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2.
J Clin Immunol ; 39(7): 702-712, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401750

RESUMO

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.

3.
J Rheumatol ; 46(11): 1502-1508, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30824651

RESUMO

OBJECTIVE: Deficiency in alpha-1 antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical effect of AAT deficiency remains poorly established in this setting. This study aimed to describe the clinical phenotypes and outcomes of AAV according to AAT phenotypes. METHODS: This study was conducted retrospectively at Caen University Hospital and included all consecutive granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with positive proteinase 3-ANCA or myeloperoxidase-ANCA, from January 2000 or September 2011, respectively, to June 2016. AAT dosage (nephelometry) and phenotyping (isoelectric focusing in agarose gel) were performed. RESULTS: Among the 142 patients with AAV, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a nonpolymerogenic M-variant phenotype, 18 (13%) had the deficient allele MZ, 12 (8%) had MS, 2 (1%) had ZZ, 2 (1%) had SZ, and 1 (1%) had SS. M, Z, and S allele frequencies were 84%, 8%, and 6%, respectively. No association was observed between AAT deficiency and ANCA subtype or AAV phenotype, except for intraalveolar hemorrhage (IAH), which was more frequent in patients harboring at least 1 of the deficient Z or S alleles than in those without any deficient alleles (p < 0.01). Global, renal, or relapse-free survival rates were similar for all subgroups. CONCLUSION: This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of IAH. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient patients with AAV.

4.
BMC Nephrol ; 19(1): 317, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413153

RESUMO

BACKGROUND: The risk of early death is particularly high in patients over the age of 65 presenting with antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis. We hypothesized that by combining disease severity markers, a comorbidity index and serious adverse event reports, we would be able to identify early predictors of one-year mortality in this population. METHODS: We performed a multicentre, retrospective study in the nephrology and internal medicine departments of six tertiary hospitals in northern France. A total of 149 patients (median [interquartile range (IQR)] age: 72.7 [68.5-76.8] years) presenting with ANCA-associated vasculitis and renal involvement were included between January 2002 and June 2015. The primary endpoint was the one-year mortality rate. RESULTS: Renal function was severely impaired at presentation (median [IQR] peak serum creatinine (SCr): 337 [211-522] µmol/l), and 45 patients required dialysis. The Five-Factor Score (FFS, scored as + 1 point for each poor prognostic factor (age > 65 years, cardiac symptoms, gastrointestinal involvement, SCr ≥150 µmol/L, and the absence of ear, nose, and throat involvement)) was ≥3 in 120 cases. The one-year mortality rate was 19.5%. Most of the deaths occurred before month 6, and most of these were related to severe infections. In a univariate analysis, age, a high comorbidity index, a performance status of 3 or 4, a lack of co-trimoxazole prophylaxis, early severe infection, and disease activity parameters (such as the albumin level, haemoglobin level, peak SCr level, dialysis status, and high FFS) were significantly associated with one-year mortality. In a multivariable analysis, the best predictors were a high FFS (relative risk (RR) [95% confidence interval (CI)] = 2.57 [1.30-5.09]; p = 0.006) and the occurrence of a severe infection during the first month (RR [95%CI] = 2.74 [1.27-5.92]; p = 0.01). CONCLUSIONS: When considering various disease severity markers in over-65 patients with ANCA-associated renal vasculitis, we found that an early, severe infection (which occurred in about a quarter of the patients) is a strong predictor of one-year mortality. A reduction in immunosuppression, the early detection of infections, and co-trimoxazole prophylaxis might help to reduce mortality in this population.

5.
Autoimmun Rev ; 17(12): 1153-1168, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30316994

RESUMO

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.

6.
Infection ; 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30194635

RESUMO

BACKGROUND: Primary immunodeficiency (PID) in adults is rare and mostly revealed by infections. MATERIAL AND METHODS: Adults without predisposing factors who were admitted to an intensive care unit (ICU) for infection were screened for PID. RESULTS: Six PID cases were diagnosed, mostly revealed by encapsulated bacterial infections. CONCLUSION: Investigation of PID after ICU discharge should be considered to improve early detection.

7.
Oncoimmunology ; 7(8): e1450712, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30221042

RESUMO

Objectives. In Erdheim-Chester disease (ECD), the empirical single dose (SD, 100 mg/day) anakinra sometimes induces only partial responses. Since SD is usually well tolerated, doubling the dose might improve response while maintaining an acceptable safety profile. Methods. A retrospective analysis was performed of outcomes under double-dose (DD) of anakinra in 4 ECD patients who did not exhibit a complete response (CR) under SD treatment. Bone, retroperitoneal, neurologic/orbital, peritoneal, pericardial, right atrium, and pleural involvements were recorded. CR, partial response (PR), stable disease, progressive disease (PD) and tolerance of DD were assessed. Results. SD treatment was a second or third line treatment in three patients after interferon-therapy failure. Two patients, including one with a BRAF mutation, achieved a CR and one patient with a NRAS mutation achieved a PR with DD treatment. The fourth patient, wild-type for both genes, did not respond to a first DD treatment, but then achieved CR under SD associated with a reduced dose of vemurafenib (960 mg/d). Bone and retroperitoneal lesions partially improved on imaging with SD in all patients, but were further improved under DD with two patients achieving CR. With SD treatment, two patients with right atrial masses showed sustained CR. Under DD treatment, two patients with massive serositis refractory to SD, showed PR. Conclusion. DD improved the response to anakinra and lead to two CRs and a PR in three out of four ECD patients, with minor and comparable side-effects to those of SD, while failures were essentially related to massive serositis.

8.
Eur J Intern Med ; 57: 96-104, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30054122

RESUMO

BACKGROUND: The aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA). METHODS: GCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded. RESULTS: Twenty patients with a median (IQR) age of 72 (69-78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study. CONCLUSION: This study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01910038).

9.
J Clin Immunol ; 38(4): 503-512, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29855752

RESUMO

PURPOSE: Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient's life quality index (LQI). METHODS: This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%. RESULTS: Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p = 0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump. CONCLUSIONS: Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician's armamentarium which is preferred by some patients and is cost-effective. CLINICALTRIALS. GOV IDENTIFIER: NCT02180763 CLINICAL IMPLICATIONS: Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week. This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician's armamentarium.

10.
Brain ; 141(6): 1609-1621, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29741608

RESUMO

Dermatomyositis is an acquired auto-immune disease characterized by skin lesions and muscle-specific pathological features such as perifascicular muscle fibre atrophy and vasculopathy. Dermatomyositis patients display an upregulation of type I interferon-inducible genes in muscle fibres, endothelial cells, skin and peripheral blood. However, the effect of type I interferon on muscle tissue has not yet been determined. Our aim was to study the pathogenicity of type I interferon in vitro and to evaluate the efficacy of the type I interferon pathway blockade for therapeutic purposes. The activation of type I interferon in differentiating myoblasts abolished myotube formation with reduced myogenin expression while in differentiated myotubes, we observed a reduction in surface area and an upregulation of atrophy-associated genes. In vitro endothelial cells exposure to type I interferon disrupted vascular network organization. All the pathogenic effects observed in vitro were abolished by ruxolitinib. Finally, four refractory dermatomyositis patients were treated with ruxolitinib and improvement ensued in skin lesions, muscle weakness and a reduced serum type I interferon levels and interferon-inducbile genes scores. We propose JAK inhibition as a mechanism-based treatment for dermatomyositis, a finding that is relevant for the design of future clinical trials targeting dermatomyositis.

11.
Rheumatology (Oxford) ; 57(6): 1047-1055, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554340

RESUMO

Objectives: Comprehensive analyses of cause-specific death patterns in GCA are sparse. We studied the patterns and time trends in GCA-related mortality using a large death certificate database. Methods: We obtained multiple-cause-of-death data from the French national death certificate database for 1980-2011. GCA-associated deaths were defined as decedents ⩾55 years old with GCA listed as an underlying or non-underlying cause of death. Time trends of death rates were analysed and the mean age at death with GCA and in the general population ⩾55 years old were calculated. Standardized mortality odds ratios (SMORs) were calculated for 17 selected causes of death (based on 2000-11 data). Results: The analyses pertained to approximately 15 000 death certificates listing GCA (including approximately 6300 for 2000-11). Annual standardized death rates for GCA increased to a peak in 1997 and then decreased (Spearman's correlation test, both P < 0.0001). Mean age at death was higher for GCA than for general population decedents (Student's t-test, P < 0.0001). GCA deaths were frequently or strongly associated with aortic aneurysm and dissection (1.85% of death certificates, SMOR: 3.09, 95% CI: 2.48, 3.82), hypertensive disease (20.78%, SMOR: 2.22, 95% CI: 1.97, 2.50), diabetes mellitus (11.27%, SMOR: 1.96, 95% CI: 1.72, 2.23), certain infectious and parasitic diseases (12.12%, SMOR: 1.76, 95% CI: 1.55, 2.00) and ischaemic heart disease (16.54%, SMOR: 1.45, 95% CI: 1.35, 1.64). Conclusion: GCA is associated with increased risk of dying from large-vessel disease, other cardiovascular diseases and potentially treatment-related co-morbidities. These findings help provide better insights into the outcomes of GCA.


Assuntos
Doenças Cardiovasculares/epidemiologia , Atestado de Óbito , Arterite de Células Gigantes/epidemiologia , Neoplasias/epidemiologia , Sistema de Registros , Idoso , Causas de Morte/tendências , Comorbidade/tendências , Bases de Dados Factuais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
12.
Ann Nucl Med ; 32(5): 319-327, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29560563

RESUMO

OBJECTIVE: The identification of cardiac sarcoidosis is challenging as there is no gold standard consensually admitted for its diagnosis. The aim of this study was to evaluate the diagnostic value of the assessment of cardiac dynamic 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET/CT) and net influx constant (Ki) in patients suspected of cardiac sarcoidosis. METHODS: Data obtained from 30 biopsy-proven sarcoidosis patients suspected of cardiac sarcoidosis who underwent a 50-min list-mode cardiac dynamic 18F-FDG PET/CT after a 24 h high-fat and low-carbohydrate diet were analyzed. A normalized coefficient of variation of quantitative glucose influx constant, calculated as the ratio: standard deviation of the segmental Ki (min-1)/global Ki (min-1) was determined using a validated software (Carimas® 2.4, Turku PET Centre). Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare criteria. Receiving operating curve analysis was performed to determine sensitivity and specificity of cardiac dynamic 18F-FDG PET/CT analysis to diagnose cardiac sarcoidosis. RESULTS: Six out of 30 patients (20%) were diagnosed as having cardiac sarcoidosis. Myocardial glucose metabolism was significantly heterogeneous in patients with cardiac sarcoidosis who showed significantly higher normalized coefficient of variation values compared to patients without cardiac sarcoidosis (0.513 ± 0.175 vs. 0.205 ± 0.081; p = 0.0007). Using ROC curve analysis, we found a cut-off value of 0.38 for the diagnosis of cardiac sarcoidosis with a sensitivity of 100% and a specificity of 91%. CONCLUSIONS: Our results suggest that quantitative analysis of cardiac dynamic 18F-FDG PET/CT could be a useful tool for the diagnosis of cardiac sarcoidosis.


Assuntos
Fluordesoxiglucose F18 , Cardiopatias/diagnóstico por imagem , Coração/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sarcoidose/diagnóstico por imagem , Adulto , Idoso , Dieta com Restrição de Carboidratos , Dieta Hiperlipídica , Ecocardiografia , Feminino , Glucose/metabolismo , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio , Miocárdio/metabolismo , Miocárdio/patologia , Curva ROC , Estudos Retrospectivos , Sarcoidose/metabolismo , Sarcoidose/patologia , Software
13.
Autoimmun Rev ; 17(4): 391-398, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29427822

RESUMO

OBJECTIVES: Large-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA. PATIENTS AND METHODS: A retrospective multicenter study enrolled 248 GCA patients with LVI and 301 GCA patients without LVI on imaging. Factors associated with aortic dilation were identified in a multivariable model. RESULTS: The patients with LVI were younger (p<0.0001), more likely to be women (p=0.01), and showed fewer cephalic symptoms (p<0.0001) and polymyalgia rheumatica (p=0.001) but more extracranial vascular symptoms (p=0.05) than the patients without LVI. Glucocorticoids (GC) management did not differ between the two groups, but the GC discontinuation rate was lower in the patients with LVI (p=0.0003). Repeated aortic imaging procedures were performed at 19months [range: 5-162months] and 17months [range: 6-168months] after diagnosis in 154 patients with LVI and 123 patients without LVI, respectively, of whom 21% and 7%, respectively, presented new aortic dilations (p=0.0008). In the patients with LVI, aortic dilation occurred on an aorta segment shown to be inflammatory on previous imaging in 94% of patients. In the multivariate analysis, LVI was the strongest predictor of aortic dilation (hazard ratio: 3.16 [range: 1.34-7.48], p=0.009). CONCLUSIONS: LVI represents a distinct disease pattern of GCA with an increased risk of aortic dilation. Control of the aortic morphology during follow-up is required.


Assuntos
Doenças da Aorta/diagnóstico , Arterite de Células Gigantes/diagnóstico , Idoso , Doenças da Aorta/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Autoimmun Rev ; 17(4): 331-343, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29427823

RESUMO

PURPOSE: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not. RESULTS: Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed. CONCLUSION: Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.


Assuntos
Testes Diagnósticos de Rotina/métodos , Uveíte/diagnóstico , Uveíte/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Uveíte/patologia
15.
J Rheumatol ; 45(3): 425-429, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29335349

RESUMO

OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD). METHODS: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7). RESULTS: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively. CONCLUSION: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment.

16.
Joint Bone Spine ; 85(3): 345-351, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28528280

RESUMO

OBJECTIVE: To assess prevalence of aortic involvement in relapsing polychondritis (RP) patients; to evaluate clinical features and long-term outcome of RP patients exhibiting aortitis, aortic ectasia and/or aneurysm. METHODS: One hundred and seventy-two RP patients underwent aortic computed tomography (CT)-scan; they were seen in 3 medical centers. RESULTS: Eleven patients (6.4%) had aortic involvement, occurring within a median time of 2 years after RP diagnosis. CT-scan showed isolated aortitis (n=2); the 9 other patients exhibited: aortitis and aortic aneurysm (n=2) or ectasia (n=1), isolated aortic aneurysm (n=4) or ectasia (n=2); aortic localizations were as follows: thoracic (n=6), abdominal (n=2), thoracic and abdominal (n=4) aorta. Patients exhibited: resolution (n=3) improvement (n=3), stabilization (n=4) or deterioration (n=1) of aortic localization. Five patients experienced recurrence of aortic localization; one patient died of aortic abdominal aneurysm rupture. Predictive factors of death related to aortic complications were: aortitis on CT-scan, higher median levels of erythrocyte sedimentation rate. Predictive parameters of aortic relapses were: aortitis on CT-scan and involvement of the abdominal aorta. CONCLUSIONS: This study underlines that aortic involvement is severe in RP. Furthermore, we suggest that RP patients exhibiting poor prognostic factors, including panaortitis and higher values of ESR, may require more aggressive therapy.

17.
Eur J Intern Med ; 46: 66-70, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28865740

RESUMO

OBJECTIVE: 18F-FDG PET/CT can detect large-vessel involvement in giant-cell arteritis (GCA) with a good sensitivity. In patients with clinically and biologically controlled disease, we aimed to assess how vascular uptakes evolve on repetitive FDG-PET/CT. PATIENTS AND METHODS: All included patients had to satisfy the 4 following criteria: 1) diagnosis of GCA was retained according to the criteria of the American College of Rheumatology or based on the satisfaction of 2 criteria associated with the demonstration of large-vessel involvement on FDG-PET/CT; 2) all patients had a positive PET/CT that was performed at diagnosis before treatment or within the first 10days of treatment; 3) another FDG-PET/CT was performed after at least 3months of controlled disease without any relapse; 4) patients were followed-up at least for 12months. RESULTS: Twenty-five patients (17 [68%] women, median age: 69 [65-78]) with large-vessel inflammation on a baseline FDG-PET/CT and with repetitive imaging during the period with controlled disease were included and followed-up for 62 [25-95] months. Four repeated procedures revealed total extinction of vascular uptakes at 11.5 [8-12] months after the first FDG-PET/CT. Eight PET/CT revealed decreased numbers of vascular uptakes, and 10 procedures revealed no changes. The 3 remaining procedures indicated worsening of the numbers of vascular uptakes in the absence of relapse. CONCLUSIONS: Our study revealed long-term persistent vascular uptake on repeated FDG-PET/CT in >80% of our GCA patients with large-vessel inflammation and clinical-biological controlled disease. Prospective studies are required to confirm these findings.


Assuntos
Arterite de Células Gigantes/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Feminino , Fluordesoxiglucose F18/administração & dosagem , França , Humanos , Masculino , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos
18.
J Clin Immunol ; 37(7): 715-726, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28842786

RESUMO

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID. METHODS: The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed. RESULTS: Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0-1400]*106/L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35-4.4]. Most patients presented increased numbers of CD21low CD38low B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process. CONCLUSION: Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an "alarm bell" considering patients' presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.


Assuntos
Imunodeficiência de Variável Comum/epidemiologia , Neutropenia/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Imunodeficiência de Variável Comum/sangue , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Comorbidade , Feminino , França/epidemiologia , Humanos , Imunoglobulinas/sangue , Lactente , Recém-Nascido , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/genética , Neutropenia/imunologia , Sequenciamento Completo do Exoma , Adulto Jovem
19.
Autoimmun Rev ; 16(9): 963-969, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28709761

RESUMO

BACKGROUND: Although peripheral nervous system involvement is common in eosinophilic granulomatosis with polyangiitis (EGPA), central nervous system (CNS) manifestations are poorly described. This study aimed to describe CNS involvement in EGPA. PATIENTS AND METHODS: This retrospective, observational, multicenter study included patients with EGPA and CNS involvement affecting cranial nerves, brain and/or spinal cord. We also undertook a systematic literature review. RESULTS: We analyzed 26 personal cases and 62 previously reported cases. At EGPA diagnosis, asthma was noted in 97%, eosinophilia in 98%, peripheral neuropathy in 55% and cardiac involvement in 41%. 38/71 (54%) were ANCA-positive, with a perinuclear-labeling pattern and/or anti-MPO specificity. CNS was involved in 86% at EGPA diagnosis, preceded EGPA in 2%, and occurred during follow-up in 12% after a median of 24months. Main neurological manifestations were ischemic cerebrovascular lesions in 46 (52%), intracerebral hemorrhage and/or subarachnoid hemorrhage in 21 (24%), loss of visual acuity in 28 (33%) (15 with optic neuritis, 9 with central retinal artery occlusion, 4 with cortical blindness), and cranial nerves palsies in 18 (21%), with 25 patients having ≥1 of these clinical CNS manifestations. Among the 81 patients with assessable neurological responses, 43% had complete responses without sequelae, 43% had partial responses with long-term sequelae and 14% refractory disease. After a mean follow-up of 36months, 11 patients died including 5 from intracerebral hemorrhages. CONCLUSION: EGPA-related CNS manifestations form 4 distinct neurological pictures: ischemic lesions, intracerebral hemorrhages, cranial nerve palsies and loss of visual acuity. Such manifestation should prompt practitioners to consider EGPA in such conditions. Long-term neurological sequelae were common, and intracerebral hemorrhages had the worst prognostic impact.


Assuntos
Encéfalo/patologia , Eosinofilia/patologia , Granulomatose com Poliangiite/patologia , Adulto , Idoso , Asma/diagnóstico por imagem , Asma/patologia , Encéfalo/diagnóstico por imagem , Eosinofilia/diagnóstico por imagem , Eosinofilia/tratamento farmacológico , Feminino , Granulomatose com Poliangiite/diagnóstico por imagem , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Oclusão da Artéria Retiniana/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento
20.
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
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