Subgroups of Sjögren syndrome patients according to serological profiles

Sjögren Syndrome (SS) is a systemic, autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands. Different clinical associations have been described for each of the diverse autoantibodies found in SS patients. Antibodies directed against the Ro/La ribonucleoprotein complexes have been correlated with younger age, more severe dysfunction of the exocrine glands and a higher prevalence of extraglandular manifestations. Anti-nuclear antibodies and rheumatoid factors have been associated to extraglandular manifestations and an active immunological profile, while cryoglobulins are markers of more severe disease and correlate to lymphoma development and death. Antibodies to cyclic citrullinated peptides are scarce in SS and have been linked in some cases to the development of non-erosive arthritis. Furthermore, the presence of anti-mitochondrial antibodies and anti-smooth muscle antibodies in the sera of primary SS patients is considered indicative of primary biliary cirrhosis and autoimmune hepatitis, respectively. In addition, anti-centromere antibodies have been associated with a clinical phenotype intermediate between primary SS and systemic sclerosis, while antibodies against carbonic anhydrase have been related to renal tubular acidosis. Finally, an association of anti-muscarinic antibodies with cytopenias and a higher disease activity has also been described in primary SS. In conclusion, although not all of the above mentioned antibodies are useful for predicting distinct patient subgroups in SS, knowledge of the clinical associations of the different autoantibody specificities encountered in SS can advance our understanding of the disease and improve patient management. © 2012 Elsevier Ltd

Therapeutic Inhibition of Tyrosine Kinases in Systemic Sclerosis: A Review of Published Experience on the First 108 Patients Treated with Imatinib

Objective: Experimental and clinical evidence suggest a therapeutic role for the tyrosine kinase inhibitor imatinib in fibrosing conditions. We evaluated published data on the safety and efficacy of imatinib for patients with systemic sclerosis (SSc), a severe autoimmune disease with significant morbidity and mortality. Methods: A careful search for all original articles and abstracts on the use of imatinib in SSc published in English from 2008 through February 2012 was performed.Twoadditional patients from our center are also described. Results: Five small observational clinical trials on the use of imatinib in severe SSc have been conducted and case reports and small series of refractory to current approaches patients have been reported, adding to a total of 108 patients having received this drug to date. In most of these patients imatinib was given for skin or pulmonary fibrosis. Encouraging results were reported in 3 of 4 studies, whereas the fifth study was prematurely terminated for safety reasons. Overall, clinical results are highly variable, ranging from ineffective or toxic responses to extremely encouraging clinical improvements in some severely ill patients. These discrepancies could partly reflect imatinib-related safety issues, in particular, SSc patients or idiosyncratic resistance to imatinib, as happens in chronic myelogenous leukemia and gastrointestinal stromal tumors, the drug's approved indications. Conclusions: The limited available experience suggests that imatinib could be considered as an individualized treatment approach in severe SSc and underscores the need to identify markers for selecting particular patients, who will safely respond to therapeutic inhibition of tyrosine kinases. © 2013 Elsevier Inc

Impact of non-steroidal anti-inflammatory drugs on cardiovascular risk: Is it the same in osteoarthritis and rheumatoid arthritis?

Although large-scale population studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of myocardial infarction, this is not confirmed in patients with rheumatoid arthritis (RA). Herein, we review the litterature on the differential effects of NSAIDs on cardiovascular risk in osteoarthritis (OA) versus RA and discuss possible explanations for this discrepancy. To assess a potential additive effect of age in non-RA populations, we compared weighted mean age between RA patients and unselected NSAID users included in cohort and case–control studies that estimate the cardiovascular risk of NSAIDs, assuming that the main indication for NSAID usage in elderly populations is OA. Our hypothesis that advanced age in osteoarthtitis compared to RA patients confounds the effect of NSAIDs on cardiovasular risk was not confirmed. Several other hypotheses that can be proposed to explain this counterintuitive effect of NSAIDs on the cardiovascular risk of RA patients are discussed. We conclude that patients with RA have a lower cardiovascular disease risk associated with the use of NSAIDs, probably due to the nature of their disease per se, until further research indicates differently. © 2016 Japan College of Rheumatology

Predictors of morbidity and mortality in early systemic sclerosis: Long-term follow-up data from a single-centre inception cohort

Objectives: To determine predictors of morbidity and mortality in systemic sclerosis (SSc) in a long-term follow-up of an inception cohort of early SSc patients. Methods: We evaluated clinical manifestations, laboratory and lung function tests at disease onset as predictors of morbidity and mortality in 3rd, 6th and 9th year in SSc patients recruited within 12 months of disease onset. Results: A total of 115 SSc patients (97 women, mean age 48.1 ± 13.5 years, 54 diffuse subtype) were included. In multivariate regression analysis, predictors at disease onset for the presence of pulmonary fibrosis in 6th year of follow-up were diffuse subtype (OR: 4.4, p = 0.033), digital ulcers (OR: 7.9, p = 0.014) and esophageal involvement (OR: 4.79, p = 0.038). Arrythmias at disease onset predicted pulmonary hypertension (OR: 6.05, p = 0.022), while age (OR: 1.12, p = 0.002) and anti-Scl70 (OR: 4.3, p = 0.038) predicted arrhythmias in 6th year. During a follow-up of 101.8 ± 48.5 months, 23/115 patients died. Cox proportional hazard models analysis revealed 6 independent predictors of mortality present at disease onset: age at disease onset (45–59 years (HR: 3.0, p = 0.098), ≥60 years (HR: 4.3, p = 0.073), male gender (HR: 3.63, p = 0.025), diffuse subtype (HR: 2.83, p = 0.095), pulmonary fibrosis (HR: 3.7, p = 0.032), echocardiography-diagnosed pulmonary hypertension (HR = 7.49, p = 0.008) and DLCO < 60% (HR: 3.17, p = 0.035). Mortality rates at 3 and 6 years were 14% and 24% for patients with 3 independent predictors and 46% and 53% for patients with 4–6 predictors, respectively. Conclusion: Clinical phenotypes at disease onset may predict morbidity and mortality in SSc and guide treatment decisions. © 2018 Elsevier B.V