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Background Over the last decade, new therapies, screening optimization, and cardiovascular management have changed the cardiovascular prognosis of patients with multiple myeloma (MM). Older studies suggested that MM could be associated with increased risk of heart failure (HF). Based on a nationwide hospitalization database, we aimed to assess the risk of hospitalization for Heart failure (HF) and/or Atrial fibrillation (AF). Methods From 1st January 2013 to 31st December 2013, 3,381,472 adults (age ≥18 years) were hospitalized for any reason in French hospitals and then had at least 5 years of complete follow-up (or suffered death earlier). We identified 15,774 patients diagnosed with known MM at baseline. The outcome analysis on hospitalization for new onset HF or AF was performed with follow-up (FU) starting at the time of last event. For each patient with MM, a propensity score-matched patient with no MM was selected (1:1) using the one-to-one nearest neighbor method (n=15774 in each group). Findings In the propensity-score-matched population, mean±SD FU was 3.7±2.3 years, median (IQR)5.0 (1.3–5.7) years, mean age was 71±12y, and most were female (55%). When compared with patients without MM, MM patients were more likely to have history of HF (16.8% vs. 10.5%, p Interpretation From a large nationwide hospitalization database, we show that patients with MM had a higher risk of new onset HF and AF. Our findings highlight the key issue of cardiovascular management in patients with MM. Funding Acknowledgement Type of funding sources: None.

La arteritis de celulas gigantes (ACG) y la seudopoliartritis rizomelica (SPR) son dos enfermedades inflamatorias frecuentemente asociadas que afectan a pacientes mayores de 50 anos. La ACG es una vasculitis granulomatosa de los vasos de gran calibre. La SPR, que puede ser aislada o asociarse a la ACG en el 20% de los casos, es un reumatismo inflamatorio que afecta a las cinturas escapular y pelvica. El diagnostico de ACG o de SPR se sospecha clinicamente. El analisis biologico evidencia un sindrome inflamatorio en mas del 90% de los casos. El diagnostico de SPR recurre cada vez mas a criterios de pruebas de imagen, en especial con la deteccion de afectaciones inflamatorias articulares o periarticulares de los hombros y las caderas. La confirmacion del diagnostico de ACG requiere la deteccion de signos directos o indirectos de vasculitis mediante el examen de la biopsia de la arteria temporal o mediante una prueba de imagen vascular no invasiva (eco-Doppler, angiografia por tomografia computarizada, angiografia por resonancia magnetica y tomografia por emision de positrones). El tratamiento de la ACG y de la SPR se basa en la corticoterapia por via sistemica. En caso de recaida o de corticodependencia, es posible recurrir a tratamientos sin corticoides, en especial el metotrexato y el tocilizumab.

The first line treatment of immune thrombocytopenic purpura (ITP) is well established and based on short course of corticosteroids associated with intravenous immunoglobulins (IVIg) for the most severe forms. Predniso(lo)ne is the corticosteroid agent usually given but dexamethasone appears as an alternative. Some guidelines recommend to use dexamethasone as first line when a rapid increase of platelet count is required. Dexamethasone could be used rather than IVIg for moderate to severe but non life-threatening bleeding manifestations. Other therapeutic options such as anti FcRn monoclonal antibodies or recombinant FcγR currently in development for ITP could be an option in the future. In newly diagnosed ITP, we unfortunately lack robust predictive risk factors of severity and chronic outcome. Identifying such factors could be helpful for considering the early use of some treatments which are commonly used as second or third line.

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an immune peripheral destruction of platelets and an inappropriate platelet production. The pathogenesis of ITP is now better understood: it involves a humoral immune response which dependents on the stimulation of B cells by specific T cells called T follicular helper cells, leading to their differentiation into plasma cells that produce antiplatelet antibodies thus promoting the phagocytosis of platelets mainly by splenic macrophages. The deciphering of ITP pathogenesis has led to a better understanding of the inefficiency of treatments such as rituximab, although it has not provided yet the determination of biological predictive factor of response to treatments. Moreover, new therapeutic perspectives have been opened in the last few years with the development of molecules targeting Fcγ receptor signalling such as Syk inhibitor, or molecules increasing the clearance of pathogenic autoantibodies such as inhibitors of the neonatal Fc receptor (FcRn).

BackgroundPolymyalgia rheumatica (PMR) is an inflammatory rheumatic disease (1) associated in 16 to 21% of cases with giant cell arteritis (GCA). The association of these two conditions raises the question of a pathophysiological continuum between PMR and GCA. An early study reported mature arterial wall dendritic cells (DC) in patients with GCA or PMR leading, during GCA, to CD4+ T cell recruitment and the development of vasculitis (2). However, these data have never been confirmed in other studies. There are 3 main types of DC: plasmacytoid DC (expressing CD123), conventional DC (cDC) expressing CD141 (cDC1) or CD1c (cDC2) and monocyte-derived DC (mo-DC) expressing CD14.ObjectivesThe aim of this study was to describe the arterial wall infiltrating DCs, their phenotype and maturation state, during PMR and GCA.MethodsUsing temporal artery biopsies (TAB) from patients with PMR, GCA and healthy controls, the level of expression of CD11c, CD83, CCR7, CCR6, CD1c, CCL18, CCL19, CCL20, CCL21, GM-CSF, CD3, CD68 genes was assessed by RT-PCR. Expression of markers of DC lineage (CD209), DC maturation state (CD83 and CCR7) and DC origin (CD14, CD68, CD1c, CD141) were studied by confocal microscopy.ResultsFourty-one patients were included (14 GCA, 16 PMR, 11 controls). Within the arterial wall, DCs were identified in GCA patients, with a mature DC phenotype (CD209+CD83+CCR7+). DC were present in all three layers of the arterial wall and also expressed CD14 and often CD68 but neither CD1c nor CD141, which could be explained by a monocytic/macrophage origin. TAB from GCA patients were characterized by a high level of expression of CD83, CCR7, CCR6, CCL18, CCL19, CCL20, CD11c, GM-CSF, CD3 and CD68 gene. This expression was significantly higher (pConfocal microscopy analyses of arteries from the PMR and controls did not detect the presence of DCs into the arterial wall. In addition, level of expression of CD83, CCR7, CCL18, CCL19, CCL21 and CD68 genes in temporal arteries was comparable between PMR and healthy controls.ConclusionThis work confirms the presence of mature CD209+CD83+CCR7+ DCs within the arterial wall in GCA. The phenotype of these DCs mainly fits with DC of monocytic origin (mo-DCs). However, both by RT-PCR and confocal microscopy, we did not identify DCs in the arterial wall of PMR patients. This discrepancy with previous work (3) could be explained by a better diagnosis of GCA in PMR patients since the development of imaging techniques.References[1]Weyand CM, Goronzy JJ. Giant-Cell Arteritis and Polymyalgia Rheumatica. N Engl J Med. 2014;371:50-7.[2]Samson M, Corbera-Bellalta M, Audia S, Planas-Rigol E, Martin L, Cid MC, et al. Recent advances in our understanding of giant cell arteritis pathogenesis. Autoimmun Rev. 2017;16:833-44.[3]Ma-Krupa W, Jeon M-S, Spoerl S, Tedder TF, Goronzy JJ, Weyand CM. Activation of Arterial Wall Dendritic Cells and Breakdown of Self-tolerance in Giant Cell Arteritis. J Exp Med. 2004;199:173-83.Disclosure of InterestsNone declared.

BackgroundGiant cell arteritis (GCA) is a large-vessel vasculitis mainly involving the aorta and cranial arteries. It is the most frequent vasculitis in adults over 50 years. When they are stimulated by interferon-gamma (IFN-γ), vascular smooth muscle cells (VSMC) contribute to GCA pathogenesis by producing chemokines triggering the recruitment of pro-inflammatory T cells and monocytes (1).ObjectivesCurrent knowledge about the interaction between resident cells of the vascular wall (VSMC, myofibroblasts [MF]) and immune cells is limited. The aim of our research was to better characterize the interactions between VSMC, MF and T cells in GCA.MethodsFresh fragments of temporal artery biopsies (TAB) performed at Dijon university hospital (France) were prospectively sent to our research unit. Fresh sections of positive and negative TAB were fixed and embedded in optimal cutting temperature OCT and stored at -80°C. Then, cryostat sections were fixed, permeabilized, blocked and incubated with primary antibodies (anti-alpha smooth muscle actin [α-SMA], anti-myosin heavy chain 11 [MHC11], anti-Desmin, anti CD90, anti-CD45, anti-HLA-DR, anti-phospho STAT1 [pSTAT1] and anti-pSTAT3) and secondary antibodies for confocal microscopy analyses. Fresh sections of healthy TAB were embedded in MATRIGEL and covered by DMEM to obtain vascular cells in culture. Cells were treated with trypsina-EDTA between each passage. Vascular cells were used after 4-7 doubling passages. Cells were analyzed by immunofluorescence, flow cytometry and RT-PCR and their proliferation was evaluated by impedancemetry (iCELLigence system). Peripheral blood mononuclear cells (PBMC) and vascular cells thus obtained were co-cultured for 7 days in different conditions. Vascular cells were cultured in the presence or absence of IFN-γ and tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) and soluble receptor of IL-6 for 72 hours. When cells reached confluence, they were cultured alone or with allogenic PBMC activated with anti-CD3/CD28 microbeads. After 7 days of culture, cells were separated with a treatment with EDTA and studied by flow cytometry.ResultsConfocal microscopy analyses of GCA arteries showed that neointima was mainly composed of myofibroblasts (MF) (α-SMA+Desmin+MHC11lowCD90+) in contact with CD45+ cells and that MF expressed HLA-DR, the phosphorylated form of STAT1 (pSTAT1) and in a lesser extent pSTAT3, strongly suggesting the activation of the IFN-γ signaling pathway rather than the IL-6 pathway. The phenotype of cultured vascular cells isolated from fresh TAB was consistent with MF. When MF were exposed to IFN-γ and TNF-α in vitro, their proliferation capacity decreased and their levels of expression of HLA-DR and CD86 increased (median fluorescence intensity [MFI] from 0 to 57 [p=0.03] and from 34 to 103 [p=0.03], respectively). In addition, co-cultures of MF and activated PBMC revealed that MF maintained the polarization of T cells into Th1 and Tc1 cells (p≤0.001) and to a lesser extent into Th17 and Tc17 cells (p=0.03). This effect was even more significant when MF were previously exposed to IFN-γ and TNF-α but not when they were exposed to IL-6.ConclusionOur results show that myofibroblasts are present in the neointima of GCA patients and that these MF activate signaling pathways indicative of IFN-γ exposure. Moreover, these MF, especially when exposed to IFN-γ, maintain the polarization of T cells into Th1 and Tc1 cells, which contributes to amplify the production of IFN-γ and thus initiate a pro-inflammatory amplification loop that likely participates in vascular inflammation and remodelling.References[1]Corbera-Bellalta M, Planas-Rigol E, Lozano E, Terrades-Garcia N, Alba MA, Prieto-Gonzalez S, et al. Blocking interferon gamma reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis. Ann Rheum Dis 2016;75:1177-86.Disclosure of InterestsNone declared

Fertility preservation is routinely performed in cancerology but less systematically used in the field of immune diseases, even though the use of gonadotoxic treatments in young patients may be required and even though the disease itself can alter fertility. This review aimed to clarify the indications and methods of fertility preservation in this context. Cyclophosphamide is the only immunosuppressive drug requiring fertility preservation in women. In men, fertility preservation should be proposed before treatment with cyclophosphamide, methotrexate, mycophenolate mofetil or mTOR inhibitors. Other factors inherent to the disease or the patient may alter fertility. Thus, screening for infertility and fertility preservation have to be implemented as much as possible to increase the chances of successful procreation in patients with immune disease. For women, the choice between the different preservation methods depends on the patient's age, disease activity, the time available before the start of treatment, the possibility of future pregnancy and the woman's and even couple's wishes. Before puberty, the only accepted method is cryopreservation of ovarian tissue. After puberty, the first-line method is the cryopreservation of mature oocytes. If the treatment has to be started in an emergency, if ovarian hyperstimulation/oocyte retrieval is contraindicated or if the patient refuses this option, cryopreservation of ovarian tissue or GnRH agonists could be proposed. For men, the accepted method is sperm cryopreservation. For prepubertal boys, the cryopreservation of spermatogonia after testicular biopsy is still experimental.

To report the clinical efficacy and mid-term outcomes of endovascular treatment in patients with chronic, symptomatic, post-thrombotic femoro-iliac venous obstruction.Forty-two patients with post-thrombotic syndrome (PTS) presenting with femoro-iliac venous obstructive lesions treated in our institution by endovascular approach between March 2012 and October 2017 were retrospectively included. There were 27 women and 15 men with a mean age of 47.3±17 (SD) years (range: 22-86 years). Procedure included first venous recanalization, then pre-dilatation and self-expandable metallic stenting of the narrowed or occluded iliac and/or femoral veins. Severity of PTS and quality of life were assessed at baseline and 3 months after the intervention respectively, using Villalta score and Chronic Venous Insufficiency Questionnaire (CIVIQ-20) scale. Imaging follow-up evaluation of stent patency was based on the results of duplex Doppler ultrasound and computed tomography.Immediate technical success was achieved in 41/42 (97.6%) patients, without any major complications. Primary patency, primary assisted patency and secondary patency at the end of the median imaging follow-up of 18.1 months (IQR, 9.7-34.4) were achieved in 29/42 (66.7%) patients, 33/42 (78.6%) patients and 37/42 (88.1%) patients, respectively. Median Villalta and CIVIQ-20 scores decreased from 14 (IQR, 10-19) and 57 (IQR, 39-72) at baseline, respectively, to 5 (IQR, 2-9) and 30 (IQR, 24-50) 3 months after the procedure, respectively (P0.0001), showing significant decrease in the severity of PTS and improvement in the quality of life. The multiple linear regression model showed that both baseline Villalta and CIVIQ-20 scores ([95% CI: -7.80-3.79; P0.0001] and [95% CI: 0.07-0.20; P0.0001], respectively), age (95% CI: 0.04-0.19; P=0.002) and stenting expanse (95% CI: 0.97-5.65; P=0.006) were independent variables related to Villalta gain. Baseline Villalta (95% CI: 0.89-2.23; P0.0001) was the single independent variable related to CIVIQ-20 gain.This study confirms the high clinical efficacy and favorable mid-term outcomes of endovascular stenting in patients with chronic symptomatic femoro-iliac venous obstructive lesions.

International audience; Primary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P

Giant cell arteritis (GCA) is the most common vasculitis in adults. GCA is a granulomatous large-vessel vasculitis involving the aorta and its major branches in people50 years. Glucocorticoids (GC) remain the cornerstone of GCA treatment. Prednisone is usually started at 0.7 or 1mg/kg/day depending on the occurrence of ischemic complications. Then, GC are progressively tapered and stopped after a mean duration of 18 months. GC are very efficient but relapses often occur during their tapering. Moreover, GC-related side effects are very common during this long term GC therapy. Thus, it can be assumed that GC are not the ideal treatment for GCA and that GC-sparing strategies have to be developed. The pathogenesis of GCA is not fully understood but major advances have been achieved in the recent years. If the trigger of GCA, which is suspected to be infectious, is still not identified, mechanisms triggering the granulomatous inflammation of the arterial wall and the progressive vascular remodeling leading to the occurrence of ischemic events have been better and better deciphered. Thanks to these advances in the knowledge of GCA pathogenesis, new therapeutic targets have emerged such as blockade of the activation of T cells or inhibition of the interleukin-6 (IL-6), IL-12/23 or IL-1β pathways.

International audience; BACKGROUND:In 2014, the European Society for Immune Deficiencies (ESID) revised the common variable immunodeficiency (CVID) diagnosis criteria by incorporating new clinical and biological markers. The new definition appeared more restrictive but had not yet been evaluated in a large cohort of patients.OBJECTIVE:The objective of this study was to evaluate the impact of this new definition in a large cohort of patients with primary hypogammaglobulinemia.METHODS:Evaluation of 3 different CVID definitions (ESID/Pan-American Group for Immunodeficiency [PAGID] 1999, ESID 2014, DEFI 2015) in 521 patients included in the French DEFI study with a diagnosis of primary hypogammaglobulinemia.RESULTS:Using the ESID/PAGID 1999 definition, 351 patients were classified as CVID. The new ESID 2014 definition excluded 62 (18%) patients. Most of them (n = 56; 90%) had a less severe disease, whereas 6 (10%) presented with a severe disease with major T-cell defect. We propose different criteria (occurrence of opportunistic infection or very low naive CD4+ T-cell count) to define this population with severe T-cell defect. Sixty-two patients fulfilled these criteria, represented 20% of the initial CVID population but accounted for 77% of the deaths, with a 5-year overall survival of 67.6% (95% confidence interval, 51.0-79.6), and were considered as late onset combined immunodeficiency (LOCID).CONCLUSIONS:The new ESID definition for CVID still fails to exclude a large number of patients with severe T-cell defect. We propose a new definition (DEFI 2015) that excluded more patients with a T-cell defect and consider these patients as LOCID. This population has a poor outcome and should be considered as a distinct group requiring specific care.

Background. POEMS syndrome is a rare form of B cell dyscrasia combining a proliferation usually of plasma cells, a polyneuropathy, osteocondensing bone lesions and multiple other clinical signs. The pathogenesis is not well understood but VEGF plays a major role. In patients with one or two sclerotic plasmacytoma and no bone marrow involvement, first line therapy should include radiation. For patients with diffuse sclerotic lesions, bone marrow involvement or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation systemic therapy is indicated, the most effective being high dose chemotherapy with autologous stem cell transplant (ASCT). Radiation of a single lesion is effective in about every other case and is accompanied by a fairly slow improvement of the neurological symptoms, often after initial worsening. ASCT seems to be accompanied by a number of important complications, in particular engraftment syndrome. Outside these 2 treatments there is no consensus therapy. Lenalidomide (LEN), a drug without serious neurological toxicity, has the advantage of being both anti-angiogenic and cytotoxic to malignant plasma cells (Richardson PG, Blood 2002;100(9):3063-7). We have recently reported a series of 20 French patients with POEMS syndrome treated by LEN with a good efficacy. We now report the first 27 patients of a prospective phase II trial using LEN + dexamethasone (LEN-DEX), 2 cycles preceding radiation or high dose treatment trying to obtain a rapid clinical response and to avoid engraftment syndrome or 9 cycles followed by 1 year LENalone in patients who cannot receive radiation or ASCT. Methods. Newly diagnosed or relapsing patients with POEMS syndrome who needed to be treated were eligible. Patients who can be treated by local radiation or intensive treatment with stem cell support receive two 28 day cycles of LEN 25 mg PO Days 1-21 and DEX 40 mg PO Days 1,8,15,22 before radiation or intensive treatment (Group 1), the other patients receive 9 cycles of the same LEN-DEX (Group 2) and then 12 cycles of continuous low dose LEN (10 mg). LEN dose was tapered to 10 mg for patients with a creatinine clearance between 30 and 50 ml/min and DEX to 20 mg for patients above 75 years of age and for those who were frail patients. Main eligibility criteria included a diagnosis of POEMS syndrome according to criteria by Dispenzieri et al (Am J Hematol 2012;87(8):804-14), an age of 18 or more, a creatinine clearance above 30 ml/min, no prior treatment with or contraindication to LEN and no uncontrolled thrombosis. Serum and plasma VEGF, serum electrophoresis, immunofixation and free light chain measurements were centrally monitored. Neurologic evaluations were performed using the Overall Neuropathy Limitations Scale (ONLS), the Neurological Impairment Scale (NIS) and the 10 meter walk test (10MWT). The primary endpoint was evaluation of the effectiveness of LEN-DEX combination using biological responses (decrease of monoclonal protein and serum VEGF level) and secondary endpoints were clinical and particularly neurological responses. Results. Twenty-seven patients have been included in 12 centres, median age was 61 (range 32-75), the median follow-up was 6.6 months (range 2-24). Eighteen patients were in group 1, with radiotherapy in 10 patients and ASCT in 8 patients; 9 patients were in group 2. Nineteen patients were in first line and 8 already treated. Only 2 patients experienced grade 3-4 adverse events due to LEN (cytopenia) and 2 patients had allergic rashes, no thrombotic event occurred. No engraftment syndrome was noted in the 5 patients already treated with ASCT. To date, no patient have died. Evolution of VEGF median values in serum and plasma, M-spike and dFLC levels and evolution of neurological measurements are reported in table 1. Neurological improvement was very rapid in some patients, using ONLS and 10MWT 11/18 evaluable patients had a neurological improvement after 2 cycles with an improvement of 1 or more of the ONLS score and/or change of 0.1 m/s or more in the 10MWT. Only one patient who progressed after nine cycles received another therapy. Conclusion. This is the first prospective trial of LEN-DEX in POEMS syndrome. This combination seems well tolerated in this disease with a good efficacy on VEGF measurements and rapid neurological improvement in the majority of patients. Updated data will be presented at the meeting. Download : Download high-res image (32KB) Download : Download full-size image Figure 1 . Disclosures Jaccard:Celgene: Drug supply to Trial Other. Tournilhac:mundipharma: Honoraria, Other, Research Funding; GSK: Honoraria, Other, Research Funding; Roche: Honoraria, Other, Research Funding. Moreau:celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are two granulomatous vasculitis affecting large arteries that present specific epidemiological and clinical features. Their pathogenesis is not fully understood but major advances have been obtained during the last years, thus allowing the emergence of new therapeutic strategies. GCA and TA develop on a specific genetic background but share some similarities regarding the immunological pathways involved in their pathogenesis. The trigger of these diseases is not clearly identified but it is thought that an infectious agent could activate and lead to the maturation of dendritic cells that are localized in the adventitia of arteries. Then, the cells of the adaptative immune response are recruited and activated: CD4 T cells that polarize into Th1 and Th17 cells, cytotoxic CD8 T cells and Natural Killer cells. Furthermore, the T regulatory cells (Treg) are decreased both in GCA and TA. Humoral immune response seems also to be involved, especially in TA. Then, the cytokines produced by T lymphocytes (especially IL-17 and IFN-γ) trigger the recruitment and activation of monocytes and their differentiation into macrophages and multinuclear giant cells that produce IL-1β and IL-6 that are responsible for general symptoms of GCA and TA, and cytotoxic mediators and growth factors that trigger the remodeling of the arterial wall leading to aneurysms and ischemic manifestations of GCA an TA.

To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE).Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified.Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia.These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of systemic vasculitis in which cardiac involvement is frequent and severe, and accounts for half of EGPA-related deaths. ANCA-positive EGPA differs from ANCA-negative EGPA in that the former is significantly associated with renal involvement, peripheral neuropathy and biopsy proven vasculitis, whereas the latter is associated with cardiac involvement. Herein, we report a case of EGPA with myocarditis in a woman, who was successfully treated with steroids and cyclophosphamide. This report highlights the importance of diagnosing cardiac involvement in EGPA early, especially in ANCA-negative patients.

Interleukin-12 (IL-12) is an important cytokine in the control of cell-mediated immunity. We have previously shown that endogenous IL-12 plays a role in the development of human allogeneic response. In the present study, we investigated the relationship between Cyclosporin A (CsA)-inhibitory effect and IL-12 pathway during human alloreaction in vitro. CsA addition at the sensitizing phase of primary mixed lymphocyte reaction (MLR) resulted in the inhibition of both p40 and p70 IL-12 production in a dose-dependent manner. In contrast, CsA had no effect on IL-12-receptor beta 1 chain (IL-12 R beta 1) expression in T cells induced upon allogeneic activation. Addition of exogenous IL-12 significantly restored CsA-inhibited alloreactive cytotoxic T lymphocyte (CTL) generation and had a marginal effect on T cell proliferative response. The IL-12-induced restoration of CTL generation was IFN gamma-mediated, as it was significantly altered when anti-IFN gamma was added. The restoration of CTL activity by exogenous IL-12 correlated with the capacity of this cytokine to partially restore granzyme B mRNA expression in alloreactive CTL. This study indicates that inhibition of IL-12 production is a novel additional mechanism for the inhibitory effect of CsA on the development of human allogeneic cytotoxic response.

Scalp vein thrombosis is an unusual complication during giant cell arteritis. Revealed by headache, it can be misdiagnosed as a disease relapse. An ultrasound scan should rapidly be performed to make the diagnosis, avoiding inappropriate treatment escalation.

Differentiation of naive CD4(+) T helper (T(H)) cells is a major step of the adaptative immune response. When activated by pathogens in a specific cytokine environment, CD4(+) T cells differentiate into different subsets of T(H) cells with specific effector functions. T(H)1 lymphocytes orchestrate cellular immune response by producing interferon-γ and stimulating cytotoxic cells whereas T(H)2 cells orchestrate humoral immune response by producing interleukin-4 (IL-4), IL-5 and IL-10, leading to immunoglobulin production. Conversely, regulatory T cells (Treg) are capable of inhibiting immune response. Recently discovered, T(H)17 cells are characterized by their ability to produce IL-17 and play an important role in anti-infectious and inflammatory immune responses. This review focuses on present knowledge about T(H)17 cells: their induction, phenotype, functions, implications in host defense and human disease, and their potential to represent possible therapeutic targets.

Immune thrombocytopenia (ITP) is an auto-immune disease associating a peripheral platelet destruction without increased central production.Forty patients with chronic ITP were retrospectively analyzed for clinical and biological presentation and response to treatment.Mean age at diagnosis was 54 years. ITP was revealed by hemorrhage in 65 % of the patients. Despite very low platelet count, no life threatening hemorrhage was observed. Platelet associated antibodies were found in 66 %, usually directed against GPIIb/IIIa. Corticosteroids were used as first line treatment, with response in 54 %, and relapse in 86 %. A response was observed in 42.1 % with dapsone, which was well tolerated, a relapse occurring in 37.5 % of the patients. Rituximab (RTX) allowed a response rate of 42.1 %, prolonged in 40 % of the patients. A response was achieved in 42.9 % cases after splenectomy, without any relapse. No factor was identified to predict the response to treatment.ITP is a rare disorder occurring most frequently in middle aged patients. Because of high relapse or no response rates, many treatments should be used. Dapsone offers a good efficacy without major side effects. RTX is well tolerated and allows a good response rate. The use of new agents like thrombopoietin receptor agonist or new therapeutics against B lymphocytes should be defined.

Immune thrombocytopenia is an autoimmune disease characterized by a peripheral destruction of platelets. B lymphocytes play a key role but pathogenesis is more complex, involving humoral and cellular immunity associated with an inappropriate platelet production. In this article, we review the different pathogenic pathways, leading to new therapeutic strategies.

Endomyocardial fibrosis with apical obliteration is the best known involvement among heart lesions induced by hypereosinophilia. However, hypereosinophilic heart disease may involve all three heart layers, with a polymorphic clinical and echocardiographic presentation.Retrospective descriptive study of five patients highlighting the various manifestations of hypereosinophilic heart disease.We report five cases illustrating the variety of hypereosinophilic heart disease and review the pathophysiology of this potentially severe illness: cytotoxicity of eosinophils is mediated by the release of granular proteins that primarily damage the endocardium, leading to thrombosis and embolic complications, then to fibrosis and valvular complications; myocardial involvement may induce a dreadful acute eosinophilic myocarditis; finally, pericardial involvement may cause tamponade.These observations highlight the whole spectrum of the heart manifestations of hypereosinophilia, remind that the vital prognosis may be involved in the acute phase and underline that functional prognosis depends on early detection and treatment to reduce the risk of early thromboembolic and late fibrotic complications.