Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study.

Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.

Anticuerpos Anti Ro 52/Ro 60 y su correlación clínica- serológica. Estudio descriptivo unicéntrico

Introducción: La interpretación de los diversos anticuerpos vinculados a las Enfermedades Autoinmunes Sistémicas (EAS) es un reto clínico. Entre los anticuerpos específicos, los anti Ro son los de mayor frecuencia. Se asocian a un fenotipo clínico, relacionados tanto a manifestaciones clínicas diversas como a EAS establecidas. Metodología : Estudio descriptivo, observacional, transversal, realizado en Hospital Maciel (Montevideo, Uruguay). Resultados: Se enrolaron 70 pacientes, la mayoría de sexo femenino. 60 pacientes (85%) presentaron Ro52, 40 (57%) Ro60 y 31 (44%) ambos anticuerpos. Del total de los pacientes que tuvieron Ro positivo en 59 (93%) se evidenciaron manifestaciones clínicas. Las más frecuentes fueron: fotosensibilidad 26 (42%); Raynaud 18 (30%); xerostomía 26 (42%), xeroftalmia 25 (41%), enfermedad pulmonar intersticial 10 (15%), nefropatía 20 (32%), y manifestaciones hematológicas 16 (23%). En 59 casos (86%) se diagnosticó una enfermedad autoinmune. Las más frecuentes fueron Síndrome de Sjögren 26 (41%), Lupus eritematoso sistémico 26 (41%), Artritis reumatoidea 14 (22%), Esclerosis sistémica 10 (16%), Hepatopatías autoinmunes 10 (14%). Se evidenciaron otros autoanticuerpos positivos en el 68 (97%) de los casos. El ANA fue positivo en 67 pacientes (95%). La proporción de pacientes con Ro60 positivo fue significativamente mayor en pacientes que presentaron fotosensibilidad (p 0.006), Lupus cutáneo agudo (p 0.003), manifestaciones articulares (p 0.031) y nefropatía (p 0.016). La positividad de ambos Ro52/60 fue significativamente mayor en pacientes con manifestaciones musculares (p 0.028) y nefropatía (p 0.047). En cuanto al tipo de enfermedad autoinmune se evidenció una proporción significativa de pacientes con Ro60 y LES (p 0.004), así como de ambos anticuerpos y ES (p 0.04). Hubo mayor proporción de pacientes con Ro60 y anti SCL 70 (p 0.008) que aquellos que no lo presentaban, así mismo sucede con Ro60 y el FR (p 0.018); y Ro 52/60 con anti La (p 0.049) y anti SCL 70 (p 0.027). Conclusiones: Los anticuerpos específicos Ro52/60 son frecuentes, predominando el Ro52. La mayoría de los pacientes que presentan positividad tienen una enfermedad autoinmune de base, observándose también en pacientes con patología oncológica. Conocer sus asociaciones es de suma importancia dado que presentan un rol diagnóstico, pronostico, y ayudan a predecir el fenotipo clínico.

Introduction: The interpretation of the various antibodies linked to systemic autoimmune diseases is a clinical challenge. Among the specific antibodies, anti Ro are the most frequent. They are associated with a clinical phenotype, related to both diverse clinical manifestations and established SAD. Methodology: descriptive, observational, cross-sectional study carried out at the Maciel Hospital, Montevideo, Uruguay. Results: 70 patients were enrolled, most of them female. 60 patients (85%) presented Ro52, 40 (57%) Ro60 and 31 (44%) both antibodies. Of the total number of patients who had positive Ro in 59 (93%) clinical manifestations were evidenced. The most frequent were: photosensitivity 26 (42%); Raynaud 18 (30%); Xerostomia 26 (42%), Xerophthalmia 25 (41%), interstitial lung disease 10 (15%), nephropathy 20 (32%), and hematological manifestations 16 (23%). In 59 cases (86%) an autoimmune disease was diagnosed. The most frequent were: Sjögrens syndrome 26 (41%), systemic lupus erythematosus 26 (41%), rheumatoid arthritis 14 (22%), systemic sclerosis 10 (16%), autoimmune liver diseases 10 (14%). Other positive autoantibodies were found in 68 (97%) of the cases. ANA was positive in 67 patients (95%). The proportion of patients with positive Ro60 was significantly higher in patients with photosensitivity (p: 0.006), acute cutaneous lupus (p: 0.003), joint manifestations (p: 0.031), and nephropathy (p: 0.016). The positivity of both Ro52/60 was significantly higher in patients with muscular manifestations (p 0.028) and nephropathy (p 0.047). Regarding the type of autoimmune disease, there was a significant proportion of patients with Ro60 and SLE (p 0.004), as well as both antibodies and SE (p 0.04). There was a higher proportion of patients with Ro60 and anti SCL 70 (p 0.008) than those who did not, the same happens with Ro60 and RF (p 0.018); and Ro 52/60 with anti La (p 0.049) and anti SCL 70 (p 0.027). Conclusions: Ro52/60 specific antibodies are frequent, predominating Ro52. Most of the patients who present positivity have an underlying autoimmune disease, which is also observed in patients with oncological pathology. Knowing their associations is of the utmost importance given that they present a diagnostic and prognostic role, and help to predict the clinical phenotype.

Introdução: A interpretação dos vários anticorpos ligados a doenças autoimunes sistêmicas é um desafio clínico. Dentre os anticorpos específicos, os anti Ro são os mais frequentes. Eles estão associados a um fenótipo clínico, relacionado tanto a várias manifestações clínicas quanto a EAS estabelecido. Metodologia: estudo descritivo, observacional, transversal, realizado no Hospital Maciel, Montevidéu, Uruguai. Resultados: foram incluídos 70 pacientes, a maioria do sexo feminino. 60 pacientes (85%) apresentaram Ro52, 40 (57%) Ro60 e 31 (44%) ambos os anticorpos. Do total de pacientes que apresentaram Ro positivo em 59 (93%) manifestações clínicas foram evidenciadas. Os mais frequentes foram: fotossensibilidade 26 (42%); Raynaud 18 (30%); Xerostomia 26 (42%), Xeroftalmia 25 (41%), doença pulmonar intersticial 10 (15%), nefropatia 20 (32%) e manifestações hematológicas 16 (23%). Em 59 casos (86%) foi diagnosticada doença autoimune. As mais frequentes foram: síndrome de Sjögren 26 (41%), lúpus eritematoso sistêmico 26 (41%), artrite reumatoide 14 (22%), esclerose sistêmica 10 (16%), hepatopatias autoimunes 10 (14%). Outros autoanticorpos positivos foram encontrados em 68 (97%) dos casos. O ANA foi positivo em 67 pacientes (95%). A proporção de pacientes com Ro60 positiva foi significativamente maior em pacientes com fotossensibilidade (p: 0,006), lúpus cutâneo agudo (p: 0,003), manifestações articulares (p: 0,031) e nefropatia (p: 0,016). A positividade de ambos Ro52/60 foi significativamente maior em pacientes com manifestações musculares (p 0,028) e nefropatia (p 0,047). Em relação ao tipo de doença autoimune, houve proporção significativa de pacientes com Ro60 e LES (p 0,004), assim como anticorpos e SE (p 0,04). Houve maior proporção de pacientes com Ro60 e anti SCL 70 (p 0,008) do que aqueles que não apresentaram, o mesmo ocorre com Ro60 e RF (p 0,018); e Ro 52/60 com anti La (p 0,049) e anti SCL 70 (p 0,027). Conclusões: Anticorpos específicos Ro52/60 são frequentes, predominando Ro52. A maioria dos pacientes que apresentam positividade tem uma doença autoimune de base, também observada em pacientes com patologia oncológica. Conhecer suas associações é de extrema importância, pois têm papel diagnóstico e prognóstico, além de ajudar a predizer o fenótipo clínico.

Estudio multicéntrico descriptivo de enfermedades pulmonares intersticiales asociadas a enfermedades autoinmunes en centros de salud en Montevideo, Uruguay / Multicentric descriptive study of interstitial lung disease associated with autoimmune diseases in health centers in Montevideo, Uruguay / Estudio multicêntrico descritivo de enfermarias pulmonares intersticiales asociadas a enfermedades autoinmunes en centros de saúde en Montevideo, Uruguay

Resumen: Introducción: Las enfermedades pulmonares intersticiales (EPI) son una manifestación frecuente en algunas enfermedades autoinmune sistémica (EAIS). Objetivos: Describir las características de los pacientes que presentaron una EPI asociada a una EAIS, en centros de referencia de Montevideo. Valorar clínica, patrón imagenológico y severidad en pruebas de función respiratoria al momento diagnóstico. Metodología: Estudio multicéntrico descriptivo, observacional, de cohorte histórica, entre diciembre 2008 a diciembre 2017. Resultados: se enrolaron 59 pacientes, mujeres 88%, edad media 61 años. La clínica más frecuente fue la disnea. Las EAIS identificadas fueron: artritis reumatoidea (AR) 28%, esclerosis sistémica difusa (ESD) 22%, enfermedad mixta 6%, otras 42%. Debut con EPI previo a EAIS 9%; 47% presentó EPI en el primer año de diagnóstico de EAIS. Los patrones imagenológicos hallados fueron: neumonía intersticial no especifica (NINE) 64%, neumonía intersticial usual (NIU) 27%, neumonía organizativa 5%, neumonía intersticial linfoide 1%. Dentro del patrón NIU la enfermedad más prevalente fue la AR, en patrón NINE la ESD. La capacidad vital forzada (CVF) media fue de 80%, la DLCO media fue de 71%. En los pacientes con DLCO y CVF menor a 50% predominó la ESD. Conclusiones: la AR y ESD fueron las EAIS más asociadas a EPI. El diagnostico de EPI se realizó durante el primer año del diagnóstico de la EAIS, siendo NINE el patrón imagenológico más frecuente. El patrón NIU fue el más prevalente en AR y NINE en ESD.

Abstract: Introduction: The Interstitial Lung Disease (ILD) is a common manifestation from Connective Tisuue Disease (CTD). Objectives: Describe the characteristics of a population with ILD related to CTD in different hospitals of Montevideo. Analize the clinic manifestations, imagenologic pattern and severity of respiratory function evaluated by spirometry. Methods: Retrospective-descriptive of historical study of cohort, between 2008 december and december 2017. Results: 59 patients were enrolled, female 88%, mean age 61.The first symptom in diagnosis was dyspnea. The CTD identified were: Rheumatoid Arthritis (AR) 28%, Sclerodermia (SL) 22%, Mixed-CTD 7%. Debut of ILD before CTD 9%. The 47% of de patients have ILD in the first year of de diagnosis. The imagenologic pattern were: non specific interstitial pneumonia (NSIP) 65%, usual interstitial pneumonia (UIP) 27%, organizing pneumonia 5%, lymphocytic interstitial pneumonia (LIP) 1%. The most common illness in UIP pattern was AR, in NINE was SL. Forced vital capacity (FVC) media was 80%, DLCO media 71%, SL predominate in patients with FVC and DLCO less than 50%. Conclusions: AR and SL were the most common ILD. Almost half of the patients have ILD in the first year of the diagnosis, the NSIP pattern was the most frequent. UIP was most prevalent in AR and NSIP in SL.

Resumo: Introdução: A doença pulmonar infecciosa intersticial (EPI) tem uma manifestação frequente em várias doenças auto-imunes sistêmicas (EAIS). Objetivos: Descrever as características dos doentes que apresentam uma EPI associada a uma EAIS, nos centros de referência de Montevideu. Valorar clínica, patologia imaginária e gravidade em provas de função respiratória no momento diagnóstico. Metodología: Estudio multicêntrico descritivo, observacional, de cohorte, diciembre de 2008 a diciembre 2017. Resultados: se enrolaron 59 pacientes, mujeres 88%, edad media 61 godina. A clínica mais frecuente fue la disnea. Las EAIS têm fueron: artrite reumatóide (AR) 28%, esclerose sistêmica difusa (ESD) 22%, enfermedad mixta 6%, otras 42%. Estréia com EPI previo a EAIS 9%; 47% presentó EPI no primer año de diagnóstico de EAIS. Los patrones imagenológicos hallados fueron: neumonía intersticial não especifica (NOVE) 64%, neumonía intersticial usual (NIU) 27%, neumonía organizativa 5%, neumonía intersticial linfoide 1%. Dentro do parque NIU a enfermaria mais prevalente fue la AR, en patrón NINE la ESD. A capacidade vital forçada (CVF) media de 80%, o DLCO media de 71%. Os pacientes com DLCO e CVF menor a 50% predominaram na ESD. Conclusões: la AR e ESD fueron las EAIS más asociadas a EPI. O diagnóstico de EPI realiza-se durante o primer ano do diagnóstico do EAIS, siendo NINE o patrón imagenológico mais frecuente. El patrón NIU fue el mais prevalente en AR y NINE en ESD.

Citopenias hematológicas en enfermedades autoinmunes sistémicas / Blood cytopenias in systemic autoimmune conditions

Las citopenias hematológicas son un hallazgo frecuente y potencialmente grave en las Enfermedades Autoinmunes Sistémicas. Sus causas pueden ser muy variadas, de ahí la importancia de un abordaje diagnóstico sistematizado que asegure además el tratamiento correcto. En este artículo se revisan las generalidades de las citopenias hematológicas en cuanto a frecuencia, causas, así como su enfoque diagnóstico y terapéutico.

The hematologic cytopenias are a frequent and potentially dangerous finding in the Systemic Autoimmune Diseases. It may have different etiologies, and for that reason it is important a systematic approach to ensure the correct diagnosis and treatment. In this article, the frequency, etiology, diagnostic approach and treatment of the hematologic cytopenias are reviewed.

Prevalencia de cefaleas primarias y subtipos en un grupo de pacientes con enfermedades autoinmunes sistémicas / Prevalence of primary headaches and subtypes in a group of patients with systemic autoimmune diseases

Objetivos: Conocer prevalencia global de cefalea y subtipos en Enfermedades Autoinmunes Sistémicas (EAS) y compararla con la población general. Establecer en pacientes con Lupus Eritematoso Sistémico (LES) la relación entre cefalea y anticuerpos antifosfolípidos (aPL), actividad, otras manifestaciones neurológicas. Comparar la eficacia entre la segunda clasificación de la International Headache Society (ICHD-II), 2004, y la del American College of Rheumatology (ACR), 1999, para clasificar cefaleas en LES. Métodos: Noventa pacientes fueron evaluados con un cuestionario basado en criterios de la ICHD-II. En pacientes con LES también se aplicó la clasificación de cefaleas del ACR. Prevalencia anual de cefalea y migraña se comparó con la de Uruguay. Resultados: La prevalencia anual de cefalea en EAS fue similar a la población general (50,6 por ciento vs 58,4 por ciento). Fueron primarias 47 (52 por ciento): Tipo tensional 31 (34,4 por ciento), migraña 16 (17,8 por ciento), sin aura 13. Se halló asociación significativa entre EAS y migraña, teniendo 2,87 más posibilidades de presentarla estos individuos que la población general (17,8 por ciento vs 6,2 por ciento, P = 0,0001). De 19 lúpicos con cefalea, relación con actividad: 1, aPL positivos: 13, otras manifestaciones neurológicas: 5. Aplicando la ICHD-II se diagnosticó el 100 por ciento de cefaleas en LES; con la clasificación del ACR se diagnosticó el 86 por ciento. Conclusión: La prevalencia de cefalea fue similar ala población general. Predominaron las primarias, tipo tensional y migraña. La migraña fue más prevalente en las EAS. En LES no se demostró asociación entre cefalea y actividad, aPL, otros síndromes neuropsiquiátricos. La ICHD-II debería utilizarse en LES, y la clasificación del ACR debería revisarse.

Objectives: Learn the global prevalence of headache and its subtypes in Systemic Autoimmune Diseases (SADs); compare it with the general population. In Systemic lupus erythematosus (SLE), to establish the relationship between headache and: antiphospholipid antibodies (APA), activity, other neurological manifestations. To compare the efficacy between the second classification of the International Headache Society (ICHD-II), 2004 and the classification of the American College of Rheumatology (ACR) 1999 to classify headaches in SLE. Methods: Ninety patients were evaluated with a questionnaire based on criteria of the ICHD-II. In patients with SLE the criteria of the ACR were also used. The annual prevalence of headache and migraine was compared with Uruguay’s. Results. The annual prevalence of headache in SADs was similar to the general population (50.6 percent vs. 58.4 percent). There were 47 primary headaches (52 percent): 31 tension type (34,4 percent), 16 migraines (17,8 percent), 13 without aura. A significant association was found between SADs and migraine; these patients had a 2.86 times greater chance of presenting migraines than the general population (17.8 percent vs. 6.2 percent, P = 0,0001). In the case of the 19 patients with SLE and headache, there was a relationship with activity in 1 case, 13 were APA positive, 5 had other neurologic manifestations. Applying the ICHD-II criteria 100 percent of headaches were diagnosed in SLE, applying those of the ACR, 86 percent. Conclusion: The primary headaches predominated, with the same prevalence and subtypes (tension type and migraine) than in the general population. Individuals with SADs have a higher possibility of suffering from migraine. In SLE, no relationship was demonstrated between headache and activity, APA or other neuropsychiatric syndromes. The ICHD-II should be the one to be used in SLE patients, the ACR classification should be revised.

Prevalence and characteristics of immunomediated neuropathies in a group of patients with autoimmune diseases.

OBJECTIVE: To determine the prevalence and the clinical-neurophysiological characteristics of immunomediated peripheral neuropathies (PN) in a group of patients with systemic autoimmune diseases. METHOD: Fifty-nine patients with proved systemic autoimmune diseases were included. Patients underwent clinical examination and nerve conduction studies to diagnose the PN. RESULTS: Immune PNs were detected in 18 patients (30.5%). Out of the total number of PNs (18), 39% were sensory-motor polyneuropathies, 33% mononeuritis multiplex, 11% pure sensory polyneuropathies, 11% cranial neuropathies, and 6% proximal motor neuropathies, such as the Guillain-Barré syndrome. Nine PNs (50%) appeared at the onset of the connective tissue disorders, and the rest of the cases appeared during the course of the disease. Of the total of PNs detected in this study, only 45% had a previous diagnosis. Vasculitis was the disease that presented more associated PNs. Systemic lupus erythematosus showed the widest range of PN clinical varieties. CONCLUSIONS: The first national prevalence rate of PNs in patients with systemic autoimmune diseases was provided: 30.5%. No comparative data were found in the international bibliography. Sensory-motor polyneuropathy was the most frequently observed form of PN, followed by mononeuritis multiplex. The NPs appeared with the same frequency both at the onset and during the course of the diseases under study; these predominated at the onset of vasculitis and primary Sjögren syndrome. The compromise of the peripheral nervous system is underdiagnosed.

Aterogénesis en las enfermedades autoinmunes sistémicas / Atherogenesis in systemic autoimmune diseases

Objetivo. Estudiar la prevalencia de aterosclerosis clínica y subclínica en pacientes con enfermedades autoinmunes (EAI) sistémicas. Pacientes y método. Se estudió a 65 pacientes con EAI: lupus eritematoso sistémico, artritis reumatoide, síndrome de Sjögren y vasculitis. La edad media fue de 47 años, y el 89% pertenecía al sexo femenino. Respecto a la actividad de la EAI, se definieron 2 estadios evolutivos: remisión completa y enfermedad activa, que incluye remisión parcial, estabilidad sin progresión y progresión de la enfermedad, considerando que expresan persistencia de la actividad inflamatoria clínica. La aterosclerosis clínica se estudió a partir de los antecedentes de episodios cardiovasculares y del examen físico. Se realizó estudio Doppler carotídeo a 32 pacientes seleccionados al azar, valorando la aterosclerosis subclínica (placa de ateroma, espesor de la íntima media) y la disfunción endotelial. En todos se dosificó proteína C reactiva ultrasensible (PCRus) plasmática y lipidograma. Resultados. Se detectó aterosclerosis clínica en el 53,8%, con una asociación estadísticamente significativa con la actividad de EAI. La prevalencia de aterosclerosis fue del 75%. Entre los 32 pacientes estudiados con Doppler, el 43,8% tenía placas carotídeas y el 25% presentó lesiones subclínicas. Se observó un 53% con disfunción endotelial. El 37,5% de los casos tenían placas sin manifestaciones clínicas. Como un marcador útil de presencia de placas, el 64% de los pacientes con lesiones tenían la PCRus patológica. Conclusiones. Destaca la elevada frecuencia de aterosclerosis clínica y subclínica en pacientes con enfermedades autoinmunes, relacionada con la actividad inflamatoria, que requiere diagnóstico precoz con Doppler (AU)

Objective. To study the prevalence of clinical and subclinical atherosclerosis in patients with systemic autoimmune diseases (SAD). Patients and method. Sixty-five patients with one of the following SAD were studied: systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and vasculitis. The mean age was 47 years, and 89% of the patients were female. Two stages of SAD were defined: complete remission and active disease. To evaluate the degree of chronic inflammation, the latter stage included partial remission, stable disease without progression, and disease progression. Clinical atherosclerosis was studied through previous cardiovascular events and physical examination. Carotid Doppler examination was performed in 32 randomly selected patients with measurement of subclinical atherosclerosis (atheroma plaques, intimal-medial thickness) and endothelial dysfunction. In all patients C-reactive protein (CRP) was measured using an ultrasensitive assay and lipid tests were performed. Results. Clinical atherosclerosis was detected in 53.8% of the patients, with a statistically significant association with SAD activity. The prevalence of atherosclerosis was 75%. Among the 32 patients who underwent Doppler study, carotid plaques were observed in 43.8% and subclinical lesions were found in 25%. Endothelial dysfunction was observed in 53%. Plaques were found in 37.5% without clinical symptoms. Sixty-four percent of patients with lesions showed pathological ultrasensitive C-reactive protein levels, indicating the utility of this protein as a marker of atherosclerotic plaques. Conclusions. The prevalence of clinical and subclinical atherosclerosis in patients with SAD was high and was related to inflammatory activity. Early diagnosis through Doppler evaluation is required (AU)