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1.
Nat Commun ; 10(1): 5120, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719529

RESUMO

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

2.
Rheumatol Adv Pract ; 3(1): rkz003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31431991

RESUMO

Objective: ANCA-associated vasculitis (AAV) is a rare multisystem disease. Modern therapeutic protocols have turned AAV from an acute, frequently fatal disease into a chronic disease requiring long-term immunosuppression. Patients must often manage substantial burdens related to chronic illness and treatment-related side effects, requiring help from informal carers. This study aimed to explore the experience of patients and of informal carers of patients with AAV about the impact of managing a rare rheumatic condition. Methods: A qualitative approach using semi-structured interviews was used. Interviews were conducted with a purposeful sample of 18 pairs of patients with AAV and their informal carers. The interviews were used to explore the participants' experience and effects of caring. The interviews were recorded and transcribed as verbatim text and analysed using the framework technique. Results: Eighteen patients (seven female; disease: 10 granulomatosis with polyangiitis; four microscopic polyangiitis; four eosinophilic granulomatosis with polyangiitis; age range 34-78 years; disease duration 1-20 years). Caregiver and patient perspectives were shared. The emerging themes were the physical and psychological impacts of the disease, the need for constant vigilance and fear of the future. Conclusion: Both patients and carers faced a range of challenges in managing a rare condition, including the seriousness of the illness, dealing with the emotional toll and knowing what to expect. This study offers insight into the experiences of patients and informal carers, and health-care professionals should address individuals' fears and expectations for recovery.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31325308

RESUMO

OBJECTIVES: PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. METHODS: Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. RESULTS: In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. CONCLUSION: PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.

5.
Int J Rheum Dis ; 22 Suppl 1: 21-27, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29707909

RESUMO

The classification of the systemic vasculitides has been controversial for several decades. The Chapel Hill consensus Conference definitions originally developed in 1994, but revised and extended in 2012 are now widely accepted. The American College of Rheumatology (ACR) criteria were first published in 1990, are now generally accepted to be out of date and new criteria are needed. More recently the classical division of the ANCA vasculitides using clinical phenotype has come under scrutiny with evidence from epidemiological, genetic and outcome studies that perhaps these conditions should be classified on the basis of ANCA specificity into PR3-ANCA positive and MPO-ANCA positive groups. The traditional distinction between giant cell arteritis and Takayasu arteritis has been questioned and some recent studies of GCA have included patients with only extra-cranial disease. The Diagnostic and Classification Criteria of Vasculitis study (DCVAS) will provide new validated classification criteria for the systemic vasculitides.


Assuntos
Pesquisa Biomédica/tendências , Reumatologia/tendências , Vasculite Sistêmica/classificação , Vasculite Sistêmica/diagnóstico , Terminologia como Assunto , Consenso , Conferências de Consenso como Assunto , Previsões , Humanos , Fenótipo , Vasculite Sistêmica/genética , Vasculite Sistêmica/imunologia
7.
Best Pract Res Clin Rheumatol ; 32(1): 3-20, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-30526896

RESUMO

Classification of the vasculitides has been traditionally based on vessel size. The American College of Rheumatology (ACR) criteria were developed in the 1980s and published in 1990 before the development of ANCA testing and modern imaging techniques such as MRI and PET scanning, and therefore, these criteria are not fit for use in 2010s. The Chapel Hill Consensus Conference provided a framework for defining various types of vasculitis. In the next two years, new classification criteria will be published from the DCVAS study, which will provide a modern system for the classification of vasculitis for clinical studies. The epidemiology of vasculitides is increasingly well studied; however, there remain gaps in our knowledge of the occurrence of vasculitis in many populations, especially from the third world or those with health care systems that do not permit ready collection of accurate epidemiological data. Giant cell arteritis presents in the elderly and those of Northern European ancestry; ANCA-associated vasculitis appears to have a consistent overall occurrence, but there are differences in the occurrence of MPO and PR3 vasculitis between populations. Kawasaki disease occurs most commonly in Asian populations, especially Japanese, and in those aged less than 5 years. It is currently the most common cause of acquired cardiac disease in those populations.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Humanos
9.
Rheumatology (Oxford) ; 57(6): 1002-1010, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29529281

RESUMO

Objectives: We aimed to provide insights into the aetiology of granulomatosis with polyangiitis (GPA), by conducting a large case-control study using a general population-based, prospectively collected database of healthcare records. Methods: We compared all incident cases of GPA in the Clinical Practice Research Datalink 1990-2014, with up to 10 age-, sex- and general practice-matched controls. We identified potential risk factors, recorded numbers of cases and controls exposed to each, and calculated odds ratios (ORs) using conditional logistic regression. Our main analysis excluded data recorded during 1 year before diagnosis, to prevent early symptoms being mistaken for risk factors. Results: We identified 757 people with GPA and matched 7546 controls. People with GPA were five times more likely to have a previous diagnosis of bronchiectasis (OR = 5.1, 95% CI: 2.7, 9.4; P < 0.0001), and these effects remained stable in diagnoses recorded >5 years prior to diagnosis. People with GPA were two to three times more likely than controls to have previous diagnoses of autoimmune diseases or chronic renal impairment, and these effects also remained stable >5 years prior to diagnosis. People with GPA were more likely to have a diagnosis of pulmonary fibrosis (OR = 5.7, 95% CI: 1.7, 19.5; P = 0.01) and sinus infections (OR = 2.7, 95% CI: 1.8, 4.2; P < 0.0001) recorded in the 3 years before diagnosis, but not before this. We also found former smoking, some medications and higher socio-economic status significantly, but less strongly, associated. Conclusion: We found novel long-term associations between GPA and pre-existing bronchiectasis and autoimmune diseases.


Assuntos
Doenças Autoimunes/complicações , Bronquiectasia/complicações , Medicina Geral/estatística & dados numéricos , Granulomatose com Poliangiite/etiologia , Vigilância da População/métodos , Sistema de Registros , Medição de Risco , Idoso , Doenças Autoimunes/diagnóstico , Bronquiectasia/diagnóstico , Bases de Dados Factuais , Feminino , Seguimentos , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Reino Unido/epidemiologia
11.
Rheumatol Adv Pract ; 2(2): rky025, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31431971

RESUMO

Objectives: We aimed to conduct a large audit of routine care for patients with ANCA-associated vasculitis. Methods: We invited all 34 hospitals within one health region in England to undertake a retrospective case note audit of all patients newly diagnosed or treated with CYC or rituximab (RTX) for ANCA-associated vasculitis from April 2013 to December 2014. We compared clinical practice to the British Society for Rheumatology guidelines for the management of adults with ANCA-associated vasculitis and the use of RTX with the National Health Service (NHS) England commissioning policy and National Institute for Health and Care Excellence (NICE) technology appraisal. Results: We received data from 213 patients. Among 130 newly diagnosed patients, delay from admission to diagnosis ranged from 0 to 53 days (median 6, interquartile range 3-10.5) for those diagnosed as inpatients. BVAS was recorded in 8% of patients at diagnosis. Remission at 6 months was achieved in 83% of patients. The 1-year survival was 91.5%. A total of 130 patients received CYC for new diagnosis or relapse. The correct dose of i.v. CYC (within 100 mg of the target dose calculated for age, weight and creatinine) was administered in 58% of patients. A total of 25% of patients had an infection requiring hospital admission during or within 6 months of completing their CYC therapy. Seventy-six patients received RTX for new diagnosis or relapse. A total of 97% of patients met the NHS England or NICE eligibility criteria. Pneumocystis jiroveci pneumonia prophylaxis (recommended in the summary of product characteristics) was given in only 65% of patients. Conclusion: We identified opportunities to improve care, including compliance with safety standards for delivery of CYC. Development of a national treatment protocol/checklist to reduce this heterogeneity in care should be considered as a priority.

12.
Rheumatology (Oxford) ; 56(11): 1962-1969, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968886

RESUMO

Objectives: There are few data on clinical profiles of ANCA-associated vasculitis (AAV) in different ethnic populations. The aim of this study was to examine the differences in the ANCA type and clinical features of AAV between populations using the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) dataset. Methods: The DCVAS is an international, multicentre, observational study recruiting in 133 sites. Eight ethnic categories were analysed: Northern European, Caucasian American, Southern European, Middle Eastern/Turkish, Chinese, Japanese, Indian subcontinent and other. ANCA type was categorized as myeloperoxidase (MPO), PR3 and ANCA negative. Organ system involvement was recorded using a standard dataset. Differences were analysed by chi-squared tests using a Bonferroni correction and logistic regression (adjusting for age and sex). Northern European was the reference population. Results: Data from 1217 patients with AAV were available and the 967 (79.5%) patients recruited by rheumatology departments were analysed to reduce confounding by recruitment specialty. There were differences in ANCA type between ethnic categories (P < 0.001): MPO-ANCA was more common than PR3-ANCA in Japanese, Chinese and Southern Europeans; PR3-ANCA was more common in the other groups. Compared with Northern Europeans, Japanese had a nearly 60-fold increased chance of having MPO-ANCA (vs PR3-ANCA) [odds ratio (OR) 59.2 (95% CI 8.0, 440.7), P < 0.001] and Chinese had a nearly 7-times increased chance [OR 6.8 (95% CI 2.6, 17.8), P < 0.001]. Ophthalmologic and otorhinolaryngologic involvement were less common in Japanese and Chinese populations than Northern Europeans; otherwise, there were few differences in organ involvement between ethnic groups. Conclusion: This study confirms the previously observed differential occurrence of MPO-AAV and PR3-AAV between different ethnic groups.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Oftalmopatias/fisiopatologia , Nefropatias/fisiopatologia , Otorrinolaringopatias/fisiopatologia , Dermatopatias/fisiopatologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etnologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Árabes , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Europa (Continente)/epidemiologia , Grupo com Ancestrais do Continente Europeu , Oftalmopatias/etiologia , Feminino , Doenças Urogenitais Femininas/etiologia , Doenças Urogenitais Femininas/fisiopatologia , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Índia/epidemiologia , Japão/epidemiologia , Nefropatias/etiologia , Masculino , Doenças Urogenitais Masculinas/etiologia , Doenças Urogenitais Masculinas/fisiopatologia , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Mieloblastina/imunologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , Razão de Chances , Otorrinolaringopatias/etiologia , Peroxidase/imunologia , Doenças Respiratórias/etiologia , Doenças Respiratórias/fisiopatologia , Dermatopatias/etiologia , Turquia/epidemiologia , Estados Unidos/epidemiologia
13.
Rheumatology (Oxford) ; 56(7): 1154-1161, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28379475

RESUMO

Objectives: Advances in diagnostic techniques have led to better distinction between types of vasculitis, potentially affecting the utility of the 1990 ACR classification criteria for vasculitis. This study tested the performance of these criteria in a contemporary vasculitis cohort. Methods: The Diagnosis and Classification in Vasculitis Study provided detailed clinical, serological, pathological and radiological data from patients with primary systemic vasculitis and clinical context-specific comparator conditions. Fulfilment of six ACR criteria sets and their diagnostic performance was evaluated in patients with a given type of vasculitis and its comparator conditions. Results: Data from 1095 patients with primary systemic vasculitis and 415 with comparator conditions were available. For classification, sensitivities and specificities for ACR classification criteria were, respectively, 81.1% and 94.9% for GCA; 73.6% and 98.3% for Takayasu's arteritis; 65.6% and 88.7% for granulomatosis with polyangiitis; 57.0% and 99.8% for eosinophilic granulomatosis with polyangiitis; 40.6% and 87.8% for polyarteritis nodosa; 28.9% and 88.5% for microscopic polyangiitis; and 72.7% and 96.3% for IgA-vasculitis. Overall sensitivity was 67.1%. Of cases identified by their respective criteria, 16.9% also met criteria for other vasculitides. Diagnostic specificity ranged from 64.2 to 98.9%; overall, 113/415 comparators (27.2%) fulfilled at least one of the ACR classification criteria sets. Conclusion: Since publication of the ACR criteria for vasculitis, the sensitivity for each type of vasculitis, except GCA, has diminished, although the specificities have remained high, highlighting the need for updated classification criteria.


Assuntos
Reumatologia/normas , Vasculite Sistêmica/classificação , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Granulomatose com Poliangiite/classificação , Granulomatose com Poliangiite/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Poliarterite Nodosa/classificação , Poliarterite Nodosa/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Sociedades Médicas , Vasculite Sistêmica/diagnóstico , Arterite de Takayasu/classificação , Arterite de Takayasu/diagnóstico , Fatores de Tempo , Estados Unidos
17.
Rheumatology (Oxford) ; 56(4): 589-596, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28013209

RESUMO

Objective: To estimate the incidence, prevalence and mortality of granulomatosis with polyangiitis in the UK. Methods: We conducted a historical cohort study using data from the Clinical Practice Research Datalink and Hospital Episode Statistics (HES). We calculated incidence rate ratios, adjusted for age, gender and ethnicity, using Poisson regression. Results: We identified 462 cases diagnosed between 1997 and 2013. Our overall estimate of incidence was 11.8 (95% CI: 10.7, 12.9)/million person-years. The incidence was 0.88 (95% CI: 0.40, 1.96) in children (aged <16 years) and 14.0 (95% CI: 12.8, 15.4) in adults. The incidence was lower in females (adjusted incidence rate ratio = 0.68; 95% CI: 0.56, 0.81) and highest in the 55-69 year age group (adjusted incidence rate ratio = 6.8, 95% CI: 4.9, 9.6; reference group 16-39 years). The incidence was not significantly different in the Black/Minority Ethnic population from that in the White population (adjusted odds ratio = 0.78, 95% CI: 0.53, 1.13, P = 0.13). The prevalence in 2013 was 134.9 (95% CI: 121.3, 149.6)/million. Mortality was 13.6% at 1-year, and higher in the HES- than in the Clinical Practice Research Datalink-identified cases (hazard ratio = 3.16, 95% CI: 2.19, 4.56, P < 0.001). Conclusion: By combining primary and secondary care datasets, we have found the incidence and mortality of granulomatosis with polyangiitis to be higher than previously reported. We predict that at present each year in the UK there will be ∼700 new cases, of whom 95 will die within 12 months.


Assuntos
Granulomatose com Poliangiite/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Granulomatose com Poliangiite/etnologia , Granulomatose com Poliangiite/mortalidade , Humanos , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Reino Unido/epidemiologia , Adulto Jovem
18.
Rheumatology (Oxford) ; 56(4): 524-528, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-27940595

RESUMO

Objective: Blindness is a recognized complication of GCA; however, the frequency of and risk factors for this complication have not been firmly established. The aim of this study was to examine the incidence and determinants of blindness in patients with GCA, using a large international cohort. Methods: The analysis was conducted among subjects recruited into the Diagnosis and Classification Criteria in Vasculitis Study. The study captures consecutive patients presenting to clinic-based physicians. New-onset blindness was assessed 6 months after diagnosis by completion of the Vasculitis Damage Index. Logistic regression analysis was used to assess the association between blindness and clinical variables. Results: Of 433 patients with GCA from 26 countries, 7.9% presented with blindness in at least one eye at 6 months. Risk factors identified at baseline for blindness at 6 months were identified and included prevalent stroke [odds ratio (OR) = 4.47, 95% CI: 1.30, 15.41] and peripheral vascular disease (OR = 10.44, 95% CI: 2.94, 37.03). Conclusion: This is the largest study to date of subjects with incident GCA and confirms that blindness remains a common complication of disease and is associated with established vascular disease.Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov , NCT01066208.


Assuntos
Cegueira/etiologia , Arterite de Células Gigantes/complicações , Idade de Início , Idoso , Complicações do Diabetes/etiologia , Feminino , Transtornos da Cefaleia/etiologia , Humanos , Masculino , Doenças Vasculares Periféricas/etiologia , Fatores de Risco , Acidente Vascular Cerebral/etiologia
19.
Rheumatol Adv Pract ; 1(1): rkx001, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31431941
20.
Oxf Med Case Reports ; 2016(11): omw081, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28031846
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