Delia Reina

Diagnosis of tuberculosis infection by tuberculin skin test and a whole-blood interferon-γ release assay in patients considered for anti–tumor necrosis factor-α therapy

To assess the performance of QuantiFERON®-TB Gold in-Tube (QFT-GIT; Cellestis, Carnegie, Australia) and tuberculin skin test (TST) in patients with immune-mediated inflammatory diseases (IMID), before anti-tumor necrosis factor-α (TNF-α) therapy, and to compare the results with those from the healthy population. Three hundred fourteen subjects (214 with IMID and 100 controls) underwent simultaneous QFT-GIT and TST. QFT-GIT was positive in 21% of IMID patients and in 16% of controls (P = 0.29). Among IMID patients, 21% tested positive by QFT-GIT and 24%, by TST (P = 0.30). Positive QFT-GIT results were not affected by immunosuppressive therapy (odds ratio, 0.78; 95% confidence interval [CI], 0.36-1.68; P = 0.52). Agreement between both tests in those patients who tested positive by one of the tests was 50% (95% CI, 37.2-62.8). QFT-GIT is useful for identifying IMID patients requiring treatment of latent tuberculosis before anti-TNF therapy. However, given the poor agreement between TST and QFT-GIT, we advocate a strategy of simultaneous testing to optimize diagnostic sensitivity.

IL-6 blockade reverses the abnormal STAT activation of peripheral blood leukocytes from rheumatoid arthritis patients.

Considering the interplay of multiple STATs in response to cytokines, we investigated how IL-6 and its blocking affect STAT signaling in rheumatoid arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab treatment and healthy donors (HDs) were cytokine-stimulated and STAT phosphorylation was analyzed by cytometry. RA patients had significantly fewer pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After 24weeks of treatment, percentages of IFNγ-induced pSTAT1+ and IL-10-induced pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs. pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and levels of pSTAT+ cells at baseline were higher in patients with good EULAR response to tocilizumab. IFNγ-induced pSTAT1+ cells correlated inversely with memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status.

The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab

BACKGROUNDnIL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses.nnnMETHODSnHeparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients.nnnRESULTSnThree statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups.nnnCONCLUSIONSnRA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.

Kala-azar en un paciente con artritis reumatoide tratada con metotrexato

Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome.

Ecografía en el diagnóstico y manejo de los xantomas tendinosos en la hipercolesterolemia familiar

Hyperlipidaemia can present accompanied by tendon xanthomatosis. Xanthomas are clusters of collagen and cholesterolfilled macrophages. The Achilles tendon, extensor tendons of the hand, and the elbow tendons are principally affected. Joint ultrasound can be a very useful tool for diagnosing and monitoring the course of tendon xanthomas. Clinicians usually request screening for xanthoma in patients with suspected family hypercholesteraemia (FH), since the presence of xanthomas forms part of the diagnostic criteria of the disease.

Ecografía en el diagnóstico de metástasis cutánea de adenocarcinoma de próstata

The patient was a 53-year-old man with no significant medical history. He presented with a painless mass in anterior forearm, reporting no previous injury. Physical examination confirmed the presence of a hard, immobile mass measuring less than 1 cm. He came to the rheumatologic examination room, where he underwent soft tissue ultrasound (Toshiba Aplio®300). A round mass measuring less than 1 cm was observed. It was iso/hypoechoic on gray scale images, was moderately well-defined, and was joined to a vessel that fed it (Fig. 1). On color Doppler, there was high echo intensity throughout the entire lesion, more intense on the periphery (Figs. 2 and 3). As there were findings that raised suspicion, such as heterogeneity, the marked vascularity and the marked Doppler signal (grade 3), magnetic resonance imaging was performed. This study revealed a round, well-defined form measuring 1 cm, with hyperintensity on T1-weighted images, which pointed to a metastatic lesion (Fig. 4).

FRI0634-HPR Non Attending Rheumatology Nursing Consultations, High Resolution of Urgent Demand

Background Patients with rheumatic diseases may require routine control and strict monitoring of their disease and side effects of treatment [1]. The possibility of providing nursing consultations for rheumatology patients via telephone or email rather than at clinic attendance [2], can potentially result in a lower rate of clinic visits, better informed and supported patients and families, more appropriate use of healthcare resources and real cost saving [3-5]. Objectives To describe the content of the non-face consultations with rheumatology nursing. Methods Descriptive study of a cohort of patients treated in the outpatient Rheumatology department at our Hospital. The period analysed was from January 2013 to December 2014. An Access database, specifically developed for this purpose, was used for data collection. The variables studied were age, sex, diagnosis, reason for query (doubts about their illness, medication, blood testing, other tests and/or administrative aspects) and query resolution. Nurses responded as soon as possible by telephone or via email between 8-15hrs Monday–Friday. SPSS v18 was used to analyse the data. Results A total of 377 consultations were received, made by 217 patients, 74% of whom were women, diagnosed with Rheumatoid Arthritis (42%), Spondyloarthropathies (21%), Osteoporosis (15%), Systemic Lupus Erythematosus (2%), Osteoarthritis (2%) and other (18%); with a mean age of 57±14 years. Of these 217 patients, 84 of them consulted on more than one occasion. Of the 377 consultations, 361 consultations were made via telephone, 14 via email and 2 via text message. The reasons for the consultation can be divided into 5 categories (see Image 1). Of the 377 consultations, there were 399 reasons for consultation. 371 out of 377 consultations were resolved by the nurse, (131 without no help). In 240, the medical and/or other professional collaboration was necessary. Image 1. Reasons for consultation (n=399). Conclusions The majority of queries were related to disease (flare up) or to medication. “Non attending” skilled nursing consultation, is shown to be an excellent alternative to face to face consultations, in the management of low complexity processes. It demonstrates a high degree of resolution that does not require an attending visit, thereby decreasing the rate of repeated visits to a rheumatologist. It also provides higher confidence, information and loyalty to patients and because of the overall reduction of patients at clinic visits, enables patients to access specialists when face to face consultations with a nurse or physician is needed. Few patients used email option for consultation and the possibility of promoting this alternative is considered. References Valencian Rheumatology Nursing Society (GESVR), 2013. Najera C, et al. 2014. Hughes RA et al. 2002. Royal College of Nursing, 2006. Ferreira R et al. 2014. Acknowledgements Claire Hale Disclosure of Interest None declared

Eficacia y seguridad de los glucocorticoides en la artritis reumatoide: revisión sistemática de la literatura

OBJECTIVESn1) To systematically and critically review the evidence on the characteristics, efficacy and safety of glucocorticoids (CS) in rheumatoid arthritis (RA); 2) to generate practical recommendations.nnnMETHODSnA systematic literature review was performed through a sensitive bibliographic search strategy in Medline, Embase and the Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of CS in patients with RA. Two reviewers performed the first selection by title and abstract. Then 10 reviewers selected the studies after a detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. In a nominal group meeting, based on the results of the systematic literature review, related recommendations were reached by consensus.nnnRESULTSnA total of 47 articles were finally included. CS in combination with disease-modifying antirheumatic drugs help control disease activity and inhibit radiographic progression, especially in the short-to-medium term and in early RA. CS can also improve function and relieve pain. Different types and routes of administration are effective, but there is no standardized scheme (initial dose, tapering and duration of treatment) that is superior to others. Adverse events when using CS are very frequent and are dose-dependent and variable severity, although most are mild. Seven recommendations were generated on the use and risk management of CS.nnnCONCLUSIONSnThese recommendations aim to resolve some common clinical questions and aid in decision-making for CS use in RA.

AB0424 Il-6 receptor blockade induced a different immune response in rheumatoid arthritis patients with and without remission

Background Tocilizumab (TCZ) is a humanised antibody that blocks IL-6 receptor. Despite its effectiveness in rheumatoid arthritis (RA), there are patients that do not respond to the IL-6R blockade. The immune characteristics that would explain this lack of response are not known. Objectives Our aim was to determine the tocilizumab-induced changes in CD4 +T cells of patients that achieve, or not, remission at 12u2009m. Methods Prospective, multicenter study in 47 RA patients treated with TCZ during one year following standard clinical practice. Demographic, disease and treatment characteristics were collected at each visit. Ultrasound (US) grey scale and power doppler were assessed for joints and tendons using a semiquantitative scale from 0–3 points. Phenotyping of T lymphocytes was determined by flow cytometry and the plasma cytokine concentration was quantified by ELISA. Results Forty seven patients were treated with a mean age of 54±11u2009y and 85% were women. Years of disease were 13±8. We segregated patients according to the DAS28-remission. 44% achieved remission at month 12. We observed that absolute counts of neutrophils and CD4 +T lymphocytes decreased significantly in the remission group but not in the other one. Both memory and naïve CD4 +T cells decreased in the remission group. The analysis of T cells classified according to chemokine receptors showed that memory (29.1±4.0u2009vs 22.7±2.7 × 104u2009cells/mL; p=0.06) and naïve (22.6±4.1u2009vs 17.2±2.8; p=0.04) CD4 +with CXCR3 +and with CCR4 +wereu2009the subsets that decreased significantly in the remission group but not in the non-remission group. Since the expression of chemokine receptors defines the different Th subpopulations, we analysed them in the two groups of patients. Th1 tended to decreased in the remission group (3.5±0.7u2009vs 2.5±0.4; p=0.06) and Th9 decreased significantly in both groups (R: 5.0±0.8u2009vs 2.5±0.3; p=0.006u2009and Non R 5.5±0.8u2009vs 3.1±0.4; p=0.001). In regard to the cytokines produced by CD4 +T lymphocytes, IL-17 (2.1±1.1u2009vs 1.2±0.5u2009ng/ml; p=0.04) and VEGF (0.5±0.2u2009vs 0.3±0.1u2009ng/ml; p=0.05) but not IL-6 and IL-22 changed significantly in the remission group. Interestingly, IL-17 and VEGF correlated with US findings before the initiation of the treatment (grey scale R=0.378, p=0.01u2009and R=0.322, p=0.03; power Doppler R=0.415, p=0.004u2009and R=0.320, p=0.03u2009respectively). Conclusions Tocilizumab induced changes in specific subsets of CD4 +T cells and their inflammatory associated cytokines in the remission group. Disclosure of Interest None declared

AB0301 Characteristics of rheumatoid arthritis patients with adverse effects after the initiation of tocilizumab therapy

Background Tocilizumab is a humanized monoclonal antibody that blocks IL-6 mediated pro-inflammatory signalling in rheumatoid arthritis patients. The safety profile of tocilizumab has been extensively evaluated in clinical trials. However, there is little data on markers at the initiation of tocilizumab therapy that may predict the development of adverse effects requiring drug withdrawal. Objectives To identify markers that predict the development of secondary effects that required drug withdrawal the 6 first months after initiating tocilizumab therapy. Methods Forty-six rheumatoid arthritis patients treated with tocilizumab in routine clinical practice were retrospectively evaluated 24 weeks after initiating therapy. Demographic and clinical data, complete blood cell counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), titers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies, serum cytokines (IL-6, IL-15 and IL-17) and the frequency of activated CD4+, CD8+ and Treg cells were collected before tocilizumab administration (baseline). Characteristics of patients with and without adverse effects were compared. Results Twelve (26.1%) patients developed adverse effects that required drug withdrawal during the first six months of tocilizumab therapy. Seven patients suffered an allergic or infusional reaction and two patients had neutropenia. All recovered after drug withdrawal. Two further patients suffered an infection requiring hospitalization (salpingitis and periappendiceal abscess) and one patient had a myocardial infarction. Patients with and without adverse effects had comparable ages and disease evolution. Patients with adverse effects had lower neutrophil counts (4.1±2.6 vs 5.6±1.8, p<0.05) and lower DAS28-CRP (5.1±1.2 vs 4.3±1.2, p<0.05) at baseline than those without. No significant differences in IgG, IgM and IgA were observed between the two groups. However, fewer patients with higher CRP, titers of anti-CCP antibodies, or serum concentrations of IL-6 and IL-15 were observed in the group with adverse effects (Table 1). There were no differences in the frequency of T cell subsets and Tregs between patients with and without adverse effects before the treatment. Conclusions Patients with adverse effects presented fewer prognostic markers of severe disease. Higher levels of some markers (CRP, anti-CCP antibodies, IL-6, IL-15 and neutrophil counts) may identify patients less likely to suffer adverse effects due to tocilizumab therapy. Disclosure of Interest None Declared