RESUMO
Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1-/- ) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren's syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking ß1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating ß1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c+ dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3+ regulatory T cells (Tregs), and increased number of CD8+ T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren's syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8+ T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.
Assuntos
Doenças Autoimunes/patologia , Galectina 1/fisiologia , Tolerância Imunológica/imunologia , Glândulas Salivares/patologia , Sialadenite/patologia , Síndrome de Sjogren/patologia , Linfócitos T Reguladores/imunologia , Adulto , Fatores Etários , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Estudos de Casos e Controles , Células Dendríticas/imunologia , Feminino , Glicosilação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Pessoa de Meia-Idade , N-Acetilglucosaminiltransferases/fisiologia , Polissacarídeos/metabolismo , Glândulas Salivares/imunologia , Glândulas Salivares/metabolismo , Sialadenite/imunologia , Sialadenite/metabolismo , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismoRESUMO
OBJECTIVE: To assess the prevalence of parotid gland swelling (PGS) and its association with features of SS and other causes of sialadenosis in a Latin-American cohort of primary SS. METHODS: We included 668 patients from Argentina, Brazil, Mexico and Paraguay. We retrospectively registered demographics, disease duration, oral/ocular symptoms, serology and scored the basal ESSDAI. We defined PGS as a recurrent or persistent increase of volume of any parotid glands during adulthood (self-reported and/or physical examination). We registered the presence of diabetes mellitus, dyslipidaemia, body mass index and alcohol consumption. We used logistic regression analysis reporting odds ratio (OR) and 95% CI. RESULTS: PGS was present in 242 patients (36.2%): 78 previous to SS diagnosis, 86 concomitantly, 73 during follow-up and five unknown. At the multivariate analysis, PGS was associated with RF (OR 2.47, 95% CI: 1.1, 6.5, P = 0.0001), basal articular ESSDAI domain (OR 1.63, 95% CI: 1.01, 2.6, P = 0.04) and alcohol consumption (OR 2.42, 95% CI: 1.41, 4-15). Patients with PGS during the follow-up had a higher prevalence of alcohol consumption (45.3%) compared with the remaining PGS cases (26.8%; OR 2.41 95% CI: 1.2, 4.7), or patients without parotid gland swelling (15.6%; OR 3.8 95% CI: 1.7, 8.2) in all the adjusted models. CONCLUSION: PGS generally precedes or presents concomitantly with SS diagnosis, and is related to RF and articular activity. Alcohol consumption is an additional factor in PGS, especially during follow-up. The meaning of this last finding as well as its prognostic implications remains to be elucidated and deserves further evaluation in prospective studies.
Assuntos
Glândula Parótida , Síndrome de Sjogren , Adulto , Estudos de Coortes , Humanos , Estudos Prospectivos , Índice de Gravidade de Doença , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologiaRESUMO
OBJECTIVES: In this observational, analytical, cross-sectional study we aimed to describe the impact of primary Sjögren's syndrome (pSS) on work productivity and activities of daily living (ADL) to assess the association between ADL impairment and clinical manifestations and to compare ADL impairment according to patients' socioeconomic condition. METHODS: Patients diagnosed with pSS attending 11 centres from Argentina were included. To evaluate work productivity and ADL impairment, a work productivity and activity impairment questionnaire (WPAI) was used. A multiple linear regression model was performed, considering deterioration on ADL due to health as a dependent variable, adjusted for potential confounders. RESULTS: 252 patients were included, 98.4% were women, with a mean age of 52.6 years (±14.8). The average percentage of time lost due to health was 15.7 hours (±30.1 95% CI: 9.6-21.9); the decrease in work productivity was 27.2 (±30.2 95% CI: 21.3-33.1), the total disability was 33.7 (±35.8 95% CI: 26.4-4) and ADL deterioration was 34.2 (±30.9. 95% CI: 30.4-38). In the multivariate analysis, xerostomia, arthritis and depression showed significant and independent association. The mean of ADL impairment was 38.2 (±30.7) in patients attending public centres versus 28 (± 30.6) in private centres, which was a statistically significant difference. CONCLUSIONS: We found a compromise in all WPAI domains. Arthritis, xerostomia and depression were associated significantly and independently with ADL impairment. Deterioration in ADL was greater in patients treated in public centres. Considering these aspects will allow a better understanding of patients who suffer from this disease.
Assuntos
Atividades Cotidianas , Síndrome de Sjogren , Argentina , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologiaRESUMO
OBJECTIVES: To assess the use of antimalarials and to evaluate their association with damage accrual in a Latino-American cohort of patients with primary Sjögren's syndrome (pSS). METHODS: We included 377 patients attending three tertiary referral centers from: Argentina (n=110), Brazil (n=49) and Mexico (n=218). We retrospectively registered demographics, disease duration and use of prednisone (PDN), immunosupressors and antimalarials. We scored the cumulative ESSDAI and the SSDDI at last follow-up. RESULTS: Most patients were females, median disease duration 6 years, mean SSDDI score 2.7±1.8, mean cumulative ESSDAI score 9.3±8.3, 39% used PDN and 37.4% immunosupressors. A total of 191 patients (50.6%) had ever used antimalarials, mean use 43.5±40 months, being the main indication arthritis. These patients had a longer disease duration, used more PDN and immunosupressors and had lower SSDDI scores. The pleuro-pulmonary domain was significant different among groups (6.7% antimalarials users vs.14.9% not users, p=0.01). At the logistic regression, the pleuro-pulmonary domain (OR 0.37, 95% CI 0.17-0.78, p=0.01), the age (OR 0.97, 95% CI 0.96-0.99, p=0.01) and the disease duration (OR 1.07, 95% CI 1.03-1.1, p=0.0001) were associated with antimalarials use. When we compared patients with a SSDDI ≥3 vs. SSDDI<3, in the multivariate analysis the use of antimalarial was protective (OR 0.58, 0.36-0.93 CI 95%, p=0.02) and the cumulative ESSDAI a risk factor for damage accrual (OR 1.1, 1.07-1.15 CI 95%, p<0.001). CONCLUSIONS: Antimalarials were frequently used in pSS and seemed to protect against damage accrual, specifically at the pleuro-pulmonary domain. This finding should be confirmed in prospective studies.
Assuntos
Antimaláricos/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Adulto , Antimaláricos/efeitos adversos , Argentina , Brasil , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Centros de Atenção Terciária , Fatores de Tempo , Resultado do TratamentoRESUMO
Our objective was to analyze the effects of cigarette smoking on disease activity, functional capacity, radiographic damage, serology and presence of extraarticular manifestations in patients with rheumatoid arthritis and undifferentiated arthritis. This is a cross-sectional study of 1,305 patients (729 with rheumatoid arthritis and 576 with undifferentiated arthritis) from CONAART, the Argentine Consortium for Early Arthritis that includes patients older than 16 years with <2 years of disease. Sociodemographic data, clinical characteristics of the disease and smoking history were collected. In patients with rheumatoid arthritis the disease activity score of 28 joints was 5.4 ± 1.3 in current smokers, 5.2 ± 1.4 in former smokers and 5.1 ± 1.4 in never smokers (p = 0.011). The simple erosion narrowing score was higher in current smokers and former smokers than in never smokers (M 14.0, R Q 6.0-21.0; M 15.0, R Q 7.0-24.0; M 10.0, R Q 5.0-17.0; p = 0.006). Current smokers had higher rheumatoid factor titer (M 160.0, R Q 80.0-341.0) than former smokers (M 146.8, R Q 6.03-255.5) and never smokers (M 15.0, R Q 9.0-80.0) (p = 0.004). The variable independently associated with tobacco exposure was simple erosion narrowing score (OR = 1.03, 95 % CI 1.00-1.05; p = 0.012). In patients with undifferentiated arthritis, an association between smoking status and parameters of activity or radiographic damage was not observed. Neither was tobacco exposure related to the presence of extraarticular manifestations or to the degree of disability in any of the two groups of patients. No relation was found between disease activity and severity, and number of packs smoked per year. Tobacco.
Assuntos
Artrite Reumatoide/epidemiologia , Articulações do Pé/diagnóstico por imagem , Articulação da Mão/diagnóstico por imagem , Fumar/epidemiologia , Adulto , Fatores Etários , Idoso , Argentina/epidemiologia , Artrite/diagnóstico por imagem , Artrite/epidemiologia , Artrite/imunologia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/imunologia , Sedimentação Sanguínea , Proteína C-Reativa/imunologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Fator Reumatoide/imunologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/imunologiaRESUMO
OBJECTIVES.: To analyze the budget impact of upadacitinib (UPA) 15 mg + methotrexate (MTX) for the treatment of moderate-to-severe rheumatoid arthritis (RA) in patients with an inadequate response to conventional disease-modifying antirheumatic drugs (cDMARD-IR) from the perspective of social security and the private health sector in Argentina. MATERIALS AND METHODS.: A budget impact analysis model was developed for a hypothetical cohort of 100,000 adults with health insurance coverage who were diagnosed with RA over a 5-year time horizon. The model parameters were obtained through literature review and validated by local experts. The costs are expressed in 2024 US dollars (USD). RESULTS.: The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR resulted in minimal increase, with a five-year total cumulative incremental cost of USD 1,855 for social security and USD 1,812 for the private health sector, representing 2% of the total budget. The acquisition cost of UPA was the most influential variable in the sensitivity analysis. CONCLUSIONS.: The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR can provide an effective treatment option with a minimal increase in costs for the healthcare system in Argentina, which is especially important in developing countries where health system budgets are more limited. Providing evidence-based estimates is a valuable tool for informing healthcare policies and can help policymakers make informed decisions about the allocation of healthcare resources to improve patient outcomes while also managing costs.Motivation for the study. Rheumatoid arthritis (RA) is a disease that hasn't cure, so it's important to know the budget impact of treatment with upadacitinib (UPA) 15 mg + methotrexate (MTX) in patients with moderate to severe RA who didn't respond well to conventional antirheumatic drugs. Main findings. UPA + MTX would entail a minimal increase in costs for the healthcare system in Argentina, potentially making this effective treatment option more accessible to patients with RA. Access to this treatment can improve the outcome of patients with RA. Public health implications. In resource-constrained settings such as Argentina, providing evidence-based cost estimates can help healthcare managers allocate resources efficiently while improving patient outcomes. This study provides evidence to inform healthcare policies and decisions regarding the inclusion of UPA + MTX in treatment guidelines or formularies for RA management.
Assuntos
Antirreumáticos , Artrite Reumatoide , Orçamentos , Compostos Heterocíclicos com 3 Anéis , Metotrexato , Argentina , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Metotrexato/economia , Metotrexato/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/economia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Índice de Gravidade de Doença , Quimioterapia CombinadaRESUMO
OBJECTIVES: To evaluate the trajectory of students enrolled in the specialty training in rheumatology. METHODS: Retrospective analysis (2009-2016). Promotion, repetition, and dropout rates were determined. Analysis was performed to define variables associated with academic success. RESULTS: Out of 119 students, the actual promotion rate was 66.4%, 11.8% failed an exam (at least) and completed the course after the stipulated time, and the dropout rate was 7.6%. Among residents, the promotion rate was 82.5% vs. 48.2% among the rest (pâ¯<â¯0.001), the lagging students' repetition rate was 3.2% vs. 21.4% among the rest (p 0.005), and the dropout rate was 3.2% vs. 12.5% among the rest (p = 0.06). A higher average score in medical school increased the chances of success in the postgraduate programme (OR 3.41 CI 95% 2.0-6.4; pâ¯<â¯0.001). CONCLUSIONS: The residency was associated with higher rates of academic success in postgraduate studies. The average score in medical school can help identify students at risk of failure.
Assuntos
Internato e Residência , Reumatologia , Estudantes de Medicina , Humanos , Estudos Retrospectivos , Reumatologia/educaçãoRESUMO
BACKGROUND: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it's clinical, serological and histologic characteristics. MATERIALS AND METHODS: This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up. RESULTS: 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1-5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8-12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not. CONCLUSIONS: Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients.
Assuntos
Doenças Autoimunes , Síndrome de Sjogren , Xerostomia , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologiaRESUMO
OBJECTIVE: The aim of the present study is to describe the general characteristics of a cohort of patients with early arthritis in Argentina. METHODS: CONAART (Consorcio Argentino de Artritis Temprana--Argentine Consortium for Early Arthritis) is an initiative of seven rheumatology centres across Argentina. Patients were included if they had at least one or more swollen joints and <2 years of disease duration. Social, demographic, familiar, hereditary, clinical and laboratory data were recollected. At first visit and every year, X-rays of hands and feet were performed and working characteristics and pharmaco-economic data were re-collected. RESULTS: A total of 413 patients were included. Of them, 327 (79.2%) were women with a median age of 49 years and a median disease duration of 6 months. Of the total, 183 (44.3%) had RA (ACR 1987) and 167 (40.4%) undifferentiated arthritis (UA). Other diagnoses included: 12 crystalics, 11 PsA, 6 uSpA, 6 other CTD, 1 AS and 27 other diagnosis. As 85% of our population had RA and UA, we only compared these two groups of patients. Patients with RA had significantly worse activity parameters of the disease (DAS of 28 joints), functional capacity (HAQ) and quality of life (Rheumatoid Arthritis Quality of Life) than patients with UA. The frequency of RF and anti-CCP, and symmetrical distribution were also significantly higher in patients with RA compared with UA patients. All patients with RA initiated early specific treatment, in a period no longer than 6 months from the beginning of the disease. CONCLUSION: Early arthritis clinics are a useful tool to identify and treat patients with different forms of joint involvement.
Assuntos
Artrite/fisiopatologia , Reumatologia/educação , Índice de Gravidade de Doença , Adulto , Argentina , Estudos de Coortes , Avaliação da Deficiência , Educação Médica Continuada , Feminino , Humanos , Articulações , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de TempoRESUMO
BACKGROUND: Clinically evident interstitial lung disease (ILD) affects between 10 and 42% of the patients with rheumatoid arthritis (RA). Airway involvement seems to be even more common. Most of the available evidence comes from studies performed in established RA patients. The aim of our study was to know the prevalence of non-diagnosed lung disease (airway and interstitial involvement) in patients with early RA and look for associated factors. METHODS: We designed an observational, multicenter, cross-sectional study, and included patients with RA of less than two years since diagnosis. We performed a structured questionnaire, HRCT and lung functional tests looking for lung disease, together with joint disease evaluation. We analyzed which variables were associated with the presence of lung disease on HRCT. RESULTS: We included 83 patients, 83% females. The median (IQR) of time since RA diagnosis was 3 (1-6) months. In the HRCT, 57 patients had airway compromisea (72%), and 6 had interstitial abnormalities (7.5%). The most common altertion found in lung functional tests was a reduced DLCO (14%). The presence of at least one abnormality in the physical exam was associated with lung involvement on HRCT [13 (21.6%) vs 0 (0%); p = 0.026]. Also, patients with lung involvement presented significantly lower values of FVC% and DLCO%, and higher values of RV/TLC. No variable related to joint involvement was found associated with alterations in HRCT. CONCLUSION: Our study shows that a large proportion of early RA patients has abnormal findings in HRCT. Further studies are required to confirm these findings.
Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais , Artrite Reumatoide/epidemiologia , Estudos Transversais , Feminino , Humanos , Doenças Pulmonares Intersticiais/epidemiologia , Masculino , PrevalênciaRESUMO
This review aims to identify information on epidemiological parameters and estimate the cost of moderate to severe rheumatoid arthritis (RA). A search for related literature was carried out in major databases. A consensus of local rheumatology experts was used to find the most realistic parameters, using a modified Delphi method. Direct medical costs were estimated, using information collected from the cost per unit database of the Instituto de Efectividad Clínica y Sanitaria de Argentina. Indirect costs were estimated using the human resources approach. Costs were expressed in US dollars (USD) as of November 2017. The reported prevalence of RA in Argentina was 0.94% (95%CI: 0.86 to 1.02), with an annual incidence rate of 19 per 100,000 people (95%CI: 17 to 20). The annual cost of disease-modifying drugs was 33,936.10 USD per patient. The cost attributed to serious infections was 2,474.6 USD. The cost of bilateral knee replacement per patient was $5,276.8 USD; and the cost for total hip replacement was $9,196.4. Both, the cost of hospitalization days per patient per year, and the indirect costs of RA increased as the disability score increased. This review reports useful information on epidemiological and cost parameters of moderate to severe RA, in the era of biological agents, in order to be useful for conducting economic evaluations regarding health in Argentina.
La presente revisión tiene como objetivo identificar información sobre parámetros epidemiológicos y estimar el costo de la artritis reumatoidea (AR) moderada a severa. Se llevó a cabo una búsqueda de la literatura en las principales bases de datos. Se recurrió a un consenso de expertos locales en reumatología para encontrar los parámetros más realistas, utilizando un método Delphi modificado. Se estimaron los costos médicos directos, utilizando información recopilada en la base de datos de costos unitarios del Instituto de Efectividad Clínica y Sanitaria de Argentina. Los costos indirectos se estimaron a través del enfoque del capital humano. Los costos se expresaron en dólares estadounidenses (USD) a noviembre de 2017. La prevalencia reportada de AR en Argentina fue 0,94% (IC95%: 0,86 a 1,02), con una tasa de incidencia anual de 19 cada 100 000 personas (IC95%: 17 a 20). El costo anual de las drogas modificadoras de la enfermedad fue de USD 33 936,10 por paciente. El costo atribuido a las infecciones serias fue de USD 2474,6. El costo del reemplazo bilateral de rodillas por paciente fue de USD 5276,8, y el del reemplazo total de cadera, de USD 9196,4. El costo por paciente por año de días de hospitalización y los costos indirectos de la AR se acrecentaron al aumentar el puntaje de discapacidad. La revisión reporta información útil acerca de parámetros epidemiológicos y de costos de la AR moderada a severa en la era de los agentes biológicos, con el fin de resultar de utilidad para la conducción de evaluaciones económicas de salud en Argentina.
Assuntos
Artrite Reumatoide , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Recursos em Saúde , Argentina/epidemiologia , Artrite Reumatoide/economia , Artrite Reumatoide/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , HumanosRESUMO
OBJECTIVE: To adapt the EULAR Activity Index for primary Sjögren's syndrome (ESSDAI) to the Argentine population. METHODS: observational, cross-sectional study that included patients in a period of ten months. Three Argentine rheumatologists adapted and translated to Spanish the original version in English and the final version was translated back into English by a research associate whose mother language was English. In order to estimate the constructive validity of the index, the visual analogous scale (VAS) of disease activity was used by experts. A subgroup of patients attended a second visit in order to evaluate test-retest reliability. RESULTS: 51 patients were included, 49 (96.1%) were female, the median age was 58 ((interquartile range (IQR): 49-69)). The median global VAS was 10 (IQR: 4-22.25) and the median total ESSDAI score was 5 (IQR: 3-9). The correlation between the global VAS and the total ESSDAI score of the scale was 0.79. The intraclass correlation coefficient was 0.67 (95% CI: 0.32-0.92) for the total score and 0.98 (95% CI: 0.92-0.995) for the global VAS. The results of the correlation coefficient between the VAS and the scale for each domain were: constitutional symptoms: 0.46; lymphadenopathy: 0.76; glandular: 0.78; joint: 0.61; skin: 1; respiratory: 0.83; renal: 1; muscular:- (no patient had myositis); peripheral nervous system: 0.72; central nervous system: 0.67; hematological: 0.96; biomarkers: 0.86. CONCLUSION: The results of this study showed that the ESSDAI is a reliable and valid index for this pSS argentinian population.
RESUMO
OBJETIVOS. Analizar el impacto presupuestario de upadacitinib (UPA) 15 mg + metotrexato (MTX) para el tratamiento de la artritis reumatoide (AR) moderada a grave en pacientes con respuesta inadecuada a los fármacos antirreumáticos modificadores de la enfermedad convencionales (RI-DMARc) desde la perspectiva de la seguridad social y los sectores de salud privados en Argentina. MATERIALES Y METODOS. Se desarrolló un modelo de análisis de impacto presupuestario para una cohorte hipotética de 100,000 adultos con cobertura de seguro de salud que fueron diagnosticados con AR en un horizonte de tiempo de 5 años. Los parámetros del modelo se obtuvieron a través de una revisión de la literatura y se validaron con expertos locales. Los costos se expresan en dólares estadounidenses (USD) para el 2024. RESULTADOS. La introducción de UPA 15 mg + MTX para el tratamiento de AR moderada a grave y RI-DMARc resultó en un costo incremental mínimo, con un costo acumulado total a cinco años de USD 1.855 para la seguridad social y USD 1.812 para el sector privado de salud, lo que representa aproximadamente el 2% del presupuesto total. El costo de adquisición de UPA fue la variable más influyente en el análisis de sensibilidad. CONCLUSIONES.La introducción de UPA 15 mg + MTX para el tratamiento de AR genera un incremento de costos marginal para el sistema de salud en Argentina, lo cual es especialmente importante en contextos de presupuestos limitados. Proporcionar estimaciones basadas en la evidencia es una herramienta valiosa para ayudar a tomar decisiones informadas sobre la asignación eficiente de recursos en salud.
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Patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) in the CONAART database (Argentine Consortium for Early Arthritis) were assessed for genetic risk factors for RA, specifically for HLA-DRB1 alleles and the PTPN22 rs2476601 polymorphism associated with progression to RA. This is a case-control study. Blood samples were obtained to determine HLA-DRB1 genotypes by PCR-SSO Luminex and PTPN22 (rs2476601) polymorphism by allelic discrimination. A control group of individuals from the general Argentinian population were obtained from the national register of cadaveric organ donors. A total of 1859 individuals were included in this analysis: 399 patients from the CONAART database (347 patients with RA at study end and 52 patients with UA at study end, mean follow-up time 25 ± 18 months) and 1460 individuals from the general Argentinian population. Compared with the controls, the HLA-DRB1*04 and DRB1*09 alleles were more commonly detected in patients with RA diagnosis (OR (95% CI) 2.23 (1.74-2.85) and 1.89 (1.26-2.81)) respectively. Both patients with UA and the general population showed higher frequency of DRB1*07, DRB1*11 and DRB1*15 alleles than patients with RA. PTPN22 rs2476601 polymorphism frequency was higher in RA and UA vs the general population; however, this was significantly different only for RA vs control group (OR [95% CI] = 1.81 [1.10-3.02], P = 0.018. HLA-DRB1 typing and PTPN22 allelic discrimination could distinguish between patients with UA, patients with early RA, and the general population in Argentina. This is the first study of HLA-DRB1 alleles and PTPN22 polymorphism associations with progression to early RA in an Argentinian population.
Assuntos
Artrite Reumatoide/genética , Cadeias HLA-DRB1/genética , Adulto , Idoso , Alelos , Argentina , Artrite/genética , Bases de Dados Factuais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Proteína Tirosina Fosfatase não Receptora Tipo 22/genéticaRESUMO
Introducción: recientemente, en Europa y en idioma inglés, se ha desarrollado el Clinical EULAR Sjögren's Syndrome Disease Activity Index (ClinESSDAI) para evaluar la actividad en pacientes con síndrome de Sjögren primario (SSp). Objetivos: validar el ClinESSDAI en pacientes con SSp en Argentina. Materiales y métodos: estudio de corte transversal. Se utilizó la versión en castellano del EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) validada en Argentina. Para evaluar la validez del constructo, se usó la escala visual análoga (EVA) desarrollada por un reumatólogo experto por dominio del ClinESSDAI y de la EVA global para el puntaje total del ClinESSDAI, mientras que otro profesional en la materia realizó el ESSDAI y ClinESSDAI. Para analizar la reproducibilidad, se estudió a un subgrupo de pacientes, sin mediar cambios en el tratamiento ni en la condición clínica, 10 días después de la evaluación basal. Todos los médicos examinaron a los pacientes desconociendo la evaluación de los demás colegas. Resultados: se incluyeron 47 pacientes con SSp. La correlación entre la EVA global y el ClinESSDAI fue muy buena (Rho 0,7), así como la correlación de la EVA y el ClinESSDAI de cada dominio. El coeficiente de correlación intraclase (CCI) entre el ESSDAI y el ClinESSDAI fue de 0,98. La reproducibilidad fue de 0,93. Conclusiones: el ClinESSDAI es una herramienta válida y reproducible en nuestra población, equiparable al ESSDAI.
Introduction: the Clinical EULAR Sjögren's Syndrome Disease Activity Index (ClinESSDAI) has recently been developed in Europe and in the English language to evaluate activity in patients with primary Sjögren's syndrome (pSS). Objectives: validate the ClinESSDAI in patients pSS in Argentina. Materials and methods: a cross-sectional study. The Spanish version of the ESSDAI, validated in Argentina, was used. To evaluate construct validity, the Visual Analog Scale (VAS) was used, performed by an expert rheumatologist per ClinESSDAI domain, and the global VAS was used for the total score of the ClinESSDAI, while another professional performed the ESSDAI and ClinESSDAI. To evaluate reproducibility, a subgroup of patients was evaluated without changes in treatment or clinical condition 10 days after the baseline evaluation. All physicians were blind to each other's evaluation. Results: 47 patients with pSS were included. The correlation between global VAS and ClinESSDAI was very good (Rho 0.7), as well as the correlation of the VAS and ClinESSDAI of each domain. The intraclass correlation coefficient (ICC) between ESSDAI and ClinESSDAI was 0.98. The reproducibility was 0.93. Conclusions: the ClinESSDAI is a valid and reproducible tool in our population, comparable to the ESSDAI.
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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.
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Terapia Biológica , Terapia de Alvo Molecular , Medicamentos SintéticosRESUMO
Objetivos: evaluar si los pacientes con lupus eritematoso sistémico (LES) al momento del diagnóstico con baja actividad de la enfermedad presentaron un curso más benigno de la enfermedad vs. aquellos que tuvieron actividad moderada/severa. Materiales y métodos: estudio observacional, analítico, de cohorte retrospectiva. Se revisaron historias clínicas de pacientes con diagnóstico de LES según criterios del American College of Rheumatology (ACR 1982/1997), del Systemic Lupus International Collaborating Clinics (SLICC 2012) o del ACR/European League Against Rheumatism (EULAR 2019), con un seguimiento mínimo de un año, que acudieron a la Sección de Reumatología del Hospital Rivadavia de la Ciudad Autónoma de Buenos Aires. Resultados: se incluyeron 100 pacientes con diagnóstico de LES, de los cuales el 44% presentaba actividad leve, mientras que el 56% tenía actividad moderada o severa al diagnóstico. Se observaron diferencias estadísticamente significativas entre ambos grupos en la cantidad de brotes a lo largo de la evolución de la enfermedad (mediana del grupo con actividad leve 0 (RIC 0-1) vs. mediana del grupo actividad moderada o severa 1 (RIC 1-2); p<0,01). Se detectó un menor compromiso de órganos durante la evolución de la enfermedad en aquellos con actividad basal leve en comparación con actividad basal moderada/severa, con diferencias estadísticamente significativas en el compromiso renal (15,91% vs. 55,36%; p<0,01). Conclusiones: los pacientes con actividad basal baja tuvieron un curso más benigno de la enfermedad y una menor cantidad de brotes severos, en comparación con quienes presentaron actividad moderada/severa al inicio de la enfermedad.
Objectives: to assess whether patients with systemic lupus erythematosus (SLE) and low disease activity at the time of diagnosis have a more benign course of the disease vs those who have moderate/severe activity at the time of diagnosis. Materials and methods: observational, analytical, retrospective cohort study. Clinical records of patients diagnosed with SLE according to ACR 1982/1997 Criteria, SLICC 2012 or ACR/EULAR 2019, who attended the Rheumatology Section of Rivadavia hospital in CABA, Argentina, were reviewed. Results: a total of 100 patients diagnosed with SLE were included, of which 44% had mild activity, while the remaining 56% had moderate or severe activity at diagnosis. Statistically significant differences were observed between the group that had mild baseline activity vs the group that presented moderate/severe baseline activity, with the first group presenting fewer flares throughout the course of the disease (median of the first group 0 (IQR 0-1) vs median of the second, 1 (IQR 1-2); p<0.01). Less organ involvement was observed throughout the course of the disease in those with mild baseline activity compared with moderate/severe baseline activity, with statistically significant differences in renal involvement (15.91% versus 55.36%; p<0.01). Conclusions: patients with low baseline activity had a more benign disease course, presenting fewer severe flares compared to patients who presented moderate to severe activity at disease onset.
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La granulomatosis con poliangitis (GPA) es una condición clínico-patológica que cursa con inflamación granulomatosa del tracto respiratorio superior e inferior, glomerulonefritis necrotizante focal y vasculitis necrotizante de vasos de pequeño y mediano tamaño (capilares, vénulas, arteriolas y arterias). La afectación de la GPA orbitaria oscila entre el 7 y el 45%. En ocasiones, la glándula lagrimal puede estar afectada de forma aislada y ser la manifestación inicial de la enfermedad. Presentamos el caso de una paciente con GPA y fístula nasolagrimal.
Granulomatosis with polyangiitis (GPA) is a clinical-pathological condition that presents with granulomatous inflammation of the upper and lower respiratory tract, focal necrotizing glomerulonephritis and necrotizing vasculitis of small and medium-sized vessels (capillaries, venules, arterioles and arteries). Orbital GPA involvement ranging from 7-45%. The lacrimal gland can occasionally be affected in isolation and be the initial manifestation of the disease. We present the case of a patient with GPA and nasolacrimal fistula.
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Septo NasalRESUMO
Introducción: la disfunción sexual (DS) es común entre las mujeres con enfermedades crónicas, incluyendo esclerosis sistémica (ES). Se ha asociado con características como la duración de la enfermedad, dolor, disminución de la actividad funcional, entre otras. Desde nuestro conocimiento, aún no contamos con datos locales. Objetivos: evaluar la frecuencia de DS en mujeres con ES; describir las características sociodemográficas, clínicas y psicológicas asociadas con la DS en mujeres con ES. Materiales y métodos: estudio observacional, analítico y de corte transversal. Se incluyeron mujeres de entre 20 y 59 años con diagnóstico de ES, según los criterios de clasificación del European League Against Rheumatism/American College of Rheumatology (ACR/EULAR 2013). Se excluyeron pacientes con enfermedades crónicas no controladas, otras patologías reumatológicas autoinmunes, e inactividad sexual o patología genitourinaria no relacionadas a ES en las últimas 4 semanas. La DS se evaluó con la versión en español del cuestionario índice de función sexual femenina (Female sexual function index, FSFI). Resultados: se incluyeron 56 pacientes. El 78,57% presentó DS y 19,64% era sexualmente inactiva debido a la enfermedad. Escala visual análoga (EVA) de fatiga (coeficiente ß: -0,08, IC 95%: -0,14 a -0,02; p<0,01), edad (coeficiente ß: -0,23, IC 95%: -0,40 a -0,05; p=0,01) y fibromialgia (coeficiente ß: -11,90, IC 95%: -17,98 a -5,82; p<0,01) mostraron una asociación significativa e independiente con DS en el análisis multivariado. Conclusiones: la DS es frecuente entre las mujeres con ES, y las pacientes más jóvenes, sin fibromialgia y con menor fatiga presentaron una mejor funcionalidad sexual.
Introduction: sexual impairment (SI) is common among women with chronic diseases, including systemic sclerosis (SSc). It has been associated with characteristics such as the duration of the disease, pain, decreased functional activity, among others. To the best of our knowledge, we still do not have local data. Objectives: to evaluate the frequency of SI in women with SSc. To describe the sociodemographic characteristics, disease itself and psychological items associated with SI in women with SSc. Materials and methods: observational, analytical, cross-sectional study. We included women between 20 and 59 years diagnosed with SSc according to 2013 classification criteria ACR/EULAR. We excluded patients with uncontrolled chronic diseases or other autoimmune rheumatologic diseases and patients who, in the last 4 weeks, had dyspareunia or were sexually inactive due to causes not attributable to their disease. SI was assessed using the Spanish version of female sexual function index questionnaire (FSFI). Results: 56 patients were included. 78.57% presented SI and 19.64% of them were sexually inactive patients due to the disease. Fatigue VAS (ß coefficient: -0.08, CI 95%: -0.14 to -0.02; p<0.01), age (ß coefficient: -0.23, CI 95%: -0.40 to -0.05; p=0.01) and fibromyalgia (ß coefficient: -11.90, CI 95%: -17.98 to -5.82; p<0.01) showed significant and independent association with SI in the multivariate analysis. Conclusions: SI is frequent among women with SSc, and younger patients, without fibromyalgia and with less fatigue have better sexual function.
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Feminino , Escleroderma Sistêmico , Comportamento Sexual , Disfunções Sexuais Fisiológicas , Mulheres , SexualidadeRESUMO
Abstract Background: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it's clinical, serological and histologic characteristics. Materials and methods: This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up. Results: 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1-5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8-12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not. Conclusions: Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients. Key points Patients with primary Sjögren's Syndrome may develop another connective tissue disease during follow-up. The most frequently connective tissue disease developed during follow-up in the population of patients with primary Sjogren's Syndrome studied was rheumatoid arthritis. It is important to be aware of this to make an early and proper diagnosis.