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1.
Presse Med ; 48(9): 956-967, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31327542

RESUMO

Aortitis, defined by aortic parietal thickening, is noted in about 50% of patients with giant cell arteritis (GCA). Aortic structural lesions, ectasia or aneurism, may occur with or without inflammatory aspect of the aorta, sometimes since the diagnosis of GCA, but more frequently during follow-up. Assessment of aortic involvement, which has to be searched in each patient at the diagnosis of GCA, can be assessed using aortic imaging, angio-CT, angio-MRI or PET-CT. Prognosis of aortitis and its complications remains poorly known, but mortality due to serious events like aneurism rupture or aortic dissection, could be potentially reduced with precocious diagnosis and regular monitoring. Treatment of GCA-related aortitis is based on high-dose glucosteroids, with an initial prednisone dose at 0.7 mg/kg/d, as recommended by the French Study Group for large vessel vasculitis (GEFA). Aortic ectasia and aneurisms have to be monitored, in order to propose aortic surgery in the best conditions as possible.


Assuntos
Aortite/diagnóstico por imagem , Arterite de Células Gigantes/diagnóstico por imagem , Corticosteroides/administração & dosagem , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/cirurgia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/etiologia , Ruptura Aórtica/cirurgia , Aortite/complicações , Aortite/tratamento farmacológico , Aortite/patologia , Angiografia por Tomografia Computadorizada , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/patologia , Fidelidade a Diretrizes , Humanos , Imagem por Ressonância Magnética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisona/administração & dosagem , Prognóstico , Ultrassonografia Doppler
2.
Rheumatology (Oxford) ; 58(12): 2107-2116, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31056661

RESUMO

OBJECTIVE: In a previous controlled trial, 1-year adjunction of AZA to glucocorticoids (GC) for patients with non-severe, newly diagnosed eosinophilic granulomatosis with polyangiitis (EGPA) failed to lower remission failure, vasculitis relapse and isolated asthma/rhinosinus exacerbation rates, or cumulative GC use at month (M) 24. The aim of this study was to analyse longer-term outcomes to determine whether subsequent vasculitis relapse or isolated asthma/rhinosinus exacerbation (IARE) rates differed. METHODS: After M24, patients were followed prospectively, being treated based on physicians' best judgment. Flares and reasons for increased GC dose or immunosuppressant use were recorded, and reviewed according to randomization group to distinguish vasculitis relapses from IAREs according to EGPA Task Force recommendations. RESULTS: Fifty EGPA trial participants were followed for a median (interquartile range) of 6.3 (5.4-7.6) years; two (4%) died 11 months post-inclusion. By M24, vasculitis had relapsed in 21/49 (43%) patients and 14/50 (28%) had IAREs. Another patient died 4.8 years post-inclusion (infection). Among nine patients with subsequent vasculitis relapses, three had a major relapse and three had their first relapse after M24; among 25 patients with later IAREs, 17 occurred after M24. At 5 years, respective vasculitis relapse and IARE rates were 48% (95% CI 34.0, 62.6) and 56% (95% CI 41.7, 70.8), with no between-arm differences (P = 0.32 and 0.13). No entry clinical or biological parameter was associated with these outcomes during follow-up. CONCLUSION: These results confirmed that 1-year AZA and GC induction obtained good overall survival but no long-term benefit for non-severe EGPA patients. Vasculitis relapses, occurring mostly during the first 2 years, and IAREs, occurring throughout follow-up, require other preventive treatments. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00647166.

3.
Autoimmun Rev ; 18(7): 714-720, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059846

RESUMO

BACKGROUND: Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify. METHODS: We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50-60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis. RESULTS: We included 183 LVV50-60 and 183 gender-matched LVV>60. LVV50-60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50-60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50-60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50-60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.


Assuntos
Arterite de Células Gigantes/epidemiologia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
J Autoimmun ; 103: 102283, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31130367

RESUMO

Large-vessel involvement (LVI) in giant cell arteritis (GCA) includes different clinical and imaging patterns that are rarely described separately at diagnosis and whose specific cardiovascular outcomes are unknown. We conducted a nationwide retrospective study and included GCA patients with LVI demonstrated on imaging at diagnosis between 2007 and 2017. We analyzed the prognosis of three different imaging patterns of LVI present at diagnosis, with some of them overlapping but with the first one present in all patients: 1) inflammation of the aorta and/or its branches; 2) dilation of the aorta; and 3) stenosis of the aortic branches. A control group of GCA patients without LVI was constituted. We included 183 patients with LVI and 105 controls without LVI. Altogether, among the 183 patients who all showed inflammation of the aorta and/or its main branches, concomitant aortic dilation and large-vessel stenosis were observed in 27 (15%) and 55 (30%) patients, respectively. During the follow-up period, new cardiovascular events occurred in 49% and 11% of LVI patients and controls, respectively (p < 0.0001). Inflammation of the aorta and/or its branches (HR: 3.42 [2.09-5.83], p < 0.0001) and large-artery stenosis (HR: 2.75 [1.80-4.15], p < 0.0001) were independent predictive factors of new cardiovascular events. Conversely, the use of an immunosuppressant besides corticosteroids was a protective factor against new cardiovascular events (HR: 0.44 [0.29-0.66], p < 0.0001) and the development of aortic dilation (HR: 0.43 [0.23-0.77], p = 0.005). This study suggests different forms of cardiovascular events according to the initial imaging pattern of LVI.

5.
Autoimmun Rev ; 18(5): 476-483, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844551

RESUMO

INTRODUCTION: Juvenile temporal arteritis (JTA) is a recently-described and little-known inflammatory disease and its etiology is undetermined. Less than forty cases have been published. This paper is aimed at reporting the largest JTA series and to compare it to literature data to better evaluate its characteristics at diagnosis, its evolution and treatment options. MATERIAL AND METHODS: We conducted a retrospective and descriptive multicentric study in France by identifying adult patients under the age of 50 which had a pathological temporal artery biopsy owing to the presence of a temporal arteritis. Patients with temporal arteritis as a manifestation of systemic vasculitis were excluded. RESULTS: We included 12 patients and the literature review identified 32 cases described in 27 articles, thus a total of 44 patients - 34 men and 10 women - with a median age of 30 and a maximum of 44. All patients presented either a lump in the temporal region or prominent temporal arteries, and 47.7% of patients suffered from headaches. Only 11.4% of patients presented general symptoms and 6.8% a biological inflammatory syndrome; 34.1% had peripheral blood eosinophilia; 83.7% presented a single episode and complete excision without further treatment was documented for 72.7%. Pathology analysis revealed infiltrate of inflammatory cells in the arterial wall in 97.6% of patients but also sparse giant cells for 25% and granuloma for 22.9%, perivascular extension of the inflammation for 82.6%, and presence of lymphoid follicles or germinal centres for 60%. Clinical relapses were present in 16.3% of cases. CONCLUSION: JTA is a rare, localized and benign disease. The majority of cases have only one episode which is cured by local surgery.


Assuntos
Arterite de Células Gigantes , Artérias Temporais/patologia , Adolescente , Adulto , Biópsia , Feminino , França/epidemiologia , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/patologia , Arterite de Células Gigantes/terapia , Cefaleia/diagnóstico , Cefaleia/etiologia , Cefaleia/terapia , Humanos , Masculino , Estudos Retrospectivos , Síndrome , Adulto Jovem
6.
J Am Acad Dermatol ; 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30738125

RESUMO

BACKGROUND: Episodic Angioedema with eosinophilia (EAE, Gleich's syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia and frequent elevated serum Immunoglobin M. METHODS: We conducted a retrospective multicenter nationwide study regarding the clinical spectrum and therapeutic management of patients with EAE in France. RESULTS: Thirty patients were included with a median age at diagnosis of 41 years [5-84]. The median duration of each crisis was 5.5 days [1-90] with swelling affecting mainly the face and the upper limbs. Total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%) among which 5 (17%) showed evidence of clonal TCR γ gene rearrangement. Median follow-up duration was 53 months [31-99]. The presence of an abnormal T-cell population was the sole factor associated with a shorter time to flare (hazard ratio 4.15 [CI 95% 1.18-14.66; p=0.02). At last follow-up, 3 patients (10%) were able to withdraw all treatments and 11 (37%) were in clinical and biological remission with less than 10 mg of daily prednisone. CONCLUSION: EAE is a heterogeneous condition that encompasses several disease forms. Although patients usually respond well to glucocorticoids, those with evidence of abnormal T-cell phenotype have a shorter time to flare.

7.
Arthritis Rheumatol ; 71(4): 641-650, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30375745

RESUMO

OBJECTIVE: To compare the effects of rituximab (RTX) and conventional immunosuppressants (CIs) on CD4+ T cells, Treg cells, and CD8+ T cells in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: A thorough immunophenotype analysis of CD4+, Treg, and CD8+ cells from 51 patients with AAV was performed. The production of cytokines and chemokines by CD8+ T cells stimulated in vitro was assessed using a multiplex immunoassay. The impact of AAV B cells on CD8+ T cell response was assessed using autologous and heterologous cocultures. RESULTS: CD4+ and Treg cell subsets were comparable among RTX-treated and CI-treated patients. In contrast, within the CD8+ T cell compartment, RTX, but not CIS, reduced CD45RA+CCR7- (TEMRA) cell frequency (from a median of 39% before RTX treatment to 10% after RTX treatment [P < 0.01]) and efficiently dampened cytokine/chemokine production (e.g., the median macrophage inflammatory protein 1α level was 815 pg/ml in patients treated with RTX versus 985 pg/ml in patients treated with CIs versus 970 pg/ml in those with active untreated AAV [P < 0.01]). CD8+ T cell subsets cocultured with autologous B cells produced more proinflammatory cytokines in AAV patients than in controls (e.g., for tumor necrosis factor-producing effector memory CD8+ T cells: 14% in AAV patients versus 9.2% in controls [P < 0.05]). In vitro disruption of AAV B cell-CD8+ T cell cross-talk reduced CD8+ T cell cytokine production, mirroring the reduced CD8+ response observed ex vivo after RTX treatment. CONCLUSION: The disruption of a pathogenic B cell/CD8+ T cell axis may contribute to the efficacy of RTX in AAV. Further studies are needed to determine the value of CD8+ T cell immunomonitoring in B cell-targeted therapies.

8.
Autoimmun Rev ; 17(10): 984-989, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30114520

RESUMO

OBJECTIVE: To investigate differences between childhood (cPAN)- and adult-onset polyarteritis nodosa (aPAN) patients. METHODS: cPAN patients' clinical findings at onset and outcomes were compared to those of aPAN patients from the French Vasculitis Study Group registry matched for year of enrollment and initial systemic versus cutaneous disease. Their information on medications, disease activity and damage were collected. Kaplan-Meier relapse-free survival curves and the log-rank test were used to analyze cPAN versus aPAN differences for predefined outcomes. RESULTS: Twenty-one children with systemic and 13 with cutaneous PAN were compared with 84 systemic- and 27 cutaneous-matched aPAN patients. Median follow-up exceeded 5 years for both groups. At study entry, mononeuritis multiplex was less frequent in systemic cPAN than systemic aPAN (P = 0.04), and purpura and myalgias were less frequent in cutaneous cPAN than cutaneous aPAN (P < 0.03). During follow-up, systemic cPAN relapsed more often than matched systemic aPAN (P < 0.0001), while relapse rates were similar for cutaneous disease (P > 0.05). Mostly minor relapses, predominantly involving the skin, occurred in all 4 groups. At last visit, damage accrual was comparable for cPAN and aPAN patients, but fewer systemic cPAN patients were treatment-free (15% versus 42%; P = 0.03). Two (6%) cPAN and 8 (7%) aPAN patients died. CONCLUSION: Systemic PAN is equally severe in children and adults and carries a higher risk of relapse. The main cutaneous PAN features seem not to be influenced by age at disease onset.


Assuntos
Poliarterite Nodosa/fisiopatologia , Adulto , Idade de Início , Criança , Humanos , Poliarterite Nodosa/tratamento farmacológico , Poliarterite Nodosa/epidemiologia , Recidiva
9.
Ann Rheum Dis ; 77(8): 1143-1149, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29695500

RESUMO

OBJECTIVE: To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). METHODS: Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group. RESULTS: Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations. CONCLUSION: AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions. TRIAL REGISTRATION NUMBER: NCT01731561; Results.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Antirreumáticos/administração & dosagem , Rituximab/administração & dosagem , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Subpopulações de Linfócitos B/efeitos dos fármacos , Biomarcadores/sangue , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Recidiva , Indução de Remissão/métodos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Índice de Gravidade de Doença
10.
Ann Rheum Dis ; 77(4): 563-570, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29306872

RESUMO

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. TRIAL REGISTRATION NUMBER: NCT02339441.


Assuntos
Esclerodermia Difusa/diagnóstico , Índice de Gravidade de Doença , Testes Cutâneos/estatística & dados numéricos , Adulto , Área Sob a Curva , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Modelos Logísticos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , RNA Polimerase III/análise , Curva ROC , Esclerodermia Difusa/enzimologia , Esclerodermia Difusa/patologia , Pele/patologia
11.
Semin Arthritis Rheum ; 48(1): 70-76, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29336783

RESUMO

OBJECTIVES: To assess the prevalence of bronchiectasis in a Western cohort with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) and its correlations with disease presentation and outcome. METHODS: Retrospective study of ANCA-associated vasculitis (AAV) patients followed at Nantes University Hospital (2005-2015). Clinical, biological, and follow-up data were collected through chart review. Two experienced radiologists blinded to the clinical data interpreted chest high-resolution CTs according to the Feischner Society criteria. RESULTS: Fifty-eight patients were included: 30 had MPA (51.7%) and 28 had GPA (48.3%). The median age at AAV diagnosis was 65.5 years. Anti-MPO-ANCA and anti-PR3-ANCA were present in 39 (67.2%) and 19 (32.8%) patients, respectively. Overall, bronchiectasis was found in 22 patients (37.9%), all of whom had anti-MPO ANCA. In multivariate analysis, bronchiectasis was independently associated with anti-MPO-ANCA, female gender and age at AAV diagnosis. Furthermore, anti-MPO ANCA patients with bronchiectasis had more frequent peripheral nerve involvement (54.5 vs. 17.6%, p = 0.019) and less frequent renal involvement than those without bronchiectasis (40.9% vs. 82.3%, p = 0.009). Disease course, survival and risk of severe pulmonary infection were similar in patients with and without bronchiectasis on chest CT. CONCLUSIONS: This study shows that bronchiectasis is a highly prevalent pre-existing respiratory condition in Caucasian patients with anti-MPO AAV. This subset of patients exhibits a distinct presentation. Further studies are needed to confirm these findings and clarify the clinical implications of this association. Whether the respiratory tract could be the site of initiation of anti-MPO auto-immunity remains to be investigated.


Assuntos
Bronquiectasia/epidemiologia , Granulomatose com Poliangiite/epidemiologia , Pulmão/diagnóstico por imagem , Poliangiite Microscópica/epidemiologia , Peroxidase/imunologia , Idoso , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/imunologia , Comorbidade , Feminino , Granulomatose com Poliangiite/diagnóstico por imagem , Granulomatose com Poliangiite/imunologia , Humanos , Masculino , Poliangiite Microscópica/diagnóstico por imagem , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores Sexuais
12.
Rheumatology (Oxford) ; 57(2): 370-381, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29207002

RESUMO

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.


Assuntos
Avaliação da Deficiência , Fadiga/fisiopatologia , Dor/fisiopatologia , Esclerodermia Difusa/fisiopatologia , Índice de Gravidade de Doença , Adulto , Efeitos Psicossociais da Doença , Europa (Continente) , Fadiga/etiologia , Feminino , Dedos , Força da Mão , Inquéritos Epidemiológicos , Humanos , Masculino , Dor/etiologia , Estudos Prospectivos , Esclerodermia Difusa/complicações , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia
14.
Eur Respir J ; 50(4)2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29051271

RESUMO

Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide (TLCO) is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning TLCO into membrane conductance (diffusing capacity) for carbon monoxide (DMCO) and alveolar capillary blood volume (VC) through combined measurement of TLCO and transfer factor of the lung for nitric oxide (TLNO) is more effective to identify pulmonary hypertension in SSc patients compared with TLCO alone. Here, the objective was to determine whether combined TLCO-TLNO partitioned with recently refined equations could more accurately detect pulmonary hypertension than TLCO alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients. TLCO, TLNO and VC were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for TLCO (0.82, 95% CI 0.79-0.85) and TLNO (0.80, 95% CI 0.76-0.83), but lower for VC (0.75, 95% CI 0.71-0.78) and DMCO (0.66, 95% CI 0.62-0.70).Compared with TLCO alone, combined TLCO-TLNO does not add capability to detect pulmonary hypertension in unselected SSc patients.


Assuntos
Monóxido de Carbono/metabolismo , Hipertensão Pulmonar , Óxido Nítrico/metabolismo , Capacidade de Difusão Pulmonar/métodos , Escleroderma Sistêmico , Adulto , Barreira Alveolocapilar , Permeabilidade Capilar , Diagnóstico Precoce , Intervenção Médica Precoce , Feminino , França , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar , Reprodutibilidade dos Testes , Testes de Função Respiratória/métodos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia
15.
Arthritis Rheumatol ; 69(11): 2175-2186, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28678392

RESUMO

OBJECTIVE: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). METHODS: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. RESULTS: Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. CONCLUSION: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.


Assuntos
Azatioprina/uso terapêutico , Síndrome de Churg-Strauss/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Poliangiite Microscópica/tratamento farmacológico , Poliarterite Nodosa/tratamento farmacológico , Adulto , Idoso , Asma/induzido quimicamente , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Rinite/induzido quimicamente , Sinusite/induzido quimicamente
16.
Am J Med ; 130(10): 1219.e19-1219.e27, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28602874

RESUMO

BACKGROUND: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. METHODS: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. RESULTS: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. CONCLUSIONS: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.


Assuntos
Síndrome de Vazamento Capilar/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Paraproteinemias/diagnóstico por imagem , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/mortalidade , Síndrome de Vazamento Capilar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraproteinemias/complicações , Paraproteinemias/mortalidade , Paraproteinemias/patologia , Análise de Sobrevida , Terbutalina/uso terapêutico , Teofilina/uso terapêutico
17.
Semin Arthritis Rheum ; 46(6): 759-766, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28214014

RESUMO

OBJECTIVES: Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan. METHODS: ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up. RESULTS: Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 (p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 (p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 (p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 (p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI (p = 0.04), CHFS (p = 0.04), and pain score (p = 0.046). CONCLUSIONS: In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability.


Assuntos
Antagonistas dos Receptores de Endotelina/uso terapêutico , Mãos/fisiopatologia , Qualidade de Vida , Escleroderma Sistêmico/tratamento farmacológico , Úlcera Cutânea/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Bosentana , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia , Resultado do Tratamento
18.
Ann Rheum Dis ; 76(7): 1207-1218, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28188239

RESUMO

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Esclerodermia Difusa/tratamento farmacológico , Adulto , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Estudos de Coortes , Intervenção Médica Precoce , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/imunologia , Estudos Prospectivos , RNA Polimerase III/imunologia , Esclerodermia Difusa/imunologia , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
19.
Autoimmun Rev ; 16(4): 377-384, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28232167

RESUMO

BACKGROUND: As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature. METHODS: 46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed. RESULTS: We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome). CONCLUSION: Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Estudos de Coortes , Feminino , França , Humanos , Imunoglobulinas Intravenosas/farmacologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/patologia , Resultado do Tratamento
20.
Clin Appl Thromb Hemost ; 23(1): 45-51, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26259913

RESUMO

BACKGROUND: Assessment of venous thromboembolism (VTE) risk is important to determine optimal primary prophylaxis in hospitalized patients. The Padua score helps to recognize patients with high VTE risk, but quantifying a VTE risk is often challenging in medical patients. Thrombin generation assay (TGA) reflects the pro-/anticoagulant balance and thus could help to better quantify VTE risk in medical hospitalized patients. AIM: To analyze the relation between TGA and VTE risk according to Padua score in medical hospitalized patients. METHODS: Between May and October 2013, 105 patients were included in an unselected cohort group of patients admitted to an internal medicine department in a large, university hospital. Within the 36 hours after admission and before any anticoagulant therapy, Padua score was calculated and sample for TGA was collected for each patient. Thrombin generation assay (velocity, peak, and endogenous thrombin potential [ETP]) was performed with 1 and 5 picomol/l (pM) tissue factor (TF) reagent. RESULTS: In patients with high Padua score (n = 29), velocity, peak, and ETP differed from patients with low Padua score. This difference was present at 1 and 5 pM TF, in ETP (P < .0001 and P = .003 respectively), in peak (P < .0001 in both conditions), and in velocity (P < .0001). According to multivariate analysis, myeloid disorders, older age, higher body mass index, myocardial infarction, C-reactive protein >5 mg/L, reduced mobility with bed rest significantly increased velocity 1 pM TF value. CONCLUSION: Single thrombin generation measurement could help to identify patients at risk of VTE in medical hospitalized patients.


Assuntos
Testes de Coagulação Sanguínea/métodos , Tromboembolia Venosa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Adulto Jovem
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