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Abstract Background Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. Methods We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and nonhospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. Results We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. Conclusion Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.

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Abstract Background Patients with psoriatic arthritis (PsA) experience reduced physical function and impaired quality of life. Better patient-reported functional outcomes are found when lower disease activity is achieved. Objectives To evaluate the variation of physical function by HAQ-DI over time in PsA patients treated with standard therapy in a real-life setting: to verify predictors of achieving a minimum clinically important difference (MCID) in function by HAQ-DI (ΔHAQ-DI ≤ − 0.35) and to measure the impact of achieving REM/LDA on long-term function by HAQ-DI. Methods This is a longitudinal analysis of a real-life retrospective cohort. Data from PsA patients with at least 4 years of follow-up in the PsA clinic from 2011 to 2019 were extracted from electronic medical records. The variations of physical function by HAQ-DI and disease activity by DAPSA over time were calculated. A multivariate hierarchical regression model was applied to verify predictors of MCID in HAQ-DI. A comparison of HAQ-DI variation between patients with DAPSA REM, LDA, moderate and high disease activity was made using the generalized estimating equation model (GEE), adjusted by Bonferroni test. The Spearman correlation method was applied to verify the correlation of ΔDAPSA and ΔHAQ-DI over time. Statistical analysis was performed in SPSS program version 21.0. Results Seventy-three patients were included in the analysis. Physical function measured by HAQ-DI was determined by PsA disease activity measured by DAPSA (p < 0.000). A moderate and statistically significant correlation between ΔDAPSA and ΔHAQ-DI was observed (rs = 0.60; p < 0.001). Only patients in DAPSA REM demonstrated a constant decline in HAQ-DI scores during the follow-up. White ethnicity and older age at baseline were predictors for not achieving MCID in HAQ-DI [RR 0.33 (0.16–0.6795% CI p = 0.002) and RR 0.96 (0.93–0.9895% CI p < 0.000), respectively, while higher scores of HAQ-DI at baseline were predictors of achieving MCID [RR 1.71 (1.12–2.6095%CI p = 0.013)]. Conclusion In PsA, patients who maintained DAPSA REM/LDA over time had better long-term functional outcomes. Higher HAQ-DI scores at baseline, non-white ethnicity and younger age were predictors for achieving a clinical meaningful improvement of HAQ-DI.

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Abstract Background Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis. Methods In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained. Results In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphospho-nate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration. Conclusions The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

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Abstract Background Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols. Objectives This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity. Methods The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman's correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ). Results The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS–13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). Conclusion The Brazilian Portuguese version of the RAKAS (RAKAS–13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study.

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Abstract Objective Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. Methods Mice received 0.1 mg/25μL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 μL or saline per os (systemic) or 500 μg/25 μL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. Results MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. Conclusion MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

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Abstract Introduction Chronic back pain (CBP) is a major cause of years lived with disability. Social inequalities increase the prevalence and burden of CBP. Management of CBP was affected by restricted access to non-pharmacological treatments and outdoor activities during COVID-19 pandemic. Objectives To determine the prevalence of CBP among patients with COVID-19 as well as the impact of having CBP in COVID-19 outcome in our low-income population. Methods Retrospective cohort of individuals with confirmed COVID diagnosis from May 2020 - March 2021, at Hospital Regional UNIMED (HRU) in Fortaleza, Ceará, Brazil. Data included comorbidities and household income. Results Among 1,487 patients, 600 (40.3%) were classified as having CBP. Mean age as well as income were similar in CBP and non-CBP groups, with more women in the CBP group. Hypertension and asthma, but not diabetes, were more prevalent in those with CBP. Need for emergency care, hospitalization, and admission to intensive care unit were similar regardless of having CBP. Dyspnea was more common in CBP vs. non-CBP groups, with 48.8% vs. 39.4% percentages, respectively (p = 0.0004). Conclusion Having CBP prior to COVID did not impact the acute clinical outcome of COVID individuals of a low- income population.

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Abstract Background Hip fractures in the older adults lead to increased morbidity and mortality. Although a low bone mineral density is considered the leading risk factor, it is essential to recognize other factors that could affect the risk of hip fractures. This study aims to evaluate the contribution of clinical characteristics, patient-reported outcomes, and muscle and aerobic capacity for hip fractures in community-dwelling older adults. Methods This is a retrospective cohort study with real world-data from subjects ≥ 60 years old attending an outpatient clinic in Minas Gerais, Brazil, from May 1, 2019, to August 22, 2022. Data about clinical characteristics (multimorbidity, medications of long-term use, sedative and or tricyclic medications, number of falls), patient-reported outcomes (self-perception of health, self-report of difficulty walking, self-report of vision problems, and self-report of falls) and muscle and aerobic capacity (calf circumference, body mass index, and gait speed) were retrieved from an electronic health record. The association of each potential risk factor and hip fracture was investigated by a multivariable logistic regression analysis adjusted for age and sex. Results A total of 7,836 older adults were included with a median age of 80 years (IQR 72–86) and 5,702 (72.7%) were female. Hip fractures occurred in 121 (1.54%) patients. Multimorbidity was associated with an increased risk of hip fracture (OR = 1.12, 95%CI 1.06–1.18) and each episode of fall increased the chance of hip fracture by 1.7-fold (OR = 1.69, 95%CI 1.52–1.80). Patient-reported outcomes associated with increased fracture risk were regular or poor self-perception of health (OR = 1.59, 95%CI 1.06–2.37), self-report of walking difficulty (OR = 3.06, 95%CI 1.93–4.84), and self-report of falls (OR = 2.23, 95%CI 1.47–3.40). Body mass index and calf circumference were inversely associated with hip fractures (OR = 0.91, 95%CI 0.87–0.96 and OR = 0.93, 95%CI 0.88–0.97, respectively), while slow gait speed increased the chance of hip fractures by almost two-fold (OR = 1.80, 95%CI 1.22–2.66). Conclusion Our study reinforces the importance of identified risk factors for hip fracture in community-dwelling older adults beyond bone mineral density and available fracture risk assessment tools. Data obtained in primary care can help physicians, other health professionals, and public health policies to identify patients at increased risk of hip fractures.

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Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

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Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .

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Abstract Background Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. Methods In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. Results Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. Conclusions The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.

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Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54–0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

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Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min–max) SLEDAI-2 K scores were 9 (0–38), median (min–max) SLICC/ACR-DI (SDI) score were 1 (1–5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

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Abstract Background Nail involvement is frequent in patients with psoriasis (Pso) and psoriatic arthritis (PsA) and there is a relationship between nail involvement and inflammation of the enthesis. The main objective of the present study is to describe the ultrasound findings and clinical characteristics of nails from patients with psoriasis and psoriatic arthritis with and without nail dystrophy. Methods A cross-sectional study including consecutive patients with PsO and PsA was carried out. The study patients were divided into 4 groups, totaling 120 participants. Group 1: patients with psoriasis vulgaris and clinically normal nails; Group 2: patients with psoriasis vulgaris and onychodystrophy; Group 3: patients with psoriatic arthritis and clinically normal nails; Group 4: patients with psoriatic arthritis and onychodystrophy; All patients were submitted to dermatological and rheumatological clinical analysis. Ultrasound examinations was performed by a single examiner, blinded to all clinical data, with ultrasound high resolution, in B-mode or gray-scale (GS), Power Doppler (PD) and Spectral Doppler. Results A significant difference was found between the groups regarding the variable Psoriasis Area and Severity Index (PASI) (p = 0.008) and body surface area (BSA) (p = 0.005), with patients with psoriatic arthritis having lower PASI and BSA compared to patients with only cutaneous psoriasis. A positive relationship was found with the average ultrasound thickness of the nail bed and the Nail Psoriasis Severity Index (NAPSI) in correlation analysis (rho = 0.344). When we grouped patients with psoriasis and psoriatic arthritis, there was no significant difference between the cutaneous psoriasis groups and the psoriatic arthritis groups in terms of nail plate GS (p = 0.442), nail bed PD (p = 0.124). Conclusion Greater nail bed thickness indicates early psoriatic nail disease, as confirmed in our study correlating NAPSI with nail bed thickness. Ultrasonography is a low-cost exam, promising in the evaluation, showing that the ultrasound grayscale is consistent with those who have dystrophic nails, but it can't distinguish psoriasis from psoriatic arthritis, even in those with nail dystrophy.

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Abstract Background To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). Methods This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient’s global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Results Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Conclusions Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

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Abstract Background Enteropathic spondyloarthritis is underdiagnosed and inflammatory biomarkers and ultrasonography (US) could be useful for screening inflammatory bowel disease (IBD) patients. The objective of this study was to evaluate the prevalence of spondyloarthritis (SpA) in IBD patients, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria and the correlation of results of US of entheses and joints with plasma calprotectin levels. Methods This was an observational cross-sectional study. Patients from the IBD outpatient clinic of a reference center were evaluated according to ASAS criteria classification, results of US of entheses and joints, and inflammatory biomarker measurements (erythrocyte sedimentation rates, C-reactive protein levels, fecal and plasma calprotectin levels). A p value lower than 0.05 was considered significant. Results A total of 30.5% of the studied sample (n = 118) of patients with IBD presented at least one inflammatory musculoskeletal manifestation. The overall prevalence of enteropathic SpA was 13.55%, with 10.16% axial SpA and 4.23% peripheral SpA according to the ASAS criteria. A total of 42.1% of patients had an MASEI score greater than 18, 35.2% had synovitis, and 14.7% had tenosynovitis on US, increasing the frequency of diagnosis of entero- pathic SpA to 22.8%. Plasma calprotectin levels were similar to those in healthy controls, and correlated only with the fecal calprotectin level (p 0.041). Conclusions A total of 13.5% of patients met the criteria in accordance with the ASAS criteria for enteropathic SpA, which increased to 22.8% with the addition of US. The prevalence of enthesitis, synovitis and tenosynovitis by US of symptomatic joints and entheses were 42%, 35% and 14.7% respectively. Plasma calprotectin was correlated with fecal calprotectin but not with inflammatory biomarkers or US or ASAS criteria.

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Abstract Background To illustrate how (standardised) effect sizes (ES) vary based on calculation method and to provide considerations for improved reporting. Methods Data from three trials of tanezumab in subjects with osteoarthritis were analyzed. ES of tanezumab versus comparator for WOMAC Pain (outcome) was defined as least squares difference between means (mixed model for repeated measures analysis) divided by a pooled standard deviation (SD) of outcome scores. Three approaches to computing the SD were evaluated: Baseline (the pooled SD of WOMAC Pain values at baseline [pooled across treatments]); Endpoint (the pooled SD of these values at the time primary endpoints were assessed); and Median (the median pooled SD of these values based on the pooled SDs across available timepoints). Bootstrap analyses were used to compute 95% confidence intervals (CI). Results ES (95% CI) of tanezumab 2.5 mg based on Baseline, Endpoint, and Median SDs in one study were - 0.416 (- 0.796, - 0.060), - 0.195 (- 0.371, - 0.028), and - 0.196 (- 0.373, - 0.028), respectively; negative values indicate pain improvement. This pattern of ES differences (largest with Baseline SD, smallest with Endpoint SD, Median SD similar to Endpoint SD) was consistent across all studies and doses of tanezumab. Conclusion Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies. Trial Registration Clinicaltrials.gov NCT02697773, NCT02709486, and NCT02528188.

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Abstract Background There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). Methods The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. Results A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. Conclusions Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

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Abstract Introduction Psoriasis (PsO) is an immune-mediated chronic inflammatory disease that results in severe outcomes that impact the patient's quality of life and work productivity. We investigated the effectiveness of secukinumab in patients with chronic plaque psoriasis and psoriatic arthritis (PsA) over a 12-month period. Methods This was a longitudinal, retrospective study of the medical records of 81 patients with psoriasis and/or psoriatic arthritis who had been treated with secukinumab for at least 12 weeks. Results The Psoriasis Area Severity Index (PASI), Body Surface Area (BSA) percentage, and Dermatology Quality of Life Index (DLQI) among patients with PsO and PsO-PsA showed a statistically significant decrease from baseline over 12 months by approximately 9.86, 19.3%, and 9.7, respectively (p values < 0.001 for each). Moreover, there was a statistically significant decrease in the overall Disease Activity in Psoriatic Arthritis score (DAPSA) by approximately 22.35 from baseline over 12 months of treatment (p < 0.001). Considering the patients who started secukinumab 12 months or more prior to the study cutoff date, the 12-month retention rate was 85%. Conclusion In a Saudi real-world setting, secukinumab proved to be an efficient medication with high efficacy and retention rates.

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Abstract Background While ultrasound and MRI are both superior to clinical examination in the detection of joint inflammation, there is presently a lack of data whether thermography may be similarly useful in the assessment of joint inflammation in patients with RA. Our study aims to evaluate the use ofthermography in detecting subclinical joint inflammation at clinically quiescent (non-tender and non-swollen) metacarpophalangeal joints (MCPJs) in patients with rheumatoid arthritis (RA). The outcomes from thermography in our study will be compared with ultrasonography (which is a more established imaging tool used for joint inflammation assessment in RA). Methods The minimum (Tmin), average (Tavg) and maximum (Tmax) temperatures at the 10 MCPJs of each patient were summed to obtain the Total Tmin, Total Tavg and Total Tmax, respectively. Ultrasound grey-scale (GS) and power Doppler (PD) joint inflammation (scored semi-quantitatively, 0–3) at the 10 MCPJs were summed up to derive the respective TGS and TPD scores per patient. Pearson's correlation and simple linear regression were respectively used to assess correlation and characterize relationships between thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TGS, TPD and the number of joint(s) with PD ≥ 1 or GS ≥ 2). Results In this cross-sectional study, 420 clinically non-swollen and non-tender MCPJs from 42 RA patients were examined. All thermographic parameters (Total Tmin, Total Tavg and Total Tmax) correlated significantly (P-values ranging from 0.001 to 0.0012) with TGS score (correlation coefficient ranging from 0.421 to 0.430), TPD score (correlation coefficient ranging from 0.383 to 0.424), and the number of joint(s) with PD ≥ 1 or GS ≥ 2 (correlation coefficient ranging from 0.447 to 0.465). Similarly, simple linear regression demonstrated a statistically significant relationship (P-values ranging from 0.001 to 0.005) between all thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TPD and TGS). Conclusion For the first time, thermographic temperatures were shown to correlate with ultrasound-detected joint inflammation at clinically quiescent MCPJs. The use of thermography in the detection of subclinical joint inflammation in RA appears promising and warrants further investigation.

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Abstract Objective It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. Methods We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. Results Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014–7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046–6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). Conclusion Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.

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Abstract Background This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. Methods The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. Results Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/ hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. Conclusions This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

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Abstract Background Juvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA). Methods Cross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups. Results Thirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA. Conclusion The main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.

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Abstract Background Musculoskeletal chronic pain is a leading cause of global disability and laboral incapacity. However, there is a lack of population-based studies that investigate the relationship between chronic pain and mental disorders with a control group, particularly among low- and middle-income countries. Chronic pain is a serious public health problem in terms of human suffering, and in terms ofsocioeconomic implications. Frequent association with different mental disorders increases disability, decreases quality of life, and makes diagnosis and treatment challenging. The present study aimed to evaluate the presence of mental disorders in patients with chronic musculoskeletal pain and compare with a control group without pain. Methods We selected 100 patients in a regular follow-up at the Musculoskeletal Pain Outpatient Clinic of the University Hospital and compared them with 100 painless individuals from the control group from June 2016 to June 2018. The instruments used were the Mini International Neuropsychiatric Interview (MINI-PLUS) and a structured questionnaire to collect sociodemographic data. Statistical analysis used t-test, chi-square, Fisher's exact test, Mann-Whitney, Kolmogorov-Smirnov tests, and multiple logistic regression. Results In the sample evaluated, the majority of patients were women (83%), of brown color (54%), with lower-level education (51%), lower salary range (73%) and high absenteeism rate at work (60,7%). Patients with chronic pain had more psychiatric disorders (88% vs. 48% in the control group; p < 0.001). The most frequent diagnoses were anxiety disorders with panic attacks (44%), generalized anxiety (36%), mixed anxiety and depression disorder (33%), social phobia (30%), agoraphobia (29%), suicide risk (28%), and major depression (27%). Conclusion Positive correlations of mental disorders and chronic musculoskeletal pain have been documented. This suggests that psychiatric components must be taken into account in the management of chronic pain syndromes. The use of Mini Plus as a diagnostic tool for psychiatric disorders can contribute to optimizing the diagnosis and treatment of patients with chronic pain and encourage the creation of policies with strategies and criteria for quick access to Multi-professional Services.

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Abstract Background The diagnostic and prognostic relevance of Human Leukocyte Antigen B-27 (HLA-B27) in Axial Spondyloarthritis (AxSpA) is undeniable, with 70% of Ankylosing Spondylitis (AS) patients carrying the B27 gene, contrasted with a mere 4.35% in the general population. Flow cytometry (FC) and Polymerase Chain Reaction (PCR) have emerged as the predominant techniques for routine HLA-B27 typing. While various studies have compared these methods, none have catered to the unique characteristics of the Brazilian demographic. Therefore, this research aims to compare FC and PCR in a Brazilian cohort diagnosed with AxSpA. Methods An analytical cross-sectional study was undertaken involving 62 AxSpA outpatients from a Brazilian University Hospital. Both FC and PCR-SSP assays were utilized to ascertain HLA-B27 typing. The outcomes (either confirming or refuting the allele’s presence) underwent rigorous scrutiny. Agreement between the methodologies was assessed using the kappa statistic. A p-value of < 0.05 was deemed statistically significant. Results Of the participants, 90.3% (n= 56) were HLA-B27 positive according to FC, while 79% (n= 49) were identified as positive using the PCR method. FC exhibited a sensitivity rate of 98% paired with a specificity of 38.5%. The Positive Predictive Value for FC stood at 85.7%, and the Negative Predictive Value was 83.5%. Consequently, the overall accuracy of the FC method was gauged at 85.5%. A kappa coefficient of κ = 0.454 was derived. Conclusions FC demonstrated noteworthy sensitivity and satisfactory accuracy in HLA-B27 detection, albeit with a reduced specificity when contrasted with PCR-SSP. Nevertheless, given its cost-effectiveness and streamlined operation relative to PCR, FC remains a pragmatic option for preliminary screening in clinical practice, especially in low-income regions. To optimize resource allocation, we advocate for a refined algorithm that initiates by assessing the relevance of HLA-B27 typing based on Choosing Wisely recommendations. It then leans on FC, and, if results are negative yet clinical suspicion persists, advances to PCR. This approach aims to balance diagnostic accuracy and financial prudence, particularly in regions contending with escalating medical costs.

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Abstract Introduction Takayasu’s arteritis (TAK) patients are at an elevated risk of metabolic syndrome and cardiovascular diseases (CVD). Currently, there are no well-validated biomarkers to assess this risk in this population. Previous research in different cohorts has linked serum levels of osteoprotegerin (OPG) and its polymorphisms to accelerated atherosclerosis and a marker of poor prognosis in CVD. Thus, we assessed this protein as a potential biomarker of CVD in TAK patients. Objectives To evaluate the serum levels of OPG and its SNPs (single nucleotide polymorphisms) in TAK patients and healthy controls, and to associate these parameters with clinical data. Methods This bicentric cross-sectional study included TAK patients who were compared with healthy individuals (control group). The serum levels of OPG and the frequency of OPG SNPs [1181G > C (rs2073618), 245 A > C (rs3134069), 163T > C (rs3102735), and 209 C > T (rs3134070)] were compared between the both groups and associated with clinical data. Results In total, 101 TAK patients and 93 controls were included in the study. The serum levels of OPG (3.8 ± 1.9 vs. 4.3 ± 1.8pmol/L, respectively; P = 0.059), and its four polymorphisms were comparable between both groups. In an additional analysis of only TAK patients, serum OPG levels and its four genes were not associated with any CVD parameters, except for higher OPG levels among patients without dyslipidemia. Conclusion No significant differences were observed in serum OPG levels or in the genotype frequencies of OPG SNPs between the patient and control groups. Similarly, no correlation was found between laboratory parameters and clinical data on CVD risk in TAK patients.

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Abstract Objectives Research has demonstrated that obesity may be associated with rheumatoid arthritis (RA). In addition, gut microbiota and its metabolites contribute to the occurrence and development of RA and obesity. However, the mechanism by which obesity affects RA remains unclear. In this study, we aimed to investigate whether gut microbiota and their metabolites alter the effects of high fat diet (HFD) on the severity of collagen-induced arthritis (CIA) in mice. Methods Briefly, mice were divided into normal group (N), CIA model group (C), HFD group (T), and HFD CIA group (CT). Hematoxylin and Eosin staining(HE) and Safranin O-fast green staining were conducted, and levels of blood lipid and inflammatory cytokines were measured. 16S rDNA sequencing technique and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics were performed to explore changes in the microbiota structure to further reveal the pathomechanism of HFD on CIA. Results HFD aggravated the severity of CIA in mice. The CT group had the highest proportion of microbial abundance ofBlautia, Oscillibacter, Ruminiclostridium-9, andLachnospiraceaeUCG 006 at the genus level, but had a lower proportion of Alistipes. Additionally, the fecal metabolic phenotype of the combined CT group shows significant changes, with differential metabolites enriched in 9 metabolic pathways, including primary bile acid biosynthesis, arginine biosynthesis, sphingolipid metabolism, purine metabolism, linoleic acid metabolism, oxytocin signaling pathway, aminoacyl-tRNA biosynthesis, the pentose phosphate pathway, and sphingolipid signaling pathway. Correlation analysis revealed that some of the altered gut microbiota genera were strongly correlated with changes in fecal metabolites, total cholesterol (TC), triglyceride (TG), and inflammatory cytokine levels. Conclusions This study shows that HFD may aggravate inflammatory reaction in CIA mice by altering the gut microbiota and metabolic pathways.

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Abstract Introduction Sjögren’s disease (SD) is an immune-mediated chronic inflammatory disease that affects epithelial tissues, mainly salivary and lacrimal glands. It also presents extraglandular manifestations. The main renal manifestation is tubulointerstitial nephritis (TIN), which can manifest as renal tubular acidosis (RTA). Urinary citrate may be a biomarker of RTA in these patients. The objective of this study was to evaluate whether hypocitraturia is a predictive biomarker of RTA in a sample of patients with SD in a tertiary hospital in southern Brazil. Methods All patients with SD who met the inclusion criteria and who participated in the rheumatology outpatient clinic of the Irmandade Santa Casa de Misericórdia de Porto Alegre were included. Demographic, SD, serological and urinary data were obtained. RTA was considered in those patients who persistently presented urinary pH above 5.5 and serum pH below 7.35. Patients who persistently had urinary pH above 5.5 underwent a urinary acidification test with furosemide and fludrocortisone. These patients received 1 mg of fludrocortisone and 40 mg of furosemide and had their urine samples tested 2, 4 and 6 h after taking the medications. The test was stopped at any urine sample with pH 5.5 or less. The variables were expressed as mean and standard deviation or interquartile range. The association between hypocitraturia and RTA was assessed using the chi-square. Results Forty-two patients were included, 95.2% female with a median age of 61.73 years. The prevalence of complete distal RTA was 4.88%. Twenty-eight patients underwent urine acidification testing. Five patients had hypocitraturia, and two of them had complete distal RTA. The association between hypocitraturia and RTA was statistically significant (p < 0.012), with a sensitivity of 100%, specificity of 91.2% and accuracy of 91.7%. The negative predictive value was 100%. The global renal assessment of the population demonstrated two patients with RTA, one patient with decreased renal function and six patients with proteinuria greater than 0.5 g/24 h. Conclusion The prevalence of RTA in the studied population was 4.88%. Hypocitraturia had high sensitivity and accuracy for the diagnosis of RTA.

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Abstract Background Fibroblast-like synoviocytes (FLSs) are involved in osteoarthritis (OA) pathogenesis through pro-inflammatory cytokine production. TAK-242, a TLR4 blocker, has been found to have a significant impact on the gene expression profile of pro-inflammatory cytokines such as IL1-β, IL-6, TNF-α, and TLR4, as well as the phosphorylation of Ikβα, a regulator of the NF-κB signaling pathway, in OA-FLSs. This study aims to investigate this effect because TLR4 plays a crucial role in inflammatory responses. Materials and methods Ten OA patients’ synovial tissues were acquired, and isolated FLSs were cultured in DMEM in order to assess the effectiveness of TAK-242. The treated FLSs with TAK-242 and Lipopolysaccharides (LPS) were analyzed for the mRNA expression level of IL1-β, IL-6, TNF-α, and TLR4 levels by Real-Time PCR. Besides, we used western blot to assess the protein levels of Ikβα and pIkβα. Results The results represented that TAK-242 effectively suppressed the gene expression of inflammatory cytokines IL1-β, IL-6, TNF-α, and TLR4 which were overexpressed upon LPS treatment. Additionally, TAK-242 inhibited the phosphorylation of Ikβα which was increased by LPS treatment. Conclusion According to our results, TAK-242 shows promising inhibitory effects on TLR4-mediated inflammatory responses in OA-FLSs by targeting the NF-κB pathway. TLR4 inhibitors, such as TAK-242, may be useful therapeutic agents to reduce inflammation and its associated complications in OA patients, since traditional and biological treatments may not be adequate for all of them.

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Abstract Introduction Patients with psoriatic arthritis have some lipid metabolism changes and higher risk of metabolic syndrome (MetS) and cardiovascular diseases, regardless of traditional risk factors, suggesting that chronic inflammation itself plays a central role concerning the atherosclerosis. However, there is a lack of information regarding atherogenic pattern and lipoprotein subfractions burden in these individuals. Aim To evaluate the HDL and LDL-cholesterol plasmatic levels and their subfractions after a nutritional intervention in patients with psoriatic arthritis (PsA). Methods This was a randomized, placebo-controlled clinical trial of a 12-week nutritional intervention. PsA patients were randomly assigned to 1-Placebo: 1 g of soybean oil daily, no dietetic intervention; 2-Diet + Supplementation: an individualized diet, supplemented with 604 mg of omega-3 fatty acids, three times a day; and 3-Diet + Placebo: individualized diet + 1 g of soybean oil. The LDL subfractions were classified as non-atherogenic (NAth), atherogenic (Ath) or highly atherogenic (HAth), whereas the HDL subfractions were classified as small, medium, or large particles, according to the current recommendation based on lipoproteins electrophoresis. Results A total of 91 patients were included in the study. About 62% of patients (n = 56) had an Ath or HAth profile and the main risk factors associated were male gender, longer skin disease duration and higher BMI. Thirty-two patients (35%) had a high-risk lipoprotein profile despite having LDL plasmatic levels below 100 mg/dL. The 12-week nutritional intervention did not alter the LDL subfractions. However, there were significant improvement of HDL subfractions. Conclusion Recognizing the pro-atherogenic subfractions LDL pattern could be a relevant strategy for identifying PsA patients with higher cardiovascular risk, regardless total LDL plasmatic levels and disease activity. In addition, a short-term nutritional intervention based on supervised and individualized diet added to omega-3 fatty acids changed positively the HDLLARGE subfractions, while LDLLARGE subfraction was improved in hypercholesterolemic individuals. ClinicalTrials.gov identifier: NCT03142503 (http://www.clinicaltrials.gov/).

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Abstract Background In general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody. Methods This is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist’s final diagnosis being “abnormal finding of serum immunological test” (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist’s chart. Descriptive statistics were used for data analysis. Results A total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist’s appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia’s investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics). Conclusions Most patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.

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Abstract Objective To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. Materials and methods The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. Results Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. Conclusion The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

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Abstract Objective To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). Methods Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. Results All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. Conclusion This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

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Abstract Sjogren’s disease (SjD) is an autoimmune disease that is characterized not only by the sicca symptoms it causes but also by its systemic nature, which is capable of several and not yet fully understood extraglandular manifestations. To gain a clearer understanding of these manifestations as well as a better practical approach, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of the extraglandular manifestations present in ESSDAI (EULAR Sjogren´s syndrome disease activity index), followed by a voting panel with recommendations for clinical practice. This publication is complementary to others already published and covers cutaneous and hematological manifestations, with prevalence data generated by a meta-analysis of 13 clinical or laboratory manifestations and 6 clinical management recommendations.

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Abstract Background Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. Methods A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. Results Six recommendations were elaborated regarding the pharmacological treatment of Raynaud’s phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. Conclusion These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

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Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE.

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Abstract Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.

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Abstract Background A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil. Methods This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources. Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE. Results Overall, 300 patients with SLE were included (92.3% female, mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001). Conclusion These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country.

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Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.

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Abstract Hereditary connective tissue disorders include more than 200 conditions affecting different organs and tissues, compromising the biological role of the extracellular matrix through interference in the synthesis, development, or secretion of collagen and/or its associated proteins. The clinical phenotype includes multiple signs and symptoms, usually nonspecific but of interest to rheumatologists because of musculoskeletal involvement. The patient's journey to diagnosis is long, and physicians should include these disorders in their differential diagnoses of diseases with systemic involvement. In this review, insights for the diagnosis and treatment of osteogenesis imperfecta, hypermobility spectrum disorder/Ehlers–Danlos syndrome, Marfan, Loeys–Dietz, and Stickler syndromes are presented.

Resumo em Inglês:

Abstract Immunoglobulin G4-related disease is a systemic immune-mediated disease with insidious evolution characterized by fibroinflammatory lesions over virtually any organ system. Despite the remarkable progression of knowledge, its etiology remains undefined. Due to its relapse-remitting pattern, it could accumulate irreversible damage, increasing comorbidities and mortality. This paper emphasizes key concepts for diagnosing and treating patients with this condition.

Resumo em Inglês:

Abstract Trigger finger (TF) is a disorder characterized by snapping or locking a finger. It has a prevalence of greater than 3% in the general population; however, this estimate could be increased to 5% up to 20% in diabetic patients. Some unreal ambiguity about definition, pathophysiology, site of lesion, and etiology are found among researchers and clinicians, leading to a lack of understanding of all aspects of the disease and improper management as many clinicians proceed to anti-inflammatory medications or steroids injection without in-depth patient evaluation. Original articles cited up to 2022, found through a Google search using the specified keywords, have been used in this review. Close-access articles were accessed through our researcher account with the Egyptian Knowledge Bank. In this review, we will focus on pathophysiology to present all possible findings and etiology to represent all risk factors and associated diseases to assess and confirm a diagnosis and the exact location of pathology hence better treatment modalities and reducing the recurrence of the pathology.