Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Muscle involvement in systemic lupus erythematosus: multimodal ultrasound assessment and relationship with physical performance.

OBJECTIVES: The objectives of this study were (1) to explore US findings for muscle mass, muscle quality and muscle stiffness in SLE patients and healthy subjects; (2) to investigate the relationship between the US muscle findings and physical performance in SLE patients and healthy subjects. METHODS: Quadriceps muscle thickness was used for assessment of muscle mass, muscle echogenicity (using a visual semi-quantitative scale and grayscale analysis with histograms) for assessment of muscle quality, and point shear-wave elastography (SWE) for assessment of muscle stiffness in 30 SLE patients (without previous/current myositis or neuromuscular disorders) and 15 age-, sex- and BMI-matched healthy subjects. Hand grip strength tests and short physical performance battery (SPPB) tests were carried out in the same populations. RESULTS: No difference was observed between SLE patients and healthy subjects for quadriceps muscle thickness (35.2 mm ±s.d. 6.8 vs 34.8 mm ± s.d. 6.0, respectively, P = 0.79). Conversely, muscle echogenicity was significantly increased in SLE patients (visual semi-quantitative scale: 1.7 ± s.d. 1.0 vs 0.3 ± s.d. 0.5, respectively, P < 0.01; grayscale analysis with histograms: 87.4 mean pixels ± s.d. 18.8 vs 70.1 mean pixels ± s.d. 14.0, respectively, P < 0.01). Similarly, SWE was significantly lower in SLE patients compared with healthy subjects {1.5 m/s [interquartile range (IQR) 0.3] vs 1.6 m/s (IQR 0.2), respectively, P = 0.01}. Muscle echogenicity was inversely correlated with grip strength (visual semi-quantitative scale, Rho: -0.47, P = 0.01; grayscale analysis with histograms, Rho: -0.41, p < 0.01) and SPPB (visual semi-quantitative scale, Rho: -0.50, P < 0.01; grayscale analysis with histograms Rho: -0,46, P < 0.01). CONCLUSIONS: US assessment of muscle echogenicity and stiffness is useful for the early detection of muscle involvement in SLE patients.

Ultrasound and magnetic resonance imaging as diagnostic tools for sarcopenia in immune-mediated rheumatic diseases (IMRDs).

Sarcopenia is characterized by loss of muscle mass, altered muscle composition, fat and fibrous tissue infiltration, and abnormal innervation, especially in older individuals with immune-mediated rheumatic diseases (IMRDs). Several techniques for measuring muscle mass, strength, and performance have emerged in recent decades. The portable dynamometer and gait speed represent the most frequently used tools for the evaluation of muscle strength and physical efficiency, respectively. Aside from dual-energy, X-ray, absorptiometry, and bioelectrical impedance analysis, ultrasound (US) and magnetic resonance imaging (MRI) techniques appear to have a potential role in evaluating muscle mass and composition. US and MRI have been shown to accurately identify sarcopenic biomarkers such as inflammation (edema), fatty infiltration (myosteatosis), alterations in muscle fibers, and muscular atrophy in patients with IMRDs. US is a low-cost, easy-to-use, and safe imaging method for assessing muscle mass, quality, architecture, and biomechanical function. This review summarizes the evidence for using US and MRI to assess sarcopenia.

Demographic and clinical characteristics of patients with ANCA-positive vasculitis in a Colombian University Hospital over a 12-year period: 2005-2017.

Vasculitides associated with anti-neutrophil cytoplasmic antibodies are heterogeneous, systemic, low prevalence and high morbidity and mortality entities. They include granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. In Latin America, there are few descriptive registries of these patients. The objective of the study was to describe the demographic and clinical characteristics and in-hospital morbidity and mortality of patients with vasculitis associated with anti-neutrophil cytoplasmic antibodies in a university hospital in Colombia. This was a cross-sectional descriptive study. We performed computer searches with terms related to patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, between 2005 and 2017 who met the American College of Rheumatology classification criteria for vasculitis associated with anti-neutrophil cytoplasmic antibodies, and their clinical and laboratory characteristics. One hundred and six patients with anti-neutrophil cytoplasmic antibody-associated vasculitis were included in the study. The average age was 55 years, and 57.5% were women. In 68.8% of the cases, the diagnosis was made during hospitalization, with an average hospital stay of 16.6 days (± 12.22). The distribution by type of vasculitis was: granulomatosis with polyangiitis 52%, microscopic polyangiitis 45.2% and eosinophilic granulomatosis with polyangiitis 1.8%. Alveolar hemorrhage occurred in 35% of patients; 20.7% had variable renal involvement, of which 53.8% progressed to advanced kidney disease. Treatment included glucocorticoids 91.5%, cyclophosphamide 62.2%, plasmapheresis 14.1%, and 41.5% required renal replacement therapy. In-hospital mortality was 16.5%, Sepsis was the most common cause of death. We present clinical information on a group of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis; renal involvement was the the most common type of affectation. Both the clinical and serological characteristics of our registry were similar to those described in other Latin American and European cohorts, and a lower in-hospital mortality rate was evidenced.

Prioritising referrals of individuals at-risk of RA: guidance based on results of a 10-year national primary care observational study.

BACKGROUND: Musculoskeletal (MSK) symptoms are among the commonest reasons for primary care assessments; however, few individuals will be diagnosed with an inflammatory arthritis (IA) within the following year. The purpose of this study was to investigate, in individuals with new MSK symptoms, the association between patient factors and risk of progression to IA, in order to optimise primary care referrals to rheumatology. METHODS: Individuals ≥16 years old with new non-specific MSK symptoms and no clinical synovitis were recruited by primary care across the UK from July 2007 until May 2019. Those testing positive for the anti-CCP2 assay (anti-CCP+) were invited to Leeds for follow-up. Subjects with a negative result (anti-CCP-) were sent a 1-year questionnaire, and general practitioners were contacted to confirm whether the individual had been diagnosed with an IA by a rheumatologist. Predictors for progression were assessed using multivariable regression analysis. RESULTS: Six thousand seven hundred eighty individuals were recruited: 3% were anti-CCP+, of whom 45% progressed to IA, predominantly rheumatoid arthritis. Anti-CCP+ participants with high antibody levels had an odds ratio (OR) for progression to IA of 9.42 [P < 0.001, 95% CI (3.13-28.30)], hand pain, OR 2.74 [P = 0.043, 95% CI (1.03-7.27)] and foot pain, OR 4.10 [P = 0.003, 95% CI (1.59-10.54)]. In low-level anti-CCP+ individuals, absence of pain in hands or feet had a negative predictive value of 96% for progression to IA. One-year follow-up data were available for 5640 anti-CCP- individuals, of whom 53 were diagnosed with IA (0.93%). Pain in hands, OR 2.51 [P = 0.018, 95% CI (1.17-5.39)] or knees, OR 3.03 [P = 0.003, 95% CI (1.47-6.25)] were associated with development of IA within 12 months. CONCLUSIONS: This is the largest prospective primary care study of individuals at risk of IA, and the first one to prospectively investigate the outcome of MSK symptoms in a large anti-CCP- cohort. High anti-CCP levels and pain in hands/feet indicated an increased likelihood of progression to IA. In patients with low anti-CCP level and no pain in the hands/feet, progression is unlikely. In anti-CCP- patients, those with hand or knee pain were at increased risk of progression. This study demonstrates that routinely available tests and joint symptoms provide useful discrimination that may be used to prioritise referrals to rheumatology and avoid a delayed diagnosis. TRIAL REGISTRATION: NCT, NCT02012764 . Registered 25 January 2007.

Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study.

Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0-3) and a continuous quantitative measurement ("VAS echogenicity," 0-100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall's Tau and Pearson's Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57-0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68-0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. "VAS echogenicity" showed a high reliability both in the inter-observer [ICC = 0.80 (0.75-0.85)] and intra-observer [ICC = 0.88 (0.88-0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and "VAS echogenicity" [ICC = 0.52 (0.50-0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.

Lessons for rituximab therapy in patients with rheumatoid arthritis.

B-cell depletion therapy is an effective option for the treatment of rheumatoid arthritis but often does not result in complete B-cell depletion. Complete B-cell depletion after rituximab treatment is associated with clinical response, and this outcome leads to long-term maintenance of therapy. Low pretreatment plasmablast counts, concomitant treatment with disease-modifying antirheumatic drugs, no smoking exposure, the presence of anticitrullinated protein antibodies or rheumatoid factor, and a low interferon signature are all predictive of complete B-cell depletion and clinical response. Half of patients who initially show complete B-cell depletion and clinical response after rituximab treatment eventually lose responsiveness with further infusions. However three-quarters of these patients regain this outcome in their following treatment cycle, suggesting that loss of response is reversible and that patients can still benefit from rituximab retreatment. The efficacy of reduced doses of rituximab is being investigated, but preliminary results suggest that these strategies are best used for maintenance therapy, particularly in patients who suffer adverse events or who are at a high risk of infection. Infusion-related reactions are the most common adverse events associated with rituximab treatment, and monitoring of IgG concentrations is crucial, as low concentrations are correlated with an increased risk of infection.

Association of ERAP2 polymorphisms in Colombian HLA-B27+ or HLA-B15+ patients with SpA and its relationship with clinical presentation: axial or peripheral predominance.

OBJECTIVE: To determine the association between endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 single-nucleotide polymorphisms (SNPs) and human leukocyte antigens (HLA)-B27+ or HLA-B15+ patients with spondyloarthritis (SpA). METHODS: 104 patients with SpA according to Assessment of Spondyloarthritis International Society criteria were included in the study. HLA typing was performed by PCR. The polymorphisms were determined by real-time PCR on genomic DNA using customised probes for SNPs rs27044, rs17482078, rs10050860 and rs30187 in ERAP1, and rs2910686, rs2248374 and rs2549782 in ERAP2. RESULTS: 70 of the104 patients with SpA were HLA-B27+ and 34 were HLA-B15+. The distribution of ERAP1 and ERAP2 SNPs between the HLA-B15+ and HLA-B27+ patients with SpA did not reveal differences. Likewise, no differences in the frequencies of ERAP1 SNP haplotypes and alleles HLA-B15 or HLA-B27 were found. Interestingly, however, the frequencies of three particular haplotypes formed by ERAP2 SNPs rs2549782/rs2248374/rs2910686 varied between HLA-B15+ and HLA-B27+ patients: the ERAP2 SNPs haplotype TGT was more common in HLA-B15+ patients with SpA (OR 2.943, 95% CI 1.264 to 6.585; P=0.009), whereas the ERAP2 SNP haplotypes TGC and CAT were more associated with HLA-B27+ patients with SpA: (OR 4.483, 95% CI 1.524 to 13.187; p=0.003) and (OR 9.014, 95% CI 1.181 to 68.807; p=0.009), respectively. CONCLUSION: An association was found between HLA-B15+ patients with SpA and haplotype TGT of ERAP2 SNPs. On the other hand, HLA-B27+ patients with SpA were associated with ERAP2 haplotypes TGC and CAT. These associations could be related to the clinical presentation of the disease, specifically with a peripheral or axial predominance, respectively.

Pharmacogenetic aspects of methotrexate in a cohort of Colombian patients with rheumatoid arthritis.

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). However, over time, ~40% of patients may experience therapeutic failure or drug toxicity. The genetic variability of the enzymes involved in the MTX metabolic pathway seem to serve an important role in the eventual therapeutic failure or drug toxicity. Depending on the enzymes affected, the toxicity or the therapeutic response may change. The present study reports some of the polymorphisms identified in enzymes in the MTX metabolic pathway that are present in a group of Colombian patients with RA, and assesses the associations of these polymorphisms with toxicity or therapeutic response to the medication. A total of 400 patients with RA were evaluated, of which 76% were women. the average age was 60.7±13.9 years and the duration of the disease was 13.2±10.9 years. The disease activity scoring method, DAS28-CRP, was used to evaluate the therapeutic response. Toxicity was determined based on reports of adverse events during the evaluation of the patients. The single nucleotide polymorphisms (SNPs) assessed using reverse transcription-PCR in the present study were MTHFR C677T, A1298C, ATIC C347G, RFC-1-G80A, FPGS-AG and DHFR-CT. The SNPs of MTHFR C677T (P=0.05) and A1298C (P=0.048) were significantly associated with the efficacy of MTX, and DHFR-CT (P=0.01) and ATIC C347 (P=0.005) were significantly associated with documented toxicity. Haematological, hepatic or renal toxicity was not associated with any of the SNPs. The results obtained in Colombian patients with RA receiving MTX are similar to those reported in other populations; however, the SNPs associated with a lack of response previously reported in the literature were not observed in our data. The SNPs identified in the present study may be used as biomarkers to predict response to MTX in terms of efficacy and toxicity in Colombian patients with RA.

Comparison of quality of life in patients with musculoskeletal symptoms, those with other comorbidities, and healthy people, in a Colombian open population study / Comparación de la calidad de vida de pacientes con síntomas musculoesqueléticos, comorbilidades asociadas y personas sanas en un estudio abierto de población colombiano

A b s t r a c t Purpose: To describe health-related QOL (HRQOL) in patients with musculoskeletal symptoms, compared to a population with other comorbidities, and a healthy population. Methods: A cross-sectional study was carried out on an open population involved in a community-oriented program for control of rheumatic diseases (COPCORD) study in Colombia, using EQ-5D-3L for estimating QOL, and the health assessment questionnaire disability index (HAQ-DI) for functional capacity. Results: Out of the total 4020 individuals evaluated, 2274 had rheumatic diseases, 642 had non-rheumatic diseases, and 1104 were healthy subjects. Spondyloarthritis (SpA) and rheumatoid arthritis (RA) patients had more complaints regarding pain/discomfort and mobility. As for daily activities, the diseases that mostly affected them were systemic lupus erythematosus (SLE) and RA. RA and fibromyalgia (FM) patients had the worst scores as regards anxiety/depression and self-care dimensions. FM patients had the lowest QOL measured by EQ-VAS (57.7 ± 26.2). The most frequent non-rheumatic diseases were cardiovascular and mental disorders, with 20% of these patients having a moderate level of pain/discomfort and anxiety/depression. The rheumatic patients reported a decrease in functional capacity (HAQ: 0.49), in contrast to the healthy population (0.01), and the population having other diseases (0.06). Conclusion: Rheumatic disease patients in Colombia had the worst QOL compared to the healthy population and patients with other comorbidities. Rheumatic patients had greater functional limitations, even more so when having comorbidities. This study revealed potential factors of interest requiring the attention of public health authorities, and for improving patients' QOL.

RESUMEN Objetivo: Describir la calidad de vida relacionada con la salud en pacientes con síntomas musculoesqueléticos, en comparación con pacientes con enfermedades no reumáticas y una población sana. Métodos: Se realizó un estudio transversal en comunidad abierta, en personas involucradas en un programa orientado a la comunidad para el control de enfermedades reumáticas (COP-CORD) en Colombia, utilizando el EQ-5D-3L para estimar la calidad de vida y el cuestionario de evaluación de la salud (HAQ- DI) para la capacidad funcional. Resultados: Se evaluaron 4.020 individuos; 2.274 tenían enfermedades reumáticas, 642 tenían enfermedades no reumáticas y 1.104 eran sujetos sanos. Los pacientes con espondiloartritis (SpA) y artritis reumatoide (AR) tuvieron mayores quejas con respecto al dolor/malestar y la movilidad. En cuanto a las actividades diarias, los enfermos con lupus eritematoso sistémico (LES) y AR fueron los más afectados. Los pacientes con AR y fibromialgia (FM) tuvieron las peores puntuaciones en ansiedad/depresión en las dimensiones de cuidado personal. Los pacientes con FM tuvieron la calidad de vida más baja medida por EQ-VAS (57,7 ± 26,2). Las enfermedades no reumáticas más frecuentes fueron los trastornos cardiovasculares y mentales; el 20% de estos pacientes tenía un nivel moderado de dolor/malestar y ansiedad/depresión. Los pacientes reumáticos reportaron una disminución de la capacidad funcional (HAQ: 0,49); en contraste con la población sana (0,01) y la población con otras enfermedades (0,06). Conclusión: Los pacientes con enfermedades reumáticas en Colombia tuvieron la peor calidad de vida en comparación con la población sana y los pacientes con otras enfermedades. Los pacientes reumáticos tuvieron una mayor limitación funcional, incluso más que los que tenían otras enfermedades. Este estudio reveló posibles factores relacionados con las enfermedades reumáticas que requieren la atención de las autoridades de salud pública con el objetivo de mejorar la calidad de vida de los pacientes.