Examining the functions of the vascular endothelial growth factor/hypoxia-inducible factor signaling pathway in psoriatic arthritis.

Objectives: The present study aimed to examine the roles of the vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), and heme oxygenase-1 (HO-1) in psoriatic arthritis (PsA). Patients and methods: In this cross-sectional study conducted between November 2020 and May 2021, 64 patients (43 female, 21 male; mean age: 43.2±10.4 years; range, 22 to 60 years) with active PsA were included in the patient group, and 64 healthy volunteers (43 female, 21 male; mean age: 42.8±10.5 years; range, 23 to 61 years) were included in the control group. The demographic features of all cases were recorded. The following indices were used to assess the activity of PsA: Bath Ankylosing Spondylitis Disease Activity Index, Disease Activity Score in 28 joints (DAS28), and Visual Analog Scale. Additionally, Disease Activity in Psoriatic Arthritis (DAPSA) and Psoriasis Area and Severity Index (PASI) were used to evaluate the patients. The biochemical parameters of the patients were calculated. The serum levels of VEGF, HIF, and HO-1 were determined using an enzyme-linked immunosorbent assay. Results: When the molecule levels and clinical features of the groups were evaluated, it was found that the VEGF and HIF-1 levels were higher in the patient group compared to the control group (p<0.05). No difference was observed in the comparison of the HO-1 levels of the patient group and the control group (p<0.05). A positive correlation was found between VEGF, HIF-1, and HO-1 (p<0.05). A positive relationship was found between VEGF and HIF-1 and erythrocyte sedimentation rate, C-reactive protein, DAPSA score, and PASI score (p<0.05). It was also determined that there was a positive relationship between the HIF molecule and DAS28 (p<0.05). Conclusion: According to the results obtained in the present study, VEGF and HIF play a role in the etiology of PsA, and the observation of intermolecular correlation suggests that these molecules move together in pathogenesis.

Could serum HMGB1 levels be a predictor associated with psoriatic arthritis?

Background/aim: Psoriasis is a chronic autoimmune disease that predominantly affects the skin and musculoskeletal system. We hypothesized that HMGB1, an inflammatory nuclear protein, may play a role in the musculoskeletal involvement of psoriasis. Methods: Forty patients with psoriasis and 45 with psoriatic arthritis were involved in the study; the results were compared with 22 healthy controls. Serum HMGB1 levels were evaluated from peripheral blood samples. Results: Serum HMGB1 levels were found to be significantly higher in patients with psoriasis regardless of joint involvement (p < 0.001). Also, HMGB1 levels were correlated with the extent of psoriasis. Conclusion: Serum HMGB1 levels may contribute to the progression of psoriasis to psoriatic arthritis and correlate with the severity of skin involvement.

Psoriasis is an autoimmune skin disease that may also affect the joints. Factors leading to the progression of psoriasis to psoriatic arthritis are still a mystery despite an increasing number of animal studies and real-life data. HMGB1 is a nuclear protein that leads to an increase in molecules that increase inflammation (TNF-α, IL-1 and IL-6) in the body. Until now, there was no report about the relationship between psoriatic arthritis and serum HMGB1 levels. Our study aimed to find any difference in HMGB1 levels between healthy and psoriatic patients. Psoriatic arthritis patients had higher levels of serum HMGB1 than patients with psoriasis. Also, HMGB1 levels were correlated with the severity of skin involvement. Our results showed that serum HMGB1 may indicate a high risk for developing psoriasis that involves the joints. Therefore the HMGB1 level in psoriasis patients can potentially serve as a predictor associated with disease severity and the risk of developing psoriatic arthritis.

Diagnostic delay in psoriatic arthritis: insights from a nationwide multicenter study.

This study aimed to investigate the duration of diagnostic delay in patients with psoriatic arthritis (PsA) and identify potential contributing factors using a comprehensive, population-based approach. Data were obtained from the Turkish League Against Rheumatism (TLAR)-Network, involving patients who met the CASPAR criteria. Diagnostic delay was defined as time interval from symptom onset to PsA diagnosis, categorized as ≤ 2 years and > 2 years. Temporal trends were assessed by grouping patients based on the year of diagnosis. Various factors including demographics, clinical characteristics, disease activity, quality of life, physical function, disability, fatigue, and well-being were examined. Logistic regression models were used to identify factors associated with diagnostic delay. Among 1,134 PsA patients, mean diagnostic delay was 35.1 months (median: 12). Approximately 39.15% were diagnosed within 3 months, and 67.02% were diagnosed within 24 months. Patients experiencing longer delays had higher scores in Psoriatic Arthritis Quality of Life Questionnaire (PsAQoL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), patient's global assessment (PtGA) and physician's global assessment (PhGA). Diagnostic delay has decreased over time, with median delay falling from 60 to 24 months throughout pre-2010 and 2015-2019 terms. Several factors were identified as significant contributors to delayed diagnosis, including lower levels of education (OR = 2.63), arthritis symptoms preceding skin manifestations (OR = 1.72), low back pain at first visit (OR = 1.60), symptom onset age (OR = 0.96), and psoriasis subtype (OR = 0.25). Timely diagnosis of PsA is crucial for effective management and improved outcomes. Despite recent improvements, about one-third of PsA patients still experience delays exceeding 2 years. By identifying influential factors such as education level, arthritis symptoms preceding skin manifestations, initial visit symptoms, age of symptom onset, and psoriasis subtype, healthcare practitioners may create specific techniques to help in early detection and intervention.

Beyond expectations: disease duration and psychological burden in psoriatic arthritis.

This study aims to investigate the relationship between disease duration and psychological burden in PsA and to identify the risk factors associated with psychological distress. Patients with PsA who met CASPAR classification criteria enrolled by Turkish League Against Rheumatism (TLAR)-Network. Patients were categorized into three groups based on disease duration: early stage (< 5 years), middle stage (≥ 5, < 10 years), and late stage (≥ 10 years). All patients underwent clinical and laboratory assessment using standardized protocol and case report forms. The associations between psychological variables and clinical parameters were assessed by a multivariate analysis. Of the 1113 patients with PsA (63.9% female), 564 (%50.7) had high risk for depression and 263 (%23.6) for anxiety. The risk of psychological burden was similar across all PsA groups, and patients with a higher risk of depression and anxiety also experienced greater disease activity, poorer quality of life, and physical disability. Multivariate logistic regression revealed that female gender (OR = 1.52), PsAQoL (OR = 1.13), HAQ (OR = 1.99), FiRST score (OR = 1.14), unemployment/retired (OR = 1.48) and PASI head score (OR = 1.41) were factors that influenced the risk of depression, whereas the current or past enthesitis (OR = 1.45), PsAQoL (OR = 1.19), and FiRST score (OR = 1.26) were factors that influenced the risk of anxiety. PsA patients can experience a comparable level of psychological burden throughout the course of their disease. Several socio-demographic and disease-related factors may contribute to mental disorders in PsA. In the present era of personalized treatment for PsA, evaluating psychiatric distress can guide tailored interventions that improve overall well-being and reduce disease burden.

Evaluation of hepatitis serology and frequency of viral reactivation in patients with inflammatory arthritis receiving biologic agents: a multicenter observational study.

To evaluate of hepatitis serology and reactivation frequency in patients with rheumatic disease receiving biologic agents. Our study included patients with inflammatory rheumatic diseases from 23 centers, who were followed up with biological therapy. Demographic and clinical characteristics of the patients, duration of drug use and hepatitis serology and the state of viral reactivation were analyzed. A total of 4060 patients, 2095 being males, were included in our study. Of the patients, 2463 had Ankylosing Spondylitis (AS), 1154 had Rheumatoid Arthritis (RA), 325 had Psoriatic Arthritis (PsA), and 118 had other inflammatory rheumatic diseases. When the viral serology of the patients was evaluated, 79 patients (2%) who were identified as HBs Ag positive, 486 (12%) patients who were HBs Ag negative and anti-HBc IgG positive and 20 patients (0.5%) who were anti-HCV positive. When evaluated on a disease-by-disease basis, the rate of HBsAg was found to be 2.5% in RA, 2% in AS and 0.9% in PsA. Viral reactivation was detected in 13 patients while receiving biologic agents. HBs Ag was positive in nine patients with reactivation and negative in four patients. Anti-HBc IgG, however, was positive. Six of these patients had AS, four had RA, and three had PsA. The development of hepatitis reactivation in 11.4% of HBs Ag positive patients and 0.82% of anti-HBc IgG positive patients due to the use of biologic agents is an important problem for this group of patients. Antiviral prophylaxis is recommended to be started especially in patients who are HBs Ag positive and who are using biologic agents due to viral reactivation. Therefore, it is important to carry out hepatitis screenings before biologic agent treatment and to carefully evaluate the vaccination and prophylaxis requirements.

The impact of nail psoriasis on disease activity, quality of life, and clinical variables in patients with psoriatic arthritis: A cross-sectional multicenter study.

AIM: Nail involvement is common in psoriatic arthritis. This study assesses clinical characteristics, nail psoriasis prevalence, and impact of nail psoriasis on disease activity in patients with psoriatic arthritis (PsA). METHOD: This cross-sectional multicenter study was conducted by the Turkish League Against Rheumatism using PsA patients recruited from 25 centers. Demographic and clinical characteristics of PsA patients, such as disease activity measures, quality of life, and nail involvement findings were assessed during routine follow-up examinations. Patients were divided into two groups according to the presence or absence of nail psoriasis and compared using the χ2 test or Fisher exact test for categorical variables and the t-test or Mann-Whitney U test for continuous variables. RESULTS: In 1122 individuals with PsA, 645 (57.5%) displayed nail psoriasis. The most frequent features of fingernails were ridges (38%), followed by pitting (21%) and onycholysis (19%). More females were present in both groups (with and without nail psoriasis; 64% vs 67%, P < 0.282). Patients with nail psoriasis were older, indicated more pain and fatigue, experienced greater swelling, tender joint counts, and skin disease severity, and had a higher disease activity score compared with those without nail psoriasis (all P < 0.05). CONCLUSION: We demonstrate an increased prevalence of nail psoriasis observed in patients with psoriatic arthritis. Patients with nail involvement experience increased disease activity, lower quality of life, and diminished mental and physical status compared with those without nail involvement.

Inconsistencies of the Disease Activity Assessment Tools for Psoriatic Arthritis: Challenges to Rheumatologists.

OBJECTIVE: Currently, concerning the evaluation of psoriatic arthritis (PsA), there is no agreement on a standardized composite index for disease activity that includes all relevant domains. The present study sought to assess the rates of remission (REM)/low disease activity (LDA) and disease states [minimal disease activity (MDA), very low disease activity (VLDA)] as defined by diverse activity scales (DAPSA, DAS28-ESR) in an attempt to display discrepancies across these assessment tools for peripheral PsA. METHODS: The study involved 758 patients (496 females, 262 males; mean age 47,1 years) with peripheral PsA who were registered to the Turkish League Against Rheumatism (TLAR) Network. The patients were assessed using the DAS28-ESR, DAPSA, MDA, and VLDA. The overall yield of each scale was assessed in identifying REM and LDA. The presence or absence of swollen joints was separately analysed. RESULTS: The median disease duration was 4 years (range 0-44 years). According to DAPSA and DAS28-ESR, REM was achieved in 6.9% and 19.5% of the patients, respectively. The rates of MDA and VLDA were 16% and 2.9%, respectively. Despite the absence of swollen joints, a significant portion of patients were not considered to be in REM (296 (39.1%) patients with DAS28-ESR, 364 (48%) with DAPSA, and 394 (52%) with VLDA). CONCLUSION: Patients with peripheral PsA may be assigned to diverse disease activity levels when assessed with the DAS28-ESR, DAPSA, MDA and VLDA, which would inevitably have clinical implications. In patients with PsA a holistic approach seems to be necessary which includes other domains apart from joint involvement, such as skin involvement, enthesitis, spinal involvement, and patient-reported outcomes.

The impact of COVID-19 on familial Mediterranean fever: a nationwide study.

The study aimed to evaluate the impact of the coronavirus disease 2019 (COVID-19) in patients with familial Mediterranean fever (FMF) and to assess the relationships between FMF characteristics and severe COVID-19 outcomes such as hospitalization. The study was planned within a national network of 21 different centers. Demographics, FMF-related clinical and genetic characteristics, and COVID-19 outcomes were obtained. A total of 822 patients with FMF (mean age of 36 years) were included in the study. Fifty-nine of them (7%) had a COVID-19 diagnosis confirmed by real-time PCR test or chest CT findings. Most FMF patients with COVID-19 (58) had mild and moderate disease activity. All patients were on colchicine treatment. However, 8 of them (13.6%) were not compliant with colchicine use and 9 of them (15.3%) were colchicine resistant. Twelve FMF patients with COVID-19 were hospitalized. There were 4 patients requiring oxygen support. COVID-19 related complications were observed in 2 patients (1 thromboembolism, 1 acute respiratory distress syndrome). Hospitalized COVID-19 patients with FMF were older than non-hospitalized patients (median ages: 51 and 31 years, respectively; p: 0.002). Other FMF-related characteristics were similar between the groups. FMF-related characteristics were not found to be associated with poor outcomes in COVID-19. Thus, FMF may not be a risk factor for poor COVID-19 outcomes.

Gender-related differences in disease activity and clinical features in patients with peripheral psoriatic arthritis: A multi-center study.

OBJECTIVE: This study sought to compare disease activity, clinical features, and patient-reported outcomes concerning anxiety, depression, fatigue, function, quality of life, and fibromyalgia between female and male patients with peripheral PsA in a Turkish population. METHODS: This multi-center Turkish League Against Rheumatism (TLAR) Network study included 1038 patients (678 females, 360 males) diagnosed with peripheral PsA according to the CASPAR criteria. The demographic and clinic parameters of the patients were recorded. Disease activity was evaluated using the scores of DAS28 and cDAPSA. Remission, minimal disease activity (MDA), and very low disease activity (VLDA) were determined. Health Assessment Questionnaire (HAQ), Short-Form-36 (SF-36), Hospital Anxiety and Depression Scale (HAD), fatigue VAS (0-10), and Fibromyalgia Rapid ScreeningTool (FiRST) were used. Disease activity and patient-reported outcomes were compared in male and female patients, and the predictors of MDA for both genders were analyzed. RESULTS: The patients' mean age was 47.6years (SD: 12) for females and 46.3years (SD: 12.3) for males. In terms of DAS28 and cDAPSA, female patients had significantly higher disease activity scores, while male patients had significantly higher remission rates (P<0.05). There was a significant difference in the rate of MDA in favor of males (P<0.05), but not in VLDA. The incidences of dactylitis, enthesitis, tenosynovitis, and inflammatory bowel disease were similar in male and female patients, except for spondylitis, which was higher in males (P<0.05). Overall, although there was no significant between-group difference in age and disease duration, female patients had significantly higher BMI and late-onset disease (P<0.05). Female patients had higher HAD, HAQ, and FiRST and lower SF-36 scores than males (P<0.05). In both male and female patients, the disease activity score of cDAPSA was significantly correlated with the scores of FiRST, HAD, VAS-F, and HAQ (P<0.05). In regression analysis, tender joint count, swollen joint count, PASI, pain VAS, and enthesitis were the MDA predictors in both genders. CONCLUSION: In patients with peripheral PsA, males are more likely to develop spondylitis while other extraarticular manifestations are similar. Female patients appear to have lower rates of remission and MDA and higher levels of disease activity. Female patients experience a more severe course of PsA, with higher levels of pain and fatigue, lower quality of life, and increased functional limitations. The predictors of MDA, i.e., tender joint count, swollen joint count, PASI, pain VAS, and enthesitis are similar between the two genders.

The effect of gender on disease activity and clinical characteristics in patients with axial psoriatic arthritis.

OBJECTIVES: In this study, we aimed to evaluate the effect of gender on clinical findings, disease activity, functional status and quality of life in patients with axial involvement in Turkey. METHODS: Patients with PsA who met the CASPAR classification criteria were enrolled consequently in this cohort. Turkish League Against Rheumatism (TLAR)-Network was formed with the participation of 25 centres. The demographic variables, fatigue, diagnostic delay, the beginning of peripheral arthritis, enthesitis, dactylitis and spine involvement, inflammatory low back pain, BASFI, HAQ, HAQ-s, visual analogue scale-pain (VAS-pain), anxiety, depression and disease activity parameters (ESR, DAS28, BASDAI) were recorded. Axial involvement was assessed according to clinical and radiological data according to modified New York (MNYC) or Assessment of SpondyloArthritis international Society (ASAS) criteria. RESULTS: A total of 1018 patients with PsA were included in this study. Of the 373 patients with axial involvement, 150 were male (40.2%) and 223 (59.8%) were female. Spondylitis was detected in 14,7% of men and 21,9% of women in all patients. Pain score (VAS) (p < .002), fatigue (p < .001), ESR (p < .001), DAS28 (p < .001), BASDAI score (p < .001), PsAQoL (p < .001), HAQ score (p < ,01), HAQ-S score (p < .001), anxiety (p < .001), depression (p < .024), FACIT (p < .001) and FiRST (p < .001) scores were statistically significantly worse in women than males with axial PsA. However, quality of life was better (p < .001) and PASI score (p < .005) were statistically worse in male patients than in female patients with axial involvement. CONCLUSION: This study has shown that the burden of disease in axial PsA has significant difference between genders. Disease activity, physical disability, functional limitation, depression and anxiety scores were higher in female patients, while quality of life were better and PASI score were higher in male patients. Therefore, we suggest that new strategies should be developed for more effective treatment of axial PsA in female patients.

The impact of fatigue on patients with psoriatic arthritis: a multi-center study of the TLAR-network.

Fatigue is a substantial problem in patients with psoriatic arthritis (PsA) that needs to be considered in the core set of domains. This study aimed to evaluate fatigue and its relationship with disease parameters, functional disability, anxiety, depression, quality of life, and correlation with disease activity as determined by various scales. A total of 1028 patients (677 females, 351 males) with PsA who met the CASPAR criteria were included [Turkish League Against Rheumatism (TLAR) Network multicenter study]. The demographic features and clinical conditions of the patients were recorded. Correlations between fatigue score and clinical parameters were evaluated using the Disease Activity Score 28 (DAS28), Disease Activity in Psoriatic Arthritis (DAPSA), Clinical DAPSA (cDAPSA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Fibromyalgia Rapid Screening Tool (FiRST), minimal disease activity (MDA), and very low disease activity (VLDA). Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT-F) and a 10-point VAS (VAS-F). The mean age of the patients was 47 (SD: 12.2) years, and the mean disease duration was 6.4 (SD: 7.3) years. The mean VAS-F score was 5.1 (SD: 2.7), with fatigue being absent or mild, moderate, and severe in 12.8%, 24.6%, and 62.5% of the patients, respectively. Fatigue scores were significantly better in patients with DAS28 remission, DAPSA remission, cDAPSA remission, MDA, and VLDA (p < 0.001). Fatigue scores significantly increased with increasing disease activity levels on the DAS28, DAPSA, and cDAPSA (p < 0.001). VAS-F scores showed correlations with the scores of the BASDAI, BASFI, PsAQoL, HAD-A, FiRST, pain VAS, and PtGA. FiRST scores showed fibromyalgia in 255 (24.8%) patients. FACIT-F and VAS-F scores were significantly higher in patients with fibromyalgia (p < 0.001). In regression analysis, VLDA, BASDAI score, FiRST score, high education level, HAD-Anxiety, and BMI showed independent associations with fatigue. Our findings showed that fatigue was a common symptom in PsA and disease activity was the most substantial predictor, with fatigue being less in patients in remission, MDA, and VLDA. Other correlates of fatigue were female gender, educational level, anxiety, quality of life, function, pain, and fibromyalgia.