RESUMO
OBJECTIVES: The natural evolution of undifferentiated connective tissue diseases (UCTD) has not yet been established. The aim of our study was to analyse the clinical outcomes of a cohort of UCTD patients followed in a routine outpatient setting and to establish which clinical, serological or capillaroscopy features are associated with an increased risk of evolution to definite connective tissue disease (CTD). METHODS: Data for this study were collected by a retrospective review of 758 patients referred to our hospital, between 1999 and 2008, with suspected CTD. After selection criteria, 98 patients were considered eligible and their records, laboratory findings and nailfold-capillaroscopy pattern (NCP) were analysed until clinical outcome. Three groups of patient outcomes were established: remission, UCTD, and definite CTD. Logistic regression analysis was performed to study the association of baseline clinical features, including NCP progression during monitoring, with clinical outcomes. RESULTS: After a mean follow-up of 11±3 years, 62% of the patients continued to suffer from UCTD, 24% regressed to a remission state and 14% developed definite CTD. Cytopenias (p=0.030), positivity for antibody specificities (ENA) (p=0.008), anti-Ro (p=0.036) and antiphospholipid antibodies (p=0.032), and the presence of an altered NCP (p=0.026) at baseline proved different between groups and were more frequently encountered in the group that evolved to definite CTD when compared with the others two groups. Specifically, cytopenias (odds ratio -OR- 4.20 [1.30-13.56] p=0.016), the presence of an antinuclear antibody (ANA) titre ≥1/640 (OR 7.00 [1.99-24.66], p=0.002) and anti-centromere positivity (OR 3.77 [1.03-13.79], p=0.045) at baseline and NCP progression (OR 6.63 [1.70-25.87], p=0.007) were associated with the future presence of definite CTD. CONCLUSIONS: Most patients with UCTD remain in an undifferentiated state after routine outpatient clinic follow-up. High ANA titres or the presence of cytopenias at baseline, as well as progression of NCP during follow-up, are the leading factors associated with evolution to definite CTD.
Assuntos
Anticorpos Antinucleares/sangue , Capilares/patologia , Doenças do Tecido Conjuntivo/diagnóstico , Angioscopia Microscópica , Unhas/irrigação sanguínea , Testes Sorológicos , Adulto , Assistência Ambulatorial , Biomarcadores/sangue , Doenças do Tecido Conjuntivo/sangue , Doenças do Tecido Conjuntivo/classificação , Doenças do Tecido Conjuntivo/patologia , Progressão da Doença , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Terminologia como Assunto , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. METHODS AND ANALYSIS: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects' subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. ETHICS AND DISSEMINATION: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. TRIAL REGISTRATION NUMBER: 2020-000130-18; NCT04798755.
Assuntos
Uveíte Anterior , Uveíte , Adalimumab/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Análise Custo-Benefício , Humanos , Metotrexato/uso terapêutico , Estudos Multicêntricos como Assunto , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Proteômica , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Resultado do Tratamento , Uveíte/tratamento farmacológico , Uveíte Anterior/tratamento farmacológicoRESUMO
AIM: The aim of this study was to evaluate the association between periodontal parameters related with the periodontal disease severity and the presence and levels of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: This cross-sectional study included 164 RA patients. Socio-demographics and RA disease characteristics, including ELISA-detected ACPA (anti-CCP-2), were recorded. Exposure was assessed by periodontal parameters: plaque index (PI), bleeding on probing (BoP), probing pocket depth, and clinical attachment levels (CAL). Presence and levels of ACPAs (outcome) and exposure variables were compared by both parametric and non-parametric tests and associations were evaluated by adjusted odds ratio (OR). RESULTS: A significant association was observed between the presence of anti-CCP antibodies and severity of periodontal outcomes such as the mean CAL (OR 1.483, p = 0.036), mean PI (OR 1.029, p = 0.012), and the number of pockets ≥ 5 mm (OR 1.021, p = 0.08). High anti-CCP antibodies levels were associated with mean CAL, mean PI, and number of pockets ≥ 5 mm with an OR of 1.593 (p = 0.043), 1.060 (p < 0.001), and 1.031 (p = 0.031), respectively. Furthermore, a significant increase of 4.45 U/mL in anti-CCP antibodies levels (p = 0.002) in RA patients was found for each pocket ≥ 5 mm after adjusting for age, gender, smoking, time of disease evolution, and RA activity. CONCLUSIONS: In RA patients, the severity of periodontal conditions such as mean CAL, mean PI, and the number of pockets ≥ 5 mm were linearly associated with both the presence and levels of anti-CCP antibodies.
Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Periodontite/imunologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A high prevalence of periodontitis has been reported in rheumatoid arthritis (RA) patients, although the strength of this association, its temporal link and the possible relationship between the severity of periodontitis and RA disease activity remain unclear. The objective of this work was to investigate whether periodontitis is associated with RA and whether periodontitis severity is linked to RA disease activity. METHODS: This case-control study included 187 patients diagnosed with RA and 157 control patients without inflammatory joint disease. RA disease activity and severity were evaluated by the Disease Activity Score 28, the Simplified Disease Activity Index, the Clinical Disease Activity Index, rheumatoid factor, anti-citrullinated protein antibody titers, the erythrocyte sedimentation rate, C-reactive protein, presence of extra-articular manifestations and type of RA therapy. Exposure severity was assessed by the following periodontal parameters: plaque index, bleeding on probing, probing pocket depth and clinical attachment levels. Sociodemographic variables and comorbidities were evaluated as confounding variables. Outcome and exposure variables were compared by both parametric and nonparametric tests, and possible associations were assessed through regression analysis with a calculation for the adjusted odds ratio (OR). RESULTS: A significant association was demonstrated between periodontitis and RA with an adjusted OR of 20.57 (95% CI 6.02-70.27, p < 0.001). Compared with controls, all parameters related to periodontal status (plaque index, bleeding on probing, probing pocket depth and clinical attachment levels) were significantly worse in RA patients (p < 0.001). Periodontitis severity was significantly associated with RA disease activity (p < 0.001), showing in an ordinal logistic regression model an association between periodontal severity and disease activity with an adjusted OR of 2.66 (95% CI 1.24-5.74, p = 0.012). CONCLUSION: A significant association was demonstrated between periodontitis and RA, independent of other confounders. This association was more evident in patients with pronounced periodontal disease and higher RA disease activity.
Assuntos
Artrite Reumatoide/complicações , Periodontite/complicações , Índice de Gravidade de Doença , Adulto , Idoso , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/terapia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Índice Periodontal , Periodontite/sangue , Periodontite/terapia , Fator Reumatoide/sangueRESUMO
The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time.
RESUMO
OBJECTIVE: To compare the prevalence of the main comorbidities in 2 large cohorts of patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), with a focus on cardiovascular (CV) diseases. METHODS: This was a cross-sectional multicenter study where the prevalence of more relevant comorbidities in 2 cohorts was compared. Patients under followup from SJOGRENSER (Spanish Rheumatology Society Registry of Primary SS) and RELESSER (Spanish Rheumatology Society Registry of SLE), and who fulfilled the 2002 American-European Consensus Group and 1997 American College of Rheumatology classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex, and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when appropriate. RESULTS: A total of 437 primary SS patients (95% female) and 2,926 SLE patients (89% female) were included. The mean age was 58.6 years (interquartile range [IQR] 50.0-69.9 years) for primary SS patients and 45.1 years (IQR 36.4-56.3 years) for SLE patients (P < 0.001), and disease duration was 10.4 years (IQR 6.0-16.7 years) and 13.0 years (IQR 7.45-19.76 years), respectively (P < 0.001). Smoking, dyslipidemia, and arterial hypertension were associated less frequently with primary SS (odds ratio [OR] 0.36 [95% confidence interval (95% CI) 0.28-0.48], 0.74 [95% CI 0.58-0.94], and 0.50 [95% CI 0.38-0.66], respectively) as were life-threatening CV events (i.e., stroke or myocardial infarction; OR 0.57 [95% CI 0.35-0.92]). Conversely, lymphoma was associated more frequently with primary SS (OR 4.41 [95% CI 1.35-14.43]). The prevalence of severe infection was lower in primary SS than in SLE (10.1% versus 16.9%; OR 0.54 [95% CI 0.39-0.76]; P < 0.001). CONCLUSION: Primary SS patients have a consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma is greater.
Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Síndrome de Sjogren/epidemiologia , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de RegistrosRESUMO
PURPOSE: To report a case of central retinal artery occlusion (CRAO) in a patient with biopsy-verified Wegener's granulomatosis (WG) with positive C-ANCA. METHODS: A 55-year-old woman presented with a 3-day history of acute painless bilateral loss of vision; she also complained of fever and weight loss. Examination showed a CRAO in the left eye and angiographically documented choroidal ischemia in both eyes. RESULTS: The possibility of systemic vasculitis was not kept in mind until further studies were carried out; methylprednisolone pulse therapy was then started. Renal biopsy disclosed focal and segmental necrotizing vasculitis of the medium-sized arteries, supporting the diagnosis of WG, and cyclophosphamide pulse therapy was administered with gradual improvement, but there was no visual recovery. CONCLUSION: CRAO as presenting manifestation of WG, in the context of retinal vasculitis, is very uncommon, but we should be aware of WG in the etiology of CRAO. This report shows the difficulty of diagnosing Wegener's granulomatosis; it requires a high index of suspicion, and we should obtain an accurate medical history and repeat serological and histopathological examinations. It emphasizes that inflammation of arteries leads to irreversible retinal infarction, and visual loss may occur.