Central sensitization significantly deteriorates functionality and the interpretation of self-reported disease activity in primary Sjögren's syndrome.

BACKGROUND: Central sensitization has a major role in health-related parameters in musculoskeletal conditions. There is still a lack of understanding regarding the impact of central sensitization on the interpretation of disease activity and functional disability in primary Sjögren's syndrome (pSS). METHODS: The Central Sensitization Inventory (CSI) was used to screen for central sensitization. Disease-related parameters, including objective tests, medication use, the EULAR SS Patient Reported Index (ESSPRI), and the EULAR SS Disease Activity Index (ESSDAI), were assessed. Functionality, quality of life, sleep, and mental health were evaluated by the Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Jenkins Sleep Evaluation Scale (JSS), and Hospital Anxiety and Depression Scale (HADS), respectively. The effect of central sensitization on functionality and disease activity measures was assessed by regression analyses. RESULTS: The frequency of central sensitization was 65% in patients with pSS (n = 60). Patients with central sensitization had higher HAQ-DI, ESSPRI, HADS, and JSS and lower SF-36 subdomain scores (p < 0.05 for all). A significant positive correlation was observed between the CSI score and the ESSPRI, JSS, HAQ-DI, and HADS scores (Spearman's rho ranging from 0.342 to 0.739). The multiple regression analysis indicated that CSI was independently associated with HAQ-DI (adjusted R2 = 0.19, B = 0.01) and ESSPRI (adjusted R2 = 0.45, B = 0.08) (p < 0.001 for all). CONCLUSION: This study confirms that central sensitization has a major impact on functionality and the interpretation of self-reported disease activity in pSS. When devising strategies for the management of patients with pSS, it is crucial to consider these close relationships. Key Points • The frequency of central sensitization accompanying primary Sjögren's syndrome is considerable. • Central sensitization was independently associated with functionality and self-reported disease activity assessment. • This close association leads to challenges in functionality, evaluating treatment response, and planning or switching between therapies in primary Sjögren's syndrome.

Evaluation of inflammatory biomarkers and the ratio of hemoglobin-red cell distribution width in patients with rheumatoid arthritis treated with tumor necrosis factor-alpha inhibitors.

BACKGROUND: The aim of this study was to examine pre-treatment and post-treatment hemogram-derived inflammatory biomarkers in patients with rheumatoid arthritis (RA) who received anti-tumor necrosis factor (TNF)-α treatment. MATERIAL AND METHODS: The data of 1182 patients with RA were screened. Among them, 207 patients who met the eligibility criteria were included in the retrospective study. Demographic parameters, disease activity, and blood cell-derived indexes were evaluated. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and hemoglobin-red cell distribution width (Hb/RDW) rates were evaluated before treatment and at the third month of treatment in patients with RA who received anti-TNF-α treatment. RESULTS: According to the EULAR response criteria, 12.6% of the 207 patients responded to anti-TNF-α treatment as none, 21.3% as good, and 66.2% as moderate, respectively. Post-treatment NLR and PLR values were significantly lower than pre-treatment values (p < 0.001), whereas post-treatment LMR and Hb/RDW values were significantly higher than pre-treatment values (respectively, p = 0.001 and p = 0.012). The difference between pre-treatment and post-treatment values of LMR and Hb/RDW was significantly higher when compared to the moderate + good response groups than the none-response group (p = 0.002 and p = 0.014, respectively). However, in the receiver operating characteristic curve analysis, these parameters were not found to be significant in predicting treatment response. CONCLUSION: Significant changes were detected in hemogram-derived inflammatory markers of the groups responding to anti-TNF-α treatment. They can be used as a guide during treatment follow-up. Yet, they do not predict treatment response. Key Points • RA may manifest with periods of remission and activation, and regular follow-up is essential. • There is a demand for readily available, reproducible, and cost-effective parameters to assess treatment response. • Hemogram-derived inflammatory markers differ in relation to anti-TNF-α treatment response in RA. • None of those markers demonstrate an acceptable predictive performance in distinguishing patients based on their response to TNF-α inhibitors.

The effect of balance exercises on central sensitization in patients with knee osteoarthritis.

The aim of this study was to evaluate the effectiveness of balance exercises on functional status, pain, balance, and central sensitization in patients with knee osteoarthritis (OA). Patients diagnosed with bilateral Kellgren-Lawrence grade ≥ 2 primary knee OA and associated central sensitization were included in the study. Patients were randomized into two groups. Both groups were provided with verbal and written information on knee OA. In addition, the intervention group received a supervised balance exercise program for 6 weeks, 3 days a week on alternating days. The outcome measures were the changes in the Central Sensitization Inventory (CSI), Visual Analog Scale (VAS) pain, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Berg Balance Scale, and Y Balance Test. Evaluations were performed at baseline, immediately after treatment (6th week) and at 12th week. The study included 40 patients, 20 patients in each group. At the end of the treatment period (6th week), the improvement in CSI score, WOMAC pain, WOMAC physical function, WOMAC total score, Y Balance Test scores, and VAS pain during activity was significantly greater in the intervention group than that in the control group (p < 0.001). Regarding the changes from baseline to the 12th week, the intervention group experienced greater improvement in most of the outcome measures. Yet, the change in WOMAC pain score, Berg Balance Scale score, and VAS pain at rest was similar between the study groups (p = 0.05, p = 0.257, and p = 0.385, respectively). A two-model multiple linear regression analysis revealed that the changes in VAS pain (during activity) after the treatment and at follow-up [(p = 0.004, adjusted R2: 0.346) and (p = 0.002, adjusted R2: 0.391), respectively], as well as changes in WOMAC pain from baseline to follow-up (p = 0.020, ΔR2 = 0.245) significantly affected central sensitization. However, changes in Y Balance Test and WOMAC total scores did not appear to have a significant impact on the improvement in central sensitization (p > 0.05). Balance exercises may provide improvement in central sensitization, functional status, and dynamic balance among patients with knee OA. The improvement in central sensitization depends mostly on the pain relief effect of balance exercises.

Central sensitization: its prevalence and impact on quality of life among hemodialyzed patients.

BACKGROUND/AIM: Data on the role of central sensitization in hemodialyzed patients are scarce. The aim was to identify the impact of central sensitization on quality of life and elucidate the risk factors for the development of central sensitization in patients receiving hemodialysis. METHODS: Central sensitization, quality of life, psychological well-being, and sleep were assessed by the Central Sensitization Inventory (CSI), abbreviated version of the World Health Organization Quality of Life Instrument (WHOQOL-BREF), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Evaluation Scale (JSS), respectively. The effect of central sensitization on quality of life and the predictors of the development of central sensitization were assessed by regression analyses. RESULTS: The frequency of central sensitization was 48% in the study population (n = 100). Patients with central sensitization had significantly higher pain intensity, worse sleep quality, and more impaired psychological status (p < 0.05 for all). The CSI score negatively affected all quality of life domains on its own (p < 0.001 for all, adjusted R2 ranged from 0.17 to 0.47). Dialysis vintage (OR, 0.8; 95% CI, 0.7 to 1.0), pain (OR, 1.5; 95% CI, 1.1 to 2.0), JSS (OR, 1.3; 95% CI, 1.1 to 1.5), and HADS-total (OR, 1.1; 95% CI, 1.0 to 1.2) were determined as the independent risk factors for central sensitization (p < 0.05 for all). CONCLUSION: This study confirms that given the high frequency of central sensitization and its significant negative impact on quality of life, the presence of central sensitization should be investigated in patients undergoing hemodialysis.

The effect of lumbosacral transitional vertebra on lumbar spine degeneration and spondylolisthesis among patients with low back pain.

AIM: To examine the impact of lumbosacral transitional vertebra (LSTV) on lumbar spine degeneration, disc protrusion, and spondylolisthesis among patients with low back pain. METHODS: The records of the patients who had undergone anterioposterior lumbar radiographs and lumbar magnetic resonance imaging (MRI) for low back pain between November 2014 and September 2021 were extracted retrospectively and assessed for eligibility. Of the remaining patients, those with LSTV were assigned as "case group." Age- and sex-matched patients without LSTV were assigned as "control group." On digitalized lumbar MRIs, Modic degeneration (type I-III) and Pfirrman's disc degeneration (grade I-V) immediately cephalad to the transitional level were evaluated; intervertebral disc height (mm), disc protrusion (mm), and percentage of vertebral slippage (%) were measured. RESULTS: Of the 501 patients with low back pain, 128 ineligible patients were excluded; 113 patients with LSTV and 117 age- and sex-matched controls were included in the study. LSTV group revealed decreased intervertebral disc height, increased vertebral endplate degeneration, and slippage, as well as increased disc degeneration and protrusion when compared with controls (p < 0.001). Patients with type III LSTV had greater disc protrusion and higher percentage of slippage compared to those with type I LSTV (p = 0.008 and p = 0.009, respectively). Vertebral endplate degeneration, disc height, and disc degeneration did not differ across categories of LSTV type. CONCLUSION: Lumbosacral transitional vertebra malformation is related to decreased intervertebral disc height, increased disc degeneration, vertebral endplate degeneration, disc protrusion, and slippage above the level of transition. Patients with type III LSTV revealed the highest percentage of slippage and disc protrusion.

Why is polymyalgia rheumatica a disease of older adults? Explanations through etiology and pathogenesis: a narrative review.

Polymyalgia rheumatica is one of the most common inflammatory rheumatic conditions in older adults. The disease is characterized by pain and stiffness in the shoulder and pelvic girdle. Polymyalgia rheumatica is almost always observed in adults over the age of 50. The current article aimed to provide explanations for the age preference of polymyalgia rheumatica by reviewing the literature regarding disease etiology and pathogenesis. Potential factors related to the association between polymyalgia rheumatica and aging include immunosenescence/inflammaging, increased risk of infections by aging, endocrinosenescence, and age-related changes in gut microbiota. These factors and their potential contributions to immune-mediated inflammation will be discussed.

Exercise therapy for improving cardiovascular health in rheumatoid arthritis.

There is increased risk of cardiovascular disease in patients with rheumatoid arthritis. Primary cardiovascular disease prevention in rheumatoid arthritis patients is difficult, especially in those with high disease activity. According to current evidence, people with rheumatoid arthritis can significantly improve clinical indices and patient-reported outcomes by engaging in organized physical activity such as resistance training and aerobic activities. Additionally, participating in an exercise regimen can lower the risk of experiencing cardiovascular problems. Nevertheless, the percentage of patients with sedentary lifestyle habits is high among individuals with rheumatoid arthritis. Patient education regarding the benefits of physical activity/exercise is essential. The cardiovascular effects of exercise depend on several mechanisms such as (i) increased vascular function, (ii) decreased systemic inflammation, (iii) restoration of the autonomic system, (iv) improved lipid profile, and (v) increased muscular function. Maintaining the exercise routine is crucial for continuing benefits. A customized exercise plan helps to improve adherence and compliance. Engaging patients in shared decision-making is important since their personal choices can alter depending on several factors such as the severity of the disease, the cost, and accessibility. The current narrative review aimed to explore the recent evidence related to exercise therapy for cardiovascular health in patients with rheumatoid arthritis.

The relation of psychological status and type D personality with central sensitization in knee osteoarthritis: everything is in your mind!

To evaluate the relation of psychosocial parameters and type D personality with central sensitization in knee osteoarthritis (OA). The study included 126 patients with knee OA according to the American College of Rheumatology criteria. Sociodemographic variables (age, gender, education, marital status, annual income), alcohol consumption/smoking, body mass index, comorbidities, and duration of symptoms were noted. Radiographic evaluation was performed according to the Kellgren-Lawrence grading system. The Western Ontario and McMaster Universities Osteoarthritis Index was used for clinical evaluation. Type D personality, negative affectivity, and social inhibition were evaluated using the type D Scale-14 (DS14). Central sensitization was assessed by the central sensitization inventory (CSI), while psychological status, quality of life, and sleep were assessed by the Hospital Anxiety and Depression Scale (HADS), an abbreviated version of the World Health Organization Quality of Life Instrument (WHOQOL-BREF), and the Jenkins Sleep Evaluation Scale (JSS), respectively. The effect of type D personality on study parameters including central sensitization, as well as the risk factors for the development of central sensitization were assessed by regression analyses. Patients with type D personality had higher CSI, HADS scores and lower WHOQOL-BREF scores for psychological health, social relationship, environment and general quality of life. Linear regression analysis showed that the DS14 total score has a significant positive relation with CSI (ß = 0.4, p < 0.05), HADS-depression (ß = 0.4, p < 0.05), HADS-anxiety (ß = 0.5, p < 0.05), and HADS-total scores (ß = 0.5, p < 0.05). It also had a significant negative effect on all domains of WHOQOL-BREF (p < 0.05 for all). Logistic regression analysis revealed that JSS [Odds ratio (OR) 0.83, 95% CI 0.73-0.94; p = 0.003] and negative affectivity (OR 0.78, 95% CI 0.65-0.94; p = 0.008) were independent risk factors for the development of central sensitization in knee OA. Type D personality has an impact on quality of life, central sensitization, and psychological health, with negative affectivity and sleep impairment serving as independent risk factors for central sensitization. While managing patients with knee OA, these intimate relationships should be taken into consideration.

Biopsychosocial factors should be considered when evaluating central sensitization in axial spondyloarthritis.

To identify the determinants of central sensitization (CS) in patients with axial spondyloarthritis (axSpA). Central Sensitization Inventory (CSI) was used to determine CS frequency. Disease-related variables including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP/-ESR), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) and Numeric Rating Scale (NRS)GLOBAL were assessed. Biopsychosocial variables were evaluated by the Multidimensional Scale of Perceived Social Support (MSPSS), Brief Illness Perception Questionnaire (B-IPQ), Hospital Anxiety and Depression Scale (HADS) and subscales for Anxiety (HADS-A) and Depression (HADS-D), and Jenkins Sleep Evaluation Scale (JSS). To determine the predictors of the development and severity of CS, multiple linear and logistic regression analyses were performed. The frequency of CS was 57.4% in the study population (n = 108). CSI score was correlated with the duration of morning stiffness, BASDAI, ASDAS-CRP, ASDAS-ESR, NRSGLOBAL, BASFI, MASES, ASOoL, JSS, HADS, and B-IPQ total scores (ρ ranged from 0.510 to 0.853). Multiple regression analysis indicated that BASDAI (OR: 10.44, 95% CI: 2.65-41.09), MASES (OR: 2.47, 95% CI: 1.09-5.56) and HADS-A (OR: 1.62, 95% CI: 1.11-2.37) were independent predictors of the development of CS. Additionally, higher NRSGLOBAL, JSS, HADS-D, and HADS-A scores appeared to determine the severity of CS. This study confirms that worse disease activity, more enthesal involvement, and anxiety independently predict the development of CS. Additionally, higher patient-perceived disease activity, sleep impairment and poor mental health significantly contribute to the severity of CS.

Type D personality and self-esteem in patients with fibromyalgia: a cross-sectional case-control study.

Fibromyalgia (FM) is a complex disease related to several factors. Psychosocial elements, such as type D personality and low level of self-esteem, might increase disease burden. The current study aimed to investigate type D personality and self-esteem in patients with FM. Female patients with FM and age-matched, healthy controls were enrolled in this cross-sectional study. Type D personality was evaluated using the type D scale (DS-14). The Rosenberg self-esteem scale (RSES) was used to assess self-esteem and psychosomatic symptoms. Type D personality was observed in 58.6% of the patients (n = 70) and in 21.7% of the controls (n = 60) (p < 0.001). When compared to patients with non-type D personality, those with type D personality revealed lower self-esteem and poorer health status (p < 0.05 for both), and higher anxiety and depression scores (p < 0.001 for both). In binary logistic regression analysis, the odds of FM were 3.6 times higher (OR = 3.653, 95% CI 1.547-8.625) for patients with type D personality, after adjusting for age and education level. In addition, depression (OR= 1.178, Cl 95% 1.055 - 1.316) and lower education level (OR= 0.818, Cl 95% 0.682 - 0.982) were significantly related to type D personality in FM. Type D personality is closely associated with FM. Type D personality is more common in female patients with FM when compared to healthy women. Depression and lower education level are potential confounders of type D personality in FM.

A multi-center, double-blind, randomized parallel-group Phase IV study comparing the efficacy and safety of thiocolchicoside ointment versus placebo in patients with chronic mechanical low back pain and an acute muscle spasm.

Objectives: This study aims to evaluate the efficacy and safety of thiocolchicoside (TCC) ointment treatment compared to placebo in patients with chronic mechanical low back pain (LBP) accompanied by acute muscle spasms. Patients and methods: A total of 292 adult patients (106 males, 186 females; mean age: 38.5±11.2 years; range, 18 to 64 years) were randomized to TCC group (n=147) and placebo group (n=145) in 12 centers between March 2020 and March 2021. Eight patients from each group were excluded from the analysis. The primary endpoint was pressure pain threshold (PPT) on Day 3, which was measured using a pressure algometer. Secondary endpoints were PPT on Day 7, patient, and physician Visual Analog Scales-pain (VAS-pain) on Days 3 and 7, and safety. Results: The PPT values on Day 3 was not significantly different between the treatment groups (p=0.701). Similarly, TCC and placebo group had similar VAS-pain scores over trial period (p=0.577 or higher for comparisons). Significantly higher PPT values and lower VAS-pain scores on Days 3 and 7 were observed in both groups (p<0.001 for all). In patients with a PPT value of ≥3.87, TCC arm had higher PPT on Day 3 compared to placebo (p=0.029). Three patients (two in the TCC arm and one in the placebo arm) discontinued the trial due to an adverse event. Conclusion: Topical TCC can be an appropriate option in a subset of patients with mild chronic LBP accompanied by muscle spasms. In a subset of patients with milder pain intensity, topical TCC may improve pain earlier. The results of this trial are compatible with the treatment approaches used in daily practice.

Antirheumatic drugs in older adults and polypharmacy issues.

Older individuals experience various noninflammatory and autoimmune inflammatory rheumatic diseases. Given the increased incidence of rheumatic conditions in older adults, it is of great importance for healthcare providers to be aware of the potential benefits and risks of antirheumatic drugs. The present article aims to provide a comprehensive review regarding antirheumatic drug use in older patients, particularly by focusing on safety issues and polypharmacy. Antirheumatic medications include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and disease-modifying antirheumatic drugs (DMARDs), which comprise conventional synthetic DMARDs, targeted synthetic DMARDs and biological DMARDs. Due to the alteration in drug pharmacokinetics and pharmacodynamics in old people, antirheumatic drug efficiency and safety may be different than in the younger population. Polypharmacy and multimorbidity are other potential challenges to be faced during the treatment of older patients with rheumatic diseases. The current review also discusses the strategies to minimize adverse reactions due to antirheumatic drugs.

The evaluation of nailfold capillaroscopy pattern in patients with fibromyalgia.

OBJECTIVES: This study aims to evaluate nailfold capillaroscopic pattern in patents with fibromyalgia and to assess the relation of capillaroscopic parameters with clinical variables and disease-related measures. PATIENTS AND METHODS: This cross-sectional, case-control study included 60 participants (4 males, 56 females; mean age: 44.0±8.2 years; range, 26 to 64 years) between August 2019 and November 2019. All participants were divided into two groups as the primary fibromyalgia group (n=30) who met the 2016 modified American College of Rheumatology Diagnostic Criteria for Fibromyalgia and the control group (n=30) consisting of age- and sex-matched healthy individuals. Nailfold capillaroscopy was performed by a digital microscope under a magnification of 200X. Capillary density, capillary loop diameter, number of dilated, giant and neoangiogenic capillaries, capillary shape, number of avascular areas, micro-aneurysms and micro-hemorrhages were evaluated by an assessor who was blind to the group allocation. In the fibromyalgia group, Widespread Pain Index, Symptom Severity Scale scores, and Fibromyalgia Severity scores were calculated. Health status and presence of benign joint hypermobility syndrome (BJHS) were evaluated using the Fibromyalgia Impact Questionnaire (FIQ) and revised Brighton criteria, respectively. RESULTS: Of the capillaroscopic parameters, the mean capillary loop diameter, number of micro-aneurysms, avascular areas, and neoangiogenic capillaries were significantly higher in the patient group compared to the controls (p<0.001, p=0.016, p=0.038, and p=0.04, respectively). Nailfold capillaroscopic findings did not significantly differ between the patients with (n=16) and without concomitant BJHS (n=14). Of the disease-related measures, only FIQ score showed a weak correlation with the number of dilated capillaries (p=0.324). CONCLUSION: Patients with fibromyalgia have distinct capillaroscopic patterns than healthy population. Capillaroscopic features, in general, are not related to clinical variables and disease-related measures.

Static foot posture and its relation to clinical variables in ankylosing spondylitis.

AIM: Postural abnormalities of the foot are common in rheumatic diseases. Static foot posture is a poorly studied clinical parameter in ankylosing spondylitis (AS). The aim of the study was to evaluate static foot posture in patients with AS and to determine the potential impact of clinical variables on foot posture. METHOD: Fifty patients with AS and 40 age- and sex-matched healthy controls were enrolled in the study. Disease activity was measured using the Ankylosing Spondylitis Disease Activity Score. Axial mobility was evaluated with the Bath Ankylosing Spondylitis Metrology Index three-point answer scale. Functional status was assessed by the Bath Ankylosing Spondylitis Functional Index and Health Assessment Questionnaire-Disability Index. Enthesitis and foot posture were evaluated by the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and Foot Posture Index-6, respectively. RESULTS: Patients with AS revealed significantly higher scores of foot posture index when compared with controls (P = 0.005). Abnormal foot posture (pronated and supinated) was more common in the patient group (P < 0.01). According to the multinomial logistic regression analysis, a higher MASES score was associated with supinated foot posture in AS patients (odds ratio 1.47, 95% confidence interval 1.03-2.09, P = 0.035). In addition, supinated foot posture was associated with enthesitis of the Achilles tendon (P = 0.002). CONCLUSION: Enthesitis is related to deteriorated static foot posture in patients with AS. Enthesitis of the Achilles tendon is closely associated with the supinated foot posture.