Multicenter lupus register from Argentina, the RELESSAR database: Influence of ethnicity on disease phenotype.

OBJECTIVE: The objective is to describe the main characteristics of patients with systemic lupus erythematosus (SLE) in Argentina and to examine the influence of ethnicity on the expression of the disease. PATIENTS AND METHODS: RELESSAR is a multicentre register carried out by 106 researchers from 67 rheumatologic Argentine centres. It is a cross-sectional study of SLE (1982/1997 ACR) patients. RELESSAR electronic database includes demographic, cumulative SLE manifestations, SELENA-SLEDAI, SLICC-SDI, Katz's severity and Charlson's comorbidity indexes and treatment patterns. RESULTS: We included 1,610 patients, 91.7% were female with a median age at diagnosis of 28.1 ± 12.8; 96.2% met ≥4 ACR 1982/97 criteria. Frequent manifestations were arthritis (83.5%), malar rash (79.5%), photosensitivity (75.3%), haematological (63.8%) and renal disease (47.4%), antinuclear antibodies (96%), anti-dsDNA (66.5%) and anti-Smith antibodies (29%). The mean Selena-SLEDAI score at last visit was 3.18 (SD 4.3) and mean SDI was 1 (SD 1.3). The accumulated treatments most frequently used were antimalarials (90.4%), corticosteroids (90%), azathioprine (31.8%), intravenous cyclophosphamide (30.2%), mycophenolate mofetil or mycophenolic acid (24.5%), methotrexate (19.3%), belimumab 5.3% and rituximab 5.1%. Refractory lupus was diagnosed in 9.3% of the cases. The main causes of death were lupus activity (25.0%), activity and concomitant infections (25.0%), infections (18.2%), vascular disease (13.6%) and cancer (4.5%). Mortality was associated with higher SLEDAI, Katz, damage indexes and comorbidities. Of the 1610 patients included, 44.6% were Caucasian, 44.5% Mestizo, 8.1% Amerindian and 1.2% Afro-Latin American. Mestizo patients had higher male representation, low socioeconomic status, more inadequate medical coverage, fewer formal years of education and shorter disease duration. Polyadenopathies and Raynaud's phenomenon were more frequent in Caucasians. In the logistic regression analysis higher damage index (OR 1.28, CI 95% 1.02-1.61, p = 0.03) remained associated to mestizo ethnicity. CONCLUSIONS: This study represents the largest number of adult patients with SLE studied in Argentina. Caucasian patients were differentiated by having Raynaud's phenomenon and polyadenopathy more frequently, while patients of Mestizo origin had higher damage indexes.

Analysis of 65 Renal Biopsies From Patients With Rheumatoid Arthritis (1976-2015): Change in Treatment Strategies Decreased Frequency and Modified Histopathological Findings.

INTRODUCTION: No inherent renal lesions are known in rheumatoid arthritis (RA), but urinary abnormalities and renal dysfunction have been described. OBJECTIVE: First, we describe the histopathological findings of renal biopsies (RBs) in patients with RA and associated clinical manifestations. Second, we evaluated time evolution of RA and the relationship between drugs and renal disease. Last, we investigate whether changes in the management of RA from 1976 to 2015 influenced RBs indication, frequency, and type of histopathological findings. PATIENTS AND METHODS: This is a retrospective and observational study conducted at a university hospital from Argentina. Patients with a diagnosis of RA (ACR, 1987) and RBs between 1976 and 2015 were included. Sixty-five patients met the inclusion criteria. The histopathological findings and associated clinical manifestations were evaluated. Time evolution of RA and the relationship between drugs and renal disease were also determined. To clarify these issues, we characterized 3 groups according to changes in the management of RA: 1976-1989, 1990-2002, and 2003-2015. RESULTS: The most common histopathological finding was renal amyloidosis in 31% (n = 20), followed by mesangial glomerulonephritis in 18% (n = 12), membranous nephropathy in 17% (n = 11), extracapillary proliferative glomerulonephritis in 15% (n = 10), focal segmental glomerular sclerosis in 9% (n = 6), minimal change nephropathy in 5% (n = 3), and tubulointerstitial nephritis in 5% (n = 3). Time evolution of renal amyloidosis was significantly higher than other RBs (15 ± 12 vs 7 ± 6.5 years). Nephrotic syndrome was the most common clinical manifestation (60%) followed by hematuria (46%) with or without proteinuria. Membranous nephropathy was related to the use of gold salts in 45% of cases, and its frequency decreased since 1990. Before 2003, renal amyloidosis was the leading cause of kidney disease, but mesangial glomerulonephritis reached the same frequency between 2003 and 2015. We found that RBs decreased 20% in the second period (1990-2002) and 40% in the last period (2003-2015). Nephrotic syndrome remained the main RB indication during the entire study period. CONCLUSION: This is the first report on RBs findings in patients with RA from Latin America. We found a significant reduction in RBs frequency and modified histological patterns throughout the study period, although RB indication was not modified. Changes in the management of RA might have influenced these findings.

[Shrinking lung syndrome in systemic lupus erythematosus: A study of 9 patients]. / Síndrome del pulmón encogido asociado a lupus eritematoso sistémico: estudio de 9 pacientes.

INTRODUCTION: Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. Our aim was to describe the clinical, radiological, and functional characteristics of a cohort with SLS and its evolution over time. METHODS: A retrospective study was conducted between 2009 and 2018. Demographic, clinical, functional, radiological, and treatment data were collected. RESULTS: Out of a total of 225 patients, 11 presented with SLS (prevalence of 4.8%). Two patients were excluded. The mean age was 39.33±16 years, and 6 were female. The main symptoms were dyspnea and pleuritic pain. The mean forced vital capacity was 49%, total lung capacity was 60%, carbon monoxide diffusing capacity was 66%, carbon monoxide transference factor was 128%, maximal inspiratory pressure was 66%, and maximal expiratory pressure was 82%. All patients received corticosteroids. After a median follow-up of 19 months, 4 cases showed improvement, and 4 cases remained stable. CONCLUSIONS: SLS should be considered in every lupus patient with unexplained dyspnea. Although it often shows improvement, many cases experience persistent deterioration despite treatment.

Description of a single centre cohort of patients with systemic sclerosis from the University Hospital of Buenos Aires and factors associated with lung function deterioration. A retrospective study.

INTRODUCTION: Given the paucity of data in Latin America and especially in Argentina regarding the epidemiology of SSc, the prevalence of ILD, its course, and particularly the response to treatment, our objective was to evaluate a cohort of SSc patients evaluated in a single University Hospital in Buenos Aires. PATIENTS/METHODS: We included 152 patients with SSc, followed from disease onset to last pulmonary function test and with at least two PFT and up to 30 months between each. RESULTS: Sixty-one percent had diffuse SSc (DSSc) and 32% limited SSc (LSSc). The only significant clinical differences between these groups were a higher initial mRodnan score and prevalence of ILD in the DSSc. These also had significantly more anti Scl-70 (Topoisomerase 1) antibodies compared to the LSSC group who had significantly more anti centromere antibodies. The DSSc group also had significantly more extensive damage on HRCT with no differences in terms of imaging patterns. Comparing patients with and without ILD by HRCT, those with ILD had significantly more extensive damage, significantly more anti Scl-70 antibodies, and significantly fewer anti centromere antibodies than those without ILD. Patients whose ILD progressed had a smoking history (OR 4.97) and prior immunosuppressive treatment (OR 15.6) (multivariate analysis). Overall disease duration was significantly shorter in those who progressed. CONCLUSIONS: Our SSc population had similar characteristics to those described elsewhere as well as prevalence of ILD and its progression. We found a shorter disease duration, smoking, and prior immunosuppressive treatment to be associated with ILD progression.

[Factors associated with the development of interstitial lung disease in patients with systemic sclerosis]. / Factores asociados al desarrollo de enfermedad pulmonar intersticial en esclerosis sistémica.

INTRODUCTION: interstitial lung involvement occurs in 80% of chest CT scans of patients with systemic sclerosis (SS) and has a great impact on morbidity and mortality. The aim of the study was to describe factors associated with the development of interstitial lung disease (ILD) in patients diagnosed with SS in our division. METHODS: a retrospective case-control study of patients followed up between 2005-2021 who met the classification criteria for SS was performed. ILD was defined as the finding of interstitial manifestations on high-resolution chest tomography (HRCT): non-specific interstitial pneumonia pattern (NSIP) or usual interstitial pneumonia (UIP), and/or findings on pulmonary function tests (FVC less than 80% and DLCO less than 80%). Patients with ILD (cases) and without it (controls) were identified. Demographic, clinical and serological variables were analyzed. Percentage, mean (SD) and median (IQR) measurements were calculated for each variable. A univariate and multivariate analysis was performed using logistic regression to establish its association with ILD. RESULTS: Seventy nine patients with SS were included, 31 with ILD. Univariate analysis showed that sclerosis subtype (according to Le Roy classification), lung function measures, and anticentromere antibody positivity were factors associated with ILD in a statistically significant way. In the multivariate analysis, only the presence of anti-centromere antibodies was statistically significant. DISCUSSION: the analysis of risk factors to determine the development and progression of lung damage is of vital importance for an early implementation of treatment, which would impact the mortality rate of patients with SS.

Introducción: el compromiso pulmonar intersticial se presenta en 80% de las tomografías de tórax de pacientes con esclerosis sistémica (ES) y tiene gran impacto en la morbimortalidad. El objetivo de este trabajo fue describir factores asociados al desarrollo de enfermedad pulmonar intersticial (EPI) en pacientes con diagnóstico de ES de nuestra división. Métodos: Se realizó un estudio retrospectivo, casos y controles, de pacientes seguidos entre 2005-2021 que cumplían criterios de ES. Se definió EPI al hallazgo de manifestaciones intersticiales en tomografía de tórax con cortes de alta resolución (TACAR): patrón neumonía intersticial no específica (NINE) o neumonía intersticial usual (NIU), y/o hallazgos en pruebas de función pulmonar (CVF menor al 80% y DLCO menor al 80%). Se identificaron pacientes con EPI (casos) y sin ella (controles). Se analizaron variables demográficas, clínicas y serológicas. Se calcularon medidas de porcentaje, media (DS) y mediana (RIQ) en cada variable. Se efectuó análisis univariado y multivariado, mediante regresión logística para establecer su asociación con EPI. Resultados: Se incluyeron 79 pacientes con ES, 31 con EPI. El análisis univariado demostró que el subtipo de esclerosis (según clasific ación Le Roy), las medidas de función pulmonar y positividad del anticuerpo anticentrómero fueron factores asociados en forma estadísticamente significativa con EPI. En el análisis multivariado solo la presencia de anticuerpos anti-centrómero fue estadísticamente significativa. Discusión: el análisis de los factores de riesgo para determinar desarrollo y progresión de daño pulmonar tiene vital importancia para una implementación temprana del tratamiento, lo que impactaría en la tasa de mortalidad de los pacientes con ES.

Reasons for hospitalisation in patients with systemic lupus erythematosus in a university hospital in Buenos Aires.

OBJECTIVE: To determine the reasons for hospitalisation in patients with systemic lupus erythematosus (SLE) admitted to the Hospital de Clínicas "José de San Martín" Buenos Aires, Argentina. METHODS: We retrospectively analysed the clinical histories of SLE patients (SLICC 2012) during or prior to hospitalisation, from 1-2014 to 12-2017. Demographic data, reasons for hospitalisation, treatments, SLEDAI-2 K and comorbid conditions. RESULTS: 121 hospitalisations corresponding to 72 patients, 25 patients (34.7%) were hospitalised more than once. Females (83.3%), the median length of disease until admission was 5 years. There was more than one reason for hospitalisation in 32, a total of 164 reasons. The main reason was relapse of disease (52.4%). The most frequent manifestations were renal involvement, serositis and pulmonary involvement. Infections were the second reason for hospitalisation (26.8%); urinary tract, pneumonia and soft tissue. Cardiovascular involvement 4.9%. Hospitalisation in a closed unit 14.05%, mortality 2.48%. CONCLUSION: Relapse of disease and infections were the main reasons for hospitalisation; admission secondary to infection was higher than that reported in other series.

Reasons for Hospitalisation in Patients with Systemic Lupus Erythematosus in a University Hospital in Buenos Aires. / Causas de internación en pacientes con lupus eritematoso sistémico en un hospital universitario de Buenos Aires.

OBJECTIVE: To determine the reasons for hospitalisation in patients with systemic lupus erythematosus (SLE) admitted to the Hospital de Clínicas «José de San Martín¼ Buenos Aires, Argentina. METHODS: We retrospectively analysed the clinical histories of SLE patients (SLICC 2012) during or prior to hospitalisation, from 1-2014 to 12-2017. Demographic data, reasons for hospitalisation, treatments, SLEDAI-2K and comorbid conditions. RESULTS: 121 hospitalisations corresponding to 72 patients, 25 patients (34.7%) were hospitalised more than once. Females (83.3%), the median length of disease until admission was 5 years. There was more than one reason for hospitalisation in 32, a total of 164 reasons. The main reason was relapse of disease (52.4%). The most frequent manifestations were renal involvement, serositis and pulmonary involvement. Infections were the second reason for hospitalisation (26.8%); urinary tract, pneumonia and soft tissue. Cardiovascular involvement 4.9%. Hospitalisation in a closed unit 14.05%, mortality 2.48%. CONCLUSION: Relapse of disease and infections were the main reasons for hospitalisation; admission secondary to infection was higher than that reported in other series.

Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Neutropenia al diagnóstico de lupus eritematoso sistémico: prevalencia y correlaciones clínicas y serológicas. Nuestra cohorte / Neutropenia at diagnosis of systemic lupus erythematosus: prevalence and clinical and serological correlations. Our cohort

Introducción: las manifestaciones hematológicas en el lupus eritematoso sistémico (LES) son frecuentes. La leucopenia se presenta del 50 al 60% de los casos, pero solo el 17% tiene un recuento leucocitario <1.000/mm3. La neutropenia en pacientes con leucopenia ocurre entre un 20-40% (según el valor de corte del laboratorio). Los mecanismos posibles de neutropenia descriptos son: aumento en la destrucción de granulocitos periféricos por anticuerpos antineutrófilos, opsonización y destrucción por monocitos; cambios en el pool esplénico y marginal; y disminución en la producción medular. La formación de trampas extracelulares de neutrófilos (neutrophil extracellular traps, NETs) contribuye en la producción de interferón tipo 1 (IFN-1) a partir de plasmocitos y células dendríticas causando daño endotelial y cambios protrombóticos. La NETosis y el clearence anormal de material apoptótico promueven mayor liberación de antígenos y la consiguiente formación de autoanticuerpos. Las consecuencias infecciosas de la neutropenia al diagnóstico de LES se desconocen. Los objetivos del presente estudio fueron conocer la prevalencia de la neutropenia al diagnóstico de LES, determinar su correlación con otras variables de la patología, y estudiar su relación con una mayor probabilidad de actividad, daño, infecciones y mortalidad. Materiales y métodos: estudio descriptivo, retrospectivo. Se incluyeron pacientes con diagnóstico de LES (Systemic Lupus International Collaborating Clinics, SLICC 2012) de la cohorte del Sanatorio, desde enero de 2010 a diciembre de 2020. Se consignaron variables demográficas y asociadas a la enfermedad (criterios clínicos y de laboratorio). Escala de actividad: Systemic Lupus Erythematosus Disease Activity Index 2k (SLEDAI-2k). Se dividieron en dos grupos según la presencia de neutropenia (<1.500/mm3). Se definió un subgrupo de neutropenia severa: <500/mm3. En pacientes con neutropenia se evaluó la presencia de infección viral, bacteriana y tratamiento con factor de crecimiento de colonias de granulocitos y monocitos (GM-GSF). Análisis estadístico: los datos descriptivos se presentaron como medias y sus desvíos estándar (±DS) (variables continuas) y porcentajes (variables categóricas). Se compararon variables independientes de acuerdo con su distribución con test Mann Whitney. Se utilizó prueba t de Student para comparación de medias, y chi cuadrado (X2) para variables cualitativas. Se consideró como estadísticamente una p≤0,05. Resultados: se incluyeron 70 pacientes. Mujeres 59 (84%), edad media 38,6 años (18-72). Leucopenia 24 (34%), linfopenia 30 (42,8%), neutropenia 12 (17%), neutropenia severa 2 (2,8%) y plaquetopenia 7 (10%). Grupo con neutropenia (n=12): Sicca 12 (100%). Media índice neutrófilo/linfocito (INL) 1,33 (DS 0,69), infecciones: virus de Epstein-Barr (VEB) IgM (+) uno, parvovirus y CMV solicitados y negativos dos. PAMO realizada una: normal. Pacientes en tratamiento con GM-GSF: dos, sin eventos adversos. Dos infecciones urinarias. Conclusiones: en nuestro estudio se observó correlación entre neutropenia con síntomas Sicca, leucopenia y linfopenia, y un INL menor. Se desconoce si se relacionó a peor evolución. La presencia de infección fue baja (16%). Dos pacientes requirieron GM-GSF (con neutropenia severa), sin haber presentado eventos adversos.

Introduction: hematological manifestations are frequent in systemic erythematosus lupus (SLE). Leukopenia is seen in between 50 to 60% of cases, but only 17% has a leukocyte count <1,000/mm3. Neutropenia in patients with leukopenia occurs between 20-40% of cases, depending on the cut-off value used. Possible described mechanisms for neutropenia are: an increase in destruction of granulocytes by anti-neutrophil antibodies, opsonization and destruction by monocytes; change in the splenic and marginal neutrophil pool; a diminished production in the bone marrow. The formation of NETs contributes to the production of INF-1 from plasmocytes and dendritic cells, causing endothelial damage and pro-thrombotic changes. NETosis and apoptotic abnormal clearence promote the formation of antigens and subsequent autoantibodies. Infectious consequences of neutropenia in SLE are still unknown. The objectives of this article were to know the prevalence of neutropenia at diagnosis of SLE in our hospital, and secondly to determine its correlation with other variables of the disease and to investigate whether it's related with a greater probability of infections. Materials and methods: descriptive, retrospective study. Patients with diagnosis of SLE (SLICC 2012) from our cohort were included. Demographic and related to disease variables were stated. Activity scale: SLEDAI-2k. Patients were divided into two groups according to the presence or absence of neutropenia (<1.500/mm3 ) and multivariate analysis was performed to clinical and analytical variables. A subgroup with severe neutropenia (<500/mm3) was evaluated. Multivariate analysis was performed to detect correlations between a diminished neutrophil count and clinical manifestations, disease severity, autoantibodies profile, infections, and associated diseases. In neutropenic patients, the presence of viral or bacterial infection and the use of GM-GSF were evaluated. Statistical analysis was performed as mean +/-SD for continuous variables and percentage for categorical variables. T-Test or Mann-Whitney were used to compare independent variables according to distribution. Student's T and Chi-Square for qualitative variables. Statistical significance: p<0.05. Results: 70 patients were included. Female 59 (84%), mean age 38.6 years (18- 72). Leukopenia 24 (34%), lymphopenia 30 (42.8%), neutropenia 12 (17%), severe 2 (2.8%), thrombocytopenia 7 (10%). Neutropenic group: Sicca 12 (100%), neutrophil/lymphocyte index (NLI) 1.33 (DS 0.69), infections: EBV IgM+1/12, parvovirus and CMV negative 2/12. BMA 1/12, without pathologic findings. GM-GSF 2/12. Infections: 2/12 (urinary). Conclusions: we observed a correlation between Sicca symptoms, leuko and lymphopenia, and a lower NLI. The clinical significance of these findings was uncertain. The presence of infection was low (16%). Two required GM-GSF, having not presented adverse events.

Factor reumatoide en vasculitis ANCA asociadas / Rheumatoid factor in ANCA associated vasculitis

Introducción: las pruebas de factor reumatoide (FR) se utilizan principalmente para el diagnóstico de artritis reumatoidea (AR), sin embargo, también pueden estar presentes en otras enfermedades. Su significado clínico en contexto de vasculitis ANCA asociadas (VAA) todavía es incierto. El objetivo de este estudio fue establecer el significado clínico y pronóstico del FR en pacientes con VAA. Materiales y métodos: se realizó un estudio observacional, retrospectivo. Se evaluaron pacientes con diagnóstico de VAA (granulomatosis con poliangitis -GPA-, poliangitis microscópica -PAM- y granulomatosis eosinofílica con poliangitis -GEPA-), mayores de 18 años, con FR solicitado antes del inicio del tratamiento. Se recolectaron los siguientes datos: edad, sexo, tipo de VAA, duración de la enfermedad, tratamiento, órganos afectados, Birmingham Vasculitis Activity Score (BVAS), Five Factor Score (FFS), eritrosedimentación, proteína C reactiva, requerimiento de diálisis, asistencia respiratoria mecánica, mortalidad y causa de muerte. Se calculó el odds ratio (OR) y su intervalo de confianza del 95% (IC 95%) para determinar la fuerza de asociación entre las variables. Resultados: incluimos 32 pacientes en los que encontramos 31,2% de FR positivo. Comparados con aquellos con FR negativo, no hubo diferencias significativas con respecto a manifestaciones clínicas, ni actividad de la enfermedad medida por el BVAS y reactantes de fase aguda. La presencia de factor reumatoide se asoció a menor ingreso a diálisis (OR 0.14 IC 0,02-0,8; p=0,02) y mortalidad (p=0,04). No hubo diferencias significativas con respecto al FFS. Conclusiones: en nuestro estudio la presencia de FR en pacientes con vasculitis ANCA se asoció a menor requerimiento de diálisis y menor mortalidad. Estos hallazgos no se correlacionaron estadísticamente con el FFS. No se encontró asociación entre la presencia de FR y el compromiso de órgano, actividad de la enfermedad, ni requerimiento de asistencia respiratoria mecánica.

Introduction: rheumatoid factor tests are mainly used for the diagnosis of rheumatoid arthritis (RA); however, it may also be present in other diseases. Its clinical significance in the context of ANCA associated vasculitis (AAV) is still uncertain. The objective was to establish the clinical and prognostic significance of RF in patients with AAV. Materials and methods: a retrospective observational study was carried out. Patients with a diagnosis of AAV (GPA, MAP and AGEP) over 18 years of age with RF requested before the start of treatment were evaluated. The following data were collected: age, sex, type of AAV, disease duration, treatment, affected organs, Birmingham Vasculitis Activity Score (BVAS), Five Factor Score (FFS), erythrocyte sedimentation rate, C-reactive protein, dialysis requirement, attendance mechanical ventilation, mortality and cause of death. The odds ratio (OR) and its 95% confidence interval (95%CI) were calculated to determine the strength of association between variables. Results: we included 32 patients in whom we found 31.2% positive RF. Compared to those with negative RF, there were no significant differences with respect to clinical manifestations, nor disease activity measured by BVAS and acute phase reactants. The presence of the rheumatoid factor was associated with lower admission to dialysis (OR 0.14 CI 0.02-0.8 p=0.02) and mortality (p=0.04). There were no significant differences with respect to FFS. Conclusions: in our study, the presence of RF in patients with ANCA vasculitis was associated with a lower requirement for dialysis and lower mortality. These findings were not statistically correlated with the FFS. No association was found between the presence of RF and organ involvement, disease activity, or mechanical ventilation requirement.

Immune diffuse alveolar hemorrhage: Clinical presentation and outcome.

BACKGROUND: Diffuse alveolar haemorrhage (DAH) is a manifestation of several immune and nonimmune diseases. OBJECTIVE: The objective of this study was to characterize the clinical characteristics and short-term outcomes of patients with immune-mediated DAH requiring hospital admission. METHODS: A retrospective study from December 2010 to December 2015, was conducted by analyzing the clinical records of 39 patients with DAH with a proven immunological origin. The diagnosis of individual collagen vascular diseases (CVD) was made according to the criteria of the corresponding societies. RESULTS: Thirty-nine patients were included (median age 44.8 years, range 16-76). The main causes of DAH were ANCA-related vasculitis (74.3%) mainly granulomatosis with polyangiitis (n = 14) and microscopic polyangiitis (n = 13). Thirty patients (76.9%) had hemoptysis. An alveolar airspace filling pattern was found in most of patients (59%). All the patients had a drop in hemoglobin level that ranged from 1.0 to 3.0 g/dL. BAL fluid was macroscopically bloody in 43.6% of patients (n = 17) and showed siderophagic alveolitis on BAL cytology in 100%. All patients received high doses of corticosteroids. Other additional treatments were antibiotics (53,8%, n = 21), intravenous cyclophosphamide (87.2%, n = 34), plasma exchange (35.9%, n = 14); intravenous immunoglobulin (12.8%, n = 5) and rituximab in 5 patients (12.8%). Mortality rate was higher amongst patients who required dialysis (50.0 vs 15.4%, p = 0.045), with SaO2 <90% at admission (50.0 vs 5.3%, p = 0.003) or those who required mechanical ventilation (76.9 vs 6.8%, p = < 0.001). CONCLUSION: DAH may present without hemoptysis and requires an early bronchoscopy to confirm the diagnosis and exclude infection. Other characteristics could be included in the abstract which are relevant to the paper. (relation between mortality, dialysis, ventilation, etc.).

Factores asociados al desarrollo de enfermedad pulmonar intersticial en esclerosis sistémica / Factors associated with the development of interstitial lung disease in patients with systemic sclerosis

Resumen Introducción: el compromiso pulmonar intersticial se presenta en 80% de las tomografías de tórax de pacientes con esclerosis sistémica (ES) y tiene gran impacto en la morbimortalidad. El objeti vo de este trabajo fue describir factores asociados al desarrollo de enfermedad pulmonar intersticial (EPI) en pacientes con diagnóstico de ES de nuestra división. Métodos: Se realizó un estudio retrospectivo, casos y controles, de pacientes seguidos entre 2005-2021 que cumplían criterios de ES. Se definió EPI al hallazgo de manifestaciones intersticiales en tomografía de tórax con cortes de alta resolución (TACAR): patrón neumonía intersticial no específica (NINE) o neumonía intersticial usual (NIU), y/o hallazgos en pruebas de función pulmonar (CVF menor al 80% y DLCO menor al 80%). Se identificaron pacientes con EPI (casos) y sin ella (controles). Se analizaron variables demográficas, clínicas y serológicas. Se calcularon medidas de porcentaje, media (DS) y mediana (RIQ) en cada variable. Se efectuó análisis univariado y multivariado, mediante regresión logística para establecer su asociación con EPI. Resultados: Se incluyeron 79 pacientes con ES, 31 con EPI. El análisis univariado demostró que el subtipo de esclerosis (según clasific ación Le Roy), las medidas de función pulmonar y positividad del anticuerpo anticentrómero fueron factores asociados en forma estadísticamente significativa con EPI. En el análisis multivariado solo la presencia de anticuerpos anti-centrómero fue estadísticamente significativa. Discusión: el análisis de los factores de riesgo para determinar desarrollo y progresión de daño pulmonar tiene vital importancia para una implementación temprana del tratamiento, lo que impactaría en la tasa de mortalidad de los pacientes con ES.

Abstract Introduction: interstitial lung involvement occurs in 80% of chest CT scans of patients with systemic sclerosis (SS) and has a great impact on morbidity and mortality. The aim of the study was to describe factors associated with the development of interstitial lung disease (ILD) in patients diagnosed with SS in our division. Methods: a retrospective case-control study of patients followed up between 2005-2021 who met the classification criteria for SS was performed. ILD was defined as the finding of interstitial manifestations on high-resolution chest tomography (HRCT): non-specific interstitial pneumonia pattern (NSIP) or usual interstitial pneumonia (UIP), and/or findings on pulmonary function tests (FVC less than 80% and DLCO less than 80%). Patients with ILD (cases) and without it (controls) were identified. Demographic, clinical and serological variables were analyzed. Percentage, mean (SD) and median (IQR) measurements were calculated for each variable. A univariate and multivariate analysis was performed using logistic regression to establish its association with ILD. Results: Seventy nine patients with SS were included, 31 with ILD. Univariate analysis showed that sclerosis subtype (according to Le Roy classification), lung function measures, and anticentromere antibody positivity were factors associated with ILD in a statistically significant way. In the multivariate analysis, only the presence of anti-centromere antibodies was statistically significant. Discussion: the analysis of risk factors to determine the development and progression of lung damage is of vital importance for an early implementation of treatment, which would impact the mortality rate of patients with SS.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Causas de internación en pacientes con lupus eritematoso sistémico en un hospital universitario de Buenos Aires / Reasons for Hospitalisation in Patients with Systemic Lupus Erythematosus in a University Hospital in Buenos Aires

Objetivo: Determinar causas de hospitalización en pacientes con lupus eritematoso sistémico (LES) internados en Hospital de Clínicas «José de San Martín», Buenos Aires, Argentina. Métodos: Se analizaron retrospectivamente historias clínicas de pacientes LES (SLICC 2012) durante o previo a la internación, desde 1-2014 hasta 12-2017. Datos demográficos, motivos de hospitalización, tratamientos, SLEDAI 2 K y condiciones comórbidas. Resultados: 121 hospitalizaciones correspondientes a 72 pacientes, 25 pacientes (34,7%) tuvieron más de una hospitalización. Mujeres (83,3%), mediana de duración de la enfermedad hasta la admisión 5 años. Más de una causa de internación en 32, total de 164 motivos. La principal causa fue recaída de la enfermedad (52,4%). La manifestación más frecuente fue compromiso renal, serositis y compromiso pulmonar. Las infecciones fueron la segunda causa de hospitalización (26,8%); tracto urinario, neumonía y partes blandas. Compromiso cardiovascular 4,9%. Hospitalización en unidad cerrada 14,05%, mortalidad 2,48%. Conclusión: Recaída de la enfermedad e infecciones, fueron las principales causas de hospitalización; la admisión secundaria a infección fue superior a la reportada en otras series.(AU)

Objective: To determine the reasons for hospitalisation in patients with systemic lupus erythematosus (SLE) admitted to the Hospital de Clínicas «José de San Martín» Buenos Aires, Argentina. Methods: We retrospectively analysed the clinical histories of SLE patients (SLICC 2012) during or prior to hospitalisation, from 1-2014 to 12-2017. Demographic data, reasons for hospitalisation, treatments, SLEDAI-2K and comorbid conditions. Results: 121 hospitalisations corresponding to 72 patients, 25 patients (34.7%) were hospitalised more than once. Females (83.3%), the median length of disease until admission was 5 years. There was more than one reason for hospitalisation in 32, a total of 164 reasons. The main reason was relapse of disease (52.4%). The most frequent manifestations were renal involvement, serositis and pulmonary involvement. Infections were the second reason for hospitalisation (26.8%); urinary tract, pneumonia and soft tissue. Cardiovascular involvement 4.9%. Hospitalisation in a closed unit 14.05%, mortality 2.48%. Conclusion: Relapse of disease and infections were the main reasons for hospitalisation; admission secondary to infection was higher than that reported in other series.(AU)