Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
1.
Arthritis Res Ther ; 23(1): 70, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658052

RESUMO

BACKGROUND: Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE. METHODS: This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy. Patients received 10 IV infusions of ATO within 24 days. The first group received 0.10 mg/kg per injection, with dose-escalating to 0.15 mg/kg in a second group, and to 0.20 mg/kg in a third group. The primary endpoint was the occurrence of adverse events (AEs) and secondary endpoints were the number of SLE Responder Index 4 (SRI-4) responders at week 24 and reduction of corticosteroid dosage. In an exploratory analysis, we collected long-term data for safety and attainment of lupus low disease activity state (LLDAS). RESULTS: Four serious AEs occurred (grade 3 neutropenia, osteitis, neuropathy), 2 of which were attributable to ATO (neutropenia in the 2 patients treated with mycophenolate). Two patients suffered a severe flare during the last 4 weeks of the trial. At W24, five patients among 10 were SRI-4 responders. Overall, mean corticosteroid dosage decreased from 11.25 mg/day at baseline to 6 mg/day at W24 (P < 0.01). In the long term, 6 patients attained LLDAS at W52, which continued at last follow-up (median LLDAS duration 3 years, range 2-4). CONCLUSIONS: A short course of ATO has an acceptable safety profile in SLE patients and encouraging efficacy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01738360  registered 30 November 2012.

2.
Front Immunol ; 11: 588322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324407

RESUMO

Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. Objective: To determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. Methods: We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Results: Spontaneous TNFα, IL-6, IL-1ß, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1ß serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (p = 0.04). Conclusion: Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1ß, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra.

3.
Arthritis Res Ther ; 22(1): 272, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208192

RESUMO

OBJECTIVE: To report on the characteristics and long-term course of rheumatic manifestations in Schnitzler syndrome (SchS). METHODS: A retrospective cohort study of patients with SchS followed between 2000 and 2020. Inclusion criteria included a diagnosis of SchS (Strasbourg criteria). All available bone scans were reviewed and scored according to the intensity and number of pathological sites. The scintigraphic score was compared with the clinical activity score, CRP level, and treatments. RESULTS: Twenty-five patients were included. Median age at diagnosis was 68 years. Eighty patients (72%) had SchS-related rheumatic pain. Most patients had a long-standing isolated rash before constitutional and/or rheumatic symptoms appeared. The monoclonal component level was usually very low (IgMκ in 22/25). Rheumatic pain predominated around the knees. Bone scans revealed abnormal tracer uptake in 15/18 (85%). The scintigraphic score correlated with clinical activity (r = 0.4, p < 0.02) and CRP level (r = 0.47, p < 0.01). The scintigraphic score was lower in patients receiving corticosteroids or IL1Ra (interleukin 1 receptor antagonist) than in untreated patients (median scores:2, 0, and 13, respectively; p < 0.05). Two patients developed Waldenström macroglobulinemia. Of the 22 surviving patients, median age at follow-up was 76 years. IL1Ra was used in 13 patients, with dramatic efficacy on both symptoms and bone scan features. CONCLUSIONS: Rheumatic manifestations are very prevalent in SchS. However, bone pain can be misleading and contribute to misdiagnosis. Bone scan abnormalities are very prevalent and correlate with disease activity and treatments. IL1-Ra has a dramatic and durable efficacy but may not be required in every patient early on.

4.
Clin Nucl Med ; 45(12): 973-974, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33031244

RESUMO

Cardiac valvular involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is very rare. We report the case of a patient seen in 2019, followed for ANCA-associated vasculitis for 15 years, who had a first relapse with cardiac valvular involvement in 2012, and who underwent a second histologically proven vasculitis relapse involving mitral periprosthetic endocardium. PET/CT imaging showed an intense and focal FDG activity of paramitral bioprosthesis leak site. Mitral bioprosthesis was replaced, and the patient improved with steroids and rituximab. Through this exceptional case, we suggest that FDG PET/CT could be of interest in the follow-up of ANCA-associated vasculitis with cardiac valvular involvement.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32789447

RESUMO

OBJECTIVES: This study aimed to examine the sensitivity of muscle biopsy (MB) in ANCA-associated vasculitis (AAV), identify factors predicting MB positivity and assess the prognostic value of a positive MB. METHODS: We conducted a single-centre retrospective study of AAV with an MB performed at diagnosis. AAV classification [granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA)] followed the European Medicines Agency algorithm. A logistic regression model was used to identify the factors associated with MB positivity. Survival curves were generated using the Kaplan-Meier method. RESULTS: Among 276 AAV patients (1995-2018), 101 had an MB. Seventy-eight patients were included: 33 with GPA, 25 with MPA and 20 with EGPA. MB samples were positive in 45 cases (58%): 17 GPA, 16 MPA and 12 EGPA. Univariate analysis focussed on GPA and revealed that the MB yield was higher in females [22/31 (71%) vs 11/27 (41%); P = 0.02] and in anti-MPO patients [25/37 (68%) vs 6/19 (32%) for anti-PR3; P = 0.01]. By multivariate analysis, three factors predicted MB positivity: anti-MPO ANCA [odds ratio (OR) 10.67 (CI 2.09, 81.68)], female sex [OR 5.3 (CI 1.16, 32.35)] and neutrophil count [OR 1.33 (CI 1.07, 1.8)]. MB positivity had no impact on relapse, death or end-stage renal disease-free survival. CONCLUSIONS: MB is a safe and efficient diagnostic tool for AAV. Predictors of MB yield include ANCA type, sex and neutrophil count. MB cannot substitute for kidney biopsy when indicated, but should be considered in other cases.

6.
Ann Intern Med ; 173(3): 179-187, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32479166

RESUMO

BACKGROUND: Biannual rituximab infusions over 18 months effectively maintain remission after a "standard" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). OBJECTIVE: To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen. DESIGN: Randomized controlled trial. (ClinicalTrials.gov: NCT02433522). SETTING: 39 clinical centers in France. PATIENTS: 68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy. INTERVENTION: Rituximab or placebo infusion every 6 months for 18 months (4 infusions). MEASUREMENTS: The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0. RESULTS: From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) (P = 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) (P = 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients [12%]) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients [9%]). No deaths occurred in either group. LIMITATION: Potential selection bias based on previous rituximab response and tolerance. CONCLUSION: Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy. PRIMARY FUNDING SOURCE: French Ministry of Health and Hoffmann-La Roche.

7.
J Thromb Thrombolysis ; 50(1): 211-216, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32451823

RESUMO

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous. The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis. In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included. A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected. Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected. Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis. D-dimers at baseline were significantly higher in patients with DVT (p < 0.001). Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE. The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE. The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively. The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer. Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients. Increased D-dimer concentrations of more than 1.0 µg/ml predict the risk of venous thromboembolism. D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.


Assuntos
Anticoagulantes/uso terapêutico , Infecções por Coronavirus/complicações , Enoxaparina/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pneumonia Viral/complicações , Tromboembolia Venosa/epidemiologia , Idoso , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Tromboembolia Venosa/sangue , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/virologia
8.
J Cardiol Cases ; 21(3): 110-113, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32153686

RESUMO

We report the case of a 40-year-old veterinary surgeon who was admitted for spiking fevers, arthralgia, and a complete atrioventricular block. Tests revealed an inflammatory syndrome, hepatic cytolysis, neutrophilic leukocytosis, and increased troponin levels. Cardiac magnetic resonance imaging showed a small myocarditis but no tissue abnormality on the conduction pathways. In the absence of evidence-based infection and favorable evolution under broad spectrum antibiotherapy, an adult-onset Still's disease was suspected and corticosteroid therapy administered. Evolution was then impressively favorable, with a persistent sinus heart rhythm 3 days later. Learning objective: Febrile conductive disorders occurring during a systemic disorder with negative infection and auto-immunity work-up should lead to consider an adult-onset Still's disease, which can be treated and cured, especially with steroids. Moreover, fever, polyarthritis, neutrophilic leukocytosis, pericarditis, and myocarditis should lead to consideration of adult-onset Still's disease.

9.
Br J Haematol ; 189(5): 869-878, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32191819

RESUMO

Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose <50 mg/m2 . Disease progression rates were 20% and 30% at two and five years, respectively. Partial response (PR) to 2CdA was predictive of disease progression. Among eight re-treated patients, five went into CR, two in PR, and one died. Single-agent 2CdA is effective in reactivated a-LCH, including at intermediate doses. Toxicity, significant but acceptable, warrants infectious prophylaxis. Complete responders may enter prolonged remission. Further studies are needed to determine 2CdA sequencing with other agents (vinblastine, cytarabine).

10.
Clin Rheumatol ; 39(9): 2707-2713, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32206974

RESUMO

OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed. METHODS: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015. RESULTS: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study. CONCLUSION: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.

12.
J Rheumatol ; 47(10): 1522-1531, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31787599

RESUMO

OBJECTIVE: To report on a large series of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and bronchiectasis, with a specific focus on the timeline of occurrence of both features. METHODS: Retrospective nationwide multicenter study of patients diagnosed with both AAV and bronchiectasis. RESULTS: Sixty-one patients were included, among whom 27 (44.25%) had microscopic polyangiitis (MPA), 27 (44.25%) had granulomatosis with polyangiitis (GPA), and 7 (11.5%) had eosinophilic GPA. Thirty-nine (64%) had myeloperoxidase (MPO)-ANCA and 13 (21%) had proteinase 3-ANCA. The diagnosis of bronchiectasis either preceded (n = 25; median time between both diagnoses: 16 yrs, IQR 4-54 yrs), was concomitant to (n = 12), or followed (n = 24; median time between both diagnoses: 1, IQR 0-6 yrs) that of AAV. Patients in whom bronchiectasis precedes the onset of AAV (B-AAV group) have more frequent mononeuritis multiplex, MPA, MPO-ANCA, and a 5-fold increase of death. The occurrence of an AAV relapse tended to be protective against bronchiectasis worsening (HR 0.6, 95% CI 0.4-0.99, P = 0.049), while a diagnosis of bronchiectasis before AAV (HR 5.8, 95% CI 1.2-28.7, P = 0.03) or MPA (HR 18.1, 95% CI 2.2-146.3, P = 0.01) were associated with shorter survival during AAV follow-up. CONCLUSION: The association of bronchiectasis with AAV is likely not accidental and is mostly associated with MPO-ANCA. Patients in whom bronchiectasis precedes the onset of AAV tend to have distinct clinical and biological features and could carry a worse prognosis.

13.
Eur J Ophthalmol ; : 1120672119889008, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744325

RESUMO

OBJECTIVE: We describe a clinico-radiological presentation of inflammatory optic neuropathy that mimicked optic neuritis. METHODS: Retrospective single-center case series and literature review of optic neuropathy without orbital pseudotumor. RESULTS: Five local patients fulfilled the inclusion criteria. Clinical presentation revealed rapidly progressive severe unilateral visual loss, retrobulbar pain (n = 4), and paralytic strabismus (simultaneous = 2, protracted = 2) without proptosis. Optic nerve abnormality was not appreciated on initial scan review. Patients did not have any general activity of the granulomatosis with polyangiitis. Upon follow-up magnetic resonance imaging and initial imaging review, all patients revealed orbital apex anomalies. Visual acuity improved in three patients who received high-dose intravenous glucocorticosteroids immediately. Relapse was frequent and visual outcome was poor (final vision > 20/40 in two patients only). Literature review identified 16 well-documented cases of granulomatosis with polyangiitis-related isolated optic neuropathies. Magnetic resonance imaging revealed no abnormality (n = 6), optic nerve and/or sheath involvement (n = 9), apex infiltration (n = 3), and/or pachymeningitis (n = 7). CONCLUSION: Granulomatosis with polyangiitis is a rare yet potentially blinding cause of inflammatory optic neuropathy. Optic neuropathy in granulomatosis with polyangiitis may occur in the absence of systemic symptoms of disease activity and is challenging to distinguish from other inflammatory and non-inflammatory disorders affecting visual acuity. Several clinical and imaging clues suggest that optic neuropathy results from the development of an extravascular granulomatous process within the optic nerve sheath in the orbital apex, a place that is difficult to image. In a granulomatosis with polyangiitis patient with unexplained visual loss and a seemingly normal workup (fundoscopy, biology, and imaging), clinician should keep a high index of suspicion.

14.
Haemophilia ; 25(3): 527-534, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31050100

RESUMO

INTRODUCTION: Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of autoantibodies against coagulation factor VIII (FVIII). The mortality rate remains high. International recommendations define complete remission as undetectable inhibitor (<0.6 Bethesda Units [BU]) and normal FVIII activity (FVIII:C) that persists after immunosuppressive therapy stopped. For patients achieving remission, the risk of relapse reaches 20%. The risk factors for this relapse are not well known. AIM: In this study, we examined the accuracy of the FVIII/W ratio (FVIII:C/von Willebrand Factor Antigen (VWF:Ag) ratio) to predict relapse in 64 consecutive patients with AHA. RESULTS: In this cohort, all patients had a very low FVIII/W ratio at the time of diagnosis, and this value progressively increased in the first weeks of immunosuppressive treatment. In our study, 9/55 (14%) did not achieve complete remission. Twenty-seven patients were followed long enough (more than a year) to show that in the 22 patients who did not relapse, the FVIII/W ratio remained durably normalized. By contrast, in the five patients who relapsed during follow-up, we noted either no normalization of the FVIII/W ratio, or a secondary decrease to an abnormal value of <0.7 after initial normalization. In all patients who relapsed, the ratio was the first abnormal biological result to be observed, always preceding changes in the activated partial thromboplastin time (aPTT), FVIII:C and anti-FVIII reappearance. CONCLUSION: These data suggest that the FVIII/W ratio could be considered a sensitive biological marker to predict recovery and/or relapse in AHA.


Assuntos
Fator VIII/metabolismo , Hemofilia A/sangue , Hemofilia A/diagnóstico , Fator de von Willebrand/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos
15.
Rheumatology (Oxford) ; 58(12): 2107-2116, 2019 12 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.


Assuntos
Azatioprina/uso terapêutico , Síndrome de Churg-Strauss/tratamento farmacológico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Adulto , Idoso , Asma/epidemiologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão , Rinite/epidemiologia , Índice de Gravidade de Doença , Sinusite/epidemiologia , Resultado do Tratamento
16.
Arthritis Rheumatol ; 71(4): 641-650, 2019 04.
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.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Imunossupressores/farmacologia , Rituximab/farmacologia , Idoso , Linfócitos B/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Imunofenotipagem , Imunossupressores/imunologia , Masculino , Pessoa de Meia-Idade , Rituximab/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Resultado do Tratamento
18.
Haematologica ; 103(8): 1278-1287, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29724903

RESUMO

Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.


Assuntos
Deficiência de GATA2/epidemiologia , Mutação em Linhagem Germinativa , Adulto Jovem , Adolescente , Adulto , Bélgica , Criança , Pré-Escolar , França , Deficiência de GATA2/complicações , Deficiência de GATA2/genética , Deficiência de GATA2/terapia , Neoplasias Hematológicas/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Recém-Nascido , Infecções/etiologia , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Inquéritos e Questionários
19.
Crit Care ; 22(1): 88, 2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29642928

RESUMO

BACKGROUND: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disorder. A few patients develop organ complications that can be life-threatening. Our objectives were to describe the disease course and phenotype of life-threatening AOSD, including response to therapy and long-term outcome. METHODS: A multicenter case series of intensive care medicine (ICU) patients with life-threatening AOSD and a systematic literature review. RESULTS: Twenty patients were included. ICU admission mostly occurred at disease onset (90%). Disease manifestations included fever (100%), sore throat (65%), skin rash (65%), and arthromyalgia (55%). Serum ferritin was markedly high (median: 29,110 ng/mL). Acute respiratory failure, shock and multiple organ failure occurred in 15 (75%), 10 (50%), and 7 (35%) cases, respectively. Hemophagocytosis was demonstrated in eight cases. Two patients died. Treatment delay was significant. All patients received corticosteroids. Response rate was 50%. As second-line, intravenous immunoglobulins were ineffective. Anakinra was highly effective. After ICU discharge, most patients required additional treatment. Literature analysis included 79 cases of AOSD with organ manifestations, which mainly included reactive hemophagocytic syndrome (42%), acute respiratory failure (34%), and cardiac complications (23%). Response rate to corticosteroids was 68%. Response rates to IVIgs, cyclosporin, and anakinra were 50%, 80%, and 100%, respectively. CONCLUSIONS: AOSD should be recognized as a rare cause of sepsis mimic in patients with fever of unknown origin admitted to the ICU. The diagnosis relies on a few simple clinical clues. Early intensive treatment may be discussed. IVIgs should be abandoned. Long-term prognosis is favorable.


Assuntos
Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/terapia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Ciclosporina/uso terapêutico , Feminino , França , Humanos , Imunoglobulinas/uso terapêutico , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Prognóstico , Escala Psicológica Aguda Simplificada , Estatísticas não Paramétricas , Doença de Still de Início Tardio/mortalidade , Tomografia Computadorizada por Raios X/métodos
20.
Autoimmunity ; 51(2): 89-95, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29463118

RESUMO

In this study, we aimed at evaluating the contribution of an extended myositis-related antibodies (Abs) determination by immunoblot to the diagnosis, classification, and prognosis of idiopathic inflammatory myositis (IIM). Medical records of all the patients (n = 237) with myositis-related Ab requests addressed to our department over a one-year period were retrospectively analyzed. Patients were classified as IIM, auto-immune disease (AID) other than IIM, and other diagnosis, and examined for their Ab profiles as determined by immunoblot. Ab positivity was qualified semi-quantitatively as low or strong according to the manufacturer's recommendations. Among the 45 Ab-positive patients, 49% were diagnosed an IIM, 22% another AID, and 29% another diagnosis. The clinico-serological patterns of the myositis-related Ab+ patients fully recapitulated those described in the literature. Among non-IIM patients, anti-PM-Scl was the most frequently detected Ab (38%), followed by anti-Mi-2 (15%), and anti-OJ (12%). Importantly, strong Ab positivity was significantly more detected in IIM vs. non-IIM patients (82% vs. 35%; p = .002). This difference was further increased when comparing MSAs only (95% vs. 36%; p = .0004). Accordingly, strong Ab positivity associated with high specificity (96%) and positive likelihood ratio (pLR =12) for IIM. Our data suggest that while myositis-related Ab, including MSA, can be detected by immunoblot in non-IIM patients, strong positivity is nevertheless highly predictive of IIM. In conclusion, this work suggests that relevant clinical contribution to IIM is provided by the immunoblot determination of myositis-related Ab, more especially when considering strong positive detection of MSA.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Immunoblotting/métodos , Miosite/sangue , Miosite/diagnóstico , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Humanos , Miosite/imunologia , Prognóstico , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...