Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies

Objective. To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria. Methods. The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immu-nological phenotypes: Double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/ SSB, and immunonegative. Results. The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥ 1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/ SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in com-parison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/ SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group. Conclusion. Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Objective: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Cross-national health care database utilization between Spain and France: results from the EPICHRONIC study assessing the prevalence of type 2 diabetes mellitus

Guillaume Moulis,1–3,* Berta Ibañez,4–6,* Aurore Palmaro,2,3 Felipe Aizpuru,6–8 Eduardo Millan,6,8 Maryse Lapeyre-Mestre,2,3,9 Laurent Sailler,1–3 Koldo Cambra5,6,10 1Department of Internal Medicine, Toulouse University Hospital, Toulouse, France; 2UMR1027 INSERM, University of Toulouse, Toulouse, France; 3Clinical Investigation Center 1436, Toulouse University Hospital, Toulouse, France; 4Navarrabiomed, Health Department, Public University of Navarra, Pamplona, Spain; 5IdiSNA, Pamplona, Spain; 6Health Service Research on Chronic Patients Network (REDISSEC), Pamplona, Spain; 7Research Unit Araba (BioAraba), Osakidetza-Basque Health Department, Vitoria-Gasteiz, Spain; 8Healthcare Services Sub-directorate, Osakidetza-Basque Health Service, Araba, Spain; 9Department of Medical and Clinical Pharmacology, Toulouse University Hospital, Toulouse, France; 10Institute of Public Health and Labour Health of Navarra, Pamplona, Spain *These authors contributed equally to this work Aim: The EPICHRONIC (EPIdemiology of CHRONIC diseases) project investigated the possibility of developing common procedures for French and Spanish electronic health care databases to enable large-scale pharmacoepidemiological studies on chronic diseases. A feasibility study assessed the prevalence of type 2 diabetes mellitus (T2DM) in Navarre and the Basque Country (Spain) and the Midi-Pyrénées region (France). Patients and methods: We described and compared database structures and the availability of hospital, outpatient, and drug-dispensing data from 5.9 million inhabitants. Due to differences in database structures and recorded data, we could not develop a common procedure to estimate T2DM prevalence, but identified an algorithm specific to each database. Patients were identified using primary care diagnosis codes previously validated in Spanish databases and a combination of primary care diagnosis codes, hospital diagnosis codes, and data on exposure to oral antidiabetic drugs from the French database. Results: Spanish and French databases (the latter termed Système National d’Information Inter-Régimes de l’Assurance Maladie [SNIIRAM]) included demographic, primary care diagnoses, hospital diagnoses, and outpatient drug-dispensing data. Diagnoses were encoded using the International Classification of Primary Care (version 2) and the International Classification of Diseases, version 9 and version 10 (ICD-9 and ICD-10) in the Spanish databases, whereas the SNIIRAM contained ICD-10 codes. All data were anonymized before transferring to researchers. T2DM prevalence in the population over 20 years was estimated to be 6.6–7.0% in the Spanish regions and 6.3% in the Midi-Pyrénées region with ~2% higher estimates for males in the three regions. Conclusion: Tailored procedures can be designed to estimate the prevalence of T2DM in population-based studies from Spanish and French electronic health care records. Keywords: epidemiology, pharmacoepidemiology, electronic health care database, cross-national study, population-based study, type 2 diabetes mellitu