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.

[HLA-B58.01 and allopurinol hypersensitivity renal vasculitis in a Chinese patient]. / HLA-B58.01 et vascularite rénale d'hypersensibilité à l'allopurinol chez un patient chinois.

INTRODUCTION: Allopurinol, widely used in the treatment of hyperuricemia and gout, has been shown to cause severe cutaneous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as systemic reactions such as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). The HLA-B*5801 allele is known to be a risk factor for severe cutaneous manifestations of hypersensitivity to allopurinol, mostly in Asian populations. OBSERVATION: We report the observation of a 47-year-old Chinese patient, with no previous medical history, carrying the HLA-B*5801 allele, who developed an isolated allopurinol hypersensitivity necrotizing renal vasculitis without cutaneous manifestations. DISCUSSION: . The identification of this allele should be proposed before prescribing allopurinol in patients originating from certain regions of Asia, and the imputability of allopurinol should be evoked in case of necrotizing renal vasculitis, even without associated cutaneous involvement.

Not only disease activity but also chronic hypertension and overweight are determinants of pregnancy outcomes in patients with systemic lupus erythematosus.

INTRODUCTION: Pregnancies in women with lupus nephritis are at high-risk of complications, while scarcity of scientific knowledge on prognostic factors impedes a fair medical counseling. We aimed to identify determinants associated with maternal and fetal complications. MATERIALS: We retrospectively reviewed medical charts of pregnancies that lasted more than 22 weeks in 66 patients with pre-existing lupus nephritis between 2004 and 2013 in France. Univariate and multivariate analyses were conducted to identify determinants for maternal complications, lupus renal flare and fetal prematurity or death. RESULTS: Eighty-four pregnancies were identified. A maternal complication occurred in 31 pregnancies (36.9%): mostly preeclampsia (17 pregnancies, 20.2%) and renal flares (12 pregnancies, 14.3%). Overall fetal survival was 94.0% (79/84). Maternal pregnancy complications were independently associated with prepregnancy body mass index >25 kg/m2 (OR 3.81, 95% CI 1.03-14.09) and immunological activity (positive anti-dsDNA antibodies or Farr assay lupus) (OR 4.95, 95% CI 1.33-18.43). Renal lupus flares were independently associated with maternal age (OR 1.50, 95% CI 1.12-2.01) and prepregnancy immunological activity (OR 15.99, 95% CI 1.57-162.68) while a remission time >12 months had a protective effect (OR 0.17, 95% CI 0.04-0.68). Three parameters were associated with a higher risk of fetal prematurity or death: a prepregnancy body mass index >25 kg/m2 (HR 3.58, 95% CI 1.45-8.83), hypertension (HR 8.97, 95% CI 3.32-24.25), and immunological activity (HR 3.34, 95% CI 1.30-8.63). CONCLUSION: Maternal age, prepregnancy hypertension, body mass index >25 kg/m2 and lupus immunological activity may be considered as the main determinants for fetal and maternal complications. A remission time above 12 months for patients with lupus nephritis could be associated with a reduced risk of renal flare during pregnancy.

[Chronic lymphoid leukemia and renal complication: Report on 10 cases from Marseille over 16 years]. / Néphropathies au cours de la leucémie lymphoïde chronique : à propos d'une étude monocentrique de 10 cas.

INTRODUCTION: Chronic lymphoid leukemia (CLL) is a hematological malignant disease, associated with a clonal B cell proliferation. The incidence is 4400 new cases per year in France. The prevalence increases with age with a median age at diagnostic of 65 years. Renal involvement is rare and estimated at 1.2% of patients with CLL. Renal pathological diagnoses associated with CLL are variable and are not always related to the hematological disease. We report here on cases of patients with CLL who underwent a renal biopsy over the past 16 years in Marseille. METHODS: All cases of renal biopsies performed in patients with CLL between2000 and 2016 in Marseille were included. Pathological analysis was performed by the same experimented pathologist. Data were collected at the time of biopsy and after treatment. RESULTS: Ten patients were included in this study. The reason for renal biopsy was acute kidney injury or the onset of nephrotic syndrome. We report on 4 cases of membranous nephropathy, 1 minimal change disease, 1 cryglobulinemia-related membrano-proliferative glomerulonephritis, 1 light chain amyloidosis, 1 fibrillary glomerulonephritis, 1 interstitial monoclonal infiltration and one case of non-specific tubular lesions. Only one patient was treated before the biopsy, 7 patients received a specific hematological treatment of CLL because of its renal involvement. Renal and hematological responses were variable. CONCLUSION: Renal involvement of CLL is rare and is not mentioned in the Binet classification. Yet, it can be severe, with acute kidney injury or nephrotic syndrome, and can lead to the initiation of a specific treatment. The most frequent presentation this series was secondary MN, which differs from previous series.

Disease severity of proliferative lupus nephritis in Maghrebians.

Objective To study the influence of Maghrebian ethnicity on lupus nephritis. Methods We retrospectively reviewed the files of a cohort of 194 patients with proliferative lupus nephritis followed in seven lupus centres belonging to three groups: Europeans living in Belgium/France (E; n = 111); Maghrebians living in Europe, in casu Belgium/France (ME; n = 43); and Maghrebians living in Morocco (MM; n = 40). Baseline presentation was compared between these three groups but complete long-term outcome data were available only for E and ME patients. Results At presentation, the clinical and pathological characteristics of lupus nephritis did not differ between E, ME and MM patients. Renal relapses were more common in ME patients (54%) than in E patients (29%) ( P < 0.01). Time to renal flare and to end-stage renal disease was shorter in ME patients compared to E patients ( P < 0.0001 and P < 0.05, respectively). While proteinuria measured at month 12 accurately predicted a serum creatinine value of less than 1 mg/dl at 7 years in E patients, this was not the case in the ME group, in whom serum creatinine at month 12 performed better. Conclusion Despite a similar disease profile at onset, the prognosis of lupus nephritis is more severe in Maghrebians living in Europe compared to native Europeans, with a higher relapse rate.

Opportunistic autoimmunity secondary to cancer immunotherapy (OASI): An emerging challenge.

With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists. Within irAEs, we propose to individualize the induced autoimmunity by the term "Opportunistic Autoimmunity Secondary to Cancer Immunotherapy" (OASI). The aims of this article are (1) to present the different available checkpoint inhibitors and the OASIs reported with these treatments and (2) to propose practical recommendations for diagnosis, pre-therapeutic assessment and management of OASIs. The need for predictive biomarkers of OASIs occurrence will also be discussed.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

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

Diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography in cyst infection in patients with autosomal dominant polycystic kidney disease.

Cyst infection is a common complication of autosomal dominant polycystic kidney disease (ADPKD). Diagnosis is challenging with standard imaging techniques. We aimed to evaluate the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG PET-CT) for the diagnosis of cyst infections among ADPKD patients, in comparison with computed tomography (CT) and magnetic resonance imaging (MRI). All APKD patients who underwent 18-FDG PET-CT for suspected cyst infection between 2006 and 2013 in a French teaching hospital were included. Diagnosis of cyst infection was retained a posteriori on an index of clinical suspicion. 18-FDG PET-CT findings were was considered to be positive in cases of cyst wall hypermetabolism. CT or MRI findings were were considered to be positive in cases of cyst wall thickening (and enhancement if contrast medium was injected) and infiltration of the adjacent fat. A control group of ADPKD patients with 18-FDG PET-CT performed for other reasons was included. Thirty-two 18-FDG PET-CT scans were performed in 24 ADPKD patients with suspected cyst infection. A diagnosis of cyst infection was retained in 18 of 32 cases: 14 with positive 18-FDG PET-CT findings, and four false negatives. There were no false positives and no hypermetabolism of cyst walls in nine ADPKD control patients. 18-FDG PET-CT had a sensitivity of 77%, a specificity of 100%, and a negative predictive value of 77%. 18-FDG PET-CT allowed a differential diagnosis in three patients. In contrast, CT had a sensitivity of 7% and a negative predictive value of 35% (p <0.001 vs. 18-FDG PET-CT). Only eight MRI scans were performed. The diagnostic performance of 18-FDG PET-CT is superior to that of CT in cyst infections, for comparable radiation doses and with no injection of nephrotoxic contrast medium, in ADPKD patients.

Characteristics and information searched for by French patients with systemic lupus erythematosus: A web-community data-driven online survey.

INTRODUCTION: To provide information about the needs of patients with systemic lupus erythematosus (SLE) using Carenity, the first European online platform for patients with chronic diseases. METHODS: At one year after its creation, all posts from the Carenity SLE community were collected and analysed. A focused cross-sectional online survey was performed. RESULTS: The SLE community included 521 people (93% females; mean age: 39.8 years). Among a total of 6702 posts, 2232 were classified according to disease-related topics. The 10 most common topics were 'lupus and …' either 'treatment', 'fatigue', 'entourage', 'sun exposure', 'diagnosis', 'autoimmune diseases', 'pregnancy', 'contraception', 'symptoms' or 'sexuality'. 112 SLE patients participated in the online survey. At the time of diagnosis, only 17 (15%) patients had heard of SLE and 84 (75%) expressed a need for more information on outcomes (27%), treatments (27%), daily life (14%), patients' associations (11%), symptoms (8%), the disease (8%) and psychosocial aspects (7%). When treatment was initiated, 48 patients (43%) would have liked more information about side effects (46%), long-term effects (21%), treatment duration/cessation (12.5%) and type (10%) and mechanism of action (8%) of treatments. All participants except one had used the internet to find information about SLE. Sources of information included healthcare providers (51%/61%/67%), journals/magazines (7%/12%/6%), lupus Websites (51%/77%/40%), web forums/blogs (34%/53%/19%), patients' associations (11%/23%/9%) accessed at 'just before diagnosis', 'just after diagnosis' and 'before treatment initiation'. CONCLUSIONS: Online patient communities provide original unbiased information that can help improve provision of information to SLE patients.

Outcome of patients with systemic lupus erythematosus on chronic dialysis: an observational study of incident patients of the French National Registry 2002-2012.

OBJECTIVES: The objective of this article is to describe the outcome (mortality, kidney transplantation) of patients with systemic lupus erythematosus (SLE) on chronic dialysis. METHODS: The overall and cardiovascular (CV) mortality and access to kidney transplantation were studied in all SLE patients incident on chronic dialysis in France between 2002 and 2012 (REIN registry). They were compared to age- and sex-matched patients with diabetic nephropathy and with autosomal dominant polycystic kidney disease (PKD) on chronic dialysis. RESULTS: A total of 368 SLE patients were included in the national REIN registry between 2002 and 2012. Cumulative incidence of death was 16.9% at five years, with no difference between haemodialysis and peritoneal dialysis. Independent risk factors of death were age, past history of cardiovascular disease (CVD) and chronic respiratory insufficiency. At five years, CV and all-cause mortality in SLE patients were lower than in matched diabetic patients, but three-fold higher than in matched PKD patients. Access to the kidney transplant waiting list and to kidney transplantation was higher in SLE patients than in matched diabetic patients, but lower than in matched PKD patients. CONCLUSIONS: SLE patients on chronic dialysis are a population at high risk of death influenced by CV burden and chronic respiratory failure, but not by the method of dialysis. Their outcome, in terms of mortality and access to kidney transplantation, is intermediate between diabetic patients and patients with PKD.

[Thymic disease associated with nephrotic syndrome: a new case with membranous nephropathy and literature review]. / Les syndromes néphrotiques para-thymiques : revue de la littérature à propos d'une observation.

INTRODUCTION: Malignant thymoma or thymic hyperplasia is associated with various autoimmune diseases. Renal disease has rarely been reported in this condition. We report a new case with improvement of renal disease after thymectomy. CASE REPORT: A 77-year-old-women with nephritic syndrome was found to have associated thymic mass. Renal pathology showed membranous nephropathy. The thymic mass pathology showed a B2 type thymoma. After thymectomy the nephrotic syndrome improved. CONCLUSION: Glomerulopathy can be secondary to an acquired thymic disease. Membranous nephropathy but also other glomerular diseases can be observed often presenting with nephritic syndrome. Despite the rarity of this association this clinical observation underlines that a thymoma should be searched in the presence of a glomerulopathy. The glomerulopathy can be improved by the treatment of the thymoma.

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Survival of patients with ANCA-associated vasculitis on chronic dialysis: data from the French REIN registry from 2002 to 2011.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) can lead to end-stage renal disease in patients with renal involvement. OBJECTIVE: This study evaluated the survival of AAV patients on chronic dialysis in France. METHODS: Between 2002 and 2011, a total of 425 AAV patients started chronic dialysis and were registered in the Renal Epidemiology and Information Network. We analysed survival censored for renal transplantation, recovery of renal function and loss to follow-up. AAV patients were compared with 794 matched non-AAV patients on chronic dialysis. RESULTS: A total of 166 (39%) patients with microscopic polyangiitis and 259 (61%) patients with granulomatosis with polyangiitis were registered. Within a median follow-up of 23 months, 58 (14%) patients received a renal allograft and 19 (4%) recovered renal function. Median survival on dialysis was 5.35 years (95% CI, 4.4-6.3) and survival rates at 3 months, 1, 3 and 5 years were 96%, 85%, 68% and 53%, respectively. A total of 143 (41%) patients died after a median of 16 months. Causes of death were cardiovascular (29%), infections (20%), malnutrition (13%), malignancies (4%), AAV relapse (2%), miscellaneous (14%) and unknown (18%). Multivariate logistic regression identified three independent risk factors associated with AAV patients' mortality: age (HR = 1.05/year, P < 0.001), peripheral artery disease (HR = 2.62, P = 0.003) and frailty (HR = 2.43, P < 0.001). Survival of AAV patients did not differ from non-AAV controls, but infectious mortality was higher in AAV patients (20% vs. 8%, P < 0.001). CONCLUSION: Survival of AAV patients in chronic dialysis, although poor, was comparable to survival of non-AAV controls on dialysis. There was a similar burden of cardiovascular mortality, but higher infectious mortality.