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1.
J Rheumatol ; 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31203229

RESUMO

OBJECTIVE: To analyze the role that infections play on the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) outcome. METHODS: A retrospective study of adult patients with AAV diagnosed in a tertiary center. Clinical features, laboratory findings, treatment, relapses, major infections, and outcome were evaluated. RESULTS: Included were 132 patients [51 microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), 29 eosinophilic GPA (EGPA)] with a mean followup of 140 (96-228) months. ANCA were positive in 85% of cases. A total of 300 major infections, mainly bacterial (85%), occurred in 60% patients during the followup. Lower respiratory tract (64%) and urinary tract infections (11%) were the most frequent, followed by bacteremia (10%). A total of 7.3% opportunistic infections were observed, most due to systemic mycosis. Up to 46% of all opportunistic infections took place in the first year of diagnosis, and 55% of them under cyclophosphamide (CYC) treatment. Bacterial infections were associated with Birmingham Vasculitis Activity Score (version 3) > 15 at the disease onset, a total cumulative CYC dose > 8.65 g, dialysis, and development of leukopenia during the followup. Leukopenia was the only factor independently related to opportunistic infections. Forty-four patients died, half from infection. Patients who had major infections had an increased mortality from any cause. CONCLUSION: Our results confirm that major infections are the main cause of death in patients with AAV.

2.
PLoS One ; 13(12): e0209343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586461

RESUMO

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.


Assuntos
Fator Ativador de Células B/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Escleroderma Sistêmico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Redes Reguladoras de Genes/genética , Técnicas de Genotipagem , Arterite de Células Gigantes/patologia , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/patologia
3.
Clin Exp Rheumatol ; 36(6 Suppl 115): 40-44, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29745871

RESUMO

OBJECTIVES: To describe the characteristics of patients with Behçet's disease (BD) who presented with venous thrombosis. In addition, we identified the factors associated with this venous involvement and those related with recurrent venous thrombosis. METHODS: Up to January 2015, 544 BD patients from 20 Spanish hospitals had been included in the REGEB (REGistro de la Enfermedad de Behçet as Spanish nomenclature). We selected those patients who presented venous thrombosis. Descriptive analysis was performed and factors related with venous thrombosis were identified. RESULTS: Overall, 99 (18.2%) BD patients had vascular thrombosis, 91 (16.7%) of them (16.7%) involving venous vessels and 18 (19.7%) suffered from venous thrombotic relapse. Lower limbs were the most common location of deep venous thrombosis present in up to 60% of patients. In 12 (13.2%) patients, venous thrombosis affected two vascular territories simultaneously and in 6 (6.6%) the venous and arterial involvement coincided in time. Overall, at the diagnosis of venous thrombosis, 97.6% of patients presented concomitantly other clinical symptoms attributable to BD. In logistic regression multivariate analysis factors associated to venous thrombosis were male sex (Odds ratio [OR] 4.3, 95% confidence interval [CI] 2.5-7.7), erythema nodosum (OR 2.4, 95%CI 1.4-4.1), fever (OR 2.0, 95%CI 1.1-3.8), and central nervous system (CNS) involvement (OR 2.5, 95%CI 1.3-4.8). Considering relapses, CNS involvement was an independent risk factor according logistic regression. However, Cox multivariate analysis did not confirm this finding. CONCLUSIONS: We identified factors related with venous involvement in patients included in the REGEB cohort.


Assuntos
Síndrome de Behçet/epidemiologia , Trombose Venosa/epidemiologia , Adolescente , Adulto , Síndrome de Behçet/diagnóstico , Feminino , Humanos , Masculino , Prognóstico , Recidiva , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo , Trombose Venosa/diagnóstico , Adulto Jovem
4.
Ann Hematol ; 97(8): 1349-1356, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29572561

RESUMO

The coexistence of autoimmune disorders (AD) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) has been widely recognized, although with distinct results regarding their prevalence and impact on the outcomes of the underlying hematological process. This study was aimed to analyze the prevalence, clinical characteristics, and outcomes of MDS with AD in a series of 142 patients diagnosed with MDS and CMML. AD was ascertained by both the presence of clinical symptoms or compatible serological tests. In total, 48% patients were diagnosed as having AD, being hypothyroidism the most commonly reported clinical AD (8%) and antinuclear antibodies the most frequent serological parameter identified (23.2%). The presence of AD was associated with female gender, lower hemoglobin levels, and higher IPSS-R. Overall survival for patients with AD was inferior to those with no AD (69 vs. 88% at 30 months; HR 2.75, P = 0.008). Notably, clinical but not isolated immune serological parameters had an impact on the outcomes of patients with AD. Finally, in a multivariate analysis, the presence of AD (HR 2.26) along with disease risk categories (very low and low vs. intermediate, high, and very high IPSS-R; HR 4.62) retained their independent prognostic value (P < 0.001). In conclusion, AD are prevalent in MDS and CMML patients and have prognostic implications, especially in lower-risk MDS patients.


Assuntos
Doenças Autoimunes/complicações , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Biomarcadores , Feminino , Humanos , Incidência , Leucemia Mielomonocítica Crônica/epidemiologia , Leucemia Mielomonocítica Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Avaliação de Resultados da Assistência ao Paciente , Prevalência , Prognóstico , Adulto Jovem
5.
JAMA Oncol ; 4(3): 384-388, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29188284

RESUMO

Importance: The histiocytic neoplasms Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are highly enriched for BRAF V600 mutations and have been previously shown to be responsive to treatment with vemurafenib, an inhibitor of the BRAF V600 kinase. However, the long-term efficacy and safety of prolonged vemurafenib use in these patients are not defined. Here we analyze the final efficacy and safety data for vemurafenib in patients with ECD and LCH enrolled in the VE-BASKET study. Objective: To determine the efficacy and safety of vemurafenib in adults with ECD or LCH enrolled in the VE-BASKET study. Design, Setting, and Participants: The VE-BASKET study was an open-label, nonrandomized, multicohort study for patients with nonmelanoma cancers harboring the BRAF V600 mutation. Patients with BRAF V600-mutant ECD or LCH were enrolled in an "other solid tumor" cohort of the VE-BASKET study, and they were enrolled in the present study. Interventions: Patients received vemurafenib, 960 mg, twice daily continuously until disease progression, study withdrawal, or occurrence of intolerable adverse effects. Main Outcomes and Measures: The primary end point was confirmed objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Secondary end points included progression-free survival (PFS), overall survival (OS), metabolic response by modified positron-emission tomography (PET) Response Criteria in Solid Tumors (PERCIST) using 18F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT), and safety. Results: A total of 26 patients from the VE-BASKET trial (22 with ECD, 4 with LCH) were included in the present study (14 women and 12 men; median age, 61 years; age range, 51-74 years). The confirmed ORR was 61.5% (95% CI, 40.6%-79.8%) in the overall cohort and 54.5% (95% CI, 32.2%-75.6%) in patients with ECD. All evaluable patients achieved stable disease or better. The median PFS and OS had not been reached in the overall cohort at study closure despite a median follow-up of 28.8 months; 2-year PFS was 86% (95% CI, 72%-100%), and 2-year OS was 96% (95% CI, 87%-100%). All 15 patients evaluated by FDG-PET/CT achieved a metabolic response, including 12 patients (80%) with a complete metabolic response. The most common adverse events (AEs) in the overall cohort included arthralgia, maculopapular rash, fatigue, alopecia, prolonged QT interval, skin papilloma, and hyperkeratosis. Hypertension and dermatologic AEs occurred at higher rates than those reported in metastatic melanoma. Conclusions and Relevance: In this study, vemurafenib had prolonged efficacy in patients with BRAF V600-mutant ECD and LCH and warrants consideration as a new standard of care for these patients.


Assuntos
Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/genética , Histiocitose de Células de Langerhans/tratamento farmacológico , Mutação de Sentido Incorreto , Proteínas Proto-Oncogênicas B-raf/genética , Vemurafenib/uso terapêutico , Idoso , Substituição de Aminoácidos/genética , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/mortalidade , Feminino , Fluordesoxiglucose F18 , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Valina/genética
6.
Medicine (Baltimore) ; 96(8): e6083, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28225490

RESUMO

The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome.A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ±â€Š17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ±â€Š2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Comorbidade , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Clin Exp Rheumatol ; 35 Suppl 108(6): 27-31, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28079503

RESUMO

OBJECTIVES: Cryopyrin-associated periodic syndromes (CAPS) usually start during infancy as an urticarial-like rash and a marked acute phase response, with additional manifestations appearing during its evolution. The aim of this study was to expand the clinical diversity of CAPS by the description of novel atypical features. METHODS: Clinical data were collected from patients' medical charts. Sanger sequencing analyzed NLRP3. Response to anti-IL-1 blockade was evaluated by clinical assessments and by measurements of laboratory parameters. RESULTS: Seventeen patients from two families (A and B), carrying the p.Ala439Thr and p.Arg260Trp NLRP3 mutations respectively, were enrolled. The disease was unexpectedly atypical in all members of Family A, with a 16-year-old asymptomatic carrier, and onset in adulthood associated with absence of skin lesions in four affected members. Surprisingly, one patient from each family suffered from severe haemorrhagic cystitis due to AA amyloidosis in the urinary bladder. Members of Family B displayed a classical phenotype, with two patients suffering from olfactive disorders. CONCLUSIONS: Our evidence suggests that CAPS may occasionally be presented as a late-onset, recurrent inflammatory disease without urticarial-like rash. In some patients, AA amyloidosis in strange locations like urinary bladder may complicate the clinical course. The response to IL-1 blockade in these atypical CAPS was similar to that described in classical forms. Consequently, we suggest that CAPS should be included in the differential diagnosis of adult patients with unexplained, recurrent inflammatory diseases, and once confirmed, the early initiation of anti-IL-1 blockade will probably prevent the development of life-threatening complications.


Assuntos
Amiloidose/etiologia , Síndromes Periódicas Associadas à Criopirina/complicações , Cistite/etiologia , Nefropatias/etiologia , Adolescente , Idade de Início , Idoso , Amiloidose/tratamento farmacológico , Amiloidose/genética , Amiloidose/imunologia , Doenças Assintomáticas , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/genética , Síndromes Periódicas Associadas à Criopirina/imunologia , Cistite/tratamento farmacológico , Cistite/genética , Cistite/imunologia , Feminino , Predisposição Genética para Doença , Hematúria/etiologia , Humanos , Imunossupressores/uso terapêutico , Interleucina-1/antagonistas & inibidores , Interleucina-1/imunologia , Nefropatias/tratamento farmacológico , Nefropatias/genética , Nefropatias/imunologia , Masculino , Mutação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Linhagem , Fenótipo , Resultado do Tratamento
10.
Med Clin (Barc) ; 132(20): 767-71, 2009 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-19403146

RESUMO

BACKGROUND AND OBJECTIVE: Livedo reticularis racemosa and cerebrovascular lesions characterize Sneddon's syndrome. We report 23 patients with livedo racemosa and describe the association with thrombotic events. Our objective was to determine whether livedo racemosa may be an independent clinical marker for the development of thrombotic events in patients who test negative for anti-phospholipid antibodies. METHODS: Twenty-three patients with widespread livedo racemosa were studied. None of the patients were positive for anti-phospholipid antibodies. The clinical protocol included a register of thrombotic events, fetal death or miscarriages, hypertension, and valvular heart disease. Cerebral MRI and echocardiography were systematically performed in all patients. RESULTS: Nineteen patients (82.60%) had thrombotic events. Fifteen (65.21%) had arterial thrombosis and eleven (47.82%) presented venous occlusions. Seven patients (30.43%) had both arterial and venous thrombosis. Fetal losses were recorded in seven cases (30.43%), with a total number of 33; five patients had 3 or more fetal losses. Eleven out of 23 patients (47.82%) had valvular heart disease. Arterial hypertension was detected in 16 (69.56%) patients. Four patients did not have thrombotic events but had other clinical manifestations. After anti-coagulation therapy was withdrawn, a new thrombotic event was observed in 9 out of the 14 treated patients (64.28%). CONCLUSIONS: Livedo racemosa seems to be a good clinical marker for the detection of hypercoagulable states even in the absence of anti-phospholipid antibodies or other known biologic markers of thrombosis. Long-term anti-coagulation is probably warranted in patients with livedo racemosa and a previous thrombotic event.


Assuntos
Livedo Reticular/etiologia , Trombose/complicações , Anticorpos Antifosfolipídeos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Trombose/diagnóstico
11.
Med. clín (Ed. impr.) ; 132(20): 767-771, mayo 2009. tab
Artigo em Espanhol | IBECS | ID: ibc-73181

RESUMO

Background and objective: Livedo reticularis racemosa and cerebrovascular lesions characterize Sneddon's syndrome. We report 23 patients with livedo racemosa and describe the association with thrombotic events. Our objective was to determine whether livedo racemosa may be an independent clinical marker for the development of thrombotic events in patients who test negative for anti-phospholipid antibodies. Methods: Twenty-three patients with widespread livedo racemosa were studied. None of the patients were positive for anti-phospholipid antibodies. The clinical protocol included a register of thrombotic events, fetal death or miscarriages, hypertension, and valvular heart disease. Cerebral MRI and echocardiography were systematically performed in all patients. Results: Nineteen patients (82.60%) had thrombotic events. Fifteen (65.21%) had arterial thrombosis and eleven (47.82%) presented venous occlusions. Seven patients (30.43%) had both arterial and venous thrombosis. Fetal losses were recorded in seven cases (30.43%), with a total number of 33; five patients had 3 or more fetal losses. Eleven out of 23 patients (47.82%) had valvular heart disease. Arterial hypertension was detected in 16 (69.56%) patients. Four patients did not have thrombotic events but had other clinical manifestations. After anti-coagulation therapy was withdrawn, a new thrombotic event was observed in 9 out of the 14 treated patients (64.28%).Conclusions: Livedo racemosa seems to be a good clinical marker for the detection of hypercoagulable states even in the absence of anti-phospholipid antibodies or other known biologic markers of thrombosis. Long-term anti-coagulation is probably warranted in patients with livedo racemosa and a previous thrombotic event (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Trombose/diagnóstico , Dermatopatias Vasculares/complicações , Biomarcadores , Dermatopatias Vasculares/etiologia , Anticorpos Antifosfolipídeos , Valor Preditivo dos Testes
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