The role of orexin in fatigue and sleep quality in patients with primary Sjögren's syndrome.

BACKGROUND: Sleep disorders and fatigue are prevalent symptoms affecting primary Sjögren's syndrome (pSS) patients. This study aimed to assess the sleep quality of pSS patients as well as its relationship to fatigue and orexin level. METHODS: This is a cross-sectional study evaluating fatigue in pSS using the Fatigue Severity Scale (FSS). Sleep quality was evaluated using the Pittsburg Sleep Quality Index (PSQI). The European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) were calculated. RESULTS: Forty-one patients met the sample criteria and were involved in the final report. They were all females, with a mean (± SD) age and median disease duration of 40.87 ± 10.84 and 36 (6-180) months, respectively. The mean ESSDAI was 0.92 ± 1.3, while the mean ESSPRI was 5.8 ± 2.13. Based on the FSS, 32 (78.04%) patients had a positive test with a mean score of 5.07 ± 1.54. The total PSQI score showed that 60.97% had poor sleep, and the orexin level was lower in patients with pSS than in healthy controls. There was no correlation between orexin level and the presence of fatigue nor the PSQI score. CONCLUSION: In conclusion, serum orexin levels were lower in patients with pSS than healthy controls, It could be related to impairments in sleep and fatigue in patients with pSS.

Evaluation of subclinical atherosclerosis by ultrasound radiofrequency data technology in patients with psoriatic arthritis.

OBJECTIVE: This study aimed to assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis using ultrasound radiofrequency data technology. METHODS: In all, 29 psoriatic arthritis patients and 42 age- and sex-matched healthy controls were included in this cross-sectional study. Arterial stiffness and carotid intima-media thickness measurements were performed in bilateral common carotid arteries using ultrasound radiofrequency data technology in all participants. RESULTS: In psoriatic arthritis patients, the mean carotid intima-media thickness, α and ß stiffness indices, and pulsed wave velocity value were significantly higher than those in the control group (542.3 (81.3) vs. 487.9 (64.1), 9.3 (6.3) vs. 3.9 (0.1), 18.7 (17.7) vs. 8.04 (4.2), and 10.2 (3.8) vs. 6.4 (1.5), p<0.05). The mean distensibility coefficient and compliance coefficient values of the patient group were significantly lower than those of the control group (0.014 (0.01) vs. 0.03 (0.01) and 0.57 (0.33) vs. 1.02 (0.4), p<0.05). No significant correlation was found between carotid artery hemodynamic parameters and symptom duration, duration of diagnosis and treatment, disease activity index for psoriatic arthritis scores, erythrocyte sedimentation rate, and C-reactive protein levels (p>0.05). CONCLUSION: In the results of our study, evidence of subclinical atherosclerosis has been detected in psoriatic arthritis patients without clinically evident cardiovascular disease or traditional cardiovascular risk factors.

Determination of serum vascular endothelial growth factor (VEGF) and VEGF receptor levels with VEGF gene polymorphisms in patients with Behçet's uveitis.

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Uveitis is frequently seen in patients with BD, especially in Turkish population. OBJECTIVES: To investigate vascular endothelial growth factor (VEGF) gene polymorphisms along with the levels of VEGF and VEGF receptors in patients with Behçet's uveitis (BU). MATERIAL AND METHODS: Fifty-five BD-associated uveitis patients and 30 ageand sex-matched controls were included in this case-control study. The genotypes of the single nucleotide poymorphisms (SNPs): rs2010963 (+405G), rs3025039 (+936T) and rs699947 (-2598A) of the VEGF-A gene were determined using real-time polymerase chain reaction (RT-PCR) and serum levels of VEGF and VEGF receptors were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: No associations of the VEGF gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024). Although there were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3) levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively). In addition, VEGF-C/soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) ratio was significantly higher (p < 0.001), while VEGF-A/VEGFR-1 and VEGF-C/sVEGFR-3 ratios were significantly lower (p < 0.001 and p = 0.033, respectively) in BD patients compared to controls. Also, VEGF-C/sVEGFR-3 (p = 0.024, r = 0.37) and VEGF-C/sVEGFR-2 (p = 0.020, r = 0.38) ratios were positively correlated with disease duration. CONCLUSIONS: The significant changes in sVEGFR-3 levels and VEGF-C/sVEGFR-3 ratio has shown that lymphangiogenesis processes might take place in the pathogenesis of BD uveitis, and these parameters can be important indicators of evaluation of BD patients with uveitis together with disease duration.

Evaluation of subclinical atherosclerosis by ultrasound radiofrequency data technology in patients with psoriatic arthritis

SUMMARY OBJECTIVE: This study aimed to assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis using ultrasound radiofrequency data technology. METHODS: In all, 29 psoriatic arthritis patients and 42 age- and sex-matched healthy controls were included in this cross-sectional study. Arterial stiffness and carotid intima-media thickness measurements were performed in bilateral common carotid arteries using ultrasound radiofrequency data technology in all participants. RESULTS: In psoriatic arthritis patients, the mean carotid intima-media thickness, α and β stiffness indices, and pulsed wave velocity value were significantly higher than those in the control group (542.3 (81.3) vs. 487.9 (64.1), 9.3 (6.3) vs. 3.9 (0.1), 18.7 (17.7) vs. 8.04 (4.2), and 10.2 (3.8) vs. 6.4 (1.5), p<0.05). The mean distensibility coefficient and compliance coefficient values of the patient group were significantly lower than those of the control group (0.014 (0.01) vs. 0.03 (0.01) and 0.57 (0.33) vs. 1.02 (0.4), p<0.05). No significant correlation was found between carotid artery hemodynamic parameters and symptom duration, duration of diagnosis and treatment, disease activity ındex for psoriatic arthritis scores, erythrocyte sedimentation rate, and C-reactive protein levels (p>0.05). CONCLUSION: In the results of our study, evidence of subclinical atherosclerosis has been detected in psoriatic arthritis patients without clinically evident cardiovascular disease or traditional cardiovascular risk factors.

Endocan: A Novel Marker for Colchicine Resistance in Familial Mediterranean Fever Patients?

Introduction: Familial Mediterranean fever (FMF) patients had 5-10% colchicine resistance. Although FMF attacks are characterized by acute phase elevation, there are no biomarkers that can show colchicine resistance yet. The serum endocan levels may elevate in inflammatory and auto-inflammatory diseases. Objectives: This study aimed to evaluate serum endocan levels in FMF patients according to whether attack and colchicine resistance or not and also compare them with classical acute phase reactants. Methods: In this single-center and cross-sectional study, a total of 111 FMF patients and 60 healthy individuals were enrolled. All patients' basic demographic and clinical data were recorded and blood samples were collected. Results: A total of 46 (41.4%) FMF patients had colchicine resistance. In comparison to the FMF patients according to colchicine response, colchicine resistance patients had a significantly higher median (IQR) endocan levels than colchicine responsive patients [36.98 ng/ml (97.41) vs. 13.57 ng/ml (27.87), p = 0.007], but there were no differences between in terms of median ESR and CRP levels. Inversely, serum endocan levels were similar during an attack and attack-free period in FMF patients, although ESR and CRP levels were significantly different. Interestingly, the highest serum endocan levels were in the control group. Conclusion: In conclusion, serum endocan levels were higher in colchicine resistance than colchicine responsive patients, but attack state had no effect on serum endocan levels in our study. Unlike ESR and CRP, serum endocan may be a novel biomarker for detection of colchicine resistance and distinguish the FMF attacks.

An investigation of thiol/disulfide homeostasis in patients with Behçet's disease.

INTRODUCTION: Behçet's disease (BD) is a relapsing systemic inflammatory disorder. The diagnosis of BD is primarily based on clinical findings. Current biomarkers are not yet sufficient to diagnose and cannot anticipate the course of the disease and response to treatment. The aim of this study was to evaluate the relationship between the thiol-disulfide balance and disease activity and organ involvement in BD. MATERIAL AND METHODS: A hundred fifty patients with BD and 100 age- and gender-matched healthy controls were included in the study. Disease activity was assessed with the BD Current Activity form score. Serum levels of native thiol (NT), total thiol (TT), and disulfide were measured and the disulfide/native thiol, disulfide/total thiol and native thiol/total thiol levels were calculated for the patient and control groups. RESULTS: Native thiol, total thiol, native thiol/total thiol values of the BD patients were significantly lower than those of the control group. The disulfide/native thiol, disulfide/total thiol values of BD patients were higher compared to the control group and the disulfide value of the BD group was slightly higher compared to the control group. No correlation was determined between thiol levels and disease activity and organ involvement in BD. CONCLUSIONS: In patients with Behcet's disease, the thiol-disulfide homeostasis balance shifted towards disulfide formation due to thiol oxidation. It may be used as a novel marker in BD because it is easy, practical, fully automated and relatively inexpensive.

Thiol/Disulfide homeostasis in patients with rheumatoid arthritis.

BACKGROUND: Oxidative stress may play an important role in rheumatoid arthritis (RA) etiopathogenesis. The thiol group is a very strong antioxidant. In this study, we aimed to investigate the presence of oxidative stress in patients with RA by evaluating thiol/disulfide homeostasis. MATERIAL AND METHODS: A total of 50 female RA patients and 50 healthy female controls were included in this study. Thiol and disulfide values were calculated utilizing novel methods. RESULTS: Native thiol (p < 0.001) and total thiol (p < 0.001) levels of RA patients were significantly lower compared to values in the control group. However, the disulfide (p < 0.001) levels of RA patients were strongly higher than in healthy individuals. A negative correlation was found between thiol and disease activity score-28 among the patients, whereas a positive correlation was found between disulfide and disease activity score-28 among the patients. CONCLUSION: We found that the thiol-disulfide rate deteriorated in RA patients, with the proportion of disulfide increasing. There is a strong correlation between the decrease in thiol levels, increase in disulfide levels and the disease activity scores.

The relationship between bristol rheumatoid arthritis fatigue scales and disease activity of patients with rheumatoid arthritis.

Fatigue is a symptom that affects the 40-80% of patients with rheumatoid arthritis (RA) and impairs the quality of life. The aim of this study was to assess multidimensional fatigue scales, the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) and the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS) and to evaluate their relationship with disease activity in Turkish RA patients. The study included 180 patients with RA. The Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) were used to evaluate disease activity. The participants comprised of 142 females and 38 males. The mean ± standard deviations of DAS28, CDAI, and SDAI were 3 ± 1.24, 9.51 ± 7.96, and 10.5 ± 8.38 respectively. All scales except the emotional subscale were correlated with disease activity. The emotional subscale correlated with CDAI and SDAI but not with DAS28. The results of the study indicated that fatigue and disease activity were correlated. Fatigue is a symptom that impairs the quality of life but it can be easily coped with by controlling disease activity. Thus, it should be assessed in a multidimensional perspective.

Do the European League Against Rheumatism (EULAR) Sjögren's syndrome outcome measures correlate with impaired quality of life, fatigue, anxiety and depression in primary Sjögren's syndrome?

INTRODUCTION: The aim of the study was to investigate whether there is a relationship between the European League Against Rheumatism (EULAR) outcome measures and quality of life (QoL), fatigue, anxiety and depression in patients with pSS and to define determinants which could affect quality of life. MATERIAL AND METHODS: The study included 105 pSS patients and 72 age/sex-matched healthy controls (HCs). Cross-sectional clinical data were collected, including the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Assessment of Fatigue (MAF) scale, the Short Form (SF-36), EULAR Sjögren's syndrome disease activity index (ESSDAI) and EULAR Sjögren's syndrome patient reported index (ESSPRI). RESULTS: The SF-36 scores were significantly lower and anxiety, depression and fatigue scores were significantly higher in the pSS group than in the control group (all p-value < 0.05). ESSDAI was negatively correlated with SF-36 scores and positively with MAF. ESSPRI was negatively correlated with SF-36 scores except for the mental health subdimension, and a positive correlation was determined with MAF, HADS-A and HADS-D. Multiple linear regression analysis revealed that HADS-A, HADS-D, MAF, ESSPRI and ESSDAI were associated with most SF-36 subscales. CONCLUSIONS: The results of this study provide further evidence supporting the use of ESSDAI and ESSPRI in daily practice. Quality of life was diminished in patients with pSS and was associated with different symptoms. This should be taken into account when managing patients with pSS.

The relationship of serum VEGF and sVEGFR-1 levels with vascular involvement in patients with Behçet's disease.

Behçet's disease (BD) is a rare, chronic, inflammatory disorder characterized by multisystemic vasculitis including mucocutaneous, neurologic, and ophthalmic involvement. Our aim is to compare vascular endothelial growth factor (VEGF) and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) levels in BD, among the patients having or not having organ involvement, disease activation and especially vascular involvement. Fifty-five patients with BD, 25 of which were accompanied by vascular involvement, and 31 control subjects were included in the study. Disease activity was assessed with the Turkish version of Behçet Disease Current Activity Form (BDCAF) and active vasculitis lesions at the time of study were recorded. Age at diagnosis was 32.2 ± 4.6, while the mean duration of BD was 96.3 (72.3) months. The median for BDCAF score was 2.0 (range 0, 3.0), and 29 (52%) of patients had active BD. The serum VEGF and sVEGFR-1 levels in patients with BD were significantly higher than that in controls [(298 (338.5) pg/mL; 93 (93.5) pg/mL in patients and 136.2 (73) pg/mL; 56.5 (48.5) pg/mL in controls, respectively, p < .001 for both values] while difference in VEGF/sVEGFR-1 ratio was obtained close to borderline of significance (p = .03). Our study is the first report indicating elevated serum VEGF, sVEGFR-1, and more importantly VEGF/sVEGFR-1 ratio could play an important role in the development of trombosis in BD. VEGF and/or sVEGFR-1 should not be evaluated independently in the same patient group and the ratio of these two parameters is a more important indicator, especially in the evaluation of BD especially with vascular involvement together with the duration of disease.

Short report: correlates of functional disability with disease activity in elderly patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) prevalence increases with age and old people are special patient population. The recognition of functional disability related to RA could be challenging in elderly patients because aging itself and potential co-morbid disease may also cause functional disability. In this study, we aimed to look at the correlation between disease activity and functional disability in elderly RA patients. Elderly RA patients, ≥65 years old at their routine visits were included in the study. The composite 'disease activity score' in 28 joints (DAS-28) was used to determine disease activity groups. Health assessment questionnaire (HAQ) scores were calculated to describe the functional disability and compared across the disease activity groups. Two hundred and fifty-eight RA patients with the mean age of 71 ± 5 (65-90) and a total disease duration of 8.4 ± 8.5 (.5-50) years were recruited. The proportion of patients with high and moderate disease activity was 70%. HAQ scores were significantly correlated with disease activity (p < .05). Functional disability estimated by HAQ was correlated with disease activity in elderly patients with RA.

Serum calprotectin and ischemia modified albumin levels as markers of disease activity in Behçet's disease.

INTRODUCTION: Behçet's disease (BD) is a complex multisystemic inflammatory disorder which is characterized by recurrent attacks of acute inflammation. As there is no universally recognized pathognomonic laboratory marker of BD, its diagnosis is still based on clinical findings. AIM: To evaluate the role of calprotectin and ischemia modified albumin (IMA) as biomarkers in the assessment of disease activity of BD. MATERIAL AND METHODS: A total of 93 patients with BD and 62 age- and gender-matched healthy controls were included in the study. Disease activity was assessed with the BD Current Activity Form (BDCAF) score. Serum levels of calprotectin, high-sensitivity C-reactive protein (hsCRP) and IMA were measured in the patient and control groups. RESULTS: Serum levels of calprotectin, IMA and hsCRP in patients with BD were higher than those of the healthy control group (p < 0.001 for all). No correlations between calprotectin and IMA, hsCRP, erythrocyte sedimentation rate, CRP, or BDCAF score were found. CONCLUSIONS: As the calprotectin level are increased in BD patients, it could be a candidate biomarker which plays a role in BD pathogenesis.

Follow-Up of Treatment Response With Dynamic Doppler Ultrasound in Raynaud Phenomenon.

OBJECTIVE: The purpose of this study was to investigate the role of flow parameters obtained with dynamic Doppler ultrasound in the objective follow-up of treatment response in patients with Raynaud phenomenon (RP). SUBJECTS AND METHODS: The study included 33 patients with newly diagnosed primary RP, 31 with secondary RP, and 26 healthy participants (control subjects). Both groups of patients with RP underwent sonography before and after treatment. The control group underwent sonography once. Baseline digital arterial diameter and flow volume were measured at room temperature. After cold provocation, diameter and flow volume were measured again, and flow starting time and flow normalizing time were recorded. Data were measured as mean (± SD) values. RESULTS: Baseline diameter did not significantly increase in either group after treatment (p > 0.05) (primary RP pretreatment, 0.79 ± 0.17 mm; posttreatment, 0.82 ± 0.19 mm; secondary RP pretreatment, 0.66 ± 0.13 mm; posttreatment, 0.68 ± 0.14 mm). Baseline flow volume increased significantly in both groups (p < 0.01) (primary RP pretreatment, 3.08 ± 2.96 mL/min; posttreatment, 3.91 ± 3.39 mL/min; secondary RP pretreatment, 2.14 ± 1.94 mL/min; posttreatment, 2.80 ± 2.15 mL/min). Cold provocation diameter increased significantly in both groups after treatment (p < 0.01) (primary RP pretreatment, 0.63 ± 0.15 mm; posttreatment, 0.70 ± 0.16 mm; secondary RP pretreatment, 0.56 ± 0.15 mm; posttreatment, 0.63 ± 0.13 mm). Cold provocation flow volume increased significantly in both groups after treatment (p < 0.01) (primary RP pretreatment, 1.18 ± 1.26 mL/min; posttreatment, 2.17 ± 2.16 mL/min; secondary RP pretreatment, 1.07 ± 1.40 mL/min; posttreatment, 1.46 ± 1.67 mL/min). After treatment, there was no statistically significant increase in flow starting time in patients with primary RP (p > 0.05), but there was a significant increase in patients with secondary RP (p < 0.05) (primary RP pretreatment, 1.15 ± 2.27 minutes; posttreatment, 0.61 ± 1.41 minutes; secondary RP pretreatment, 3.13 ± 4.81 minutes; posttreatment, 1.58 ± 2.36 minutes). After treatment, flow volume normalizing time improved significantly in both groups (p < 0.01) (primary RP pretreatment, 7.24 ± 7.60 minutes; posttreatment, 3.84 ± 3.39 minutes; secondary RP pretreatment, 9.58 ± 8.49 minutes; posttreatment, 4.32 ± 3.56 minutes). Among patients with primary RP, the posttreatment flow starting time was similar to that in the control group. Despite improvements, all remaining parameters differed in the treatment group compared with the control group. CONCLUSION: Doppler ultrasound can be used effectively to monitor RP treatment. Blood flow volume can be measured without cold provocation to facilitate follow-up care of patients with RP.

Can the Thiol/Disulfide Imbalance Be a Predictor of Colchicine Resistance in Familial Mediterranean Fever?

Familial Mediterranean fever (FMF) is a chronic autoinflammatory condition characterized by fever attacks and recurrent polyserositis. Subclinical inflammation that persists during attack-free periods can result in oxidative stress (OS) damage. Thiol groups bind to reactive oxygen radicals and protect cells and tissues from OS damage. The aim of this study was to investigate the relationship between thiol-disulfide balance and colchicine resistance in FMF patients during an attack or attack-free period. A newly developed spectrophotometric method was used to measure native thiol (NT) and disulfide (DS) levels in FMF patients and an age-sex matched group of healthy controls. NT and DS levels were compared in FMF patients 1) with vs. without colchicine resistance; and 2) during an attack (FMF-AP) vs. attack-free period (FMF-AFP). A total of 118 FMF patients and 60 healthy controls were studied. NT (P < 0.001) and total thiol (TT) (P < 0.001) levels in FMF patients were significantly lower compared to healthy controls. NT (P = 0.030) and TT (P = 0.010) levels of FMF-AP patients were significantly lower than that of FMF-AFP patients. FMF-AP patients had significantly higher DS levels than FMF-AFP patients (P = 0.039). Compared to FMF patients without colchicine resistance, elevated levels of DS (P = 0.019) but not NT (P = 0.620) and TT (P = 0.718) were found in those with colchicine resistance. Thiol-disulfide homeostasis is altered in FMF patients during an attack period and this imbalance may be associated with colchicine resistance.

Fatigue in rheumatic diseases.

Fatigue is a common and important problem in many diseases including rheumatologic illnesses, and it has a negative impact on health-related quality of life. Fatigue is described as having an impact on multiple aspects of a patient's life. There is a need for knowledge about causes of and treatments for fatigue to ensure that patient outcomes are improved. There are several effective treatment strategies available for fatigue including pharmacological and non-pharmacological therapies. We aim to provide an overview of fatigue in rheumatologic disorders and some recommendations on its optimal management.