The Role of Lung Ultrasound in Systemic Sclerosis: A Systematic Review.

BACKGROUND: In systemic sclerosis (SSc), high-resolution computed tomography (HRCT) of the chest is the standard criterion for the diagnosis of interstitial lung disease (ILD). However, recent evidence suggests that lung ultrasound (LUS) can also detect ILD, without radiation exposure. Thus, our goal was to perform a systematic review, aiming to clarify the role of LUS in the detection of ILD in SSc. METHODS: A systematic review was carried out in PubMed and EMBASE (PROSPERO register number CRD42022293132), to identify studies that compared LUS with HRCT in the detection of ILD in patients with SSc. Risk of bias was assessed with the QUADAS-2 () tool. RESULTS: Three hundred seventy-five publications were identified. After screening, 13 were included in the final analysis. No study presented high risk of bias. Lung ultrasound protocol was highly heterogeneous between authors, specifically concerning transducer, intercostal spaces evaluated, exclusion criteria, and definition of positive LUS. Most authors evaluated the presence of B-lines as a surrogate of ILD, with only 4 focusing on pleural changes. A positive correlation between LUS findings and ILD detected by HRCT was reported. Results also revealed high sensitivity (74.3%-100%) but variable specificity (16%-99%). Positive predictive value varied between 16% and 95.1%, and negative predictive value between 51.7% and 100%. CONCLUSION: Lung ultrasound is sensitive in the detection of ILD, but specificity must be optimized. The value of pleural evaluation also requires further investigation. Moreover, a consensus is needed to define a uniform LUS protocol to implement in future investigations.

Osteolysis in Systemic Sclerosis: A Scoping Review.

OBJECTIVE: To perform a scoping review focusing on osteolysis in systemic sclerosis (SSc). METHODS: This review was performed in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) recommendations. RESULTS: From a total of 351 results, 29 articles were included for the final analysis. The publications included proved to be heterogeneous regarding the population and inclusion criteria. The lack of a standardized method of detection of osteolysis further enhanced these inequalities. Most studies reported location/prevalence of osteolysis and associations with other manifestations, with only a minority focusing on topics like predictors of osteolysis and its prognostic value. None of the authors addressed treatment approach. The most frequently analyzed and prevalent location was acro-osteolysis (AO). Diffuse cutaneous subtype and anti-topoisomerase I antibody correlated positively with AO. Disease duration, calcinosis, and digital ischemia were the features more frequently associated with AO, but only the last 2 predicted AO. Ultrasound showed high sensitivity for detection of AO. CONCLUSION: Despite the effect that osteolysis has on patients with SSc, there is a significant lack of studies on this area. Notably, there are no studies that we know of focused on treatment. Also, there is a lack of longitudinal studies that would allow a reliable assessment of its prognostic value and predictors.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

2018 Update of the EULAR recommendations for the management of large vessel vasculitis.

BACKGROUND: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

Systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis: focus on giant cell arteritis.

Objectives: To analyse the current evidence for the management of large vessel vasculitis (LVV) to inform the 2018 update of the EULAR recommendations. Methods: Two systematic literature reviews (SLRs) dealing with diagnosis/monitoring and treatment strategies for LVV, respectively, were performed. Medline, Embase and Cochrane databases were searched from inception to 31 December 2017. Evidence on imaging was excluded as recently published in dedicated EULAR recommendations. This paper focuses on the data relevant to giant cell arteritis (GCA). Results: We identified 287 eligible articles (122 studies focused on diagnosis/monitoring, 165 on treatment). The implementation of a fast-track approach to diagnosis significantly lowers the risk of permanent visual loss compared with historical cohorts (level of evidence, LoE 2b). Reliable diagnostic or prognostic biomarkers for GCA are still not available (LoE 3b).The SLR confirms the efficacy of prompt initiation of glucocorticoids (GC). There is no high-quality evidence on the most appropriate starting dose, route of administration, tapering and duration of GC (LoE 4). Patients with GCA are at increased risk of dose-dependent GC-related adverse events (LoE 3b). The addition of methotrexate or tocilizumab reduces relapse rates and GC requirements (LoE 1b). There is no consistent evidence that initiating antiplatelet agents at diagnosis would prevent future ischaemic events (LoE 2a). There is little evidence to guide monitoring of patients with GCA. Conclusions: Results from two SLRs identified novel evidence on the management of GCA to guide the 2018 update of the EULAR recommendations on the management of LVV.

Management of Takayasu arteritis: a systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis.

Objective: To collect available evidence on management of large vessel vasculitis to inform the 2018 update of the EULAR management recommendations. Methods: Two independent systematic literature reviews were performed, one on diagnosis and monitoring and the other on drugs and surgical treatments. Using a predefined PICO (population, intervention, comparator and outcome) strategy, Medline, Embase and Cochrane databases were accessed. Eligible papers were reviewed and results condensed into a summary of findings table. This paper reports the main results for Takayasu arteritis (TAK). Results: A total of 287 articles were selected. Relevant heterogeneity precluded meta-analysis. Males appear to have more complications than females. The presence of major complications, older age, a progressive disease course and a weaker inflammatory response are associated with a more unfavourable prognosis. Evidence for details on the best disease monitoring scheme was not found. High-quality evidence to guide the treatment of TAK was not found. Glucocorticoids are widely accepted as first-line treatment. Conventional immunosuppressive drugs and tumour necrosis factor inhibitors were beneficial in case series and uncontrolled studies. Tocilizumab failed the primary endpoint (time to relapse) in a randomised controlled clinical trial; however, results still favoured tocilizumab over placebo. Vascular procedures may be required, and outcome is better when performed during inactive disease. Conclusions: Evidence to guide monitoring and treatment of patients with TAK is predominantly derived from observational studies with low level of evidence. Therefore, higher-quality studies are needed in the future.

Translation, cross-cultural adaptation and validation of the Osteoarthritis Quality of Life (OAQoL) questionnaire for use in Portugal.

Osteoarthritis (OA) is the most prevalent rheumatic disease and is a leading cause of decreased quality of life (QoL). The OA Quality of Life questionnaire (OAQoL) is an OA-specific patient-reported outcome measures. The aim of this study was to translate and validate the original UK English version of the Osteoarthritis Quality of Life (OAQoL) questionnaire into European Portuguese. The translation of the questionnaire was carried out according to a dual panel methodology (bilingual panel followed by lay panel). This was followed by cognitive debriefing interviews (CDIs) with OA patients to assess comprehension and relevance of the translated questionnaire. Finally, a validation survey was conducted to assess its psychometric properties. The Portuguese OAQoL, a comparator scale (the Nottingham Health Profile-NHP) as well as questions relating to demographic and disease information were administered to OA patients. A sub-sample of patients also completed the Portuguese OAQoL two weeks later, to assess test-retest reliability. The internal consistency, construct validity and known group validity (according to perceived OA severity) of the scale was also assessed. Both the bilingual and lay panels consisted of five individuals and no major difficulties relating to the translation process were identified. A total of ten patients with OA participated in the CDIs. The mean time to complete the questionnaire was 5 min. These interviews revealed that the Portuguese version of the OAQoL was clear, relevant and easy to complete. Finally, 53 OA patients (44 females; mean age of 67.6 years) completed the validation survey. Cronbach's alpha coefficient was 0.87, demonstrating high internal consistency. Test-retest reliability, assessed by Spearman's rank correlation coefficient, was 0.86. Moderate correlations were found with the majority of the NHP sections, providing evidence of construct validity. Significant differences in OAQoL scores were found between patients who differed according to their perceived OA severity, providing evidence of known group validity. The Portuguese version of the OAQoL is a valid and reliable questionnaire that can be used to assess QoL in OA, both in clinical practice and for research purposes.

Biologic therapy use and pregnancy outcomes in women with immune-mediated inflammatory rheumatic diseases.

INTRODUCTION: Concerns about the side effects and interactions of biologic drugs with reproduction and pregnancy have been always an issue between experts. The safety of these therapies during conception and/or pregnancy is not fully understood. The aim of this study was to assess the exposure to biologic drugs before and/or during conception/pregnancy and the risk of adverse pregnancy outcomes in women with rheumatic diseases. METHODS: We conducted a cohort study of pregnancies reported in women with immune-mediated rheumatic diseases registered at the Rheumatic Diseases Portuguese Registry (Reuma.pt) and exposed to biologic drugs. Data concerning fetal and maternal outcomes (live birth, spontaneous abortion, neonatal and intrauterine death, intrauterine growth restriction, premature delivery, congenital malformations, neonatal lupus, voluntary or medical interruption of pregnancy, disease flares and need for treatment with other drugs) was extracted. RESULTS: In total, 69 pregnancies from 56 females were analysed, the majority with the diagnosis of spondyloarthritis or rheumatoid arthritis. In almost half of the cases (n=32, 46.4%) the biologic was stopped for pregnancy planning, in 31 cases (44.9%) it was stopped when pregnancy was diagnosed and in 6 pregnancies (8.7%) biologic therapy was maintained, at least until the 2nd trimester. There were 76.8% of live births and 22% of spontaneous abortions. Congenital anomalies were reported in 2 newborns. CONCLUSIONS: In half cases, it was decided to stop biologic therapy in the family planning period. Using biologic disease-modifying anti-rheumatic drugs before and/or during pregnancy doesn't seem to affect the overall maternal and fetal outcomes. Pregnancy planning and treatment options should be discussed and a shared decision should be established between physician and patient.

The use of ultrasound in the management of large-vessel vasculitis: an evolving concept.

Imaging is increasingly recognised as an essential element in the management of several rheumatologic conditions. Ultrasound is in widespread use as a safe, reproducible, and directly interpretable method for diagnosis and evaluation of arthritis and increasingly of large-vessel vasculitis (LVV). Indeed, the diagnosis and management of LVV are being transformed through the use of imaging. Increasing and more standardised evidence is being produced on the role of colour duplex sonography in the management of LVV. Nonetheless, some controversies and unresolved issues remain. This review describes current findings and reviews future perspectives in the use of ultrasound for the diagnosis and management of LVV.

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis - 2016 update.

OBJECTIVE: To update the recommendations for the treatment of axial spondyloarthritis (axSpA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting, the 7 recommendations included in this document were discussed and updated. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication and the level of agreement among Portuguese Rheumatologists was anonymously assessed using an online survey. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching of biological therapies in patients with axSpA. In total, seven recommendations were produced. The first recommendation is a general statement indicating that biological therapy is not a first-line drug treatment option and should only be used after conventional treatment has failed. The second recommendation is also a general statement about the broad concept of axSpA adopted by these recommendations that includes both non-radiographic and radiographic axSpA. Recommendations 3 to 7 deal with the definition of active disease (including the recommended threshold of 2.1 for the Ankylosing Spondylitis Disease Activity Score [ASDAS] or the threshold of 4 [0-10 scale] for the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), conventional treatment failure (nonsteroidal anti-inflammatory drugs being the first-line drug treatment), assessment of response to treatment (based on an ASDAS improvement  of at least 1.1 units or a BASDAI improvement of at least 2 units [0-10 scale] or at least 50%), and strategy in the presence of an inadequate response (where switching is recommended) or in the presence of long-term remission (where a process of biological therapy optimization can be considered, either a gradual increase in the interval between doses or a decrease of each dose of the biological therapy). CONCLUSION: These recommendations may be used for guidance in deciding which patients with axSpA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.

Concerns of patients with systemic lupus erythematosus and adherence to therapy - a qualitative study.

PURPOSE: The objectives of this study were 1) to identify the impact of systemic lupus erythematosus (SLE) on patients' lives and their reactions to this, as well as their main concerns and expectations regarding their disease and treatments; and 2) to assess the relationship between these concerns and the adherence to treatments, medical visits, and diagnostic tests. PATIENTS AND METHODS: Qualitative study, using a convenient sample of SLE patients attending an outpatient rheumatology clinic. Semistructured interviews were conducted and audiotaped. The full transcripts were analyzed by two different coders using content analysis methodology. RESULTS: Fifteen participants were included. SLE had a major impact on these patients' lives. Their main concerns were fear of disease worsening and becoming dependent on other people, fear of not being able to take care of their children or provide for the family, and the possibility of transmitting SLE to their offspring. The main reasons for adherence to therapy were the wish to avoid manifestations of SLE and trust in the rheumatologist and routine. Nonadherence was more common in the beginning of the treatment because of the difficulty in accepting a chronic disease that requires lifelong therapy. CONCLUSION: Our data underlined the important interplay between adherence to medication and the possibility to gather accurate information and proper support during the treatment process. Good communication and efficient patient education strategies, focused on improving their knowledge about the disease and its treatments, may be important to improve adherence to therapy in SLE.

Portuguese Recommendations for the use of biological therapies in patients with rheumatoid arthritis- 2016 update.

OBJECTIVE: To update the recommendations for the treatment of Rheumatoid Arthritis (RA) with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 10 recommendations were discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. RESULTS: These recommendations cover general aspects as shared decision, prospective registry in Reuma.pt, assessment of activity and RA impact and treatment objective. Consensus was also achieved regarding specific aspects as initiation of biologic therapy, assessment of response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with biological therapies in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

Portuguese recommendations for the use of methotrexate in rheumatic diseases - 2016 update.

BACKGROUND: Methotrexate (MTX) is the first-line drug in the treatment of rheumatoid arthritis (RA) and the most commonly prescribed disease modifying anti-rheumatic drug. Moreover, it is also used as an adjuvant drug in patients under biologic therapies, enhancing the efficacy of biologic agents. OBJECTIVES: To review the literature and update the Portuguese recommendations for the use of MTX in rheumatic diseases first published in 2009. METHODS: The first Portuguese guidelines for the use of MTX in rheumatic diseases were published in 2009 and were integrated in the multinational 3E Initiative (Evidence Expertise Exchange) project. The Portuguese rheumatologists based on literature evidence and consensus opinion formulated 13 recommendations. At a national meeting, the recommendations included in this document were further discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the updated recommendations. RESULTS: Results presented in this article are mainly in accordance with previous guidelines, with some new information regarding hepatitis B infection during MTX treatment, pulmonary toxicity monitoring, hepatotoxicity management, association with hematologic neoplasms, combination therapy and tuberculosis screening during treatment. CONCLUSION: The present recommendations combine scientific evidence with expert opinion and attained desirable agreement among Portuguese rheumatologists. The regular update of these recommendations is essential in order to keep them a valid and useful tool in daily practice.

Predictors of response to TNF blockers in patients with polyarticular psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory rheumatic disease with a broad clinical spectrum. PsA can affect the axial skeleton, peripheral joints, entheses, synovial sheaths of tendons, skin, nails and extra-articular organs. Tumour necrosis factor alpha blockers (TNF blockers) were a breakthrough development in the treatment of PsA. Identifying predictors of response to biological therapies in patients with PsA is of utmost importance, especially in view of the costs and potential side effects of these agents. The aims of the present study were to determine baseline predictive factors of response to biological therapies, at 3 and 6 months, in PsA patients with polyarticular involvement (with or without axial involvement). Data were collected from the Rheumatic Diseases Portuguese Register (Reuma.pt). Eligible patients had to be anti-TNF-naive at baseline and to have at least 3 months of follow-up after the beginning of TNF blocker therapy. Only patients with information on at least one of the response measures (at 3 or 6 months of follow-up) were included in the analysis. Univariable logistic regression analysis of potential baseline predictors of European League Against Rheumatism (EULAR) good clinical response, EULAR good/moderate response, 28-joint Disease Activity Score with three variables including the erythrocyte sedimentation rate (DAS28-3V-ESR) remission and Health Assessment Questionnaire (HAQ) response were performed. Multivariable logistic regression using a forward selection procedure was used until the best-fit model was obtained, taking confounding effects into account. A total of 180 patients were eligible for the study (mean age 52 years, 54% women). In multivariable analysis at 3 months, females were less likely to attain a good EULAR response [OR=0.082 (95% CI=0.024, 0.278)], a DAS28-3V-ESR remission [OR=0.083 (95% CI=0.017, 0.416)], a moderate or good EULAR response [OR=0.091 (95% CI=0.011, 0.091)] and a HAQ response [OR=0.074 (95% CI=0.009, 0.608)]. At 6 months, female gender was also less likely to achieve a good EULAR response [OR=0.060 (95% CI=0.011, 0.325)], DAS28-3V-ESR remission [OR=0.060 (95% CI=0.012, 0.297)], and a HAQ response [OR=0.138 (95% CI= 0.029, 0.654)]. In this study we found that gender was the most consistent predictor of response to TNF blocker therapy in patients with polyarticular PsA, with females having a lower probability of response compared to males. These findings suggest that gender-related biochemical, hormonal and psychological factors could play an important role in the response to TNF blocker therapy in PsA.

Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and achieved PsARC response more rapidly than late PsA. In this cohort, comedication with csDMARDs was beneficial over 2 years.