Search

Background: Cladophialophora bantiana is one of the most virulent phaeohyphomycetes, typically causes non-angiogenic single (or sometimes multiple) cystic brain lesions, and has resulted in a mortality rate of up to 70%. Most C bantiana cases are described either in a series of isolated reports or in very small cohorts. The aim of this retrospective nation-based study was to share the data on C bantiana phaeohyphomycosis cases reported in France and French overseas territories over the past two decades to improve understanding of this disease., Methods: Patients with C bantiana infection were processed through the active surveillance programme of invasive fungal infections launched by the National Reference Center for Mycoses and Antifungals, Institut Pasteur (Paris, France), and the French Surveillance Network of Invasive Fungal Infections, which involved 29 hospitals from mainland France and overseas French territories. Only proven and probable cases of infection, according to the revised and updated consensus definitions from the European Organization for Research and Treatment of Cancer and Mycoses Study Group, were included in the study. Patients were diagnosed or confirmed, or both, using a polyphasic approach at the Institut Pasteur between 2002 and 2022. Patients were separated into two groups: those with CNS involvement and those with no CNS involvement. The primary outcome was the survival rate., Findings: A total of 23 patients with a C bantiana invasive infection were included during the study period (Jan 1, 2002, to Dec 31, 2022). The median age was 56 years in the CNS involvement group and 65 years in the non-CNS involvement group. Until 2021, the annual number of cases varied between zero and two, with six cases observed in 2022, the warmest year recorded in France since 1900. CNS involvement was observed in 15 (65%) patients, including three disseminated cases; skin and soft tissue involvement in seven (30%) patients and an isolated lung infection in one case. Diabetes was observed in five patients, and any immunodepression factor was observed in 14 (61%) of 23 patients. When considering only patients with CNS involvement, 9-month survival appeared higher in patients who underwent exeresis or large drainage (three [75%] of four patients vs three [27%] of 11 patients; p=0·24) and significantly higher in those treated for 2 or more weeks with triple antifungal therapy (liposomal amphotericin B plus posaconazole and flucytosine; seven [78%] of nine patients vs one [17%] of six patients; p=0·040). Two patients were treated with excision surgery alone (one patient with success, and the other patient lost to follow-up)., Interpretation: This study shows that the clinical presentations and underlying medical conditions of C bantiana infections are more diverse than previously described. It also emphasises a significant difference in mortality rate between those with and without CNS involvement. The prognosis improved when surgery was performed and triple antifungal therapy was administered. Such rare and devastating invasive fungal infections should be managed by a multidisciplinary team., Funding: Santé Publique France., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19., Methods: Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25-100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs)., Results: The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval, .47-2.64]; P = .81), nor did organ dysfunction or secondary outcomes., Conclusions: Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19., Clinical Trials Registration: NCT04606563., Competing Interests: Potential conflicts of interest . J. A. R. reports patents owned by the University of British Columbia that are related to (i) the use of PCSK9 inhibitor(s) in sepsis, (ii) the use of vasopressin in septic shock, and (iii) a patent owned by Ferring for use of selepressin in septic shock; J. A. R. is an inventor on these patents. J. A. R. was a founder, director, and shareholder in Cyon Therapeutics Inc (now closed) and is a shareholder in Molecular You Corp; is the Senior Research Advisor of the British Columbia, Canada Post COVID–Interdisciplinary Clinical Care Network (PC-ICCN); reports receiving consulting fees in the last 3 years as a funded member of the data and safety monitoring board of a National Institutes of Health–sponsored trial of plasma in COVID-19 (PASS-IT-ON; 2020–2021); has received grants for COVID-19 and for pneumonia research from CIHR and the St Paul's Foundation; and was a nonfunded science advisor and member of the government of Canada COVID-19 Therapeutics Task Force (June 2020–2021). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To evaluate the ability of 18 FDG PET/CT, at diagnosis of giant cell arteritis (GCA) and during follow-up, to predict occurrence of relapse in large-vessel GCA (LV-GCA)., Methods: We conducted a retrospective study using the French Study Group for Large-Vessel Vasculitis (GEFA) network. Data from patients with LV-GCA diagnosed by PET/CT and who had PET/CT in the following year were collected. For each PET/CT, PET vascular activity score (PETVAS) and total vascular score (TVS) were assessed, and their ability to predict the occurrence of subsequent relapse was assessed., Results: A total of 65 LV-GCA patients were included, of whom 55 had undergone a follow-up PET/CT 3 to 12 months after the diagnosis of GCA. Patients for whom the second PET/CT (PET2) was performed during active GCA were excluded. PETVAS and TVS decreased between PET1 and PET2 in all patients (p < 0.001). There was no correlation between vascular activity scores in PET2 and time to prednisone taper. For relapse prediction, at PET1, the AUC of the TVS and PETVAS were respectively 51.9 and 41.9 at 6 months, 55.3 and 49.7 at 1 year, 55 and 55.7 at 2 years. For PET2, the AUC were respectively 46.1 and 46.7 at 6 months, 52.1 and 48.9 at 1 year, 58.4 and 52.3 at 2 years., Conclusion: PET vascular activity scores at diagnosis and at follow-up PET/CT performed outside a period of GCA activity do not display high performance to predict the occurrence of subsequent relapse in LV-GCA patients., Competing Interests: Disclosures Maxime Samson: Argenx (consulting), Boerhinger Ingelheim (consulting), Chugai (consulting), CSL Vifor (consulting), Fresenius Kabi (consulting), GSK (consulting), Novartis (consulting and research grant), (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Main Objective: To prospectively assess the cost-consequence of a standardized diagnostic strategy as to compared to an open one for the etiological diagnosis of uveitis., Design: This was a prospective, non-inferiority, multicentre, randomized controlled trial., Methods: We included all consecutive patients with uveitis who had visited at least one of the Departments of Ophthalmology. In the standardized group, patients had a minimal work-up regardless of the type of uveitis (including evaluation of the CBC, ESR, C-reactive protein, tuberculin skin test, syphilis serology and chest X-ray). Depending on ophthalmological findings, further investigations could be performed. In the open strategy, ophthalmologists were free to order any kind of investigation. The main outcome was the mean cost per patient of each strategy., Results: 903 uveitis patients were included from January, 2010 to May, 2013. The mean cost per patient of the standardized strategy was 182.97 euros [CI 95% (173.14; 192.80)], and the mean cost per patient of the open strategy was 251.75 euros [CI 95% (229.24; 274.25)]. Therefore, the mean cost per patient of the standardized strategy was significantly lower than the mean cost per patient of the open strategy (p<0.001). There were significantly fewer visits (p<0.001), fewer radiological procedures (p<0.004) and fewer laboratory investigations (p<0.001) in the standardized group., Conclusion: A standardized strategy is a cost-saving approach for the etiological diagnosis of uveitis., Competing Interests: The authors have declared that no competing interests exist.

Objective: Deficiency in alpha-1 antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical effect of AAT deficiency remains poorly established in this setting. This study aimed to describe the clinical phenotypes and outcomes of AAV according to AAT phenotypes., Methods: This study was conducted retrospectively at Caen University Hospital and included all consecutive granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with positive proteinase 3-ANCA or myeloperoxidase-ANCA, from January 2000 or September 2011, respectively, to June 2016. AAT dosage (nephelometry) and phenotyping (isoelectric focusing in agarose gel) were performed., Results: Among the 142 patients with AAV, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a nonpolymerogenic M-variant phenotype, 18 (13%) had the deficient allele MZ, 12 (8%) had MS, 2 (1%) had ZZ, 2 (1%) had SZ, and 1 (1%) had SS. M, Z, and S allele frequencies were 84%, 8%, and 6%, respectively. No association was observed between AAT deficiency and ANCA subtype or AAV phenotype, except for intraalveolar hemorrhage (IAH), which was more frequent in patients harboring at least 1 of the deficient Z or S alleles than in those without any deficient alleles (p < 0.01). Global, renal, or relapse-free survival rates were similar for all subgroups., Conclusion: This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of IAH. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient patients with AAV.

Purpose: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles., Methods: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included., Results: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04)., Conclusion: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode.

Introduction: Some studies suggest that there is an increased risk of malignancies in giant cell arteritis (GCA). We aimed to describe the clinical characteristics and outcomes of GCA patients with concomitant malignancy and compare them to a GCA control group., Method: Patients with a diagnosis of GCA and malignancy and with a maximal delay of 12 months between both diagnoses were retrospectively included in this study and compared to a control group of age-matched (3:1) patients from a multicenter cohort of GCA patients., Results: Forty-nine observations were collected (median age 76 years). Malignancies comprised 33 (67%) solid neoplasms and 16 (33%) clonal hematologic disorders. No over-representation of a particular type of malignancy was observed. Diagnosis of GCA and malignancy was synchronous in 7 (14%) patients, while malignancy succeeded GCA in 29 (59%) patients. Malignancy was fortuitously diagnosed based on abnormalities observed in laboratory tests in 26 patients, based on imaging in 14 patients, and based on symptoms or clinical examination in the nine remaining patients. Two patients had a concomitant relapse of both conditions. When compared to the control group, patients with concomitant GCA and malignancy were more frequently male (p < 0.001), with an altered general state (p < 0.001), and polymyalgia rheumatica (p < 0.01)., Conclusions: This study does not indicate an over-representation of any particular type of malignancy in GCA patients. Initial follow-up dictated by vasculitis may have led to an early identification of malignancy. Nevertheless, GCA male patients with an altered general state and polymyalgia rheumatica might more frequently show concomitant malignancies.

Background: Data on survival and prognosis factors in incident cohorts are scarce in systemic sclerosis (SStc). To describe survival, standardized mortality ratio (SMR), and prognosis factors in systemic sclerosis (SSc), we analyzed a multicenter French cohort of incident patients and performed a systematic review of the literature and meta-analysis., Methods: A multicenter, French cohort study was conducted between January 1, 2000, and December 31, 2013. Patients were followed-up until July 1, 2016. A systematic review of the literature was carried out in MEDLINE and EMBASE up to July 2017. Meta-analysis was performed using all available data on SMR and hazard ratios of prognosis factors., Results: A total of 625 patients (493 females, 446 lcSSc) were included. During the study period, 104 deaths (16.6%) were recorded and 133 patients were lost to follow-up. Overall survival rates at 1, 3, 5, and 10 years from diagnosis were 98.0%, 92.5%, 85.9%, and 71.7% respectively in the French cohort. Overall SMR was 5.73 (95% CI 4.68-6.94). Age at diagnosis > 60 years, diffuse cutaneous SSc, scleroderma renal crisis, dyspnea, 6-min walking distance (6MWD), forced vital capacity < 70%, diffusing capacity of the lungs for carbon monoxide < 70%, pulmonary hypertension (PH), telangiectasia, valvular disease, malignancy, anemia, and CRP > 8 mg/l were associated with a poorer survival after adjustment. Eighteen studies (11,719 patients) were included in the SMR meta-analysis and 36 studies (26,187 patients) in the prognosis factor analysis. Pooled SMR was 3.45 (95%CI 3.03-3.94). Age at disease onset, male sex, African origin, diffuse cutaneous SSc, anti-Scl70 antibodies, cardiac and renal involvement, interstitial lung disease, PH, and malignancy were significantly associated with a worse prognosis. Anti-centromere antibodies were associated with a better survival., Conclusions: Overall, our study highlights a high mortality rate in SSc patients and confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.

Background: Primary immunodeficiency (PID) in adults is rare and mostly revealed by infections., Material and Methods: Adults without predisposing factors who were admitted to an intensive care unit (ICU) for infection were screened for PID., Results: Six PID cases were diagnosed, mostly revealed by encapsulated bacterial infections., Conclusion: Investigation of PID after ICU discharge should be considered to improve early detection.

Background: The risk of early death is particularly high in patients over the age of 65 presenting with antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis. We hypothesized that by combining disease severity markers, a comorbidity index and serious adverse event reports, we would be able to identify early predictors of one-year mortality in this population., Methods: We performed a multicentre, retrospective study in the nephrology and internal medicine departments of six tertiary hospitals in northern France. A total of 149 patients (median [interquartile range (IQR)] age: 72.7 [68.5-76.8] years) presenting with ANCA-associated vasculitis and renal involvement were included between January 2002 and June 2015. The primary endpoint was the one-year mortality rate., Results: Renal function was severely impaired at presentation (median [IQR] peak serum creatinine (SCr): 337 [211-522] μmol/l), and 45 patients required dialysis. The Five-Factor Score (FFS, scored as + 1 point for each poor prognostic factor (age > 65 years, cardiac symptoms, gastrointestinal involvement, SCr ≥150 μmol/L, and the absence of ear, nose, and throat involvement)) was ≥3 in 120 cases. The one-year mortality rate was 19.5%. Most of the deaths occurred before month 6, and most of these were related to severe infections. In a univariate analysis, age, a high comorbidity index, a performance status of 3 or 4, a lack of co-trimoxazole prophylaxis, early severe infection, and disease activity parameters (such as the albumin level, haemoglobin level, peak SCr level, dialysis status, and high FFS) were significantly associated with one-year mortality. In a multivariable analysis, the best predictors were a high FFS (relative risk (RR) [95% confidence interval (CI)] = 2.57 [1.30-5.09]; p = 0.006) and the occurrence of a severe infection during the first month (RR [95%CI] = 2.74 [1.27-5.92]; p = 0.01)., Conclusions: When considering various disease severity markers in over-65 patients with ANCA-associated renal vasculitis, we found that an early, severe infection (which occurred in about a quarter of the patients) is a strong predictor of one-year mortality. A reduction in immunosuppression, the early detection of infections, and co-trimoxazole prophylaxis might help to reduce mortality in this population.

Background: The aim of this study was to evaluate tocilizumab (TCZ) as an add-on therapy to glucocorticoids (GC) during the first 3 months of treatment of giant cell arteritis (GCA)., Methods: GCA patients, as defined by ≥3/5 ACR criteria and positive temporal artery biopsy (TAB) or angio-CT-scan or PET-scan-proven aortitis, were included in this prospective open-label study. Prednisone was started at 0.7 mg/kg/day and then tapered according to a standardized protocol. All patients received four infusions of TCZ (8 mg/kg/4 weeks) after inclusion. The primary endpoint was the percentage of patients in remission with ≤0.1 mg/kg/day of prednisone at week 26 (W26). Patients were followed for 52 weeks and data prospectively recorded., Results: Twenty patients with a median (IQR) age of 72 (69-78) years were included. TAB were positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all cases. At W26, 15 (75%) patients met the primary endpoint. Ten patients experienced relapse during follow-up, mainly patients with aortitis (P = 0.048), or CRP >70 mg/L (P = 0.036) or hemoglobin ≤10 g/dL (P = 0.015) at diagnosis. Among 64 adverse events (AE) reported in 18 patients, three were severe and 30, mostly non-severe infections (n = 15) and hypercholesterolemia (n = 8), were imputable to the study., Conclusion: This study shows that an alternative strategy using a short-term treatment with TCZ can be proposed to spare GC for the treatment of GCA. However, 50% of patients experienced relapse during the 9 months following TCZ discontinuation, especially patients with aortitis, or CRP > 70 mg/L or Hb ≤ 10 g/dL at diagnosis., Trial Registration: ClinicalTrials.gov (NCT01910038)., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: To assess prevalence of aortic involvement in relapsing polychondritis (RP) patients; to evaluate clinical features and long-term outcome of RP patients exhibiting aortitis, aortic ectasia and/or aneurysm., Methods: One hundred and seventy-two RP patients underwent aortic computed tomography (CT)-scan; they were seen in 3 medical centers., Results: Eleven patients (6.4%) had aortic involvement, occurring within a median time of 2 years after RP diagnosis. CT-scan showed isolated aortitis (n=2); the 9 other patients exhibited: aortitis and aortic aneurysm (n=2) or ectasia (n=1), isolated aortic aneurysm (n=4) or ectasia (n=2); aortic localizations were as follows: thoracic (n=6), abdominal (n=2), thoracic and abdominal (n=4) aorta. Patients exhibited: resolution (n=3) improvement (n=3), stabilization (n=4) or deterioration (n=1) of aortic localization. Five patients experienced recurrence of aortic localization; one patient died of aortic abdominal aneurysm rupture. Predictive factors of death related to aortic complications were: aortitis on CT-scan, higher median levels of erythrocyte sedimentation rate. Predictive parameters of aortic relapses were: aortitis on CT-scan and involvement of the abdominal aorta., Conclusions: This study underlines that aortic involvement is severe in RP. Furthermore, we suggest that RP patients exhibiting poor prognostic factors, including panaortitis and higher values of ESR, may require more aggressive therapy., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD)., Methods: We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7)., Results: Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively., Conclusion: These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment.

Objective: We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS)., Methods: We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up., Results: Ninety-seven patients [46 (47%) female, median age: 46 (18-78) years at diagnosis] were followed up for a median of 55 (5-198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3-18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P < 0.0001). Thirty-two (33%) patients experienced relapse [10 (22%) had received maintenance therapy while 22 (45%) had not, P = 0.01]; four subsequently died from relapse. In the multivariate analysis, maintenance therapy was the only independent predictor of good outcome [odds ratio (OR) = 7.8 (95% CI: 3.21, 20.36), P < 0.0001]., Conclusion: The results of this long-term follow-up study suggest that maintenance therapy in adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: Data on adult IgA vasculitis (Henoch-Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population., Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models., Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10-12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28-10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29-2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00-3.20; P = 0.049)., Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first-line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain., (© 2017, American College of Rheumatology.)

Purpose: We aimed to describe the initial treatment that was used in a common hospital-based practice in patients with giant-cell arteritis with and without large-vessel involvement at diagnosis as well as the outcomes in both groups., Methods: This retrospective multi-center cohort included patients with giant-cell arteritis diagnosed between 2005 and 2015, all of whom had fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (FDG-PET/CT) performed at giant-cell arteritis diagnosis and were followed up for ≥12 months. We compared the features, treatment, and outcomes of patients with large-vessel involvement demonstrated on FDG-PET/CT with those of patients with a negative PET/CT., Results: Eighty patients (50 women, median age: 71 [53-87] years) were included, 40 of whom had large-vessel involvement demonstrated on FDG-PET/CT and 40 who did not. After a median 56-month follow-up time, 42 (53%) patients had discontinued glucocorticoid (GC) treatment. Patients with and without large-vessel involvement were indistinguishable in the initial median dose of prednisone (0.74 mg/kg vs 0.75 mg/kg, P = .56), overall GC duration (P = .77), GC discontinuation rate (P = .65), relapse rate (P = .50), frequency of GC-dependent disease requiring GC-sparing treatments (P = .62), and fatality rate (P = .06)., Conclusion: In the setting of tertiary hospital recruitment, large-vessel involvement at giant-cell arteritis diagnosis using a PET/CT study had no influence on the choice of initial GC dose and had no impact on outcomes. Prospective studies are required to confirm these findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.

A few reports suggest combination of ANCA-associated vasculitis (AAV) and neutrophilic dermatoses (ND). We aimed to describe the main characteristics of patients presenting with both AAV and ND in a French cohort and through a systematic literature review, and to discuss the possible common pathogenic process involved. We conducted a retrospective study of patients with both conditions. Patients were selected via the French Internal Medicine Society (SNFMI) and the French Vasculitis Study Group (FVSG). A literature review focusing on a combination of both conditions, concentrated only on publications with well-established diagnoses and individual detailed data. Seventeen patients diagnosed with AAV and ND were identified in this cohort. Twelve patients had granulomatosis with polyangiitis (GPA), 4 had microscopic polyangiitis (MPA) and one had eosinophilic GPA (EGPA). Eight patients, all with GPA, displayed pyoderma gangrenosum (PG). Sweet's syndrome was observed in 6 patients (4 with MPA, one with GPA and one with EGPA) and erythema elevatum diutinum in the other three (2 with GPA and 1 with MPA). The literature review identified 33 additional patients with both conditions, including 26 with GPA. Altogether, of the 50 patients (17 from our study and 33 from the literature review), 33 (66%) patients presented with PG associated with GPA in 29 cases (89%). Corticosteroids were the first-line treatment in conjunction with an immunosuppressive agent in most cases. Outcomes were good and a total of 15 patients experienced a relapse. Patients who relapsed were more likely to have ear, nose and throat manifestation than patients who did not [12/15 (80%) relapsing patients vs. 15/35 (43%) non-relapsing patients; p = 0.03)]. In our stud, the most frequent association concerned GPA and PG. ND should be considered and specifically researched within the spectrum of cutaneous manifestations observed in AAV.

The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records. Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission. MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission.

The use of plasma exchanges (PLEX) in systemic necrotizing vasculitides (SNV) still need to be codified. To describe indications, efficacy and safety of PLEX for the treatment of SNV, we conducted a multicenter retrospective study on patients with ANCA-associated vasculitis (AAV) or non-viral polyarteritis nodosa (PAN) treated with PLEX. One hundred and fifty-two patients were included: GPA (n = 87), MPA (n = 56), EGPA (n = 4) and PAN (n = 5). PLEX were used for rapidly progressive glomerulonephritis (RPGN) in 126 cases (86%), alveolar hemorrhage in 64 cases (42%), and severe mononeuritis multiplex in 23 cases (15%). In patients with RPGN, there was a significant improvement in renal function compared to baseline value (P < 0.0001), the plateau being reached at month 3 after PLEX initiation, and estimated glomerular filtration rate improved especially as the number of PLEX increased. In patients with alveolar hemorrhage, mechanical ventilation was discontinued in all patients after a median time of 15 days. Patients treated for mononeuritis multiplex showed improvement of severe motor weakness. After a median follow of 22 months, 18 deaths (12%) were recorded, mainly in patients with RPGN and within the first 6 months. Incidence of end-stage renal disease and/or death was similar between groups of different baseline renal function, but was increased in MPO-ANCA compared to PR3-ANCA. Adverse events attributable to PLEX were recorded in 63%. No death occurred during PLEX. This large series describes indications, efficacy and safety of PLEX in daily practice. Randomized controlled studies are ongoing to define optimal indications, PLEX regimen and concomitant medications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To describe characteristics and outcomes of a multicenter cohort of patients diagnosed as having primary angiitis of the central nervous system (PACNS)., Methods: In 2010, we initiated a cohort study of adults diagnosed as having PACNS ≤15 years ago and with followup of >6 months (unless they died earlier of biopsy-proven PACNS). Its first analysis was planned at 2 years. Multidisciplinary investigators verified that appropriate investigations were done and excluded patients with possible alternative diagnoses. We analyzed patient demographics and symptoms, laboratory, radiographic, and histologic findings, and treatments. Studied outcomes included treatment response(s), relapse, death, and disability., Results: We included 52 patients (30 males; median age at diagnosis 43.5 years [range 18-79 years]) in whom PACNS was diagnosed between 1996 and 2012. Nineteen (61%) of 31 patients who had undergone brain biopsy had histologic vasculitis (biopsy-proven PACNS), while the other 12 patients had normal or noncontributive biopsy samples. An additional 21 patients had signs suggestive of PACNS on conventional cerebral angiography. All but 1 patient received corticosteroids, and 44 patients received cyclophosphamide (CYC). After a median followup of 35 months (range 2-148 months) postdiagnosis (1 patient with biopsy-proven PACNS died 2 months after diagnosis), 32 patients responded to treatment with improved modified Rankin scale scores, 4 patients (8%) did not respond, 14 patients (27%) had relapse of their disease at least once, and 3 patients (6%) died (1 patient after a relapse). Relapse was more common in patients with than in those without meningeal gadolinium enhancements on magnetic resonance imaging (MRI) (8 of 10 [80%] versus 6 of 32 [19%]; P = 0.001) and more common in patients with than in those without seizures at diagnosis (8 of 17 [47%] versus 6 of 35 [17%]; P = 0.04)., Conclusion: In this cohort of patients with PACNS, most patients received corticosteroids and CYC, and mortality was low. Patients with seizures at diagnosis or meningeal enhancements on MRI may be prone to relapse and require a different treatment strategy., (Copyright © 2014 by the American College of Rheumatology.)

Increasing rituximab prescription for ANCA-associated necrotizing vasculitides justifies the publication of recommendations for clinicians. Rituximab is approved in the United States to induce and maintain remission. In Europe, rituximab was recently approved for remission induction. However, governmental agencies' approvals cannot replace clinical practice guidelines. Herein, the French Vasculitis Study Group Recommendations Committee, comprised of physicians with extensive experience in the treatment of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience., (Copyright © 2013. Published by Elsevier Masson SAS.)

Objective: Earlier studies of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), with limited patient numbers and followup durations, demonstrated that clinical presentation at diagnosis, but not outcome, differed according to antineutrophil cytoplasmic antibody (ANCA) status. This study was undertaken to describe the main characteristics of a larger patient cohort and their long-term outcomes., Methods: A retrospective study of EGPA patients in the French Vasculitis Study Group cohort who satisfied the American College of Rheumatology criteria and/or Chapel Hill definitions was conducted. Patient characteristics and outcomes were compared according to ANCA status and year of diagnosis., Results: We identified 383 patients diagnosed between 1957 and June 2009 (128 [33.4%] before 1997 or earlier) and followed up for a mean±SD of 66.8±62.5 months. At diagnosis, their mean±SD age was 50.3±15.7 years, and 91.1% had asthma (duration 9.3±10.8 years). Main manifestations included peripheral neuropathy (51.4%); ear, nose, and throat (ENT) signs (48.0%); skin lesions (39.7%); lung infiltrates (38.6%); and cardiomyopathy (16.4%). Among the 348 patients tested at diagnosis for ANCA, the 108 ANCA-positive patients (31.0%) had significantly more frequent ENT manifestations, peripheral neuropathy, and/or renal involvement, but less frequent cardiac manifestations, than the ANCA-negative patients. Vasculitis relapses occurred in 35.2% of the ANCA-positive versus 22.5% of the ANCA-negative patients (P=0.01), and 5.6% versus 12.5%, respectively, died (P<0.05). The 5-year relapse-free survival rate was 58.1% (95% confidence interval [95% CI] 45.6-68.6) for ANCA-positive and 67.8% (95% CI 59.8-74.5) for ANCA-negative patients (P=0.35). Multivariable analysis identified cardiomyopathy, older age, and diagnosis during or prior to 1996 as independent risk factors for death and lower eosinophil count at diagnosis as predictive of relapse., Conclusion: The characteristics and long-term outcomes of EGPA patients differ according to their ANCA status. Although EGPA relapses remain frequent, mortality has declined, at least since 1996., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To study the frequency and characteristics of patients with Wegener's granulomatosis (WG) strictly and persistently localized to one organ., Methods: Retrospective analysis of the French Vasculitis Study Group (FVSG) WG cohort., Results: Sixteen patients (3.2% of the cohort) were identified who had isolated lung nodules, ear-nose-throat, or ocular involvement that did not progress to systemic disease (median followup, 58 mo) over the period of observation. Ten received first-line therapy with cyclophosphamide, which was effective in 4. Cotrimoxazole alone achieved remission in one, combined with corticosteroids in 3. Eight required subsequent treatments because of first-line failure or relapse., Conclusion: Strictly and persistently localized WG is uncommon. Optimal treatment remains to be determined.

Objective: Previous studies of polyarteritis nodosa (PAN) included patients with microscopic polyangiitis, because these entities were not distinguished prior to the Chapel Hill Consensus Conference (CHCC). This study was undertaken to describe the main characteristics of and long-term outcomes in patients with well-characterized PAN diagnoses., Methods: We conducted a systematic retrospective study of 348 patients who were diagnosed as having PAN between March 1963 and October 2005, were registered in the French Vasculitis Study Group database, and satisfied the American College of Rheumatology and CHCC criteria. Patient characteristics and outcomes were analyzed and compared according to hepatitis B virus (HBV) status., Results: At diagnosis, the mean +/- SD age was 51.2 +/- 17.3 years. The most frequent findings were general symptoms (93.1%), neurologic manifestations (79%), skin involvement (49.7%), abdominal pain (35.6%), and hypertension (34.8%); 66.2% had renal artery microaneurysms; 70.1% had histologically proven PAN. Patients with HBV-related PAN (n = 123) had more frequent peripheral neuropathy, abdominal pain, cardiomyopathy, orchitis, and hypertension compared with patients with non-HBV-related PAN (n = 225). During a mean +/- SD followup of 68.3 +/- 63.5 months, 76 patients (21.8%) relapsed (63 with non-HBV-related PAN [28%] versus 13 with HBV-related PAN [10.6%]; P < 0.001); 86 patients (24.7%) died (44 with non-HBV-related PAN [19.6%] versus 42 with HBV-related PAN [34.1%]; P = 0.003). Five-year relapse-free survival rates were 59.4% (95% confidence interval [95% CI] 52.6-67.0) versus 67.0% (95% CI 58.5-76.8) for non-HBV-related PAN and HBV-related PAN, respectively. Multivariate analysis retained age >65 years, hypertension, and gastrointestinal manifestations requiring surgery or at least consultation with a surgeon as independent predictors of death, whereas patients with cutaneous manifestations or non-HBV-related PAN had a higher risk of relapse., Conclusion: Our findings indicate that the rate of mortality from PAN remains high, especially for the elderly, and relapses do occur, particularly in patients with non-HBV-related PAN with cutaneous manifestations.