Serum metabolomic profiling identifies potential biomarkers in arthritis in older adults: an exploratory study.

BACKGROUND: Seronegative elderly-onset rheumatoid arthritis (EORA)neg and polymyalgia rheumatica (PMR) have similar clinical characteristics making them difficult to distinguish based on clinical features. We hypothesized that the study of serum metabolome could identify potential biomarkers of PMR vs. EORAneg. METHODS: Arthritis in older adults (ARTIEL) is an observational prospective cohort with patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples were compared at baseline with 18 controls. A thorough clinical examination was conducted. A Bruker Avance 600 MHz spectrometer was used to acquire Nuclear Magnetic Resonance (NMR) spectra of serum samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification.Student t-test, one-way ANOVA, binary linear regression and ROC curve, Pearson's correlation along with pathway analyses were conducted. RESULTS: Twenty-eight patients were diagnosed with EORAneg and 20 with PMR. EORAneg patients had a mean disease activity score (DAS)-Erythrocyte Sedimentation Rate (ESR) of 6.21 ± 1.00. All PMR patients reported shoulder pain, and 90% reported pelvic pain. Fifty-eight polar metabolites were identified. Of these, 3-hydroxybutyrate, acetate, glucose, glycine, lactate, and o-acetylcholine (o-ACh), were significantly different between groups. Of interest, IL-6 correlated with different metabolites in PMR and EORAneg suggesting different inflammatory activated pathways. Finally, lactate, o-ACh, taurine, and sex (female) were identified as distinguishable factors of PMR from EORAneg with a sensitivity of 90%, specificity of 92.3%, and an AUC of 0.925 (p < 0.001). CONCLUSION: These results suggest that EORAneg and PMR have different serum metabolomic profiles that might be related to their pathobiology and can be used as biomarker to discriminate between both diseases.

Long-term survival of biological therapy in psoriatic arthritis: 18-year analysis of a cohort in a tertiary hospital.

To study retention of biologic disease-modifying anti-rheumatic drugs (bDMARDs) or apremilast and potential predictors of lack of response in patients with psoriatic arthritis (PsA). A single-center retrospective analysis of PsA patients who received ≥ 1 bDMARD or apremilast during 2000-2018. The main endpoint was lack of response (primary or secondary failure). Analyses included retention of DMARDs (Kaplan-Meier curves) and potential predictors of lack of response (bivariate and multivariate logistic regression models). A total of 159 patients with PsA received up to 8 DMARDs: etanercept (34%), adalimumab (30%), infliximab (9%), golimumab (9%), apremilast (7%), ustekinumab (5%), certolizumab (4%), and secukinumab (2%). Therapy was discontinued in 96 cases (60%), mainly owing to secondary failure (37%), followed by primary failure (25%) and adverse effects (24%). Retention was analyzed based on 313 units of analysis. Duration of follow-up was 846.1 treatment-years (maximum 14.8 years, median 2.75 years). A total of 172 DMARDs were discontinued. The probability of continuing the initial treatment was 37% at 5 years, 22% at 10 years, and 12% at 14 years. The longest medium retention time was observed for infliximab (6.2 years) and etanercept (4.5 years). Predictors of lack of response included male sex, number of swollen joints, and, especially, depression (OR = 35.2). The sensitivity and specificity of the model were 86.4% and 85.7%, respectively, with a coefficient of determination (R2) of 45.6 (ROC, 0.912). Rates of discontinuation due to primary and secondary failure are high in PsA. Retention is better for anti-TNF agents than for other agents.

Interobserver reliability of Masei index validation by a multicenter collaborative group of rheumatologists.

MASEI is the main validated ultrasound score for the evaluation of enthesis. The lack of studies facing the agreement to achieve for the interpretation of the MAdrid Sonographic Enthesis Index (MASEI) among researchers from different centers in multicenter studies is of concern. The aim of this multicenter was to evaluate the interobserver reliability of MASEI. An experienced ultrasonographer-rheumatologist performed ultrasound scans of the areas included in MASEI index in three patients with Ankylosing Spondylitis and Psoriatic Arthritis. Videos were captured. The videos were then evaluated by 24 rheumatologists of the ultrasound working group of the Catalan Society of Rheumatology (EcoCAT). A face-to-face training meeting was held. Ten days after the workshop, the study participants evaluated the videos. A reliability assessment was performed. The ICC for the MASEI scores after the workshop was of 0.97 (95% CI 89-99). Reliability did not vary statistically with examiner experience. Globally, no problems of reliability by structures were seen, and all the ICCs were above 0.90 and improved slightly after the educational program. However, the correlation observed between examiners at plantar aponeursis and triceps tendon was weak. The small variability observed in the results of the index validation in our study, suggests that the MASEI index is reproducible by different observers when those are well trained and show awesome results of the enthesis when examined by ultrasound.

Estado actual de la reumatología en el sector sanitario público de Cataluña / Rheumatology Manpower in the Public System in Catalonia (Spain)

Objetivo: Determinar el estado actual de la reumatología en Cataluña, y actualizar la información respecto a los estudios previos. Material y métodos Diseño: Estudio observacional, descriptivo y transversal. Recogida de datos de enero a junio de 2017. Muestra: Reumatólogos que ejercen actividad asistencial pública en Cataluña. Se envió un cuestionario en línea recabando información tanto de forma individual como colectiva de los servicios de reumatología. Resultados: Se obtuvo información de 34 hospitales y de 109 reumatólogos: 39 varones y 70 mujeres; edad media: 47±9 años. El número de reumatólogos aumentó un 8% en los últimos 5 años. La obtención del título fue en 101 (92,7%) casos por vía MIR. Noventa y seis (88,1%) facultativos tenían dedicación completa. Un 50% de los reumatólogos ejercían además en el sector privado. La actividad asistencial suponía un 76% de la jornada laboral. Se constató que 24 (70%) servicios de reumatología dependían jerárquicamente de otra especialidad. En 6 hospitales de Cataluña no disponen de reumatólogo. Conclusiones: El número de reumatólogos aumentó respecto hace 5 años. La edad media de los reumatólogos es avanzada y existe un claro predominio femenino en la especialidad. Un gran número de unidades de reumatología dependen de otros servicios. La actividad reumatológica se centra en Barcelona.(AU)

Objective: To determine the current state of Rheumatology in Catalonia and to update the information regarding previous studies. Material and methods Design: Observational, descriptive and cross-sectional study. Data collection from January to June 2017. Sample: Rheumatologists practising public healthcare activity in Catalonia. An online questionnaire was sent to gather individual data and data from rheumatology services/sections. Results: Information was obtained on 109 rheumatologists: 39 men and 70 women; mean age: 47±9 years. The number of rheumatologists has increased by 8% over the past 5 years. One hundred and one (92.7%) doctors qualified as rheumatologists through the MIR. Rheumatology practice was mostly in a hospital setting: 68 (62.4%) physicians. Ninety-six (88.1%) rheumatologists were full-time practitioners. Fifty-four (50%) rheumatologists also practiced in the private sector. Clinical practice was predominant: 76% of daily time was devoted to this area. Of note, it was found that most of the rheumatology services, 24 (705), were dependent hierarchically on other services, namely internal medicine and orthopaedic surgery. There are still 6 hospitals in Catalonia without a rheumatologist. Conclusions: The number of rheumatologists in the public health sector of Catalonia has increased over the past 5 years. The mean age of rheumatologists is advanced and there is a clear predominance of female practitioners in the specialty. Many rheumatology services depend on other services. Rheumatology activity is primarily focussed in the city of Barcelona.(AU)

Rheumatology manpower in the public system in Catalonia (Spain).

OBJECTIVE: To determine the current state of Rheumatology in Catalonia and to update the information regarding previous studies. MATERIAL AND METHODS DESIGN: Observational, descriptive and cross-sectional study. Data collection from January to June 2017. SAMPLE: Rheumatologists practising public healthcare activity in Catalonia. An online questionnaire was sent to gather individual data and data from rheumatology services/sections. RESULTS: Information was obtained on 109 rheumatologists: 39 men and 70 women; mean age: 47±9 years. The number of rheumatologists has increased by 8% over the past 5 years. One hundred and one (92.7%) doctors qualified as rheumatologists through the MIR. Rheumatology practice was mostly in a hospital setting: 68 (62.4%) physicians. Ninety-six (88.1%) rheumatologists were full-time practitioners. Fifty-four (50%) rheumatologists also practiced in the private sector. Clinical practice was predominant: 76% of daily time was devoted to this area. Of note, it was found that most of the rheumatology services, 24 (705), were dependent hierarchically on other services, namely internal medicine and orthopaedic surgery. There are still 6 hospitals in Catalonia without a rheumatologist. CONCLUSIONS: The number of rheumatologists in the public health sector of Catalonia has increased over the past 5 years. The mean age of rheumatologists is advanced and there is a clear predominance of female practitioners in the specialty. Many rheumatology services depend on other services. Rheumatology activity is primarily focussed in the city of Barcelona.

Usefulness of cardiac screening in patients with systemic lupus erythematosus and anti-Ro/SSA antibodies.

OBJECTIVES: Recent data suggest that some adult patients with autoimmune rheumatic diseases may develop cardiac conduction and repolarization abnormalities mediated by anti-Ro/SSA antibodies. We aim to investigate the utility of a cardiac screening in patients with systemic lupus erythematous (SLE) and anti-Ro/SSA positivity. METHODS: SLE patients who consecutively attended a Rheumatology clinic during 1 year where evaluated for the presence and levels of anti-Ro/SSA antibodies, and clinical and biological markers of organ damage and disease activity. All participants underwent a cardiovascular anamnesis and physical examination, ECG, echocardiography, and 24-hour Holter. RESULTS: Of the 145 recruited patients, 49 (32%) had anti-Ro/SSA positivity. None had any degree of atrioventricular block in the ECG or Holter monitoring. No significant differences were observed between anti-Ro/SSA-positive vs. negative patients in terms of PR, QRS or QTc intervals. No clinically significant arrhythmias were recorded during Holter monitoring and no differences in average heart rate, heart rate variability, or atrial or ventricular ectopy burden were observed. Finally, no differences were found in echocardiographic measurements. CONCLUSIONS: In this study of SLE patients, anti-Ro/SSA positivity was not associated with significant alterations in ECG, echocardiography, or 24-hour Holter. These findings do not support ordinary cardiac evaluation in these patients. (Clinicaltrials.gov registration number: NCT02162992).

Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults.

Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in older adults. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritis symptoms in older adults were related to oxylipin-related perturbations. Arthritis in older adults (ARTIEL) is an observational prospective cohort with 64 patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C-reactive protein) of 5.77 (SD 1.02). One hundred percent of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3-derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthrtis in older adults and that the imbalance between n-6- and n-3-derived oxylipins might be related to pathobiology in this population.

Anemia y eosinofilia secundaria a Strongyloides en un paciente tratado con anti-TNF alfa / Anaemia and eosinophilia secondary to strongyloides in a patient treated with anti-TNF-Alpha

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Manifestations, clinical course and prognostic markers in cutaneous polyarteritis nodosa.

BACKGROUND AND OBJECTIVES: Cutaneous polyarteritis nodosa (CPAN) is a comparatively rare form of vasculitis that affects small arteries and arterioles in the panniculus and dermo-subcutaneous junction. Limited information is available regarding its course in the European population. The aim of this study is to characterize the manifestations and prognostic markers of recurrence in CPAN. PATIENTS AND METHODS: We report a retrospective study of patients with clinical and histopathologic evidence of CPAN, which was treated at two tertiary referral centers in Spain between 1989 and 2019. RESULTS: 31 patients were included. The most frequent manifestation was subcutaneous nodules (90.3 %); ulcers were frequent at diagnosis (35.5 %). Two thirds of the patients had at least one extracutaneous manifestation. Seventeen patients (54.8 %) experienced relapse. The strongest predictor of recurrence was ulceration in the initial episode (OR 18.6; 95 % CI 2.73-38; p < 0.01). The pre-treatment results of laboratory parameters associated with inflammation (such as C-reactive protein and neutrophil-to-lymphocyte ratio) were significantly higher in the relapsing group. There were no disease-related deaths and none of the patients developed systemic PAN. CONCLUSIONS: Although CPAN is a vasculitis limited to the skin, symptoms may involve adjacent skeletal muscle or peripheral nerves. While the condition is not life-threatening, the presence of ulceration and elevation of certain laboratory parameters predicts a worse prognosis.

Rheumatology Manpower in the Public System in Catalonia (Spain). / Estado actual de la reumatología en el sector sanitario público de Cataluña.

OBJECTIVE: To determine the current state of Rheumatology in Catalonia and to update the information regarding previous studies. MATERIAL AND METHODS DESIGN: Observational, descriptive and cross-sectional study. Data collection from January to June 2017. SAMPLE: Rheumatologists practising public healthcare activity in Catalonia. An online questionnaire was sent to gather individual data and data from rheumatology services/sections. RESULTS: Information was obtained on 109 rheumatologists: 39 men and 70 women; mean age: 47±9 years. The number of rheumatologists has increased by 8% over the past 5 years. One hundred and one (92.7%) doctors qualified as rheumatologists through the MIR. Rheumatology practice was mostly in a hospital setting: 68 (62.4%) physicians. Ninety-six (88.1%) rheumatologists were full-time practitioners. Fifty-four (50%) rheumatologists also practiced in the private sector. Clinical practice was predominant: 76% of daily time was devoted to this area. Of note, it was found that most of the rheumatology services, 24 (705), were dependent hierarchically on other services, namely internal medicine and orthopaedic surgery. There are still 6 hospitals in Catalonia without a rheumatologist. CONCLUSIONS: The number of rheumatologists in the public health sector of Catalonia has increased over the past 5 years. The mean age of rheumatologists is advanced and there is a clear predominance of female practitioners in the specialty. Many rheumatology services depend on other services. Rheumatology activity is primarily focussed in the city of Barcelona.

Coexistencia de artritis séptica y microcristalina: un reto diagnóstico. A propósito de 25 casos / Coexistence of septic and crystal-induced arthritis: a diagnostic challenge. A report of 25 cases

OBJETIVO: La artritis séptica es una urgencia médica y la artritis microcristalina es un factor de riesgo para su aparición. Si ambas cursan de forma simultánea, la identificación de microcristales puede enmascarar el diagnóstico de la infección y causar un retraso en la instauración del tratamiento antibiótico. MÉTODO: Análisis retrospectivo de pacientes con coexistencia de artritis séptica y microcristalina. Se incluye únicamente a los enfermos con aislamiento del germen en líquido articular y/o hemocultivo e identificación de cristales en el líquido articular. RESULTADOS: Se identificaron un total de 25 pacientes (17 varones y 8 mujeres) con una media de edad de 67 años. La articulación que se afectó con mayor frecuencia fue la rodilla. Los cristales de urato monosódico fueron los que con mayor frecuencia se identificaron en el estudio citológico del líquido sinovial. Los factores de riesgo más frecuentes fueron la diabetes mellitus y la insuficiencia renal crónica. El germen aislado con mayor frecuencia fue el Staphylococcus aureus sensible a meticilina (48%), seguido del Staphylococcus aureus resistente a meticilina (12%) y Mycobacterium tuberculosis (12%). El 36% de los pacientes precisaron desbridamiento quirúrgico (excluyendo los causados por M. tuberculosis). La evolución fue favorable en el 56% de los pacientes, aunque la presencia de complicaciones intercurrentes fue habitual (40%). La mortalidad fue del 8%. CONCLUSIONES: La coexistencia de artritis séptica y microcristalina representa un reto diagnóstico y requiere un alto índice de sospecha. La artropatía por cristales de urato monosódico es la más prevalente y S. aureus el germen causal más frecuente, con una tasa elevada de infección por S. aureus resistente a meticilina. Si se instaura de forma precoz el tratamiento adecuado, la evolución suele ser favorable, por lo que el estudio microbiológico del líquido sinovial es imperativo

OBJECTIVE: Septic arthritis is a medical emergency and crystal-induced arthritis is a risk factor for its development. If both occur simultaneously, crystal-induced arthritis may mask the diagnosis of infection and delay antibiotic therapy. METHOD: Retrospective analysis of patients with coexistence of septic and crystal-induced arthritis. We included only patients with isolation of crystals in synovial fluid analysis and positive culture of synovial fluid and/or blood culture. RESULTS: A total of 25 patients (17 men and 8 women) with a mean age of 67 years. The most commonly affected joint was the knee. In synovial fluid cytological studies, the most frequently identified crystals were monosodium urate. Risk factors included diabetes and chronic renal failure. The most frequently isolated germs were methicillin-sensitive S. aureus (48%), methicillin-resistant S. aureus (12%) and Mycobacterium tuberculosis (12%). In all, 36% of subjects required surgical drainage (excluding those caused by M. tuberculosis). Clinical outcome was favorable in 56%, although intercurrent complications were usual (40%). Mortality was 8%. CONCLUSIONS: Coexistence of septic and crystal-induced arthritis represents a diagnostic challenge and requires a high index of suspicion. Gout was the most prevalent crystal-induced arthritis. S. aureus was the most commonly causative pathogen, with a high rate of methicillin-resistant S. aureus infection. If treated early, the outcome is usually favorable, making synovial fluid microbiological study imperative

Coexistence of septic and crystal-induced arthritis: A diagnostic challenge. A report of 25 cases. / Coexistencia de artritis séptica y microcristalina: un reto diagnóstico. A propósito de 25 casos.

OBJECTIVE: Septic arthritis is a medical emergency and crystal-induced arthritis is a risk factor for its development. If both occur simultaneously, crystal-induced arthritis may mask the diagnosis of infection and delay antibiotic therapy. METHOD: Retrospective analysis of patients with coexistence of septic and crystal-induced arthritis. We included only patients with isolation of crystals in synovial fluid analysis and positive culture of synovial fluid and/or blood culture. RESULTS: A total of 25 patients (17 men and 8 women) with a mean age of 67 years. The most commonly affected joint was the knee. In synovial fluid cytological studies, the most frequently identified crystals were monosodium urate. Risk factors included diabetes and chronic renal failure. The most frequently isolated germs were methicillin-sensitive S. aureus (48%), methicillin-resistant S. aureus (12%) and Mycobacterium tuberculosis (12%). In all, 36% of subjects required surgical drainage (excluding those caused by M. tuberculosis). Clinical outcome was favorable in 56%, although intercurrent complications were usual (40%). Mortality was 8%. CONCLUSIONS: Coexistence of septic and crystal-induced arthritis represents a diagnostic challenge and requires a high index of suspicion. Gout was the most prevalent crystal-induced arthritis. S. aureus was the most commonly causative pathogen, with a high rate of methicillin-resistant S. aureus infection. If treated early, the outcome is usually favorable, making synovial fluid microbiological study imperative.

Lesión osteolítica cervical como presentación del síndrome SAPHO / SAPHO syndrome presenting as an osteolytic lesion of the neck

Se expone un caso de osteítis vertebral múltiple de presentación aguda con marcada afectación del estado general. Los hallazgos radiológicos, gammagráficos y de resonancia magnética obligaron al diagnóstico diferencial de un proceso neoplásico infiltrativo y de un origen infeccioso vertebral frente a la etiología inflamatoria. Por la presencia de osteítis múltiple no infecciosa, artritis esternoclavicular y la ulterior aparición de pustulosis plantar, se orientó como síndrome SAPHO. El tratamiento con infliximab consiguió la mejoría clínica, analítica y de las alteraciones radiológicas (AU)

We report a case of acute-onset multifocal vertebral osteitis with a marked impact on the patient's general health. The radiological, scintigraphic and magnetic resonance findings made it necessary to carry out a differential diagnosis to distinguish it from an infiltrative neoplastic process and determine whether it had an infectious or an inflammatory etiology. The presence of noninfectious multifocal osteitis and sternoclavicular arthritis and the subsequent development of plantar pustulosis pointed to SAPHO syndrome. Treatment with infliximab led to improvement in the clinical symptoms, laboratory values and radiological abnormalities (AU)