriatic disease/uveitis Cohort 2: Uveitis/psoriatic disease	5,508,878	Age, sex, comorbidities, and socioeconomic status
Chi et al.¹⁰	Cohort study	2000-2012	Taiwan, China	Psoriatic disease/uveitis	295,908	Age, sex, diabetes, hypertension, and hyperlipidemia
Charlton et al.¹¹	Cohort study	1998-2014	United Kingdom	Psoriatic arthritis/uveitis	33,915	Age, sex, smoking status, and body mass index
Brandon et al.¹²	Cohort study	2000-2013	United States	Psoriatic disease/uveitis	49,764	Variables positively associated with the outcome in univariate analysis (details not provided)
Aletaha et al.¹³	Cohort study	2006-2015	United States	Cohort 1: Psoriatic disease/uveitis Cohort 2: Uveitis/psoriatic disease	398,935	Sex, age, insurance plan type, and state of residence
Kaine et al.¹⁴	Cohort study	2008-2015	United States	Psoriatic arthritis/uveitis	49,935	Age, sex, region, health plan type, urbanicity, index year, and comorbidities
Bengtsson et al.¹⁵	Cohort study	2001-2016	Sweden	Psoriatic arthritis/uveitis	121,921	Sex, birth year, and county of residence
Chen et al.¹⁶	Cohort study	2001-2013	Taiwan, China	Uveitis/psoriatic disease	585,375	Age, sex, insurance cost, hypertension, diabetes, hyperlipidemia, and obesity
Meer et al.¹⁷	Case-control study	1994-2015	United Kingdom	Uveitis/psoriatic disease	1,308,244	Age, sex, year of diagnosis, and comorbidities
Kim et al.¹⁸	Cohort study	2010-2021	Korea	Psoriatic disease/uveitis	953,820	Age, sex, diabetes, hypertension, and hyperlipidemia
Hijazi et al.¹⁹	Cohort study	2005-2020	Israel	Psoriatic arthritis/uveitis	30,146	Age, sex, cohort entry date, ethnicity, duration of follow-up, socioeconomic status, and comorbidities
Patt et al.²⁰	Cohort study	2000-2020	Israel	Psoriatic disease/uveitis	305,015	Age, sex, and uveitis-related comorbidities

Quality Assessment of Included Studies

According to the NOS assessment, 6 studies were awarded 8 stars,^9,13-16,18 5 studies^10-12,19,20 were awarded 7 stars, and 1 study¹⁷ was awarded 6 stars. Details are present in Supplemental Appendix S4. Among the studies, 11^9-16,18-20 were considered as good quality and 1¹⁷ was considered as fair quality.

Meta-Analysis

Ten studies^9-15,18-20 reported results investigating the impact of psoriatic disease on uveitis. The meta-analysis indicated that psoriatic disease was associated with an increased risk of uveitis (OR: 2.14, 95% CI: 1.57-2.90, I² = 98.7%). Six studies^{9,10,12,13,18,20} reported results investigating the impact of psoriasis without arthritis on uveitis. The meta-analysis indicated that psoriasis without arthritis had no impact on uveitis (OR: 1.40, 95% CI: 0.91-2.14, I² = 99.2%). Ten studies^9-15,18-20 reported results investigating the impact of psoriatic arthritis on uveitis. The meta-analysis indicated that psoriatic arthritis was associated with an increased risk of uveitis (OR: 3.13, 95% CI: 2.10-4.67, I² = 96.0%) Figure 2.

Four studies^9,13,16,17 reported results investigating the impact of uveitis on psoriatic disease. The meta-analysis indicated that uveitis was associated with an increased risk of psoriatic disease (OR: 2.56, 95% CI: 1.66-3.96, I² = 98.6%). Three studies^9,13,16 reported results investigating the impact of uveitis on psoriasis without arthritis. The meta-analysis indicated that uveitis was associated with an increased risk of psoriasis without arthritis (OR: 1.99, 95% CI: 1.12-3.53, I² = 99.0%). Four studies^9,13,16,17 reported results investigating the impact of uveitis on psoriatic arthritis. The meta-analysis indicated that uveitis was associated with an increased risk of psoriatic arthritis (OR: 3.53, 95% CI: 2.08-5.99, I² = 94.8%) Figure 3.

Publication Bias Analysis

In the meta-analysis for the impact of psoriatic disease on uveitis, Egger’s test indicated no significant publication bias (P = .30, see Supplemental Figure S1). Similarly, we found no significant publication bias (P = .29, see Supplemental Figure S2) in the meta-analysis for the impact of uveitis on psoriatic disease.

Discussion

We performed this updated meta-analysis after a thoroughgoing review of the current literature, and found that psoriatic diseases were associated with an increased risk of uveitis. The positive association was more likely to exist in patients with psoriatic arthritis but not in those with psoriasis without arthritis. In addition, we also found that patients with uveitis had higher risk of developing psoriasis and psoriatic arthritis.

Our findings were consistent with those of 3 previous meta-analyses related to this topic, all of which suggested a positive association between psoriasis and the risk of uveitis.^2-4 Compared with previous ones, the present meta-analysis mainly focused on the incidence rather than the prevalence of uveitis, and included more cohort or case-control studies. Therefore, the results of our study could provide stronger evidence for the impact of psoriasis and psoriatic arthritis on uveitis.

Li et al reported that the incidence of uveitis significantly increased no matter in patients with psoriasis or in those with psoriatic arthritis.⁴ Different from their findings, our meta-analysis indicated that patients with psoriatic arthritis were more likely to have the risk of developing uveitis. Compared with healthy controls, the incidence of uveitis in patients with psoriasis was higher without statistically significant difference between groups. Compared with Li et al’s meta-analysis, ours included 2 recently published population-based cohort studies.^18,20 Kim et al found that psoriasis mildly increased the risk of uveitis using the nationwide data from the Korean Health Insurance Review and Assessment Service,¹⁸ while the other Israeli study concluded that psoriasis was not associated with the risk of uveitis using the data from the Ethics Committee of the Meuhedet Health Maintenance organization. In these 2 studies, evidence supporting a positive association between psoriasis without arthritis and the risk of uveitis was weak. However, both of these 2 studies suggested a significant association between psoriatic arthritis and the risk of uveitis. Briefly, we found that psoriatic arthritis, compared with psoriasis, showed a greater association with the incidence of uveitis. Notably, Lam et al’s meta-analysis of cross-sectional studies have reported similar results.³ Nevertheless, there is lack of reasonable explanations for these observational results. It remains unclear whether the severity of psoriasis plays a role in the development of uveitis or as speculated, spondyloarthritis-related diseases mediated the association between psoriasis and uveitis. Therefore, much evidence is required.²⁰

Another finding of the present meta-analysis is that uveitis was associated with an increased risk of psoriasis or psoriatic arthritis. Compared with Li et al’s meta-analysis of 2 cohort studies,⁴ the present one included 4 studies with 9 cohorts, and our results were consistent with the previous one. Moreover, we noticed that all included studies had reported positive associations between uveitis and the risk of psoriasis or psoriatic arthritis, although the estimates across them differed. However, the biological mechanisms of the observational association have not been fully understood. Since there is a significant overlap of inflammatory pathways between uveitis and psoriasis or psoriatic arthritis, inflammatory mediators released into systemic circulation by uveitis may promote the development of psoriasis and psoriatic arthritis.

The heterogeneity across included studies was significant, which is the main limitation of our meta-analysis. There are several possible explanations. First is the potential bias from observational studies. All included in our meta-analysis were cohort or case-control studies. Such study designs are suitable to investigate the association between 2 diseases, and moreover, the researchers in the original studies have considered possible confounders. However, residual confounding was inevitable owing to the lack of randomization. In addition, the potential effect modification might partly explain the observational heterogeneity across studies. The present meta-analysis indicated that psoriasis with arthritis has a greater association with uveitis than psoriasis without arthritis. Nevertheless, it remains unknown that whether there are other specific variables that might have modified the association between psoriasis and uveitis. Therefore, more studies are required to verify the hypothesis.

In summary, our study suggested that psoriatic diseases were bidirectionally associated with uveitis. Notably, such positive association was more likely to exist only in patients with psoriatic arthritis. The biologic mechanisms linking psoriatic diseases and uveitis need to be further clarified which could better explain these findings from observational studies.

Supplemental Material

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Footnotes

Author Contributions

Jia Liu and Shun Guo were responsible for the entire meta-analysis. Miao miao, Jiong Yan, and Yujin Sun performed literature search, data extraction, risk of bias assessment, and data synthesis. Miao miao wrote the manuscript, and Jiong Yan revised the manuscript. All authors have read and approved the final manuscript for submission.

Data Availability Statement

All data analyzed in this study are from these published articles (9-20).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics Statement

No human participants were involved in this study, and ethics approval was not required.

ORCID iD

Jia Liu

Supplemental Material

Supplemental material for this article is available online.

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