Vascularites double-positives ANCA et anti-MBG : mise au point sur les spécificités cliniques et thérapeutiques et comparaison aux deux vascularites éponymes

Double-positive vasculitis with anti-polynuclear cytoplasm (ANCA) and anti-glomerular basement membrane (GBM) antibodies is a rare entity of systemic vasculitis defined by the presence of ANCA and anti-GBM antibodies. The gradual accumulation of clinical and therapeutic data shows the usefulness of identifying and differentiating this entity from the two vasculitis respectively associated with the isolated presence of each of these two antibodies. Indeed, the double-positive ANCA and anti-GBM vasculitis appears to associate the characteristics of the demography and the extra-renal and pulmonary involvement of the ANCA-associated vasculitis on the one hand, and of the histological type and severe renal prognosis of the anti-MBG vasculitis on the other hand, with the renal involvement which is the only involvement consistently observed in double-positive vasculitis. The aim of this focus is to describe the epidemiological, clinico-biological, histological and prognostic characteristics of this entity, in light of recent literature and ongoing therapeutic changes in the two eponymous vasculitis.     

Antineutrophil cytoplasmic antibody-associated vasculitis with alveolar hemorrhage and ruptured renal aneurysm: A case report and literature review

Rationale:Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing damage to small-vessel vasculitis and mainly occurs in the kidney or lung. We report a rare case of AAV manifesting as alveolar hemorrhage and a renal aneurysm.Patient concerns:A 50-year-old Chinese man presented with repeated coughing, expectoration, fever, hypoxemia, and respiratory failure. The patient suffered from rupture of the renal aneurysm during immunosuppressive therapy.Diagnosis:Considering the clinical picture (fever, progressive hypoxemia, renal insufficiency, hemorrhagic bronchoalveolar lavage fluid, and left retroperitoneal hematoma) along with cANCA-PR3 positivity, and lung biopsy findings, the patient was finally diagnosed with granulomatosis with polyangiitis complicated by alveolar hemorrhage and renal aneurysm.Interventions:The patient was initially treated with immunosuppressive therapy combined with plasma exchange and subsequently with renal arterial embolization due to rupture of the renal aneurysm.Outcomes:The general condition and inflammatory reaction improved with immunosuppressive therapy combined with plasma exchange. Unfortunately, the patient did not respond to treatment and eventually died of respiratory failure and acute kidney injury after the rupture of the renal aneurysm.Lessons:We encountered unprecedented difficulties and challenges with renal aneurysm rupture. The possibility of aneurysmal rupture should be carefully considered and frequently checked for immunosuppressive therapy for AAV.     

54例原发ANCA相关性小血管炎的肾脏病理及预后的分析

目的探讨原发小血管炎肾脏病理特点及与肾功能预后的关系。方法 54例确诊并行肾活检的原发AN-CA相关小血管炎患者,分别按年龄及性别分组,对比统计各组病理类型和病理特点并随访。结果①肾脏病理类型检出率最高的是硬化性和轻度系膜增生性肾炎各占22.2%,其次是局灶节段硬化性肾炎（18.5%）;60岁以上组轻度系膜增生的患者比例偏高,P=0.05;②肾脏病理急慢性损害检出率较高为：中重度间质炎细胞浸润（48.1%）,中重度间质小管损害（46.3%）,纤维新月体（38.9%）,中重度增生硬化（35.2%）,细胞性新月体（24.1%）,袢坏死检出率（14.8%）;各年龄段相比,中重度增生硬化在30岁以下检出率相对较高,差异有统计学意义,P〈0.05;③随访1年,9例进入尿毒症期（16.7%）。发生尿毒症的相关风险是肾脏慢性指数,P〈0.05。结论肾小球硬化及严重的肾脏病理损害发生率高尤以年轻患者多见;发生终末期肾的相关风险因素是肾脏慢性指数。     

Anti-neutrophil cytoplasmic antibody seropositivity in young adults aged up to 35 years: kidney histopathological findings and patient outcomes

ObjectiveTo investigate the clinical features, pathological renal findings, and outcomes in young adults with anti-neutrophil cytoplasmic antibody (ANCA) seropositivity.MethodsAdults aged ≤35 years, with ANCA seropositivity, who underwent renal biopsy and received treatment comprising a combination of corticosteroids and cyclophosphamide between January 2004 and May 2018, were retrospectively enrolled.ResultsThirteen patients with ANCA seropositivity were included, all of whom presented with kidney disease at diagnosis: 10 (76.9%) with ANCA-associated pauci-immune glomerulonephritis, one with ANCA-associated crescentic glomerulonephritis with immune complex deposition, one with immunoglobulin A nephropathy, and one with membranous nephropathy. The median serum creatinine level was 183.2 μmol/l (range, 55.0–1024.0 μmol/l). Respiratory symptoms (9/13 [69.2%]) and nonspecific gastrointestinal symptoms (5/13 [38.5%]) were the most common extrarenal manifestations. Remission was achieved in 10 (91%) of 11 ANCA-associated nephritis cases, and median interval from diagnosis to relapse was 30 months (range, 9–63 months). Cumulative relapse-free survival rates at 1 and 5 years were 100% and 88.9%, respectively. Overall, 1-year and 5-year renal survival rates were 80.8% and 58.9%, respectively.ConclusionRenal histopathology varied in young adults with ANCA seropositivity. Although relapse rates in this young adult population were generally low, long-term renal survival rates remain unsatisfactory.     

ANCA-associated vasculitides: Pathogenetic aspects and current evidence-based therapy

A lot of progress has been made regarding the therapy of ANCA-associated vasculitides in the past decades. Cyclophosphamide still is standard therapy for remission induction in generalized disease, however, duration and cumulative dose of cyclophosphamide have been curtailed successfully to reduce toxicity. MTX is a safe alternative for remission induction in early systemic disease and medications available for remission maintenance have been extended. Rituximab and TNFalpha-antagonists represent promising options for refractory disease. The current evidence of therapy of ANCA-associated vasculitides is summarized in this review.     

Rituximab as rescue therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-centre experience with 15 patients

Background. B-cell depletion with rituximab, a chimeric anti-CD20antibody, is a novel treatment for refractory and relapsingANCA-associated small-vessel vasculitis. Data are limited andmost reports describe single patients or small numbers of patientsfollowed prospectively. Methods. We report a single-centre experience with 15 patientswho received rituximab for refractory or relapsing ANCA-associatedvasculitis. All patients had been treated with corticosteroidsand cyclophosphamide and a variety of other second-line immunosuppressiveagents. None of the patients had evidence of infection and receivedfour infusions of 375 mg/m² of rituximab. Disease activity wasassessed in accordance with the Birmingham Vasculitis ActivityScore (BVAS). BVAS, C-reactive protein and ANCA titres wererecorded at baseline and during follow-up. Results. B-cell depletion was achieved in all patients. Partialor complete remission was seen in 14 of 15 patients with a significantdecline in BVAS compared to baseline (P < 0.007). One patientwith granulomatous ANCA-associated vasculitis did not respondto rituximab. There were no side effects during rituximab infusion.Transient leucopenia was observed in two patients. One patientwith bronchial stenosis died of pneumonia 5.5 months after theinitiation of rituximab treatment. One initially anti-HBc-positive/HBsAg-negativepatient experienced a reactivation of hepatitis B, developedend-stage renal failure and died after refusal of dialysis. Conclusions. We report the largest case series of rituximabuse for ANCA-associated vasculitis so far. Our data supportthat the drug is capable of inducing partial or complete remissionin refractory or relapsing patients. Leucopenia and infectiouscomplications remain a matter of concern.     

Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review

Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. Studies suggest that an imbalance between “NETosis,” which is a process by which NETs are formed, and NET degradation may be associated with autoimmune diseases. Neutrophils, interleukin-8, ANCA and other inflammatory molecules are considered to play a key role in NET formation. Prolonged exposure to NETs-related cascades is associated with autoimmunity and increases the chance of systemic organ damage. In this review, we discuss the roles of various inflammatory molecules in relation to NETs. We also describe the role of NETs in the pathogenesis of autoimmune diseases and discuss the possibility of using targeted therapies directed to NETs and associated molecules to treat autoimmune diseases.     

Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome

Objective

Atypical manifestations have been described in patients with ANCA-associated vasculitides (AAV), such as pachymeningitis, orbital mass or chronic periaortitis. Because these manifestations have been associated to the spectrum of IgG4-related disease (IgG4-RD), we hypothesized that both diseases could overlap.