Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Tobacco differentially affects the clinical-biological phenotypes of ANCA-associated vasculitides.

OBJECTIVES: To describe the clinical-biological phenotype of ANCA-associated vasculitides (AAV) according to tobacco consumption. METHODS: We conducted a descriptive study to describe that phenotype at diagnosis according to tobacco use. AAV patients entered in the French Vasculitis Study Group database with data on smoking habits were analysed. The clinical-biological phenotypes at diagnosis were compared according to current tobacco use (current smokers) or not (including previous and never smokers). RESULTS: AAV diagnoses were: granulomatosis with polyangiitis (GPA) for 583 (50%), eosinophilic granulomatosis with polyangiitis (EGPA) for 326 (28%) and microscopic polyangiitis (MPA) for 256 (22%). Among them, 973 patients (84%) never smoked, 116 (10%) were previous smokers and only 76 (6%) were current smokers. Current smokers were younger age (p=0.01), male gender (p=0.004), less frequently EGPA (p=0.017) and MPA (p=0.036), and had less frequent kidney involvement (p=0.10). Among GPA patients, current smokers, compared to non-current smokers, were younger age (p=0.02), male gender (p=0.08), more frequent skin involvement (p=0.03) and less frequent ENT involvement (p=0.06). Among EGPA patients, current smokers, compared to non-current smokers, were also younger (p=0.028) and had less frequent constitutional symptoms (p=0.02), arthralgias (p=0.04), renal involvement (p=0.025) and MPO-ANCA (p=0.02). Finally, analysis of MPA patients was impossible because only 6 (2%) were current smokers. CONCLUSIONS: These results suggest that tobacco use could differentially affect GPA and EGPA clinical-biological phenotypes, and support the role of environmental exposures in AAV development and its phenotype.

Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis.

The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus (HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illumina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio=2.16, P=1.16E-07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 × 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region.

Expansion of autoreactive unresponsive CD21-/low B cells in Sjögren's syndrome-associated lymphoproliferation.

OBJECTIVE: Primary Sjögren's syndrome (SS) is an autoimmune disease associated with a high risk of developing non-Hodgkin's lymphoma. This study was undertaken to determine the nature of B cells driving lymphoproliferation in primary SS. METHODS: B cell subsets and function were analyzed in peripheral blood from 66 adult patients with primary SS (including 14 patients with B cell lymphoproliferative disease [LPD]) and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. The reactivity of recombinant antibodies isolated from single B cells from patients with primary SS and LPD was tested using an enzyme-linked immunosorbent assay. RESULTS: We observed an expansion of an unusual CD21-/low B cell population that correlated with lymphoproliferation in patients with primary SS. A majority of CD21-/low B cells from patients with primary SS expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment, since their Ig genes were mutated. They were unable to induce calcium flux, become activated, or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. However, CD21-/low B cells from patients with primary SS remained responsive to Toll-like receptor (TLR) stimulation. Molecules specifically expressed in CD21-/low B cells that are likely to induce their unresponsive stage were detected in gene array analyses. CONCLUSION: Patients with primary SS who display high frequencies of autoreactive and unresponsive CD21-/low B cells are susceptible to developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.

Large-vessel involvement in ANCA-associated vasculitis: A multicenter case-control study.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management. METHODS: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type. RESULTS: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %). CONCLUSION: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.

[Scleritis and episcleritis]. / Sclérite et épisclérite.

Scleritis and episcleritis are rare ocular inflammatory diseases but deserve to be known by internists because of their frequent association with systemic autoimmune diseases. It is important to distinguish them between because their prognosis, therapeutic management and potential complications are very different. Episcleritis represents a superficial ocular inflammation with usually benign visual prognosis, no complication with local treatment, and is associated with a systemic autoimmune disease in rare cases. In contrast, scleritis is a potentially serious ophthalmological condition that can threaten the visual prognosis in the absence of appropriate systemic treatment. It is associated with an underlying disease in 40-50% of cases, in particular a systemic autoimmune disease (25-35% of cases) or an infectious cause (5-10% of cases). Rheumatoid arthritis and systemic vasculitides, particularly antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, are the main autoimmune causes of scleritis and episcleritis. Scleritis can reveal the underlying autoimmune disease and requires systematic etiological investigations. Aggressive, complicated, refractory forms or those associated with a systemic autoimmune disease require glucocorticoids or even immunosuppressants, and close collaboration between ophthalmologists and internists is required. The development of biologic agents offers new effective therapeutic tools in the management of these difficult cases.

Impact of rituximab on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with autoimmune diseases.

SARS-CoV-2 infection is more severe in patients undergoing rituximab (RTX) treatment. Humoral response to vaccination is severely impaired in patients already treated with RTX, but data on antibody persistence in patients initiating RTX are lacking. We evaluated the impact of RTX initiation on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with immune-mediated inflammatory diseases. We performed a retrospective, multicenter study evaluating the evolution of anti-spike antibodies and breakthrough infections after initiation of RTX in previously vaccinated patients with protective levels of anti-SARS-CoV-2 antibodies. Threshold for anti-S antibodies positivity and protection were 30 and 264 BAU/mL, respectively. We included 31 previously vaccinated patients initiating RTX (21 female, median age 57 years). At first RTX infusion, 12 (39%) patients had received 2 doses of vaccine, 15 (48%) had received 3 doses, and 4 (13%) had received 4 doses. The most frequent underlying diseases were ANCA-associated vasculitis (29%) and rheumatoid arthritis (23%). Median anti-S antibody titers at RTX initiation, 3 months, and 6 months were 1620 (589-2080), 1055 (467-2080), and 407 (186-659) BAU/mL, respectively. Overall, antibody titers waned by almost two-fold at 3 months and four-fold at 6 months. Median antibody titers were significantly higher in patients who received ≥3 doses compared to those who received only 2 doses. Three patients developed SARS-CoV-2 infection without any severe symptom. Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after RTX initiation similarly to general population. Specific monitoring is useful to anticipate prophylactic strategies. Key Points • Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after rituximab initiation similarly to the general population. • The number of dose of vaccine before rituximab initiation is associated with higher antibody titers at month 3. • Monitoring antibody levels is mandatory to initiate prophylactic strategies in this population.

[Anti-IL-5 in severe asthma associated with eosinophilic granulomatosis with polyangiitis. Real-life study]. / Anti-IL-5 dans l'asthme sévère associé à une granulomatose éosinophilique avec polyangéite. Étude en vie réelle.

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose. METHODS: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%. RESULTS: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders. CONCLUSIONS: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA.

Evolution of biomarkers of liver fibrosis and liver insufficiency in hepatitis C virus-infected patients treated with pegylated interferon plus ribavirin and rituximab.

Therapeutic options in hepatitis C virus (HCV)-related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG-IFN/RBV)], and/or the downstream B-cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG-IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty-eight untreated HCV-related vasculitis patients with severe liver fibrosis (Metavir F3-F4) were included: 14 patients received RTX plus PEG-IFN/RBV and 14 patients PEG-IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow-up. Baseline epidemiological, clinical, virological and immunological features were similar between the groups. The virological response did not differ between cases and controls. The alanine aminotransferase (ALT) level and HCV viral load did not increase in patients treated with RTX. Serum albumin levels increased in patients treated with RTX at M3 and M6 (108% and 111% of baseline value; P = 0.06 and P = 0.13), whereas it was stable in patients treated without RTX. FibroTest values decreased from 0.70 at baseline to 0.59 at M3 (P = 0.5) and returned to 0.69 at M24 in the RTX-PEG-IFN/RBV group, whereas they were stable in the PEG-IFN/RBV group. RTX is safe in patients with severe HCV liver fibrosis and vasculitis. No beneficial effects of RTX were evidenced on liver fibrosis progression, but we found interesting correlations with the serum albumin level, FibroTest values and B-cell count.

Off-label use of biologics for the treatment of refractory and/or relapsing granulomatosis with polyangiitis.

OBJECTIVE: To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). METHODS: We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. RESULTS: Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3-6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3-8) and 2 (1-6), and 20 (13-30) mg/day and 20 (15-25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6-13) and 11 months (IQR 6-18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. CONCLUSION: This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.

Antifibroblast antibodies from systemic sclerosis patients bind to {alpha}-enolase and are associated with interstitial lung disease.

OBJECTIVE: To identify target antigens of antifibroblast antibodies (AFA) in systemic sclerosis (SSc) patients. PATIENTS AND METHODS: In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) and 36 idiopathic PAH patients, tested in pooled sera for groups of three, were compared with a sera pool from 14 healthy controls (HC). Serum IgG reactivity was analysed by the use of a two-dimensional electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for two groups: 158 SSc, 67 idiopathic PAH and 100 HC; and 35 SSc and 50 HC was tested against alpha-enolase from Saccharomyces cerevisiae and recombinant human (rHu) alpha-enolase, respectively, on ELISA. RESULTS: In the first part, alpha-enolase was identified as a main target antigen of AFA from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) idiopathic PAH patients and 4/100 (4%) HC (p<0.001) had anti-S cerevisiae alpha-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu alpha-enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae alpha-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2% vs 89.7%; p<0.001) and diffusion capacity for carbon monoxide (47.4% vs 62.3%; p<0.001), and antitopoisomerase 1 antibodies (46% vs 21%; p = 0.005) but not anticentromere antibodies (11% vs 34%; p = 0.006). Results were similar with rHu alpha-enolase testing. CONCLUSION: In SSc, AFA recognise alpha-enolase and are associated with ILD and antitopoisomerase antibodies.

Antimyeloperoxidase antibodies are a useful marker of disease activity in antineutrophil cytoplasmic antibody-associated vasculitides.

OBJECTIVE: To evaluate the relevance of monitoring antimyeloperoxidase antibody levels in the management of antimyeloperoxidase-associated vasculitides. METHODS: Thirty-eight patients with antimyeloperoxidase-associated vasculitides were included: microscopic polyangiitis (n = 18), Wegener's granulomatosis (n = 15) and Churg-Strauss syndrome (n = 5). Baseline characteristics and outcomes were recorded. Serial measurements of antimyeloperoxidase antibody levels were performed (ELISA, positive > or = 20 IU/ml). RESULTS: All patients achieved vasculitis remission after a mean time of 2.0 months (SD 0.9), with a significant decrease in the mean antimyeloperoxidase antibody level at remission (478 vs 41 IU/ml (SD 598 vs 100); p<0.001). Twenty-eight (74%) patients became antimyeloperoxidase antibody negative. After a mean follow-up of 54 months (SD 38), 12 cases of clinical relapse occurred in 11/38 (29%) patients. Relapses were associated with an increase in antimyeloperoxidase antibody levels in 10/11 (91%) patients (34 vs 199 IU/ml (88 vs 314); p = 0.002). The reappearance of antimyeloperoxidase antibodies after achieving negative levels was significantly associated with relapse (odds ratio 117; 95% CI 9.4 to 1450; p<0.001). Antimyeloperoxidase antibodies showed a positive predictive value of 90% and a negative predictive value of 94% for relapse of vasculitis. Up to 60% of cases of relapse occurred less than 12 months after the reappearance of antimyeloperoxidase antibodies. Relapse-free survival was significantly worse for patients who exhibited a reappearance of antimyeloperoxidase antibodies than in those with persistent negative antimyeloperoxidase antibodies (p<0.001). The antimyeloperoxidase antibodies serum level was strongly correlated with the Birmingham vasculitis activity score and the disease extent index (r = +0.49; p = 0.002). CONCLUSION: Through monitoring, antimyeloperoxidase antibodies are a useful marker of disease activity and a good predictor of relapse in antimyeloperoxidase-associated vasculitides.

Serum-free light chain assessment in hepatitis C virus-related lymphoproliferative disorders.

OBJECTIVE: To evaluate the relevance of serum-free light chain (FLC) assessment in hepatitis C virus (HCV)-related lymphoproliferative disorders, including mixed cryoglobulinemia (MC) and B cell non-Hodgkin lymphoma (B-NHL). PATIENTS AND METHODS: A total of 59 patients infected with HCV were prospectively followed, including patients without MC (n = 17), with asymptomatic MC (n = 7) and with MC vasculitis (n = 35, 9 of whom had B-NHL). Clinical and biological data were recorded at the time of the initial evaluation and at the end of follow-up. Serum FLC quantitation was carried out using a serum FLC assay. RESULTS: The mean (SD) serum kappa FLC level was higher in patients with asymptomatic MC (27.9 (8.6) mg/litre), MC vasculitis (36.7 (46.2) mg/litre) and B-NHL (51.3 (78.3) mg/litre) than without MC (21.7 (17.6) mg/litre) (p = 0.047, 0.025 and 0.045, respectively). The mean serum FLC ratio was higher in patients with MC vasculitis (2.08 (2.33)) and B-NHL (3.14 (3.49)) than in patients without MC (1.03 (0.26)) (p = 0.008). The rate of abnormal serum FLC ratio (>1.65) correlated with the severity of HCV-related B cell disorder: 0/17 (0%) without MC, 0/7 (0%) asymptomatic MC, 6/26 (23%) MC vasculitis without B-NHL and 4/9 (44%) B-NHL (p = 0.002). Serum kappa FLC levels and the serum FLC ratio correlated with the cryoglobulin level (r = 0.32, p<0.001 and r = 0.25, p = 0.002, respectively) and the severity of the B cell disorder (r = 0.26, p = 0.045 and r = 0.41, p = 0.001, respectively). Among patients with an abnormal serum FLC ratio at baseline, the FLC ratio correlated with the virological response to HCV treatment. CONCLUSIONS: In patients infected with HCV, an abnormal serum FLC ratio appears to be a very interesting marker, as it is consistently associated with the presence of MC vasculitis and/or B-NHL. After antiviral therapy, the serum FLC ratio could be used as a surrogate marker of the control of the HCV-related lymphoproliferation.

Osteomalacia revealing celiac disease and primary biliary cirrhosis-related Fanconi syndrome in a patient with systemic sclerosis.

Systemic sclerosis (SSc) may affect the gastrointestinal tract and cause very rarely malabsorption syndrome related to bacterial overgrowth. Malabsorption syndrome may be responsible for weight loss, diarrhea, osteomalacia, and iron and vitamins deficiency. We report the case of a SSc patient who developed osteomalacia caused by the combination of two exceptional conditions in the setting of SSc: celiac disease (CD) and primary biliary cirrhosis (PBC)-related Fanconi syndrome. Oral prednisone with angiotensin-converting enzyme inhibitors, was initiated because of active lesions of tubulitis, and led to the complete regression of bone pains, and by the improvement of renal function and regression of the features of proximal tubulopathy. Thus, in the presence of vitamin deficiencies in a patient with SSc, together with a search for malabsorption syndrome secondary to bacterial overgrowth, CD and/or PBC-associated Fanconi syndrome should be investigated.

[Hypocomplementemic urticarial vasculitis]. / Les vascularites urticariennes hypocomplémentémiques.

Hypocomplementemic urticarial vasculitis (HUV), called anti-C1q vasculitis in the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides, is a rare systemic vasculitis of unknown etiology, affecting small vessels. HUV is characterized by urticarial lesions, hypocomplementemia and systemic manifestations, mostly musculoskeletal and ocular, but also gastrointestinal, pulmonary and kidney involvement. Anti-C1q antibodies are detected in only half of the patients, and low C1q seems to represent a more sensitive marker. Published data on the therapeutic management are scarce in the literature. Hydroxychloroquine and colchicine seem to represent effective first-line therapies. In patient with relapsing or refractory disease, response rates appeared slightly higher for corticosteroids together with conventional immunosuppressive agents, in particular azathioprine, mycophenolate mofetil, or cyclophosphamide, while a rituximab-based regimen tended to have higher efficacy. The best strategy for treating HUV has yet to be defined.

[Acquisition of clinical observation skills by medical students improves with discipline-based teaching. The example of neurological examination]. / L'enseignement par discipline de la sémiologie en deuxième année de médecine améliore l'acquisition des compétences. Exemple de la sémiologie neurologique.

INTRODUCTION: Since 2014-2015, practical teaching of clinical observation skills for 2nd year medical students at our faculty has been discipline-based; previously, each clinical lecturer had to cover all medical fields. We assessed the impact of this teaching reform on the neurological examination skills of medical students in a before-and-after study. METHODS: Pre-reform 3rd and post-reform 2nd and 3rd year medical students (n=62, n=71 and 52, respectively) had to perform 7 neurological examination items, for which performance criteria had been pre-defined. Subsequently, we assessed whether the mean grade in neurological examination skills during the test at the end of the 2nd year was different between students who had received neurological teaching from a neurologist (n=29) or another specialist (n=102). RESULTS: The median [interquartile range] number of items acquired by post-reform 3rd year students (4 [2-5]) was higher than that of pre-reform 3rd year students (2 [1-3]; P<0.001), but lower than that of post-reform 2nd year students (5 [4-6]; P=0.01). The mean grade obtained during the practical test was not different in students trained by a neurologist or another specialist. CONCLUSION: Acquisition of neurological examination skills improved after the teaching reform which consisted of: (1) a discipline-based practical teaching of clinical observation skills; (2) a training of clinical lecturers to teach a limited list of educational objectives; and (3) the introduction of a practical test at the end of the 2nd year of medical studies. However, there was a decline in clinical observation skills between 2nd and 3rd year medical students.

[Simulation-based learning and internal medicine: Opportunities and current perspectives for a national harmonized program]. / Simulation en santé et médecine interne : quel avenir ?

Simulation-based learning (SBL) is developing rapidly in France and the question of its use in the teaching of internal medicine (IM) is essential. While HAS encourages its integration into medical education, French Young Internists (AJI) set up a working group to reflect on the added-value of this tool in our specialty. Different sorts of SBL exist: human, synthetic and electronic. It enables student to acquire and evaluate technical skills (strengths, invasive procedures, etc.) and non-technical skills (relational, reasoning…). The debriefing that follows the simulation session is an essential time in pedagogical terms. It enables the acquisition of knowledge by encouraging the students' reflection to reshape their reasoning patterns by self-correcting. IM interns are supportive of its use. The simulation would allow young internists to acquire skills specific to our specialty such as certain gestures, complex consulting management, the synthesis of difficult clinical cases. SBL remains confronted with human and financial cost issues. The budgets allocated to the development and maintenance of simulation centres are uneven, making the supply of training unequal on the territory. Simulation sessions are time-consuming and require teacher training. Are faculties ready to train and invest their time in simulation, even though the studies do not allow us to conclude on its pedagogical validity?

[Progressive multifocal leukoencephalopathy in a non-AIDS patient: high efficiency of combined cytarabine and cidofovir]. / Leucoencéphalite multifocale progressive en dehors du sida: efficacité de l'association cytarabine-cidofovir.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system, occurring in immunocompromised patients. Treatment, not codified to date, is more often inefficient with a rapid and fatal deterioration. CASE RECORD: A 48-year-old woman, treated with immunosuppressant agents for systemic lupus, presented with PML mimicking neurolupus flare. A complete remission was obtained with cytarabine and cidofovir. CONCLUSION: Combined cytarabine and cidofovir appears a promising therapeutic option in PML associated with autoimmune systemic disorders.

[Inventory of training of internal medicine in France: Results of a national survey]. / État des lieux de l'enseignement théorique et pratique de 3e cycle de médecine interne en France : résultats d'une enquête nationale.

OBJECTIVE: To make an inventory of training of Internal Medicine in France. METHOD: This study was conducted between May and September 2015 with coordinators (interviews of 45minutes) of local Internal Medicine training and fellows (online questionnaire). RESULTS: All coordinators (n=28) responded to the interviews. Local training of Internal Medicine exists in 86% of regions (3.1±3.1hours/month) and an interregional training in all interregions (34.7±13.9hours/year). When excluding Île-de-France, no correlation between the number of teachers and the amount of lessons was noted (P=0.61). Of the 550 fellows in Internal Medicine in 2014-2015, 223 (41%) responded to the online questionnaire. Mean level was 5.5±2.7 semesters. The rate of satisfaction (1=very dissatisfied and 5=very satisfied) was 3.0±1.0 and 3.8±0.8 for regional and interregional teaching, respectively (P<0.0001). Regional teaching satisfaction was correlated with the perceived expanse of diseases covered into the program (P<0.0001). In addition, 89% of fellows wish to evaluate themselves online, 66% wish to have a practical evaluation at the bedside and 70% in simulation centers. Finally, 91% of fellows support the establishment of a national program for the training of Internal Medicine. CONCLUSION: This survey states for the first time an inventory of training of Internal Medicine dedicated to fellows in France. This report highlights that fellows wish to have a national program, be further evaluated and have access to more interactive approach of teaching.