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Abstract Background: Coexisting fibromyalgia (FM) to psoriatic arthritis (PsA) has been identified and it has been associated with more severe symptoms, impaired function, and greater disability. It was aimed to explore the effect of the presence of FM on fatigue in patients with PsA comparing with controls. Methods: Fifty patients with PsA and 34 sex-age matched controls were enrolled. In patients; pain was assessed by Visual Analogue Scale, disease activity by DAS-28, enthesitis by The Leeds Enthesitis Index. Fatigue level of all participants was evaluated by Multidimensional Assessment of Fatigue. In all participants, FM was determined according to 2010 American College of Rheumatology criteria. Results: Seventeen patients with PsA (34%) and 4 controls (11.8%) were diagnosed with FM and all of them were women. There was significant difference between the patients and controls in terms of presence of FM (p < 0.05). Patients' fatigue scores were significantly higher than controls' (p = 0.001). There were significant differences between the PsA patients with and without FM with regard to gender, enthesitis, DAS-28 and pain scores (p < 0.05); fatigue scores (p < 0.001). The significant effect of the presence of FM on fatigue was found by univariate analysis of variance in patients (p < 0.001). Conclusion: It was observed that FM presence and fatigue were more common in PsA patients than controls and comorbid FM had significant effect on fatigue in these patients. Physicians should be aware of the possibility of concomitant FM in patients with PsA.

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Abstract Background: The aims of this article were to assess the prevalence of nephrolithiasis and the factors associated with nephrolithiasis in Brazilian patients with primary gout. Methods: One hundred twenty-three patients with primary gout were recruited from a tertiary referral hospital in São Paulo, Brazil. All patients underwent ultrasonography and had their clinical and laboratory characteristics assessed. Results: One hundred fifteen (93.5%) patients were male, with a mean age of 62.9 ± 9.4 years. Twenty-three (18.7%) patients had asymptomatic nephrolithiasis (detected only by ultrasonography), 7 (6.0%) had symptomatic nephrolithiasis (detected by ultrasonography and a positive clinical history), and 13 (10.0%) had a history of kidney stones, but ultrasonography at evaluation did not show nephrolithiasis. Therefore, 35.0% of the patients had nephrolithiasis (detected either by ultrasonography and/or a positive clinical history). Nephrolithiasis was associated with male gender (43 [100%] vs 72 [90%], p = 0.049), the use of potassium citrate (13 [30.2%] vs 0, p < 0.001) and the use of medications for diabetes (10 [23.3%] vs 8 [10%], p = 0.047) and dyslipidemia (15 [34.9%] vs 10 [12.5%], p = 0.003); benzbromarone had an inverse association with nephrolithiasis (21 [48.8%] vs 55 [68.8%], p = 0.030). In patients with and without nephrolithiasis, no differences were found in the laboratory and ultrasonography characteristics, including serum uric acid levels, urinary uric acid excretion and urine pH. Conclusions: The prevalence of nephrolithiasis in primary gout was 35.0%, and 18.7% of the patients were asymptomatic. Nephrolithiasis was associated with male gender, diabetes and dyslipidemia. A positive history of nephrolithiasis probably biased the prescription of potassium citrate and benzbromarone.

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Abstract Background: Granulomatosis with polyangiitis (GPA) is a granulomatous necrotizing vasculitis with high morbidity and mortality. Anti-neutrophil cytoplasmic antibody is a valuable diagnostic marker, however its titer lacks predictive value for the severity of organ involvement. Platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) has been regarded as a potential marker in assessing systemic inflammation. We aimed to explore the value of PLR and MPV in the assessment of disease activity and manifestations of disease in GPA. Methods: 56 newly diagnosed GPA patients and 53 age-sex matched healthy controls were included in this retrospective and cross-sectional study with comparative group. Complete blood count was performed with Backman Coulter automatic analyzer, erythrocyte sedimentation rate (ESR) with Westergen method and C-reactive protein (CRP) levels with nephelometry. The PLR was calculated as the ratio of platelet and lymphocyte counts. Result: Compared to control group, ESR, CRP and PLR were significantly higher and MPV significantly lower in GPA patients. In patients group, PLR was positively correlated with ESR and CRP (r = 0.39, p = 0.005 and r = 0.51, p < 0.001, respectively). MPV was negatively correlated with ESR and CRP (r = – 0.31, p = 0.028 and r = – 0.34 p = 0.014, respectively). Patients with renal involvement had significantly higher PLR than patients without renal involvement (median:265.98, IQR:208.79 vs median:180.34 IQR:129.37, p = 0.02). PLR was negatively correlated with glomerular filtration rate (r = – 0.27, p = 0.009). A cut-off level of 204 for PLR had 65.6% sensitivity and 62.5 specificity to predict renal involvement. Conclusion: PLR exhibit favorable diagnostic performance in predicting renal involvement in patients with GPA.

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Abstract Background: Nephritis occurs frequently in systemic lupus erythematosus (SLE) and may worsen disease morbidity and mortality. Knowing all characteristics of this manifestation helps to a prompt recognition and treatment. Aim: To compare the differences in clinical data, serological profile and treatment response of nephritis of early and late onset. Methods: Retrospective study of 71 SLE patients with biopsy proven nephritis divided in early nephritis group (diagnosis of nephritis in the first 5 years of the disease) and late nephritis (diagnosis of nephritis after 5 years). Epidemiological, serological, clinical and treatment data were collected from charts and compared. Results: In this sample, 70. 4% had early onset nephritis and 29.6% had late onset. No differences were noted in epidemiological, clinical, serological profile, SLICC and SLEDAI, except that late onset nephritis patients were older at nephritis diagnosis (p = 0.01). Regarding renal biopsy classification, C3 and C4 levels, serum creatinine, 24 h proteinuria and response rate to treatment the two groups were similar (p = NS). Patients with early onset had lower levels of hemoglobin at nephritis onset than those of late onset (p = 0.02). Conclusions: Most of SLE patients had nephritis in the first 5 years of disease. No major differences were noted when disease profile or treatment outcome of early and late onset nephritis were compared.

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Abstract Background: Fabry disease (FD) is an X-linked lysosomal disorder due to mutations in the GLA gene resulting in defective enzyme alpha-galactosidase A. FD patients are frequently misdiagnosed, commonly for rheumatic diseases. Determining pathogenicity of a mutation depends of in silico predictions but mostly on available clinical information and interpretation may change in light of evolving knowledge. Similar signs and symptoms in carriers of GLA gene genetic variants of unknown significance or of benign variants may hamper diagnosis. This study reviews rheumatic and immune-mediated manifestations in a cohort of Brazilian FD patients with classic mutations and also in subjects with GLA gene A143T and R118C mutations. Misdiagnoses, time to correct diagnosis or determination of GLA gene status, time to treatment initiation and reasons for treatment prescription in A143T and R118C subjects are reviewed. Methods: Genotype confirmed classic FD patients (n = 37) and subjects with GLA gene mutations A143T and R118C (n = 19) were referred for assessment. Subjects with R118C and A143T mutations had been previously identified during screening procedures at hemodialysis units. All patients were interviewed and examined by a rheumatologist with previous knowledge of disease and/or mutation status. A structured tool developed by the authors was used to cover all aspects of FD and of common rheumatic conditions. All available laboratory and imaging data were reviewed. Results: Thirty-seven consecutive FD patients were interviewed – 16 male / 21 female (mean age: 43.1 years) and 19 consecutive subjects with GLA gene mutations R118C and A143T were evaluated – 8 male / 11 female (mean age: 39.6 years); 15 [R118C] / 4 [A143T]. Misdiagnosis in FD patients occurred in 11 males (68.8%) and 13 females (61.9%) of which 10 males and 9 females were previously diagnosed with one or more rheumatic conditions, most frequently rheumatic fever or “rheumatism” (unspecified rheumatic disorder). Median time for diagnosis after symptom onset was 16 years (range, 0–52 years). Twenty-two patients were treated with enzyme replacement therapy (ERT) – 13 male and 9 female. Median time to ERT initiation after FD diagnosis was 0.5 years (range, 0–15 years). Rheumatic manifestations occurred in 68.4% of R118C and A143T subjects. Two subjects had been prescribed ERT because of renal disease [R118C] and neuropsychiatric symptoms [A143T]. Conclusion: Misdiagnoses occurred in 64.8% of FD patients, most frequently for rheumatic conditions. Median time for correct diagnosis was 16 years. Rheumatic manifestations are also frequent in subjects with GLA gene R118C and A143T mutations. These results reinforce the need to raise awareness and increase knowledge about Fabry disease among physicians, notably rheumatologists, who definitely have a role in identifying patients and determining disease burden. Decision to start treatment should consider expert opinion and follow local guidelines.

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Abstract Background: EpiFibro (Brazilian Epidemiological Study of Fibromyalgia) was created to study patients with fibromyalgia (FM). Patients were included since 2011 according to the classification criteria for FM of the American College of Rheumatology of 1990 (ACR1990). Objective: To analyze the therapeutic measures prescribed by Brazilian physicians. Materials and methods: Cross-sectional study of a multicenter cohort. The therapeutic measures were described using descriptive statistics. Results: We analyzed 456 patients who had complete data in the registry. The mean age was 54.0 ± 11.9 years; 448 were women (98.2%). Almost all patients (98.4%) used medications, 62.7% received health education, and less than half reported practicing physical exercise; these modalities were often used in combination. Most patients who practiced exercises practiced aerobic exercise only, and a significant portion of patients combined it with flexibility exercises. The most commonly used medication was amitriptyline, followed by cyclobenzaprine, and a minority used medication specifically approved for FM, such as duloxetine and pregabalin, either alone or in combination. Combinations of two or three medications were observed, with the combination of fluoxetine and amitriptyline being the most frequent (18.8%). Conclusion: In this evaluation of the care of patients with FM in Brazil, it was found that the majority of patients are treated with a combination of pharmacological measures. Non-pharmacological methods are underused, with aerobic exercise being the most commonly practiced exercise type. The most commonly prescribed single drug was amitriptyline, and the most commonly prescribed combination was fluoxetine and amitriptyline. Drugs specifically approved for FM are seldom prescribed.

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Abstract Background: The current diagnostic cornerstone for septic arthritis contains gram stains, bacterial culture, and cell count with a differential of aspirated synovial fluid. Recently, a synovial leukocyte esterase (LE) test has been used for diagnosing septic arthritis. Since this test measures the esterase activity of leukocytes, there is always a dilemma for using this test in patients with inflammatory arthritis. Methods: We collected the synovial fluid specimens as part of the general diagnostic protocol for patients suspected of Juvenile Idiopathic Arthritis (JIA) or Septic Arthritis (SA). Each group included 34 patients. We compared the result of the synovial LE test with the result of the culture of each patient. Results: The mean ages of patients were 64.14 ± 31.27 and 50.88 ± 23.19 months in the JIA group and septic arthritis group, respectively. The LE test results were positive in 30 specimens, trace in 3 and negative in one in the first-time test and were positive in 31 specimens and trace in 3 in the second-time test, while it was negative in all patients with JIA. Hence, the sensitivity of the synovial LE test was 80.8%, the specificity, PPV, and NPV were 78.6, 70.0, 86.8% respectively based on a positive culture. Conclusion: The leukocyte esterase strip test can be used as a rapid, bedside method for diagnosing or excluding bacterial infections in different body fluids. The synovial LE test can be used as an accurate test to rapidly rule in or out an acute articular bacterial infection, even in patients with concurrent inflammatory arthritis.

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Abstract İntroduction: Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation. Anti-interleukin-1 (Anti-IL-1) treatments are recommended in colchicine resistant and/or intolerant FMF patients. This study aims to evaluate the efficacy of anakinra and canakinumab in FMF patients that are resistant/intolareted to colchicine or complicated with amyloidosis. Methods: Between January 2014 and March 2019, 65 patients following-up at Sivas Cumhuriyet University (Medical Faculty Rheumatology-Internal Medicine Department) who were diagnosed with FMF according to the criteria of Tel-Hashomer were included in the study. The laboratory values and clinical features of patients and disease activities were recorded at least every 3 months, and these data were analyzed. Results: Forty-one (63.1%) patients used anakinra (100 mg/day) and 24 (36.9%) patients used canakinumab (150 mg/8 week). The median duration of anti-IL-1 agents use was 7 months (range, 3–30). Fifteen (23.1%) cases were complicated with amyloidosis. Seven (10.8%) patients had renal transplantation. Overall, the FMF 50 score response was 96.9%. In the group that had a glomerular filtration rate (GFR) ≥ 60 ml/min/m2, the median proteinuria decreased from 2390 mg/day (range, 1400–7200) to 890 mg/day (range, 120–2750) (p = 0.008). No serious infections were detected, except in one patient. Conclusions: Anti-IL-1 agents are effective and safe in the treatment of FMF patients. These agents are particularly effective at reducing proteinuria in patients with GFR ≥ 60 ml/min/m2, but less effective in cases with FMF associated with arthritis and sacroiliitis. Large and long follow-up studies are now needed to establish the long-term effects of these treatments.

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Abstract Background: The neutrophil/ lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have the potential to be inflammatory markers that reflect the activity of many inflammatory diseases. The aim of this study was to evaluate the NLR and PLR as potential markers of disease activity in patients with ankylosing spondylitis. Methods: The study involved 132 patients with ankylosing spondylitis and 81 healthy controls matched in terms of age and gender. Their sociodemographic data, disease activity scores using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and white blood cell, neutrophil, lymphocyte and platelet counts were recorded. The patients with ankylosing spondylitis were further divided according to their BASDAI scores into patients with inactive disease (BASDAI < 4) and patients with active disease (BASDAI ≥4). The correlations between the NLR, PLR and disease activity were analysed. Results: There was a statistically significant difference in the NLR and PLR between the active and inactive ankylosing spondylitis patients (2.31 ± 1.23 vs. 1.77 ± 0.73, p = 0.002), (142.04 ± 70.98 vs. 119.24 ± 32.49, p < 0.001, respectively). However, there was no significant difference in both the NLR and PLR between the healthy control group and ankylosing spondylitis patients (p > 0.05). In addition, the PLR was significantly higher in both the active and inactive groups compared to those in the healthy control group (142.04 ± 70.98 vs. 99.32 ± 33.97, p = 0.014), (119.24 ± 32.49 vs. 99.32 ± 33.97, p = 0.019). The BASDAI scores were positively correlated with the PLR (r = 0.219, p = 0.012) and the NLR, but they were not statistically significant with the later (r = 0.170, p = 0.051). Based on the ROC curve, the best NLR cut-off value for predicting severe disease activity in ankylosing spondylitis patients was 1.66, with a sensitivity of 61.8% and a specificity of 50.6%, whereas the best PLR cut-off value was 95.9, with a sensitivity of 70.9% and a specificity of 55.5%. Conclusion: The PLR may be used as a useful marker in the assessment and monitoring of disease activity in AS together with acute phase reactants such as the ESR.

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Abstract Introduction: Atrial fibrillation (AF) is the leading cause of ischemic stroke and is one of the most common arrhythmias. Previous studies have shown that impaired diastolic functions, P wave dispersion (Pd), and prolonged atrial conduction times (ACT) are associated with increased incidence of atrial fibrillation (AF). The aim of this study was to evaluate diastolic functions, Pd, and ACT in fibromyalgia syndrome (FMS) patients to determine whether there is an increase in the risk of developing AF. Methods: The study included a total of 140 female patients (70 FMS group, 70 healthy control group). Pd was evaluated using 12 lead electrocardiography (ECG), and diastolic functions and ACT with echocardiography. The ECG and echocardiographic evaluations were performed by different cardiologists blinded to the clinical information of the subjects. Results: There was no difference between the two groups in laboratory and clinical parameters. Patients with FMS had significantly higher echocardiographic parameters of ACT known as left-sided intra-atrial (13.9 ± 5.9 vs. 8.1 ± 1.8, p < 0.001), right-sided intra-atrial (21.9 ± 8.2 vs. 10.4 ± 3.5, p < 0.001) and interatrial [40 (25–64) ms vs. 23 (14–27) ms p < 0.001] electromechanical interval (EMI) compared with the control group. Pd was significantly greater in the FMS group compared with the control group [46 (29–62) ms vs. 32 (25–37) ms, p < 0.001]. In the FMS group, there was no significant relationship of the echocardiographic parameters of ACT, Pmax and Pd with age, E/A ratio and deceleration time (DT); while all these five parameters were significantly correlated with left atrial dimension, isovolumetric relaxation time (IVRT), fibromyalgia impact questionnaire (FIQ) and visual analogue scale (VAS). There was a strong correlation between FIQ and VAS and echocardiographic parameters of ACT, Pmax and Pd. Conclusions: Impaired diastolic functions, an increase in Pd, and prolongation of ACT were observed in FMS. Current disorders are thought to be associated with an increased risk of AF in FMS. The risk of developing AF increases with the severity of FMS and clinical progression.

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Abstract Background: Urinary parameters, anti-dsDNA antibodies and complement tests were explored in patients with childhood-Systemic Lupus Erythematosus (cSLE) early-onset lupus nephritis (ELN) from a large multicenter cohort study. Methods: Clinical and laboratory features of cSLE cases with kidney involvement at presentation, were reviewed. Disease activity parameters including SLEDAI-2 K scores and major organ involvement at onset and follow up, with accrued damage scored by SLICC-DI, during last follow up, were compared with those without kidney involvement. Autoantibodies, renal function and complement tests were determined by standard methods. Subjects were grouped by presence or absence of ELN. Results: Out of the 846 subjects enrolled, mean age 11.6 (SD 3.6) years; 427 (50.5%) had ELN. There was no significant difference in the ELN proportion, according to onset age, but ELN frequency was significantly higher in non-Caucasians (p = 0.03). Hematuria, pyuria, urine casts, 24-h proteinuria and arterial hypertension at baseline, all had significant association with ELN outcome (p < 0.001). With a similar follow up time, there were significantly higher SLICC-DI damage scores during last follow up visit (p = 0.004) and also higher death rates (p < 0.0001) in those with ELN. Low C3 (chi-square test, p = 0.01), but not C3 levels associated significantly with ELN. High anti-dsDNA antibody levels were associated with ELN (p < 0.0001), but anti-Sm, anti-RNP, anti-Ro, anti-La antibodies were not associated. Low C4, C4 levels, low CH50 and CH50 values had no significant association. High erythrocyte sedimentation rate (ESR) was associated with the absence of ELN (p = 0.02). Conclusion: The frequency of ELN was 50%, resulting in higher morbidity and mortality compared to those without ELN. The urinary parameters, positive anti-dsDNA and low C3 are reliable for discriminating ELN.

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Abstract Introduction: Takayasu's arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset. Methods: Women aged more than 18 years with Takayasu's arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI. TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR. Results: Of the 64 women interviewed, aged 29 (24–38) years and disease duration 5 (4–10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18–30) years. Type 5 disease was the most common ( n = 32, 59.3%), and an equal number of patients had Ishikawa's class I and II disease ( n = 26, 40.6%). Median ITAS ( n = 44) was 13 (7–16), DEI. Tak 12.5 (9–16.75) and TADS 8 (6.5–10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8–8.5), P < 0.001] as well as fetal complications [RR = 2.0 (1.2–3.4), p = 0.001]. Hypertension was the most common maternal complication and occurred most often in the last trimester. The baby weight at birth was lower in pregnancies after disease (2.3 vs. 3.0, p = 0.01). Wong's score greater than or equal to 4 predicted lower birth weight ( p = 0.04). ITAS, ITAS-A, DEI. Tak and TADS could not predict obstetric outcomes, and ITAS score exhibited moderate correlation with DEI. Tak ( r = 0.78) and TADS ( r = 0.58). Conclusion: Women with TA suffer from extremely high risk of poor maternal and foetal outcomes. Wong's scoring can be useful to predict birth weight.

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Abstract Objective: Correlate serum magnesium (Mg) and Calcium (Ca) levels with body composition and metabolic parameters in women with fibromyalgia (FM). Patients and methods: Cross-sectional study compared with a control group paired by age and body mass index (BMI) of adult women diagnosed with fibromyalgia. All participants went through assessment of their body composition through dual-energy X-ray absorptiometry (DXA) and had blood samples collected for dosing of Mg, Ca, C-reactive Protein (CRP), lipidogram and glycemia. Results: 53 women with FM (average age 48.1 ±8.2 years, average BMI 26.6 ±4.5 kg/m2) and 50 control women (average age 47.1 ±9.9 years, average BMI 25.6 ± 3.6 kg/m2) participated in the study. Serum levels turned out to have inverse correlation with CRP in the FM group (r = −0.29, p = 0.03) and with BMI and glycemia in the control group (r = 0.31; p = 0.02 and r = 0.48; p = 0.0004 respectively). Serum levels of calcium correlated with triglycerides (r = 0.29; p = 0.03) in the FM group and with glycemia in the control group (r = 0.64; p = 0.0001). Conclusions: In patients with FM, magnesemia turned out to have inverse correlation with CRP and calcemia had positive association with triglycerides.

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Abstract Background: In Brazil, socioeconomic differences in the incidence of rheumatoid arthritis (RA) have been demonstrated, which are important in the formulation of hypotheses regarding the association between environmental factors, lifestyle and the risk of disease development. This study examines how the socioeconomic condition of the patient with RA in Brazil, assessed according to social class, educational level, employment situation and use of caregivers, affects the times between the beginning of symptoms and diagnosis and the beginning of the use of disease-modifying antirheumatic drugs, as well as the presence of erosive disease and functional status. Methods: This work is part of a multicentric study called REAL - Rheumatoid Arthritis in Real Life in Brazil, which is a prospective observational cohort study. Results: As described in the REAL study, we included a total of 1115 patients. It was noted that patients with an educational classification of up to second grade incomplete presented with erosion percentages above those with a higher grade complete. Patients with caregivers presented a higher percentage of erosion than patients without caregivers. We verified that patients from economic classes above B2 presented fewer occurrences of erosion than those from classes C2, D-E. We also analyzed the average time differences from the beginning of symptoms and diagnosis and the beginning of treatment, according to academic level, erosion and economic classification. Patients with first grade complete showed an HAQ-DI averages higher than those with second grade complete. The patients who had employment showed lower HAQ-DI averages than patients who were not employed. The patients with erosion showed an HAQ-DI value higher than those without erosion. Patients with caregivers showed an HAQ-DI average higher than that of without caregivers. Conclusion: This study showed that the therapeutic window of RA is not being reached, and therefore we should have a policy to expand and ensure access to public health for all patients, especially those with lower levels of education and income. Trial registration: This study was approved by the National Commission of Ethics in Research.

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Abstract Background: The mat Pilates method is the therapeutic modalities which can be used in fibromyalgia treatment. Although there are no well-designed studies that prove the effectiveness of the mat Pilates method in this population. The objective was to evaluate the effectiveness of the mat Pilates method for improving symptoms in women with fibromyalgia. Methods: A single blind randomized controlled trial in which 42 women with fibromyalgia were randomized into two groups: mat Pilates and aquatic aerobic exercise. The exercises were performed twice a week for 12 weeks. Two evaluations were performed: one at baseline (T0), and another at 12 weeks after randomization (T12). The primary outcome was pain measured by the Visual Analogue Scale (VAS). Secondary outcomes were function (Fibromyalgia Impact Questionnaire), sleep (Pittsburgh Sleep Quality Index [PSQI]), quality of life (Short Form 36 [SF-36]), fear avoidance (Fear Avoidance Beliefs Questionnaire [FABQ-BR]) and pain catastrophizing (Pain-Related Catastrophizing Thoughts Scale [PRCTS]). Results: There was improvement in both groups in relation to pain and function (p < 0.05). The aspects related to quality of life and the FABQ questionnaire only showed improvement in the mat Pilates group (p < 0.05). There was improvement in the PSQI and PRCTS variables only in the aquatic aerobic exercise group (p < 0.05), but no differences were observed between the groups for any of the evaluated variables. Conclusion: Significant improvements were observed in the two groups in relation to the disease symptoms, and no differences were observed between mat Pilates and aquatic aerobic exercise in any of the measured variables. Trial registration: ClinicalTrials.gov Identifier (NCT03149198), May 11, 2017. Approved by the Ethics Committee of FACISA/UFRN (Number: 2.116.314).

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Abstract Background: Fibromyalgia syndrome (FMS) has adverse effects on the quality of sleep. The aim of this study was to investigate the validity and reliability of Jenkins Sleep Scale (JSS-TR) in Turkish FMS patients. Methods: FMS patients who met the 2016 fibromyalgia diagnostic criteria were included in the study. Clinical and demographic data of the patients were noted. The relationship between this scale and other functional parameters such as Pittsburgh Sleep Quality Index (PSQI), European Quality of Life Scale-5 Dimensions (EQ-5D), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI) was examined. Fibromyalgia Impact Questionnaire (FIQ) was used to evaluate the functional status of the patients and the progression of the disease. Test-retest reliability was calculated by re-applying the questionnaire to patients at 2-week intervals. Duloxetine treatment was initiated in newly diagnosed patients and sensitivity to change was tested at the end of the treatment. Spearman correlation coefficient was used. P < 0.05 was accepted as significant. Results: Eighty-one FMS patients (71 females, 10 males) were included in the study. The mean age was 44.2 ± 10.7 years. The strongest correlation of JSS-TR was with another sleep questionnaire, PSQI (rho = 0.79, p < 0.0005). The correlation with other functional parameters and FIQ was moderate. In test-retest validity, intraclass correlation coefficient was found to be 0.98 (p < 0.0005). Chronbach α value calculated for internal consistency was found to be 0.741. Conclusions: JSS-TR is a valid, simple and feasible sleep instrument that can be easily applied to FMS patients both in researches and clinical settings.

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Abstract Objective: To translate and cross-culturally adapt the Home Falls and Accidents Screening Tool Self-report Into Brazilian Portuguese and to correlate with the history of falls. Methods: The translation and transcultural adaptation process followed international parameters. The Home Falls and Accidents Screening Tool Brazil Self-report, the Mini-Mental State Examination and the history of falls were applied to 10 elderly in the pre-test and to 41 in the final. Demographic and anthropometric data were also evaluated. Spearman correlation coefficient was performed. Results: The participants considered the questionnaire easy to understand and did not report any doubts to answer the final version. There was significant correlation between: Home Falls and Accidents Screening Tool Brazil Self-report score and number of falls (p = 0.31, p = 0.02) and the lighting and bathroom domains with presence of falls at home (p = 0.44, p = 0.00 and p = 0.33, p = 0.02, respectively). The questionnaire indicated fall's risk scoring, 10(±2). Conclusion: The Home Falls and Accidents Screening Tool Brazil Self-report showed to be comprehensible and feasible tool for self-assessment of domiciliary falls risk in Brazilian older people. The scores indicated fall's risk and were associated with the history of falls.

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Abstract Background: Rheumatoid arthritis (RA) is an inflammatory and chronic autoimmune disease that leads to muscle mass loss and functional capacity impairment, potentiated by physical inactivity. Despite evidences demonstrate neuromuscular impairments in RA patients, aging effects may have masked the results of similar previous studies. The aim of study was to verify (i) the effects of RA on functional capacity and muscle properties in middle-aged patients and (ii) the association between age, clinical characteristics, quadriceps muscle properties and functional capacity. Methods: Thirty-five RA women and 35 healthy age-matched women were compared with the following outcomes: (i) physical activity level through the International Physical Activity Questionnaire (IPAQ); (ii) timed-up and go (TUG) test; (iii) isometric knee extensor muscular strength; and (iv) vastus lateralis muscle activation and muscle architecture (muscle thickness, pennation angle and fascicle length) during an isometric test. An independent Student t-test and partial correlation (controlled by physical activity levels) were performed, with p < 0.05. Results: Compared with healthy women, RA presented (i) lower physical activity level (- 29.4%; p < 0.001); (ii) lower isometric knee extensor strength (- 20.5%; p < 0.001); (iii) lower TUG performance (- 21.7%; p < 0.001); (iv) smaller muscle thickness (- 23.3%; p < 0.001) and pennation angle (- 14.1%; p = 0.011). No differences were observed in muscle activation and fascicle length. Finally, the correlation demonstrated that, with exception of TUG, muscle strength and muscle morphology were not associated with age in RA, differently from healthy participants. Conclusion: Middle-aged RA patients’ impairments occurred due to the disease independently of the aging process, except for functional capacity. Physical inactivity may have potentiated these losses.

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Abstract Introduction Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. Objective – methods Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. Results In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls ( p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls ( p < 0.001). Conclusion We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.

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Abstract Background: Currently, magnetic resonance imaging (MRI) is used to evaluate active inflammatory sacroiliitis related to axial spondyloarthritis (axSpA). The qualitative and semiquantitative diagnosis performed by expert radiologists and rheumatologists remains subject to significant intrapersonal and interpersonal variation. This encouraged us to use machine-learning methods for this task. Methods: In this retrospective study including 56 sacroiliac joint MRI exams, 24 patients had positive and 32 had negative findings for inflammatory sacroiliitis according to the ASAS group criteria. The dataset was randomly split with ∼ 80% (46 samples, 20 positive and 26 negative) as training and ∼ 20% as external test (10 samples, 4 positive and 6 negative). After manual segmentation of the images by a musculoskeletal radiologist, multiple features were extracted. The classifiers used were the Support Vector Machine, the Multilayer Perceptron (MLP), and the Instance-Based Algorithm, combined with the Relief and Wrapper methods for feature selection. Results: Based on 10-fold cross-validation using the training dataset, the MLP classifier obtained the best performance with sensitivity = 100%, specificity = 95.6% and accuracy = 84.7%, using 6 features selected by the Wrapper method. Using the test dataset (external validation) the same MLP classifier obtained sensitivity = 100%, specificity = 66.7% and accuracy = 80%. Conclusions: Our results show the potential of machine learning methods to identify SIJ subchondral bone marrow edema in axSpA patients and are promising to aid in the detection of active inflammatory sacroiliitis on MRI STIR sequences. Multilayer Perceptron (MLP) achieved the best results.

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Abstract Background: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. Methods: Mice received 100 μg/25 μL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. Results: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. Conclusion: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.

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Abstract Background The severity of nail disease, the presence of arthralgia and fatigue are predictors of development of psoriatic arthritis (PsA) in patients with psoriasis (Pso). In children, little is known about the musculoskeletal (MSK) impairment in patients with Pso and its effect on health-related quality of life (HRQoL). Objectives To determine the frequencies of pain and MSK inflammation (i.e., arthritis, enthesitis, and sacroiliitis) among children and adolescents with Pso and its relationship to HRQoL and fatigue. Methods Pediatric patients with Pso underwent a rheumatologic physical examination to evaluate synovitis, enthesalgia, sacroiliac joint (SIJ) pain and tender points of fibromyalgia. The core set of domains recommended by the GRAPPA - OMERACT to be measured in PsA studies was assessed. Ultrasound (US) was performed in clinical cases of enthesitis, and magnetic resonance imaging (MRI) was performed in cases of SIJ pain. Results Forty-three participants (10 ± 2.9 years old) were evaluated. Pain on palpation of the entheses was observed in 10 (23.2%) patients and pain on SIJ palpation was observed in 3 (7%). No patient presented with synovitis; one presented with enthesitis on US, but MRI did not confirm sacroiliitis in any case. Patients with MSK pain had greater skin disease severity (PASI 5.4 vs. 2, p < 0.01), worse fatigue, and lower HRQoL scores on all instruments used. The estimated risk of HRQoL impairment was eight times higher in the presence of MSK pain, which was an independent predictive factor. With a NAPSI greater than 30, the probability of pain was greater than 80%. Conclusion MSK pain is frequent among children with Pso, related to the severity of skin and nail disease, and negatively affects HRQoL. The typically used complementary exams might not detect the inflammatory process caused by Pso.

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Abstract Objectives Fibromyalgia Syndrome (FMS), is a chronic pain disorder with poorly understood pathophysiology. In recent years, repetitive transcranial magnetic stimulation (rTMS) has been recommended for pain relief in various chronic pain disorders. The objective of the present research was to study the effect of low frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) on pain status in FMS. Methods Ninety diagnosed cases of FMS were randomized into Sham-rTMS and Real-rTMS groups. Real rTMS (1 Hz/1200 pulses/8 trains/90% resting motor threshold) was delivered over the right DLPFC for 5 consecutive days/week for 4 weeks. Pain was assessed by subjective and objective methods along with oxidative stress markers. Patients were followed up for 6 months (post-rTMS;15 days, 3 months and 6 months). Results In Real-rTMS group, average pain ratings and associated symptoms showed significant improvement post rTMS. The beneficial effects of rTMS lasted up to 6 months in the follow-up phase. In Sham-rTMS group, no significant change in pain ratings was observed. Conclusion Right DLPFC rTMS can significantly reduce pain and associated symptoms of FMS probably through targeting spinal pain circuits and top-down pain modulation . Trial registration: Ref No: CTRI/2013/12/004228.

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Abstract Background: Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more effective and safer. This study aimed to compare evidence of the efficacy and safety of duloxetine compared with amitriptyline in the treatment of adult patients with fibromyalgia. This work contributes to guiding clinicians on the use of duloxetine or amitriptyline for the treatment of fibromyalgia and provides information for public health decision-makers. Methods: Overview of systematic reviews of clinical trials comparing duloxetine and amitriptyline in the treatment of fibromyalgia. The reviews were screened in Cochrane, PubMed, EMBASE, and SRDR with no restrictions on language and year of publication, considering that the research was conducted in July 2018 and updated until May 2020. The selection was based on the following criteria: adult patients with a diagnosis of fibromyalgia treated with duloxetine or amitriptyline, comparing the efficacy and safety in pain, fatigue, sleep, and mood disorder symptoms and quality of life, in addition to the acceptability of these antidepressants. The methodological quality and strength of evidence were assessed using the AMSTAR and GRADE instruments. Results: Eight systematic reviews were selected. Amitriptyline had low evidence for pain, moderate evidence for sleep and fatigue, and high evidence for quality of life. Duloxetine had high quality of evidence in patients with mood disorders. With low evidence, duloxetine has higher acceptability, but is safer in older patients, while amitriptyline is safer for non-elderly individuals. Conclusion: Both antidepressants are effective in the treatment of fibromyalgia, differing according to the patient's symptoms and profile. Registration: PROSPERO: CRD42019116101.

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Abstract Background: Juvenile Idiopathic Arthritis (JIA) and its related symptoms (e.g. pain) have been associated with interference in the daily life of adolescents with JIA including their friendships. There is little research in that sense and in consequence, interventions designed to improve this area. The objectives of this study are 1) to gain knowledge about the needs of adolescents with JIA, particularly focused on their friendships; 2) to explore the potential of the Internet to help them, and 3) to determine what kind of online resource would be the best and what elements it should include. Methods: To achieve the proposed objectives we designed a qualitative study including two phases: the first one exploratory (semi-structured interviews) and the following, confirmatory (online focus group). Results: 14 adolescents were interviewed and 7 participated in the focus group. They reported some social challenges related to their illness: feeling different, criticized by peers, or not believed. Additionally, they specified some of the coping strategies they used, such as disclosing to others that they have JIA, using communication skills, maintaining activities with friends, trying to minimize pain, and ignoring negative comments. Adolescents considered an online resource useful and mentioned that they would like to find general information and to have the possibility to interact with others. They considered Instagram and WhatsApp as good platforms to implement the online resource. Conclusions: According to their perceptions, adolescents with JIA can benefit from an online resource which delivers information, strategies and facilitates interaction with others.

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Abstract Background: To verify the validity of the 2016-revised Fibromyalgia Survey Questionnaire (FSQ) by telephone interview compared to self-administration and to produce a valid version of FSQ in Brazilian Portuguese language. Methods: The Brazilian version of FSQ was produced following the recommendations for cross-cultural adaptation. Validity of Brazilian FSQ self-administration was assessed by checking agreement of its results with fibromyalgia diagnosis according the 1990 American College of Rheumatology (ACR) criteria. Reproducibility and validity of FSQ by telephone were assessed by comparing its results with the previous FSQ self-administration. Results: A Brazilian Portuguese version (FSQ-Brazil) was produced. FSQ-Brazil had good internal consistency (Cronbach's alpha between 0.73 and 0.94). Agreement between the results obtained by self-administration of FSQ-Brazil and by telephone interview was substantial or almost perfect for almost all questions about pain sites and all questions about other somatic symptoms (Cohen's kappa higher than 0.6). There were small but significant bias toward higher scores of widespread pain index and fibromyalgia severity scale in the telephone interview compared to self-administration. Fibromyalgia definition by self-administration and telephone interview with FSQ-Brazil both revealed substantial agreement with the diagnosis based on ACR 1990 criteria (Cohen's kappa 0.62 and 0.65; respectively). Conclusions: FSQ-Brazil demonstrated good internal consistency, reproducibility and validity both by self-administration and by telephone interview. However, caution must be taken with the interpretation of quantitative scores of widespread pain index and symptoms severity scale, which slightly differed according the method (self-administration or interview) in our study.

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Abstract Background: Annexins are a group of conserved proteins which exert several regulatory functions on various cellular activities. Increased frequency and levels of antibodies against annexin V have already been observed in several autoimmune diseases including systemic sclerosis (SSc), but their role as a vascular biomarker is unknown. The aim of this study was to determine the serum levels and the dynamical behavior of anti-annexin V antibodies over a 24 months follow-up in patients with SSc. Methods: In this bicentric cross-sectional study, 70 patients with SSc were consecutively selected from March 2016 to April 2017. Demographic and clinical features, including the presence of active DUs, were collected. Serum anti-annexin V IgG and IgM antibodies were measured at baseline and after 6, 12 and 24 months of follow-up. Videocapillaroscopy was performed in all patients. Results: Among the 70 SSc patients included anti-annexin V IgG was found in 11 patients (15.7%) (range of 15.88–39.48 U/mL) and anti-annexin V IgM in 10 patients (14.3%) (range of 14.16-22.69 U/mL) at baseline. During follow-up, the number of patients who were positive for anti-annexin V IgG and IgM remained stable over 24 months. Among the patients with positive anti-annexin V IgG at baseline the frequency of patients with necrosis or amputation of extremities, forced vital capacity less than 70% and pulmonary arterial hypertension (PAH) was significantly higher than in patients with negative anti-annexin V IgG antibodies. Patients with anti-annexin V IgG had also a higher Raynaud's Condition Score and a higher Health Assessment Questionnaire Disability Index (HAQ-DI) than patients without these antibodies at baseline. Patients with positive anti-annexin V IgM at baseline presented a higher frequency of PAH, compared to those with negative anti-annexin V IgM at baseline. Conclusions: Anti-annexin V antibodies are stable and do not change their positivity during a 24 month follow-up in SSc patients. Anti-annexin V IgG was associated with more severe interstitial lung involvement and digital microangiopathy, and patients with anti-annexin V IgG or IgM had a higher occurrence of PAH indicating an association of these biomarker with more severe disease.

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Abstract Background: Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome that impacts negatively patient's daily lives. Its pathogenesis is characterized by a complex relationship between biological and psychosocial factors not fully understood yet. Pain catastrophizing is associated with FM and is an important predictor of outcomes. This study aimed to answer two questions: (i) whether the allele and genotype frequencies of BDNF Val66Met (rs6265) polymorphism differs between FM patients and healthy controls (HC); and (ii) if the BDNF Val66Met polymorphism is a factor that predicts pain catastrophizing in FM. Methods: In a cross-sectional design, 108 FM patients and 108 HC were included. FM patients responded to the Brazilian Portuguese version of the Pain Catastrophizing Scale (BP-PCS) to assess pain catastrophizing, as well as other validated tools for anxiety (The State-Trait Anxiety Inventory - STAI), depression (Beck Depression Inventory II -BDI-II) and functional aspects (Fibromyalgia Impact Questionnaire - FIQ; Central Sensitization Inventory validated and adapted for Brazilian population - CSI-BP; Pittsburgh Sleep Quality Index - PSQI; and Resilience Scale). All subjects were genotyped for the BDNF Val66Met polymorphism. Results: Val allele was significantly more frequent in FM patients compared to the control group (p < 0.05). Also, FM patients with Val/Val genotype showed more pain catastrophizing thoughts, and this genotype was significantly associated with magnification and rumination dimensions of BP-PCS (p < 0.05). Furthermore, there were significant differences in levels of anxiety and symptoms of depression, years of education, and the functional situation between the FM and control groups. Conclusions: The findings show an association of BDNF Val66Met polymorphism with pain catastrophizing in FM, which opens new avenues to comprehend the interplay between molecular genetic characteristics and neuroplasticity mechanisms underpinning FM.

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Abstract Background: It is known that physical activity and muscular performance are reduced in fibromyalgia (FM) syndrome. This study aims to compare the performance of trunk muscles in women with FM and healthy controls and evaluate the correlation between trunk muscle strength and FM severity. Methods: Forty-six patients with FM and 42 age- and body mass index-matched healthy housewives without FM were included in the FM and control groups, respectively. The Fibromyalgia Impact Questionnaire (FIQ) was used for the assessment of FM severity. The pain intensity was evaluated using the visual analogical scale (VAS). An isokinetic dynamometer was used to measure the isokinetic trunk muscle strength. The peak torque (PT) values were recorded. The psychological status of the patients was evaluated using the Beck Depression Inventory. Results: There was no statistically significant difference in terms of age, BMI, and BDI scores in two groups (p > 0.05, for all). The isokinetic trunk extensor PT values were significantly lower in the FM group (p = 0.002 for 60°/s, and p < 0.001 for 90°/s and 120°/s) than control group. There was a statistically significant negative correlation between FIQ score and isokinetic extensor muscle parameters. Conclusion: The results indicate that trunk extensor muscles were significantly weaker in FM patients. Trunk extensor muscle strength decreased as FM severity increased in FM patients.

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Abstract Background: Hand osteoarthritis (HOA) is a complex disorder with various subtypes characterized with predominance of different features. It is challenging to estimate the severity of hand disability in HOA, since contribution of different disease components to clinical burden is yet to be clarified. The aim of the study is to investigate hand functions in nonerosive interphalangeal hand osteoarthritis (HOA) without inflammatory features, and search for effects of osteophyte formations detected by radiography and ultrasound on functionality. Methods: Thirty one HOA patients and 20 healthy subjects with similar age, gender, body mass index were included. Hand functions were evaluated by self-reported questionnaires and objective strength and dexterity measurements. A total of 459 interphalangeal joints were evaluated and scored by radiography and ultrasound for ostephyte formations. Results: Strength and dexterity measurements were similar between groups. Self-reported functionality was hampered in HOA group but not statistically significant. Osteophyte scores obtained by ultrasound and radiography were significantly higher in HOA group. Osteophyte scores obtained by ultrasound were higher than the scores obtained by radiography. Ultrasound scores showed no correlation with any of the parameters while osteophytes scores obtained by radiography partially showed a significant negative correlation with assembly part of dexterity testing. Conclusions: No significant difference observed in hand strength and dexterity in nonerosive interphalangeal HOA patients withouth signs of inflammation when compared to healthy subjects. Osteophyte formations prominent enough to be deteceted by radiography may have a negative effect on hand dexterity.

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Abstract Background: Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. Methods: Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. Results: Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. Conclusion: Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.

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Abstract Background: Methotrexate (MTX) intolerance is frequent, and its early identification may impact treatment, leading to timely changes in medication that may promote patient compliance and better control of rheumatoid arthritis (RA). The objective of this study was to identify the frequency of, and risk factors for, MTX intolerance using the Brazilian Portuguese version of the Methotrexate Intolerance Severity Score (MISS) questionnaire in patients with RA. Methods: This cross-sectional study was performed between April 2018 and April 2019 and enrolled patients with RA in regular use of oral or subcutaneous MTX for at least 3 months. Patients were invited to answer the Brazilian Portuguese version of the MISS questionnaire, and MTX intolerance was defined by a score ≥ 6 points. Age, sex, disease duration, time of MTX use, dose, route of administration, concomitant medications, comorbidities, smoking, and Disease Activity Score for 28joint (DAS28) data were collected from institutional medical records. Results: Among 120 patients, 103 (85.8%) were female, the mean age was 61 (±12.5) years, the mean duration of disease was 16 (±10.3) years, and the average duration of MTX use was 7 (±5.5) years. The frequency of MTX intolerance was 21.6%. The most frequent symptoms reported after the use of MTX were nausea (92.3%), abdominal pain (46.1%), and vomiting (30.7%). Behavioral symptoms occurred in 96.1% of patients with MTX intolerance, the most frequent being restlessness and irritability. Patients who used corticosteroids were more likely to develop MTX intolerance than those not using corticosteroids (odds ratio = 2.73; 95% confidence interval, 1.06 to 7.06; p = 0.038). Conversely, increasing age showed marginally significant association with decreased risk of MTX intolerance (p = 0.059). Conclusions: The use of the MISS questionnaire disclosed high frequencies of anticipatory, associative, and behavioral symptoms in MTX-intolerant patients, and the use of corticosteroid increases the risk of MTX intolerance. We suggest that the MISS questionnaire be used routinely in clinical practice.

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Abstract Background Anti-ribosomal P (anti-Rib-P) antibody is a specific serological marker for systemic lupus erythematosus (SLE) and routinely tested by targeting the common epitope of three ribosomal proteins of P0, P1 and P2. This study aimed to investigate if testing antibodies against individual ribosomal protein, but not the common epitope, is required to achieve the best diagnostic benefit in SLE. Methods The study included 82 patients with SLE and 22 healthy donors. Serum antibodies were determined by ELISA and immunoblot. Results The prevalence of each antibody determined by ELISA was 35.4% (anti-Rib-P), 45.1% (anti-Rib-P0), 32.9% (anti-Rib-P1) and 40.2% (anti-Rib-P2) at 99% specificity, respectively. Of 53 patients with negative anti-Rib-P antibody, 21 (39.6%) were positive for anti-Rib-P0, 9 (17.0%) for anti-Rib-P1 and 12 (22.6%) for anti-Rib-P2 antibody. The positive rate of anti-Rib-P antibody detected by ELISA was close to the results by immunoblot (33.4%). Patients with any of these antibodies were featured by higher disease activity and prevalence of skin rashes than those with negative antibodies. Moreover, each antibody was particularly related to some clinical and laboratory disorders. The distribution of subclasses of IgG1–4 was varied with each antibody. Anti-Rib-P0 IgG1 and IgG3 were strongly correlated with disease activity and lower serum complement components 3 and 4. Conclusions Anti-Rib-P antibody is not adequate to predict the existence of antibodies against ribosomal P0, P1 and P2 protein. The examination of antibodies against each ribosomal protein is required to achieve additional diagnostic benefit and to evaluate the association with clinical and serological disorders as well.

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Abstract Background Chronic low back pain (CLBP) represents a problem in the occupational environment, often associated with disability, sick-leave demands, loss of productivity, anxiety, depression and high socioeconomic cost. The emergence of functional neuroimaging allowed new insights into brain structure and physiology in normality and chronic pain. While occupational related aspects are recognized as important risk factors for chronicity there have not been thus far evaluated by fMRI experiments. The overall objective of this study is to compare the neuronal correlates between groups of individuals CLBP with or without sick-leave demands. Methods A total of 74 individuals were divided into three groups: chronic low back pain with sick-leave demands [CLBP_L]; chronic low back pain without sick-leave demands [CLBP_NL]; individuals without pain or sick-leave demands [Control]. Functional magnetic resonance imaging was used to assess brain function during moderate acute pain stimulation task (thumb controlled pressure). Results After acute painful stimulation, a higher brain response was found in the anterior cingulate and superior and medium frontal gyrus was observed in CLBP_NL vs. CLBP_L ( p < 0,001) and increased brain response in the frontal pole and paracingulate region in control vs. CLBP_L ( p < 0.001) during acute pain stimulation. Conclusion The modulation of acute pain participates in the mechanism propagating chronic pain perception. The lower activation in the superior frontal gyrus observed in the CLBP_L group compared to CLBP_NL, reinforces the idea of an already existing activation in this area.

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Abstract Background The reproducibility and reliability of the modified Rodnan's Skin Score (mRSS) are debated due to investigator-related subjectivity. Here, we evaluate if durometry correlates with mRSS in patients with diffuse systemic sclerosis (SSc). Methods This cross-sectional study was conducted from December 2018 to June 2019, including 58 diffuse SSc patients. Two certified researchers, blind to each other's scores, performed the mRSS, followed by durometry at 17 predefined skin sites. For durometry and mRSS, individual scores per skin site were registered. Durometry and mRSS results measured by each researcher, as well as scores from different researchers, were compared. Skin thickness measurements from forearm skin biopsies were available in a subset of the patients, for comparisons. Statistical analyses included Cohen's Kappa Coefficient, Intraclass Correlation Coefficient, Kendall's Coefficient and Spearman's test. Results Mean (standard deviation, SD) patient age was 44.8 (12.9) years, and 88% were female. Inter-rater agreement varied from 0.88 to 0.99 (Intraclass correlation coefficient) for durometry, and 0.54 to 0.79 (Cohen's Kappa coefficient) for mRSS, according to the specific evaluated sites. When data were compared with skin thickness assessed in forearm biopsies, durometry correlated better with skin thickness than mRSS. Conclusion Durometry may be considered as an alternative method to quantify skin involvement in patients with diffuse SSc. The strong inter-rater agreement suggests that the method may be useful for the assessment of patients by multiple researchers, as in clinical trials.

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Abstract Background: Hemorrhoid disease (HD) is one of the most common gastrointestinal complaints worldwide, affecting 4.4% of the general population in the United States. Since antiphospholipid syndrome (APS) may lead to intra-abdominal thrombosis, one may expect that this condition can impact the risk for HD development. Additionally, as APS patients are more prone to thrombosis and treatment with anticoagulants may increase risk of bleeding, one may also infer that rates of HD complications may be higher in this scenario. Nevertheless, no data in these regards have been published until now. The objective of the present study is to evaluate frequency of HD and describe its complications rates in antiphospholipid syndrome APS patients. Methods: We consecutively invited patients who fulfilled APS criteria to undergo proctological examination. After examination, patients were divided in two groups, based on the presence of HD, and compared regarding different clinical manifestations and antiphospholipid profile. We performed the analysis of the data, using chi-square and Mann Whitney U when applicable and considering a significance level of 0.05. Multivariate regression analysis included age and variables with p < 0.10 in the bivariate analysis. Results: Forty-one APS patients agreed to undergo proctological examination. All were female and overall median age was 43 (36–49). Seventeen (41.4%) patients were diagnosed with HD, with the following frequency distribution: 7 internal (41.2%), 4 external (23.5%) and 5 mixed hemorrhoids (29.4%). Of the internal hemorrhoids, 5 patients were classified as grade I (71.4%), 1 grade II (14.3%), and 1 grade IV (14.3%). Prior gestation ( p = 0.067) and constipation ( p = 0.067) correlated with a higher frequency of HD. In multivariate analysis, constipation remained as an important risk factor (OR 3.92,CI95% 1.03–14.2, p = 0.037). Five out of 17 patients (29.4%) reported anal bleeding, but it did not correlate with warfarin dose ( p = 0.949). Surgical treatment was indicated for 10 patients (58.8%). Other anorectal findings were anal fissure, plicoma, condyloma and one chlamydial retitis. Conclusion: We found an unexpected high frequency of hemorrhoids in APS patients, with a great proportion requiring surgical treatment.

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Abstract Objective: Gout is characterized by inflammatory arthritis with hyperuricaemia and deposition of monosodium urate (MSU) crystals in the joints. Several animal models have been proposed based on MSU crystals injection or high-fat diet feeding; however, neither hyperuricaemia model nor acute gout model can effectively reflect clinical features of gout. This study aimed to assess the effectiveness of a compound gout model induced by the combination of MSU crystals injection and high-fat diet feeding. Methods: The compound gout model was induced by high-fat diet feeding per day and the intraplantar injection of MSU crystals (1 mg) into the footpad of each mouse every 10 days. Serum uric acid, foot swelling and pain analyses were performed at days 22, 32 and 42. Gout inflammation, serum proinflammatory cytokines and gut microbiota analyses were performed only at day 42. Results: Compared to hyperuricaemia model or acute gout model, the compound gout model showed little advantages of elevating serum uric acid, causing foot swelling and gout inflammation, while it caused more severe serum inflammation and gut microbiota dysbiosis. Severe serum inflammation in the compound gout model could be reflected by the increased levels of IL-1 α, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IFN-γ, KC, MCP-1 and MIP-1β. In addition, the compound gout model induced more alterations in the gut microbiota, including increasing levels of Desulfovibrio and Parasutterella. Conclusion: The injection of MSU and feed of high-fat diet have a combined effect on elevating serum inflammation and causing gut microbiota disorders in the process of establishing a gout model.

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Abstract Background: Adverse drug reactions (ADRs) are the sixth leading causes of death worldwide; monitoring them is fundamental, especially in patients with disorders like chronic rheumatic diseases (CRDs). The study aimed to describe the ADRs investigating their severity and associated factors and resulting interventions in pediatric patients with CRDs. Methods: A retrospective, descriptive and analytical study was conducted on a cohort of children and adolescents with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). The study evaluated medical records of the patients to determine the causality and the management of ADRs. In order to investigate the risk factors that would increase the risk of ADRs, a logistic regression model was carried out on a group of patients treated with the main used drug. Results: We observed 949 ADRs in 547 patients studied. Methotrexate (MTX) was the most frequently used medication and also the cause of the most ADRs, which occurred in 63.3% of patients, followed by glucocorticoids (GCs). Comparing synthetic disease-modifying anti-rheumatic drugs (sDMARDs) vs biologic disease-modifying antirheumatic drugs (bDMARDs), the ADRs attributed to the former were by far higher than the latter. In general, the severity of ADRs was moderate and manageable. Drug withdrawal occurred in almost a quarter of the cases. In terms of risk factors, most patients who experienced ADRs due to MTX, were 16 years old or younger and received MTX in doses equal or higher than 0.6 mg/kg/week. Patients with JIA and JDM had a lower risk of ADRs than patients with JSLE. In the multiple regression model, the use of GCs for over 6 months led to an increase of 0.5% in the number of ADRs. Conclusions: Although the ADRs highly likely affect a wide range of children and adolescents with CRDs they were considered moderate and manageable cases mostly. However, triggers of ADRs need further investigations.

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Abstract Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc. Methods: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed. Results: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34). Conclusions: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease. Trial registration: This study is not a clinical trial study.

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Abstract Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013. A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed. These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

Resumo em Inglês:

Abstract Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.

Resumo em Inglês:

Abstract Background: The results of investigations on the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and the risk of systemic sclerosis (SSc) are inconsistent. To comprehensively evaluate the influence of KIR polymorphisms on the risk of SSc, this meta-analysis was performed. Methods: A systematic literature search was performed in electronic databases including Scopus and PubMed/ MEDLINE to find all available studies involving KIR gene family polymorphisms and SSc risk prior to July 2019. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were measured to detect associations between KIR gene family polymorphisms and SSc risk. Results: Five articles, comprising 571 patients and 796 healthy participants, evaluating the KIR gene family polymorphisms were included in the final meta-analysis according to the inclusion and exclusion criteria, and 16 KIR genes were assessed. None of the KIR genes were significantly associated with the risk of SSc. Conclusions: The current meta-analysis provides evidence that KIR genes might not be potential risk factors for SSc risk.

Resumo em Inglês:

Abstract The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself. Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena. Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS- CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.