OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan's syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.
- MeSH
- Behcetův syndrom klasifikace diagnóza MeSH
- Churgův-Straussové syndrom diagnóza klasifikace MeSH
- dítě MeSH
- granulomatóza s polyangiitidou * klasifikace diagnóza MeSH
- IgA vaskulitida diagnóza klasifikace MeSH
- lidé MeSH
- mikroskopická polyangiitida klasifikace diagnóza MeSH
- mladiství MeSH
- polyarteritis nodosa klasifikace diagnóza MeSH
- prediktivní hodnota testů MeSH
- předškolní dítě MeSH
- retrospektivní studie MeSH
- revmatologie normy MeSH
- senzitivita a specificita * MeSH
- Takayasuova arteriitida * klasifikace diagnóza MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a heterogenous autoimmune disease. While traditionally stratified into two conditions, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the subclassification of ANCA-associated vasculitis is subject to continued debate. Here we aim to identify phenotypically distinct subgroups and develop a data-driven subclassification of ANCA-associated vasculitis, using a large real-world dataset. METHODS: In the collaborative data reuse project FAIRVASC (Findable, Accessible, Interoperable, Reusable, Vasculitis), registry records of patients with ANCA-associated vasculitis were retrieved from six European vasculitis registries: the Czech Registry of ANCA-associated vasculitis (Czech Republic), the French Vasculitis Study Group Registry (FVSG; France), the Joint Vasculitis Registry in German-speaking Countries (GeVas; Germany), the Polish Vasculitis Registry (POLVAS; Poland), the Irish Rare Kidney Disease Registry (RKD; Ireland), and the Skåne Vasculitis Cohort (Sweden). We performed model-based clustering of 17 mixed-type clinical variables using a parsimonious mixture of two latent Gaussian variable models. Clinical validation of the optimal cluster solution was made through summary statistics of the clusters' demography, phenotypic and serological characteristics, and outcome. The predictive value of models featuring the cluster affiliations were compared with classifications based on clinical diagnosis and ANCA specificity. People with lived experience were involved throughout the FAIRVASVC project. FINDINGS: A total of 3868 patients diagnosed with ANCA-associated vasculitis between Nov 1, 1966, and March 1, 2023, were included in the study across the six registries (Czech Registry n=371, FVSG n=1780, GeVas n=135, POLVAS n=792, RKD n=439, and Skåne Vasculitis Cohort n=351). There were 2434 (62·9%) patients with GPA and 1434 (37·1%) with MPA. Mean age at diagnosis was 57·2 years (SD 16·4); 2006 (51·9%) of 3867 patients were men and 1861 (48·1%) were women. We identified five clusters, with distinct phenotype, biochemical presentation, and disease outcome. Three clusters were characterised by kidney involvement: one severe kidney cluster (555 [14·3%] of 3868 patients) with high C-reactive protein (CRP) and serum creatinine concentrations, and variable ANCA specificity (SK cluster); one myeloperoxidase (MPO)-ANCA-positive kidney involvement cluster (782 [20·2%]) with limited extrarenal disease (MPO-K cluster); and one proteinase 3 (PR3)-ANCA-positive kidney involvement cluster (683 [17·7%]) with widespread extrarenal disease (PR3-K cluster). Two clusters were characterised by relative absence of kidney involvement: one was a predominantly PR3-ANCA-positive cluster (1202 [31·1%]) with inflammatory multisystem disease (IMS cluster), and one was a cluster (646 [16·7%]) with predominantly ear-nose-throat involvement and low CRP, with mainly younger patients (YR cluster). Compared with models fitted with clinical diagnosis or ANCA status, cluster-assigned models demonstrated improved predictive power with respect to both patient and kidney survival. INTERPRETATION: Our study reinforces the view that ANCA-associated vasculitis is not merely a binary construct. Data-driven subclassification of ANCA-associated vasculitis exhibits higher predictive value than current approaches for key outcomes. FUNDING: European Union's Horizon 2020 research and innovation programme under the European Joint Programme on Rare Diseases.
- MeSH
- ANCA-asociované vaskulitidy * klasifikace diagnóza epidemiologie krev imunologie MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida klasifikace epidemiologie krev diagnóza imunologie MeSH
- registrace * statistika a číselné údaje MeSH
- senioři MeSH
- shluková analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Mikroskopická polyangiitida je ANCA vaskulitida, která se vyznačuje přítomností protilátek proti myeloperoxidáze (anti-MPO). Jedná se o vaskulitidu malých cév s fokálně nekrotizující glomerulonefritidou bez tvorby granulomů v dýchacích cestách. Na začátku onemocnění jsou přítomny nespecifické příznaky. Mezi ně patří artralgie, artritidy a myalgie. Difuzní alveolární hemoragie (DAH) je klinický syndrom charakterizovaný akutním nástupem alveolárních infiltrátů a hypoxemií, které vedou k progresivnímu difuznímu alveolárnímu krvácení vyžadujícího okamžitou léčbu. Kazuistika popisuje pacientku s nově diagnostikovanou mikroskopickou polyangiitidou (MPA), jejíž první manifestací byla difuzní alveolární hemoragie. Základní onemocnění bylo dále komplikováno těžkým hypoxickým respiračním selháním s nutností zavedení extrakorporální membránové oxygenace (V-V ECMO), obtížným weaningem (odpojení od umělé plicní ventilace) a recidivujícími infekty včetně multirezistentních kmenů. Pacientka byla léčena vysokodávkovými pulzy glukokortikoidů, cyklo- fosfamidem v redukované dávce a aplikací imunoglobulinů. Po osmiměsíční úspěšné léčbě byla propuštěna domů, nyní je její stav nadále uspokojivý.
Microscopic polyangiitis (MPA) is an ANCA-associated vasculitis characterized by the presence of anti-myeloperoxidase (anti-MPO) antibodies. It is a small vessel vasculitis with focally necrotizing glomerulonephritis without granuloma formation in the airways. Constitutional symptoms are present at the onset of the disease. These include arthralgia, arthritis, and myalgia. Diffuse alveolar hemorrhage (DAH) is a clinical syndrome characterized by acute onset of alveolar infiltrates and hypoxemia leading to progressive diffuse alveolar hemorrhage requiring immediate treatment. This case report describes a patient with newly diagnosed microscopic polyangiitis whose first manifestation was diffuse alveolar hemorrhage. The underlying disease was further complicated by severe hypoxic respiratory failure with the need for extracorporeal membrane oxygenation (V-V ECMO), difficult weaning (disconnection from artificial pulmonary ventilation), and recurrent infections including multidrug-resistant strains. The patient was treated with high-dose pulses of glucocorticoids, reduced-dose cyclophosphamide, and immunoglobulin administration. After eight months of successful treatment, she was discharged home and her condition remains satisfactory.
- Klíčová slova
- difuzní alveolární hemoragie,
- MeSH
- akutní poškození plic diagnostické zobrazování diagnóza etiologie MeSH
- dospělí MeSH
- lidé MeSH
- mikroskopická polyangiitida * diagnóza farmakoterapie imunologie komplikace MeSH
- mimotělní membránová oxygenace metody MeSH
- rentgendiagnostika hrudníku klasifikace metody MeSH
- syndrom dechové tísně * diagnostické zobrazování diagnóza etiologie imunologie klasifikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
- MeSH
- ANCA-asociované vaskulitidy * farmakoterapie epidemiologie komplikace MeSH
- granulomatóza s polyangiitidou * farmakoterapie epidemiologie komplikace MeSH
- lidé MeSH
- mikroskopická polyangiitida * farmakoterapie epidemiologie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- registrace MeSH
- správnost dat MeSH
- ukládání a vyhledávání informací MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
BACKGROUND: Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting several prospective randomized controlled trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS as well as to identify potential prognostic factors. METHODS: Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995-2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models. RESULTS: A total of 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (44%) had microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. The median follow-up time was 8 years (interquartile range 2.9-13.6). During the observation period there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared with a matched cohort (regarding country, age group and sex) from the background population there were 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. The estimated median survival time (from diagnosis) was 17.8 years (95% confidence interval 15.7-20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate and low platelet count were identified as predictors of death in a multivariate Cox model. CONCLUSIONS: Patients with AAV still have an increased risk of mortality compared with the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival and infections remain the leading cause of mortality among patients with AAV.
- MeSH
- ANCA-asociované vaskulitidy * terapie farmakoterapie MeSH
- dospělí MeSH
- granulomatóza s polyangiitidou * diagnóza terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida * komplikace diagnóza MeSH
- předškolní dítě MeSH
- prognóza MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a group of diseases characterised by necrotizing inflammation of small vessels such as arterioles, venules, and capillaries. ANCA-associated vasculitides (AAV) are referred to as small vessel vasculitides. Three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA), are defined according to clinical features. The most common disease with renal involvement in AAV is MPA Approximately 90% of patients with MPA have renal involvement. While this rate is 70-80% in GPA, less than half of EGPA patients have renal involvement. Untreated survival in AAVs is less than one year. With appropriate immunosuppressive therapy, the 5-year renal survival rate is 70-75%. Without therapy, the prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. In this review, we described the treatment of renal involvement in AAV in line with current studies.
- MeSH
- ANCA-asociované vaskulitidy * komplikace farmakoterapie MeSH
- Churgův-Straussové syndrom * farmakoterapie MeSH
- granulomatóza s polyangiitidou * komplikace farmakoterapie MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- mikroskopická polyangiitida * farmakoterapie MeSH
- nemoci ledvin * farmakoterapie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates.
- MeSH
- ANCA-asociované vaskulitidy * komplikace farmakoterapie MeSH
- chronické selhání ledvin * etiologie terapie MeSH
- Churgův-Straussové syndrom * MeSH
- glomerulonefritida * farmakoterapie MeSH
- granulomatóza s polyangiitidou * terapie MeSH
- lidé MeSH
- mikroskopická polyangiitida * terapie MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ANCA-asociované vaskulitidy * diagnóza farmakoterapie patologie MeSH
- aniliny farmakologie terapeutické užití MeSH
- Churgův-Straussové syndrom diagnóza farmakoterapie patologie MeSH
- cyklofosfamid farmakologie terapeutické užití MeSH
- glomerulonefritida etiologie klasifikace MeSH
- glukokortikoidy farmakologie terapeutické užití MeSH
- granulomatóza s polyangiitidou diagnóza farmakoterapie patologie MeSH
- kyseliny nipekotinové farmakologie terapeutické užití MeSH
- lidé MeSH
- mikroskopická polyangiitida diagnóza farmakoterapie patologie MeSH
- plazmaferéza mortalita MeSH
- rituximab farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
