Clinical Edge Journal Scan

Commentary: Genetics, Juvenile PsA, and Weight Loss in PsA, September 2023

Dr. Chandran scans the journals, so you don't have to!

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Vinod Chandran, MBBS, MD, DM, PhD

A large majority of patients with psoriatic arthritis (PsA) develop inflammatory musculoskeletal disease after the onset of cutaneous psoriasis. Identifying molecular markers and mechanisms underlying the transition from psoriasis alone to PsA can help develop tools for early diagnosis as well as preventive interventions. With the aim of identifying epigenetic markers that predict PsA in patients with psoriasis, Cruz-Correa and colleagues this month reported the results of a nested case-control study that included 58 patients with psoriasis who later developed PsA matched to 59 patients who did not develop PsA. They conducted genome-wide DNA methylation analyses on blood samples from the patients recruited for this study. Their predictive model, based on 36 highly relevant methylation markers across 15 genes and intergenic regions (including FBXO27 and ZNF385D), could identify patients with psoriasis who developed PsA from those who did not, with an excellent AUC (area under the receiver operating characteristic curve) of 0.964. These results are exciting but require further internal and external validation.

Although the usual age at onset of PsA is in the fourth or fifth decade of life, children may develop juvenile-onset PsA (JPsA). Less attention has been paid to this form of juvenile idiopathic arthritis (JIA), and the impact of JPsA vis-à-vis other forms of JIA is not well known. In addition, only about half of the patients with JPsA have cutaneous psoriasis. The impact of psoriasis on children with JPsA is not known. In order to evaluate differences in disease outcomes in patients with JPsA, Low and colleagues evaluated 1653 children and young people with JIA who were recruited to the Childhood Arthritis Prospective Study, of whom 111 had JPsA at diagnosis. They demonstrated that there were no significant differences in patient-reported outcomes between children with JPsA and other JIA categories. However, children with JPsA and psoriasis at JPsA diagnosis had more depressive symptoms compared with those without psoriasis. Moreover, children with JPsA vs other JIA categories had 2.35 times higher odds of having persistently poor well-being scores despite improvements in joint counts and physician global scores. Thus, children with JPsA have poorer well-being scores and a higher prevalence of depression, which requires multidisciplinary care.

Apart from immunomodulatory therapies, weight loss leads to improvement in disease activity in patients with obesity and PsA. However, the mechanisms by which weight loss improves PsA is currently not known, but is likely to be due to changes in adipokines and inflammation-related cytokines. In a recent study1that included patients with PsA and obesity, it was demonstrated that weight loss through a Very Low Energy Diet (VLED) resulted in significant improvements in PsA disease activity. Landgren and colleagues now aimed to determine the effects of VLED on cytokines and adipokines. They obtained blood samples from patients with PsA and obesity (n = 41) and matched control individuals without rheumatic disease or psoriasis (n = 39) who were on VLED. At month 6, along with significant weight loss, serum levels of interleukin-23 and leptin decreased significantly, while those of total adiponectin and high-molecular-weight adiponectin increased significantly in patients with PsA and control individuals. The change in body mass index correlated positively with a reduction in serum interleukin-23 (rS = 0.671, P < .001) and improvement in PsA disease activity (P = .003). This study highlights the anti-inflammatory effect of weight loss in patients with PsA. Weight loss can complement immunomodulatory therapy in PsA patients with obesity.

Additional Reference

  1. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21:17. doi: 10.1186/s13075-019-1810-5

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