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Maria de la Vega, Generoso Guerra Bautista, Ricardo Machado Xavier, César Pacheco-Tena, Gastón Solano, Ronald D. Pedersen, Annette Eva Szumski, Cecilia Borlenghi, Karina Santana, Bonnie Vlahos
Published: 8 September 2021
Advances in Rheumatology, Volume 61, pp 1-8; https://doi.org/10.1186/s42358-021-00213-4

Abstract:
Background Determining potential predictors of clinical response would allow a more personalized rheumatoid arthritis (RA) treatment approach in heterogeneous populations such as Latin American (LA) patients. Methods Post hoc analysis to identify baseline characteristics predictive of clinical remission in response to treatment with etanercept (ETN) plus methotrexate (MTX) in LA patients with moderate to severe MTX-resistant RA. We report data from the group of patients who received ETN 50 mg/week plus MTX (ETN + MTX, n = 281) in a clinical trial consisting of an initial 24-week open-label phase, followed by a 104-week extension. Remission was defined as 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) score < 2.6. Cutoff values to dichotomize baseline variables maximizing the detection of remission were obtained from Receiver Operator Curve analyses. Baseline dichotomized and categorical variables were analyzed altogether in a stepwise logistic regression model. Odds of attaining response at Weeks 24 and 128 were estimated for each significant predictor. Results At Week 24 and Week 128, 27% (66/241) and 42% (91/219) of patients in the ETN + MTX group achieved remission. On average, patients achieving remission were younger and had lower baseline ESR, lower Physician Global Assessment (PGA) scores, lower total Health Assessment Questionnaire (HAQ) scores, and lower visual analog scale (VAS) Pain scores compared with patients who did not achieve remission. The best subset of baseline variables predicting Week 24 remission in the stepwise regression model were age ≤ 49 years (odds ratio [OR] 2.93), body mass index (BMI) > 28.5 kg/m2 (OR 3.24), disease duration > 3.7 years (OR 2.22), ESR ≤ 42 mm/h (OR 2.72), PGA ≤ 6 (OR 3.21), tender joint count ≤ 14 (OR 2.25), and total HAQ score ≤ 1.6 (OR 2.86). At Week 128, age ≤ 42 years (OR 2.21), SF-36 Mental Health Scale score > 39.6 (OR 2.16), White race (OR 4.07), > 18 swollen joints (OR 2.11), and VAS Pain ≤ 41 (OR 6.05) at baseline were the best subset of significant predictors of remission. Conclusions In LA patients with RA, younger age, higher BMI, longer disease duration, higher SF-36 Mental Health Scale score, higher swollen joint count, and overall lower disease activity predicted clinical response to ETN + MTX therapy. Trial registration: ClinicalTrials.gov Identifier: NCT00848354.
Fabiola Reis Oliveira, Valeria Valim, Sandra Gofinet Pasoto, Marilena Leal Mesquita Silvestre Fernandes, Maria Lucia Lemos Lopes, Sonia Cristina De Magalhães Souza Fialho, Aysa César Pinheiro, Laura Caldas dos Santos, Simone Appenzeller, Tania Fidelix, et al.
Published: 3 September 2021
Advances in Rheumatology, Volume 61, pp 1-13; https://doi.org/10.1186/s42358-021-00208-1

Abstract:
Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs. Women with SS often experience gynecological symptoms due to the disease and need extra care regarding their sexual activity, reproductive health and during pregnancy, conditions that are not properly conducted in the clinical practice. To cover this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of symptoms, diagnosis, monitoring, prognosis, and treatment of these manifestations. A Focus Group meeting was held and included experts in the field and methodologists, based on a previously developed script, with themes related to the objective of the study. The most important topics were summarized and 11 recommendations were provided.
Published: 3 September 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00211-6

Abstract:
Background Anti-rheumatic drugs can increase the predisposition to infection, and patients may be unaware of continuing their treatment during the COVID-19 pandemic. Objective This study aimed to assess whether patients maintain their treatment for rheumatic conditions during the pandemic period and determine the factors responsible for discontinuation. Methods Patients were randomly selected from the prospectively collected database of our tertiary referral center. The patients were interviewed by telephone through a standardized closed-ended questionnaire, which is targeting the continuity of the treatment plan and the considerations related to the individual choice. The patients were asked whether they hesitated to visit the hospital for follow-up or intravenous drug administration. Results A total of 278 patients completed the questionnaire. While 62 of the patients (22.3%) had reduced or interrupted the treatment, only 11 patients (3.9%) stopped the treatment completely. A significant difference was observed between the duration of illness and the discontinuation of treatment. (p = 0.023) There was a significant difference in disease activity between the group that stopped treatment and continued treatment. (p = 0.001) There was no statistically significant difference in other demographic characteristics. One hundred thirty-five patients (48.6%) made the treatment decision by themselves, and 80% continued the treatment. Reasons for stopping the treatment were anxiety (48.4%), not being able to go to the hospital for intravenous treatment (45.1%), and not being able to find the drug (6.5%). Conclusion Since patients with long-term illnesses were found to be significantly more likely to stop their treatment, this group of patients should be monitored.
Francisco Paulin, Anastasia Secco, Federico Benavidez, Juan José Rodríguez Moncalvo, Orlando Gabriel Carballo, Fernanda Ingenito, Martin Eduardo Fernández, Agustina Cáceres, Fabian Caro, Patricia Sasaki, et al.
Published: 24 August 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00209-0

Abstract:
Background Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. Methods We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis. We performed a structured questionnaire, HRCT and lung functional tests looking for lung disease, together with joint disease evaluation. We analyzed which variables were associated with the presence of lung disease on HRCT. Results We included 83 patients, 83% females. The median (IQR) of time since RA diagnosis was 3 (1–6) months. In the HRCT, 57 patients had airway compromisea (72%), and 6 had interstitial abnormalities (7.5%). The most common altertion found in lung functional tests was a reduced DLCO (14%). The presence of at least one abnormality in the physical exam was associated with lung involvement on HRCT [13 (21.6%) vs 0 (0%); p = 0.026]. Also, patients with lung involvement presented significantly lower values of FVC% and DLCO%, and higher values of RV/TLC. No variable related to joint involvement was found associated with alterations in HRCT. Conclusion Our study shows that a large proportion of early RA patients has abnormal findings in HRCT. Further studies are required to confirm these findings.
, Alp Çetin
Published: 23 August 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00210-7

Abstract:
Background The aim of this study was to evaluate social media use in patients with fibromyalgia syndrome (FMS) and determine the effect of social media use on disease severity and sleep quality. Materials and methods In total, 205 social media using patients with similar characteristics were included in the study. The study group consisted of 103 patients with FMS, and the control group consisted of 102 patients without FMS. The FMS symptom severity scale and diffuse pain index were used to determine the disease severity in FMS patients, the sleep disorder short form questionnaire (PROMIS) was used to evaluate sleep quality, and the Social Media Addiction Scale-Adult Form was used to evaluate social media addiction. A visual analog scale was applied to evaluate pain in both the patient and control groups, and social media usage times were recorded. Results We found that pain severity, sleep disturbance and social media addiction were higher in patients with FMS than in the control group, and there was no relationship between the rates of social media use in patients with FMS and the severity and prevalence of the disease. Conclusion The use of social media is more frequent in patients with FMS, which can motivate healthcare professionals to evaluate social media habits in individuals with FMS.
Renato Vicente Ferreira, , Vera Lucia Szejnfeld
Published: 9 August 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00206-3

Abstract:
Background Osteoporosis is an underdiagnosed condition, and its seriousness is not considered until severe complications arise. This study aimed to evaluate general dentists’ knowledge about osteoporosis and their ability to identify patients with this disease by assessing mandibular cortical width (MCW) and mandibular cortical index (MCI) on panoramic dental radiographs using a visual method. Methods In this cross-sectional study, an email questionnaire regarding the diagnosis and prevention of osteoporosis was sent to 20,773 dentists in 2016. Those who completed the questionnaire were invited to participate in radiomorphometric training and then to analyze the MCI and MCW of 114 panoramic radiographs of postmenopausal women who underwent both panoramic radiography and bone densitometry. Based on the radiomorphometric indices and while blinded to the densitometry results, the dentists determined whether they would indicate densitometry for these patients. Results The response rate was 2.3%: 485 dentists completed the questionnaire, and 50 evaluated panoramic radiographs using the MCW and MCI. All of them reported some knowledge about osteoporosis, but 41.6% demonstrated a misleading conceptualization of the disease. Approximately 90% reported minimal access to this information during graduation, and only 27.0% were exposed to the topic during their postgraduate studies. Interest in osteoporosis prevention was expressed by 70.7% of the respondents, and interest in learning the radiomorphometric indices was expressed by 99.0%. The sensitivity in the detection of low bone mineral density through the MCW and MCI was 52.9%, and the specificity was 64%. Conclusions Brazilian dentists demonstrated insufficient knowledge about osteoporosis and a low ability to detect osteopenia or osteoporosis by applying radiomorphometric indices.
John M. Stacy, Jacob R. Greenmyer, James R. Beal, Abe E. Sahmoun, Erdal Diri
Published: 9 August 2021
Advances in Rheumatology, Volume 61, pp 1-6; https://doi.org/10.1186/s42358-021-00205-4

Abstract:
Background The ACR/EULAR recommendations endorse the use of glucocorticoids (GCs) for rheumatoid arthritis (RA) patients’ flares and as a bridge to a DMARD. However, the recommendation of low dose short-term monotherapy with (GCs) remains open to the discretion of the clinician. The aim of this study was to assess whether a short-term use of low dose prednisone monotherapy was effective in inducing remission in newly diagnosed RA patients. Methods A retrospective analysis of patients newly diagnosed with RA at a Community Health Center in North Dakota was performed based on the ACR/EULAR RA classification criteria. Demographic and clinical data were abstracted from patients’ medical charts. Patients treated with (< 10 mg/day) of prednisone up to 6 months were included. Response to prednisone was analyzed according to pre- and post-treatment DAS28-ESR score and EULAR response criteria. Results Data on 201 patients were analyzed. The mean prednisone dose was 8 mg/day (range: 5–10; SD = 1.2) and the mean treatment duration was 42.2 days (12–177; 16.9). Disease severity significantly improved from baseline to follow-up for: tender joint count (8.6 ± 4.8 vs. 1.5 ± 3.3; P < 0.001), swollen joint count (6.2 ± 5.0 vs. 1.4 ± 3.0; P < 0.001), and visual analog pain score (4.8 ± 2.6 vs. 2.1 ± 2.5; P < 0.001). DAS28-ESR disease severity significantly improved from baseline to follow-up: (5.1 ± 1.2 vs. 2.7 ± 1.3; P < 0.001). Per EULAR response criteria, 69.7% of patients showed good response to treatment and 20.4% showed moderate response. 54.2% of patients reached remission. Conclusion Short-term use of low dose prednisone monotherapy induced disease remission and improved clinical severity of RA in the majority of newly diagnosed patients.
, José Alexandre Mendonça, Penelope Ester Palominos, Charles Lubianca Kohem, Tania Ferreira Cestari, Rafael Mendonça Da Silva Chakr
Published: 28 July 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00207-2

Abstract:
Background Nail psoriasis occurs frequently in patients with psoriatic disease, it can lead to functional impairment, pain, discomfort, decreased quality of life and can also be a predictor for the development of arthritis. Early recognition of this condition can provide early and effective treatment and prevent structural impairment. This study aims to identify nail ultrasonographic characteristics in three groups: psoriasis (PsO), psoriatic arthritis (PsA) and controls patients, to determine if the ultrasonography (US) can identify early signs of nail psoriatic impairment or local inflammation. We conducted nail US to determine nail matrix resistance index (NMRI), nail bed resistance index (NBRI), and power Doppler (PD) and grayscale (GS) parameters in these 3 groups. Methods Single-center, cross-sectional study. GS, PD, and spectral doppler images of bilateral 2nd and 3rd fingernails were acquired from 35 PsO, 31 PsA, and 35 controls patients. An US equipment with an 18 MHz linear transducer for GS and 8.0 MHz for PD was used. PD, NMRI, NBRI, nail plate thickness (NPT), nail bed thickness (NBT), nail matrix thickness (NMT), and morphostructural characteristics of the trilaminar structure (TS) were evaluated in saved images, blind. Results Mean NMRI and NBRI did not differ between groups. Linear regression analysis detected no relationships between PsO or PsA and NMRI or NBRI. Nail PD grade did not differ between groups. Type I and IV TS changes were more frequent in PsO; types II and III changes were more frequent in PsA (p < 0.001). NPT was greater in PsA and PsO groups than controls: PsA 0.73 ± 0.14 mm, PsO 0.72 ± 0.15 mm, Controls 0.67 ± 0.10 mm (p = 0.001). Conclusion Echographic TS characteristics of the nail plate and NPT evaluated by GS are useful and can distinguish PsO and PsA nails from controls. NMRI, NBRI, and US nail microcirculation parameters could not distinguish psoriatic nails. Trial registration 72762317.4.0000.5327 (Certificate of Presentation of Ethical Appreciation – CAAE - Plataforma Brasil) Avaiable in https://plataformabrasil.saude.gov.br/login.jsf.
, Vanessa Barrili Busato, Romulo Gomes da Silveira, Aline Defaveri Do Prado, Cynthia Goulart Molina-Bastos, Sheila Hickmann, Guilherme Kopik Bongiorno, Camila De David Cruz, Sheron Zamboni, Julio César Simon, et al.
Published: 20 July 2021
Advances in Rheumatology, Volume 61; https://doi.org/10.1186/s42358-021-00203-6

Abstract:
To evaluate the quality of referrals for a first Rheumatology consultation at a tertiary care center in a southern Brazilian capital (Porto Alegre, RS), having as background findings from a similar survey performed in 2007/2008. Since then, our state has implemented referral protocols and a triage system with teleconsulting support exclusively for referrals from locations outside the capital, permitting a comparison between patients screened and not screened by the new system. Physicians of the Rheumatology Service at Hospital Nossa Senhora da Conceição prospectively collected information regarding first visits over a 6-month period (Oct 2017 to March 2018). We recorded demographic characteristics, diagnostic hypotheses, date of referral, and the municipality of origin (within the state of Rio Grande do Sul). We considered adequate referrals from primary health care when a systemic autoimmune inflammatory disease (SIRD) was suspected at first evaluation by the attending rheumatologist. Three hundred fifty-seven patients/appointments were eligible for analysis (193 from the capital and 164 from small and medium towns). In 2007/2008, suspected SIRD occurred in 76/260 (29.2%) and 73/222 (32.9%) among patients from the capital and outside counties, respectively (P = 0.387). In 2017/2018, suspected SIRD occurred in 75/193 (38.9%) and 111/164 (67.7%) in patients from the capital and outside counties, respectively (difference: 28.8, 95% CI: 19.0 to 38.9, P < 0.001), indicating a marked improvement in referrals submitted to the new triage system. The quality of Rheumatology referrals in our state improved over the 10-year interval under study, particularly among patients from locations submitted to referral protocols and teleconsulting support.
, Alessandro Conforti, Paola Cipriani, Roberto Giacomelli, Marco Tasso, Luisa Costa, Francesco Caso
Published: 8 July 2021
Advances in Rheumatology, Volume 61, pp 1-11; https://doi.org/10.1186/s42358-021-00204-5

Abstract:
As the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly, there are still many unresolved questions of how this virus would impact on autoimmune inflammatory joint diseases and autoinflammatory disorders. The main aim of this paper is to describe the main studies focusing their attention on COVID-19 incidence and outcomes of rheumatoid arthritis (RA), spondylarthritis (SpA), and autoinflammatory disease cohorts. We also revised possible pathogenic mechanisms associated with. Available data suggest that, in patients with RA and SpA, the immunosuppressive therapy, older age, male sex, and the presence of comorbidities (hypertension, lung disease, diabetes, CVD, and chronic renal insufficiency/end-stage renal disease) could be associated with an increased risk of infections and high rate of hospitalization. Other studies have shown that lower odds of hospitalization were associated with bDMARD or tsDMARDs monotherapy, driven largely by anti-TNF therapies. For autoinflammatory diseases, considering the possibility that COVID-19 could be associated with a cytokine storm syndrome, the question of the susceptibility and severity of SARS-CoV-2 infection in patients displaying innate immunity disorders has been raised. In this context, data are very scarce and studies available did not clarify if having an autoinflammatory disorder could be or not a risk factor to develop a more severe COVID-19. Taking together these observations, further studies are likely to be needed to fully characterize these specific patient groups and associated SARS-CoV-2 infection.
, Bruno Camargo Ochi, Carmen Flora Lessa
Published: 8 July 2021
Advances in Rheumatology, Volume 61, pp 1-10; https://doi.org/10.1186/s42358-021-00197-1

Abstract:
Background Infections are a major cause of morbidity and mortality in systemic lupus (SLE). Vaccination would be an effective method to reduce infection rate. Coverage for influenza and pneumococcus appears to be low in Latin America. The objective of this study was to evaluate vaccination coverage for influenza and pneumococcus in Latin America, causes of non-vaccination and to compare it with European patients. Methods A survey was conducted through social networks targeting Latin American lupus patients. A self-report was used to assess the demographics, risk factors for pneumonia, vaccination status, and causes of non-vaccination. The same method was used for European patients. We used binary logistic regression to identify factors associated with pneumococcal and influenza vaccination. Results There were 1130 participants from Latin America. Among them, 97% were women with an average of 37.9 years (SD: 11.3) and 46.5% had more than 7 years of disease duration. Two or more risk factors for pneumonia were found in 64.9%. Coverage for influenza and pneumococcal was 42.7 and 25% respectively, being lower than in Europe. Tetanus coverage was the most important predictor for receiving influenza and pneumococcal vaccination. Lack of prescription was the most common cause of non-application (64.6%). Conclusions Vaccination coverage for influenza and pneumonia is low in Latin America, especially compared to Europe. It is necessary to make specialists aware of their role in vaccine control and to implement measures to improve coordination between them and general practitioners.
Renata Casseb De Souza Carboni, Gustavo Luiz Behrens Pinto,
Published: 5 July 2021
Advances in Rheumatology, Volume 61; https://doi.org/10.1186/s42358-021-00199-z

Abstract:
Background The protein chitinase-3-like-1 (YKL-40) is rarely analyzed in patients with myositis. Therefore, we aimed to evaluate YKL-40 serum levels; correlate them with laboratory and clinical parameters, disease status, and treatment schemes; and analyze the YKL-40 expression in the muscle tissues of patients with antisynthetase syndrome (ASSD). Methods This cross-sectional single-center study included 64 adult patients with ASSD who were age-, gender-, and ethnicity-matched to 64 healthy control individuals. Their YKL-40 serum levels were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) kit method, while YKL-40 expression in muscle tissues was analyzed using an immunohistochemical technique. Disease status was assessed using the International Myositis Assessment and Clinical Studies Group (IMACS) set scores. Results The patients’ mean age was 44.8 ± 11.8 years, and median disease duration was 1.5 (0.0–4.0) years. These patients were predominantly female (82.8%) and Caucasian (73.4%). Most patients had stable disease. The median YKL-40 serum level was significantly higher in patients with ASSD when compared to the healthy individuals: 538.4 (363.4–853.1) pg/mL versus 270.0 (201.8–451.9) pg/mL, respectively; P < 0.001. However, YKL-40 serum levels did not correlate with any clinical, laboratory, disease status, or therapeutic parameters (P > 0.050), except tumor necrosis factor alpha (TNF-α) serum levels (Spearman’s correlation, rho = 0.382; P = 0.007). YKL-40 was highly expressed by inflammatory cells found in muscle biopsy specimens. Conclusions High YKL-40 serum levels were observed in patients with ASSD and correlated positively with TNF-α serum levels. Moreover, YKL-40 was expressed by the inflammatory cells of the muscle tissue.
, Ling Zheng, Hongbing Rui, Rihui Kang, Junmin Chen, Huaning Chen, Jizan Liu
Published: 2 July 2021
Advances in Rheumatology, Volume 61, pp 1-13; https://doi.org/10.1186/s42358-021-00202-7

Abstract:
Objectives To explore the risk factors for systemic lupus erythematosus (SLE) flare and their impact on prognosis. Methods The clinical characteristics, laboratory results, and treatment plans of 121 patients with SLE flare were retrospectively analyzed. Ninety-eight SLE outpatients with sustained remission during the same period were selected as controls. Logistic multivariate regression analysis was employed to screen for risk factors for SLE flare. Results Infection, thrombocytopenia, arthritis, anti-nucleosome antibodies positive, anti-β2-glycoprotein I (IgG) antibodies positive, and patient’s self-discontinuation of medicine maintenance therapy might be risk factors for SLE flare. Patients who discontinued medicine maintenance therapy by themselves had a significantly higher rate of severe SLE flare than patients with regular medicine maintenance therapy (P = 0.033). The incidence of anemia associated with SLE (P = 0.001), serositis (P = 0.005), and pulmonary hypertension (P = 0.003) in patients who discontinued medicine maintenance therapy were significantly higher than patients with regular medicine maintenance therapy. SLE patients with regular medicine maintenance therapy for less than 3 years had a higher risk of pulmonary hypertension than those with regular medicine maintenance therapy longer than 3 years (P = 0.034). Conclusions The accompanying thrombocytopenia, arthritis, anti-nucleosome antibodies positive and anti-β2-glycoprotein I (IgG) antibodies positive at the onset of SLE may affect the prognosis of SLE. Patient’s self-discontinuation of medicine maintenance therapy is the main cause of SLE flare, which may induce severe flare in SLE patients and lead to a significantly higher incidence of pulmonary hypertension.
Juliana Rosa Pires Vieira, , Marcos Rassi Fernandes, Nilzio Antonio da Silva
Published: 2 July 2021
Advances in Rheumatology, Volume 61; https://doi.org/10.1186/s42358-021-00201-8

Abstract:
Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by being multi-systemic and, therefore, reaching various organs and affecting mainly young women. Its pathogenesis comprehends many factors, including the interaction between microbiota and immune system. This systematic review assessed the relationship between intestinal microbiota and SLE in activity, highlighting microbiota representative patterns regarding quantity and diversity. Methods This study considered researches carried out in patients with SLE, with no restriction of age or gender, which fulfilled the classification criteria of either Systemic Lupus International Collaborating Clinic (SLICC), American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) and used the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) to classify disease in activity or remission were included. The search was carried out from October, 2020 to January, 2021 using the following databases: Medline via Pubmed, Scopus, and Embase. Five papers were included with a total of 288 participants with SLE. Results Regarding microbiota in patients with SLE in activity, there was significant increase in the following genera: Lactobacillus, Streptococcus, Megasphaera, Fusobacterium, Veillonella, Oribacterium, Odoribacter, Blautia, and Campylobacter. On the other hand, decrease in Faecalibacterium and Roseburia genera as well as Ruminococcus gnavus species was observed in remission cases, showing differences between the microbiota profile in SLE in activity and in remission. Conclusions Results suggest that dysbiosis may be involved in the disease activity process. Trial registration CRD42021229322.
, Nihal Tezel, Buse Ercan, Sadik Yigit Yildiz, Ece Unlu Akyuz
Published: 30 June 2021
Advances in Rheumatology, Volume 61, pp 1-6; https://doi.org/10.1186/s42358-021-00200-9

Abstract:
Background During the COVID-19 pandemic, individuals faced psychological stress caused by fear and anxiety due to the high transmission and mortality rate of the disease, the social isolation, economic problems, and difficulties in reaching health services. Fibromyalgia (FM) is a chronic centralized pain sensitivity disorder. Psychological, physical and/or autoimmune stressors were found to increase FM symptoms. This pilot study aimed to evaluate the COVID-19 fear and anxiety level, and to examine their effect on disease severity, sleep quality, and mood in FM patients compared to control group. Methods This pilot study conducted as a cross-sectional study, and included 62 participants. Participants were divided into two groups: FM patient group (n = 31) and control group (n = 31). Symptom severity, sleep quality, and mood were determined using the Revised Fibromyalgia Impact Questionnaire (FIQR), Pitsburg Sleep Quality Index (PSQI), and Hospital Anxiety Depression Scale (HADS), respectively. In order to evaluate the level of COVID-19 fear and anxiety, the Fear of COVID-19 Scale (FCV-19S) and Coronavirus Anxiety Scale (CAS) were used compared to control group. Results FIQR, PSQI, HAD-A, HAD-D, FCV-19S and CAS scores were significantly higher in the FM group (p = 0.01). A positive significant correlation was found between FCV-19S and CAS results and FIQR, PSQI, and HAD-anx results in FM patients (p < 0.05). Conclusion This pilot study showed that, the individuals with FM can be more affected by psychological stress, and this situation negatively affects the symptom severity, sleep quality, and mood in FM patients, so these patients should be closely monitored in terms of psychological stressors and their effects during pandemics. More studies with more participants are necessary to describe the challenges lived by fibromyalgia population.
, Wook Jang Seo
Published: 29 June 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00198-0

Abstract:
Objectives To investigate the frequency of monosodium urate (MSU) crystal deposits on dual-energy computed tomography (DECT) in patients with clinical diagnosis of gout and the factors associated MSU crystal positivity. Methods This study was conducted in patients with clinical diagnosis of gout who underwent DECT. Clinical features were compared between patients with positive and those with negative DECT results. A logistic regression analysis was performed to determine the factors associated with MSU crystal positivity on DECT. Results A total of 148 patients with clinical diagnosis of gout were included, and MSU crystal deposition on DECT was observed in 64 patients (43.3%). The patients with positive DECT results were more likely to have renal insufficiency, longer disease duration, and higher serum urate level than those with negative. In the multivariable analysis, first gout attack (odds ratio 0.462; 95% confidence interval 0.229–0.931, p = 0.031) was associated with a less likely MSU crystal deposit-positive DECT result. In the subgroup analysis of patients with first attack, serum urate level > 8 mg/dL was associated with DECT positivity. Conclusion Of the patients with clinical diagnosis of gout, those with renal insufficiency, longer disease duration, and high serum urate level were more likely to be positive of gout on DECT. First gout attack was associated with less likely to be positive for MSU crystal on DECT. Thus, performing DECT scan in the selected patients who had characteristics that highly probability of DECT positivity could increase positive predictive value.
, Özgür Zeliha Karaahmet, Ajda Bal Hastürk, Özge Başaran, Banu Çelikel Acar, Halise Hande Gezer, Aytül Çakcı
Published: 26 June 2021
Advances in Rheumatology, Volume 61, pp 1-8; https://doi.org/10.1186/s42358-021-00195-3

Abstract:
Background Juvenile idiopathic arthritis (JIA) can cause reduced exercise capacity, deterioration in functional activities, and poor health-related quality of life. This study aims to objectively reveal lower extremity involvement in the peripheral predominant forms of juvenile idiopathic arthritis through qualitative evaluations and to determine the effects of these involvements on exercise, function, and quality of life. Methods Thirty-two patients with a history of peripheral arthritis and aged between 7 and 16 years participated in the study. Demographics, JIA subtype, disease duration, arthritis and deformities of the lower extremity, disease activity score, 6-min walk test (6MWT), cycling exercise test (CYC-E), childhood health assessment questionnaire (CHAQ), and pediatric quality of life inventory (PedsQoL) scores were recorded. In case of clinical suspicion of arthritis, an ultrasonographic examination was performed for a definitive diagnosis. Regression analyses were performed to explore the most associated lower extremity involvement and patient characteristics for each of the dependent variables including 6MWT, CYC-E, CHAQ, and PedsQoL. Results Of the total number of patients, with a mean age of 12.91 (SD 2.37) years, 28.1% had knee arthritis, 15.6% foot arthritis, 12.5% hip arthritis, and 37.5% lower extremity deformity. The parameters that were most associated with CHAQ and PedsQoL were hip and knee arthritis, whereas CYC-E was found to be most associated with knee arthritis and height, and 6MWT was found to be most associated with hip arthritis, knee arthritis, and demographic characteristics. Conclusion This study emphasizes the importance of hip and knee arthritis, which are among the determinants of walking endurance, function, and quality of life; and knee arthritis, which is among the determinants of cycling performance in JIA with lower extremity involvement.
, Ivânio Alves Pereira, Gláucio Ricardo Werner de Castro, Licia Maria Henrique da Mota, Ana Paula Carnieletto, Dhara Giovanna Santin de Souza, Fabiana Oenning da Gama, Ana Beatriz Vargas Santos, Cleandro Pires de Albuquerque, Manoel Barros Bértolo, et al.
Published: 25 June 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00186-4

Abstract:
Background Rheumatoid arthritis (RA) is a common autoimmune systemic inflammatory disease. In addition to joint involvement, RA patients frequently have other comorbidities, such as cardiovascular diseases. Drugs used for RA treatment may increase or decrease the risk of a cardiovascular event. This study aims to analyze cardiovascular risk comorbidities in patients with RA and the correlation with the use of anti-rheumatic drugs. Methods Cross-sectional study conducted based on the real-life rheumatoid arthritis study database – REAL, a prospective observational cohort study. Associations between the use of anti-rheumatic drugs and the presence of comorbidities were represented by their prevalence ratio and evaluated using the Chi-square or Fisher’s Exact tests. Results We assessed 1116 patients, 89.4% women, mean age of 55.15 years and predominance of seropositive disease. 63.3% had some cardiovascular comorbidity, predominantly hypertension (49.9%). The use of glucocorticoids was observed in 47.4% of patients and there was a significant tendency of lower use of these drugs in the presence of dyslipidemia (PR: 0.790; p = 0.007). We observed that the presence of cardiovascular comorbidities was associated with higher use of bDMARDs (PR:1.147; p = 0.003). Conclusions The presence of cardiovascular risk comorbidities was confirmed to be higher in RA patients. Different treatment strategies using less glucocorticoids in the presence of dyslipidemia and more common use of bDMARDs in patients with cardiovascular comorbidities suggest that rheumatologists are aware of the potential influence of the DMARDs in the risk of cardiovascular event. Reinforcing these results, we highlight the need for a better baseline assessment to guide the choice of anti-rheumatic drugs in RA patients who have comorbidities.
Correction
Francisco Vileimar Andrade de Azevedo, Hermano Alexandre Lima Rocha, Anamaria Jones, Jamil Natour, Francisco Airton Castro da Rocha
Published: 22 June 2021
Advances in Rheumatology, Volume 61, pp 1-1; https://doi.org/10.1186/s42358-021-00196-2

Leda Magalhaes Oliveira, , Flavio Duarte Silva, Arnaldo Roizenblatt, Artur Rocha Correa Fernandes, Vera Lucia Szejnfeld
Published: 12 June 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00191-7

Abstract:
Background Trunk pelvic dissociation is fundamental to the compensatory mechanism for muscle weakness during body bending. We carried out an early investigation of gait changes in a sample of community-dwelling women ≥60 years without gait complaints. The primary objective was to correlate spine and pelvic angles with performance tests and accelerometry parameters. The secondary objective was to correlate performance tests with accelerometry. Methods In this cross-sectional study, 54 community-dwelling women ≥60 years were subjected to Falls Efficacy Scale-International (FES-I), performance tests (Berg Balance Scale, Timed Up and Go, and Gait analysis), and radiographic analysis of sagittal alignment (Thoracic and Lumbar Cobb, Pelvic Incidence, Sacral Slope, and Pelvic Tilt angles). Gait speed was assessed in a 10-m comfortable walk, and accelerometry parameters were obtained in a 30-m walk distance. Results The sample, aged 72 ± 6 years, exhibited moderate correlation between Sacral Slope and Step Length (+ 0.615). Sacral Slope weakly correlated with FES-I (− 0.339), Berg Balance Scale (+ 0.367), and with further accelerometry data in the AP plane: RMS, (+ 0.439) and Stride Regularity (+ 0.475), p < 0.05, all. Lumbar Cobb weakly correlated with the following accelerometry data in the AP plane: Step Length (+ 0.405), RMS, (+ 0.392), and Stride Regularity (+ 0.345), p < 0.05, all. Additionally, Stride Regularity in AP moderately correlated with FES-I (0,561, p < 0.05), among other weak correlations between performance tests and accelerometry data in AP. Conclusions Early alterations in Sacral Slope and gait abnormalities in the AP plane may provide understanding of the early gait changes in robust older women.
Jin Shang, Xiao-Hu Li, Shu-Qin Lu, Yi Shang, Lu-Lu Li,
Published: 12 June 2021
Advances in Rheumatology, Volume 61, pp 1-14; https://doi.org/10.1186/s42358-021-00194-4

Abstract:
Objectives To investigate the diagnostic performance of single-source dual-energy computed tomography (DECT) based on gemstone spectral imaging technology (including Discovery CT750HD and Revolution CT) in patients with suspected feet/ankles gouty arthritis, and evaluate the urate deposition with a novel semi-quantitative DECT scoring system. Methods A total of 196 patients were consecutively included. Feet and ankles were evaluated in all patients by single-source DECT scan. The 2015 EULAR/ACR criteria were used as the reference for the diagnosis of gout. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DECT for the diagnosis of gout in the early (≤1 year), middle (1–3 years), and late (> 3 years) disease durations were calculated. Besides, a novel semi-quantitative DECT scoring system was assessed for the measurement of urate deposition, and the correlation between the scores and the clinical and serological data were also evaluated. Moreover, the influences of artifacts on the diagnostic performance of DECT were also determined. Results The sensitivity, specificity, and AUC of DECT in 196 patients were 38.10, 96.43%, and 0.673 in the early-stage group; 62.96, 100.00%, and 0.815 in the middle-stage group; and 77.55, 87.50%, and 0.825 in the late-stage group, respectively. The overall diagnostic accuracies in the AUC of DECT (Discovery CT750HD and Revolution CT) in the middle and late stages of gout were higher than that in the early stage of gout. Besides, the monosodium urate crystals were deposited on the first metatarsophalangeal joints and ankles/midfeet. Age, the presence of tophus, bone erosion, and disease duration considerably affected the total urate score. No statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise artifact was found between the case and control groups. Conclusion DECT (Discovery CT750HD and Revolution CT) showed promising diagnostic accuracy for the detection of urate crystal deposition in gout but had limited diagnostic sensitivity for short-stage gout. Longer disease duration, the presence of tophus, and bone erosion were associated with the urate crystal score system. The artifacts do not remarkably affect the diagnostic performance of DECT in gout.
, Sherif M. Gamal, Nesreen Sobhy, Ibrahem Siam, Ahmed M. Soliman, Ghada W. Elhady, Tamer A. Gheita
Published: 9 June 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00193-5

Abstract:
Background Vasculitis damage index (VDI) is a validated damage index for systemic vasculitis, and as Behçet’s disease is considered one of systemic vascular disease we aimed to study the relationship of the vasculitis damage index to clinical manifestations and comorbidity in patients with Behçet’s disease (BD) to determine if VDI could be used to assess damage in patients with BD. Methods A total of 109 patients with BD were recruited from the Rheumatology Department (outpatient and inpatient clinic), Cairo University Hospitals. All patients were subjected to full history taking, clinical examination, and routine laboratory investigations. Disease activity was assessed by the BD current activity form, and the VDI was calculated in all patients. The relationship of the VDI to the disease clinical manifestations was studied. Mann–Whitney and Kruskal Wallis tests were used to estimate differences in quantitative variables. Spearman correlation test was used to test for correlation between quantitative variables. Results In the current study, the VDI ranged from 1 to 10, with a mean of 3.5 ± 1.8. It was significantly associated with total thrombosis (P = 0.022); total neurological manifestations (P = 0.000), especially stroke and cranial nerve affection; uveitis (P = 0.005); avascular necrosis (AVN) (P = 0.015); osteoporosis (P = 0.01); impaired vision (P < 0.0001); cataract (P < 0.0001); and diabetes (P = 0.012). Generally, immunosuppressive treatment was significantly associated with VDI (P = 0.039), especially cyclophosphamide (P < 0.0001), biological agent (P = 0.008), chlorambucil (P = 0.003), and anticoagulant (P = 0.02). VDI was also significantly correlated with age (P = 0.033), disease duration (P = 0.029), and duration of eye involvement (P = 0.003). Conclusion VDI is significantly associated with most disease parameters of BD, except for parameters such as mucocutaneous manifestations and uncomplicated venous thrombosis; however, further studies may be needed to establish BD-specific damage index.
Isadora Carvalho Medeiros Francescantonio, Leandro Augusto Rodrigues dos Santos, Paulo Luiz Carvalho Francescantonio, Luiz Eduardo Coelho Andrade,
Published: 9 June 2021
Advances in Rheumatology, Volume 61, pp 1-12; https://doi.org/10.1186/s42358-021-00190-8

Abstract:
Objective To evaluate the perception of rheumatologists regarding the recommendations of the Brazilian Consensus for detection of Autoantibodies (BCA) on HEp-2 Cells by Indirect Immunofluorescence assay (IFA) and how BCA recommendations help in clinical practice. Methodology A structured questionnaire regarding the BCA recommendations for detection and interpretations of autoantibodies in HEp-2 cells was applied to randomly selected rheumatologists. The results were tabulated using the Microsoft® Excel program, expressed as a simple percentage and the dichotomous data were analyzed using the Chi-square test and the Epi Info® program. Results Four hundred fuorteen rheumatologists participated in the study: 70% of them considered their knowledge of the HEp-2 IFA test satisfactory or excellent, and 43% said they knew the BCA recommendations in general, without distinguishing the edition of the BCA to which they refer. The Revista Brasileira de Rheumatologia/Advances in Rheumatology was the means of dissemination most consulted by specialists (50%). According to the rheumatologists’ opinion, the most relevant pattern was the homogeneous nuclear (78%) and 65% stated they were satisfied with the BCA recommendations at a level of satisfaction greater than or equal to 80%. There was no significant difference in the perception of rheumatologists from the several Brazilian geographic regions. Conclusion Brazilian rheumatologists are aware of the BCA guidelines and most are satisfied with the content published, considering that the BCA recommendations assist positively in the clinical practice. Most rheumatologists recognize the patterns associated with rheumatic autoimmune diseases and have used BCA recommendations to interpret the results of the HEp-2 IFA test.
Binfeng Wang,
Published: 9 June 2021
Advances in Rheumatology, Volume 61, pp 1-11; https://doi.org/10.1186/s42358-021-00187-3

Abstract:
Background Osteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells. Methods Relative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p. Results Relative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells. Conclusions Overexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.
, Vanessa Hax, Odirlei Monticielo, Tamires Ferri Macedo, Roberta Kern Menna Barreto, , Rafael Chakr
Published: 9 June 2021
Advances in Rheumatology, Volume 61, pp 1-10; https://doi.org/10.1186/s42358-021-00192-6

Abstract:
Background Systemic sclerosis (SSc) is a chronic disease characterized by autoimmunity, vasculopathy, and visceral and cutaneous fibrosis. Vitamin D has several functions in the immunological system, and different studies have suggested a potential role in triggering autoimmune diseases. Patients with SSc may present with low serum levels of vitamin D, but the association between hypovitaminosis D and disease onset or any clinical manifestation is still obscure. Our goal was to verify the causal relationship between hypovitaminosis D and SSc onset or any particular clinical manifestation in the literature. Methods A systematic literature review was performed through February 24th, 2021 on Pubmed, Lilacs/BIREME, and Cochrane databases. The eligible studies were read in full text, and, in the absence of exclusion criteria, were included in this review after consensus between two reviewers. Results Forty articles met the eligibility criteria and the main results of each study are described. In most studies, SSc patients showed a higher prevalence of vitamin D deficiency and insufficiency compared to controls. Additionally, in some reports serum levels of vitamin D were inversely correlated with the severity of SSc. Oral supplementation did not seem to affect serum levels of vitamin D. Four of the included studies were with experimental models. Conclusion In conclusion, vitamin D deficiency seems to have a role in susceptibility to SSc, as well as in the clinical manifestations of the disease.
Hülya Kaçmaz, Esin Aldemir, Ayşe Tanatar, Şerife Gül Karadağ, Mustafa Çakan, Hafize Emine Sönmez,
Published: 5 June 2021
Advances in Rheumatology, Volume 61, pp 1-5; https://doi.org/10.1186/s42358-021-00188-2

Abstract:
Background Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serositis. Sacroiliitis can be observed in some FMF patients. This study aimed to compare the demographic, clinical, and laboratory findings, and treatment in children with FMF and sacroiliitis, and children with juvenile spondyloarthropathy (JSpA). Methods In total, 1687 pediatric FMF patients that were followed-up between May 2010 and June 2020 were evaluated retrospectively. Among them, those with sacroiliitis (n = 63) were included in the study and compared to patients with JSpA (n = 102). Results The study included 63 FMF patients with sacroiliitis (38 males [60.3%] and 25 females [39.7%]) with a mean age of 15.2 ± 4.1 years. Mean age at symptom onset was 7.2 ± 5.05 years and mean age at diagnosis was 9.74 ± 4.67 years. The most common mutation in the FMF patients was M694V/M694V (n = 22). Patients were diagnosed with sacroiliitis with a mean of 12 months (range: 6–36 months) after the diagnosis of FMF. Among the FMF patients, 28 (44.4%) had enthesitis, 23 (36.5%) had heel pain, and 11 (17.4%) had low back pain. The study also included 102 JSpA patients (90 males [88.2%] and 12 females [11.8%]). Mean age of patients with JSpA was 16.1 ± 2.8 years. As compared to 102 JSpA patients, patients with FMF and sacroiliitis had higher acute phase reactants, whereas HLA-B27 positivity rate was lower. In addition, axial involvement rate was higher in the JSpA patients. Conclusion Sacroiliitis is a common co-morbidity in FMF patients. The phenotypic features of these patients are different from patients with JSpA.
Published: 5 June 2021
Advances in Rheumatology, Volume 61, pp 1-8; https://doi.org/10.1186/s42358-021-00189-1

Abstract:
Background The Functional Index for Hand Osteoarthritis (FIHOA) is a simple, reliable, and reproducible specific instrument to evaluate hand OA that can be applied both in clinical practice and research protocols. In order to be used in Brazil, FIHOA has to be translated into Portuguese, culturally adapted and have the reliability of the translated FIHOA version tested, which is the purpose of this study. Methods The FIHOA was translated into Brazilian Portuguese and administered to 68 patients with hand OA recruited between May 2019 and February 2020. The test-retest was applied to 32 patients and the reliability was assessed using Spearman’s correlation coefficient and intraclass correlation coefficient (ICC). The internal consistency reliability was evaluated using Cronbach’s alpha. External construction validity was assessed using the Spearman’s correlation test between FIHOA and pain, assessed with a Visual Analogue Scale (VAS), the Cochin Hand Functional Scale (CHFS) and Health Assessment Questionnaire (HAQ). Results The 30 participants that initially answered the translated version of the FiHOA did not report difficulties in understanding or interpreting the translated version. The test-retest reliability for the total score was strong (r = 0.86; ICC = 0.89). Mean differences (1.37 ± 0.68) using Bland Altman’s analysis did not significantly differ from zero and no systematic bias was observed. Cronbach’s alpha was also high (0.89) suggesting a strong internal coherence in the test items. There were also correlations between FIHOA and the CHFS (r = 0.88), HAQ (r = 0.64) and pain in the hands both at rest (r = 0.55) and in motion (r = 0.44). Conclusion The translation of the FIHOA into Brazilian Portuguese proved a valid instrument for measuring the functional capacity of patients with hand OA who understand Brazilian Portuguese.
Laiza Hombre Dias, Samira Tatiyama Miyamoto, Raquel Altoé Giovelli, Caerê Iamonde Maciel de Magalhães,
Published: 29 May 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00181-9

Abstract:
Background Few studies have evaluated the relation of quality of life (QoL) with symptoms and disease activity in primary Sjögren’s syndrome (pSS). There is also scant information on the predictors of QoL in this population. The aim of this study was to assess QoL in patients with pSS and to investigate their possible predictors. Methods In a cross-sectional study, 77 patients with pSS were evaluated using the following questionnaires: Functional Assessment of Chronic Illness Therapy Fatigue Subscale (FACIT-Fatigue), EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Short Form-36 Health Survey (SF-36) and World Health Organization Quality of Life Assessment (WHOQOL-BREF). Seventy-seven healthy controls responded to the SF-36 and WHOQOL-BREF. The Mann-Whitney test, t-test, Pearson and Spearman correlation, and multiple regression analysis were used in the statistical analysis. Results Patients with pSS and healthy controls were matched by gender and age. The mean scores for the ESSDAI, ESSPRI and FACIT-Fatigue were 3.34 ± 4.61, 6.58 ± 2.29 and 26.17 ± 11.02, respectively. Patients had a lower employment rate (36.4% versus 62.3%, p < 0.01) and higher work disability (10.4% versus 1.3%, p < 0.01). SF-36 and WHOQOL-BREF values were lower in patients with pSS (p < 0.001), except in the WHOQOL-BREF environment domain. Pain (ESSPRI), fatigue (FACIT-Fatigue), antinuclear antibody (ANA), anti-Ro-SSA and economic class (Brazilian Economic Classification Criteria - CCEB) were independent predictors of QoL. Conclusions The main predictors of poor QoL in patients with pSS were pain and fatigue, and these symptoms had an impact regardless of disease activity, age, schooling, marital status, work disability and fibromyalgia.
, , Vanessa Hax, Isadora Flesch da Silva Moreira, Carolina Yuka Ueda, Rafaella Romeiro Piovesan, Ricardo Xavier, Rafael Chakr
Published: 22 May 2021
Advances in Rheumatology, Volume 61, pp 1-11; https://doi.org/10.1186/s42358-021-00182-8

Abstract:
Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by vasculopathy and fibrosis, which can be subclassified into diffuse cutaneous (dSSc) and limited cutaneous (lSSc) subtypes. Previous studies suggest that an increase in monocytes can be a hallmark of various inflammatory diseases, including SSc. Our aim was to evaluate circulating blood monocyte subpopulations (classical, intermediate and non-classical) of SSc patients and their possible association with disease manifestations. Methods Fifty consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in a cross-sectional study. Monocyte subpopulations were identified based on their expression of CD64, CD14 and CD16, evaluated by flow cytometry, and were correlated with the clinical characteristics of the patients; furthermore, the expression of HLA-DR, CD163, CD169 and CD206 in the monocytes was studied. Thirty-eight age- and sex-matched healthy individuals were recruited as a control group. Results SSc patients had an increased number of circulating peripheral blood monocytes with an activated phenotypic profile compared to healthy subjects. Absolute counts of CD16+ (intermediary and non-classical) monocyte subpopulations were higher in SSc patients. There was no association between monocyte subpopulations and the clinical manifestations evaluated. Conclusion We identified higher counts of all monocyte subpopulations in SSc patients compared to the control group. There was no association between monocyte subpopulations and major fibrotic manifestations. CD169 was shown to be more representative in dSSc, being a promising marker for differentiating disease subtypes.
, Flavia Tasmim Techera Antunes, Camila Ferraz, Alessandra Hubner de Souza, Daniel Simon
Published: 12 May 2021
Advances in Rheumatology, Volume 61, pp 1-8; https://doi.org/10.1186/s42358-021-00183-7

Abstract:
Background The Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene is a potential biomarker of vulnerability to pain. Thus, the present study aimed to investigate the association of this polymorphism with clinical and biopsychosocial factors in patients with chronic low back pain (CLBP). Methods A total of 107 individuals with CLBP answered questionnaires that were validated and adapted for the Brazilian population, including the Brief Inventory of Pain, the Central Sensitization Inventory, the Roland Morris Disability Questionnaire, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, the Survey of Pain Attitude-Brief, and the Hospital Anxiety and Depression Scale. All of the subjects were genotyped for the BDNF Val66Met polymorphism. Results The sample showed moderate scores of disability, central sensitization, and kinesiophobia, in addition to mild anxiety, hopelessness, and ruminant thoughts. No significant association was observed between the Val66Met polymorphism and the variables analyzed. Besides, there was no relationship between the BDNF Val66Met polymorphism with CSI, catastrophization, or disabilities that were generated by CLBP. Conclusion The results showed that the Val66Met polymorphism of the BDNF gene was not associated with clinical and biopsychosocial characteristics of CLBP in the sample studied.
Luiz Claudio Lacerda Rodrigues,
Published: 12 May 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00184-6

Abstract:
Objective To evaluate the effectiveness of surgery for the management of patients with symptomatic lumbar spinal stenosis. Methods Sixty-three patients with lumbar canal stenosis were randomized into two groups: the intervention group (IG) and control group (CG). IG patients underwent surgery and both groups participated in the same physical therapy program twice a week for a period of 12 weeks and were followed up at 1 year. The primary endpoint was visual analogue scale for pain, and the secondary endpoints were function (6-min walk test, Roland Morris and Oswestry questionnaires), quality of life (SF-36 questionnaire) and satisfaction with treatment (Likert scale). Results No significant difference between groups was observed for pain over time (p = 0.145). Significant differences between groups, in favor of the IG, were observed for the Oswestry score (p = 0.006) and vitality domain score of the SF-36 (p = 0.047). Function in the Roland Morris and 6-min walk test and the role of the physical domain of SF-36 also showed significant differences between the groups; however, these differences occurred due to a worsening of the IG in the short term, and the medium-term. The Likert scale demonstrated greater satisfaction with the IG treatment compared to control group. Conclusions Lumbar stenosis surgery did not improve pain in short and medium terms. Function and vitality were better in the group that underwent surgery in the medium term, and patients were more satisfied with the surgical treatment. Trial registration Clinicaltrials.gov (NCT02879461).
Eduardo Deves, Rodrigo Novotny, Fernando Hartmann Barazzetti, Mara Cristina Scheffer, Letícia Kramer Pacheco, Adriana Fontes Zimmermann, Ivânio Alves Pereira, Maria Luiza Bazzo,
Published: 4 May 2021
Advances in Rheumatology, Volume 61, pp 1-5; https://doi.org/10.1186/s42358-021-00180-w

Abstract:
Background Chronic prostatitis has been a common disease reported with high frequency in ankylosing spondylitis (AS) even from decades ago. Infectious (Chlamydia trachomatis) or non-infectious (uric acid) prostatitis can hypothetically trigger vertebral inflammation in AS. This study aimed to assess the features of chronic prostatitis in patients with AS compared to healthy controls. Methods A cross-sectional study including male patients with AS and healthy controls who agreed to undergo a prostate examination was conducted. Structured clinical interviews, prostate physical examinations, and cytological, biochemical, and microbiological tests on urinary samples collected before and after standardized prostatic massage (pre- and post-massage test) were performed. Results Ninety participants (45 AS patients, mean age: 52.5 ± 10.0 years, with longstanding disease, 12.4 ± 6.9 years, and 45 controls, mean age: 52.8 ± 12.1 years) were included. National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) scores were similar in the AS and control groups (4.0 [1.0–12.0] vs. 5.0 [1.0–8.5], p = 0.994). The frequencies of symptoms of chronic prostatitis (NIH-CPSI Pain Domain ≥4) were also similar in both groups (23.3% vs. 22.7%, p = 0.953). Results of polymerase chain reaction tests for Chlamydia trachomatis were negative in all tested urinary samples, and uric acid concentrations and leukocyte counts were similar in all pre- and post-massage urinary samples. Conclusions In this study, chronic prostatitis occurred in male patients with AS, but its frequency and characteristics did not differ from those found in the healthy male population of similar age.
Ming-Hui Hung, Ya-Chih Tien, Ying-Ming Chiu
Published: 8 April 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00173-9

Abstract:
Background Hepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg−/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). Methods Using a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg−/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs− serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one-to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses. Results Among 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ~ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89–0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48–15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22–88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88–0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39–871.5). Conclusions Besides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg−/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.
, , Marina Scolnik, Valeria Scaglioni, Javier E. Rosa, Enrique R. Soriano
Published: 7 April 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00179-3

Abstract:
Background To compare the incidence of osteoporotic fractures in patients with rheumatoid arthritis (RA) with matched controls from a university hospital. Methods Consecutive RA patients (n = 100) were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of diagnosis for RA patients and the date of the first medical claim at the Health Management Organization (HMO) for non-RA patients. Fracture incidence rates per 1000 persons-years (PY) for distinct types of fractures were calculated. Multivariate cox regression analysis was performed to identify factors associated with fractures. Results One hundred RA patients were followed for a total of 975.1 patients-years and 200 controls for 1485.7 patients-years. No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, 95% CI 12.7–28.6 vs 12.1, 95% CI 7.7–18.7, p = 0.07). In the Cox regression analysis, only age (HR 1.06, 95% CI 1.02–1.11, p = 0.006) and history of a prior fracture (HR 9.85, 95% CI 2.97–32.64, p < 0.001) were associated with fractures after the index date. The stratified analysis of the fractures by location showed that only the vertebral fractures were more frequent in RA patients compared with controls (12.9 per 1000 PY, 95% CI 8.9–25.8, vs. 3.4, 95% CI 1.4–8.1, respectively, p = 0.01). Conclusion Patients with RA didn’t show an overall increased risk of osteoporotic fractures compared with matched controls, but vertebral fractures were more frequently observed in patients with RA.
Sinem Can Oksay, , Sebnem Tekin Neijmann, Sami Hatipoglu
Published: 1 April 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00178-4

Abstract:
Background The most important finding that affects the prognosis in Familial Mediterranean Fever is renal amyloidosis. The aim of the present study was to analyze neutrophil gelatinase-associated lipocalin levels in the urine, and to investigate whether it may be used as an early marker for renal involvement. Methods Forty attack-free children followed by diagnosis of Familial Mediterranean Fever with age range of 5 and 18 years, and 38 healthy children with similar ages and genders were enrolled into the study. Hemogram, sedimentation, C-reactive protein, urine analysis, creatinine in the spot urine, microalbumin and urinary neutrophil gelatinase-associated lipocalin levels were analyzed and evaluated statistically in the patients and controls. Results There was not any statistically significant difference between the patient and control groups for age, gender, height and body weight. Although there was not any clinical sign of attack in the patient group, sedimentation, C-reactive protein and fibrinogen levels were significantly higher than the control group (p = 0.002, p = 0.023, and p = 0.006, respectively). Similarly, urinary neutrophil gelatinase-associated lipocalin level and urinary creatinine ratio were significantly higher in the patient group (p = 0.0001, p = 0.011, respectively). We found a positive correlation between uNGAL level and uNGAL/uCr ratio and number of attacks per year in FMF patients (r = 0.743, p = 0.001 and r = 0.516, p = 0.001; respectively). Conclusions Detection of significantly higher levels of urinary neutrophil gelatinase-associated lipocalin level and urinary neutrophil gelatinase-associated lipocalin level to creatinine ratio were suggested as urinary neutrophil gelatinase-associated lipocalin level as a non-invasive marker for renal involvement better than microalbumin.
, Ui Hong Jung, Jung-Yoon Choe
Published: 19 March 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00177-5

Abstract:
Background This study identified whether Functional Index for Hand Osteoarthritis (FIHOA) is associated with pain, hand muscle strength, health-related quality of life, and radiographic severity in hand osteoarthritis (OA). Methods We consecutively recruited 95 patients with hand OA. The FIHOA was used to assess questionnaire-based physical function in hand OA. Health-related quality of life was evaluated using EuroQol-5 dimension (EQ-5D). Radiographic changes of hand joints were measured by Kellgren-Lawrence (K-L) grade, which was determined based on total radiographic severity score and number of affected joints. Other measures included patient’s visual analogue scale (VAS) score for pain and performance-based function indexes such as grip and pinch strength. Statistical analysis was performed using Mann-Whitney U test, Spearman’s correlation analysis, and multivariate logistic regression analysis. Results FIHOA score was negatively associated with grip and pinch hand strength and EQ-5D and positively correlated to VAS pain (p < 0.05 for all). There were significant differences of grip and pinch strength, VAS pain, EQ-5D index, and EQ-VAS between two FIHOA groups (≤ 4 vs. > 4) (p < 0.05 for all). Multivariate logistic regression analysis showed that higher FIHOA score (FIHOA > 4) was related with increased VAS pain and with lower EQ-5D index (p = 0.008 and p = 0.013, respectively). There was no association between FIHOA score and measures of total radiographic severity score and number of affected joints. Conclusion This study observes that FIHOA score is associated with patient-reported VAS pain, hand muscle strength indexes, and EQ-5D but not radiographic severity in hand OA.
Fernando Henrique Azevedo Lopes, Max Victor Carioca Freitas, Veralice Meireles Sales de Bruin,
Published: 16 March 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00176-6

Abstract:
Objectives To investigate the associations between sleep quality, fatigue, disease activity and depressive symptoms in women with rheumatoid arthritis (RA). Methods Female patients with previous diagnosis of RA from a Rheumatology Outpatient Clinic at a tertiary referral centre, in Fortaleza, Brazil, were consecutively recruited into the study. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI); fatigue by the Fatigue Severity Scale (FSS); daytime sleepiness by the Epworth Sleepiness Scale (ESS); and depressive symptoms by the Beck Depression Inventory II (BDI-II). RA activity was measured by the disease activity score (DAS28). Results One hundred ten women (mean age ± SD = 51.1 ± 13.0 y) were included in the study. On average, patients with depressive symptoms (BDI-II > 13), as compared to those without, showed poorer sleep quality (PSQI: 10.09 ± 4.1 vs 7.33 ± 3.55; p = 0.001 respectively), more fatigue (FSS: 4.69 ± 1.89 vs 3.34 ± 1.8; p = 0.001) and higher disease activity level (DAS28: 4.36 ± 1.53 vs 3.7 ± 1.39; p = 0,047). The logistic regression analysis showed that sleep quality is an independent predictor of depressive symptom severity. Conclusion Depressive symptoms, impaired sleep and fatigue are common in women with RA. Poor sleep is associated with greater frequency and severity of depressive symptoms in these patients, suggesting that screening for sleep and mood problems may be relevant both in clinical research and routine patient care. Future studies investigating the impact of measures to promote healthy sleep on depressive symptom control in this patient population are warranted.
Kaiyu Pan, Rongliang Tu, Xiaocong Yao,
Published: 10 March 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00174-8

Abstract:
Backgrounds It is important to improve our understanding of the roles of calcium and vitamin D in bone health for preventing osteoporosis. We aimed at exploring the associations between serum calcium, vitamin D level, and bone mineral density (BMD) in adolescents included in the National Health and Nutrition Examination Survey (NHANES) 2001–2006. Methods Weighted multivariate linear regression models were used to estimate the associations of serum calcium, 25(OH)D level with total BMD. Smooth curve fitting was used to explore the potential non-linear relationship. Results A total of 5990 individuals aged between 12 and 19 years were included in this study. The fully-adjusted model showed serum calcium positively correlated with total BMD. However, an inverted U-shaped relationship was found when we performed the smooth curve fitting method, and the inflection point was calculated at 9.6 mg/dL using the two-piecewise linear regression model. In contrast, there was a positive correlation between serum 25(OH)D and total BMD after adjusting for potential confounders. Conclusions The present study revealed a positive correlation between serum 25(OH)D level and total BMD, and an inverted U-shaped relationship between serum calcium and total BMD.
Hui-Hui Li, Xue-Quan Li, Lin-Tao Sai, Yi Cui, Jia-Hui Xu, Chi Zhou, Jing Zheng, Xing-Fu Li, ,
Published: 10 March 2021
Advances in Rheumatology, Volume 61, pp 1-9; https://doi.org/10.1186/s42358-021-00175-7

Abstract:
Background Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.
Marina Maria Vieira De Figueiredo Caldas, , Ana Clara De França Nunes, Victor Hugo de Oliveira, Isac Davidson Santiago Fernandes Pimenta, Isabela Dantas Torres de Araújo, Francisco Alves Bezerra Neto, Ana Katherine Da Silveira Gonçalves De Oliveira, Grasiela Piuvezam
Published: 27 February 2021
Advances in Rheumatology, Volume 61, pp 1-13; https://doi.org/10.1186/s42358-021-00170-y

Abstract:
Background Systemic sclerosis (SSc) is a clinically complex and challenging disease, that leads to skin fibrosis. Its most frequent complication is interstitial lung disease (ILD), which leads to a worse prognosis. In this situation, cyclophosphamide is considered the gold standard for its treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option. Objectives This paper objective was to analyze the scientific evidence on the RTX effects on SSc. Methods A systematic review (SR) was performed including clinical trials (CTs) on the use of RTX in SSc, published up to May 2020. The studies were identified through systematic searches in bibliographic databases using a predefined search strategy. The following databases were used: PUBMED, SCOPUS, SCIELO, LILACS, SCIENCE DIRECT, WEB OF SCIENCE, COCHRANE, WHOLIS, PAHO and EMBASE. Also, a manual search was performed. The methodological quality of the studies was determined using Jadad scale, Risk of Bias Tool (RoB 2.0) and Risk of Bias in Non-Randomized Studies - of Interventions tool (ROBINS-I). A meta-analysis of the randomized CTs was performed, using Review Manager. Results Ten CTs were included in this SR. Of these, three were randomized and seven were non-randomized. Five showed a statistically significant improvement in forced vital capacity (FVC) at some time during follow-up. Regarding the skin, eight studies showed statistically significant improvements according toa the modified Rodnan skin score. The meta-analysis found positive effects of RTX in SSc, with a statistical significance for lung disease. Conclusion Rituximab is a promising strategy for the SSc-associated ILD and cutaneous fibrosis treatment. PROSPERO registration number: CRD42019132018.
, Alice Heaney, Stephen P. McKenna, Jonas Braynner Carvalho, Maria Eduarda Lima Vidal, Marina Coelho Mores de Brito, Angela Luzia Branco Pinto Duarte
Published: 25 February 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00168-6

Abstract:
Introduction Psoriatic arthritis (PsA) is a multifaceted inflammatory disease that can cause joint destruction and impair quality of life. The Psoriatic Arthritis Quality of Life Questionnaire (PsAQoL) was the first disease-specific tool for determining the impact of the disease on the quality of life of people with PsA. Objectives The primary objective was to develop and validate a Brazilian Portuguese version of the PsAQoL. Methods The UK PsAQoL was translated into Brazilian Portuguese using two translation panels. This translation then checked for face validity and construct validity with new samples of patients. Finally, a test-retest validation study was conducted with 52 patients with PsA. The survey included the Nottingham Health Profile (NHP) as a comparator instrument. Results Internal consistency and reproducibility were both excellent for the new adaptation (0.91 and 0.90 respectively Scores on the PsAQoL were found to correlate as expected with the comparator measure and the instrument was able to detect differences in score related to perceived severity of PsA, general health status and presence of a flare. Conclusion The Brazilian PsAQoL was found easy to understand and complete and has excellent reliability and construct validity. The new measure will be a valuable new tool for use in routine PsA practice and clinical trials.
, Fernando Antõnanzas, Cid Manso De Mello Vianna, Paula Rojas
Published: 25 February 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00172-w

Abstract:
Background The objective of this paper is to analyze the prices of biological drugs in the treatment of Rheumatoid Arthritis (RA) in three Latin American countries (Brazil, Colombia and Mexico), as well as in Spain and the United States of America (US), from the point of market entry of biosimilars. Methods We analyzed products authorized for commercialization in the last 20 years, in Brazil, Colombia, and Mexico, comparing them to the United States of America (USA) and Spain. For this analysis, we sought the prices and registries of drugs marketed between 1999 and October 1, 2019, in the regulatory agencies’ databases. The pricing between countries was based on purchasing power parity (PPP). Results The US authorized the commercialization of 13 distinct biologicals and four biosimilars in the period. Spain and Brazil marketed 14 biopharmaceuticals for RA, ten original, four biosimilars. Colombia and Mexico have authorized three biosimilars in addition to the ten biological ones. For biological drug prices, the US is the most expensive country. Spain’s price behavior seems intermediate when compared to the three LA countries. Brazil has the highest LA prices, followed by Mexico and Colombia, which has the lowest prices. Spain has the lowest values in PPP, compared to LA countries, while the US has the highest prices. Conclusion The economic effort that LA countries make to access these medicines is much higher than the US and Spain. The use of the PPP ensured a better understanding of the actual access to these inputs in the countries analyzed.
, Ana Paula Teixeira dos Santos, Alexandra Silva Leal, Gilberto De Araújo Pereira, Sheila Soares Silva, Helio Moraes-Souza
Published: 19 February 2021
Advances in Rheumatology, Volume 61, pp 1-5; https://doi.org/10.1186/s42358-021-00169-5

Abstract:
Background Sickle cell disease (SCD) is an autosomal recessive genetic disease in which a mutation occurs in the β-globin chain gene, resulting in abnormal hemoglobin levels. In an environment with reduced oxygen concentration, red blood cells change their conformation, resulting in chronic hemolysis and consequent anemia and vaso-occlusive crises with injuries to several organs, with a significant impairment of the osteoarticular system. This study aimed to verify the chronic osteoarticular alterations and their association with clinical and laboratory characteristics of patients with SCD with a more severe phenotype (SS and Sβ0), on a steady-state fasis. Methods Fifty-five patients were referred to a medical consultation with a specialized assessment of the locomotor system, followed by laboratory tests and radiographic examinations. Results In total, 74.5% patients had hemoglobinopathy SS; 67.3% were female; and 78.2% were non-whites. The mean patient age was 30.5 years. Most patients (61.8%) reported up to three crises per year, with a predominance of high-intensity pain (65.5%). Radiographic alterations were present in 80% patients. A total of 140 lesions were identified, most which were located in the spine, femur, and shoulders. Most lesions were osteonecrosis and osteoarthritis and were statistically associated with the non-use of hydroxyurea. Conclusions There was a high prevalence of chronic osteoarticular alterations, which was statistically associated only with the non-regular use of hydroxyurea.
Vanessa Posener de Andrade, Fernando Henrique Carlos De Souza, Gustavo Luiz Behrens Pinto,
Published: 19 February 2021
Advances in Rheumatology, Volume 61, pp 1-7; https://doi.org/10.1186/s42358-021-00171-x

Abstract:
Background To assess the prevalence and clinical relevance of anti-Jo-1 autoantibodies in a representative sample of patients with definite dermatomyositis (DM). Methods This retrospective cohort study took place from 2005 to 2020 and assessed 118 adult patients from a tertiary center who were diagnosed with definite DM. A commercial kit was used to detect anti-Jo-1 autoantibodies. Results The presence of anti-Jo-1 autoantibodies was observed in 10 out of 118 (8.5%) patients with definite DM. The following variables were comparable between individuals with and without anti-Jo-1 autoantibodies: age at diagnosis, sex, ethnicity, disease duration, follow-up period, recurrence rate, complete clinical response, death rate, and cancer incidence. There was no difference in clinical features between groups, except for an increased prevalence of “mechanic’s hands,” joint involvement, and lung disease, as well as a reduced occurrence of skin findings in patients positive for anti-Jo-1 autoantibodies. No anti-Jo-1-positive patients went into remission; they required greater use of glucocorticoids and immunosuppressive drugs. Conclusions Anti-Jo-1 positivity was found in 8.5% of patients with definite DM. This autoantibody was associated with an antisynthetase syndrome phenotype and might predict clinical outcomes in patients with definite DM.
Vikas Kumar Tiwari, Srishti Nanda, Suvercha Arya, Uma Kumar, Ratna Sharma, Senthil S. Kumaran, Renu Bhatia
Published: 18 February 2021
Advances in Rheumatology, Volume 61, pp 1-8; https://doi.org/10.1186/s42358-021-00163-x

Abstract:
Background Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal symptoms, primarily attributed to sensitization of somatosensory system carrying pain. Few reports have investigated the impact of fibromyalgia symptoms on cognition, corticomotor excitability, sleepiness, and the sleep quality — all of which can deteriorate the quality of life in fibromyalgia. However, the existing reports are underpowered and have conflicting directions of findings, limiting their generalizability. Therefore, the present study was designed to compare measures of cognition, corticomotor excitability, sleepiness, and sleep quality using standardized instruments in the recruited patients of fibromyalgia with pain-free controls. Methods Diagnosed cases of fibromyalgia were recruited from the Rheumatology department for the cross-sectional, case-control study. Cognition (Mini-Mental State Examination, Stroop color-word task), corticomotor excitability (Resting motor threshold, Motor evoked potential amplitude), daytime sleepiness (Epworth sleepiness scale), and sleep quality (Pittsburgh sleep quality index) were studied according to the standard procedure. Results Thirty-four patients of fibromyalgia and 30 pain-free controls were recruited for the study. Patients of fibromyalgia showed decreased cognitive scores (p = 0.05), lowered accuracy in Stroop color-word task (for color: 0.02, for word: 0.01), and prolonged reaction time (< 0.01, < 0.01). Excessive daytime sleepiness in patients were found (< 0.01) and worsened sleep quality (< 0.01) were found. Parameters of corticomotor excitability were comparable between patients of fibromyalgia and pain-free controls. Conclusions Patients of fibromyalgia made more errors, had significantly increased reaction time for cognitive tasks, marked daytime sleepiness, and impaired quality of sleep. Future treatment strategies may include cognitive deficits and sleep disturbances as an integral part of fibromyalgia management.
Álvaro Henrique-Neto, Marianna Yumi Kawashima Vasconcelos, Juliana Bernardes Elias Dias, Daniela Aparecida de Moraes, Maynara Santana Gonçalves, Djúlio César Zanin-Silva, Talita Graminha Zucoloto, Marília De Fátima Cirioli De Oliveira, Giuliana Martinelli Dotoli, Luiz Fernando Weffort, et al.
Published: 6 February 2021
Advances in Rheumatology, Volume 61, pp 1-10; https://doi.org/10.1186/s42358-021-00166-8

Abstract:
Background In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan’s skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results Median (range) age was 35.9 (19–59), with 57 (81.4%) female and median (range) non-Raynaud’s disease duration of 2 (1–7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.
, , Kenny Carolina Garzón-González, Jairo Cajamarca-Baron, Juan Pablo Alzate-Granados,
Published: 3 February 2021
Advances in Rheumatology, Volume 61, pp 1-12; https://doi.org/10.1186/s42358-020-00158-0

Abstract:
Background Sjögren’s Syndrome compromises the exocrine function, producing xerostomia and xerophthalmia. It can appear as an isolated condition or associated with other autoimmune diseases (polyautoimmunity). The Unstimulated Salivary Flow rate (UWSF) is used to quantify saliva production. There is no objective evidence to differentiate the values in patients with Sjögren’s versus healthy people or patients with non-Sjögren’s sicca. The objective of the present review was to evaluate the UWSF in patients with Sjögren’s syndrome in comparison to controls (healthy and non-Sjögren’s sicca patients). Methods A systematic literature review was carried out (PRISMA guidelines). Analytical observational studies of cases and controls, cross-sectional studies, cohort studies and randomized clinical trials (including healthy controls) were considered. The Medline/OVID, Lilacs, Embase, and Cochrane/OVID databases were consulted. MeSH, DeCS, keywords, and Boolean operators were used. The meta-analysis (RevMan 5.2) was done through the random-effects model [mean difference (MD)]. Level and quality of evidence were evaluated by the Oxford Center Levels of Evidence and Joanna Brigs list respectively. Results Thirty-two articles were included (20 were case-control studies, 6 were cross-sectional, 2 prospective cohort, 2 retrospective cohort, and 2 studies were abstracts) and 28 were meta-analyzed. The unstimulated whole salivary flow rate in the Sjögren’s group was lower than in controls (healthy and patients with non-Sjögren Sicca syndrome) (MD-0.18 ml/min; 95% CI, − 0.24 to − 0.13; chi2-P-value < 0.00001). Heterogeneity was 97% and there was publication bias (funnel plot). The level of evidence was mostly 3 or 4. The quality of evidence was met (97% of items valued). Conclusion For the first time, the unstimulated whole salivary flow rate is found to be lower in patients with Sjögren’s syndrome compared to controls (healthy and non-SS sicca) through a meta-analysis. Trial registration PROSPERO CRD42020211325.
, Jérémie Jacques, Stéphanie Dumonteil, Sylvain. Palat, Sophie Geyl, Guillaume Gondran, Holy Bezanahary, Eric Liozon, Julie Azaïs, Stéphanie Colombie, et al.
Published: 19 January 2021
Advances in Rheumatology, Volume 61, pp 1-8; https://doi.org/10.1186/s42358-021-00164-w

Abstract:
Background Abdominal symptoms in patients with primary Sjögren syndrome (pSS) are poorly documented. The objective of the study was to describe the abdominal symptoms of patients with pSS and to assess their association with characteristics of the disease. Methods One hundred and fifty patients with pSS were evaluated using a composite global symptom score for abdominal symptoms and their severity. Data concerning the clinical and biological characteristics of pSS and abdominal disorders were also collected. Results Of the patients with pSS, 95% suffered from abdominal symptoms (median global symptom score 7.5 ± 5.5 points out of 30). More than half of the patients experienced abdominal tension (68%), upper abdominal pain (54%), abdominal discomfort (58%) and/or constipation (54%). Regarding the pSS activity, in relation to European League Against Rheumatism (EULAR) Sjögren syndrome disease activity index score items, general and central nervous system involvement wereassociated with a high global symptom score. The EULAR Sjogren Syndrome Patient Reported Index (ESSPRI) symptom score was positively correlated with the global symptom score (p < 0.01). Multivariate analysis showed a significant association between a high global symptom score and SSA seronegativity, gastroparesis, and ESSPRI score (p < 0.01 for each). Conclusions The majority of patients with pSS suffered abdominal symptoms. There is currently no therapeutic recommendation because of the lack of information on the underlying pathophysiological mechanisms. Trial registration NCT03157011. Date of registration: July 17, 2017.
, Alexandra Vacca, Tanya Jain
Published: 19 January 2021
Advances in Rheumatology, Volume 61, pp 1-17; https://doi.org/10.1186/s42358-021-00162-y

Abstract:
Background Complementary and alternative medicine (CAM) use is prevalent among patients living with arthritis. Such patients often seek information online, for the purpose of gaining a second opinion to their healthcare provider or even self-medication. Little is known about the quality of web-based consumer health information at the intersection of CAM and arthritis; thus, investigating the quality of websites containing this information was the purpose of this study. Methods Four unique search terms were searched on Google across four English-speaking countries. We assessed the first 20 results of each search, including them if they contained CAM consumer health information for the treatment and/or management of arthritis. Eligible websites were assessed in duplicate using the DISCERN instrument, which consists of 16-items designed to assess quality. Results Of total of 320 webpages, 239 were duplicates, and a total of 38 unique websites were deemed eligible and assessed using the DISCERN instrument. The mean summed DISCERN scores across all websites was 55.53 (SD = 9.37). The mean score of the overall quality of each website was 3.71 (SD = 0.63), thus the majority of websites are ranked as slightly above ‘fair’ quality. Conclusion Eligible websites generally received scores better than ‘moderate’ in terms of overall quality. Several shortcomings included a lack of transparency surrounding references used and underreporting of risks associated with treatment options. These results suggest that health providers should be vigilant of the variable quality of information their patients may be accessing online and educate them on how to identify high quality resources.
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