Vasco Crispim Romão

Objective: To stablish the predictive value of antiphospholipid antibody (aPL) negativization on recurrent thrombosis in thrombotic antiphospholipid syndrome (APS). Methods: Retrospective cohort study including all consecutive adult patients with APS followed at Hospital de Santa Maria, Lisbon, Portugal, up to December 2024. At diagnosis, all patients were positive for solid-phase aPL. Then, patients were categorized in two groups according to aPL during follow-up: 1) persistently aPL-positive; 2) aPL-negativization defined as previous aPL-positive and current aPL-negative (2 consecutive times, ≥12 months apart). Outcomes included recurrent thrombosis under antithrombotic therapy. Predictors of aPL-negativization and recurrent thrombosis were assessed using Cox regression analysis. Results: Of the 116 included patients (female, 78.4%; primary APS, 72.1%; triple positivity, 40.5%), totalling 1084 patient-year (PY), 31.9% became aPL-negative (3.4 events/100PY). The follow-up time was similar between aPL-positive and aPL-negativization groups (p = 0.681), and before and after aPL-negativization (p = 0.072). At diagnosis, triple aPL-positivity predicted against aPL-negativization, while primary APS predicted aPL-negativization. Forty-five patients (38.8%) experienced 68 recurrences (4.2 events/100PY). Age at APS onset, arterial thrombosis and persistent triple aPL-positivity predicted recurrence. Globally, aPL-negativization did not predict recurrence (HR 0.58, 95%CI 0.29–1.14). Among patients who became aPL-negative, the cumulative incidence of recurrent thrombosis did not differ before aPL-negativization (HR 0.52, 95%CI 0.26–1.06), but dropped by 88% after aPL-negativization (HR 0.12, 95%CI 0.05–0.58), even after adjusting for age, primary APS and type of initial thrombosis (p = 0.006). Conclusion: The risk of recurrent thrombosis drops significantly after aPL-negativization, highlighting the utility of serial aPL monitoring in clinical practice.

Introduction/Objectives Sjögren’s disease (SjD) and non-Sjögren sicca syndrome are characterized by salivary gland dysfunction leading to chronic xerostomia. Obstructive ductal pathology, including strictures and mucous plugs, plays a significant role in secretory impairment. This study aimed to evaluate the effectiveness and safety of parotid gland irrigation with corticosteroids, associated with sialendoscopy, in improving clinical oral dryness in patients with suspected SjD or sicca syndrome. Methods This was a retrospective longitudinal study of 17 patients (13 analyzed; mean age 67.3 ± 9.9 years; 9 with SjD) treated between January 2020 and January 2022 at a multidisciplinary SjD clinic. Patients underwent sialendoscopy and intraductal prednisolone irrigation (2 mg/ml), with an average of 5.2 ± 2.5 procedures per patient. Outcomes included Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI), and treatment tolerability (VAS). Paired t-tests and Pearson correlations were used. Results Significant improvement was observed in both CODS (mean reduction: 1.15 ± 0.32; p = 0.002) and XI (5.62 ± 2.16; p = 0.012). More severe baseline xerostomia was associated with greater improvement in CODS (r = − 0.641; p = 0.009) and XI (r = − 0.598; p = 0.016). A higher number of irrigations correlated with greater XI improvement (r = − 0.525; p = 0.033). No adverse events were reported. Conclusions Corticosteroid irrigation combined with sialendoscopy significantly improved both objective and subjective xerostomia measures in SjD and sicca patients. This minimally invasive protocol appears safe, well tolerated, and particularly beneficial in patients with early or less fibrotic glandular involvement. Further prospective controlled studies are warranted to optimize treatment protocols and patient selection. Key Points • Corticosteroid irrigation combined with sialendoscopy significantly reduces xerostomia symptoms. • Greater baseline symptom burden predicts greater clinical response. • The procedure is safe and well tolerated, with no adverse events reported. • Findings support early intervention in patients with less advanced glandular damage.

Objective: To assess the relationship of circulating and synovial immune cells with synovial molecular pathology and disease outcomes in patients with early rheumatoid arthritis (RA).Methods: Patients with early (<12 months) treatment‐naive RA (n = 144) from the Pathobiology of Early Arthritis Cohort were included in this post hoc analysis. Following ultrasound (US)‐guided synovial biopsy of the most active joint, patients received standard of care treatment and were observed for 12 months. Synovial biopsies were analyzed by immunohistochemistry and classified into synovial pathotypes. Peripheral blood (PB) samples (n = 70) underwent flow cytometry, whereas RNA sequencing from synovial tissue (n = 144) and matched PB (n = 55) were analyzed using signature‐based deconvolution.Results: T peripheral helper cells (Tph) cells, identified by flow cytometry, were the only circulating immune cell subset positively correlated with both systemic markers of inflammation (erythrocyte sedimentation rate and C‐reactive protein) and local inflammation (US synovial thickening and synovitis score). Circulating Tph cells were also significantly higher in patients who were seropositive and patients with lymphomyeloid synovitis. Conversely, circulating B cells showed a significant inverse correlation with markers of inflammation, US scores, and disease activity. Signature‐based deconvolution of matched synovial and PB identified divergent immune cell signatures. Although PB signatures showed no associations with longitudinal outcomes, synovium signatures were linked to clinical outcomes. In particular, patients achieving remission at six months (Disease Activity Score in 28 joints < 2.6) had higher baseline synovial Tph signatures and a greater posttreatment reduction of the Tph signature.Conclusion: Patients with early untreated RA showed divergent immune cell signatures between synovia and PB. Tph cells, in both compartments, emerged as key markers for inflammation, disease activity, and treatment response.

Objectives: Systemic extraglandular involvement in SS has been reported in one-third of patients but may be more frequent. We aimed to evaluate systemic disease prevalence at baseline and throughout follow-up and find its predictors. Methods: We conducted a retrospective cohort study including SS patients followed in a tertiary centre. The cumulative EULAR SS disease activity index (ESSDAI) was calculated by adding each domain’s maximum score throughout follow-up. We identified independent predictors of systemic involvement (ESSDAI ≥1 at baseline and/or follow-up) through logistic regression modelling. A survival analysis was conducted to identify predictors of new/worsening ESSDAI domains. Results: A total of 216 patients were included, most of whom had systemic involvement (86%), frequently at diagnosis (76%). Biological (53%) and articular ESSDAI domains (44%) were most commonly involved, but all were affected at least once. Around half of the patients with baseline systemic disease developed an additional/worsening domain throughout follow-up. Although most patients had low disease activity at baseline, 60% eventually reached moderately active disease. Younger age at diagnosis [odds ratio (OR) 0.95 (95% CI 0.91, 0.99)], a positive minor salivary gland biopsy [OR 4.08 (95% CI 1.40, 11.86)] and RF [OR 4.67 (95% CI 1.52, 14.33)] were independent predictors of systemic involvement. Patients with baseline constitutional involvement [hazard ratio (HR) 2.23 (95% CI 1.13, 4.40)] and RF [HR 1.89 (95% CI 1.20, 3.00)] were more likely to develop new/worsening systemic disease activity. Conclusion: Systemic involvement is seen in most SS patients. Younger and RF and salivary gland biopsy-positive patients are at higher risk of systemic disease. Around half of patients with systemic involvement experienced aggravated disease over time, especially those with constitutional involvement or RF.

Background Hepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs. Objectives To assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs. Methods A prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded. Results 62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, pConclusions HBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs.

Background Postgraduate rheumatology training programmes are already established at a national level in most European countries. However, previous work has highlighted a substantial level of heterogeneity in the organisation and, in part, content of programmes. Objective To define competences and standards of knowledge, skills and professional behaviours required for the training of rheumatologists. Methods A European Alliance of Associations for Rheumatology (EULAR) task force (TF) of 23 experts, including two members of the European Union of Medical Specialists (UEMS) section of rheumatology, was convened. The mapping phase consisted of the retrieval of key documents on specialty training in rheumatology and other related specialties across a broad set of international sources. The content of these documents was extracted and represented the foundation for the document draft that underwent several rounds of online discussion within the TF, and afterwards was also distributed to a broad group of stakeholders for collecting feedback. The list of generated competences was voted on during the TF meetings, while the level of agreement (LoA) with each statement was established by anonymous online voting. Results A total of 132 international training curricula were retrieved and extracted. In addition to the TF members, 253 stakeholders commented and voted on the competences through an online anonymous survey. The TF developed (1) an overarching framework indicating the areas that should be addressed during training, (2) 7 domains defining broad areas that rheumatology trainees should master by the end of the training programme, (3) 8 core themes defining the nuances of each domain and (4) 28 competences that trainees should acquire to cover each of the areas outlined in the overarching framework. A high LoA was achieved for all competences. Conclusion These points to consider for EULAR–UEMS standards for the training of European rheumatologists are now defined. Their dissemination and use can hopefully contribute to harmonising training across European countries.

Background Synovial tissue research has become widely developed in several rheumatology centres, however, large discrepancies exist in the way synovial tissue is handled and, more specifically, how data pertaining to biopsy procedure, quality check and experimental results are reported in the literature. This heterogeneity hampers the progress of research in this rapidly expanding field. In that context, under the umbrella of European Alliance of Associations for Rheumatology, we aimed at proposing points to consider (PtC) for minimal reporting requirements in synovial tissue research. Methods Twenty-five members from 10 countries across Europe and USA met virtually to define the key areas needing evaluation and formulating the research questions to inform a systematic literature review (SLR). The results were presented during a second virtual meeting where PtC were formulated and agreed. Results Study design, biopsy procedures, tissue handling, tissue quality control and tissue outcomes (imaging, DNA/RNA analysis and disaggregation) were identified as important aspects for the quality of synovial tissue research. The SLR interrogated four databases, retrieved 7654 abstracts and included 26 manuscripts. Three OPs and nine PtC were formulated covering the following areas: description of biopsy procedure, overarching clinical design, patient characteristics, tissue handling and processing, quality control, histopathology, transcriptomic analyses and single-cell technologies. Conclusions These PtC provide guidance on how research involving synovial tissue should be reported to ensure a better evaluation of results by readers, reviewers and the broader scientific community. We anticipate that these PtC will enable the field to progress in a robust and transparent manner over the coming years.

Aim To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. Methods People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. Results A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1–5 mg/day 1.86, 1.20 to 2.66, 6–9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. Conclusions More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. ACE activity has been shown to be higher in psoriatic patients and it suggests an oxidative stress state, as seen in many cardiovascular disorders. We aimed to explore the association between ACE activity and polymorphisms and cardiovascular risk amongst psoriatic patients. We included 64 psoriatic patients and 1091 controls and compared ACE I/D polymorphism genotype and serum activity for both groups. ACE genotypes were similar in psoriatic patients and controls. Notably, serum ACE activity was higher in psoriatic patients (19.09 ± 2.86 U/mL) compared to controls (11.85 ± 0.40 U/mL), p = 0.015. Non-HDL cholesterol was significantly lower in II polymorphism (p = 0.037). Psoriatic activity (PASI) was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r = −0.496, p = 0.007), and higher triglyceride levels (r = 0.421, p = 0.020) and TC/HDL and LDL/HDL ratios (r = 0.612, p < 0.001 and r = 0.437, p = 0.023, respectively). Patients with psoriasis have higher ACE activity levels, independent of ACE genotype. Moreover, disease activity correlated with cardiovascular risk. This could support the eventual role of ACE as a possible biomarker for disease severity and cardiovascular risk in psoriasis patients.