RESUMEN
OBJECTIVES: The study is aimed to evaluate the impact of safety events in the Eurofever registry for Autoinflammatory diseases. METHODS: This was a retrospective and longitudinal observational multicentre study. Data were retrieved from the international registry Eurofever, starting patients' enrolment since 2009. All moderate, severe, or very severe AEs reported by treating physician in Eurofever were analyzed regardless of a possible suspected causal relationship to any therapies and according to the latest release of the Medical Dictionary for Regulatory Activities. RESULTS: Complete information on safety were available in 2464 patients enrolled in the registry. In 1499 of them retrospective data encompassing the period from disease onset to enrolment were available, whereas 965 consecutive patients entered in the longitudinal part of the study. A total of 479 AEs have been reported in 275 patients. Eighty-two AEs were reported as serious and 99 were drug-related according to the physicians. Infections or infestations (94; 19.6%), gastrointestinal disorders (66; 13.8%), nervous system disorders (41; 8.6%) and systemic disorders or administration site reactions (35; 7.3%) were the most frequent reported events. The highest absolute number of drug-related AEs were related to biologic DMARDs (40/99 reports, 40,4%) and colchicine (31/99 reports, 31.3%). CONCLUSIONS: Present study shows the importance of a longitudinal and homogeneous registration of the AEs in rare conditions, with a particular focus on the safety profile of the treatments used in these conditions.
Asunto(s)
Sistema de Registros , Humanos , Femenino , Masculino , Adulto , Estudios Retrospectivos , Adolescente , Estudios Longitudinales , Adulto Joven , Persona de Mediana Edad , Niño , Preescolar , Anciano , Enfermedades Autoinflamatorias Hereditarias/epidemiología , Lactante , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Europa (Continente)/epidemiología , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricosRESUMEN
OBJECTIVES: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs). METHODS: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors. RESULTS: The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment. CONCLUSION: I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.
RESUMEN
OBJECTIVES: Patients with systemic sclerosis (SSc) are at increased risk for osteoporosis (OP) and associated fragility fractures. This study aimed to identify underlying risk factors for these conditions in patients with SSc. METHODS: This cross-sectional study was based on a large prospective cohort of patients with SSc using retrospectively collected bone health data. OP was defined as the presence of a T-score below -2.5 at the femoral neck or lumbar spine, a previous major osteoporotic fracture, or the prescription of anti-osteoporotic therapy. RESULTS: A total of 485 patients fulfilling the ACR/EULAR 2013 diagnostic criteria for SSc, followed in the Lille University Hospital, were included in the study. The prevalence of OP was 23%; fragility fractures occurred in 18% of patients. OP was associated with higher age, diffuse cutaneous subset, interstitial lung disease (ILD), anti-topoisomerase I positivity, treatment with glucocorticoids (GC) and DMARDs in univariable analysis. Multivariable analysis indicated that higher age (OR 1.06 [95%CI 1.04-1.08]), anti-topoisomerase I antibody positivity (OR 2.22 [1.18-4.16]) and treatment with GC (OR 4.48 [2.42-8.26]) were significantly and independently associated with OP. CONCLUSION: Our study shows that OP risk in patients with SSc is determined by age, disease-related factors such as diffuse cutaneous subset, ILD and anti-topoisomerase I antibody positivity, but also treatment with GC independently of other factors.
RESUMEN
OBJECTIVES: The aim of this study was to determine the association between different histological patterns and prognosis in patients with SSc and histologically proven muscle involvement. METHODS: A multicentre retrospective study was conducted of a cohort of scleroderma patients who had undergone muscle biopsy. The biopsies were reviewed in a coordinated manner to classify patients based on histological findings. Three different patterns were observed: fibrosing myopathy (FM), inflammatory myopathy (IM) and necrotizing myopathy (NM). Rates of survival, muscle relapse, and cardiac and pulmonary events were compared between these three groups. RESULTS: Among 71 scleroderma patients with muscle biopsy specimens available for review, 33 (46.5%) were classified in the FM group, 18 (25.5%) in the IM group, and 20 (28%) in the NM group. The median follow-up time was 6.4 years (interquartile range, 2.2-10.9 years) and 21 patients died during follow-up, primarily from heart disease and infections. The 10-year survival rate after the first non-Raynaud's disease symptom was 80% and the cumulative incidence of muscle relapse was 25%. Neither factor differed significantly between the three groups. The risk of pulmonary events was lowest in the OM group, significantly lower than in the FM group (hazard ratio, 0.17; 95% CI, 0.04-0.67) and non-significantly lower than in the IMNM group (hazard ratio, 0.28; 95% CI, 0.06-1.24). The risk of cardiac events did not differ significantly between the three groups. CONCLUSION: The mortality rate of scleroderma patients with muscle involvement was not associated with their histological patterns.
RESUMEN
OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.
RESUMEN
OBJECTIVES: To describe the characteristics of patients with Sjögren's disease (SjD) and inclusion-body myositis (IBM), and how they compare to SjD patients with other inflammatory myopathies (IM). METHODS: Patients were retrospectively recruited from 13 French centers and included if they met the ACR/EULAR criteria for SjD and for IM. They were categorized as SjD-IBM if sub-criteria for IBM were met, or as SjD-other IM if not. RESULTS: SjD-IBM patients (n = 22) were mostly females (86%), with a median [Q1; Q3] age of 54 [38.5; 64] years at SjD diagnosis, and 62 [46.5; 70] years at first IBM symptoms. Although most patients displayed glandular and immunological abnormalities, additional extra-glandular manifestations were uncommon, resulting in moderate disease activity at SjD diagnosis (ESSDAI 5.5 [1; 7.8]). Classic IBM features were frequent, such as progressive symptom onset (59%), asymmetrical (27%) and distal (32%) involvements, dysphagia (41%), low CPK (386.5 [221.8; 670.5] UI/l) and CRP (3.0 [3; 8.5] mg/l) levels. Immunosuppressants were reported as efficient in 55% of cases.Compared with SjD-IBM patients, SjD patients with other IM (n = 50) were significantly younger, displayed more frequent additional extra-glandular disease, higher ESSDAI score (11 [3; 30]), shorter delay between SjD diagnosis and myositis onset (0 [-0.5; 26]), more frequent CPK values over 1000 UI/l (36%), and less frequent classic IBM features. CONCLUSION: IBM can occur in SjD patients, with muscle features reminiscent of classic sporadic IBM characteristics, but mostly affecting women. In SjD patients with muscle involvement, extra-glandular manifestations, high ESSDAI score, elevated CPK values, and shorter delay after SjD diagnosis plead against IBM.
RESUMEN
OBJECTIVES: Data about hydroxychloroquine (HCQ) levels during pregnancy are sparse. We assessed HCQ whole blood levels at first trimester of pregnancy as a potential predictor of maternal and obstetric/fetal outcomes in patients with systemic lupus erythematosus (SLE). METHODS: We included pregnant SLE patients enrolled in the prospective GR2 study receiving HCQ, with at least one available first-trimester whole-blood HCQ assay. We evaluated several cut-offs for HCQ whole blood levels, including ≤200 ng/ml for severe non-adherence. Primary outcomes were maternal flares during the second and third trimesters of pregnancy, and adverse pregnancy outcomes (APOs: fetal/neonatal death, placental insufficiency with preterm delivery, and small-for-gestational-age neonates). RESULTS: We included 174 patients (median age: 32.1 years, IQR 28.8-35.2). Thirty (17.2%) patients had flares, 4 (2.3%) being severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs by HCQ level for either those with subtherapeutic HCQ levels (≤500 ng/ml vs >500 ng/ml: 23.5% vs 14.3%, p = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs >200 ng/ml: 20.0% vs 15.7%, p = 0.71). Similarly, the overall rate of maternal flares did not differ significantly by HCQ level cut-off, but patients with subtherapeutic (HCQ ≤500 ng/ml: 8.8% vs 0.7%, p = 0.02) and non-adherent HCQ levels (≤200 ng/ml: 13.3% vs 1.3%, p = 0.04) had significantly more severe flares. CONCLUSION: In this large prospective study of pregnant SLE patients, first-trimester subtherapeutic (≤500 ng/ml) and severe non-adherent (≤200 ng/ml) HCQ levels were associated with severe maternal flares, but not with APOs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02450396.
RESUMEN
BACKGROUND AND OBJECTIVE: Chronic interstitial lung disease (ILD) occurs rarely with systemic lupus erythematosus (SLE) as compared with other connective tissue diseases. This multicentric retrospective study of patients with SLE-ILD from the OrphaLung and French SLE networks during 2005-2020 aimed to describe the characteristics of patients with SLE-ILD and analyse factors associated with prognosis. METHODS: We analysed data for 89 patients with SLE-ILD (82 women, 92.1%) (median age at SLE diagnosis: 35 years [interquartile range 27-47]). All patients met the 2019 EULAR/ACR criteria for the diagnosis of SLE. RESULTS: Forty two (47.2%) patients were positive for anti-ribonuclear protein antibodies and 45 (50.6%) for anti SSA/Ro antibodies. A total of 58 (65.2%) patients had another connective tissue disease: Sjögren's syndrome (n = 33, 37.1%), systemic sclerosis (n = 14, 15.7%), inflammatory myopathy (n = 6, 6.7%), or rheumatoid arthritis (n = 6, 6.7%). ILD was diagnosed along with SLE in 25 (28.1%) patients and at a median of 6 (0-14) years after the SLE diagnosis. The most frequent CT pattern was suggestive of non-specific interstitial pneumonia (n = 41, 46.0%) with or without superimposed organizing pneumonia. After a median follow-up of 86.5 [39.5-161.2] months, 18 (20.2%) patients had died and 6 (6.7%) underwent lung transplantation. The median 5-year and 10-year transplantation-free survival were 96% (92-100) and 87% (78-97). In total, 44 (49.4%) patients showed ILD progression. Cutaneous manifestations and Raynaud's phenomenon were associated with better survival. Only forced vital capacity was significantly associated with survival and ILD progression. CONCLUSION: ILD is a rare manifestation of SLE with good overall prognosis but with possible risk of ILD progression. Patients with SLE-ILD frequently have another connective tissue disease.
Asunto(s)
Enfermedades Pulmonares Intersticiales , Lupus Eritematoso Sistémico , Humanos , Femenino , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Masculino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Enfermedad Crónica , Anticuerpos Antinucleares/sangreAsunto(s)
Anticuerpos Monoclonales Humanizados , Complejo CD3 , Síndrome Hipereosinofílico , Receptores CCR4 , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Síndrome Hipereosinofílico/tratamiento farmacológico , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/patología , Receptores CCR4/antagonistas & inhibidores , Receptores CCR4/metabolismo , Masculino , Persona de Mediana Edad , Femenino , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Resultado del Tratamiento , Anciano , Antígenos CD4/metabolismoRESUMEN
OBJECTIVES: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort. METHODS: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719). FINDINGS: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I2: 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60]). INTERPRETATION: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients.
Asunto(s)
Autoanticuerpos , Ribonucleoproteínas , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/epidemiología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Ribonucleoproteínas/inmunología , Francia/epidemiología , Fenotipo , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangre , Prevalencia , Femenino , Estudios Transversales , MasculinoRESUMEN
Background: Systemic sclerosis is a fibrotic disease. Body image assessments could be key in optimizing care; however, data are scarce. The main objective was to assess the perception of aesthetic impairment using a visual aesthetic evaluation scale in patients with systemic sclerosis compared with healthy subjects. The secondary objectives were to assess associations between the perception of aesthetic impairment and scores on standardized questionnaires for aesthetic impairment as well as clinical, psychological/quality of life, and functional parameters of patients with systemic sclerosis. Methods: This study evaluated and compared the perception of aesthetic impairment in two populations: patients with systemic sclerosis from a referral center at Lille Hospital, France, and healthy controls. Results: This study included 88 patients (69 (78.4%) women) with a median age of 52 years and 88 controls (49 (55.7%) women) with a median age of 45 years. The perception of aesthetic impairment assessed using the aesthetic evaluation scale was poorer in systemic sclerosis patients than in controls (3.7 ± 0.3 vs 2.8 ± 0.3, p = 0.028) and was statistically correlated with assessments using the adapted satisfaction with appearance, a specific aesthetic impact assessment questionnaire for patients with systemic sclerosis. Patients with anxiety or depressive symptoms had significantly higher aesthetic evaluation scale scores. Systemic sclerosis patients with facial involvement and pitting scars had a worse perception of aesthetic impairment. Compared with healthy controls, systemic sclerosis patients had a worse perception of aesthetic impairment, especially systemic sclerosis patients with anxiety or depression and those with facial and hand involvement. Conclusion: The aesthetic evaluation scale appears to be an easy-to-use tool to evaluate body image. Correlations of the aesthetic evaluation scale score with psychological and quality of life parameters reflect the importance of these parameters for body image evaluation and its complex assessment. Trial registration: Clinical Trial NCT03271320 (Registered 9 January 2017, https://www.clinicaltrials.gov/ct2/show/NCT03271320?term=NCT03271320&cntry=FR&draw=2&rank=1).
RESUMEN
OBJECTIVE: Systemic lupus erythematous (SLE) is a heterogenous disease characterised by a large panel of autoantibodies and a wide spectrum of clinical signs and symptoms that engender different outcomes. We aimed to identify distinct, homogeneous SLE patients' phenotypes. METHODS: This retrospective study enrolled SLE patients meeting the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, enrolled in the French multicentre "APS (antiphospholipid syndrome) and SLE" Registry. Based on 29 variables selected to cover a broad range of clinical and laboratory (excluding autoantibodies) SLE manifestations, unsupervised multiple correspondence analysis followed by hierarchical ascendent-clustering analysis assigned different phenotypes. RESULTS: We included 440 patients, mostly women (94.3%). Median age at SLE diagnosis was 24 (IQR 19-32) years. Cluster analysis yielded three distinct subgroups based on cumulative clinical manifestations, not autoantibody pattern. Cluster 1 (n=91) comprised mostly Caucasian patients, with APS-associated clinical and biological manifestations, e.g., livedo, seizure, thrombocytopaenia and haemolytic anaemia. Cluster 2 (n=221), the largest, included patients with mild clinical manifestations, mainly articular, more frequently associated with Sjögren's syndrome and with less frequent autoantibody-positivity. Cluster 3 (n=128) consisted of patients with the largest panel of SLE-specific clinical manifestations (cutaneous, articular, proliferative nephritis, pleural, cardiac and haematological), the most frequent autoantibody-positivity, low complement levels, and more often of Asian and sub-Saharan African origin. CONCLUSION: This unsupervised clustering method distinguished three distinct SLE patient subgroups, highlighting SLE heterogeneity.
RESUMEN
OBJECTIVE: The evidence-based DETECT pulmonary arterial hypertension (PAH) algorithm is frequently used in patients with systemic sclerosis (SSc) to help clinicians screen for PAH by using noninvasive data to recommend patient referral to echocardiography and, if applicable, for a diagnostic right-sided heart catheterization. However, the hemodynamic definition of PAH was recently updated in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines. The performance of DETECT PAH in identifying patients with a high risk of PAH according to this new definition was assessed. METHODS: In this post hoc analysis of DETECT, which comprised 466 patients with SSc, the performance of the DETECT PAH algorithm in identifying patients with a high risk of PAH as defined in the 2022 ESC/ERS guidelines (mean pulmonary arterial pressure [mPAP] >20 mm Hg, pulmonary capillary wedge pressure [PCWP] ≤15 mm Hg, and pulmonary vascular resistance >2 Wood units) was assessed using summary statistics and was descriptively compared to the known performance of DETECT PAH as defined in 2014, when it was developed (mPAP ≥25 mm Hg and PCWP ≤15 mm Hg). RESULTS: The sensitivity of DETECT PAH in identifying patients with a high risk of PAH according to the 2022 ESC/ERS definition was lower (88.2%) compared to the 2014 definition (95.8%). Specificity improved from 47.8% to 50.8%. CONCLUSION: The performance of the DETECT algorithm to screen for PAH in patients with SSc is maintained when PAH is defined according to the 2022 ESC/ERS hemodynamic definition, indicating that DETECT remains applicable to screen for PAH in patients with SSc.
Asunto(s)
Algoritmos , Hemodinámica , Guías de Práctica Clínica como Asunto , Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/fisiopatología , Esclerodermia Sistémica/diagnóstico , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico , Femenino , Masculino , Hemodinámica/fisiología , Persona de Mediana Edad , Europa (Continente) , Cateterismo Cardíaco , Anciano , Sociedades Médicas , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico , Sensibilidad y Especificidad , Resistencia Vascular/fisiología , Cardiología/normas , Presión Esfenoidal Pulmonar/fisiología , EcocardiografíaRESUMEN
OBJECTIVE: Although airway disease associated with Sjögren's disease (Sjo-AD) is common, it is poorly studied compared with interstitial lung disease (ILD). In this study, we aimed to assess factors associated with Sjo-AD, the characteristics and prognosis of this manifestation. METHODS: We performed a retrospective multicentric study involving nine centres. We included Sjo-AD patients confirmed by at least one clinician and one CT scan report. Clinical and biological data, pulmonary function test (PFT), and CT scans were collected. A single radiologist specialist in thoracic diseases reviewed CT scans. Sjo-AD patients were compared with Sjo controls without pulmonary involvement, randomly selected after matching for age and disease duration. RESULTS: We included 31 Sjo-AD and 62 Sjo controls without pulmonary history. Sjo-AD had a higher disease activity (ESSDAI) compared with controls, even when excluding the pulmonary domain of the score (7 vs 3.8, p<0.05), mainly due to the biological activity. Sjo-AD was multilobar (72%) and associated with signs of both bronchiectasis and bronchiolitis (60%). Obstructive lung disease occurred in 32% at the time of Sjo-AD diagnosis. Overall, PFT was stable after 8.7±7 years follow-up but repeated CT scans showed extended lesions in 41% of cases within 6±3.2 years. No patient developed Sjo-ILD. Sjo-AD progression was independent of the global disease activity. CONCLUSIONS: Sjo-AD preferentially affects Sjo patients with higher biological activity. It is often characterised as a diffuse disease, affecting both proximal and distal airways, with a slow evolution over time and no progression to Sjo-ILD.
Asunto(s)
Enfermedades Pulmonares Intersticiales , Síndrome de Sjögren , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Pronóstico , Estudios Retrospectivos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnósticoRESUMEN
BACKGROUND: Sjögren's disease is a heterogenous autoimmune disease with a wide range of symptoms-including dryness, fatigue, and pain-in addition to systemic manifestations and an increased risk of lymphoma. We aimed to identify distinct subgroups of the disease, using cluster analysis based on subjective symptoms and clinical and biological manifestations, and to compare the prognoses of patients in these subgroups. METHODS: This study included patients with Sjögren's disease from two independent cohorts in France: the cross-sectional Paris-Saclay cohort and the prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. We first used an unsupervised multiple correspondence analysis to identify clusters within the Paris-Saclay cohort using 26 variables comprising patient-reported symptoms and clinical and biological manifestations. Next, we validated these clusters using patients from the ASSESS cohort. Changes in disease activity (measured by the European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI]), patient-acceptable symptom state (measured by the EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI]), and lymphoma incidence during follow-up were compared between clusters. Finally, we compared our clusters with the symptom-based subgroups previously described by Tarn and colleagues. FINDINGS: 534 patients from the Paris-Saclay cohort (502 [94%] women, 32 [6%] men, median age 54 years [IQR 43-64]), recruited between 1999 and 2022, and 395 patients from the ASSESS cohort (370 [94%] women, 25 [6%] men, median age 53 years [43-63]), recruited between 2006 and 2009, were included in this study. In both cohorts, hierarchical cluster analysis revealed three distinct subgroups of patients: those with B-cell active disease and low symptom burden (BALS), those with high systemic disease activity (HSA), and those with low systemic disease activity and high symptom burden (LSAHS). During follow-up in the ASSESS cohort, disease activity and symptom states worsened for patients in the BALS cluster (67 [36%] of 186 patients with ESSPRI score <5 at month 60 vs 92 [49%] of 186 at inclusion; p<0·0001). Lymphomas occurred in patients in the BALS cluster (five [3%] of 186 patients; diagnosed a median of 70 months [IQR 42-104] after inclusion) and the HSA cluster (six [4%] of 158 patients; diagnosed 23 months [13-83] after inclusion). All patients from the Paris-Saclay cohort with a history of lymphoma were in the BALS and HSA clusters. This unsupervised clustering classification based on symptoms and clinical and biological manifestations did not correlate with a previous classification based on symptoms only. INTERPRETATION: On the basis of symptoms and clinical and biological manifestations, we identified three distinct subgroups of patients with Sjögren's disease with different prognoses. Our results suggest that these subgroups represent different heterogeneous pathophysiological disease mechanisms, stages of disease, or both. These findings could be of interest when stratifying patients in future therapeutic trials. FUNDING: Fondation pour la Recherche Médicale, French Ministry of Health, French Society of Rheumatology, Innovative Medicines Initiative 2 Joint Undertaking, Medical Research Council UK, and Foundation for Research in Rheumatology.
Asunto(s)
Linfoma , Síndrome de Sjögren , Masculino , Humanos , Femenino , Persona de Mediana Edad , Síndrome de Sjögren/diagnóstico , Estudios Prospectivos , Paris/epidemiología , Estudios Transversales , Análisis por Conglomerados , Linfoma/epidemiologíaRESUMEN
BACKGROUND: The 2022 European Society of Cardiology/European Respiratory Society guidelines define pulmonary hypertension (PH) as a resting mean pulmonary artery pressure (mPAP) > 20 mm Hg at right heart catheterization (RHC). Previously, patients with an mPAP between 21 and 24 mm Hg were classified in a "gray zone" of unclear clinical significance. RESEARCH QUESTION: What is the diagnostic performance of the main parameters used for PH screening in detecting patients with systemic sclerosis (SSc) with an mPAP of 21 to 24 mm Hg at RHC? STUDY DESIGN AND METHODS: Patients with SSc from the European Scleroderma Trials and Research (EUSTAR) database with available tricuspid annular plane systolic excursion (TAPSE), systolic PAP (sPAP), and mPAP data were included. Patients with mPAP 21 to 24 mm Hg and patients with mPAP ≤ 20 mm Hg were considered for the analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. RESULTS: TAPSE/sPAP was lower in the group of patients with SSc with mPAP 21 to 24 mm Hg than in the non-PH group (0.58 [0.46-0.72] vs 0.69 [0.57-0.81] mm/mm Hg, respectively; P < .01). No difference was found in other parameters between the two groups. Diffusing capacity of the lungs for carbon monoxide (Dlco) < 80% of the predicted value had the highest sensitivity (88.9%) and NPV (80%), but the lowest specificity (18.2%) and PPV (30.8%) in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg had the highest specificity (78.9%), PPV (50%), and accuracy (68.1%); its NPV was 75.4%, and its sensitivity was 45.1%. INTERPRETATION: Dlco < 80% of the predicted value is the parameter with the highest sensitivity and NPV in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg has the highest specificity, PPV, and accuracy and, therefore, can be a useful additional parameter to decrease the number of unnecessary RHCs.
RESUMEN
BACKGROUND: Vascular phenotype is associated with a poor prognosis in systemic sclerosis (SSc). The identification of its risk factors could facilitate its early detection. OBJECTIVES: To explore risk factors for a vascular phenotype of SSc, among them a history of pre-eclampsia. METHODS: This observational multicentre case-control study enrolled adult women fulfilling European Alliance of Associations for Rheumatology 2013 diagnosis criteria for SSc and having a pregnancy history≥6 months before SSc diagnosis in 14 French hospital-based recruiting centres from July 2020 to July 2022. Cases had specific vascular complications of SSc defined as history of digital ischaemic ulcers, pulmonary arterial hypertension, specific cardiac involvement or renal crisis. Women with SSc were included during their annual follow-up visit and filled in a self-administered questionnaire about pregnancy. A case report form was completed by their physician, reporting data on medical history, physical examination, clinical investigations and current medication. The main outcome was the presence/absence of a personal history of pre-eclampsia before SSc diagnosis, according to the validated pre-eclampsia questionnaire. RESULTS: 378 women were included: 129 cases with a vascular phenotype and 249 matched controls. A history of pre-eclampsia was reported in 5 (3.9%) cases and 12 (4.8%) controls and was not associated with a vascular phenotype (OR=0.96, 95% CI 0.28 to 3.34, p=0.9). Besides, Rodnan skin score and disease duration≥5 years were risk factors for vascular phenotype. CONCLUSIONS: In women with SSc and a pregnancy history≥6 months before SSc, a history of pre-eclampsia is not associated with a vascular phenotype.
Asunto(s)
Preeclampsia , Esclerodermia Sistémica , Adulto , Femenino , Humanos , Embarazo , Estudios de Casos y Controles , Fenotipo , Preeclampsia/diagnóstico , Preeclampsia/epidemiología , Preeclampsia/etiología , Factores de Riesgo , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnósticoRESUMEN
OBJECTIVE: Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs). METHODS: Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis. RESULTS: Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5-10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3-6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown. CONCLUSION: EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.
Asunto(s)
Anticuerpos Monoclonales , Antígenos CD20 , Infecciones por Enterovirus , Humanos , Infecciones por Enterovirus/inmunología , Infecciones por Enterovirus/diagnóstico , Masculino , Femenino , Anticuerpos Monoclonales/uso terapéutico , Antígenos CD20/inmunología , Persona de Mediana Edad , Adulto , Meningoencefalitis/inmunología , Meningoencefalitis/virología , Meningoencefalitis/etiología , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Anciano , Rituximab/uso terapéutico , Linfocitos B/inmunología , Agammaglobulinemia/inmunología , Agammaglobulinemia/complicaciones , Inflamación/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVES: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. METHODS: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. RESULTS: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. CONCLUSIONS: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.
RESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. METHODS: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. FINDINGS: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. INTERPRETATION: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. FUNDING: None.