Parameniscal cyst: an important differential diagnosis in slow growing masses of the knee.

INTRODUCTION: Parameniscal cysts are small cystic lesions, near the meniscus, involving medial and lateral compartments at equal frequency. Frequently, parameniscal cysts are so small that patients do not notice them, being asymptomatic. However, they can grow and exceed 2 centimeters in diameter, causing pain and alarm due to the slow growing mass. Magnetic Resonance Imaging (MRI) is the gold standard for diagnosis. METHODS: Case report of a patient admitted to rheumatology department in the Centro Hospitalar e Universitário de Coimbra. RESULTS: We report a case of a 47-year-old male with idiopathic juvenile arthritis, who presented with a slow-growing mass over the medial aspect of the right knee. MRI revealed a conspicuous cystic ovoid lesion, compatible with a parameniscal cyst, associated with structural heterogeneity of the posterior edge of the internal meniscus with a longitudinal fracture at this level. CONCLUSION: This is the first case of parameniscal cyst reported in patients with inflammatory rheumatic disease and the differential diagnosis with synovial cyst, baker cyst, ganglion cyst, bursitis, hematoma and neoplasms is of utmost importance.

Shear-Wave Elastography Evaluation of Major Salivary Glands in Primary Sjögren's Syndrome.

OBJECTIVES: Salivary glands ultrasonography has recently been shown to be useful in the diagnosis of Primary Sjögren's Syndrome (pSS). Shear-wave elastography (SWE) is a promising tool for the quantitative assessment of tissues stiffness, but studies evaluating its role in pSS diagnosis are limited. This study aimed at investigating the diagnostic performance of SWE in pSS. MATERIALS AND METHODS: Cross-sectional study including patients fulfilling the 2016 ACR/EULAR classification criteria for pSS and healthy subjects. The four major salivary glands were assessed using SGUS. B-mode scans were rated using the Hocevar score, and shear-wave velocity (SWV) values were obtained using SWE. Intraclass-correlation coefficient (ICC) estimates were used to assess reliability. Cut-off values for differentiating pSS patients from healthy subjects were calculated using Receiver-Operating Characteristics (ROC) curves. RESULTS: We included 50 pSS and 25 healthy subjects. Inter-rater reliability of SWE was moderate (ICC=0.64) and intra-rater reliability was moderate to good (ICC= 0.73 to 0.83). Total SWV (2.09 m/s (0.32); p < 0.001), parotid SWV (2.25 m/s (0.40)) and submandibular SWV (1.92 m/s (0.38)) were significantly higher in pSS patients. Total and parotid SWV presented good diagnostic performance for pSS diagnosis (AUROC= 0.80 and 0.81, respectively). The Hocevar score demonstrated excellent diagnostic performance (AUROC= 0.98) and combining it with total SWV did not result in statistically significant improvement (p=0.301). CONCLUSIONS: SWE may contribute to the diagnosis of pSS. Large prospective studies including sicca and secondary SS patients, as well as the standardisation of SWE protocols, are warranted to assess the role of SWE in pSS management.

Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1ß protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1ß protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients.

Osteoporosis management during the COVID-19 pandemic - Position paper.

COVID-19 pandemic significantly increased the already large number of victims of osteoporosis in Portugal. Osteoporosis outpatient clinics were either closed or had limited presential appointments. Many hospitals reduced orthopaedic services to make space for patients with COVID-19. In addition, the volunteer or forced sedentarism, as imposed by the pandemic, increased the risk of falls and fractures drastically. It urges to intensify the current efforts to improve the management of bone health and to prioritize fragility fracture care and prevention. This paper addresses the challenges in osteoporosis management during the COVID-19 pandemic and provides guidance on osteoporosis management. This position paper is a joint initiative of several health professionals and patients dedicated to osteoporosis.

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum Time Course.

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

Validation of Rheumatoid Arthritis Quality of Life (RAQoL) Questionnaire into Portuguese Language.

BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease with high impact on patients´ quality of life (QoL). The Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) is a self-completed questionnaire designed to assess QoL in patients with RA. A Portuguese adaptation of the RAQoL was available but required formal validation. AIM: To validate the RAQoL into the Portuguese language. METHODS: Patients with diagnosis of RA were included. The Portuguese RAQoL was administered on two occasions, 14 days apart. Participants also completed the Nottingham Health Profile (NHP) and Health Assessment Questionnaire (HAQ) at Time 1. Internal consistency was assessed using Cronbach's alpha and reliability through Spearman's Correlation Coefficient. Construct validity was evaluated through Spearman's correlation analyses between RAQoL, NHP and HAQ. Known-group validity was tested comparing the RAQoL across different groups, considering self-perceived general health status, flare symptoms and RA severity through non-parametric tests. RESULTS: 178 RA patients (mean age 56.6, 82% female, mean disease duration 13.6 years) were included. The mean score of RAQoL was 11, with low rates of missing data (3.9%), floor (4.5%) and ceiling (2.2%) effects. Cronbach's α was 0.95 and test-retest reliability 0.92. RAQoL scores correlated moderately with scores on the NHP Physical Mobility (r=0.77), Emotional reactions (r=0.69), Pain (r=0.68) and Energy (r=0.65) section scores. RAQoL showed to be discriminative for groups according to self-perceived general health status, flare of arthritis and disease severity. CONCLUSION: The Portuguese version of the RAQoL is a valid, feasible and reliable questionnaire, suitable for use in clinical practice and research purposes.

Adherence to the recommended prevention strategies before and after a hip fragility fracture: what makes us go blind?

OBJECTIVES: Our main objective was to evaluate the percentage of patients under anti-osteoporotic treatment (OT) at the time of hip fracture (HF) and one and four years after the HF event. We compared these results with the percentage of patients who should be under treatment at all three stages, according to the recently published Portuguese cost-effectiveness recommendations (PCER) for OT. Data regarding occurrence of new fragility fractures and mortality were also determined, one and four years after the HF event. Our secondary objective was to evaluate characteristics of patients associated with OT at the time of hip fracture.. MATERIAL AND METHODS: Patients hospitalized due to HF between May 1st and October 31st of 2013 in a single tertiary hospital, were selected for this study. Data regarding demographic, clinical features (including the clinical risk factors for fracture considered by FRAX®), level of independence in daily activities (Katz index), comorbidity (Charlson index) and OT were recorded at the time of the HF. The subsequent risk of fracture was estimated for each patient with FRAX® (without mineral bone density). Mortality and the percentage of patients receiving an OT prescription and suffering a new osteoporotic fracture, at one and four years after the HF event, were established. RESULTS: One hundred and thirty patients were included, with a mean age of 81.6±8.6 years. At the time of the HF only 28(21.5%) of the patients were receiving some form of OT. According to PCER, 115(88.5%) of these patients should be undergoing treatment according to FRAX® estimated risk, 30(23.1%) based on previous fractures and 119(91.5%) based on either criteria. The score of comorbidities was negatively associated with the prescription of OT at baseline (OR=0.17 [0.05-0.53], p=0.011) while the level of independence in daily activities was associated with higher probability of being treated (OR=3.20 [1.30-7.89], p=0.003). At one year after the HF, 39/130(30%) of patients had died. Although, according to PCER, all the remaining patients should be under OT based on the history of HF, only 11/91(12.1%) had received an OT prescription and 5/91(5.5%) suffered a new osteoporotic fracture during this period. At four years after the HF, 65/130 (50%) of patients had died. Only 6 of the remaining 65 (9.2%) were receiving an OT prescription and 9/65(13.8%) had suffered an additional fractured. CONCLUSIONS: Similar to other countries, the percentage of patients receiving OT at the time and especially after a HF is extremely low. Risk estimations with FRAX® and application of current PCER should allow clinicians to introduce appropriate primary and secondary preventive measures. Comorbidities and dependence seem to be important reasons for this undertreatment.

Effectiveness of a Referral Program for rheumatoid arthritis and axial spondyloarthritis Diagnosis at Primary Care Centers in Portugal - SIARA STUDY.

OBJECTIVES: Early diagnosis and treatment of Rheumatoid Arthritis (RA) and axial Spondylarthritis (axial SpA) can limit the impact of disease outcomes. This study evaluated the effectiveness of a referral program on the identification of patients with RA and axial SpA. METHODS: This was an observational, prospective, randomized (by clusters) study conducted in Portugal to evaluate the impact of the implementation of a set of referral support actions (RSA). The study was divided in two sub-studies, the RA sub-study and the axial SpA sub-study. 28 participating primary care units were randomly (by clusters) assigned to RSA or control group (with no intervention). Both RSA and control groups identified and referred patients with suspected RA or axial SpA to the rheumatology unit of the reference hospital. The primary objective was to evaluate the correct diagnosis of RA or axial SpA cases confirmed by the rheumatologist of the reference hospital. RESULTS: RA-Substudy: A total of 340 patients were recruited (144 in the RSA-exposed group; 196 in the control). RA diagnosis confirmation was 7.3% (95%CI, 2.1-12.5%) in RSA group versus 2.7% (95%CI, 0.0-5.7%) in control group RSA effect was positive but moderate (4.6%) and not statistically significant (95% CI, 0.0%-11.8%; p=0.222, adjusted for clustering effect). Rate of confirmed arthritis of any type was 16.9% (n=14/83) in the RSA group and 6.0% (n=5/83) in the control group. This difference was statistically significant and favorable to RSA group (OR=3.2; 95% CI 1.1-9.2; p=0.028). Axial SpA-Substudy: A total of 231 patients were recruited (108 in the RSA-exposed group; 123 in the control). Axial SpA diagnosis confirmation was 8.7% (95% CI, 2.1-15.4%) in RSA group versus 5.6% (95% CI, 0.0-11.73%) in control group. RSA effect was positive (3.1%) but not statistically significant (95% CI, -7.5- 12.9%; p=0.568, adjusted for clustering effect). CONCLUSIONS: This study showed a positive tendency for the RSA program, most relevantly on the diagnosis of patients with any type of arthritis in the RA sub-study. It is possible that a referral program more comprehensive than the one herein tested might improve early diagnosis of RA and SpA.

Exercise echocardiography for the assessment of pulmonary hypertension in systemic sclerosis: a systematic review.

BACKGROUND: Pulmonary arterial hypertension (PAH) complicates the course of systemic sclerosis (SSc) and is associated with poor prognosis. The elevation of systolic pulmonary arterial pressure (sPAP) during exercise in patients with SSc with normal resting haemodynamics may anticipate the development of PAH. Exercise echocardiography (ExEcho) has been proposed as a useful technique to identify exercise-induced increases in sPAP, but it is unclear how to clinically interpret these findings. In this systematic review, we summarize the available evidence on the role of exercise echocardiography to estimate exercise-induced elevations in pulmonary and left heart filling pressures in patients with systemic sclerosis. METHODS: We conducted a systematic review of the literature using MEDLINE, Cochrane Library and Web of Knowledge, using the vocabulary terms: ('systemic sclerosis' OR 'scleroderma') AND ('exercise echocardiography') AND ('pulmonary hypertension'). Studies including patients with SSc without a prior diagnosis of PAH, and subjected to exercise echocardiography were included. All searches were limited to English and were augmented by review of bibliographic references from the included studies. The quality of evidence was assessed by the Effective Public Health Practice Project system. RESULTS: We identified 15 studies enrolling 1242 patients, who were mostly middle-aged and female. Several exercise methods were used (cycloergometer, treadmill and Master's two step), with different protocols and positions (supine, semi-supine, upright); definition of a positive test also varied widely. Resting estimated sPAP levels varied from 18 to 35 mm Hg, all in the normal range. The weighted means for estimated sPAP were 22.2 ± 2.9 mmHg at rest and 43.0 ± 4.3 mmHg on exercise; more than half of the studies reported mean exercise sPAP ≥40 mmHg. The assessment of left ventricular diastolic function on peak exercise was reported in a minority of studies; however, when assessed, surrogate variables of left ventricular (LV) diastolic dysfunction were associated with higher sPAP on exercise. CONCLUSIONS: We found very high heterogeneity in the methods, the protocols and the estimated sPAP response to exercise. LV diastolic dysfunction was common and was associated with greater elevation of sPAP on exercise.

Outcome Measures in Polymyalgia Rheumatica. A Systematic Review.

OBJECTIVE: To identify the instruments used to assess polymyalgia rheumatica (PMR) in published studies. METHODS: A systematic literature review of clinical trials and longitudinal observational studies related to PMR, published from 1970 to 2014, was carried out. All outcome and assessment instruments were extracted and categorized according to core areas and domains, as defined by the OMERACT (Outcome Measures in Rheumatology) Filter 2.0. RESULTS: Thirty-five articles (3221 patients) were included: 12 randomized controlled trials (RCT); 3 nonrandomized trials; and 20 observational studies. More than 20 domains were identified, measured by 29 different instruments. The most frequently used measures were pain, morning stiffness, patient global assessment and physician global assessment, erythrocyte sedimentation rate, and C-reactive protein. The definition of outcomes varied considerably between studies. CONCLUSION: The outcome measures and instruments used in PMR are numerous and diversely defined. The establishment of a core set of validated and standardized outcome measurements is needed.

Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register, Reuma.pt.

OBJECTIVES: To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria. METHODS: We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders. RESULTS: Tocilizumab-treated patients (n = 95) presented higher baseline disease activity and were less frequently naïve to biologics compared to TNFi users (n = 429). Multivariate logistic regression analysis including the propensity score for receiving tocilizumab showed that patients treated with tocilizumab were more likely to achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6-21.6/3.2-12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2-6.5/1.3-5.5), or SDAI (OR = 3.6/2.5, 95% CI 1.5-8.7/1.1-5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4-12.0). However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8-4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8-4.5). CONCLUSIONS: Compared with TNFi, tocilizumab was associated with greater likelihood of achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean remission and EULAR good/moderate response did not differ significantly between groups.

Nailfold capillary abnormalities in erectile dysfunction of systemic sclerosis: a EUSTAR group analysis.

OBJECTIVE: The objective of this study was to analyse an association between nailfold capillary abnormalities and the presence and severity of erectile dysfunction (ED) in men with SSc. METHODS: A cross-sectional analysis of the prospective European League Against Rheumatism (EULAR) Scleroderma Trial and Research database was performed. Men with SSc were included if they had undergone nailfold capillaroscopy and simultaneous ED assessment with the 5-item International Index for Erectile Function (IIEF-5). RESULTS: Eighty-six men met the inclusion criteria. Eight men (9.3%) had not had sexual intercourse and could not be assigned an IIEF-5 score. Sixty-nine of the 78 men (88.5%) with an IIEF-5 score had nailfold capillary abnormalities, of whom 54 (78.3%) suffered from ED. Nine men (11.5%) had no nailfold capillary abnormalities, of whom six (66.7%) had ED (P = 0.44). ED was more frequent in older men (P = 0.002) and in men with diffuse disease (P = 0.06). Men with abnormal capillaroscopy had a higher median EULAR disease activity than men without (P = 0.02), a lower diffusing capacity of the lung (P = 0.001) and a higher modified Rodnan skin score (P = 0.04), but mean IIEF-5 scores did not differ [15.7 (S.D. 6.2) vs 15.7 (S.D. 6.3)]. IIEF-5 scores did not differ between men with early (n = 12), active (n = 27) or late (n = 27) patterns (IIEF-5 scores of 17.9, 16.3 and 14.7, respectively). There were no differences in the prevalence of early, active and late capillaroscopy patterns between men with or without ED. CONCLUSION: Neither the presence or absence of abnormal capillaroscopy findings nor the subdivision into early, active and late patterns is associated with coexistent ED in SSc.

A FRAX model for the estimation of osteoporotic fracture probability in Portugal.

INTRODUCTION: The objective of this study was to develop a Portuguese version of the World Health Organization fracture risk assessment tool (FRAX®). METHODS: All cases of hip fracture occurred at or after 40 years of age were extracted from the Portuguese National Hospital Discharge Register from 2006 to 2010. Age and sex-ranked population estimates and mortality rates were obtained from National Statistics. Age- and gender stratified incidences were computed and the average of the five years under consideration was taken. Rates for other major fractures were imputed from the epidemiology of Sweden, as undertaken for most national FRAX® models. All methodological aspects and results were submitted to critical appraisal by a wide panel of national experts and representatives of the different stakeholders, including patients. RESULTS: Hip fracture incidence rates were higher in women than in men and increased with age. The lowest incidence was observed in 40-44 years group (14.1 and 4.0 per 100,000 inhabitants for men and women, respectively). The highest rate was observed among the 95-100 age-group (2,577.6 and 3,551.8/100,000 inhabitants, for men and women, respectively). The estimated ten-year probability for major osteoporotic fracture or hip fracture increased with decreasing T-score and with increasing age. CONCLUSIONS: Portugal has one of the lowest fracture incidences among European countries. The FRAX® tool has been successfully calibrated to the Portuguese population, and can now be used to estimate the ten-year risk of osteoporotic fractures in this country. All major stakeholders officially endorsed the Portuguese FRAX® model and co-authored this paper.

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group.

INTRODUCTION: Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known. METHOD: This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively. RESULTS: Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients. CONCLUSIONS: Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

[Cyclophosphamide induced amenorrhoea in pre-menopausal women with systemic lupus erythematosus]. / Amenorreia induzida por ciclofosfamida em doentes pré-menopáusicas com lúpus eritematoso sistémico.

OBJECTIVES: To determine the frequency of ovarian failure in pre-menopausal women after cyclophosphamide (cyc) treatment for systemic lupus erythematosus (SLE); identify risk factors for this complication; estimate the occurrence and viability of pregnancy during and after treatment. METHODS: Review of the data of women treated with intravenous cyc in the department of Rheumatology of Hospitais da Universidade de Coimbra, updated by interview. Information on demographic features; gynaecologic and obstetrical history; characteristics of the disease; duration and side effects of treatment were obtained. Ovarian failure was defined as a lack of menses for, at least, four months and the diagnosis was confirmed by hormonal measurements. RESULTS: Nineteen pre-menopausal women were treated with intravenous cyc in our department. The mean age at the time of cyc initiation was 28.4 years. Lupus nephritis was the most common indication for cyc treatment (89.5%). The mean number of pulses was 9.3 over a period of 16.8 months. The mean cumulative dosage was 6.973 mg. Three patients developed ovarian failure. Those women were older than the others (P=0.0016). One patient became pregnant while on treatment. Two women delivered healthy children after cyc withdrawal. CONCLUSION: Ovarian failure developed in 15.8% of our patients. As described in the literature, the age at cyc initiation appears to be a determinant risk factor. Pregnancy may occur during cyc therapy, and thus, an effective contraception is mandatory. After cyc withdrawal, pregnancy is possible with a favourable outcome.