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Medicine Dec 2023Immune system deregulation, including AAV, is a key event that may potentially evolve into ESRD. Abnormal activation of the cAP is also a cardinal feature of TMA,...
End stage renal disease in patient with microscopic polyangiitis and atypical hemolytic-uremic syndrome arose 3 weeks after the third dose of anti-SARS-CoV2 vaccine mRNA-1273: A case report with literature revision.
RATIONALE
Immune system deregulation, including AAV, is a key event that may potentially evolve into ESRD. Abnormal activation of the cAP is also a cardinal feature of TMA, particularly aHUS. The kidney is the most frequently involved organ, and renal-limited forms of TMA are often encountered in clinical practice. Isolated case reports described the occurrence of renal TMA in AAV patients. Some cases of both de novo and relapses of AAV and/or TMAs after anti-SARS-CoV2 vaccination have been reported. We reported, for the 1st time, a case of patients with new-onset MPA and aHUS occurring 3 weeks after the third dose of mRNA-1273 vaccine anti-SARS-CoV2.
PATIENT CONCERNS
We present a 67-year-old man, affected by arterial hypertension, reported, after mRNA-1273 vaccine anti-SARS-CoV2, anuria, fatigue, anorexia and nausea. Laboratory data revealed acute renal failure.
DIAGNOSIS
Positivity of MPO-ANCA was observed. 7 days after admission, we observed a worsening of anemia and thrombocytopenia with haptoglobin reduction, LDH increase and presence of schistocytes. Plasma levels of ADAMTS-13 were normal. A renal biopsy was performed, and findings were consistent with microscopic polyangiitis, with features of micro-thrombotic glomerulopathy. Genetic tests revealed absence of hybrid genes associated with the increased risk of aHUS.
INTERVENTIONS AND OUTCOMES
We started renal replacement treatment, including hemodialysis, and pulsed methylprednisolone, with no improvement of laboratory parameters. Then, plasma exchange was performed leading to partial haematological response. Only with Eculizumab, a human C5 inhibitor, we observed a normalization of haptoglobin levels and platelets' count. However, three months after discharge, the patient still required hemodialysis.
LESSONS
To our knowledge we observed the first case aHUS, without genetic predisposition, associated with MPA occurring after the third dose of anti-SARS-CoV2 vaccine. This case report highlights the potential link between anti-SARS-CoV2 vaccine as a trigger of MPA and aHUS. This systematic review offers additional perspectives. It is plausible to hypothesize that the vaccine was the trigger for the development of these 2 diseases.Solid evidence on the mechanisms of interaction between vaccine and immune system, the role of genetic predisposition, and other variables, will shed additional light on the controversial link between anti-SARS-CoV2 vaccine and autoimmunity.
Topics: Male; Humans; Aged; Atypical Hemolytic Uremic Syndrome; 2019-nCoV Vaccine mRNA-1273; Microscopic Polyangiitis; Haptoglobins; COVID-19; Kidney Failure, Chronic; Genetic Predisposition to Disease
PubMed: 38115241
DOI: 10.1097/MD.0000000000036560 -
RMD Open Jul 2023To summarise and update evidence to inform the 2022 update of the EULAR recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitis...
Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): part 1-treatment of granulomatosis with polyangiitis and microscopic polyangiitis.
OBJECTIVE
To summarise and update evidence to inform the 2022 update of the EULAR recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitis (AAV).
METHODS
A systematic literature review (SLR) was performed to identify current evidence regarding treatment of AAV. PubMed, EMBASE and the Cochrane library were searched from 1 February 2015 to 25 February 2022. The evidence presented here is focused on the treatment of granulomatosis with polyangiitis and microscopic polyangiitis.
RESULTS
3517 articles were screened and 175 assessed by full-text review. Ninety articles were included in the final evidence synthesis. Cyclophosphamide and rituximab (RTX) show similar efficacy for remission induction (level of evidence (LoE) 1a) but RTX is more effective in relapsing disease (LoE 1b). Glucocorticoid (GC) protocols with faster tapering result in similar remission rates but lower rates of serious infections (LoE 1b). Avacopan can be used to rapidly taper and replace GC (LoE 1b). Data on plasma exchange are inconsistent depending on the analysed trial populations but meta-analyses based on randomised controlled trials demonstrate a reduction of the risk of end-stage kidney disease at 1 year but not during long-term follow-up (LoE 1a). Use of RTX for maintenance of remission is associated with lower relapse rates compared with azathioprine (AZA, LoE 1b). Prolonged maintenance treatment results in lower relapse rates for both, AZA (LoE 1b) and RTX (LoE 1b).
CONCLUSION
This SLR provides current evidence to inform the 2022 update of the EULAR recommendations for the management of AAV.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Cyclophosphamide; Rituximab; Glucocorticoids; Remission Induction
PubMed: 37479496
DOI: 10.1136/rmdopen-2023-003082 -
Joint Bone Spine Dec 2023Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), namely granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), namely granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis constitute a group of rare systemic vasculitides, affecting small vessels. Genders are equally affected, with symptoms most commonly presenting during and/or after the fifth decade of life, but AAV may also present in younger individuals. As advanced maternal age is becoming common and safe over the last decades, it is now more feasible for middle-aged women suffering from AAV to get pregnant. Although adverse pregnancy outcomes have been thoroughly investigated in other systemic diseases, the exact prevalence of pregnancy complications and unfavorable outcomes in pregnant women with AAV has not been systematically evaluated.
METHODS
We researched PubMed, Scopus, Cochrane Library and Cinahl databases until September, 2022. Three blinded investigators extracted data and assessed the risk of bias. A random effects model was used for the analysis. The outcomes studied were pre-term delivery, intrauterine growth restriction (IUGR) neonates and disease flare.
RESULTS
We included six studies with 92 pregnancies in patients with AAV. The prevalence of pre-term delivery, IUGR neonates and disease flare were 18% (CI: 0.10-0.30, P=non-significant), 20% (CI: 0.11-0.33, P=non-significant) and 28% (CI: 0.09-0.59, P<0.01), respectively.
CONCLUSION
The analysis demonstrated higher occurrence of adverse outcomes in pregnant women suffering from AAV accompanied by an increased risk of disease flare during pregnancy. These findings underline the importance of preconception counseling and the necessity of close monitoring in these patients similarly to other systemic inflammatory diseases.
Topics: Middle Aged; Infant, Newborn; Female; Humans; Male; Pregnancy; Granulomatosis with Polyangiitis; Churg-Strauss Syndrome; Pregnancy Outcome; Symptom Flare Up; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic
PubMed: 37419307
DOI: 10.1016/j.jbspin.2023.105609 -
Annals of the Rheumatic Diseases Jan 2024Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several...
BACKGROUND
Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update.
METHODS
Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations.
RESULTS
Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.
CONCLUSIONS
In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
Topics: Humans; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Cyclophosphamide; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Remission Induction; Rituximab; Practice Guidelines as Topic
PubMed: 36927642
DOI: 10.1136/ard-2022-223764 -
Rheumatology (Oxford, England) Aug 2023In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current...
OBJECTIVE
In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence.
METHODS
An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation.
RESULTS
Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering.
CONCLUSION
These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.
Topics: Humans; Consensus; Canada; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cytoplasm; Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Microscopic Polyangiitis
PubMed: 36805625
DOI: 10.1093/rheumatology/kead087 -
Biology Dec 2022: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease developed by autoantibody production against human... (Review)
Review
: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease developed by autoantibody production against human neutrophilic granulocytes, including proteinase-3 (PR3) and myeloperoxidase (MPO). The management of AAV patients is difficult due to the multiorgan involvement, high rate of relapse, and complications of immunosuppressive agents that make it challenging. This study aims to investigate the efficacy and safety of rituximab (RTX) therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) subtypes. : The PubMed/Medline database was searched for any studies related to RTX therapy in ANCA-associated vasculitis (GPA and MPA subtypes), from inception to 1 August 2022, and proceeded in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). : Our search resulted in 1082 initial records. After the elimination of review papers, irrelevant studies, and non-English records, 223 articles were included, and the data related to the efficacy and safety of RTX therapy were extracted. Several randomized and non-randomized studies showed that RTX is an effective treatment option for patients with AAV. Most of the studies showed the very effective effect of RTX in controlling disease in AAV patients, including pediatrics, adults, and elderlies, although RTX cannot completely prevent relapse. However, maintenance therapy helps delay the disease's relapse and causes sustained remission. Not only the licensed dose (375 mg/m intravenous per week for 4 weeks) could induce disease remission, but studies also showed that a single infusion of RTX could be effective. Although RTX could resolve many rare manifestations in AAV patients, there are few reports showing treatment failure. Additionally, few sudies have reported the unexpeted worsening of the disease after RTX administration. Generally, RTX is relatively safe compared to conventional therapies, but some serious adverse effects, mainly infections, cytopenia, hypogammaglobinemia, malignancy, and hypersensitivity have been reported. : RTX is an effective and relatively safe therapeutic option for AAV. Studies on the evaluation of the safety profiles of RTX and the prevention of severe RTX-related side effects in AAV patients are required.
PubMed: 36552276
DOI: 10.3390/biology11121767 -
Cureus Oct 2022Granulomatosis with polyangiitis (GPA) is a systemic disease that has variable clinical expression. GPA is the most common antineutrophilic cytoplasmic... (Review)
Review
Granulomatosis with polyangiitis (GPA) is a systemic disease that has variable clinical expression. GPA is the most common antineutrophilic cytoplasmic antibody(ANCA)-associated vasculitis (AAV). Diffuse alveolar hemorrhage (DAH) is one of the least common pulmonary manifestations in patients with GPA. DAH is clinically marked by hemoptysis, anemia, and diffuse alveolar infiltrates on imaging as well as hypoxemic respiratory failure. The diagnosis and treatment are challenging. Recommendations for ANCA-associated vasculitis, in general, are already established; however, there is a knowledge gap that addresses the association of GPA and DAH. The aim of this systematic review is to focus on the main clinical aspects and treatment of patients with GPA who present with DAH. Thorough research of available literature was performed, including studies published in the last 10 years, following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) 2020 recommendations. The following databases were included: PubMed, Medline, Embase, ClinicalTrials.com, Google Scholar, and Prospero. The search terms included: [granulomatosis] AND [polyangiitis] AND [diffuse alveolar hemorrhage] OR [diffuse pulmonary hemorrhage] NOT [microscopic polyangiitis] NOT [eosinophilic granulomatosis]. NOS was used to assess the internal validity of the study in four domains, including selection, ascertainment, causality, and reporting. Our initial search identified 8989 studies. After excluding duplicated data and using our predetermined inclusion and exclusion criteria, we were able to retrieve 18 studies. Twelve out of 18 (67%) studies were case reports. Five were retrospective cohorts and one controlled trial. The average age of patients with GPA with DAH was 49.55 ± 17.54 years (18 - 76). Male individuals had a slight predominance (59%) in comparison to female individuals (41%). The hemoglobin level at the time of presentation was 8.86 mg/dL ± 1.43. The majority of patients (61.5%) reported hemoptysis. Renal involvement was present in 66.7%. Patients who required mechanical ventilation represented 61.5%. Plasmapheresis was used in 71.4%. Mortality was 20%, and gender was not associated with mortality (p = 0.822). Hemoptysis was not associated with the need for mechanical ventilation (p = 0.928). Renal impairment was not a predictor of mechanical ventilation (p = 0.207). In summary, patients with GPA and DAH were severely ill, frequently had renal impairment upon admission, and frequently required mechanical ventilation. Steroids, rituximab, and cyclophosphamide are the first-line treatment, and plasmapheresis is still in use. Eventually, extracorporeal membrane oxygenation (ECMO) can be the salvage therapy. Randomized controlled clinical trials (RCTs) are needed to address the best therapeutic options for this population.
PubMed: 36348918
DOI: 10.7759/cureus.29909 -
Clinical Rheumatology Feb 2023Spontaneous renal hemorrhage (SRH) in ANCA-associated vasculitis (AAV) is rare but fatal. We aimed to characterize clinical manifestations and managements of AAV...
Clinical features and management of Chinese anti-neutrophil cytoplasmic antibody-associated vasculitis patients with spontaneous renal hemorrhage: a single-center report and systematic review.
INTRODUCTION
Spontaneous renal hemorrhage (SRH) in ANCA-associated vasculitis (AAV) is rare but fatal. We aimed to characterize clinical manifestations and managements of AAV patients with SRH.
METHOD
Hospitalized AAV patients were screened from January 2000 to April 2021, at Peking Union Medical College Hospital (PUMCH). Also, a systematic review was based on retrieving all the relevant literature from PubMed, MedlinePlus, and Web of Science until April 2021. Clinical features, management, and prognosis of the patients were collected and concluded.
RESULTS
In PUMCH, four out of 1640 AAV patients with SRH were included in our study; three had granulomatosis with polyangiitis (GPA) and one had microscopic polyangiitis (MPA). The ratio of men to women was 3 to 1, and the average age of onset was 55 years. The Birmingham Vasculitis Activity Score (BVAS) ranged from 21 to 23. Combining with documented reports, 13 patients were diagnosed as AAV complicated with SRH (including four from PUMCH), 7 with GPA, and 6 with MPA. Mean BVAS was 25.2 ± 6.6. The symptoms of SRH presented as severe back or abdominal pain. Patients with SRH to age- and gender-matched patients without SRH were compared, and we found that in the SRH group, the duration of disease was shorter, and BVAS, renal function, and inflammatory markers (WBC and ESR) were significantly greater, whereas Hb, Alb, and renal function greatly reduced.
CONCLUSION
This is the first summary of clinical features and treatments of SRH in AAV. Patients with AAV in early stage and with high disease activity appeared to be more likely to develop SRH. Key Points • This is the first summary of clinical features and treatments of SRH in AAV. • SRH more likely occurs in AAV patients in the early stage (≤ 3 months) and with high disease activity. • Clinicians should be aware of the possibility of SRH when AAV patients complain of back or abdominal pain.
Topics: Male; Humans; Female; Middle Aged; East Asian People; Antibodies, Antineutrophil Cytoplasmic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Microscopic Polyangiitis; Kidney; Kidney Diseases; Hemorrhage; Granulomatosis with Polyangiitis
PubMed: 36190664
DOI: 10.1007/s10067-022-06397-4 -
Modern Rheumatology Aug 2023The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis for 2023 clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis.
OBJECTIVES
The objective of this study is to provide evidence for the revision of clinical practice guidelines for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis by the Japan Research Committee for Intractable Vasculitis.
METHODS
PubMed, CENTRAL, and the Japan Medical Abstracts Society databases were searched for articles published between 2015 and 2020 to update the systematic review for existing clinical questions, while PubMed, CENTRAL, EMBASE, and the Japan Medical Abstracts Society were searched for articles published between 2000 and 2020 to conduct a systematic review for newly developed clinical questions. The certainty of evidence was assessed with the GRADE approach.
RESULTS
For remission induction, when used in conjunction with cyclophosphamide or rituximab, reduced-dose glucocorticoid lowered the risk of serious adverse events compared to standard-dose glucocorticoid. Avacopan improved sustained remission at 12 months compared to high-dose glucocorticoid. Addition of plasma exchange to remission induction therapy did not reduce the risk of death, end-stage kidney disease, or relapse. For remission maintenance, rituximab reduced the risk of relapse compared to azathioprine. Long-term rituximab or azathioprine reduced the risk of relapse compared to short-term rituximab or azathioprine, respectively.
CONCLUSIONS
This systematic review provided evidence required to develop the 2023 clinical practice guideline for the management of ANCA-associated vasculitis.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Rituximab; Glucocorticoids; Japan; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Remission Induction; Antibodies, Antineutrophil Cytoplasmic; Recurrence
PubMed: 36112482
DOI: 10.1093/mr/roac114 -
The Journal of Rheumatology Dec 2022While myocardial impairment is a predictor of poor prognosis in antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), little is known about valvular...
OBJECTIVE
While myocardial impairment is a predictor of poor prognosis in antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), little is known about valvular involvement. This study aims at describing the clinical presentation, management, and outcome of endocarditis associated with AAV.
METHODS
We conducted a multicenter retrospective study in centers affiliated with the French Vasculitis Study Group. We included patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or eosinophilic GPA with endocardial impairment. A systematic review was then performed through PubMed, Embase, and Cochrane Library from inception up to September 2020.
RESULTS
The retrospective cohort included 9 patients (82%) with GPA, 1 (9%) with MPA, and 1 (9%) with unclassified AAV. Clinical presentation included acute valvular insufficiency (n = 7, 64%), cardiac failure (n = 3, 27%), dyspnea (n = 3, 27%), and no symptoms (n = 2, 18%). The aortic valve was the most frequently affected (n = 8/10, 80%), and vegetations were noted in 4 of 10 patients (40%). Six patients (55%) underwent surgical valvular replacement. No death from endocarditis was reported. The systematic review retrieved 42 patients from 40 references: 30 (71%) had GPA, 21 (50%) presented with vegetations, the aortic valve (n = 26, 62%) was the most frequently involved. Valvular replacement was required in 20 cases (48%) and 5 patients (13%) died from the endocarditic impairment.
CONCLUSION
Endocarditis is a rare and potentially life-threatening manifestation of AAV. Acute valvular insufficiency may lead to urgent surgery. Implementing transthoracic echocardiography in standard assessment at baseline and follow-up of AAV might reduce the delay to diagnosis and allow earlier immunosuppressive treatment before surgery is needed.
Topics: Humans; Retrospective Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Microscopic Polyangiitis; Endocarditis; Cytoplasm; Granulomatosis with Polyangiitis; Multicenter Studies as Topic
PubMed: 35840158
DOI: 10.3899/jrheum.211379