New research suggests a causal effect between inflammatory bowel disease (IBD), particularly in Crohn's disease, and both psoriasis (PsO) and psoriatic arthritis (PsA), although not vice versa. Ulcerative colitis did not appear to be responsible for the causal effect. Results may allow clinicians to better manage IBD and psoriasis in clinical practice, according to a study published in JAMA Dermatology.1
“About 30% of patients with psoriasis experience psoriatic arthritis, a systemic inflammatory arthritis sharing common pathogenetic and immunologic features with psoriasis,” investigators stated. “Furthermore, it is now recognized that psoriasis is associated with other immune-mediated inflammatory conditions; in particular, IBD, including Crohn's disease and ulcerative colitis as the main subtypes, appears to frequently co-occur with the disease.”
Summary statistics from genome-wide association studies (GWASs) comprised of European individuals were collected to conduct this bidirectional 2-sample mendelian randomization study. Total and direct effects were derived using univariable and multivariable analyses. A validation IBD sample, pleiotropy-robust mendelian randomization (MR) methods, and sensitivity analyses based on a combination of PhenoScanner search and network analysis verified causal estimates. IBD, ulcerative colitis, Crohn's disease, PsA, and PsO were examined in terms of both exposures and outcomes.
In total, 12,882 cases of IBD, along with 21,770 controls, were identified based on up to 15 studies, with 5956 patients with Crohn's disease (14,927 controls) and 6968 patients with ulcerative colitis (20,464 controls). Additionally, 5621 cases of PsO and 2063 cases of PsA were obtained from the FINNGEN Consortium and compared with 252,323 controls.
In the univariable case, genetically predicted IBD was linked to a higher risk of both PsA (pooled odds ratio [OR], 1.10; 95% CI, 1.04-1.18; P = .003) and PsO (pooled OR, 1.10; 95% CI, 1.05-1.15; P < .001). Crohn's's disease was associated with PsA arthritis (OR, 1.13; 95% CI, 1.06-1.20; P < .001) and PsO (OR, 1.16; 95% CI, 1.12-1.20; P < .001). However, similar indications of causal effect were not found in ulcerative colitis.
In the multivariable MR, Crohn's disease was also associated with psoriasis (OR, 1.16; CI, 1.10-1.23; P < .001) and psoriatic arthritis (OR, 1.12; CI, 1.04-1.21; P = .002), while ulcerative colitis was not. The sensitivity analyses of the multivariable setting further supported these results.
The study is the first to examine the causal bidirectional link between IBD, including both Crohn's disease and ulcerative colitis, and PsO and PsA via a 2-sample MR analysis. This method is superior in a variety of ways as it is less prone to reverse causality, confounding, and non-differentially measured exposures with error. Heterogeneity was minimized and the reliability of point estimates was confirmed by using a more conservative approach. However, generalizability is limited as all patients were of European descent.
“The results of the study are critical because raising awareness among clinicians and primary care physicians about the potential risk of psoriasis in patients with IBD will contribute to systematic diagnosis and interdisciplinary and early personalized treatment of patients,” investigators concluded. “The investigation of pathophysiologic pathways associated with the development of psoriasis in patients with IBD should be the subject of further basic research.”
Freuer, D., Linseisen, J. and Meisinger, C., 2022. Association Between Inflammatory Bowel Disease and Both Psoriasis and Psoriatic Arthritis A Bidirectional 2-Sample Mendelian Randomization Study. JAMA Dermatol.