Marie-Paule Chauveheid

Resistance to trimethoprim/sulfamethoxazole and Tropheryma whipplei

Whipples disease (WD) is a chronic infection caused by Tropheryma whipplei. A 1-year treatment of oral trimethoprim/sulfamethoxazole (SXT) is commonly used. Advances in the culture of T. whipplei have allowed for full genome sequencing and antibiotic susceptibility testing, which has demonstrated resistance of T. whipplei to trimethoprim. Several mutations in the folP gene that encodes dihydropteroate synthase, the target of sulphonamides, has been reported for one patient with clinically acquired resistance to SXT. Here we report three new patients who experienced clinically acquired resistance to SXT during treatment and one patient with biological failure. Sixty-two folP sequences from DNA samples of 59 WD patients were also obtained. Among the detected amino acid changes, two positions (N4S and S234F) significantly predicted secondary sulfamethoxazole failure (four of five). We suggest that these mutations should be detected at the time of WD diagnosis by sequencing folP in order to avoid sulfamethoxazole monotherapy.

Increased arterial stiffness in systemic lupus erythematosus (SLE) patients at low risk for cardiovascular disease: a cross-sectional controlled study.

Cardiovascular disease (CVD) is a major cause of death in systemic lupus erythematosus (SLE) patients. Although the risk for cardiovascular events in patients with SLE is significant, the absolute number of events per year in any given cohort remains small. Thus, CVD risks stratification in patients with SLE focuses on surrogate markers for atherosclerosis at an early stage, such as reduced elasticity of arteries. Our study was designed to determine whether arterial stiffness is increased in SLE patients at low risk for CVD and analyze the role for traditional and non-traditional CVD risk factors on arterial stiffness in SLE. Carotid-femoral pulse wave velocity (PWV) was prospectively assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls (CTL). Adjustment on age or Framingham score was performed using a logistic regression model. Factors associated with PWV were identified separately in SLE patients and in controls using Pearsons correlation coefficient for univariate analysis and multiple linear regression for multivariate analysis. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (1.8±3.6% in SLE vs 1.6±2.8% in CTL, pu200a=u200a0.46). Pulse wave velocity was, however, higher in SLE patients (7.1±1.6 m/s) as compared to controls (6.3±0.8 m/s; pu200a=u200a0.01, after Framingham score adjustment) and correlated with internal carotid wall thickness (pu200a=u200a0.0017). In multivariable analysis, only systolic blood pressure (pu200a=u200a0.0005) and cumulative dose of glucocorticoids (pu200a=u200a0.01) were associated with PWV in SLE patients. Interestingly, the link between systolic blood pressure (SBP) and arterial stiffness was also confirmed in SLE patients with normal systolic blood pressure. In conclusion, arterial stiffness is increased in SLE patients despite a low risk for CVD according to Framingham score and is associated with systolic blood pressure and glucocorticoid therapy.

Immune thrombocytopenia in chronic myelomonocytic leukemia

Autoimmune disorders, including immune cytopenia, are encountered in the setting of chronic myelomonocytic leukemia (CMML). The aim of our study was to analyze the association of immune thrombocytopenia (ITP) with chronic myelomonocytic leukemia (CMML).

CD4+CXCR3+ T cells and plasmacytoid dendritic cells drive accelerated atherosclerosis associated with systemic lupus erythematosus

Cardiovascular disease due to accelerated atherosclerosis is the leading cause of death in patients with systemic lupus erythematosus (SLE). Noteworthy, accelerated atherosclerosis in SLE patients appears to be independant of classical Framingham risk factors. This suggests that aggravated atherosclerosis in SLE patients may be a result of increased inflammation and altered immune responses. However, the mechanisms that mediate the acceleration of atherosclerosis in SLE remain elusive. Based on experimental data which includes both humans (SLE patients and control subjects) and rodents (ApoE-/- mice), we herein propose a multi-step model in which the immune dysfunction associated with SLE (i.e. high level of IFN-α production by TLR 9-stimulated pDCs) is associated with, first, an increased frequency of circulating pro inflammatory CD4+CXCR3+ T cells; second, an increased production of CXCR3 ligands by endothelial cells; third, an increased recruitment of pro-inflammatory CD4+CXCR3+ T cells into the arterial wall, and fourth, the development of atherosclerosis. In showing how SLE may promote accelerated atherosclerosis, our model also points to hypotheses for potential interventions, such as pDCs-targeted therapy, that might be studied in the future.

A 70-Year-Old Woman With Acute Chest Pain and a Paracardiac Mass

70-year-old woman was admitted to our institution for acute chest pain. She had a history of obesity and hypertension. She had never smoked tobacco. The patient had returned from Tunisia by plane 7 days earlier, when she reported a left shoulder pain that resolved spontaneously. After a few days, a sudden acute left anterior chest pain occurred. The pain was intense at rest, increased by deep breathing, and was incompletely alleviated by acetaminophen. The patient did not report shortness of breath, cough, fever sensation, or upper respiratory tract symptoms.

Cystic lung disease in Sjögren's syndrome: An observational study

OBJECTIVESnTo analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjögrens syndrome (SS).nnnMETHODSnFrom June 2010 to February 2015, 90 consecutive SS patients [60.1±14.8years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin-walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records.nnnRESULTSnTwenty-one (23.3%) patients had cysts on CT scan performed 40.5±54.5months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n=6, 28.6%) or associated with other lesions, including bronchiectasis (n=5, 23.8%), micronodules (n=5, 23.8%), ground-glass opacity (n=4, 19%) and/or air trapping (n=3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3±15.3 versus 58.5±14.4years, P=0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P=0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1±17.7months), no patient developed specific lung disease or lymphoproliferative disorders.nnnCONCLUSIONSnCystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS.

High-sensitivity cardiac troponin T is a biomarker for atherosclerosis in systemic lupus erythematous patients: a cross-sectional controlled study

BackgroundCardiovascular disease (CVD) is the main cause of death in systemic lupus erythematous (SLE) patients. The Framingham score underestimates the risk for CVD in this population. Our study aimed to determine whether serum high-sensitivity cardiac troponin T (HS-cTnT) might help to identify SLE patients at risk for CVD.MethodsThe presence of carotid plaques was prospectively assessed by ultrasound in 63 consecutive SLE patients asymptomatic for CVD and 18 controls. Serum HS-cTnT concentration was measured using the electrochemiluminescence method. Factors associated with carotid plaques were identified and multivariate analysis was performed.ResultsFramingham score was low in both SLE patients (median 1 (range 1–18%)) and controls (1 (1–13%)). Nevertheless, 23 (36.5%) SLE patients, but only 2 (11.1%) controls (pu2009=u20090.039), had carotid plaque detected by vascular ultrasound. In the multivariate analysis, only age (pu2009=u20090.006) and SLE status (pu2009=u20090.017) were independently associated with carotid plaques. Serum HS-cTnT concentration was detectable (i.e. >3xa0ng/L) in 37 (58.7%) SLE patients and 6 (33.3%) controls (pu2009=u20090.057). Interestingly, 87% of SLE patients with carotid plaques, but only 42.5% of SLE patients without plaques (pu2009<u20090.001), had detectable HS-cTnT. Conversely, 54.5% of SLE patients with detectable HS-cTnT, but only 11.5% with undetectable HS-cTnT (pu2009<u20090.001), had a carotid plaque. In the multivariate analysis, only body mass index (pu2009=u20090.006) and HS-cTnT (pu2009=u20090.033) were statistically associated with carotid plaques in SLE patients. Overall, the risk of having a carotid plaque was increased by 9 (odds ratio 9.26, 95% confidence interval 1.55–90.07) in SLE patients in whom HS-cTnT was detectable in serum.ConclusionSerum HS-cTnT level is high and associated with carotid plaques in SLE patients who are at an apparently low risk for CVD according to the Framingham score. HS-cTnT may be a useful biomarker for SLE-associated atherosclerosis.

Prostaglandin D 2 amplifies lupus disease through basophil accumulation in lymphoid organs

In systemic lupus erythematosus (SLE), autoantibody production can lead to kidney damage and failure, known as lupus nephritis. Basophils amplify the synthesis of autoantibodies by accumulating in secondary lymphoid organs. Here, we show a role for prostaglandin D2 (PGD2) in the pathophysiology of SLE. Patients with SLE have increased expression of PGD2 receptors (PTGDR) on blood basophils and increased concentration of PGD2 metabolites in plasma. Through an autocrine mechanism dependent on both PTGDRs, PGD2 induces the externalization of CXCR4 on basophils, both in humans and mice, driving accumulation in secondary lymphoid organs. Although PGD2 can accelerate basophil-dependent disease, antagonizing PTGDRs in mice reduces lupus-like disease in spontaneous and induced mouse models. Our study identifies the PGD2/PTGDR axis as a ready-to-use therapeutic modality in SLE.In a lupus environment, basophils accumulate in secondary lymphoid organs where they affect pathogenesis by stimulating autoantibody production. Here the authors show this accumulation is driven by PGD2-induced CXCR4 surface expression and trafficking of basophils.

A 27-year-old man with multiple cavitary lung lesions

CASE PRESENTATIONnA 27-year-old Lebanese man was admitted to our department for multiple pulmonary lesions. The patient had reported persistent fever, cough, shortness of breath, and weight loss since his return from Lebanon 6xa0weeks earlier. He had been diagnosed with a severe form of Behçet disease 4 years ago, for which the ongoing treatment was a corticosteroid therapy associated with methotrexate and infliximab.