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Antibody to Epstein–Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjögren’s syndrome (pSS) were not established. We evaluated 100 pSS patients (American–European Criteria) and 89 age/gender/ethnicity-matched healthy controls. Disease activity was measured by EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p  = 0.501; 2.6 ± 1.1 vs. 2.5 ± 1.1 AU/mL, p  = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p  = 0.576; 141.3 ± 69.8 vs. 135.6 ± 67.5 RU/mL, p  = 0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p  < 0.0001; 38.6 ± 57.4 vs. 7.9 ± 26.3 RU/mL, p  < 0.0001). Further analysis of patients with ( n  = 36) and without ( n  = 64) anti-EA-D revealed comparable age/gender/ethnicity ( p  ≥ 0.551), current prednisone dose (4.8 ± 6.9 vs. 5.1 ± 10.4 mg/day, p  = 0.319), and current uses of prednisone (52.8 vs. 37.5 %, p  = 0.148) and immunosuppressants (44.4 vs. 31.3 %, p  = 0.201). ESSDAI values were comparable ( p  = 0.102), but joint activity was more frequent (25 vs. 9.4 %, p  = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA ( p  = 1.000), anti-La/SSB ( p  = 0.652), rheumatoid factor ( p  = 1.000), anti-α-fodrin ( p  = 0.390) or antiphospholipid antibodies ( p  = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.

Background Despite the WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)

► Seroconversion and seroprotection rates are comparable to healthy controls. ► Short and long-term disease safety was demonstrated. ► Autoantibody induction: at long-term and within the SS spectrum. ► Vaccine induces long-term changes in SS autoantibodies without deleterious effect in disease course. Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjögren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p=0.42), seroprotection (83.3 vs. 72.2%, p=0.26) and FI-GMT (p=0.85). Disease duration, prednisone (2.1±4.9mg/day), methotrexate and azathioprine did not affect seroconversion (p>0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p>0.05) and only mild side effects were reported in comparable rates to controls (p>0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p=0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p=0.0001) and anti-La/SSB (p=0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.

The objective of this study was to demonstrate the presence of mycobacterial nucleic acid sequences in peripheral blood and arteries from patients with Takayasu arteritis (TA). Polymerase chain reaction was performed to detect mycobacterial DNA from three different nucleic acid sequences including the insertion sequence (IS) 6110 , the 65-kDa heat shock protein gene ( HSP65 ), and the 16S ribosomal RNA (rRNA) gene in peripheral blood from 32 TA patients and in arterial specimens from 10 TA patients. Twenty-eight HIV-negative patients with pulmonary tuberculosis prior to therapy were tested for IS 6110 in peripheral blood as positive controls, and 24 blood donors were evaluated as healthy controls (HC). All TA patients were negative for the insertion sequence IS 6110 and for HSP65 and 16S rRNA genes in blood samples and in arterial specimens. IS 6110 sequence was found in peripheral blood from 22 (78.5 %) patients with pulmonary tuberculosis but not in HC. In conclusion, the strategy of mycobacterial-specific nucleic acid amplification in the peripheral blood and arterial specimens of TA patients was unable to lend support to the association between TA and tuberculosis long suggested in the literature.

► Pre- and post-vaccination disease and muscle parameters were comparable. ► The vaccine was well tolerated without any severe adverse effects during follow-up. ► Seroconversion, seroprotection rate, GMTs and FI in the GMTs were comparable. The goal of the present study was to evaluate the influence of the influenza A H1N1/2009 vaccine on dermatomyositis/polymyositis (DM/PM) disease parameters and the potential deleterious effect of therapy on immune response. Thirty-seven DM and 21 PM patients (Bohan and Peter's criteria) were gender- and age-matched to 116 healthy controls. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. Disease safety was determined from a muscle enzyme analysis and the DM/PM scores [patient's visual analog scale (VAS), physician's VAS, manual muscle strength (MMT-8)] evaluated pre- and post-vaccination. The mean age (43.1±9.9 vs. 43.8±8.4 years, p=0.607) and gender distribution (p=1.00) were comparable between the patients and controls. After 21 days, seroconversion (p=0.394), seroprotection (p=0.08), GMT (p=0.573) and the FI in the GMT (p=0.496) were similar in both groups. The disease and muscle parameters remained stable throughout the study, including the creatine kinase (p=0.20) and aldolase levels (p=0.98), the physicians’ VAS (p=1.00), the patients’ VAS (p=1.00) and the MMT-8 (p=1.00). Regarding the influence of treatment, the seroconversion rates were comparable between the controls and patients undergoing treatment with glucocorticoid (GC) (p=0.969), GC >0.5mg/kg/day (p=0.395) and GC+immunosuppressors (p=0.285). Vaccine-related adverse events were mild and similar in the DM/PM and control groups (p>0.05). Our data support the administration of the pandemic influenza A H1N1/2009 vaccination in DM/PM, as we found no short-term harmful effects related to the disease itself and adequate immunogenicity in spite of therapy. Further studies are necessary to identify any long-term adverse effects in patients with these diseases.

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sjögren’s syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American–European criteria) and 89 age–gender–ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (aβ2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney’s criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16 % patients and 5.6 % controls ( p  = 0.035). LA was the most common aPL in patients (9 %), followed by aβ2GPI (5 %) and aCL (4 %). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls ( p  = 0.061). Mean age at time of stroke was 35 years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney’s criteria) and were positive exclusively for LA. Comparison of patients with ( n  = 16) and without ( n  = 84) aPL revealed similar mean age, female predominance, and ethnicity ( p  > =0.387). Frequencies of livedo reticularis (25 vs. 4.8 %, p  = 0.021), stroke (12.5 vs. 0 %, p  = 0.024), and DVT (18.8 vs. 1.2 %, p  = 0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL ( p  ≥ 0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.

Mycophenolate mofetil (MMF) has recently been reported as a useful alternative immunosuppressive drug in autoimmune diseases including in Takayasu arteritis (TA). The aim of this study was to verify the efficacy and tolerability of MMF administration in controlling TA disease activity and allowing glucocorticosteroid reduction. Ten consecutive active TA patients followed at the Vasculitis Clinic were enrolled from January 2003 to 2006 and received oral MMF (2 g/day) for an average of 23.3 months. Disease activity assessed using the National Institutes of Health criteria, clinical features, and inflammatory laboratory findings were evaluated. Five patients had received at least one immunosuppressive drug before administration of MMF (four methotrexate, two azathioprine, and one chlorambucil) but had not achieved clinical and laboratory remission. The other five patients received MMF as their first immunosuppressive drug because of an important disease flare during steroid dose reduction. Clinical activity disappeared in all patients with MMF therapy, except in one patient who abandoned the study because of an important headache, attributed to the drug. Moreover, the MMF therapy allowed significant tapering of the prednisone dose in the rest of the nine patients (24.5 +/- 17.1 vs 5.8 +/- 7.8 mg/day; p = 0.0019). Reinforcing this finding, a significant reduction in inflammatory laboratory parameters, erythrocyte sedimentation rate (24.7 +/- 15.5 vs 12.8 +/- 10.8 mm/h; p = 0.036) and C-reactive protein (24.0 +/- 14.9 vs 11.2 +/- 10.7 mg/l; p = 0.0167), was observed. In summary, MMF therapy reduced clinical and laboratory parameters of TA disease activity, suggesting that this drug is a promising immunosuppressive drug, particularly in refractory cases and as a steroid-sparing agent.

Onset is usually sudden with symmetrical articular involvement of both small and large joints, occurrence of solid skin nodules, and rapid progression. Treatment is generally unrewarding. Here we report a severe and disabling case of FR responding favorably to infliximab therapy. After 32 weeks of continuous treatment, skin lesions dramatically improved and arthropathy partially regressed.

Takayasu arteritis (TA) is an idiopathic chronic inflammatory disease that affects the aorta and its main branches. According to disease involvement, patients may require surgical treatment mainly due ischemic lesions in association with medical therapy. We evaluated the impact of vascular interventions in a cohort of TA patients. Medical records from 146 TA patients were reviewed. Clinical features, medical, and surgical treatment were revised and disease activity was determined by clinical, laboratorial, and imaging parameters. Clinical parameters associated with mortality alongside vascular procedures were evaluated and their impact on mortality in our cohort was estimated. Ninety-four vascular interventions were performed in 61 patients (41.8%). A third of them were of endovascular procedures. The overall mortality was 4.1%, all due to early postoperative complications, which resulted in a rate of surgery-related mortality of 9.8%. All deaths occurred in patients with active disease. Clinical parameters known to be associated with mortality (aneurysm, secondary hypertension, aortic insufficiency, and cerebrovascular accident) were not found related with death. Patients whose disease began before age 20 years had an OR 3.54 of undergoing a vascular surgical intervention. The observed impact of vascular procedures on mortality in patients with Takayasu arteritis, especially during disease activity, supports the notion that such interventions should be performed with caution and preferably during periods of remission.

One patient with dermatomyositis (DM) who developed spontaneous pneumomediastinum (SPnM) is described. A review of 15 previously reported cases shows that this is a complication of DM but not of polymyositis. It occurs in young patients with recent onset of disease characterized by cutaneous vasculopathy, and patients treated with immunosuppressive drugs have, in general, better outcomes. We suggest that the onset of SPnM in DM patients must alert to possible vasculitic activity and that immunosuppressive agents with progressive tapering of corticosteroids are part of the most reasonable approach in these cases.