Jerome Connault

Efficacy and tolerance of infliximab in refractory Takayasu arteritis: French multicentre study

OBJECTIVEnTo analyse the efficacy and tolerance of infliximab in refractory Takayasu arteritis (TA).nnnMETHODSnFrench multicentre retrospective study that included patients with TA. Clinical disease activity was defined as new vascular and/or constitutional signs.nnnRESULTSnFifteen patients with TA [median age 41 (range 17-61) years; 13 women] were included. At initiation of infliximab therapy, 14 patients were treated with CSs [prednisone; median dose 20 (range 5-35) mg/day], MTX (nu2009=u20097) or AZA (nu2009=u20094). Infliximab was used at median 5 (range 3-5) mg/kg at a median of every 6 (range 4-8) weeks. A partial or good overall response was noted in 13 (87%) of the 15 cases, 10 (77%) of the 13 cases and 8 (73%) of the 11 cases at 3, 6 and 12 months, respectively. Clinical and biological activities significantly decreased within 3 months (from 11 at baseline to 4 patients at 12 months; Pu2009<u20090.05), and similarly for CS dose [from median 20 (range 5-35)u2009mg/day at baseline to median 6 (range 2.5-30) mg/day at 12 months; Pu2009<u20090.05]. Only one patient was still steroid-dependent at 12 months (vs 8 cases before infliximab). CRP regressed from a median 30 (range 4-70) mg/l to 5 (range 0-57) mg/l and 6 (0-50) mg/l at 3 and 6 months, respectively (Pu2009<u20090.05). Side effects were two infusion-related reactions, one pulmonary tuberculosis, one severe bacterial infection and EBV reactivation.nnnCONCLUSIONnThis study confirms the interest of infliximab in terms of clinical and biological response, as well as the steroid-sparing effect in TA.

Giant Cell Arteritis with or without Aortitis at Diagnosis. A Retrospective Study of 22 Patients with Longterm Followup

Objective. Studies have shown that aortitis may be present in half the patients with recent-onset giant cell arteritis (GCA). We assessed whether aortitis at diagnosis affects longterm outcome in patients with GCA. Methods. We retrospectively analyzed the longterm outcome of a prospective cohort of 22 patients with biopsy-proven GCA who all had aortic computed tomography (CT) evaluation at the time of diagnosis of GCA between May 1998 and November 1999. Longterm outcome, especially vascular events such as aortic aneurysm, mortality, relapses of GCA, and requirement for steroids, was assessed in 2011 by chart review and patient/physician interviews. Results. At disease onset, 10/22 patients had aortitis on CT scan. Patients with and without aortitis had similar baseline characteristics, including cardiovascular risk profile. At the time of the study, 12/22 (57%) patients had died. Vascular causes of death were more frequent in patients with aortitis (5/7 vs 0/5; p = 0.02). A higher number of vascular events was noted in patients with aortitis (mean events per patient 1.33 vs 0.25; p = 0.009). Stroke was more frequent in patients with aortitis. These patients seemed to exhibit a more chronic or relapsing disease course, and they were less likely to completely discontinue steroid therapy (p = 0.009, log-rank test). Conclusion. Our study suggests for the first time that inflammatory aortic involvement present at onset of GCA could predict a more chronic/relapsing course of GCA, with higher steroid requirements and an increased risk for vascular events in the long term.

Exploring how students think: a new method combining think-aloud and concept mapping protocols.

Medical Education 2010: 44: 926–935

teaching with cognition: Exploring how students think: a new method combining think‐aloud and concept mapping protocols

Medical Education 2010: 44: 926–935

Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients.

OBJECTIVESnThe aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis.nnnMETHODSnPatients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening >2mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared.nnnRESULTSnAmong 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70 years, p=0.003) and comprised more past/current smokers (43 vs 15%, p=0.0007). Aortic aneurisms were more frequent (38% vs 20%, p=0.03), and aortic wall thickening was more pronounced in IA. During follow-up (median=34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p=0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p=0.02). Mean age, sex ratio, inflammatory parameters, and free of aortic aneurism survival were equivalent in patients with IA ≥ 60 years when compared to patients with GCA-related aortitis.nnnCONCLUSIONSnIA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients <60 years. Most patients with IA ≥ 60 years share many features with GCA-related aortitis.

Venous thromboembolism related to warm autoimmune hemolytic anemia: A case–control study

BACKGROUNDnThe risk of venous thromboembolism (VTE) during warm autoimmune hemolytic anemia (wAIHA) is apparent in several published series. Unlike proximate disorders (autoimmune thrombocytopenia, non-immune hemolytic diseases) little is known about the presentation and risk factors for VTE in this setting.nnnOBJECTIVEnTo determine the frequency, presentation and risk factors for VTE associated with wAIHA.nnnMETHODSnWe performed a single center retrospective study of adult patients (>18years) followed for wAIHA between 2009 and 2013. VTE risk factors were systematically assessed. The characteristics of patients with or without VTE were compared. VTE presentation and precipitating factors were analyzed. The Padua VTE risk score was calculated in each case.nnnRESULTSnForty patients were included. wAIHA was idiopathic in 24 patients (60%). Twelve patients (30%) had Evans syndrome. Mean lowest hemoglobin level was 6.6g/dl [3.7-11.5]. Eight patients (20%) presented VTE after the appearance of wAIHA, at a mean age of 52.5years. All patients had pulmonary embolus, associated with a deep venous thrombosis in 4 cases. At the time of VTE 7/8 patients had frank hemolysis (median hemoglobin level: 7g/dL) and 6/8 were outpatients with a low Padua VTE risk score. The frequency of usual VTE risk factor was similar in cases and controls. By contrast, lowest hemoglobin level was significantly lower in patients that experienced VTE (5.3 vs 7.2g/dL, p=0.016). During the first episode of wAIHA, patients with concurrent VTE had a more pronounced anemia (5.3 vs 7.4g/dL, p=0.026). At the time of VTE, anemia was more severe when no other precipitating factor was present (6 vs 8.9g.dL, p=0.04).nnnCONCLUSIONnIn our cohort, 20% of patients with wAIHA presented VTE. The vast majority of VTE occurred during severe hemolytic flares and were not attributable to usual VTE risk factors. VTE prophylaxis is advisable in any patient admitted for wAIHA, irrespective of Padua VTE risk score. Prophylaxis also seems reasonable for outpatients with marked hemolysis.

Une cause rare de nécroses digitales : la maladie de Hodgkin

Les syndromes paranéoplasiques sont des manifestations systémiques diverses évoluant en parallèle d’une néoplasie solide ou d’une hémopathie maligne. L’association d’une maladie de Hodgkin (MH) à des syndromes paranéoplasiques est classiquement rapportée dans la littérature, à type de manifestations cutanées (ichtyose acquise, pemphigus. . .), neurologiques (syndrome cérébelleux, encéphalite limbique), de syndrome néphrotique. . . Les manifestations paranéoplasiques vasculaires sont rares au cours de la MH. Les nécroses digitales peuvent s’intégrer dans le cadre de syndromes paranéoplasiques. Elles accompagnent le plus souvent des tumeurs solides. Leur association à une MH est exceptionnelle dans la littérature. Nous rapportons le cas d’un patient qui a eu des nécroses digitales, révélant une MH sous-jacente.

Cas cliniqueUne cause rare de nécroses digitales : la maladie de HodgkinA rare cause of digital necrosis: Hodgkin's disease

Les syndromes paranéoplasiques sont des manifestations systémiques diverses évoluant en parallèle d’une néoplasie solide ou d’une hémopathie maligne. L’association d’une maladie de Hodgkin (MH) à des syndromes paranéoplasiques est classiquement rapportée dans la littérature, à type de manifestations cutanées (ichtyose acquise, pemphigus. . .), neurologiques (syndrome cérébelleux, encéphalite limbique), de syndrome néphrotique. . . Les manifestations paranéoplasiques vasculaires sont rares au cours de la MH. Les nécroses digitales peuvent s’intégrer dans le cadre de syndromes paranéoplasiques. Elles accompagnent le plus souvent des tumeurs solides. Leur association à une MH est exceptionnelle dans la littérature. Nous rapportons le cas d’un patient qui a eu des nécroses digitales, révélant une MH sous-jacente.

Juvenile Temporal Vasculitis: A Rare Case in a Middle-Aged Woman

BACKGROUNDnClassic giant cell arteritis affects older adults who are aged >50 years. Temporal arteritis is uncommon in young adults but juvenile temporal vasculitis (JTV) is the most frequent form found in young people. Clinical presentation is usually poor, with localized temporal inflammatory changes without consistent systemic manifestations. Generally, the patients have a benign clinical course, without ophthalmic or ischemic manifestations. In these rare JTVs, excision of the involved section of temporal artery is often curative and corticosteroid therapy is not required.nnnMETHODnThe present study reports a case of JTV in a middle-aged woman.nnnRESULTSnA 44-year-old woman complained of violent temporal headache, with a slight inflammatory syndrome. She had no vascular systemic manifestation and no cause of secondary vasculitis. Doppler ultrasonography suggested a localized inflammatory arteritis. Temporal biopsy was performed. Histologic findings were compatible with JTV (nongranulomatous panarteritis with mononuclear cells and eosinophils). All the symptoms disappeared after excision. One year later, she remains well and reports neither systemic manifestation nor recurrence.nnnCONCLUSIONnVasculitis of the temporal arteries in young people is uncommon and JTV is rare in middle-aged people. It is necessary to search for systemic or secondary vasculitis. In contrast to giant cell arteritis, steroids are not required.

Understanding the Pathophysiology of Intracranial Aneurysm: The ICAN Project

BACKGROUNDnUnderstanding the pathophysiologic mechanism of intracranial aneurysm (IA) formation is a prerequisite to assess the potential risk of rupture. Nowadays, there are neither reliable biomarkers nor diagnostic tools to predict the formation or the evolution of IA. Increasing evidence suggests a genetic component of IA but genetics studies have failed to identify genetic variation causally related to IA.nnnOBJECTIVEnTo develop diagnostic and predictive tools for the risk of IA formation and rupture.nnnMETHODSnThe French ICAN project is a noninterventional nationwide and multicentric research program. Each typical IA of bifurcation will be included. For familial forms, further IA screening will be applied among first-degree relatives. By accurate phenotype description with high-throughput genetic screening, we aim to identify new genes involved in IA. These potential genetic markers will be tested in large groups of patients. Any relevant pathway identified will be further explored in a large cohort of sporadic carriers of IA, which will be well documented with clinical, biological, and imaging data.nnnEXPECTED OUTCOMESnDiscovering genetic risk factors, better understanding the pathophysiology, and identifying molecular mechanisms responsible for IA formation will be essential bases for the development of biomarkers and identification of therapeutic targets.nnnDISCUSSIONnOur protocol has many assets. A nationwide recruitment allows for the inclusion of large pedigrees with familial forms of IA. It will combine accurate phenotyping and comprehensive imaging with high-throughput genetic screening. Last, it will enable exploiting metadata to explore new pathophysiological pathways of interest by crossing clinical, genetic, biological, and imaging information.