José Luis Andreu

Validity of enthesis ultrasound assessment in spondyloarthropathy

OBJECTIVES To develop an ultrasound enthesis score and to assess its validity in the diagnostic classification of the spondyloarthropathies (SpAs). METHODS Twenty-five patients with SpA and 29 healthy controls participated in a blinded, gender-matched, cross-sectional study involving ultrasound assessment. The following entheses were explored bilaterally: proximal plantar fascia, distal Achilles tendon, distal and proximal patellar ligament, distal quadriceps and brachial triceps tendons. The ultrasound score evaluated enthesis thickness, structure, calcifications, erosions, bursae and power Doppler signal. The value of each elemental lesion was calculated using a three-model analysis. Validity was analysed by receiver operating characteristic (ROC) curves. Inter-reader and interexplorer intraclass correlation coefficients (ICCs) were calculated. RESULTS The logistic regression model overestimated the score of three elemental lesions: calcification (0-3), Doppler (0 or 3) and erosion (0 or 3), while scoring tendon structure, tendon thickness and bursa as 0 or 1. ROC curves established an ultrasound score of >or=18 as the best cut-off point for differentiation between cases and controls. This cut-off point was exceeded by 5/29 controls (17%) and by 21/25 patients with SpA (84%). The sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-) were 83.3%, 82.8%, 4.8% and 0.2%, respectively. The inter-reader and interexplorer ICCs were 0.60 and 0.86, respectively. CONCLUSION The findings suggest that the ultrasound enthesis score could be a valid tool in the diagnosis of SpA.

Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide

OBJECTIVE To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. METHODS Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. CONCLUSIONS We present an update on the SER recommendations for the use of biologic therapy in patients with RA.

Candida arthritis in adult patients who are not intravenous drug addicts: Report of three cases and review of the literature

Candida species are an uncommon cause of infectious arthritis, although the frequency has increased during recent years. Three cases of septic arthritis caused by Candida species are reported, and the literature is reviewed. The first patient developed a popliteal cyst infected by Candida albicans after multiple intravenous antibiotic treatments. The second patient had acute myelogenous leukemia and experienced knee arthritis after chemotherapy, and the third suffered oligoarthritis after a second heart transplantation. All patients received treatment with a standard dose of intravenous amphotericin B. Responses were achieved only in the first two cases; the third patient died despite therapy. Thirty-six previously reported Candida arthritis cases are reviewed, and epidemiologic, diagnostic, therapeutic, and prognostic features are analyzed. Cases are divided into two categories: direct inoculation of fungus and hematogenously disseminated disease; these two categories are compared in terms of sex, age, pathogen species, treatment, and survival. Arthritis induced through direct inoculation of fungus is seen in older individuals, is more frequently produced by species other than C albicans (Candida parapsilosis especially), and has a better prognosis than arthritis caused by disseminated candidiasis. Arthritis can be resolved even in the persistence of the systemic disease. It is believed that the first case of Bakers cyst infected by C albicans and the first case of Candida arthritis in a heart transplant patient are reported here.

The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population.

Objective: Methotrexate (MTX) is the first-choice drug for the treatment of rheumatoid arthritis (RA) patients. However, 30% of RA patients discontinue therapy within 1 year, usually because of adverse effects. Previous studies have reported conflicting results on the association of polymorphisms in the MTHFR gene with the toxicity of MTX in RA. The aim of this study was to assess the involvement of the C677T and A1298C polymorphisms in the MTHFR gene in the toxicity of MTX in a Spanish RA population. Methods: The study included retrospectively 468 Spanish RA patients treated with MTX. Single nucleotide polymorphism (SNP) genotyping was performed using the oligonucleotide microarray technique. Allele and genotype association analyses with regard to MTX toxicity and a haplotype association test were also performed. Results: Eighty-four out of the 468 patients (18%) had to discontinue therapy due to adverse effects or MTX toxicity. The C677T polymorphism (rs1801133) was associated with increased MTX toxicity [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.01–1.98, p = 0.0428], and the strongest association was shown in the recessive model (OR 1.95, 95% CI 1.08–3.53, p = 0.0246). The A1298C polymorphism (rs1801131) was not associated with increased MTX toxicity (OR 0.94, 95% CI 0.65–1.38, p = 0.761). A borderline significant risk haplotype was found: 677T-1298A (OR 1.40, 95% CI 1.00–1.96, p = 0.0518). Conclusion: These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population.

Accuracy of physical examination in subacromial impingement syndrome

OBJECTIVE Shoulder pain is a common complaint, frequently caused by subacromial impingement syndrome (SIS). There are a number of physical examination (PE) manoeuvres that explore the subacromial space. MRI provides an accurate anatomic image of the subacromial space, being the current gold standard in the diagnosis of SIS. The aim of this study is to evaluate the accuracy of the PE in the diagnosis of SIS and/or subacromial-subdeltoid bursitis (SSB) confirmed by MRI. METHODS Consecutive outpatients with an episode of shoulder pain were prospectively included in the study. They were examined by a rheumatologist and, within 3 days, an MRI was done. Sensitivity, specificity, positive and negative predictive values, and accuracy of PE manoeuvres were calculated using a 2 x 2 table. RESULTS Fourteen males and 16 females were included. All the tests exhibited acceptable sensitivity. As a result Yocum manoeuvre was considered the most sensitive and most accurate for SIS. With regard to SSB, the Gerber test was the most sensitive. The majority of the PE manoeuvres showed low specificity. CONCLUSIONS Most PE manoeuvres identify reasonably well subacromial impingement of the shoulder, although, in general, they have low specificity. The Yocum test has the best sensitivity and precision. Our data suggest that imaging techniques should be recommended to better define shoulder lesions.

Cardiovascular Events in Systemic Lupus Erythematosus A Nationwide Study in Spain From the RELESSER Registry

Abstract This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2–66.1], and SLE duration of 212.0 months [120.8–289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02–1.04]), hypertension (1.71 [1.20–2.44]), smoking (1.48 [1.06–2.07]), diabetes (2.2 [1.32–3.74]), dyslipidemia (2.18 [1.54–3.09]), neurolupus (2.42 [1.56–3.75]), valvulopathy (2.44 [1.34–4.26]), serositis (1.54 [1.09–2.18]), antiphospholipid antibodies (1.57 [1.13–2.17]), low complement (1.81 [1.12–2.93]), and azathioprine (1.47 [1.04–2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows—for the first time—an association between diabetes and CV events in SLE patients.

Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis

Abstract Objective To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. Methods Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Results We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. Conclusions We present an update on the SER recommendations for the use of biologic therapy in patients with RA.

Anti-integrin immunotherapy in rheumatoid arthritis: protective effect of anti-α4 antibody in adjuvant arthritis

ConclusionsThe current treatment of RA does not provide acceptable control of the inflammatory process due to either the onset of adverse effects or the lack of efficacy. RA is a T-cell mediated process, in which activated T cells must migrate through the blood vessels to reach the synovium. Anti-adhesion therapies designed to block the interaction of T cells with activated endothelial cells could be of great interest to control the disease. Flow cytometry analysis, immunohistochemical and functional studies cell adhesion in vitro have shown that the interaction between VLA-4 on T cells and VCAM-1 on endothelial cells could play a relevant role in the onset and perpetuation of RA. Here we show that the treatment with HP2/1, an mAb directed against α4 subunit of VLA-4, prevents adjuvant arthritis in Lewis rats. Data suggest that treatment with anti-α4 antibodies could be of value in RA.

Role of the new azoles in the treatmentof fungal osteoarticular infections

OBJECTIVES To analyze the usefulness of the new azoles for the treatment of fungal osteoarticular infections, and to report three cases of fungal knee arthritis treated with fluconazole in our unit. METHODS The medical literature was reviewed for all cases of osteoarticular infection caused by fungi and treated with fluconazole or itraconazole registered in the MedLine Silver Platter database from 1972 to 1997. RESULTS The total number of patients included in this review was 56; 19 were treated with fluconazole and 37 with itraconazole. The most frequent causative agents implicated were fungi of the genuses Candida and Aspergillus. There were eight therapeutic failures, and there were no statistically different findings among the patients in terms of their health status. Adverse effects were unusual. CONCLUSIONS Controlled studies are necessary to establish the true role of the new azole drugs in the treatment of fungal osteoarticular infections, but they seem to be a promising therapeutic option.

Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms

OBJECTIVE To develop a model to predict RA outcome based on biochemical variables and single nucleotide polymorphisms (SNPs). METHODS We collected baseline data from RA patients. SNP genotyping was performed using an oligonucleotide microarray. Remission and severe disability were investigated as outcomes of the study. Logistic regression models and receiver operating characteristic (ROC) curves were used to determine sensitivity (S), specificity (Sp) and likelihood ratio (LR). RESULTS Six hundred and thirty-two patients (375 in the study and 257 in the validation) were included. Twenty-two out of 152, and 19 out of 208 patients had an HAQ > 2. The model obtained to predict disability included levels of the anti-cyclic citrullinated peptide (anti-CCP) antibodies, ESR and SNP rs2070874 in the IL-4 gene. Homozygous and heterozygous carriers of the IL-4 33T allele had a decreased risk of severe disability. The discriminative power had an area under the curve (AUC) of 0.792 (95% CI 0.694, 0.889), with S 41%, Sp 95% and LR +7.6. Twenty-one out of 268 and 17 out of 211 patients were in remission in the study and validation cohorts, respectively. The model included absence of anti-CCP antibodies and the SNP rs2476601 on the PTPN22 gene. Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission. The discriminative power had an AUC of 0.842 (95% CI 0.756, 0.928), with S 76%, Sp 86% and LR + 5.4. Predictive ability was confirmed on the validation cohort. CONCLUSIONS We have developed two models based on laboratory variables that are associated with relevant outcomes for RA patients at disease onset.