ANCA-associated Small Vessel Vasculitis Research Articles

LIPIDS INCREASE IN HYPERTENSIVES DURING THE FIRST YEAR STEROID TREATMENT FOR GRANULOMATOSIS WITH POLYANGIITIS (GPA)

Objective: Granulomatosis with polyangiitis (GPA) is an ANCA-associated small-vessel vasculitis. Vessel wall inflammation induces multiple vascular damages leading to accelerated atherosclerosis. Metabolic profile and cardiovascular risk are marginally known in the GPA patients. Our purpose is to evaluate lipid profile and ASCVD-risk in GPA patients. Design and method: We selected 36 patients who received GPA diagnosis (T0) and evaluated them after 1 (T1) and 2 (T2) years follow-up. All patients were treated with high-dose glucocorticoid, one-year tapered, associated with immunosuppressants. Pathological history and a complete list of drugs at different time points were recorded. Results: The study reveals noteworthy alterations in lipid profiles, with a substantial increase observed in total cholesterol during both T1 and T2 in comparison to T0. A similar trend was noted in LDLand triglycerides. Conversely, no discernible differences were identified in HDL levels. Additionally, a considerable decrease in high-sensitivity C-reactive protein was observed at T1 and T2 in relation to T0, with no significant variance between T2 and T1. Furthermore, a notable reduction in erythrocyte sedimentation rate was noted at T2 as opposed to both T1 and T0, as well as at T1 compared to T0. Moreover, an interesting observation pertains to hypertensive patients who exhibited a marked escalation in lipid levels, juxtaposed with a gradual reduction in inflammation when compared to normotensive individuals. In particular, notable distinctions emerge between the two groups at both T1 and T2 concerning total cholesterol and LDL (p=0.027), despite comparable baseline values at T0. Then, while triglyceride levels start at similar values at T0, a substantial increase is observed at T1 in hypertensive patients and, conversely, at T2, normotensive individuals experience a significant rise in triglyceride levels, accompanied by a noteworthy reduction in hypertensive subjects. Conclusions: The findings indicate that lipid profile alterations, likely influenced by glucocorticoid treatment, may not be directly linked to inflammation. Furthermore, there is a higher relation between hypertension and these alterations. Actual data doesn’t reveal increased mortality in hypertensive GPA patients but further research is required to pinpoint specific patterns characterizing cardiovascular risk and progression in this context.

Pulmonary pathology in vasculitis.

Pulmonary involvement is frequent in vasculitis, particularly in ANCA-associated small vessel vasculitis. Laboratory and radiological data alone are often sufficient to confirm the clinical hypothesis, but sometimes the pathologist plays a crucial role in the differential diagnosis and the patient's management. In this review, the pathologic features of pulmonary vasculitis and the pathologist's role in this field are illustrated.

Severe Renal Impairment in a Patient with Recent Rheumatoid Arthritis Diagnosis following Methotrexate Initiation: A Case Report

ABSTRACT Rheumatoid arthritis (RA) is a chronic autoimmune disease frequently treated with immunosuppressive agents such as methotrexate (MTX). Although MTX is generally well-tolerated, it can lead to adverse effects, including renal impairment. We present a case of a patient with newly diagnosed RA who developed severe renal impairment shortly after initiating MTX therapy. A 50-year-old male with recently diagnosed RA presented with vomiting, skin itching, mouth ulcers, and a pruritic rash, all occurring shortly after starting MTX treatment. These symptoms led to acute kidney injury (AKI), necessitating hemodialysis. The patient’s symptoms and laboratory findings were indicative of ANCA-associated small-vessel vasculitis with a picture of rapidly progressive glomerulonephritis (RPGN). Treatment included discontinuation of MTX, hemodialysis, immunosuppressive therapy with corticosteroids and cyclophosphamide, and patient education. This case emphasizes the need for close monitoring of RA patients initiated on MTX therapy and prompt evaluation of renal function. Clinicians should be vigilant for signs of renal impairment and be prepared to initiate appropriate interventions, including discontinuation of MTX and consideration of immunosuppressive therapy, to optimize patient outcomes. Further research is warranted to understand better the mechanisms underlying renal complications in RA patients receiving MTX treatment.

Renal Limited Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis: A Case Report

Background: Renal Limited Vasculitis (RLV) is a localized autoimmune vascular inflammatory disorder that is part of the Pauci Immune Glomerulonephritis (PIGN) spectrum. Over 90% of PIGN patients have circulating Anti-Neutrophil Cytoplasmic Antibodies (ANCA Ab). Anti-Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitides are a heterogeneous group of multisystemic autoimmune disorders with distinct pathological findings. They are characterized by widespread inflammation of vessels according to their size, their location, and their serotypes based on the presence or absence of ANCA antibodies, namely Myeloperoxidase (MPO-ANCA), Proteinase-3 (PR3-ANCA) or simply ANCA negative, if no antibodies are found. RLV is characterized by antibody positivity to myeloperoxidase in the majority of cases. Case Report: A 77-year-old Caucasian female was admitted with altered mental status and laboratory evidence of renal function compromise consistent with non-oliguric acute renal failure. Imaging and renal biopsy resulted in a diagnosis of pauci-immune glomerulonephritis consistent with MPO-ANCA vasculitis with a subtype that was associated with necrotizing arteritis, a severe form of the disease. She was placed on hemodialysis, intravenous cyclophosphamide, and oral prednisone, and entered remission. Conclusion: A high level of suspicion and familiarity with clinical signs and symptoms are critical in distinguishing primary RPGN subtypes from other types of ANCA-associated small vessel vasculitis. If left untreated, renal limited vasculitis can progress to widespread systemic involvement and become fatal.

Changes in Lipids in Granulomatosis with Polyangiitis Relates to Glucocorticoids and History of Hypertension.

Granulomatosis with polyangiitis (GPA) is an ANCA-associated small-vessel vasculitis. Vessel wall inflammation induces multiple vascular damages, leading to accelerated atherosclerosis. Metabolic profile and cardiovascular risk are somewhat understood in GPA patients. Cardiovascular atherosclerotic disease (ASCVD) may represent a risk for outcomes. Our purpose is to evaluate ASCVD risk in GPA patients. Thirty-six patients received GPA diagnosis (T0) and were evaluated after 1 (T1) and 2 (T2) years follow-up. All patients were treated with high-dose glucocorticoid, one-year tapered, along with immunosuppressants. Total cholesterol significantly increased in T1 vs. T0 and T2. LDL exhibited the same trend, while triglycerides increased in both T1 and T2 vs. T0. No difference was found in HDL. A significant hsCRP decrease was detected at T1 and T2 vs. T0, but not between T2 and T1. Moreover, we found a significant reduction in ESR at T2 compared with T1 and T0 and at T1 compared to T0. Hypertensive patients presented a pronounced increase in lipids, while inflammation reduced slowly compared to normotensives. Our data suggest that the increase in cholesterol and LDL in T1 is a consequence of glucocorticoids. These data can be useful in the evaluation of both CV diseases and lipid metabolism, which are closely related to vessel inflammation.

ANCA-associated large and small vessel vasculitis with aorto-pulmonary-renal syndrome

ANCA-associated large and small vessel vasculitis with aorto-pulmonary-renal syndrome

ANCA-associated small-vessel vasculitides

ANCA-associated vasculitides refer to systemic small-vessel vasculitides. The paper shows the role of antineutrophil cytoplasmic antibodies in the development of immune inflammation of blood vessels and tissues. It considers the pathogenesis of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis and presents the clinical and morphological manifestations of the diseases.

A Clinical Approach of Renal Involvement in Granulomatosis with Polyangiitis

Abstract Granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) is one of the antineutrophil cytoplasmic antibody (ANCA) - associated small vessel vasculitis, involving various organs such as nasal septum, sinuses, upper respiratory tract, lungs, and kidneys. GPA is pathologically characterized by necrotizing granulomatous inflammation. ANCA-associated small vessel vasculitis represent a major challenge in hospital admissions; therefore, early and accurate diagnosis with aggressive treatment is essential to improve the disease outcome. Renal involvement of granulomatosis with polyangiitis is characterized morphologically by extensive crescent formation (extracapillary proliferation in Bowman’s space), and clinically by crescentic or rapidly progressive glomerulonephritis that causes hematuria, erythrocyte casts, and proteinuria with progressive loss of renal function. The diagnosis of granulomatosis with polyangiitis is established most securely by biopsy specimens showing the triad of vasculitis, granulomata, and large areas of necrosis (known as geographic necrosis) admitted with acute and chronic inflammatory cells. Usually, renal involvement is severe and is the leading cause of mortality. The combination of high-dose corticosteroids and cyclophosphamide is the mainstay of treatment for vasculitis and disease resistance to this combination is rare.

A CLINICAL APPROACH OF RENAL INVOLVEMENT IN GRANULOMATOSIS WITH POLYANGIITIS

Granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) is one of the antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis involving various organs such as nasal septum, sinuses, upper respiratory tract, lungs, and kidneys. GPA is pathologically characterized by necrotizing granulomatous inflammation ANCA-associated small vessel vasculitis represent a major challenge in hospital admissions; therefore, early and accurate diagnosis with aggressive treatment is essential to improve the disease outcome. Renal involvement of Granulomatosis with Polyangiitis is characterized morphologically by extensive crescent formation (extracapillary proliferation in Bowman's space), and clinically by crescentic or rapidly progressive glomerulonephritis that causes hematuria, erythrocyte casts, and proteinuria with progressive loss of renal function. The diagnosis of Granulomatosis with Polyangiitis is established most securely by biopsy specimens showing the triad of vasculitis, granulomata, and large areas of necrosis (known as geographic necrosis) admitted with acute and chronic inflammatory cells. Usually, renal involvement is severe and is the leading cause of mortality. The combination of high-dose corticosteroids and cyclophosphamide is the mainstay of treatment for vasculitis and disease resistance to this combination is rare.

The complexity of classifying ANCA-associated small-vessel vasculitis in actual clinical practice: data from a multicenter retrospective survey.

The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.

290 ANCA-Associated Small-Vessel Vasculitis Presenting with Bilateral Leg Pain

290 ANCA-Associated Small-Vessel Vasculitis Presenting with Bilateral Leg Pain

Investigations in systemic vasculitis. The role of the laboratory.

The diagnosis of systemic vasculitis is challenging. Laboratory testing may provide useful information. Routine laboratory tests include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulin, cryoglobulin, and Hepatitis B and C serology. Although ESR and CRP are often helpful for the diagnosis of vasculitis, they are nonspecific and do not help in distinguishing between vasculitis disease activity and a concomitant infection or another source of inflammation. A few autoantibodies are helpful for diagnosis, such as anti-neutrophil cytoplasmic antibodies (ANCAs) (in ANCA-associated small-vessel vasculitis), anti-glomerular basement membrane (GBM) antibodies (in anti-GBM antibody disease), and anti-C1q antibodies (in immune complex-associated small-vessel vasculitis). The 2017 revised consensus recommendations on ANCA testing state that high-quality antigen-specific immunoassays are the preferred screening methodology for the diagnosis of ANCA-associated vasculitis. ANCA subtypes (proteinase-3-ANCA and myeloperoxidase-ANCA) are associated with different epidemiological, genetic, and clinical features.

ANCA-associated small-vessel vasculitis surrounding the temporal artery.

ANCA-associated small-vessel vasculitis surrounding the temporal artery.

Microscopic Haematuria in ANCA-Associated Vasculitis with Glomerulonephritis During Treatment and Remission

Background: ANCA-associated small vessel vasculitides (AAV) are prone to cycles of relapse and remission. Renal involvement manifests as glomerulonephritis with microscopic haematuria, red blood cell casts, proteinuria and variable decrease in renal function. Remission of renal vasculitis is defined as stabilization in serum creatinine (Creat) and resolution of haematuria while controversy exists about persistence of haematuria (during apparent disease-remission) since it may indicate smouldering disease-activity or should be considered as renal flare. Objective: To clarify the course of haematuria after diagnosis and induction therapy and its possible predictive value of long term renal function. Design: Retrospective cohort study. Participants: 96 consecutive AAV-patients with renal involvement diagnosed and treated with systemic AAV between 1st of January 2000 to 31th December 2007 were followed for 60 months. Main measures: Collected data were Creat, CRP (mg/ml), eGFR ml/min/1.73 m2, creatinine-excretion in collected 24 h urine (Ucreat/24 h), proteinuria (Uprot), ratio of proteinuria/ creatinine in 24 h urine (Uprot/creat) and haematuria. Data were analysed for the complete study population and compared for MPO-ANCA and PR3-ANCA. Key results: At twelve months after diagnosis, haematuria was no longer detectable in 92% of all patients. In the PR3-ANCA group, haematuria disappeared after 13 months, while in the MPO-ANCA group haematuria persisted in 19% of the patients. On average, haematuria disappeared almost simultaneously with stabilisation of the renal function. Conclusion: Haematuria persists for many months after diagnosis and disappears usually simultaneously with stabilisation of kidney function. There was no relation between persistence of haematuria for over 12 months and renal function during follow up. Haematuria probably acts as a sensitive marker for absence of inflammatory glomerular disease activity in most patients with systemic AAV and renal involvement. It is disappearance coincide with stabilisation of renal function and remission of the disease in almost all patients. However, if it persists, it is not predictive for worsening renal function nor for relapse. Proteinuria does not seem to be a reliable marker for renal disease remission.

Antineutrophil Cytoplasmic Antibody-Positive Small-Vessel Vasculitis Associated with Antithyroid Drug Therapy: How Significant Is the Clinical Problem?

The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis. The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis. ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.

The long-term outcomes of systemic vasculitis.

Patients with generalized ANCA-associated small vessel vasculitis (AAV) have a very poor outcome if the ANCA-associated vasculitis is not diagnosed, evaluated and treated properly. The introduction of treatment with immunosuppressive therapy has improved patient survival dramatically but with considerable side effects. Besides, almost 50% of surviving patients experience a relapse of vasculitis. Since 1995, the European Vasculitis Society (EUVAS) has designed and conducted several clinical trials on patients with AAV independently of pharmaceutical companies. The studies included patients with newly diagnosed AAV and were stratified according to renal function and generalized versus more localized forms. As the immediate patient survival has improved, the longer term outcome has become more important. There are several reports on outcome of patients with ANCA-associated vasculitis, but the patient groups were heterogeneous regarding diagnosis as well as treatment and follow-up. Therefore, EUVAS decided to further evaluate the effect and possible adverse events of the original randomized trials. This review presents an overview on long-term follow-up of patients with ANCA-associated vasculitis, with focus on relapse rate, patient and renal survival and development of cardiovascular disease and malignancy.

AB0478 Anca associated vasculitis presenting with anterior ischemic optic neuropathy

BackgroundAnterior Ischemic Optic Neuritis (AION) is caused by arteritic and non arteritic factors. Giant Cell Arteritis is one of the well-recognised causes of arteritic AION. AION is a rare but...

Clinical study of renal impairment in patients with propylthiouracil-induced small-vessel vasculitis and patients with primary ANCA-associated small-vessel vasculitis

The aim of this study was to compare renal impairment in patients with propylthiouracil (PTU)-induced small-vessel vasculitis and patients with primary anti-neutrophil cytoplasmic antibody (ANCA)-induced small-vessel vasculitis. The study compared the pathology and clinical conditions of 10 patients with PTU-associated small-vessel vasculitis and 18 patients with primary ANCA-associated small-vessel vasculitis. All patients showed manifestations of renal impairment. Compared with the primary ANCA-induced small-vessel vasculitis, patients with PTU-induced small-vessel vasculitis were mostly female (P<0.05) and deleloped the disease at a younger age (P<0.05). They had a higher positive rate of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA; P<0.05), lower 24 h proteinuria content, lower serum creatinine (P<0.05) and milder histopathological lesions (P<0.05). A number of them had gross hematuria (P<0.05). They rarely used hormone and cytotoxic drugs (P<0.05) during treatment and had a better prognosis (P<0.05). In conclusion, PTU-induced small-vessel vasculitis has a milder pathology and clinical manifestations with a better prognosis.

Long‐term outcome of antineutrophil cytoplasmic antibody‐associated small vessel vasculitis after renal transplantation

The survival after renal transplantation of patients with antineutrophil cytoplasmic antibody (ANCA)-associated to systemic vasculitis is as good as in other diseases, although most of the reports are based on small numbers of patients. Furthermore, it is not known whether comorbidities (cardiovascular [CV] disease and cancer) are more frequent than in general population. We report our experience and the analysis of the published data on this topic. The outcome after transplantation in 49 patients with ANCA-associated small vessel vasculitis was compared with a control group. The relapse rate of vasculitis was 0.01 per patient per year. Comparison with the control patients revealed no difference in long-term outcome, CV mortality or incidence of malignancies. In the published literature, patients with ANCA at transplantation and with Wegener's granulomatosis are at greater risk of relapse. Taking our own results together with the review of the literature, we conclude that patient and graft survival rates compare favorably with those in control group that the recurrence rate is very low and that there is no increase in the incidence of cancer or in CV mortality. Patients with ANCA at transplantation and with Wegener's granulomatosis have a higher relapse rate.

Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity

AbstractAntineutrophil cytoplasmic antibodies (ANCAs) target proteins normally retained within neutrophils, indicating that cell death is involved in the autoimmunity process. Still, ANCA pathogenesis remains obscure. ANCAs activate neutrophils inducing their respiratory burst and a peculiar form of cell death, named NETosis, characterized by formation of neutrophil extracellular traps (NETs), decondensed chromatin threads decorated with cytoplasmic proteins endorsed with antimicrobial activity. NETs have been consistently detected in ANCA-associated small-vessel vasculitis, and this association prompted us to test whether the peculiar structure of NET favors neutrophil proteins uploading into myeloid dendritic cells and the induction of ANCAs and associated autoimmunity. Here we show that myeloid DCs uploaded with and activated by NET components induce ANCA and autoimmunity when injected into naive mice. DC uploading and autoimmunity induction are prevented by NET treatment with DNAse, indicating that NET structural integrity is needed to maintain the antigenicity of cytoplasmic proteins. We found NET intermingling with myeloid dendritic cells also positive for neutrophil myeloperoxidase in myeloperoxidase-ANCA-associated microscopic poliangiitis providing a potential correlative picture in human pathology. These data provide the first demonstration that NET structures are highly immunogenic such to trigger adaptive immune response relevant for autoimmunity.