The impact of disease activity on health-related quality of life in patients with systemic lupus erythematosus / Impacto de la actividad clínica en la calidad de vida relacionada con la salud de pacientes con lupus eritematoso sistémico

Background and objective The aim of this research was to investigate the relationship between disease activity and health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) considering the increased interest in the management of this disease. Materials and methods HRQoL was measured at clinic visits during a 12-month follow-up period using questionnaires on fatigue (FACIT-FATIGUE); quality of life, EuroQol 5-dimension (EQ-5D-5L) health questionnaire with 5 levels; disability, Health Assessment Questionnaire (HAQ), and a Global Health Status (GHS) scale. Disease activity, organ damage and other clinical factors that could affect HRQoL were recorded. The association between disease activity and HRQoL was assessed using Bayesian linear regression models with monotonic effects. Results Data from 70 patients at the baseline visit and 42 patients with 1 year of follow-up were analyzed. At baseline, 28.57% of patients presented Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>6. In the 70 baseline patients, disease activity was associated with HRQoL in all four parameters. In the 42 patients with 12 months of follow-up, the positive association of disease activity with GHS, FACIT-FATIGUE and EQ-5D-5L and the negative association with HAQ was maintained.Patients who are smokers and those receiving immunosuppressant therapy presented low GHS and FACIT-FATIGUE scores. Moreover, older age at inclusion was significantly associated to low GHS, while low leucocyte and 25-OH-vitamin D levels were associated to fatigue perception in SLE patients. Conclusion Our results showed a statistically significant association between disease activity and HRQoL parameters. (AU)

Objetivo El objetivo del estudio fue analizar la relación entre la actividad clínica y la calidad de vida relacionada con la salud (CVRS) en pacientes con lupus eritematoso sistémico (LES).Material y métodos La CVRS se evaluó en la visita basal y durante 12 meses de seguimiento mediante un cuestionario de fatiga (FACIT-FATIGUE), calidad de vida (EQ-5D-5L), discapacidad (HAQ) y una escala analógica visual de estado general de salud (EVA). La actividad clínica, el daño acumulado y otros factores clínicos que pudieran afectar a la CVRS se analizaron mediante un modelo de regresión lineal bayesiano con efectos monotónicos. Resultados Se analizaron los datos de 70 pacientes incluidos en la visita basal y los 42 con 12 meses de seguimiento seleccionados aleatoriamente. En la visita basal el 28,57% de los pacientes presentaban un índice SLEDAI>6. La actividad clínica medida mediante el índice SLEDAI se asociaba de forma estadísticamente significativa a los 4 parámetros de CVRS. En los 42 pacientes con un año de seguimiento la relación directa entre la actividad clínica y el FACIT-FATIGUE, EVA y EQ-5D-5L, así como la relación indirecta con el HAQ, se mantuvieron. Los pacientes fumadores y aquellos bajo tratamiento inmunosupresor presentaban valores disminuidos de EVA y FACIT-FATIGUE. Además, los pacientes con edades más avanzadas presentaban valores disminuidos de EVA, y aquellos con niveles bajos de vitamina D o leucopenia presentaban mayor percepción de fatiga. Conclusión La actividad clínica se asocia a diferentes dominios de la CVRS, apoyando la evaluación de la CVRS como complemento en el manejo del LES. (AU)

The impact of disease activity on health-related quality of life in patients with systemic lupus erythematosus.

BACKGROUND AND OBJECTIVE: The aim of this research was to investigate the relationship between disease activity and health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) considering the increased interest in the management of this disease. MATERIALS AND METHODS: HRQoL was measured at clinic visits during a 12-month follow-up period using questionnaires on fatigue (FACIT-FATIGUE); quality of life, EuroQol 5-dimension (EQ-5D-5L) health questionnaire with 5 levels; disability, Health Assessment Questionnaire (HAQ), and a Global Health Status (GHS) scale. Disease activity, organ damage and other clinical factors that could affect HRQoL were recorded. The association between disease activity and HRQoL was assessed using Bayesian linear regression models with monotonic effects. RESULTS: Data from 70 patients at the baseline visit and 42 patients with 1 year of follow-up were analyzed. At baseline, 28.57% of patients presented Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>6. In the 70 baseline patients, disease activity was associated with HRQoL in all four parameters. In the 42 patients with 12 months of follow-up, the positive association of disease activity with GHS, FACIT-FATIGUE and EQ-5D-5L and the negative association with HAQ was maintained. Patients who are smokers and those receiving immunosuppressant therapy presented low GHS and FACIT-FATIGUE scores. Moreover, older age at inclusion was significantly associated to low GHS, while low leucocyte and 25-OH-vitamin D levels were associated to fatigue perception in SLE patients. CONCLUSION: Our results showed a statistically significant association between disease activity and HRQoL parameters.

Efecto de diferentes esquemas de terapia de deprivación androgénica sobre la densidad mineral ósea de pacientes con cáncer de próstata / Effect of different schemes of androgen deprivation therapy on bone mass density in prostate cancer patients

Objetivos: Evaluar aspectos del metabolismo óseo basal en pacientes con cáncer de próstata y el efecto, en práctica clínica habitual, de diferentes esquemas de tratamiento (intermitente o continuo) con agonistas de la hormona liberadora de hormona luteinizante (LH-RH) y del denosumab en la evolución de la densidad mineral ósea (DMO).MétodosEstudio observacional retrospectivo de una cohorte de pacientes con cáncer de próstata en tratamiento con agonistas LH-RH, valorados en el servicio de reumatología de un hospital de tercer nivel. Se recogieron datos demográficos, índice de FRAX, esquema de tratamiento LH-RH, tratamiento de osteoporosis, datos de laboratorio y de DMO. Se usaron modelos de regresión lineal de efecto mixto analizando la interacción de los esquemas de tratamiento LH-RH, denosumab y la evolución de DMO.ResultadosSe incluyeron 83 pacientes (73±8años). Evaluación basal: el 16% de los pacientes presentaron osteoporosis densitométrica y además un 27% un riesgo elevado de fractura (FRAX). El 80% tenían niveles de vitaminaD <30ng/l. La pauta intermitente de agonistas LH-RH y los niveles elevados de vitaminaD se asociaron a mejor DMO basal. No se detectó asociación entre la evolución de la DMO y las pautas de tratamiento de agonistas LH-RH, pero sí se encontró una correlación positiva con denosumab.ConclusionesUna elevada proporción de pacientes presentaban un alto riesgo de fractura o niveles insuficientes de vitaminaD no detectados previamente. El estudio tanto del metabolismo óseo como del riesgo de fractura son convenientes en estos pacientes. En práctica clínica habitual el efecto sobre la DMO del denosumab se detecta a corto plazo, mientras que el del esquema intermitente con agonistas LH-RH es menos evidente. (AU)

Objectives: To evaluate the aspects of the basal bone health status in prostate cancer patients. Furthermore, to evaluate in a real-world setting the effect of different schemes (intermittent or continuous) of androgen deprivation therapy (ADT) and the effect of denosumab in bone mass density (BMD).MethodsObservational, retrospective study of a cohort of prostate cancer patients in treatment with luteinizing hormone-releasing hormone (LH-RH) agonists, evaluated in the rheumatology department of a tertiary center. Demographics, FRAX score, LH-RH treatment scheme, osteoporosis treatment, laboratory data and BMD were collected. Mixed effect regression models to analyze the interaction between LH-RH treatment scheme, denosumab and BMD evolution were used.ResultsEighty-three patients (mean age 71±8years) were included. At the basal evaluation, 16% of patients presented densitometric osteoporosis and 27% of patients presented high fracture risk. Eighty percent of patients had inadequate vitaminD levels. VitaminD >30ng/mL was correlated with higher T-scores. There was no association between LH-RH treatment scheme and BMD evolution, however there was a positive association with denosumab.ConclusionA high proportion of patients presented elevated fracture risk or inadequate vitaminD levels, not previously recognized. Bone health assessment and fracture risk evaluation are convenient in these patients. In a real-world setting, the effect of denosumab in BMD is detected, however the effect of intermittent LH-RH schema treatment is less evident. (AU)

[Effect of different schemes of androgen deprivation therapy on bone mass density in prostate cancer patients]. / Efecto de diferentes esquemas de terapia de deprivación androgénica sobre la densidad mineral ósea de pacientes con cáncer de próstata.

OBJECTIVES: To evaluate the aspects of the basal bone health status in prostate cancer patients. Furthermore, to evaluate in a real-world setting the effect of different schemes (intermittent or continuous) of androgen deprivation therapy (ADT) and the effect of denosumab in bone mass density (BMD). METHODS: Observational, retrospective study of a cohort of prostate cancer patients in treatment with luteinizing hormone-releasing hormone (LH-RH) agonists, evaluated in the rheumatology department of a tertiary center. Demographics, FRAX score, LH-RH treatment scheme, osteoporosis treatment, laboratory data and BMD were collected. Mixed effect regression models to analyze the interaction between LH-RH treatment scheme, denosumab and BMD evolution were used. RESULTS: Eighty-three patients (mean age 71±8years) were included. At the basal evaluation, 16% of patients presented densitometric osteoporosis and 27% of patients presented high fracture risk. Eighty percent of patients had inadequate vitaminD levels. VitaminD >30ng/mL was correlated with higher T-scores. There was no association between LH-RH treatment scheme and BMD evolution, however there was a positive association with denosumab. CONCLUSION: A high proportion of patients presented elevated fracture risk or inadequate vitaminD levels, not previously recognized. Bone health assessment and fracture risk evaluation are convenient in these patients. In a real-world setting, the effect of denosumab in BMD is detected, however the effect of intermittent LH-RH schema treatment is less evident.

Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study / Efectividad y seguridad en el mundo real de los inhibidores de JAK en la artritis reumatoide: Estudio unicéntrico

Background/objective: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in “real world” conditions. Methods: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan–Meier survival curves. Results: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. Conclusion: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.(AU)

Antecedentes/objetivo: Evaluar la efectividad y seguridad de baricitinib y tofacitinib en los pacientes con artritis reumatoide (AR) en condiciones del «mundo real». Métodos: Se realizó un estudio retrospectivo unicéntrico que incluyó a los pacientes de AR que habían iniciado tratamiento con baricitinib o tofacitinib de septiembre de 2017 a enero de 2020. Se recopilaron las variables demográficas, clínicas, de laboratorio, de eficacia y seguridad a nivel basal, y transcurridos uno, 3, 6, 12, 18 y 24 meses. La efectividad se evaluó mediante los cambios desde el punto basal en cuanto a DAS28, SDAI, HAQ y los reactantes de fase aguda. El análisis de seguridad incluyó los episodios adversos debido a cualquier causa, incluyendo infección o intolerancia. Se consideró infección grave cuando se produjo hospitalización. El análisis estadístico consistió en modelos mixtos de regresión ordinaria de Bayes incluyendo el efecto monotónico de cada visita y las curvas de supervivencia de Kaplan-Meier. Resultados: En total se incluyeron 98 pacientes. Se observó una reducción significativa de la actividad de la enfermedad en ambos grupos. No se detectó diferencia alguna entre ninguno de los tratamientos en términos de efectividad incluso en primera línea, tras el fallo de bDMARD, en monoterapia ni en terapia combinada. Se registró un total de 54 episodios adversos, de los cuales se consideraron relevantes 18. La incidencia de la infección, incluyendo herpes zoster, fue similar en ambos grupos. Ningún paciente de cualquiera de los grupos padeció episodios adversos tales como tuberculosis, episodio tromboembólico, malignidad, muerte ni episodios adversos de tipo cardiovascular. El análisis de supervivencia no reflejó diferencia alguna entre los grupos. Conclusión: Baricitinib y tofacitinib son comparables en términos de efectividad y seguridad en condiciones del mundo real.(AU)

Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis

Background/Objective: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors.MethodsA cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors.ResultsOverall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score.ConclusionRA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor. (AU)

Objetivo: Evaluar el riesgo cardiovascular (RCV) en pacientes con artritis reumatoide (AR) mediante el empleo de la ecografía de carótidas en adición a los factores de riesgo cardiovascular clásicos.MétodosSe realizó un estudio de casos y controles transversal incluyendo pacientes con AR y controles voluntarios sin historia de eventos cardiovasculares. El estudio se llevó a cabo entre julio de 2019 y enero de 2020. Se excluyeron individuos con edad por encima de los 75 años, enfermedad cardiovascular establecida y/o enfermedad renal crónica.ResultadosEn total, se incluyeron 200 pacientes con AR y 111 controles. Las variables demográficas y clínicas fueron comparables entre los grupos de estudio. Se halló correlación entre la edad, el IMC y la presencia de hipertensión arterial en ambos grupos. Los pacientes con AR evidenciaron un mayor grosor íntima-media y una mayor presencia de placas en el estudio de ecografía carotídea respecto a los controles y además demostró guardar relación con una mayor duración de la enfermedad.ConclusionesLa AR conlleva el desarrollo de un mayor grosor íntima-media y ello correlaciona con la duración y la actividad de la enfermedad, lo cual apoya que la AR actúa como un factor de riesgo cardiovascular independiente. (AU)

Real-world Effectiveness and Safety of JAK Inhibitors in Rheumatoid Arthritis: A Single-centre Study.

BACKGROUND/OBJECTIVE: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in "real world" conditions. METHODS: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan-Meier survival curves. RESULTS: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. CONCLUSION: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.

Efectividad de belimumab en el tratamiento de la nefritis lúpica: análisis de 8 casos / Efectiveness of belimumab in the treatment of lupus nephritis: analysis of 8 cases

Introducción y objetivo: Belimumab es un anticuerpo monoclonal aprobado para pacientes con lupus eritematoso sistémico (LES), con indicación reciente para nefritis lúpica (NL).El objetivo es analizar la eficacia de belimumab en pacientes con NL.MétodosEstudio transversal, retrospectivo, que incluye pacientes diagnosticados de LES (criterios SLICC/ACR 2012), con nefritis demostrada mediante biopsia, tratados con belimumab. Se recogieron datos serológicos, función renal (creatinina y filtrado glomerular) y sedimento urinario.ResultadosSe incluyen 8 pacientes con edad media de 37,56 (7,03) años, con 15,13 (8,71) años de evolución de la enfermedad y 4,61 (2,64) años desde el inicio de belimumab.La proteinuria se redujo hasta alcanzar valores normales en 6 pacientes, manteniéndose la función renal estable desde el inicio del tratamiento en todos los casos. Se registró una reducción del nivel de anti-DNA y una normalización del complemento en los casos en que estaba reducido. En uno de los pacientes se registró un aumento del título de anti-DNA, manteniéndose el complemento normal. (AU)

Introduction and objective: Belimumab is a monoclonal antibody targeting BLyS approved for Systemic Lupus Erythematosus (SLE), with recent indication for lupus nephritis (LN).To analyze effectiveness of Belimumab in LN patients.MethodsRetrospective and cross-sectional study including SLE patients (SLICC/ACR 2012 criteria) with LN demonstrated by kidney biopsy, treated with Belimumab. A clinical history review was made and serological data, kidney function and urine sediment were collected.ResultsEight patients with LN demonstrated by kidney biopsy were included. Median age was 37.56 (7.03) years, with 15.13 (8.71) years since SLE diagnosis was made and 4.61 (2.64) years since onset of belimumab.Proteinuria was reduced to normal values in 6 patients, and renal function was stable from the beginning of treatment in all cases. There was a reduction in the anti-DNA level and normalization of complement in those cases in which it was reduced. One patient presented an increase in anti-DNA titer, with normal complement.ConclusionsIn clinical practice, belimumab can improve LN in terms of serological activity, kidney function and urine sediment. (AU)

Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis

Background and objectives: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers.Patients and methodsObservational case–control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls.ResultsA total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p<0.001), but no higher CXCL4 or CXCL8 levels. GDF15 was associated with Diffuse SSc, pulmonary arterial hypertension, interstitial lung disease, less forced vital capacity, high titles of antiScl70, disease activity, and dilated loops in capillaroscopy. CXCL4 levels were associated to a higher Rodnan punctuation, while CXCL8 was associated to C4 fraction consumption and tortuosities in capillaroscopy. (AU)

Antecedentes y objetivos: La esclerosis sistémica (ES) es una enfermedad autoinmunitaria que afecta a diferentes órganos y cuya mortalidad se relaciona fundamentalmente con su afectación pulmonar. Los pacientes con ES presentan niveles séricos elevados de algunas citocinas. Nuestro objetivo es determinar el papel de CXCL4, CXCL8 y GDF15 en la fisiopatología de la ES, y si pueden considerarse biomarcadores de daño orgánico.Pacientes y métodosEstudio observacional de casos-controles, con pacientes afectados de ES (criterios ACR/EULAR 2013) y controles sanos. Se determinaron los niveles séricos de CXCL4, CXCL8 y GDF15 en ambos grupos, y se registraron variables demográficas, clínicas, analíticas, de actividad, gravedad, percepción de salud y discapacidad de pacientes con ES, a quienes, además, se les realizó videocapilaroscopia, ecocardiograma y espirometría.ResultadosSe incluyeron 42 pacientes (95,4% mujeres), con una edad media de 59,2 años y una mediana de 4 años desde el diagnóstico, con 42 controles sanos. Se hallaron niveles significativamente mayores de GDF15 en pacientes con ES que en controles (p<0,001), pero no de CXCL4 ni CXCL8. GDF15 se asoció a ES difusa, hipertensión pulmonar, enfermedad pulmonar intersticial, menor capacidad vital forzada, títulos altos de anti-Scl70, actividad de ES y dilataciones capilares. Asimismo, los niveles de CXCL4 se asociaron a mayor afectación cutánea (Rodnan), mientras que CXCL8 se asoció a consumo de la fracción C4 del complemento y tortuosidades en la capilaroscopia. (AU)

Efectiveness of belimumab in the treatment of lupus nephritis: analysis of 8 cases. / Efectividad de belimumab en el tratamiento de la nefritis lúpica: análisis de 8 casos.

INTRODUCTION AND OBJECTIVE: Belimumab is a monoclonal antibody targeting BLyS approved for Systemic Lupus Erythematosus (SLE), with recent indication for lupus nephritis (LN). To analyze effectiveness of Belimumab in LN patients. METHODS: Retrospective and cross-sectional study including SLE patients (SLICC/ACR 2012 criteria) with LN demonstrated by kidney biopsy, treated with Belimumab. A clinical history review was made and serological data, kidney function and urine sediment were collected. RESULTS: Eight patients with LN demonstrated by kidney biopsy were included. Median age was 37.56 (7.03) years, with 15.13 (8.71) years since SLE diagnosis was made and 4.61 (2.64) years since onset of belimumab. Proteinuria was reduced to normal values in 6 patients, and renal function was stable from the beginning of treatment in all cases. There was a reduction in the anti-DNA level and normalization of complement in those cases in which it was reduced. One patient presented an increase in anti-DNA titer, with normal complement. CONCLUSIONS: In clinical practice, belimumab can improve LN in terms of serological activity, kidney function and urine sediment.

Cardiovascular risk assessment with carotid ultrasound in rheumatoid arthritis.

BACKGROUND/OBJECTIVE: To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using carotid ultrasound additionally to the traditional CV risk factors. METHODS: A cross-sectional case control study was performed including RA patients and matched controls. This study was performed from July-2019 to January-2020. Population over 75 years old, established CV disease and/or chronic kidney disease (from III Stage) were excluded. Statistical analysis included a multivariate variance analysis (Manova) and a negative binomial regression adjusted by confounding factors. RESULTS: Overall, a total of 200 cases and 111 controls were included in the study. Demographical and clinical variables were comparable between groups. A relationship between age, BMI and high blood pressure was detected in both groups. RA patients showed higher intima-media thickness and higher plaque account compared to controls and it was related to the disease duration and DAS28 score. CONCLUSION: RA leads to a higher intima-media thickness, and this is related to the disease duration and DAS28 score. These findings support that RA acts as an independent cardiovascular risk factor.

Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis.

BACKGROUND AND OBJECTIVES: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers. PATIENTS AND METHODS: Observational case-control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls. RESULTS: A total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p<0.001), but no higher CXCL4 or CXCL8 levels. GDF15 was associated with Diffuse SSc, pulmonary arterial hypertension, interstitial lung disease, less forced vital capacity, high titles of antiScl70, disease activity, and dilated loops in capillaroscopy. CXCL4 levels were associated to a higher Rodnan punctuation, while CXCL8 was associated to C4 fraction consumption and tortuosities in capillaroscopy. CONCLUSIONS: GDF15 high levels were associated with diffuse SSc, lung impairment, disease activity and changes in capillaroscopy. Moreover, CXCL4 was only associated with skin impairment, while CXCL8 was not related to organic damage.

Decreased DNA hydroxymethylation and increased DNA demethylation are associated with high antioxidant response in systemic lupus erythematosus patients / Asociación entre la disminución de hidroximetilación y el incremento de la desmetilación del ADN y la respuesta antioxidante en los pacientes de lupus eritematoso sistémico

Objectives: DNA hydroxymethylation may be induced by oxidative stress in lupus patients, so we investigated the association between DNA hydroxymethylation and demethylation with the antioxidant response.MethodsA case–control study was performed including lupus patients and matched healthy controls. Serum concentration of glutathione (GSH), glutathione disulphide (GSSG), superoxide dismutase (SOD) and total antioxidant capacity (TAC), 5-mC and 5-hmC were determined.ResultsOne hundred and forty-two patients and 34 controls were included. 5-hmC levels were lower in SLE patients than in controls. GSH and GSSG values were lower in patients, while SOD levels were higher in patients. TAC did not show significant differences, but higher demethylation and lower hydroxydemethylation were associated to increased TAC values. Lower demethylation was associated with cytopenia and lower hydroxymethylation with longer course of the disease. Lower levels of GSH and GSSG and higher SOD values were associated with accumulated damage assessed by SLICC-ACR.ConclusionsLower hydroxymethylation in patients than in controls was observed. Moreover, higher demethylation and lower hydroxymethylation leads to high TAC levels. DNA hydroxymethylation seems to be related to longer course of the disease. (AU)

Objetivos: La hidroximetilación del ADN puede estar inducida por el estrés oxidativo en pacientes de lupus, por lo que estudiamos la asociación entre hidroximetilación del ADN y desmetilación sin respuesta antioxidante.MétodosSe realizó un control de casos que incluyó a pacientes de lupus pareados con controles sanos. Se calcularon la concentración sérica de glutatión (GSH), glutatión disulfuro (GSSG), superóxido dismutasa (SOD), capacidad antioxidante total (CAT), 5-mC y 5-hmC.ResultadosSe incluyeron 142 pacientes y 34 controles. Los niveles de 5-hmC fueron menores en el grupo de pacientes de LES que en el de controles. Los valores de GSH y GSSG fueron menores en el grupo de pacientes, mientras que los valores de SOD fueron superiores en el grupo de pacientes. La CAT no reflejó diferencias significativas, pero el incremento de desmetilación y la disminución de hidroximetilación estuvieron asociados al incremento de los valores de la CAT. La disminución de la desmetilación estuvo asociada a citopenia, y la disminución de la hidroximetilación a un curso más corto de la enfermedad. Los niveles menores de GSH y GSSG, y los valores superiores de SOD estuvieron asociados a una acumulación del daño, según lo evaluado mediante SLICC-ACR.ConclusionesSe observó menor hidroximetilación en los pacientes que en los controles. Además, el incremento de la desmetilación y la disminución de la hidroximetilación conllevan unos altos niveles de CAT. La hidroximetilación del ADN parece estar relacionada con un curso más largo de la enfermedad. (AU)

[Decreased DNA hydroxymethylation and increased DNA demethylation are associated with high antioxidant response in systemic lupus erythematosus patients].

OBJECTIVES: DNA hydroxymethylation may be induced by oxidative stress in lupus patients, so we investigated the association between DNA hydroxymethylation and demethylation with the antioxidant response. METHODS: A case-control study was performed including lupus patients and matched healthy controls. Serum concentration of glutathione (GSH), glutathione disulphide (GSSG), superoxide dismutase (SOD) and total antioxidant capacity (TAC), 5-mC and 5-hmC were determined. RESULTS: One hundred and forty-two patients and 34 controls were included. 5-hmC levels were lower in SLE patients than in controls. GSH and GSSG values were lower in patients, while SOD levels were higher in patients. TAC did not show significant differences, but higher demethylation and lower hydroxydemethylation were associated to increased TAC values. Lower demethylation was associated with cytopenia and lower hydroxymethylation with longer course of the disease. Lower levels of GSH and GSSG and higher SOD values were associated with accumulated damage assessed by SLICC-ACR. CONCLUSIONS: Lower hydroxymethylation in patients than in controls was observed. Moreover, higher demethylation and lower hydroxymethylation leads to high TAC levels. DNA hydroxymethylation seems to be related to longer course of the disease.

Relation between cumulative damage in systemic lupus erythematosus and recognised disability by the National Social Security Institute of Spain (INSS) / Relación entre el daño acumulado en el lupus eritematoso sistémico y la discapacidad reconocida por el Instituto Nacional de la Seguridad Social de España

Introduction: Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease that particularly affects young women during their second and third decades. Events attributed to SLE itself and others related to the disease may impact negatively on the quality of life, employment and disability. However, there are not many studies focused on the impact that the disease may have on patients regarding those aspects. In Spain, the evaluation of disability and the assignation of a pension is given by the National Social Security Institute of Spain, INSS (“Instituto Nacional de la Seguridad Social”). Objective: To assess the relationship between cumulative damage regarding the affected organ and the percentage of disability recognised by the National Social Security Institute of Spain (INSS) in SLE patients. Methods: Cross-sectional prospective study of SLE patients according to the SLICC-2012 criteria, from the Rheumatology Service of two Spanish hospitals. We collected clinical and demographic data through personal interview and the SLICC/ACR questionnaire, and classified patients regarding a recognised disability or not. Results: 142 patients were evaluated; 30% had some percentage of official disability. We found a positive correlation between percentage of recognised disability and the SLICC/ACR index score. Musculoskeletal system is the most affected system, without differences between both groups; but we found a higher proportion of damage in nervous system, renal and vasculitis in patients with a recognised disability. Conclusion: There is a positive correlation between percentage of recognised disability in Spain and the cumulative damage in SLE.(AU)

Introducción: El lupus eritematoso sistémico (LES) es una enfermedad multisistémica autoinmune que afecta especialmente a las mujeres jóvenes durante su segunda y tercera décadas. Los eventos atribuidos al propio LES y otros relacionados con la enfermedad pueden tener un impacto negativo en la calidad de vida, el empleo y la discapacidad. Sin embargo, existen pocos datos publicados al respecto. En España, la evaluación de la discapacidad y la asignación de una pensión corresponden al Instituto Nacional de Seguridad Social de España (INSS). Objetivo: Evaluar la relación entre el daño acumulado relacionado con el órgano afectado y el porcentaje de discapacidad reconocido por el INSS en pacientes con LES. Métodos: Estudio prospectivo transversal de pacientes con LES según los criterios SLICC-2012, del servicio de reumatología de 2 hospitales de España. Recopilamos datos clínicos y demográficos mediante entrevista personal y el cuestionario SLICC/ACR, y clasificamos a los pacientes con respecto a una discapacidad reconocida o no. Resultados: Se evaluaron 142 pacientes; el 30% tenía algún porcentaje de discapacidad oficial. Encontramos una correlación positiva entre el porcentaje de discapacidad reconocida y la puntuación del índice SLICC/ACR. El sistema musculoesquelético es el sistema más afectado, sin diferencias entre ambos grupos; pero encontramos una mayor proporción de daño en el sistema nervioso, renal y vasculitis en pacientes con una discapacidad reconocida.(AU)ConclusiónExiste una correlación positiva entre el porcentaje de discapacidad reconocida en España y el daño acumulado en el LES.(AU)

Relation between cumulative damage in systemic lupus erythematosus and recognised disability by the National Social Security Institute of Spain (INSS).

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease that particularly affects young women during their second and third decades. Events attributed to SLE itself and others related to the disease may impact negatively on the quality of life, employment and disability. However, there are not many studies focused on the impact that the disease may have on patients regarding those aspects. In Spain, the evaluation of disability and the assignation of a pension is given by the National Social Security Institute of Spain, INSS ("Instituto Nacional de la Seguridad Social"). OBJECTIVE: To assess the relationship between cumulative damage regarding the affected organ and the percentage of disability recognised by the National Social Security Institute of Spain (INSS) in SLE patients. METHODS: Cross-sectional prospective study of SLE patients according to the SLICC-2012 criteria, from the Rheumatology Service of two Spanish hospitals. We collected clinical and demographic data through personal interview and the SLICC/ACR questionnaire, and classified patients regarding a recognised disability or not. RESULTS: 142 patients were evaluated; 30% had some percentage of official disability. We found a positive correlation between percentage of recognised disability and the SLICC/ACR index score. Musculoskeletal system is the most affected system, without differences between both groups; but we found a higher proportion of damage in nervous system, renal and vasculitis in patients with a recognised disability. CONCLUSION: There is a positive correlation between percentage of recognised disability in Spain and the cumulative damage in SLE.

The Role of Plasma Calprotectin in Non-infectious Uveitis.

PURPOSE: To investigate the role of plasma calprotectin in non-infectious uveitis. METHODS: This is an observational both cross-sectional and prospective study. Patients with active non-infectious uveitis were recruited as well as nonuveitic controls. Plasma calprotectin was determined and an ophthalmological examination was performed for both patients and controls. Independent variables possibly influencing levels of plasma calprotectin were recorded and analyzed. Categorical variables were compared by chi-square test (applying correction by continuity if necessary). T-test (or Kruskal-Wallis when appropriate) was used to compare averages. Multiple linear regression analysis was used to assess relationship between plasma calprotectin levels and independent variables. Spearman coefficient was calculated in order to establish correlation between plasma calprotectin and anterior chamber cell grading. Changes in plasma calprotectin levels between the flare beginning and its resolution were determined with mixed model for repeated measures. R software (version 3.6.0) was used to perform the statistical analysis. RESULTS: We included 74 patients and 40 controls in the cross-sectional study. Plasma calprotectin levels were higher in uveitis patients compared to those of controls (p = .003), being higher in younger patients and patients with posterior uveitis. No correlation between calprotectin and anterior chamber inflammation degree was found (p = .198). For the prospective study, we included 36 patients. We found no significant differences in calprotectin levels between active and inactive uveitis (p = .344). CONCLUSIONS: Plasma calprotectin levels are elevated in uveitis patients and are influenced by age and anatomical location of uveitis. Further investigation is needed to assess the relationship between calprotectin and uveitis activity.

18 F-FDG PET/TC en pacientes con polimialgia reumática: despistando vasculitis / 18 F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with polymyalgia rheumatica: Screening for vasculitis

OBJETIVO: La polimialgia reumática (PMR) puede asociarse a vasculitis de grandes vasos (VGV). Este trabajo pretende evaluar el papel de 18F-FDG PET/TC en el diagnóstico de VGV asociado a PMR. MATERIALES Y MÉTODO: Estudio retrospectivo de pacientes con PMR. Se recogieron datos clínicos, analíticos, reactantes de fase aguda (RFA) (PCR, VSG), y a quienes tenían clínica persistente, elevación de RFA, precisaban dosis elevadas de corticoterapia o cuadros atípicos de PMR (febrícula, pérdida de peso, etc.) se realizó 18F-FDG PET/TC. RESULTADOS: Veintitrés pacientes se incluyeron; el 48% (11) de los cuales tuvieron VGV asociada a PMR. La localización fue heterogénea pero en su mayoría involucró a la aorta. En cuanto al tratamiento, se añadieron fármacos modificadores de la enfermedad a más del 80% de los pacientes con VGV. Los pacientes con VGV tenían niveles de PCR elevados comparado con aquellos con PMR aislada. CONCLUSIONES: La VGV en PMR no es infrecuente, tanto la clínica como los valores de PCR elevados deben hacer sospechar la posibilidad de VGV asociada. El estudio de imagen 18F-FDG PET/TC es una herramienta útil identificando VGV asociada a PMR

OBJECTIVE: Polymyalgia rheumatica (PR) can be associated with large vessel vasculitis (LVV). We evaluate the diagnostic role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and its impact on the treatment of LVV associated with PR. MATERIALS AND METHODS: Retrospective study of patients diagnosed with PR. Data was collected from health records. Blood analysis included acute-phase reactants (APR), C-reactive protein (CRP) and erythrocyte sedimentation rate. An 18F-FDG PET/CT scan was performed in those patients whose symptoms persisted, in those with elevated APR, those who required higher doses of steroids or those who had atypical features of PR (low-grade fever, weight loss, among others). RESULTS: Twenty-three were eligible; 48% (n = 11) of the patients were diagnosed with LVV associated with PR. The site was heterogeneous, but mostly involved the aorta. In 80% of the patients with LVV, a disease-modifying antirheumatic drug was added to their treatment. Elevated CRP values were associated with the likelihood of presenting LVV. CONCLUSIONS: LVV is not uncommon, clinical features and elevated CRP levels should raise suspicion of LVV associated with PR. 18F-FDG PET/CT is useful in identifying LVV associated with PR

18 F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with polymyalgia rheumatica: Screening for vasculitis. / 18 F-FDG PET/TC en pacientes con polimialgia reumática: despistando vasculitis.

OBJECTIVE: Polymyalgia rheumatica (PR) can be associated with large vessel vasculitis (LVV). We evaluate the diagnostic role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and its impact on the treatment of LVV associated with PR. MATERIALS AND METHODS: Retrospective study of patients diagnosed with PR. Data was collected from health records. Blood analysis included acute-phase reactants (APR), C-reactive protein (CRP) and erythrocyte sedimentation rate. An 18F-FDG PET/CT scan was performed in those patients whose symptoms persisted, in those with elevated APR, those who required higher doses of steroids or those who had atypical features of PR (low-grade fever, weight loss, among others). RESULTS: Twenty-three were eligible; 48% (n = 11) of the patients were diagnosed with LVV associated with PR. The site was heterogeneous, but mostly involved the aorta. In 80% of the patients with LVV, a disease-modifying antirheumatic drug was added to their treatment. Elevated CRP values were associated with the likelihood of presenting LVV. CONCLUSIONS: LVV is not uncommon, clinical features and elevated CRP levels should raise suspicion of LVV associated with PR. 18F-FDG PET/CT is useful in identifying LVV associated with PR.

Aumento de las concentraciones de interferón-1alpha, interleucina-10 y BLyS como biomarcadores de actividad clínica en el lupus eritematoso sistémico / Increased interferon-1alpha, interleukin-10 and BLyS concentrations as clinical activity biomarkers in systemic lupus erythematosus

Fundamento y objetivo: Analizar la asociación entre concentraciones de interferón-1alpha (INF1alpha), interleucina 10 (IL-10) y BLyS con la actividad clínica en el lupus eritematoso sistémico (LES). Pacientes y métodos: Estudio observacional transversal de 142 pacientes con LES y 34 controles sanos mediante analítica de sangre y orina y revisión de la historia clínica. La concentración sérica de citocinas se determinó mediante métodos colorimétricos. El análisis bioestadístico se realizó con R (3.3.2). Resultados: El 69% de pacientes mostraron al menos una citocina aumentada. Las tres citocinas están más elevadas en pacientes que en controles (p<0,001, p=0,005 y p=0,043), siendo INF1alpha el más frecuente. Los pacientes fueron categorizados según las concentraciones de las tres citocinas. Encontramos una asociación significativa entre concentraciones elevadas de IL-10/INF1alpha y una mayor actividad clínica según SELENA-SLEDAI (p<0,0001) y, en menor medida, con concentraciones aumentadas de INF1alpha/IL-10/BLyS. Concentraciones elevadas de IL-10/INF1alpha e INF1alpha/IL-10/BLyS se relacionaron con un mayor consumo de C3-C4 (p<0,001 y p=0,001) y títulos elevados de anti-dsDNA (p=0,001 y p=0,002). Concentraciones elevadas de INF1alpha/BLyS se relacionaron con títulos más altos de anti-dsDNA (p=0,004) y positividad ENA (p<0,001). Concentraciones altas de INF1alpha/IL-10/BLyS se relacionaron con la positividad de ANA (p<0,001) y anticuerpos antifosfolípidos (p=0,004). Conclusiones: INF1alpha, IL-10 y BLyS están más elevados en pacientes con LES que en controles sanos. El aumento de IL-10, asociado o no a aumento de BLyS y/o INF1alpha, es la citocina que mejor se ajusta a la actividad clínica del LES medida con métodos clásicos

Background and objective: to analyse the association between interferon-1alpha (INF1alpha), interleukin-10 (IL-10) and BLyS concentrations and clinical activity in systemic lupus erythematosus (SLE). Patients and methods: A cross-sectional, observational study of 142 SLE patients and 34 healthy controls was performed, through a complete blood and urine test and review of their medical history. Serum concentration of INF1alpha, IL-10 and BLyS was determined by colorimetric methods. A biostatistical analysis was performed with R (3.3.2.). Results: 69% of our SLE patients showed at least one cytokine increased. INF1alpha, IL-10 and BLyS are higher in SLE patients than in healthy controls (P<.001, P=.005 and P=.043, respectively), being INF1alpha the most frequent. Patients were categorised according to low or high concentrations of the three cytokines. We found a significant association between increased IL-10/INF1alpha concentrations and a higher clinical activity measured by SELENA-SLEDAI (P<.0001) and, to a lesser extent, an association with increased INF1alpha/IL-10/BLyS concentrations. Elevated levels of IL-10/INF1alpha and INF1alpha/IL-10/BLyS related to increased C3-C4 consumption (P<.001 and P=.001 respectively) and anti-dsDNA titres (P=.001 and P=.002 respectively). Elevated INF1alpha/BLyS related to higher anti-dsDNA titres (P=.004) and ENA positivity (P<.001). Increased levels of INF1alpha/IL-10/BLyS related to positivity of ANAs (P<.001) and APL (P=.004). Conclusions: INF1alpha, IL-10 and BLyS are higher in SLE patients than in healthy controls. Increased IL-10 levels, regardless of whether or not there were also increased levels of BLyS and/or INF1alpha, was the cytokine that best fit with clinical activity in SLE measured with classic methods