In our study, metabolic factors had a greater influence on disease activity than emotional disorders in PsA patients, and this influence was greater in PsA patients than in AS patients. The differences were associated with laboratory factors associated with obesity (leptin concentration), not obesity itself. Obesity, leptin levels, and depression were associated with increased disease activity. Leptin influenced disease activity, affecting pain- and inflammation-associated variables.
We found no differences in the presence of anxiety and/or depression between the patients with PsA and the patients with AS. Only one other study directly compared patients with PsA and other spondyloarthropathies using the HADS questionnaire. The authors also found no differences, and the mean HADS questionnaire scores were similar to those in our study [10].
The prevalence of obesity is higher in PsA patients than in the general population [11]. Although PSA patients have a higher rate of obesity than AS patients, few studies have compared this comorbidity between these patient groups. Haque et al. [27] demonstrated that PsA patients had a higher metabolic rate than patients with other spondyloarthropathies. This difference was determined based on a greater abdominal circumference (102.46 vs 98.29 p < 0.02) and higher triglyceride level (163.07 vs 133.47; p < 0.001) in patients with other spondyloarthropathies [27]. We did not find differences in the waist/hip ratio, abdominal circumference, or categorized BMI between the PsA and AS groups. The difference between our results and those published previously could be due to genetic or sociocultural factors since in Haque's study, both PsA and AS patients had greater abdominal circumferences than the patients in our study (102.46 vs 90.49 and 98.29 vs 89.89, respectively). The exclusion of patients with diabetes or dyslipidaemia receiving treatment in our study could also explain this difference.
Leptin is a hormone secreted by adipocytes that acts on various metabolic pathways regulating body weight; it also has pro-inflammatory properties, as it intervenes in cellular immunity, activates the Th1 response and increases IL-1β, IL-6 and TNF-α levels [15, 16]. There are no other studies comparing leptin levels between patients with PsA and AS. In previous studies involving AS patients, serum leptin levels fluctuated substantially and were similar to those found in the control group (7.2–17.2) [18, 27]. In a study carried out in a Spanish population, the results were very similar to those in our study (8.5 vs 8.9 in men and 18.9 vs 17.01 in women) [28]. In our study, the leptin level, obesity, and depression predicted persistent clinical PsA activity. Recently, Lubrano et al. [29] demonstrated that the number of comorbidities, including general comorbidities, anxiety and fibromyalgia in particular, had an impact on the DAPSA scores. Other comorbidities, such as depression, diabetes and obesity, did not influence activity [29].
Several studies have specifically linked some comorbidities with disease activity. McDonough et al. [5] found a relationship between anxiety/depression measured by the HADS questionnaire and the SJC. This relationship can be explained in two ways: functionality limitation and loss secondary to inflammation could cause depression or anxiety, or psychologic stress affecting the hypothalamic-pituitary-adrenal axis could stimulate T-cells, promoting the secretion of cytokines (TNF-α, IL-1) [30]. For this reason, biologic treatment may improve anxiety and depressive symptoms regardless of the particular effect [31]. In our study, the rates of probable anxiety and depression were similar to those previously published. We also found a significant correlation between the SJC and HADS scores for both anxiety and depression (data not shown) [5].
Several reports support a link between obesity and disease activity. Thus, weight loss has been associated with an improved response to anti-TNF-α therapy. Moreover, obese patients are less likely to achieve minimal disease activity (MDA) than non-obese patients [32, 33]. Reports have shown that obesity influences only the pain parameter of the MDA score [33].
There are several studies on the influence of leptin on PsA disease activity. Eder et al. [21] did not find a significant correlation between leptin level and the SJC, although they did find a strong trend (p: 0.05). A study in Asian patients found an association between the leptin level and the Psoriatic Arthritis Joint Activity Index (PsAJAI); however, the authors did not analyse relationships with the different components of the index. Therefore, we do not know if the leptin level was correlated with inflammation-associated parameters [34]. A recent study revealed associations between leptin level and the VAS score and TJC [35], and other results also support the theory that leptin may be a pain modulator [36, 37]. In our study, leptin was correlated with both the SJC and TJC, suggesting it influenced inflammatory and pain variables.
As previously described, we also found a relation between BMI and leptin levels [21, 35]. In some studies on rheumatoid arthritis, leptin was correlated with disease activity, although it was not associated with BMI [38, 39]. This dissociation may be related to the fact that leptin synthesis does not occur in only abdominal fat. In osteoarthritis patients, increased leptin secretion has been found in adipocytes in infrapatellar fat [40].
One of our study limitations was that we did not compare leptin concentrations between disease groups and a control group; however, previous studies have found higher serum levels in PsA patients than in healthy subjects [34].