Addressing health disparities as a function of ethnicity in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disorder with significant health disparities, as it disproportionately and more severely affects vulnerable and disadvantaged population groups in the United States and around the world, that is, women, ethnic minorities, individuals living in poverty, less educated, and lacking medical insurance. Both, genetic and non-genetic factors, contribute to these disparities. To overcome these health disparities and reduce poor outcomes among disadvantaged SLE populations, interventions on non-genetic amendable factors, especially on social health determinants, are necessary.

Clinical and Serological Features in Latin American IgG4-Related Disease Patients Differ According to Sex, Ethnicity, and Clinical Phenotype.

BACKGROUND/OBJECTIVE: Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD. METHODS: We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation. RESULTS: The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance. CONCLUSIONS: Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype.

Does hydroxychloroquine improve patient reported outcomes in patients with lupus?

BACKGROUND: Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known. METHODS: International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity. RESULTS: Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: ß 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: ß 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: ß -9.37, 95% CI -12.24, -6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity. CONCLUSIONS: HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician's communication with decision-making regarding the use of HCQ for SLE management.

Reliability of OMERACT ultrasound elementary lesions in gout: results from a multicenter exercise.

The aim of this study was to evaluate the reliability of the outcome measures in rheumatology (OMERACT) definitions for ultrasound (US) elementary lesions in gout through an image reading exercise. Images from patients with gout (static images and videos) were collected. As an initial step, we carried out a image reading exercise within the experts of the Pan-American League of Associations for Rheumatology (PANLAR) US Study Group (n = 16). The following step consisted in a web-based exercise with the participation of larger number of sonographers (n = 63) from different centers. Images were rated evaluating the presence/absence of any US elementary lesion. Inter- and intra-reader reliabilities were analyzed using kappa coefficients. Participants were stratified according to their level of experience. In the first exercise, inter-reader kappa values were 0.45 for aggregates, 0.57 for tophus, 0.69 for erosions, and 0.90 for double contour (DC). Intra-reader kappa values were 0.86, 0.76, 0.80, and 0.90, respectively. The web-based exercise showed inter-reader kappa values for aggregates, tophus, erosions, and DC of 0.42, 0.49, 0.69, and 0.79, respectively. The intra-reader kappa values were 0.62, 0.69, 0.77, and 0.85, respectively. Reliability was not influenced by the sonographer's level of experience. The reliability of the new OMERACT US definitions for elementary lesions in gout ranged from moderate to excellent, depending on the type of lesion.

Prevalence and correlates of metabolic syndrome in patients with rheumatoid arthritis in Argentina.

BACKGROUND: The increased mortality reported among patient with rheumatoid arthritis (RA) has been attributed to cardiovascular disease. Metabolic syndrome (MS) is a cluster of major risk factors for cardiovascular disease such as dyslipidemia, obesity, hypertension, and diabetes. There is a lack of reporting on the prevalence of MS in RA patients in Argentina. OBJECTIVES: The objectives of this study were to determine and compare the frequency of MS in patients with RA and a control group and to assess the factors associated with MS. METHODS: This is a cross-sectional study involving 1033 (409 RA and 624 age- and sex-matched control subjects) patients, followed up at 9 different rheumatology units in Argentina. Metabolic syndrome was defined according to the Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF). The relationship between demographic variables, clinical data (disease duration, disease activity by Disease Activity Score of 28 joints, presence of rheumatoid factor [RF] and/or anti-cyclic citrullinated peptide antibody, presence of extra-articular manifestations), pharmacological treatment, and MS was examined by descriptive statistics. Variables with P ≤ 0.10 in these analyses were then examined by logistic regression. RESULTS: The frequency of MS in RA patients and the control group was 30% versus 39% (P = 0.002) when defined as per the ATP III and 35% versus 40% (P = 0.10) as per the IDF. Variables independently associated with MS in RA patients were age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06 [P = 0.01] for the ATP III and OR, 1.03; 95% CI, 1.01-1.05 [P < 0.001] for the IDF), the presence of RF and/or anti-cyclic citrullinated peptide antibody (OR, 2.91; 95% CI, 1.11-7.61 [P = 0.02] for the ATP III and OR, 2.37; 95% CI, 1.09-5.16 [P = 0.02] for the IDF), and the use of hydroxychloroquine (OR, 0.48; 95% CI, 0.23-0.97 [P = 0.04] only for the IDF). CONCLUSIONS: In this study, we were not able to demonstrate a higher frequency of MS in RA patients. However, older patients with positive RF or CCP have a higher risk of MS. A protective effect to develop MS was seen in the population treated with hydroxychloroquine.

[Prevalence of dyslipidemia and elevated cardiovascular risk in patients with rheumatoid arthritis]. / Prevalencia de dislipemia y riesgo cardiovascular elevado en pacientes con artritis reumatoide.

The objectives of this study were to compare the frequency of dyslipidemia (DLP) and the elevated cardiovascular risk between rheumatoid arthritis (RA) patients and a control group, to identify disease-related factors associated with the presence of DLP and to estimate the frequency of RA patients receiving treatment for DLP. This is a cross sectional study that included 409 RA patients and 624 controls. Cardiovascular (CV) risk was determined using the Framingham score, National Cholesterol Education Program (NCEP) and the Systematic Coronary Risk Evaluation (SCORE) adapted versions according to the European League Against Rheumatism (EULAR) guidelines. DLP was defined according to the Adult Treatment Panel III (ATPIII). The frequency of CV risk was similar in RA patients and controls, except when NCEP-EULAR adapted version for RA was applied (7% vs. 2%; p = 0.00002). A 43% of patients and 47% of controls had DLP (p = 0.15). RA patients with DLP tended to have extra-articular manifestations more frequently (36% vs. 24%; p = 0.01) and higher erythrocyte sedimentation rate (ESR) (21 [13-35] vs. 18 [10-30] mm; p = 0.003). RA patients treated for DLP varied between 11% and 32% according to the definition used. Patients with RA showed an elevated CV risk only when the NCEP-EULAR definition was used. Among RA patients, those with higher ESR and the presence of extra-articular manifestations were more likely to show DLP. The vast majority of patients were not receiving treatment for DLP.

[Relapse of lupus nephritis in temporal association with anti SARS-CoV-2 vaccination]. / Reactivación de glomerulonefritis lúpica en asociación temporal con vacunas anti SARS-CoV-2.

During the past two years we have witness a tremendous worldwide health crisis imposed by the coronavirus disease (COVID-19). This situation led to the urgent development and implementation of vaccines in an attempt to decrease not only the SARS-CoV-2 transmissibility but also the severe forms of COVID-19. Although these vaccines were approved based on an adequate benefit-risk ratio, at the moment of their implementation in 2021 we did not have sub-studies in special populations; patients with systemic lupus erythematosus (SLE) among them. We describe two cases of lupus nephritis flare following the immunization against SARS-CoV-2 with the first component of Sputnik V and Sinopharm. Both patients were in complete remission on maintenance therapy with mycophenolate and without glucocorticoids. The flare presented with an increased protein/creatinine ratio in urine and positive anti-DNA antibodies without other relevant accompanying findings. After treatment with prednisone (20 y 10 mg/day in case 1 and 2, respectively) and an increased dose of mycophenolate (from 1.5 g/day to 2.0 g/dayand 1.08 to 1.44 g/día of sodic mycophenolate in case 1 y 2, respectively) both patients regained renal remission. These cases are of relevance as they introduce a possible association between the different anti-SARS-CoV-2 vaccine platforms and SLE flares; at the same time to suggest the need for close control in the post vaccination period in this population of patients.

Debido el alto impacto sanitario que causó el nuevo coronavirus SARS-CoV-2, se procedió al rápido desarrollo e implementación de vacunas en un intento de disminuir su transmisibilidad y las formas graves de la COVID 19. La aprobación de estas vacunas se basó en una adecuada relación riesgo/beneficio, sin embargo, en el año 2021 no disponíamos de sub-estudios en poblaciones especiales; entre ellas, pacientes con lupus eritematoso sistémico (LES). Presentamos dos casos de brote de glomerulonefritis lúpica luego de la inmunización contra SARS-CoV-2 dado por el primer componente de Sputnik V y Sinopharm. Ambas pacientes se encontraban en remisión completa con tratamiento de mantenimiento en dosis estables de micofenolato y libre de glucocorticoides. El brote de glomerulonefritis se presentó con aumento de relación proteinuria/creatininuria y anticuerpos anti ADN positivos sin otros hallazgos acompañantes de relevancia. En ambas pacientes se reinició prednisona (20 y 10 mg/día en caso 1 y 2, respectivamente) y se aumentó la dosis de micofenolato (de 1.5 g/día a 2.0 g/día y de 1.08 a 1.44 g/día de micofenolato sódico en caso 1 y 2, respectivamente) con remisión completa del cuadro. Estos casos son de relevancia ya que introducen una posible asociación entre las diferentes plataformas vacunales anti SARS-CoV-2 y reactivación del LES, a la vez de sugerir la necesidad de un control estrecho en el período post-vacunal en esta población de pacientes.

An Argentinean cohort of patients with rheumatic and immune-mediated diseases vaccinated for SARS-CoV-2: the SAR-CoVAC Registry-protocol and preliminary data.

BACKGROUND/OBJECTIVE: To evaluate the efficacy and safety of SARS-CoV-2 vaccine in patients with rheumatic and immune-mediated inflammatory diseases (IMIDs) in Argentina: the SAR-CoVAC registry. METHODS: SAR-CoVAC is a national, multicenter, and observational registry. Adult patients with rheumatic or IMIDs vaccinated for SARS-CoV-2 were consecutively included between June 1 and September 17, 2021. Sociodemographic data, comorbidities, underlying rheumatic or IMIDs, treatments received, their modification prior to vaccination, and history of SARS-CoV-2 infection were recorded. In addition, date and place of vaccination, type of vaccine applied, scheme, adverse events (AE), disease flares, and new immune-mediated manifestations related to the vaccine were analyzed. RESULTS: A total of 1234 patients were included, 79% were female, with a mean age of 57.8 (SD 14.1) years. The most frequent diseases were rheumatoid arthritis (41.2%), osteoarthritis (14.5%), psoriasis (12.7%), and spondyloarthritis (12.3%). Most of them were in remission (28.5%) or low disease activity (41.4%). At the time of vaccination, 21% were receiving glucocorticoid treatment, 35.7% methotrexate, 29.7% biological (b) disease modifying anti-rheumatic drugs (DMARD), and 5.4% JAK inhibitors. In total, 16.9% had SARS-CoV-2 infection before the first vaccine dose. Most patients (51.1%) received Gam-COVID-Vac as the first vaccine dose, followed by ChAdOx1 nCoV-19 (32.8%) and BBIBP-CorV (14.5%). Half of them (48.8%) were fully vaccinated with 2 doses; 12.5% received combined schemes, being the most frequent Gam-COVID-Vac/mRAN-1273. The median time between doses was 51 days (IQR 53). After the first dose, 25.9% of the patients reported at least one AE and 15.9% after the second, being flu-like syndrome and local hypersensitivity the most frequent manifestations. There was one case of anaphylaxis. Regarding efficacy, 63 events of SARS-CoV-2 infection were reported after vaccination, 19% occurred during the first 14 days post-vaccination, 57.1% after the first dose, and 23.8% after the second. Most cases (85.9%) were asymptomatic or mild and 2 died due to COVID-19. CONCLUSIONS: In this national cohort of patients, the most common vaccines used were Gam-COVID-Vac and ChAdOx1 nCoV-19. A quarter of the patients presented an AE and 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild. STUDY REGISTRATION: This study has been registered in ClinicalTrials.gov under the number: NCT04845997. Key Points • This study shows real-world data about efficacy and safety of SARS-CoV-2 vaccination in patients with rheumatic and immune-mediated inflammatory diseases. Interestingly, different types of vaccines were used including vector-based, mRNA, and inactivated vaccines, and mixed regimens were enabled. • A quarter of the patients presented an adverse event. The incidence of adverse events was significantly higher in those receiving mRAN-1273 and ChAdOx1 nCoV-19. • In this cohort, 5.1% presented SARS-CoV-2 infection after vaccination, in most cases mild.

Sex Differences in Quality of Life in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) predominantly affects women. Clinical phenotype and outcomes in SLE may vary by sex and are further complicated by unique concerns that are dependent upon sex-defined roles. We aimed to describe sex differences in disease-specific quality of life (QoL) assessment scores using the Lupus Patient-Reported Outcome (LupusPRO) tool in a large international study. METHODS: Cross-sectional data from 1,803 patients with SLE on demographics, self-identified sex status, LupusPRO, and disease activity were analyzed. The LupusPRO tool has 2 constructs: health-related QoL (HRQoL) and non-HRQoL. Disease activity and damage were evaluated using the Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, respectively. Nonparametric tests were used to compare QoL and disease activity by sex. RESULTS: A total of 122 men and 1,681 women with SLE participated. The mean age was similar by sex, but the damage scores were greater among men. Men fared worse on the non-HRQoL social support domain than women (P = 0.02). When comparing disease and QoL among men and women ages ≤45 years, men were found to have greater damage and worse social support than women. However, women fared significantly worse on lupus symptoms, cognition, and procreation domains with trends for worse functioning on physical health and pain-vitality domains. CONCLUSION: In the largest study of a diverse group of SLE patients, utilizing a disease-specific QoL tool, sex differences in QoL were observed on both HRQoL and non-HRQoL constructs. Although men performed worse in the social support domain, women (especially those in the reproductive age group) fared worse in other domains. These observations may assist physicians in appropriately addressing QoL issues in a sex-focused manner.

Drivers of Satisfaction With Care for Patients With Lupus.

OBJECTIVE: Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE. METHODS: A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA-SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors. RESULTS: The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC. CONCLUSION: Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes.

Rate and causes of infliximab discontinuation in patients with rheumatoid arthritis in a private clinical practice.

OBJECTIVES: To describe the rate of infliximab discontinuation and the causes of this event in a population of rheumatoid arthritis patients. PATIENTS AND METHODS: Rheumatoid arthritis patients from an out-patient private center treated with infliximab (at least 2 consecutive doses) were retrospectively studied. The infliximab discontinuation rate was examined by the Kaplan-Meier survival method. Variables associated with infliximab discontinuation were analyzed by univariable and multivariable Cox proportional hazards regression analyses. RESULTS: Seventy-seven patients treated with infliximab between August 2000 and December 2006 were identified; of them, 33 (43%) discontinued this drug. The cumulative discontinuation rate was of 23%, 35%, and 43% at 12, 24, and 36 months, respectively. Causes of discontinuation were drug-related adverse reactions (41%), financial constraints (15%), lack of efficacy (12%), and others (32%). Variables independently associated with infliximab discontinuation were the number of tender joints on an average during infliximab treatment [hazard ratio (HR) = 1.17, 95% confidence interval (CI) 1.05-1.31; P = 0.005] and the occurrence of any adverse reaction attributed to infliximab (HR = 2.86, 95% CI 1.37-7.19; P = 0.026), whereas having full pharmacy coverage for infliximab (HR = 0.32, 95% CI 0.13-0.79, P = 0.014) was protective. CONCLUSION: Forty-three percent of patients discontinued infliximab at 3 years; most of them because of adverse reactions and financial constraints. Rheumatologists should be aware that those patients with more active disease were also at higher risk of discontinuing infliximab.

Lack of correlation between satisfaction and knowledge in clinical trials participants: a pilot study.

OBJECTIVES: To address participants' knowledge of informed consent and to explore whether knowledge level is related to clinical trial satisfaction. METHODS: One hundred and fourteen patients enrolled in three ongoing randomized controlled trials of osteoarthritis and rheumatoid arthritis were asked to complete a mailed form. The survey was related to aspects of the informed consent process: quality of information given during the informed consent process, participants' self perception of knowledge, objective evaluation of participants' knowledge and participants' overall trial satisfaction. These four aspects were categorized as high, intermediate or low. Correlation between participants' knowledge and satisfaction was measured using the Spearman's Rho test and variables associated with knowledge by standard univariable analyses. A p value< or =0.05 was considered significant. RESULTS: One hundred and five participants answered the questionnaire. The quality of information given during the informed consent process was rated as being high by 81% participants, intermediate by 15.2% and low by 3.8%. Fifty-one percent of the participants believed they had a good level of knowledge, but, objective evaluation qualified as high in only 14.3% of them. Overall trial satisfaction was high in 95% of the participants. No significant correlation was found between knowledge and satisfaction (r=0.16; p=0.086). Age was negatively associated with a higher level of knowledge (48 vs. 58 years old, p=0.008). CONCLUSIONS: We found a lack of correlation between satisfaction and knowledge in clinical trials participants. During a randomized controlled trial the investigator should consider encouraging activities to improve not only participants' satisfaction, but also their level of knowledge.

Reactivación de glomerulonefritis lúpica en asociación temporal con vacunas anti SARS-CoV-2 / Relapse of lupus nephritis in temporal association with anti SARS-CoV-2 vaccination

Resumen Debido el alto impacto sanitario que causó el nuevo coronavirus SARS-CoV-2, se procedió al rápido desarrollo e implementación de vacunas en un intento de disminuir su transmisibilidad y las formas graves de la COVID 19. La aprobación de estas vacunas se basó en una adecuada relación riesgo/beneficio, sin embargo, en el año 2021 no disponíamos de sub-estudios en poblaciones especiales; entre ellas, pacientes con lupus eritematoso sistémico (LES). Presentamos dos casos de brote de glomerulonefritis lúpica luego de la inmunización contra SARS-CoV-2 dado por el primer componente de Sputnik V y Sinopharm. Ambas pacientes se encontraban en remisión completa con tratamiento de mantenimiento en dosis estables de micofenolato y libre de glucocorticoides. El brote de glomerulonefritis se presentó con aumento de relación proteinuria/creati ninuria y anticuerpos anti ADN positivos sin otros hallazgos acompañantes de relevancia. En ambas pacientes se reinició prednisona (20 y 10 mg/día en caso 1 y 2, respectivamente) y se aumentó la dosis de micofenolato (de 1.5 g/día a 2.0 g/día y de 1.08 a 1.44 g/día de micofenolato sódico en caso 1 y 2, respectivamente) con remisión completa del cuadro. Estos casos son de relevancia ya que introducen una posible asociación entre las diferentes plataformas vacunales anti SARS-CoV-2 y reactivación del LES, a la vez de sugerir la necesidad de un control estrecho en el período post-vacunal en esta población de pacientes.

Abstract During the past two years we have witness a tremendous worldwide health crisis imposed by the coronavirus disease (COVID-19). This situation led to the urgent development and implementation of vac cines in an attempt to decrease not only the SARS-CoV-2 transmissibility but also the severe forms of CO VID-19. Although these vaccines were approved based on an adequate benefit-risk ratio, at the moment of their implementation in 2021 we did not have sub-studies in special populations; patients with systemic lupus erythematosus (SLE) among them. We describe two cases of lupus nephritis flare following the immunization against SARS-CoV-2 with the first component of Sputnik V and Sinopharm. Both patients were in complete remission on maintenance therapy with mycophenolate and without glucocorticoids. The flare presented with an increased protein/creatinine ratio in urine and positive anti-DNA antibodies without other relevant ac companying findings. After treatment with prednisone (20 y 10 mg/day in case 1 and 2, respectively) and an increased dose of mycophenolate (from 1.5 g/day to 2.0 g/dayand 1.08 to 1.44 g/día of sodic mycophenolate in case 1 y 2, respectively) both patients regained renal remission. These cases are of relevance as they intro duce a possible association between the different anti-SARS-CoV-2 vaccine platforms and SLE flares; at the same time to suggest the need for close control in the post vaccination period in this population of patients.

Riesgo de fracturas en pacientes con enfermedades reumáticas en tratamiento con corticoides orales crónicos / Risk of fractures in patients with rheumatic diseases in treatment with chronic oral corticosteroids

INTRODUCCIÓN: El tratamiento con glucocorticoides es necesario como puente de otros fármacos en el tratamiento de las enfermedades reumáticas. Evaluar el riesgo de fracturas en pacientes con enfermedades reumáticas en tratamiento crónico con glucocorticoides nos permite instaurar tratamiento a tiempo para prevenir esta complicación con alto impacto en la calidad de vida. OBJETIVO: Evaluar el riesgo de fracturas en pacientes con enfermedades reumáticas expuestos a uso crónico de corticoides orales en una clínica privada de Córdoba. MATERIAL Y MÉTODO: Estudio observacional, retrospectivo, de casos y controles, analítico. Se evaluaron los pacientes, mayores de 18 años, ambulatorios, con diagnóstico de enfermedades reumáticas en tratamiento con corticoides orales (dosis >5 mg de prednisona o equivalente) por al menos tres meses, mediante revisión de historias clínicas en Clínica Universitaria Reina Fabiola. Las características de la muestra de pacientes se reportaron con estadística descriptiva. Las variables asociadas a la presencia de fracturas se analizaron con regresión logística uní y multivariada, el nivel de significancia asignado fue p<0.05. El análisis estadístico se realizó mediante el programa SPSS1 22.0. RESULTADOS: La muestra estuvo conformada por un total de 110 pacientes, de los cuales 56 presentaban diagnóstico de enfermedades reumáticas y 55 controles. Los pacientes tenían una edad media (desviación estándar - DE) de 58.95 (14.51) años, de ellos en su mayoría fueron del sexo femenino 94 (85.5 %). Entre los pacientes con enfermedad reumática los diagnósticos fueron: artritis reumatoide 38 (35%), artritis seronegativas 7 (7%), lupus eritematoso sistémico 7 (7%), polimialgia reumática 2 (2%) y vasculitis 1 (0.9%). Cincuenta y seis pacientes recibieron terapia con corticoides, de los cuales 43 (39%) tenían una dosis media 2.5 -7.5 mg/día, 9 (8%) dosis alta > 7.5 mg/día y 4 (3.5%) una dosis baja menos de 2.5 mg/día. En cuanto al tiempo de tratamiento tuvieron una Me de 2.5 meses IRC 18 meses. La presencia de fracturas se encontró en 22 (20%) pacientes en el total de la muestra a los 18 meses. En el grupo de pacientes con corticoides orales y enfermedad reumática, la presencia de fracturas vertebrales fue de 9 (16%) y de fracturas no vertebrales de 8 (14.2%), mientras que en el grupo control hubo sólo 1 (1.8%) fractura vertebral y 4 (7.4%) no vertebrales. En relación a las variables asociadas a riesgo de fracturas en el análisis multivariado se encontró que tanto la edad 1.06 (IC 95%= 1.02-1.11), el tiempo de tratamiento con corticoides 1.02 (IC 95% 1.00-1.04) y la presencia de enfermedad reumática 1.85 (IC 95% 1.06-3.22) aumentan el riesgo relativo de fracturas. En cuanto a la presencia de fracturas vertebrales las variables asociadas al aumento del riesgo relativo fueron la edad 1.12 (IC 95% 1.03-1.20), la dosis de corticoides orales 5.84 (IC 95% 1.84-18.55) ), siendo las dosis altas las que mostraron diferencia significativas con un OR 6.58 (IC 95% 1.33-20.68) y el índice de masa corporal bajo 80.15 (IC 95% 3.18-216.63) y en las no vertebrales fueron la edad 1.03 (IC 95% 1.00-1.08) y el tiempo de tratamiento con corticoides 1.02 (IC 95% 1.00-1.04). CONCLUSIONES: La OP inducida por glucocorticoides es la causa más frecuente de OP secundaria, y se asocia a la presencia de fracturas hasta en un 30-50% de casos. El riesgo de fracturas depende de factores como edad, DMO previa, dosis diaria y acumulada de glucocorticoides y enfermedad subyacente. Nuestro estudio demuestra que la terapia crónica con glucocorticoides aumento el riesgo de fracturas con un OR 1.02, asociadas con el aumento de la edad OR 1.06 y la presencia de enfermedad reumática OR 1.85. Siendo las dosis altas mayores a 7.5 mg/día y el IMC bajo las variables independientes asociadas a riesgo de fractura vertebral.

INTRODUCTION: Glucocorticoid treatment is necessary as a bridge for other drugs in the treatment of rheumatic diseases. Assessing the risk of fractures in patients with rheumatic diseases in chronic glucocorticoid treatment allow us to establish treatment in time to prevent this complication with a high impact on the quality of life. OBJECTIVES: To evaluat the risk of fractures in patients with rheumatic diseases exposed to chronic use of oral corticosteroids in a private hospital in Córdoba. MATERIAL AND METHODS: Observational, retrospective, case-control study, analytical. Patients, over 18 years of age, outpatient, with a diagnosis of rheumatic diseases treated with oral corticosteroids (doses> 5 mg of prednisone or equivalent) for at least three months, will be evaluated by reviewing medical records at the Clínica Universitaria Reina Fabiola. The characteristics of the patient sample were reported with descriptive statistics. The variables associated with the presence of fractures were analyzed with uni and multivariate logistic regression, the level of significance assigned was p <0.05. Statistical analysis was performed using the SPSS1 22.0 program. RESULTS: The sample consisted of a total of 110 patients, of which 56 had a diagnosis of rheumatic diseases and 55 controls. The patients had a mean age (standard deviation - SD) of 58.95 (14.51) years, most of them female 94 (85.5%). Among the patients with rheumatic disease the diagnoses were: rheumatoid arthritis 38 (35%), seronegative arthritis 7 (7%), systemic lupus erythematosus 7 (7%), polymyalgia rheumatica 2 (2%) and vasculitis 1 (0.9%). Fifty-six patients received corticosteroid therapy, of which 43 (39%) had a medium dose 2.5 -7.5 mg / day, 9 (8%) high dose> 7.5 mg / day and 4 (3.5%) a lower dose less 2.5 mg / day. As for the treatment time, they had a 2.5-month IQR 18 months. The presence of fractures was found in 22 (20%) patients in the total sample at 18 months. In the group of patients with oral corticosteroids and rheumatic disease, the presence of vertebral fractures was 9 (16%) and non-vertebral fractures of 8 (14.2%), while in the control group there was only 1 (1.8%) fracture vertebral and 4 (7.4%) non-vertebral. Regarding the variables associated with fracture risk in the multivariate analysis, it was found that both age 1.06 (95% CI = 1.02-1.11), time of treatment with corticosteroids 1.02 (95% CI 1.00-1.04) and the presence of rheumatic disease 1.85 (95% CI 1.06-3.22) increase the relative risk of fractures. Regarding the presence of vertebral fractures, the variables associated with the increase in relative risk were age 1.12 (95% CI 1.03-1.20), the dose of oral corticosteroids 5.84 (95% CI 1.84-18.55), with high doses being that showed significant difference with an OR 6.58 (95% CI 1.33-20.68) and body mass index under 80.15 (95% CI 3.18-216.63) and in non-vertebral patients were age 1.03 (95% CI 1.00-1.08) and the time of treatment with corticosteroids 1.02 (95% CI 1.00-1.04). CONCLUSIONS: Glucocorticoid-induced OP is the most frequent cause of secondary OP, and is associated with the presence of fractures in up to 30-50% of cases. The risk of fractures depends on factors such as age, previous BMD, daily and cumulative dose of glucocorticoids and underlying disease. Our study demonstrates that chronic glucocorticoid therapy increases the risk of fractures with an OR 1.02, associated with increasing OR 1.06 age and the presence of OR 1.85 rheumatic disease. The high doses being greater than 7.5 mg / day and the BMI under the independent variables associated with the risk of vertebral fracture.

Preconception, pregnancy, and lactation in systemic lupus erythematosus patients / Preconcepción, embarazo y lactancia en pacientes con lupus eritematoso sistémico

ABSTRACT Systemic lupus erythematosus is a complex and chronic disease which impacts on the reproductive function of patients suffering this condition. This assertion is supported by the fact that lupus patients have a smaller family size in comparison to the general population as well as a higher risk of adverse pregnancy outcomes. While this disease per se does not affect fertility, there are several other factors affecting fertility such as age, drugs, disease activity, damage-related disease, and some comorbidities. Currently, there are several interventions to preserve fertility with very good outcomes, among them, cryopreservation or the use of gonadotropin releasing hormone agonists. It is recommended that lupus patients be in low disease activity or in remission for at least six months before conception and pregnancy. If the latter is achieved, multidisciplinary management is very important and recommended, but in particular, physicians must know how to differentiate between a lupus flare and pregnancy-related hypertension. The efficacy and safety of antimalarials throughout pregnancy has been demonstrated so its use must be continued and encouraged. Taking into account all the above, fertility and pregnancy in lupus patients must be an integral part of the management of this disease.

RESUMEN El lupus eritematoso sistémico es una enfermedad compleja y crónica que afecta la función reproductiva de los pacientes que la presentan, considerando que suelen tener un tamaño familiar reducido en comparación con la población general, así como un riesgo más alto de resultados adversos perinatales. Si bien esta enfermedad per se no afecta la fertilidad, existen otros factores que la alteran, como la edad, los fármacos, la actividad de la enfermedad, el dano relacionado con ella y algunas comorbilidades. En la actualidad, existen numerosas intervenciones para preservar la fertilidad, con muy buenos resultados, entre las cuales se encuentran la criopreservación o el uso de análogos de la hormona liberadora de gonadotropinas. Es recomendable que los pacientes lúpicos se encuentren en baja actividad de la enfermedad o en remisión por al menos seis meses antes de la concepción y el embarazo. Si esto se logra, el manejo multidisciplinario es muy importante y recomendado pero, sobre todo, los médicos deben saber cómo diferenciar entre reactivación de la enfermedad y enfermedad hipertensiva del embarazo. Se ha demostrado la eficacia y la seguridad de los antimaláricos a lo largo del embarazo, por lo cual su uso debe ser continuado y aconsejado. Teniendo en cuenta lo señalado en las líneas precedentes, la fertilidad y el embarazo en pacientes lúpicos deben ser parte del manejo integral de esta enfermedad.

Tendon involvement in patients with gout: an ultrasound study of prevalence.

The objective of the present study is to evaluate, by ultrasonography (US), the prevalence in the quadriceps, patellar, and Achilles tendon involvement of gout compared to that of patients with osteoarthritis and asymptomatic marathon runners. This is a multicenter, multinational, transverse cross-sectional, and comparative study comprising 80 patients with the diagnosis of gout according to the American College of Rheumatology (ACR) criteria, compared with two control groups: 35 patients with generalized osteoarthritis according to the ACR criteria and 35 subjects who were healthy marathon runners. Demographics and clinical characteristics, such as age, gender, comorbidity, disease duration, pain at the enthesis in the knee and ankle, frequency of disease exacerbations, uric acid level more than 7.2 mg at the time of evaluation, and type of treatment, were recorded. All participants were examined by ultrasound at the quadriceps, the patellar at its proximal and distal insertion, and the Achilles tendon to detect intra-tendinous tophus or aggregates according to the OMERACT definitions. Descriptive statistics and differences between groups were analyzed by chi-square test. Sensitivity and specificity by US were calculated. The prevalence of intra-tendinous aggregates and tophi in gout was significant compared with the other groups. Both lesions were the most frequent at the distal patellar insertion, followed by the quadriceps, Achilles, and proximal patellar insertion ones. In patients with osteoarthritis (OA), intra-tendinous hyperechoic aggregates were observed in 20 % of quadriceps tendons and in 11 % of patellar tendons at its proximal insertion, while in the healthy marathon runner group, the Achilles tendon had this kind of lesion in 17 % of the subjects. Neither the OA nor the healthy marathon runners had intra-tendinous tophi. The sensitivity and specificity of US to detect tophi or aggregates were 69.6 and 92 %, respectively, tendon involvement at the lower limbs in gout is very frequent, particularly in the patellar tendon, and US possesses good sensitivity and specificity for detecting intra-tendinous tophi.

Factors associated with patients' loss to follow-up after finishing randomized clinical trial participation.

OBJECTIVES: To study patient's follow-up after finishing participation in randomized clinical trials (RCTs), and to identify factors associated with loss to follow-up (FU). PATIENTS AND METHODS: Medical charts of 212 rheumatoid arthritis (RA) and osteoarthritis (OA) patients from a rheumatological out-patient center were analyzed. Loss to FU was considered when patients did not return to their regular appointments within the first year after finishing their participation in an RCT assessing anti-cyclooxygenase-2 non-steroidal anti-inflammatory drugs (anti-COX-2 NSAIDs). Mann-Whitney U-test, chi2 test and Wilcoxon test were performed as appropriate. Logistic regression was performed to identify factors which might be related to loss to FU. A survey was conducted to obtain lost to FU patients' opinions. p values less than 0.05 were considered significant. RESULTS: The mean frequency of patients' visits in the year before enrollment in an RCT was 3.73 SD 2.06, and during the year after participation was 2.6 SD 1.96 (p<0.0001). Fifty patients (23.6%) did not return to their usual rheumatologic visit. On multivariate analysis, the number of daily tablets of study medication (odds ratio (OR)=2.64, 95% confidence interval (CI) 1.1 to 6.3) and the frequency of clinical visits (OR=0.56, 95% CI 0.37 to 0.85) were associated with loss to FU (p<0.008). Lost to FU patients' opinions did not support these findings. CONCLUSIONS: After participating in a RCT assessing anti-COX-2 NSAIDs, many patients return with less frequency, or do not return at all to their regular rheumatologic visit. Although a high number of tablets of the investigational drug and a low frequency of protocol visits may be contributors to patient loss to FU, investigators should consider that personal situations not related to the RCTs may also influence patients' return to consultation in the private setting.

[Use of infliximab in patients of a rheumatologic center]. / Uso de infliximab en pacientes de un centro reumatológico.

The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9%) patients could decrease the doses of corticosteroids, 15/43 (34.8%) decreased the doses of antiinflammatory drugs and 12/34 (35.3%) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.

[Severe polyarthritis and tenosynovitis due to Streptococcus agalactiae in a patient with functional hyposplenia]. / Poliartritis y tenosinovitis grave por Streptococcus agalactiae en un paciente con hipoesplenia funcional.

Cases of arthritis caused by Streptococcus agalactiae are infrequent and in our knowledge there are no case reports of tenosynovitis caused by S. agalactiae. A 46-year-old woman presented with fever, polyarthralgia, myalgia, diarrhea and vomiting. She had a history of papillary thyroid carcinoma and functional hyposplenia. She was febrile, with arthritis in hands, wrists, elbows, right shoulder and left ankle joints, and presented tenosynovitis in both feet and left hand. Blood and right olecranon bursa sample cultures were positive for S. agalactiae. An ultrasound scan made at the musculus tibialis anterior of left foot revealed signs of tenosynovitis. She was treated with intravenous cefazolin for 20 days and oral cefuroxime for 12 days. The joint involvement completely subsided in 60 days. Streptococcus agalactiae can cause, infrequently, a polyarthritis and tenosynovitis syndrome similar to disseminated gonococcal infection.

[Mucocutaneous lesions in patients with systemic lupus erythematosus]. / Manifestaciones mucocutáneas en pacientes con lupus eritematoso sistémico.

The objective was to analyze the prevalence of mucocutaneous lesions in patients with systemic lupus erythematosus (SLE). During a 3-year period, we analyzed 77 patients with a diagnosis of SLE. The mucocutaneous lesions were classified into specific and non-specific. We defined skin type, sunlight exposure and photoprotection and correlated these lesions with serology and disease activity. Acute specific lesions were found in 67.5% of the patients, subacute lupus in 6.5% and chronic lesions in 26.0%. The most prevalent non-specific lesions were alopecia (59.7%), photosensitivity (57.1%), Raynaud's syndrome (46.7%), oral ulcerations (15.6%) and livedo reticularis (11.7%). Skin type 3 (35%) and exposure to mild ultraviolet radiation (74%) were seen in the majority of the patients. Appropriate sunlight protection was only used by 47% of the patients. When dermatological lesions and serology were compared, we found a significant association between malar rash, photosensitivity, livedo reticularis and alopecia with the presence of anti-Ro and Raynaud's phenomenon in patients with positive anti-Sm. The presence of malar rash, photosensitivity, Raynaud's phenomenon, diffuse alopecia and livedo reticularis was more frequent among patients with active disease. The prevalence of mucocutaneous manifestation in our population was slightly higher than data reported in other series. The presence of malar rash, diffuse alopecia, photosensitivity and livedo reticularis significantly related with the presence of anti-Ro and Raynaud's phenomenon with anti-Sm. All these lesions were more frequently seen in patients with active disease.