Haroche J.,Institute E3M |
Cohen-Aubart F.,Institute E3M |
Rollins B.J.,Dana-Farber Cancer Institute |
Donadieu J.,AP HP |
And 6 more authors.
The Lancet Oncology | Year: 2017
Histiocytoses are disorders characterised by inflammation and the accumulation of cells derived from the monocyte and macrophage lineages, which results in tissue damage. Although they are often considered rare disorders with protean clinical manifestations, considerable advances in the understanding of their genetics have led to increased clinical recognition of these conditions, and fuelled further insights into their pathogenesis. In this Review, we describe insights into the cells of origin, molecular pathology, clinical features, and treatment strategies for some of the most common histiocytic disorders, including Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease. With the discovery of recurrent mutations affecting the mitogen-activated protein kinase and mTOR–AKT pathways in some of these histiocytoses, our understanding of these diseases has now evolved from the concept of a primary inflammatory condition to that of a clonal neoplastic disease. This understanding has led to the development of effective mechanism-based therapeutic strategies for patients with histiocytic diseases. © 2017 Elsevier Ltd
Papo M.,Institute E3M |
Diamond E.L.,Sloan Kettering Cancer Center |
Cohen-Aubart F.,Institute E3M |
Emile J.-F.,University of Versailles |
And 21 more authors.
Blood | Year: 2017
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAFV600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. Insomecases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm. © 2017 by The American Society of Hematology.
Grimaldi A.,Institute E3M |
Penfornis A.,University Paris - Sud |
Consoli S.,University of Paris Descartes |
Falissard B.,University Paris - Sud |
And 3 more authors.
Advances in Therapy | Year: 2016
Background: The OPTIMA© (MSD, Courbevoie, France) questionnaire was developed to promote shared decisions and the set-up of specific micro-objectives in clinical practice by optimizing communication between type 2 diabetes (T2DM) patients and their physicians. The present study aimed to assess OPTIMA in clinical practice. Methods: A cross-sectional multicenter observational study was conducted in France from 2012 to 2014. During routine consultation, patients completed one of the five modules of the OPTIMA questionnaire (Physical activity, Diet, Treatment, Knowledge of the disease or Self-monitoring of blood glucose). The rate of SMART (specific, measurable, acceptable, realistic, timely) micro-objective set-up following the use of the questionnaire was assessed. Data on how patients felt about their diabetes management (beliefs concerning actions, how easy they were to do and how often they were done in practice) were gathered. Finally, patients’ and physicians’ opinions on OPTIMA were assessed using the PRAgmatic Content and face validity Test (PRAC-Test© (Mapi, Lyon, France) evaluation questionnaire. Results: Overall, 807 patients were included by 186 physicians. While 92.7 % of consultations led to the set-up of a micro-objective, only 22.3 % were SMART micro-objectives: Physical activity module (34.3 %), Diet module (9.6 %), Treatment module (16.4 %), Knowledge of the disease module (25.2 %), and self-monitoring of blood glucose module (29.5 %). Among patients completing the Physical activity module, 79.0 % reported that they believed physical activity was useful, 35.0 % that it was easy, and 25.8 % that they regularly practised it. PRAC-Test results showed that OPTIMA was a useful and easy-to-use questionnaire that promotes communication between physicians and their patients according to 92.8 % of patients and 69.4 % of physicians. Conclusion: The OPTIMA questionnaire facilitates communication between patients and their physicians and promotes the set-up of micro-objectives concerning T2DM management. The Physical activity module was the most likely of the five modules in the questionnaire to lead to the set-up of SMART micro-objectives. Funding: MSD France. © 2016, The Author(s).
PubMed | Service de neurologie, Institute e3M, University Paris - Sud, Service danatomo pathologie and 3 more.
Type: | Journal: La Revue de medecine interne | Year: 2016
Neurological localizations of sarcoidosis are heterogeneous and may affect virtually every part of the central or peripheral nervous system. They are often the inaugural manifestation of sarcoidosis. The diagnosis may be difficult due to the lack of extra-neurological localization. Diagnosis may be discussed in the presence of an inflammatory neurological disease, in particular in case of suggestive radiological or biological pattern. Cerebrospinal fluid analysis shows lymphocytic pleiocytosis, often with low glucose level. The diagnosis relies on a clinical, biological and radiological presentation consistent with neurosarcoidosis, the presence of non-caseating granuloma and exclusion of differential diagnoses. Screening for other localizations of sarcoidosis, in particular cardiac disease may be obtained during neurosarcoidosis. The treatment of neurosarcoidosis relies on corticosteroids although immunosuppressive drugs are usually added because of the chronic course of this condition and to limit the side effects of steroids. Treatments and follow-up may be prolonged because of the high rate of relapses.
Marlet J.,Hopital Pitie Salpetriere AP HP |
Ankri A.,Laboratoire DHematologie |
Charuel J.-L.,Hopital Pitie Salpetriere AP HP |
Ghillani-Dalbin P.,Hopital Pitie Salpetriere AP HP |
And 9 more authors.
PLoS ONE | Year: 2015
Context: Anti-DFS70 antibodies are the most frequent antinuclear antibodies (ANA) found in healthy individuals. We assessed the clinical significance of the presence of anti-DFS70 antibodies. Methods We defined a group of patients (n = 421) with anti-DFS70 antibodies and a group of patients (n = 63) with a history of idiopathic arterial and/or venous thrombotic disease and/or obstetric complication (i.e. ≥3 miscarriages, fetal death or premature birth with eclampsia). Anti- DFS70 antibodies prevalence was also assessed in a cohort of 300 healthy blood donors. Results The prevalence of thrombotic disease and/or obstetric complication in the 421 patients with anti-DFS70 antibodies was 13.1%(n = 55) and the prevalence of connective tissue disease was 19% (n = 80). Among the 63 patients with a history of thrombosis and/or obstetric complications, 7 (11.1%) had anti-DFS70 antibodies and among the latter, 5 had no common thrombophilic factor. In contrast, the prevalence of anti-DFS70 antibodies was of 3.0% (9 out of 300) in healthy donors. Finally, the Activated Partial Thromboplastin Time (aPTT) ratio of patients with a history of thrombosis and anti-DFS70 antibodies was lower than the aPTT ratio of other patients, suggesting that thrombotic patients with anti-DFS70 antibodies may have a hypercoagulable state. Conclusion We described here for the first time an immune procoagulant state involving anti-DFS70 antibodies. © 2015 Marlet et al.
Miyara M.,CNRS Immunology and Infectious Disease Center |
Chader D.,CNRS Immunology and Infectious Disease Center |
Sage E.,Hopital Foch |
Sugiyama D.,Osaka University |
And 14 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
CD4+ regulatory T (Treg) cells expressing CD25 and the transcription factor forkhead box P3 (FOXP3) are indispensable for immunological self-tolerance and homeostasis. FOXP3+CD25+CD4+ T cells in humans, however, are heterogeneous in function and differentiation status, including suppressive or nonsuppressive cells as well as resting or activated Treg cells. We have searched for cell surface markers specific for suppression-competent Treg cells by using a panel of currently available monoclonal antibodies reactive with human T cells. We found that CD15s (sialyl Lewis x) was highly specific for activated, terminally differentiated, and most suppressive FOXP3high effector Treg (eTreg) cells and able to differentiate them in various clinical settings from nonsuppressive FOXP3+ T cells secreting inflammatory cytokines. For example, CD15s+FOXP3+ eTreg cells were increased in sarcoidosis, whereas it was nonsuppressive CD15s-FOXP3+ T cells that were expanded in lupus flares. FOXP3+ cells induced from conventional CD4+ T cells by T-cell receptor stimulation hardly expressed CD15s. CD15s+CD4+ T-cell depletion was sufficient to evoke and enhance in vitro immune responses against tumor or viral antigens. Collectively, we have identified CD15s as a biomarker instrumental in both phenotypic and functional analysis of FOXP3+CD4+ T-cell subpopulations in health and disease. It allows specific targeting of eTreg cells, rather than whole FOXP3+CD4+ T cells, in controlling immune responses. © 2015 PNAS.
Jublanc C.,Institute E3M |
Bruckert E.,Institute E3M
Revue de Medecine Interne | Year: 2016
Adrenal insufficiency is a rare but life-threatening disorder. Clinical manifestations include fatigue, weight loss, gastrointestinal manifestations and skin hyperpigmentation, the latter being specific of primary adrenal failure. Because of non-specific clinical features of this rare disorder, diagnosis can be delayed and adrenal failure be revealed by an acute crisis. Adrenal insufficiency can be primary (Addison disease), most frequently autoimmune, or secondary, resulting from long term administration of exogenous glucocorticoids or more rarely from pituitary disorders. Monitoring of substitutive treatment is now well codified. Patient education is very important in this chronic disease that remains associated with a persistent high risk of adrenal crisis. © 2016 Société nationale française de médecine interne (SNFMI).
Pineton de Chambrun M.,Institute E3M |
Charron P.,Institute E3M |
Vauthier-Brouzes D.,Institute E3M |
Cluzel P.,Institute E3M |
And 4 more authors.
Medicine | Year: 2015
Idiopathic hypereosinophilic syndrome (HES) is a condition of unknown origin characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. Cardiac involvement is rare and threatening accounting for 33% to 43% of death in HES. Management of pregnant patients with HES is challenging and have rarely been reported, particularly in the setting of heart failure.We here report on the case of a 29-year-old woman with HES who developed severe endomyocardial fibrosis with heart failure during pregnancy. Outcome was favorable under treatment with prednisone and azathioprine.This case illustrates a favorable outcome of endomyocardial fibrosis during pregnancy.
PubMed | University of Paris 13, Service danatomo pathologie, Institute E3M, Center Regional Of Pharmacovigilance and University Pierre and Marie Curie
Type: Journal Article | Journal: La Revue de medecine interne | Year: 2016
Nitrofurantoin is a commonly used drug which can have liver and pulmonary adverse effects. Among hepatic nitrofurantoin-induced adverse effects, autoimmune hepatitis is a rare complication which must not be mistaken as a toxic hepatitis.We report an 86-year-old woman who presented with acute hepatitis after a 3-month course of nitrofurantoin administration for urinary tract infections. She reported a previous hepatitis after treatment by nitrofurantoin twenty years before. Biological analysis showed polyclonal hypergammaglobulinemia, positive test for antinuclear antibodies and smooth muscle antibodies. Finally, liver histology showed lymphocytic infiltration, marked necrotic and inflammatory activity consistent with the diagnosis of autoimmune hepatitis. Nitrofurantoin was discontinued. Outcome of autoimmune hepatitis was good with corticosteroids and azathioprine but two months later, the patient died from a refractory global heart failure.Nitrofurantoin-induced autoimmune hepatitis is a severe condition which must be systematically discussed in patients taking nitrofurantoin who present with acute hepatitis. Hypergammaglobulinemia is an easily obtained blood marker, which can suggest this diagnosis. Treatment relies on nitrofurantoin eviction, corticosteroids and sometimes azathioprine. Outcome is usually favorable.
PubMed | Institute E3M
Type: Journal Article | Journal: La Revue de medecine interne | Year: 2016
Adrenal insufficiency is a rare but life-threatening disorder. Clinical manifestations include fatigue, weight loss, gastrointestinal manifestations and skin hyperpigmentation, the latter being specific of primary adrenal failure. Because of non-specific clinical features of this rare disorder, diagnosis can be delayed and adrenal failure be revealed by an acute crisis. Adrenal insufficiency can be primary (Addison disease), most frequently autoimmune, or secondary, resulting from long term administration of exogenous glucocorticoids or more rarely from pituitary disorders. Monitoring of substitutive treatment is now well codified. Patient education is very important in this chronic disease that remains associated with a persistent high risk of adrenal crisis.