Utility of applying a diagnostic algorithm in giant cell arteritis based on the level of clinical suspicion. / Utilidad de la aplicación de un algoritmo diagnóstico en la arteritis de células gigantes en función del grado de sospecha clínica.

INTRODUCTION: To reach the diagnosis of giant cell arteritis (GCA), signs, symptoms, laboratory tests, imaging findings, and occasionally anatomopathological results from temporal artery biopsy are evaluated. This study describes the results of an algorithm analysis based on clinical and ultrasound evaluation of patients with suspected GCA, highlighting its diagnostic utility by contrasting its use in different clinical suspicion scenarios. METHOD: Prospective multicenter study evaluating patients referred with suspected GCA through a preferential circuit (fast track), grouping them according to low or high clinical suspicion of GCA. Each of these scenarios is evaluated by biopsy and ultrasound for all patients, resulting in positive, indeterminate, or negative outcomes, yielding six possible groups. Potential areas of improvement are explored, emphasizing that, following a negative or indeterminate ultrasound, 18-FDG-PET-CT could be recommended. We analyze the results and application of a diagnostic algorithm, confirming its efficiency and applicability based on whether there is high or low clinical suspicion. RESULTS: Sixty-nine patients (41 in the high suspicion group and 28 in the low suspicion group). There were 41 new diagnoses of GCA: 35 in the high suspicion group and 6 in the low suspicion group. Using ultrasound alone, the initial algorithm has an overall diagnostic efficiency of 72.5%, which improves to 80.5% when including 18F-FDG-PET/CT. The negative predictive value of ultrasound in patients with low clinical suspicion is 84.6%, and the positive predictive value of ultrasound in patients with high suspicion is 100%, improving sensitivity from 57.1% to 80.8% with 18F-FDG-PET/CT in this scenario. Temporal artery biopsy was performed on all patients, with no differences in sensitivity or specificity compared to ultrasound. In cases where all three tests - ultrasound, biopsy, and 18F-FDG-PET/CT - are performed, sensitivity increases to 92.3% in patients with high clinical suspicion. CONCLUSION: In situations of high clinical suspicion, the algorithm provides sufficient information for the diagnosis of GCA if ultrasound is positive. A negative ultrasound is sufficient to rule out the diagnosis in the context of low clinical suspicion. 18-FDG-PET-CT may be useful in patients with high suspicion and negative or indeterminate ultrasound results.

Efficacy of secukinumab on dactylitis in patients with active psoriatic arthritis from the FUTURE 5 study.

OBJECTIVES: Dactylitis is an important clinical domain of psoriatic arthritis (PsA) associated with significant burden of disease and impaired function. Post-hoc analysis of the FUTURE 5 study was performed to evaluate the efficacy of secukinumab in patients with dactylitis at baseline over 2 years. METHODS: Randomised patients received secukinumab 300mg with loading dose (LD)/150mg LD/150mg without loading dose/placebo. Assessment of dactylitis was based on Leeds Dactylitis Index. Exploratory analyses included resolution of dactylitis based on severity, time to first resolution of dactylitis (Kaplan-Meier estimate) and resolution of dactylitis (heatmap analysis). Clinical efficacy outcomes, composite domains of disease activity, health-related quality of life (HRQoL) and radiographic progression using van der Heijde-modified total Sharp score were assessed in patients with/without dactylitis at baseline. RESULTS: Overall, 389/996 (39%) patients presented with dactylitis at baseline, had more active clinical disease and greater disease activity than those without dactylitis at baseline. Resolution of dactylitis was observed across all treatment groups at Week 104. Improvement in joints, enthesitis, skin psoriasis, nail outcomes, physical function and HRQoL were sustained over 2 years in patients with dactylitis at baseline. With secukinumab treatment, >80% of patients did not show structural radiographic progression. The proportion of non-structural radiographic progressors were comparable across patients with/without dactylitis at baseline with secukinumab treatment over 2 years. CONCLUSIONS: Patients with dactylitis at baseline were associated with higher burden of disease. Secukinumab provided sustained improvements across all clinical outcomes, QoL and inhibition of radiographic progression in PsA patients with dactylitis at baseline over 2 years.

Altered CD39 and CD73 Expression in Rheumatoid Arthritis: Implications for Disease Activity and Treatment Response.

In rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8+CD39-CD73+ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39+CD73+ and CD39-CD73- cells. Good responders tended to have lower B CD39+CD73+ cell percentages at baseline and 3 months. Additionally, Treg, CD8+ T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4+ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4+ and CD8+ T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA.

Increase of Circulating Monocyte-Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage.

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte−PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte−PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.

Quality standard for the management of patients with psoriatic arthritis: QUANTUM Project. / Norma de calidad para el manejo del paciente con artritis psoriásica: proyecto QUANTUM.

OBJECTIVE: To generate a quality standard for the management of patients with psoriatic arthritis (PsA). METHODS: We employed qualitative methodology that included: 1) Two focus groups (one with patients with PsA and another with non-rheumatologist specialists involved in the care of PsA patients); 2) A narrative literature review of published documents related to the quality of care in PsA; 3) A nominal group meeting in which 15 expert rheumatologists generated and reached a consensus on a series of quality criteria, as well as formulas or quantifiable objective measures to evaluate them; 4) The Delphi method to establish the feasibility, priority and agreement with the quality criteria; 5) A final generation of standards of care and their attributes. A descriptive analysis of the results was carried out. RESULTS: A total of 59 standards of care was generated, 18 of mandatory compliance, grouped into 4 blocks according to specific objectives: 1) early diagnosis (n=6); 2) optimizing the management of the disease (n=26); 3) multidisciplinary collaboration (n=9); 4) monitoring improvement (n=18). To assess compliance with these standards of care, in many cases, the medical records will be reviewed. Other sources will be the records of the service and hospital and bibliographic databases. Regarding the level of compliance, for some of the standards of care this is yes/no; for others, compliance ranges from 50% to 100% and, in this range, in many cases, compliance was 80%. CONCLUSIONS: This set of standards of care should help improve quality of care in PsA patients.

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

BACKGROUND: IL-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. METHODS: Heparinized 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. RESULTS: Three 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. CONCLUSIONS: RA 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.

PASE and EARP questionnaires for the identification of enthesitis, synovitis, and tenosynovitis in patients with psoriasis.

The aim of this study was to assess the diagnostic value of the Psoriatic Arthritis Screening Evaluation (PASE) and Early Psoriatic Arthritis Screening Questionnaire (EARP) questionnaires in the ultrasonographic detection of enthesitis, synovitis, and tenosynovitis. A cross-sectional study was done in a total of 96 consecutive patients. Double blind clinical examination and echographic assessment were performed. A receiver-operating characteristic (ROC) model analysis for the questionnaires was established using echographic findings as reference variable. The optimal diagnostic point was determined following a Youden analysis model from the obtained data, calculating sensitivity and specificity along with predictive values, likelihood ratio, and diagnostic odds ratio. A logistic regression analysis was used to determine possible predictor variables of enthesitis, synovitis, and tenosynovitis. When enthesitis, synovitis, and tenosynovitis were considered as one outcome for the diagnostic study of the PASE or EARP questionnaire, there were no statistically significant differences among the score of the study groups and the rest of patients. The PASE and EARP tests had a diagnostic performance for enthesitis, synovitis, and tenosynovitis that followed the expected pattern when the prevalence of findings is low. In these cases, the tests increase their negative predictive value, being particularly interesting in ruling out the disease.

[Preference for etanercept pen versus syringe in patients with chronic arthritis. Nurse education workshop]. / Preferencia de pluma de etanercept respecto a jeringa en pacientes con artritis crónica. Taller educativo por enfermería.

OBJECTIVES: The aims of this study are to evaluate the level of fear of post-injection pain prior to the administration, the difficulty in handling the device, and the level of satisfaction of patients using a pre-filled syringe versus an etanercept pen, as well as to evaluate the usefulness of the training given by nursing staff prior to starting with the pen, and the preferences of patients after using both devices. METHOD: A prospective study was designed to follow-up a cohort of patients during a 6 months period. The data was collected using questionnaires and analyzed with SPSS 18.00. Rank and McNemar tests were performed. Statistical significance was pre-set at an α level of 0.05. RESULTS: A total of 29 patients were included, of whom 69% female, and with a mean age 52.5±10.9 years. Of these, 48% had rheumatoid arthritis, 28% psoriatic arthritis, 21% ankylosing spondylitis, and 3% undifferentiated spondyloarthropathy. There were no statistically significant differences either with the fear or pain or handling of the device between the syringe and the pen (P=.469; P=.812; P=.169 respectively). At 6 months, 59% of patients referred to being satisfied or very satisfied with the pen. Almost all (93%) found useful or very useful the training given by nursing staff prior to using the pen, and 55% preferred the pen over the pre-filled syringe. CONCLUSIONS: The etanercept pen is another subcutaneous device option for patients with chronic arthritis. According to the present study, nursing educational workshops before starting this therapy are recommended.

Sweet syndrome associated with myelodysplastic syndrome: report of a case. Review of the literature.

Sweet's syndrome or acute neutrophilic febrile dermatosis is a systemic disease of unknown etiology characterized by the appearance of skin lesions produced by a neutrophilic dermal infiltrate, fever and peripheral leukocytosis. It may be associated with hematologic diseases, including leukemia, with immune diseases as rheumatoid arthritis, or can occur in isolation. The myelodysplasias are hematological disorders characterized by one or more cytopenias secondary to bone marrow dysfunction. We present the case of a patient with Sweet's syndrome associated with myelodysplastic syndrome and treated with glucocorticoids who did not present a good clinical outcome. We discuss the different treatment of these diseases because in most cases glucocorticoids, which are the treatment of choice in Sweet's syndrome, may be insufficient.

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.

Usefulness of magnetic resonance imaging of the hand versus anticyclic citrullinated peptide antibody testing to confirm the diagnosis of clinically suspected early rheumatoid arthritis in the absence of rheumatoid factor and radiographic erosions.

OBJECTIVE: The diagnosis of rheumatoid arthritis (RA) is sometimes difficult to establish early in the disease process, particularly in the absence of its classic hallmarks. Our aim was to compare the practical usefulness of magnetic resonance imaging (MRI) of the hand versus anticyclic citrullinated peptide (anti-CCP) antibody testing to confirm the diagnosis of clinically suspected RA in the absence of rheumatoid factor (RF) and radiographic erosions. METHODS: We prospectively included patients with early inflammatory arthritis and strong clinical suspicion of RA, in whom initial complementary tests (RF and radiographs of hands, wrists, and feet) did not provide unequivocal confirmation of the diagnosis. In all patients, anti-CCP antibodies were assessed and contrast-enhanced MRI of the most affected hand was performed according to a specifically designed protocol. The MRI criterion for the diagnosis of RA was either the presence of synovitis with bone erosions or bone marrow edema, which is currently considered to be a forerunner of erosions. RESULTS: In the 40 patients (28 women), the mean age at diagnosis was 54 +/- 6 years and the median duration of symptoms was 4 +/- 2.6 months (range 1.5 to 12). Final diagnoses at 1-year follow-up were RA in 31 patients, undifferentiated arthritis in 7 (5 self-limiting), and psoriatic arthropathy (PsA) and antisynthetase syndrome in 1 patient each. Anti-CCP antibodies were positive only in 7 patients, all of whom were finally diagnosed with RA. The prevalence of anti-CCP positivity in our series of seronegative RA patients was thus 23% (7/31); in these patients the anti-CCP antibodies had a specificity of 100% (95% CI: 71.7 to 100) and sensitivity of 23% (95% CI: 9.6 to 41.1). Use of the MRI criterion led to the correct diagnosis in 100% of patients with RA and to false-positive results (1 with PsA and 1 with antisynthetase syndrome). The MRI criterion had a specificity of 78% (95% CI: 40.0 to 97.2) and sensitivity of 100% (95% CI: 90.8 to 100) for identification of seronegative RA. CONCLUSION: Although the tests are not mutually exclusive, in our experience MRI is more helpful than anti-CCP antibody determination in confirming the diagnosis of clinically suspected early RA in patients in whom the diagnosis cannot be confirmed using conventional methods.