Search

Objectives Using data of patients from the inception cohort Registro Español de Lupus Eritematoso Sistémico (RELES), we aimed to analyse the incidence of severe infection in the first two years of follow-up and how predictors of infection change during the course of systemic lupus erythematosus (SLE). Material and methods The study included 282 patients. Markers of lupus activity, prednisone doses and immunosuppressive therapy were compared between patients with and without infections in the first and second year of the disease. Drug therapy administered during the first month of follow-up has been considered as a potential predictor of infections during the first year and medications administered during the first year have been considered potential predictors of infections during the second. Results Nineteen patients (6.4%) had a documented episode of major infection during the first year of follow-up and 16 patients (5.67%) during the second. The following variables were associated with infections during the first year: hypocomplementaemia at diagnosis (p < 0.01), nephritis at diagnosis (p = 0.03), SLEDAI score (p < 0.01), prednisone >30 mg/day (p = 0.01), methylprednisolone pulses (p = 0.05) and mycophenolate use (p = 0.02). The independent variables in the final model were hypocomplementaemia (odds ratio (OR) 4.41, 95% confidence interval (CI) 0.96–20.20, p = 0.05) and a dose of prednisone >30 mg/day (OR 6.60, 95% CI 1.34–32.42, p = 0.02). The following variables were associated with infections during the second year: dose of prednisone > 7.5 mg/day (p = 0.05), methylprednisolone pulses (p = 0.07), duration of therapy with antimalarials (p = 0.09), therapy with mycophenolate (p = 0.01), therapy with cyclophosphamide (p = 0.05). The independent variables in the final model were a dose of prednisone >7.5 mg/day (OR 4.52, 95% CI 0.99–21, p = 0.054) and duration of therapy with antimalarials as a protective factor (OR 0.99, 95% CI 0.99–1.00, p = 0.053). Conclusions The low incidence of early infections in the RELES cohort is partially explained by the extended use of antimalarials and by the general avoidance of prolonged high doses of prednisone. Patients with high baseline activity are at a higher risk of infection during the first months but therapy with medium–high doses of prednisone is the main predictor of infectious events. Thus, every effort should be made to limit oral glucocorticoid use from the very beginning of the SLE course. [ABSTRACT FROM AUTHOR]

The article describes the case of a 50-year-old man with history of intramural hematoma of the aortic arch. An abnormal tracer uptake that surrounds the retroperitoneal and mediastinal aorta was revealed following 18 Fluorine-2-fluoro-2-Deoxy-d-glucose positron emission tomography/computerized tomography (F-FDG PET/CT) imaging. It notes that this finding suggests the possibility of fibrosis of the entire aorta.

Objectives: To compare the main characteristics of two inception cohorts (Italian [ITC] and Spanish [SPC]) cohorts of patients with systemic lupus erythematosus (SLE) at the time of diagnosis and at one year of follow-up., Methods: Demographic, clinical and immunological characteristics, and treatments at SLE diagnosis and at 12 months of follow-up of ITC and SPC were compared., Results: One hundred and sixty-four patients in the ITC and 231 patients in the SPC were compared. the patients from ITC were younger at SLE diagnosis (41.1±15.0 years vs. 46.4±15.6 years; p<0.001) and had a higher prevalence of arthritis (62.8% vs. 45.5%; p=0.001), serositis (25.6% vs. 16.0%; p=0.026), neurological involvement (7.9% vs. 1.7%; p=0.006), and immunological abnormalities (anti-dsDNA, anti-Sm, antiphospholipid antibodies) (93.9% vs. 77.8%; p<0.001). Conversely, photosensitivity (29.5% in ITC vs. 45.9% in SPC; p=0.001) and oral ulcers (12.4% vs. 30.3%; p<0.001) were more frequent at onset of SLE in the Spanish patients. At the first 12 months of follow-up, these differences were maintained. At SLE onset, more Italian patients received glucocorticoids (85.4% vs. 50.2%; p<0.001) and immunosuppressive agents. At 12 months of follow-up, more Spanish patients were treated with antimalarials (75.6% in ITC vs. 90.0% in SPC; p<0.001). Conversely, the use of glucocorticoids was lower in SPC (89.0% in ITC vs. 57.1% in SPC; p<0.001)., Conclusions: These cohorts presented different profiles in terms of pattern of organ/system involvement and disease treatment, possibly as a consequence of patient selection or different disease management approaches between Italy and Spain.

Objectives: This is the first Spanish multicentric inception lupus cohort, formed by SLE patients attending Spanish Internal Medicine Services since January 2009. We aimed to analyse drug therapy during the first year of follow-up according to disease severity., Methods: 223 patients who had at least one year of follow-up were enrolled upon diagnosis of SLE. Therapy with prednisone, pulse methyl-prednisolone, hydroxychloroquine, immunosuppressives and calcium/vitamin D was analysed., Results: Prednisone was given to 65% patients, at a mean (SD) daily dose of 11 (10) mg/d. 38% patients received average doses >7.5 mg/d during the first year. Patients with nephritis and with a SLEDAI ≥6 were treated with higher doses of prednisone. 81% of patients were treated with hydroxychloroquine, with higher frequency among those with a SLEDAI ≥6 (88% vs. 68%, p<0.001). The use of immunosuppressive drugs and methyl-prednisolone pulses was higher in patients with a baseline SLEDAI ≥6, however, differences were no longer significant when patients with lupus nephritis were excluded. The use of calcium/vitamin D increased with the dose of prednisone, however, 43% of patients on medium-high doses of prednisone did not take any calcium or vitamin D., Conclusions: This study gives a real-world view of the current therapeutic approach to early lupus in Spain. The generalised use of hydroxychloroquine is well consolidated. There is still a tendency to use prednisone at medium to high doses. Pulse methyl-prednisolone and immunosuppressive drugs were used in more severe cases, but not as steroid sparing agents. Vitamin D use was suboptimal.

Background and Objective: Pulmonary arterial hypertension (PAH) is an important cause of morbimortality in systemic sclerosis (SSc). Evolution is worse than that of subjects with idiopathic PAH, but prognosis improves when PAH is diagnosed early. The aim of this research is to describe results of a screening program for diagnosis of pulmonary hypertension (PH) carried out in a cohort of Spanish patients with SSc., Patients and Method: PH screening was performed by transthoracic doppler echocardiography (TTDE) in 184 patients with SSc. Patients with systolic pulmonary arterial pressure estimated by TTDE>35 mmHg were evaluated per protocol to confirm diagnosis and type of PH., Results: PAH was diagnosed in 25 patients (13.6%). Patients with diffuse and limited SSc developed PAH in a similar degree, 9/60 (15%) vs. 16/100 (16%), with no cases among patients with SSc "sine scleroderma" or "pre-scleroderma" (P<.001). The only clinical or epidemiological data characterizing patients with PAH were older age (mean age 67 years for patients with PAH vs. 56 years for those without PAH, P=.007), limited SSc, a trend toward shorter evolution of the underlying disease (median 8 years for patients with PAH vs. 10 years for those without PAH, P=.73), and a higher frequency of positive anticentromere antibodies (16 patients [64%] with PAH vs. 70 (48,3%) without PAH, P=.19)., Conclusions: Prevalence of PAH in SSc was high and supports the implementation of a regular screening program., (Copyright © 2015 Elsevier España, S.L.U. All rights reserved.)

Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population.

To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.

A biological marker can be defined as any substance that can be objectively measured and evaluated as an indicator of a normal biological process, a pathogenic process or pharmacological responses to a therapeutic intervention. In pulmonary hypertension (PH), in addition to routine markers (hemodynamic and functional), there are a growing number of biomarkers that allow an increasingly comprehensive approach to knowledge of susceptibility to this disease and to diagnosis, prognosis and treatment response. These markers can be both constitutive (genetic) and disease-related (related to right ventricular failure, such as BMP/NT-proBNP, endothelial dysfunction, such as endothelin-1, or inflammation, such as certain cytokines and chemokines). Novel insights in genomics and proteomics may allow major advances in this field., (Copyright © 2011 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.)

Background and Objective: To study severe infectious complications in a cohort of patients with systemic lupus erythematosus (SLE)., Patients and Method: Retrospective study of 705 patients followed from January 1980 to January 2008. Data are expressed in percentages., Results: The frequency of severe infectious was 38.6%. The etiology was bacterial 54.4%, viric 30.4% and opportunist in 15.2% patients. Involved organs were: Lung 38.2%, kidney 48.9%, central nervous system 43%. 43.75% patients received pulsed ciclofosfamide therapy and 88.6% received glucocorticoids (39.7% pulsed). The mortality was 27.7%., Conclusions: At present, infection is an important cause of mortality in patients with SLE. Early diagnosis of infectious complications is very important in SLE., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Objectives: 1) To study tuberculosis (TB) infection in a cohort of patients with systemic lupus erythematosus (SLE) and to compare its frequency and characteristics with that of others series. 2) To look for differential characteristic among SLE patients with and without TB. 3) To investigate if there was any relationship between TB's most severe forms and higher doses of glucocorticoids (GC) or other immunosuppressants., Patients and Method: Retrospective review of medical records of 789 SLE patients and description of the clinical characteristics of 13 cases of active TB infection among them. Bibliographical search in MEDLINE-PubMed of the SLE/TB series published, using the terms: infection, tuberculosis, systemic lupus erythematosus. Comparative study of clinical, biological and therapeutic differences between cases (SLE/TB+) and controls (SLE/TB) using χ(2) and Fisher exact test., Results: Thirteen patients with active tuberculosis were detected (10 women, average age 36 years/SD 11,2/prevalence 1,6%). Nine (69,2%) of them were primary infections and 4 (30,8%) reactivations. Microbiological diagnosis (smear examination for acid-fast bacilli and/or culture on Lowestein-Jensen medium) was established in 11 patients (84,6%). TB Pulmonary manifestations was present in 9 patients (69,2%) and extra-pulmonary manifestations were found in 8 [(61,5%); 6 of them (46%) were disseminated forms]. Nine (69,2%) patients were on GC therapy at the moment TB was diagnosed. Four of the TB patients died (30,8%). Myositis was more frequent in TB cases (p < 0,05). This data is similar to that reported in the literature., Conclusions: In our series, TB mortality was high (30,8%) in a patients with SLE. Frequency of extrapulmonary forms was double than that described in the Spanish population. Patients with higher GC dose had more severe forms of TB., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Background and Objective: Thyroid disease (TD) is more prevalent in patients with pulmonary arterial hypertension (PAH) than in the general population. The frequency and the cause of this association are not well established. We aimed to quantify and analyze the incidence and characteristics of TD in a cohort of PAH patients (idiopathic or preferentially associated with systemic diseases) and review the literature., Patients and Method: Fifty eight PAH patients were prospectively studied, according to a previously established protocol (that included right heart catheterization); TSH, T(4), and antithyroglobulin and antiperoxidase antibodies were determined. TD was defined as an abnormal TSH level and/or elevated antithyroid antibodies (TAbs). Clinical, biological and hemodynamic variables were compared between patients with and without TD., Results: TD was detected in 30 patients (51%): high TSH levels were observed in 21 (36,21%); hyperthyroidism in 2 (3,45%); and TAbs in 16 of 54 (27,59%), 7 of whom were euthyroid. In the TD group, PAH evolution time was longer (4,62 vs 2,61 years; P=.005, CI 95%, 0,63-3,38), more patients were in functional class IV (13;43,3% vs 5;15,8%, P=.046, CI 95% ,0,05-11,75), cardiac output was lower (P=.032, CI 95%, 3,16-4,89) and epoprostenol treatment was more frequently used (14;46,6% vs 4;14,3%, P=.008, CI 95%, 1,46-18,85; OR=5,25)., Conclusions: The frequency of TD detected in this PAH cohort reaches 51% and it was associated with a longer evolution time of PAH and worse hemodynamic situation. Although epoprostenol was used more frequently in TD patients, a causal relationship with TD could not be established.

Peritoneal vasculitis is a rare and severe clinical manifestation of systemic lupus erythematosus. We report a patient who presented with ascites due to peritoneal vasculitis and cutaneous, articular, hematological and renal inflammatory activity. Treatment with glucocorticoids and immunosuppressive drugs was ineffective. In view of the resistance to different therapies, 4 weekly infusions of 375mg/m2 of rituximab (RTX) were started, in association with cyclophosphamide pulses during the first and the third weeks. With this treatment strategy, the patient reached a complete response which was achieved in later flares of inflammatory activity (the second and third flares were multisystemic and with ascites again, and the fourth flare with nephritis)., (Copyright © 2009 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.)

Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.

Background and Objective: To assess the value of rituximab in systemic autoimmune diseases which are refractory to others treatments., Patients and Method: Prospective study on 12 patients -7 with systemic lupus erythematosus (SLE), 4 with Wegener's granulomatosis (WG), and 1 with overlapping connective disease and autoimmune thrombocytopenia-, controlled in a specialized unit of a tertiary hospital. Four weekly doses of rituximab, 2 biweekly doses of cyclophosphamide, and glucocorticoids were administered to all patients, and other immunosuppressants were also administered as considered necessary in each case., Results: Mean follow up after treatment with rituximab was 12.8 moths for SLE patients and 12.3 for WG patients. In SLE patients, proteinuria was reduced below 1 g daily in 5 cases (83%), with a clear parallel improvement in the urinary sediment. Serositis was resolved in both cases. One patient required 3 treatment cycles to obtain an adequate response and another required a second cycle for relapse. Only one patient with WG had a favorable response. The patient treated for autoimmune thrombocytopenia had a favorable response, with no relapses, and creatine-kinase levels also tended to return to normal. There were 2 serious adverse events (terminal renal failure and serious colitis in a patient with SLE, and death of one patient with WG), that were not adjudicated directly to rituximab. Immunoglobulin levels did not change substantially. There were no infusion reactions or associated infections., Conclusions: Rituximab was useful in patients with SLE refractory to other immunosuppressants. On the contrary, its efficacy in WG was limited. The response of thrombocytopenia was complete and maintained.

Objective: Transverse myelitis (TM) is a rare complication in patients with systemic lupus erithematosus (SLE). We reviewed a series of our SLE patients to determine the prevalence of TM, and evaluate the clinical characteristics, medical tests, evolution and response to the treatment., Patients and Method: Six patients with TM were identified and underwent a neurological evaluation, MRI, electrophysiologic study and were all subjected to the same treatment. A descriptive statistical study was conducted., Results: We observed a prevalence of 0.92% in our patients with SLE. Eighty three point three per cert had antiphospholipid antibodies and/or lupus anticoagulant. The MRI confirmed the diagnosis in 5 cases. Of the 5 patients with antiphospholypid antibodies, 3 were anticoagulated or took aspirin with a good neurological outcome, leaving 2 of them without posterior complications., Conclusions: We found a prevalence similar to that observed in other series, around 1%. The high prevalence of antiphospholypid antibodies in these patients, with good outcome in those anticoagulated or treated with antiplatelet agents suggests an important pathogenic role in the development of TM, and emphasized the possibility of adding to the standard treatment, antiplatelet agents or anticoagulation., (Copyright © 2007 Elsevier España S.L Barcelona. Published by Elsevier Espana. All rights reserved.)

Background and Objective: Congenital complete atrioventricular heart block (CHB) is due to the lesion of the cardiac conduction system by specific transplacental antibodies of maternal origin. In adults with systemic lupus erythematosus (SLE), cardiac toxicity is very questionable and has been related to treatment with synthetic antimalarial drugs (AM). Here we evaluate, in our geographic area, the presence of non congenital CHB in adult patients with SLE and its possible association with AM treatment., Patients and Methods: The frequency of CHB has been studied revising the clinical records of 595 SLE patients followed at the Unit for Systemic Diseases., Results: Five women (0.8% of the total series) suffered from CHB (2 patients developed it during a lupic crisis). All were on treatment with AM (100 versus 60% of the rest of the series) and maintained a dose of 250 mg/day (except one, with a dose of 500 mg/day) for a mean period of 90 months. The accumulated mean dose of AM was 753 g. Three patients developed cardiac insufficiency; 2 nephropathy; 2 myopathy; and one maculopathy. As accompanying processes we detected Sjögren's syndrome (2) and hypothyroidism (3). The frequency of HLA DR3, positive in 80% of the cases, is higher than observed in the total series, 34% (p = 0.053)., Conclusions: We detected the presence of CHB in 0.8% of SLE patients. They were all treated with AM. We did not verify any relationship with anti-ENA (anti-Ro/La and anti-RNP) antibodies, as communicated by others, but rather a trend to the association with HLA DR3 (at the limit of statistical significance)., (Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.)

Background and Objective: To evaluate the long term efficacy of treatment with intravenous iloprost for severe Raynaud's phenomenon (RP) and ischemic leg ulcers in patients with autoimmune systemic diseases., Patients and Method: Prospective observational study over 2 years with iloprost (intravenous infusions, 0.5 to 2 ng/kg/min, initial cycle of 5 consecutive days and maintenance infusions during 24 h monthly, lengthened when it was needed) in patients with severe RP and ischemic leg ulcers whithout response to conventional therapy. Treatment was halted in patients with a good response after one year of treatment, with regular clinical controls., Results: We treated 23 patients. Iloprost reduced significantly the mean number (SD) of monthly episodes of RP (150.38 [102.04] initially and 40.05 [78.06] at the end; p < 0.0005), the mean highest duration of episodes of RP (21.86 [26.96] min initially and 7.14 [9.87] min at the end; p = 0.013), the associated pain (p = 0.005), and the mean number of ischemic digital (4.25 [2.86] initially and 0.63 [2.25] at the end; p = 0.003) and leg ulcers (1.67 [0.52] initially and 0.33 [0.52] at the end; p = 0.01). Articular symptoms and inflammatory markers did not improve. Treatment was stopped in 8 patients (in 5 for a very good evolution and in 3 for other causes), and only 1 of them needed to be treated again. Side effects were seen in all cases but always disappeared after slowing infusion., Conclusions: Iloprost was effective in the long term treatment of severe RP and ischemic leg ulcers in patients with autoimmune systemic diseases.