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2.
Artigo em Inglês | MEDLINE | ID: mdl-32211770

RESUMO

OBJECTIVES: To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA vasculitis (IgAV). METHODS: Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared. RESULTS: One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia. CONCLUSION: GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen.

3.
Int J Cardiol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-32122700

RESUMO

BACKGROUND: Cardiac sarcoidosis (CS) is a challenging diagnosis. Patients may progress to end-stage congestive heart failure and require cardiac transplantation without ever having been diagnosed. Characteristics and outcomes of patients with granulomas in the explanted hearts are unknown. METHODS: All French heart transplantation centers were contacted to participate in the study. Each center searched through local databases for the cases of non-caseating granuloma in the explanted hearts between 2000 and 2017. Data before and after transplantation were recorded from medical charts. Survival of CS and all- cause heart transplantation patients were compared. RESULTS: Fifteen patients (10 men, 5 women) received a diagnosis of CS based on pathologic data of the explanted heart and were recruited for the study. All patients were diagnosed as non-ischemic dilated or hypertrophic cardiomyopathy and presented congestive heart failure. Eight patients (53%) had ventricular rhythm disturbances, and 3 (20%) a complete heart block. Ten out of 13 patients (77%) had extracardiac radiological signs compatible with sarcoidosis on chest computed tomography (CT) scans. One patient died 3 months after transplantation from infectious complications. The 14 remaining patients were still alive at the end of the study (median follow-up of 28.8 months). One patient had a second heart transplantation 5 years later because of chronic allograft vasculopathy. One patient presented a relapse of CS confirmed by myocardial biopsies 9 years after transplantation, requiring an escalation of immunosuppressive therapy. CONCLUSION: CS may be undiagnosed before heart transplantation. In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques.

4.
Blood ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107533

RESUMO

Erdheim-Chester disease (ECD) is characterized by the infiltration of tissues by foamy CD68+CD1a- histiocytes, with 1500 known-cases since 1930. Mutations activating the MAPK pathway are found in more than 80% of ECD patients, mainly the BRAFV600E activating mutation in 57-70% of cases, followed by MAP2K1 in close to 20%. The discovery of BRAF mutations and of other MAP kinase pathway alterations, as well as the co-occurrence of ECD with LCH in 15% of ECD patients, led to the 2016 revision of the classification of histiocytoses in which LCH and ECD belong to the "L" group. Both conditions are considered inflammatory myeloid neoplasms. Ten percent of ECD cases are associated with myeloproliferative neoplasms and/or myelodysplastic syndromes. Some of the most striking signs of ECD are the long bone involvement (80-95%), as well as the 'hairy kidney' appearance on the CT-scan (63%), the "coated aorta" (40%), the right atrium pseudo-tumoral infiltration (36%). Central nervous system (CNS) involvement is a strong prognostic factor and independent predictor of death. Interferon-alpha seems to be the best initial treatment for ECD. Since 2012, more than 200 patients worldwide with multi-system or refractory ECD have benefitted from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have an overall, robust and reproducible efficacy in ECD, with no acquired resistance to date, but their use may be best reserved for the most severe manifestations of the disease, as they may be associated with serious side-effects and as yet unknown long-term consequences.

6.
Chest ; 157(2): 323-333, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31669429

RESUMO

BACKGROUND: Destombes-Rosai-Dorfman disease (RDD) is a rare multisystemic histiocytosis. Pulmonary involvement during RDD has been poorly described. The goal of this study was to examine the clinical presentations, radiological features, and outcomes of 15 patients with RDD and lung involvement. METHODS: The cases of RDD with lung involvement were extracted from the French National Histiocytosis registry. Efficacy of the MEK inhibitor cobimetinib in treating lung disease was evaluated with an 18fluorodeoxyglucose PET scanner and chest CT scans. RESULTS: Fifteen patients (six women; median age, 40 years at RDD diagnosis) were included. All patients had evidence of systemic disease with extrapulmonary localizations of the disease (lymphadenopathy [n = 12], skin [n = 9], bones [n = 6], retroperitoneal involvement [n = 3], sinuses [n = 3], parotid gland [n = 2], submandibular gland [n = 1], and breast [n = 1]). Presenting symptoms were dominated by dyspnea and dry cough in seven patients. Restrictive physiology was observed in two of five patients. BAL showed lymphocytosis in one of five cases. Eight patients received corticosteroids, all but one with variable immunosuppressive or immunomodulatory therapies. Two patients received cobimetinib for severe lung disease, with dramatic pulmonary metabolic and tumoral responses. Two patients died during follow-up: one of hemoptysis, and the other of an unrelated cerebral tumor. CONCLUSIONS: Pulmonary involvement in RDD is rare, proteiform, and sometimes severe. The MEK inhibitor cobimetinib can lead to dramatic responses.

8.
Arthritis Rheumatol ; 72(1): 197, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31469251
10.
Ann Rheum Dis ; 79(3): 339-346, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31852672

RESUMO

OBJECTIVES: To compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease. METHODS: A monocentric, 12-month, superiority, open-label, randomised (1:1) controlled trial was conducted with 61 patients continuing 5 mg/day prednisone and 63 stopping it. Eligibility criteria were SLE patients who, during the year preceding the inclusion, had a clinically inactive disease and a stable SLE treatment including 5 mg/day prednisone. The primary endpoint was the proportion of patient experiencing a flare defined with the SELENA-SLEDAI flare index (SFI) at 52 weeks. Secondary endpoints included time to flare, flare severity according to SFI and British Isles Lupus Assessment Group (BILAG) index and increase in the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI). RESULTS: Proportion of patients experiencing a flare was significantly lower in the maintenance group as compared with the withdrawal group (4 patients vs 17; RR 0.2 (95% CI 0.1 to 0.7), p=0.003). Maintenance of 5 mg prednisone was superior with respect to time to first flare (HR 0.2; 95% CI 0.1 to 0.6, p=0.002), occurrence of mild/moderate flares using the SFI (3 patients vs 12; RR 0.2 (95% CI 0.1 to 0.8), p=0.012) and occurrence of moderate/severe flares using the BILAG index (1 patient vs 8; RR 0.1 (95% CI 0.1 to 0.9), p=0.013). SDI increase and adverse events were similar in the two treatment groups. Subgroup analyses of the primary endpoint by predefined baseline characteristics did not show evidence of a different clinical response. CONCLUSION: Maintenance of long term 5 mg prednisone in SLE patients with inactive disease prevents relapse. TRIAL REGISTRATION NUMBER: NCT02558517; Results.

11.
Postgrad Med J ; 96(1131): 21-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31467142

RESUMO

OBJECTIVES: This work aimed to study the prevalence and risk factors associated with well-being and career satisfaction among French internal medicine physicians and residents. METHODS: A total of 1689 French internal medicine physicians or trainees were surveyed to evaluate their workload, well-being and career satisfaction during February 2018. RESULTS: The response rate was 620/1689 (37%). The mean age of the participants was 37 years (±12); 49% of the participants were female, 27% worked in the Paris area, 74% worked in a university hospital and 49% were residents. Sixty-six per cent of the responders were satisfied with their work, and 66% would choose the internal medicine specialty again. However, 71% of the responders worked more than 50 hours a week, 21% worked more than 60 hours a week and 70% believed that they did not have enough time for personal/family activities. Twenty-five per cent of the responders had at least one sign of burnout (19% of the physicians in practice and 32% of the residents). Compared with the graduate physicians in practice, the residents worked more hours a week, had more activities at night, spent more time on administrative tasks, had a worse global appreciation of their work and felt that their work was less meaningful. In multivariate analysis, the factors associated with global satisfaction at work were autonomy and meaningful work. CONCLUSIONS: French internal medicine physicians have a high rate of career satisfaction. However, residents have a higher workload, less time for personal/family activities and feel that their work is less meaningful.

12.
Curr Rheumatol Rep ; 21(12): 66, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31807955

RESUMO

PURPOSE OF REVIEW: This report provides an overview of the current knowledge of molecular characterization, clinical description, and treatment of Erdheim-Chester disease (ECD), a multi-systemic adult histiocytosis of the L group. RECENT FINDINGS: The recent identification of several MAPK mutations in histiocytes of ECD lesions. Leading to targeted therapies. The discovery of the BRAFV600E mutation in ECD lesions followed by several other kinase mutations in the MAPK pathway has revolutionized our understanding of the disease pathogenesis and led to trials with targeted therapies that demonstrated robust efficacy.

13.
J Rheumatol ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31787599

RESUMO

OBJECTIVE: To report on a large series of patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) and bronchiectasis, with a specific focus on the timeline of occurrence of both features. METHODS: Retrospective nationwide multicentric study of patients diagnosed with both AAV and bronchiectasis. RESULTS: Sixty-one patients were included among which 27 (44.25 %) had microscopic polyangiitis (MPA), 27 (44.25%) had granulomatosis with polyangiitis and 7 (11.5%) had eosinophilic granulomatosis with polyangiitis. 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 IQR [4-54] years), was concomitant to (n=13) or followed (n=36; median time between both diagnoses: 1 IQR [0-6] year) 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 five-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 fortuitous 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.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31846040

RESUMO

OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment). METHODS: Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19). RESULTS: A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19-0.6%), P < 0.0001; active SLE: median = 0.61 (0.55-0.77), P < 0.0001 vs healthy controls: 2.32% (1.18-4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood. CONCLUSION: In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death.

16.
Int J Neurosci ; : 1-3, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31679396

RESUMO

Neurosarcoidosis is a rare inflammatory neurological condition. We describe a challenging radiological presentation of neurosarcoidosis. The eclipse sign refers to hypo T1-weighted parenchymal or leptomeningeal images surrounded by circular gadolinium enhancement. The eclipse sign was identified in 3 out of 46 patients with histologically-proven neurosarcoidosis. The eclipse sign may correspond to necrotizing parenchymal or leptomeningeal granuloma. This sign expands the spectrum of radiological presentations of neurosarcoidosis.

17.
Chest ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31783015

RESUMO

BACKGROUND: The antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic events that can require ICU admission because of organ dysfunction related to macrovascular and/or microvascular thrombosis. Critically ill patients with thrombosis and APS were studied to gain insight into their prognoses and in-hospital mortality-associated factors. METHODS: This French national, multicenter, retrospective study included all patients with APS and any new thrombotic manifestations admitted to 24 ICUs (January 2000-September 2018). RESULTS: During the study period, 134 patients (male/female ratio, 0.4) with 152 APS episodes were admitted to the ICU (mean age at admission, 46.0 ± 15.1 years). In-hospital mortality of their 134 last episodes was 35 of 134 (26.1%). The Cox multivariable model retained certain factors (hazard ratio [95% CI]: age ≥ 40 years, 11.4 [3.1-41.5], P < .0001; mechanical ventilation, 11.0 [3.3-37], P < .0001; renal replacement therapy, 2.9 [1.3-6.3], P = .007; and in-ICU anticoagulation, 0.1 [0.03-0.3], P < .0001) as independently associated with in-hospital mortality. For the subgroup of definite/probable catastrophic APS, the Cox bivariable model (including the Simplified Acute Physiology Score II score) retained double therapy (corticosteroids + anticoagulant, 0.2 [0.07-0.6]; P = .005) but not triple therapy (corticosteroids + anticoagulant + IV immunoglobulins or plasmapheresis: hazard ratio, 0.3 [0.1-1.1]; P = .07) as independently associated with in-hospital mortality. CONCLUSIONS: In-ICU anticoagulation was the only APS-specific treatment independently associated with survival for all patients. Double therapy was independently associated with better survival of patients with definite/probable catastrophic APS. In these patients, further studies are needed to determine the role of triple therapy.

18.
Ann Rheum Dis ; 78(12): 1669-1676, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31570366

RESUMO

OBJECTIVES: Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations. METHODS: A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively. RESULTS: Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not. CONCLUSION: Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31620787

RESUMO

OBJECTIVE: To explore, at an item-level, the effect of disease activity (DA) on specific health-related quality of life (HRQoL) in SLE patients using an item response theory longitudinal model. METHODS: This prospective longitudinal multicentre French cohort EQUAL followed SLE patients over 2 years. Specific HRQoL according to LupusQoL and SLEQOL was collected every 3 months. DA according to SELENA-SLEDAI flare index (SFI) and revised SELENA-SLEDAI flare index (SFI-R) was evaluated every 6 months. Regarding DA according to SFI and each SFI-R type of flare, specific HRQoL of remitting patients was compared with non-flaring patients fitting a linear logistic model with relaxed assumptions for each domain of the questionnaires. RESULTS: Between December 2011 and July 2015, 336 patients were included (89.9% female). LupusQoL and SLEQOL items related to physical HRQoL (physical health, physical functioning, pain) were most affected by musculoskeletal and cutaneous flares. Cutaneous flares had significant influence on self-image. Neurological or psychiatric flares had a more severe impact on specific HRQoL. Patient HRQoL was impacted up to 18 months after a flare. CONCLUSION: Item response theory analysis is able to pinpoint items that are influenced by a given patient group in terms of a latent trait change. Item-level analysis provides a new way of interpreting HRQoL variation in SLE patients, permitting a better understanding of DA impact on HRQoL. This kind of analysis could be easily implemented for the comparison of groups in a clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904812.

20.
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.

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