RESUMO
BACKGROUND: The aim of this study is to analyze if the results of the Oral Health Impact Profile-14 questionnaire (OHIP-14) in patients with primary Sjögren's syndrome (pSS) are correlated with salivary flow and level of xerostomia. METHODS: This observational cross-sectional study was conducted in 61 patients (60 women, one man, mean age 57.64 [13.52]) diagnosed of pSS according to the American-European Criteria (2002). After recording demographic, medical and dental data (decayed-missing-filled teeth index [DMFT]), unstimulated (UWS) and stimulated (SWS) salivary flows were collected. Subsequently, UWS flow was categorized into two groups (<0.1 ml/min and ≥0.1 ml/min) and SWS into three groups (<0.1 ml/min, 0.1-0.7 ml/min and >0.7 ml/min). Patients also filled out a visual analog scale (VAS) for xerostomia and OHIP-14 for self-reported quality of life (QoL). RESULTS: Data showed positive and significant correlation between OHIP-14 and xerostomia, based on VAS results (r = 0.52; p = 0.001). Furthermore, there was a negative correlation between UWS and OHIP-14 scores (r = -0.34; p = 0.006) and VAS for xerostomia (r = -0.22; p = 0.09). No significant correlation was found between SWS and OHIP-14 or VAS neither between DMFT and OHIP-14. When assessing the level of QoL by the UWS and SWS flow categories a significant association was found for UWS (p = 0.001) but not for SWS (p = 0.11). The OHIP-14 values were higher in the groups with lower salivary flow. The multiple linear regression to predict OHIP-14 only selected VAS for xerostomia as a statistically significant predictor. CONCLUSIONS: Increased level of xerostomia and reduced UWS flow decrease oral health-related QoL in patients with pSS.
Assuntos
Síndrome de Sjogren , Xerostomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Saliva , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Inquéritos e Questionários , Escala Visual Analógica , Xerostomia/diagnóstico , Xerostomia/etiologiaRESUMO
OBJECTIVES: To investigate the prevalence, associated factors, and effects of primary overt renal disease on morbidity in patients with primary Sjögren's syndrome (pSS). METHODS: All patients in the Sjögrenser (registry of adult pSS patients of the Spanish Society of Rheumatology) cohort were retrospectively investigated for the presence of clinically significant renal involvement directly related to pSS activity. RESULTS: Of the 437 patients investigated, 39 (9%) presented overt renal involvement during follow-up. Severe renal disease necessitating kidney biopsy was relatively rare (2%). Renal involvement may complicate pSS at any time during the disease course and is associated with severe disease (indicated by higher scores of involvement, activity, and damage), systemic multiorgan involvement, and a higher frequency of lymphoma. Multivariate analysis showed that older age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.07), higher European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores (OR 1.1, CI 1.03-1.18), serum anti-La/SSB positivity (OR 6.65, CI 1.41-31.372), and non-vasculitic cutaneous involvement (OR 5.47, 1.03-29.02) were independently associated with this complication. Chronic renal failure developed in 23 of 39 patients (59%); only 1 of them progressed to end-stage renal disease necessitating renal replacement therapy. Patients with overt renal disease showed higher Sjögren's syndrome disease damage index scores, higher rates of hospitalisation due to disease activity and higher rates of clinically relevant comorbidities. CONCLUSIONS: Overt renal involvement in pSS is not uncommon. Although it usually shows a favourable prognosis, is associated with significant morbidity.
Assuntos
Nefropatias , Síndrome de Sjogren , Adulto , Idoso , Estudos de Coortes , Humanos , Rim , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Estudos Retrospectivos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologiaRESUMO
OBJECTIVES: Digestive involvement (DI) has been reported in 10-30% of primary Sjögren's syndrome (pSS) patients, and few studies have systematically analysed the prevalence of DI in pSS patients. The aim of this study was to describe DI prevalence in pSS patients from the Sjögrenser Study, and to analyse its clinical associations. METHODS: All patients included in the Sjögrenser study, a Spanish multicentre randomised cohort, containing demographic, clinical and histologic data, have been analysed retrospectively. Patients were classified according to the presence of DI (oesophageal, gastric, intestinal, hepatic and pancreatic), and we have performed DI clinical associations, descriptive statistics, Student t or χ2 test, and uni and multivariate logistic regression. RESULTS: From 437 included patients, 95% were women, with a median age of 58 years, 71 (16.2%) presented DI: 21 (29.5%) chronic atrophic gastritis, 12 (16.9%) oesophageal motility dysfunction, 3 (4.2%) lymphocytic colitis, 18 (25.3%) primary biliary cholangitis, 15 (21.1%) autoimmune hepatitis, 7 (9.8%) pancreatic involvement and 5 (7%) coeliac disease. Half of them developed DI at the same time or after pSS diagnosis. Patients with DI were significantly older at pSS diagnosis (p=0.032), more frequently women (p=0.009), presented more autoimmune hypothyroidism and C3 hypocomplementaemia (p=0.040), and were treated more frequently with glucocorticoids, immunosuppressant and biologic therapies. Patients with pancreatic involvement presented more central nervous system and renal involvement, Raynaud's phenomenon, lymphoma and C3/C4 hypocomplementaemia. CONCLUSIONS: DI is frequent in Sjögrenser patients, mainly in the form of autoimmune disorders, and seem to be associated with a more severe phenotype. Our results suggest that DI should be evaluated in pSS patients, especially those with more severe disease.
Assuntos
Hepatite Autoimune , Síndrome de Sjogren , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Estudos Retrospectivos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologiaRESUMO
BACKGROUND: Primary Sjogren's syndrome (pSS) is an autoimmune disease that leads to salivary and lacrimal gland dysfunction. The adaptive immune response associated with T helper-2 lymphocytes appears to be altered in these patients. Therefore, the objective of this study was to determine the salivary levels of interleukin (IL)-6, IL-5, and IL-4 in patients with pSS when compared to a healthy control (HC) group. The secondary objectives were to study whether ILs levels in pSS patients were associated with salivary flow, patient-reported outcomes (PROMs) for xerostomia and oral health quality of life (Oral Health Impact Profile-14 [OHIP-14]), pSS classification criteria and presence of extraglandular manifestations. METHODS: A case-control study was conducted in 36 patients with pSS and 35 HCs. Cytokine levels were measured using high-sensitivity multiplex map human immunoassays. Unstimulated and stimulated whole saliva were collected and patients filled out questionnaires. The Mann-Whitney U test, chi-squared test, and Spearman correlation test were used. RESULTS: Interleukin-6 was significantly higher in pSS patients than in HCs (P = .0001). IL-6 was significantly higher in pSS patients with a positive salivary gland biopsy (P = .04), whole stimulated saliva hyposalivation (P = .02), and presence of musculoskeletal disorders (P = .03). There was a non-significant positive correlation between IL-6 levels and PROMs for xerostomia (r = .31; P = .06) and OHIP-14 (r = .07; P = .68) in pSS patients. Levels of IL-4 and IL-5 were not detected in both pSS and HCs patients. CONCLUSIONS: Salivary IL-6 levels are significantly associated with pSS patients, and therefore, it is hypothesized that this biomarker may be useful in the diagnosis and follow-up of this disease.
Assuntos
Síndrome de Sjogren , Biomarcadores , Estudos de Casos e Controles , Humanos , Qualidade de Vida , Saliva , Síndrome de Sjogren/diagnósticoRESUMO
This study aimed at determining socio-demographic and clinical factors of primary Sjögren syndrome (pSS) associated with osteoporosis (OP) and fragility fracture. SJOGRENSER is a cross-sectional study of patients with pSS, classified according to American European consensus criteria developed in 33 Spanish rheumatology departments. Epidemiological, clinical, serological and treatment data were collected and a descriptive analysis was conducted. Bivariate and multivariate analyses were performed using a binomial logistic regression to study the factors associated with OP and fragility fracture in pSS. 437 patients were included (95% women, with a median age of 58.6 years). 300 women were menopausal (76.4%). Prevalence of OP was 18.5% [in men (N = 21) this measured 19%]. A total of 37 fragility fractures were recorded. In the multivariate analysis, there was an association between OP and age: in the 51-64 age range (menopausal women), the OR measured 9.993 (95% CI 2301-43,399, p = 0.002); In the age > 64 years group, OR was 20.610 (4.679-90.774, p < 0.001); between OP and disease duration, OR was 1.046 (1.008-1085, p = 0.017); past treatment with corticosteroids, OR 2.548 (1.271-5.105, p = 0.008). Similarly, an association was found between fragility fractures and age: in the 51-64 age group, OR measured 5.068 (1.117-22,995, p = 0.035), age > 64 years, OR was 7.674 (1.675-35,151, p < 0.009); disease duration, OR 1.049 (CI 1.003-1097, p < 0.036) and the ESSDAI index, OR 1.080 (1.029-1134, p = 0.002). Patients with pSS can develop osteoporosis and fragility fractures over the course of the disease. Age, corticosteroids treatment and disease duration were associated with the development of OP. Disease duration and ESSDAI were associated with the development of fractures in patients with pSS.
Assuntos
Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Síndrome de Sjogren/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Menopausa/fisiologia , Pessoa de Meia-Idade , Fraturas por Osteoporose/etiologia , Sistema de Registros , Síndrome de Sjogren/tratamento farmacológico , Espanha/epidemiologiaRESUMO
OBJECTIVES: To assess the effects of Xerostom® toothpaste and mouthwash in primary Sjögren's syndrome (pSS) patients with xerostomia. SUBJECTS AND METHODS: A double-blinded, randomized study where patients were assigned at baseline test or control products. Patients used the products 3 times/day/28 days. We used a visual analogue scale (VAS) for xerostomia and an Oral Health Impact Profile-14 (OHIP-14), baseline and after treatment, to assess possible improvement. RESULTS: A total of 28 patients with pSS were included in this study, but only 24 finished it (all women, mean age 55.21 ± 11.87), and 13 patients received the test and 11 the control. VAS and OHIP-14 scores decreased in both groups after treatment but significant differences between groups were not found. We do not detect VAS intragroup significant differences before and after treatment in test and control groups. A significant improvement in OHIP-14 was identified in the treatment group, while no significant differences were observed in the control group. No adverse effects were present. CONCLUSIONS: Xerostom® toothpaste and mouthrinse may alleviate and improve quality of life without associated side effects, but further research with a larger number of participants and follow-up are necessary to establish the positive efficacy of these topical products in pSS patients.
Assuntos
Antissépticos Bucais/uso terapêutico , Síndrome de Sjogren/complicações , Cremes Dentais/uso terapêutico , Xerostomia/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Escala Visual Analógica , Xerostomia/etiologiaRESUMO
The objective of the study was to assess the ESSDAI index characteristics in the SJÖGRENSER cohort (Spanish Rheumatology Association's registry of patients with Primary Sjögren Syndrome [PSS]). SJÖGRENSER is a prospective multicentric study on a cohort of Spanish patients with PSS who meet the 2002 American-European consensus from rheumatology units. 298 variables were studied in patients for the inclusion of the study from an anonymous list from each department. The ESSDAI (EULAR Sjögren's syndrome disease activity index) includes 12 domains and measures systematic activity in PSS patients. Each domain is divided into 3-4 levels, (0: no activity; 1: low activity; 2: moderate activity; 3: high activity) and is attributed a weight. Each domain score is obtained by multiplying the activity level by the weight assigned. According to ESSDAI: low activity < 5; moderate activity 5-13, and high activity ≥ 14. ESSDAI was compared between several European PSS cohorts (EULAR, ASSES, GEAS, GRISS, Ducth). 437 patients were included from 33 Spanish rheumatology units. 95.2% were women with a median age of 58.63 years [p25-p75: 50.02-67.98 years] and average PSS evolution of 10.4 years (6-16 years). ESSDAI median on entering the study was 2 (0-4). 31% of patients had ESSDAI 0; low activity 49%, moderate activity 15%, and high activity 5%. Those with greater activity were the joint, haematological and biological domains, whereas the lung was the most affected organ with pleural and parenchymatous involvement. Unlike other European cohorts, the initial SJÖGRENSER cohort was characterised by low-zero systemic activity in 80% of patients, which differentiates it from other cohorts and provides a prospective study opportunity.
Assuntos
Síndrome de Sjogren/fisiopatologia , Idoso , Antirreumáticos/uso terapêutico , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Índice de Gravidade de Doença , Síndrome de Sjogren/complicações , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia , EspanhaRESUMO
INTRODUCTION: Primary Sjögren's syndrome (pSS) is an autoimmune disease, characterized by lymphocytic infiltration of exocrine glands and other organs, resulting in dry eye, dry mouth and extraglandular systemic findings. OBJECTIVE: To explore the association of severe or very severe dry eye with extraocular involvement in patients diagnosed with primary Sjögren's syndrome. METHODS: SJOGRENSER registry is a multicenter cross-sectional study of pSS patients. For the construction of our main variable, severe/very severe dry eye, we used those variables that represented a degree 3-4 of severity according to the 2007 Dry Eye Workshop classification. First, bivariate logistic regression models were used to identify the effect of each independent variable on severe/very severe dry eye. Secondly, multivariate analysis using regression model was used to establish the independent effect of patient characteristics. RESULTS: Four hundred and thirty-seven patients were included in SJOGRENSER registry; 94% of the patients complained of dry eye and 16% developed corneal ulcer. Schirmer's test was pathological in 92% of the patients; 378 patients presented severe/very severe dry eye. Inflammatory articular involvement was significantly more frequent in patients with severe/very severe dry eye than in those without severe/very severe dry eye (82.5 vs 69.5%, p = 0,028). Inflammatory joint involvement was associated with severe/very severe dry eye in the multivariate analysis, OR 2.079 (95% CI 1.096-3.941). CONCLUSION: Severe or very severe dry eye is associated with the presence of inflammatory joint involvement in patients with pSS. These results suggest that a directed anamnesis including systemic comorbidities, such as the presence of inflammatory joint involvement or dry mouth in patients with dry eye, would be useful to suspect a pSS.
Assuntos
Ceratoconjuntivite Seca/patologia , Síndrome de Sjogren/patologia , Estudos Transversais , Síndromes do Olho Seco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , XerostomiaRESUMO
OBJECTIVES: To assess fibromyalgia (FM) prevalence in a large cohort of primary Sjögren's syndrome patients (pSS) from a National Database. METHODS: Data included in the national retrospective register of pSS patients of the Spanish Society of Rheumatology (SJOGRENSER) were analysed. RESULTS: 437 pSS patients were included and a 14.6% of FM prevalence was found. FM-pSS patients significantly showed more constitutional, fatigue and arthralgia symptoms, splenomegaly, genital, skin and ear involvement and dyslipidaemia (p<0.05), as well as higher ESSPRI and SSDAI scores (p<0.01). Several symptomatic treatments were more frequently used in FM-pSS patients. No differences were observed in laboratory markers, imaging techniques or histologic inflammatory findings. Patients with FM showed statistically more fatigue than pSS without FM. In the multivariate logistic regression analysis several features were associated to pSS-FM patients. CONCLUSIONS: We show data on a reliable prevalence of FM in pSS patients and its multiple associated factors along with the presence of higher disease activity scores than patients who did not show FM. The presence of fatigue, arthralgia, constitutional symptoms and dyslipidaemia were more likely to coexist in pSS-FM patients.
Assuntos
Fibromialgia/epidemiologia , Sistema de Registros , Síndrome de Sjogren/epidemiologia , Adulto , Idoso , Artralgia/epidemiologia , Artralgia/etiologia , Dislipidemias/epidemiologia , Dislipidemias/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Estudos Retrospectivos , Reumatologia , Fatores de Risco , Síndrome de Sjogren/complicações , Síndrome de Sjogren/fisiopatologia , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Sociedades Médicas , Espanha/epidemiologia , Esplenomegalia/epidemiologia , Esplenomegalia/etiologiaRESUMO
OBJECTIVES: To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. RESULTS: Three damage clusters were identified. Cluster 1 (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 100% in clusters 2 and 3, P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 (8.0% of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. CONCLUSION: In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.
Assuntos
Doenças Cardiovasculares/mortalidade , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/mortalidade , Doenças Musculoesqueléticas/mortalidade , Índice de Gravidade de Doença , Adulto , Doenças Cardiovasculares/etiologia , Análise por Conglomerados , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/etiologia , Sistema de Registros , Espanha , Fatores de TempoRESUMO
To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources.
Assuntos
Linfoma/diagnóstico , Linfoma/etiologia , Síndrome de Sjogren/complicações , Feminino , Humanos , Masculino , Prognóstico , Fatores de RiscoRESUMO
A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P(MH)= 1.92 × 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P(MH)= 4.84 × 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P(χ2) = 2.82 × 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P(MH)= 2.82 × 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.
Assuntos
Predisposição Genética para Doença/genética , Receptores de Interleucina-12/genética , Escleroderma Sistêmico/genética , População Branca/genética , Europa (Continente)/etnologia , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos/etnologiaRESUMO
BACKGROUND AND OBJECTIVE: Rheumatic diseases account for almost 30% of consultations attended in Spanish primary care centres. The main objective was to analyse the demand for rheumatology consultations from Primary Care and their resolution using the electronic consultation system. PATIENTS AND METHODS: Retrospective descriptive study of electronic consultations from primary care centres in the health area to the Rheumatology service of a tertiary hospital, between July 2020 and May 2021. RESULTS: The last 500 consecutive consultations were collected. Mean age of patients was 59.5 years; 74.2% were women. Main reasons for consultation were osteoporosis and treatment of patients with rheumatoid arthritis and spondyloarthritis under follow-up by the department. Mean response time was 2 days. Fifty-seven per cent of patients required outpatient appointments. DISCUSSION: Over 40% of queries were resolved thanks to the electronic consultation system in an average of 2 days, otherwise patients would have been referred to specialized care.
Assuntos
Consulta Remota , Reumatologia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Centros de Atenção Terciária , Estudos Retrospectivos , Atenção Primária à SaúdeRESUMO
OBJECTIVE: Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features. METHODS: Two case-control sets of Caucasian origin from the USA and Spain, comprising a total of 2316 cases of SSc and 2347 healthy controls, were included in the study. Five single nucleotide polymorphisms (SNPs) in the PHRF1-IRF7-CDHR5 locus were genotyped using TaqMan allelic discrimination technology. A meta-analysis was performed to test the overall effect of these genetic variants on SSc. RESULTS: Four out of five analysed SNPs were significantly associated with the presence of anticentromere autoantibodies (ACA) in the patients with SSc in the combined analysis (rs1131665: p(FDR)=6.14 × 10(-4), OR=0.78; rs4963128: p(FDR)=6.14 × 10(-4), OR=0.79; rs702966: p(FDR)=3.83 × 10(-3), OR=0.82; and rs2246614: p(FDR)=3.83 × 10(-3), OR=0.83). Significant p values were also obtained when the disease was tested globally; however, the statistical significance was lost when the ACA-positive patients were excluded from the study, suggesting that these associations rely on ACA positivity. Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant. CONCLUSIONS: The results show that variation in the IRF7 genomic region is associated with the presence of ACA in patients with SSc, supporting other evidence that this locus represents a common risk factor for autoantibody production in autoimmune diseases.
Assuntos
Anticorpos Antinucleares/sangue , Doenças Autoimunes/genética , Fator Regulador 7 de Interferon/genética , Escleroderma Sistêmico/genética , Anticorpos Antinucleares/biossíntese , Doenças Autoimunes/imunologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/imunologiaRESUMO
OBJECTIVE: To evaluate the efficacy and safety of belimumab in patients with Primary Sjögren's syndrome (pSS). METHODS: The search included manuscripts assessing the efficacy or safety of belimumab in patients with pSS (American-European Consensus Criteria 2002) published between 2004 and 2017 in MEDLINE, EMBASE or Cochrane databases. Two reviewers independently selected the articles, extracted data and evaluated the quality of the evidence following Scottish Intercollegiate Guidelines Network (SIGN) recommendation grades. RESULTS: Out of 135 citations, only 3 articles were included. All of them publishing results from the same study at different time points including 28 patients. At week 28 improvement was reported for visual analogue scale (VAS) dryness score and glandular manifestations in 37% and 77% of patients, respectively, which persisted at week 52 (W52). Belimumab was well tolerated and safely administered. CONCLUSION: Published evidence to determine the efficacy of belimumab in pSS is limited. Belimumab seems to be effective to reduce systemic activity, parotid enlargement, lymphadenopathies, articular manifestation and B cell biomarkers.
RESUMO
OBJECTIVE: The aim of this study is to describe the findings of a protocolised odontological evaluation of patients with primary Sjögren's syndrome (pSS) treated in rheumatology units in the Community of Madrid. METHODS: Multicentric descriptive study in which pSS patients classified according to the American-European consensus of 2002 criteria were included. We collected the demographic, clinical and serological data of each patient. A complete oral examination was performed and salivary flow and the CAOD caries index were collected. The patients completed the visual analogue scale for xerostomia, the Oral Health Impact Profile-14 questionnaire and an oral health questionnaire. RESULTS: Sixty-one patients were recruited. Ninety-eight percent were women and the mean age of the patients was 57 years. Pathological oral signs (unstimulated salivary flow/salivary glands sialography/scintigraphy) were present in 52.5% of the patients, anti-Ro/anti-La were positive in 90.2%. Ninety-two percent of the patients reported xerostomia and 61% of the patients suffered from hyposialia. Thirty-five patients presented oral mucosa lesions. CAOD index was 16.97±7.93 and visual analogue scale for xerostomia was 46.69±14.43. The results of the OHIP-14 questionnaire were 23.13±14.16. Patients with pathological oral signs obtained a significantly higher Oral Health Impact Profile-14 score (P=.03). We also found that patients with peripheral nervous system involvement obtained a significantly higher Oral Health Impact Profile-14 score (P=.001) CONCLUSIONS: The presence of xerostomia in this cohort of pSS patients was high and hyposialia was present in 61% of the patients. Oral lesions appeared in more than half of the subjects. Oral health had a negative impact on the quality of life of patients with pSS, being higher in those with pathological objective oral signs and in those with peripheral nervous system involvement.
RESUMO
To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years, p = 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (p = 0.043) and tended to be lower than in the healthy group (p = 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination. Key points: ⢠Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered. ⢠However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required. ⢠This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.
Assuntos
Vacinas contra Hepatite B , Hepatite B , Adulto , Estudos de Coortes , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Humanos , Imunidade , VacinaçãoRESUMO
OBJECTIVE: To formulate SER recommendations for the use of biological agents in primary Sjögren's syndrome (pSS). METHODS: Relevant clinical research questions were identified on the use of biological agents in pSS. The clinical questions were reformulated into 4PICO questions. A search strategy was designed and a review of the scientific evidence of studies published until May 2017 was carried out. The scientific evidence available was systematically reviewed. The overall level of scientific evidence was assessed using the SIGN evidence levels. After that, specific recommendations were made. RESULTS: Rituximab is recommended as the biological agent of choice for extraglandular manifestations refractory to conventional treatment. The use of anti-TNF agents is discouraged. The scientific evidence with belimumab and abatacept is scarce, so they should be considered only in cases refractory to rituximab. CONCLUSIONS: Rituximab is the biological agent of choice in severe extraglandular manifestations of pSS. Belimumab or abatacept may be useful in selected cases.
Assuntos
Produtos Biológicos/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Antirreumáticos/uso terapêutico , Humanos , Rituximab/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. MATERIAL AND METHODS: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. RESULTS: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). CONCLUSIONS: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Antivirais/sangue , Terapia Biológica/efeitos adversos , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Biomarcadores/sangue , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologiaRESUMO
OBJECTIVE: The development of common variable immunodeficiency (CVID) or hypogammaglobulinemia in systemic lupus erythematosus (SLE) is rare. The purpose of this article is to provide a detailed review of lupus-associated CVID and to identify clinical characteristics and laboratory features in patients with SLE-associated CVID. METHODS: We describe 2 patients with SLE and CVID and review the cases published in the English literature highlighting both the demographic and the clinical characteristics and the laboratory and therapeutic aspects of this disorder. RESULTS: Detailed descriptions of 18 patients were available; 89% were females with a mean age at the onset of SLE of 23.8 years. In 50% of patients CVID developed within the first 5 years after the diagnosis of SLE. All patients had been treated with corticosteroids and 72% had also received immunosuppressive therapy. Sinopulmonary infections were the most frequent symptom. SLE disease activity decreased after the development of CVID in 67% of patients. Most patients (89%) were treated with gammaglobulin therapy. The most notable immunological feature was a reduced number or percentage of B-cells in 60% of patients. CONCLUSIONS: CVID should be suspected in any SLE patient with recurrent sinopulmonary infections in the absence of SLE activity and/or immunosuppressive treatment.