Microscopic polyangiitis is a rare, systemic, necrotizing, pauci-immune, ANCA associated small vessel vasculitis, with no evidence of granulomatous inflammation. Diagnosing microscopic polyangiitis is often difficult because of it´s presentation by a number of non-specific symptoms. We treated a 35-year old patient, who was admitted for migrating arthritis and fever with papulous rash. In this case, we want to point out the importance of considering the diagnosis of MPA and similar rare diseases in the process of differential diagnosis, mainly in patients presenting with non-specific symptoms, because the mortality of this disease without adequate treatment is alarmingly high.

• Klíčová slova
• ANCA, cerebritis, glomerulonephritis, pancreatitis, polyangiitis, vasculitis,
• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• glomerulonefritida * diagnóza   MeSH
• lidé MeSH
• mikroskopická polyangiitida * diagnóza   MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH

• MeSH
• granulomatóza s polyangiitidou * komplikace   diagnóza   farmakoterapie   MeSH
• lidé MeSH
• mikroskopická polyangiitida * komplikace   diagnóza   farmakoterapie   MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH

OBJECTIVE: Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown. METHODS: Consecutive patients from Sweden, the United Kingdom, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide (CYC), rituximab (RTX), and corticosteroids the first 3 months was registered. Outcomes up to 2 years from diagnosis included Vasculitis Damage Index (VDI), hospitalization, and cause of death. RESULTS: Treatment data were available for 167 of 202 patients. At 2 years, 4% had no items of damage. There was a positive association between VDI score at 2 years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using CYC or RTX. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. Myeloperoxidase-antineutrophil cytoplasmic antibody positivity and lower creatinine levels decreased the odds of readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose. CONCLUSION: Immunosuppressive treatment with CYC or RTX in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first 3 months was associated with treatment-related damage and fatal infections.

• Klíčová slova
• ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS, GRANULOMATOSIS WITH POLYANGIITIS, HOSPITALIZATION, MICROSCOPIC POLYANGIITIS,
• MeSH
• granulomatóza s polyangiitidou * komplikace   farmakoterapie   MeSH
• hospitalizace MeSH
• lidé MeSH
• mikroskopická polyangiitida * farmakoterapie   MeSH
• peroxidasa MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• peroxidasa MeSH
• protilátky proti cytoplazmě neutrofilů MeSH

• Klíčová slova
• ANCA, Granulomatosis with polyangiitis, Tumor, Vasculitis,
• MeSH
• granulomatóza s polyangiitidou * diagnóza   MeSH
• imunosupresiva MeSH
• lidé MeSH
• mikroskopická polyangiitida * diagnóza   MeSH
• nádory * MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunosupresiva MeSH
• protilátky proti cytoplazmě neutrofilů MeSH

ANCA positive vasculitis (AAV) is a serious autoimmune disease mainly affecting small vessels in various organ systems, accompanied by the presence of ANCA antibodies in serum. AAV represents a group of the most common systemic vasculitis in adulthood, and based on clinical manifestations this disease entity includes 3 phenotypes, namely: granulomatosis with polyangiitis (formerly Wegeners granulomatosis), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). Similar to other autoimmune diseases, AAV develops in patients with a predisposing genetic background who have been exposed to causative environmental factors, such as infections. The mechanisms by which ANCA antibodies cause vasculitis involves excessive neutrophil activation, that subsequently leads to release pro-inflammatory cytokines, reactive oxygen species and lytic enzymes. In addition, activated neutrophils induce the formation of neutrophil extracellular traps in a process called NETosis. The released neutrophil antigens are exposed to the immune system via antigen presenting cells, which further stimulates antibody production and creates a vicious circle with tissue destruction. Understanding the pathogenesis of AAV represents the key which provides not only optimal diagnosis and treatment, but also gives the pathologist a tool for deeper insight into the morphological features of disease progression, including the various stages of development and healing.

• Klíčová slova
• AAV, ANCA associated vasculitis, GPA, MPA, pathophysiology,
• MeSH
• ANCA-asociované vaskulitidy * patologie   MeSH
• Churgův-Straussové syndrom * MeSH
• dospělí MeSH
• granulomatóza s polyangiitidou * MeSH
• lidé MeSH
• mikroskopická polyangiitida * MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů 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 epidemiologie   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.

• Klíčová slova
• ANCA-associated vasculitis, glomerulonephritis, granulomatosis with polyangiitis, guidelines, microscopic polyangiitis,
• 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
• Názvy látek
• protilátky proti cytoplazmě neutrofilů 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.

• Klíčová slova
• Anti-neutrophil cytoplasmic antibody, Eosinophilic GPA, Granulomatosis with polyangiitis, Microscopic polyangiitis,
• 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
• Názvy látek
• imunosupresiva MeSH
• protilátky proti cytoplazmě neutrofilů MeSH

The most common group of systemic vasculitides in adulthood are anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). AAV represent autoimmune systemic vasculitides and include 3 clinical phenotypes: Granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis), Microscopic polyangiitis (MPA) and Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome). Histological features are similar to each other in all affected locations, and there are represented by necrotizing vascular inflammation of small and medium calibers, often venules, capillaries or arteriols, typically with fibrinoid vessel wall necrosis. The consequences of this condition are bleeding, as well as compromise of the lumen which may result in downstream tissue ischemia and necrosis. Typically affected locations in biopsy practice are: ENT, lung, skin, GIT, and kidney. The aim of this review is to provide a comprehensive overview of the important histopathological findings. ANCA positive vasculitis is a serious life-threatening disease and therefore requires a rapid diagnosis and appropriate therapy.

• Klíčová slova
• ANCA positive vasculitis, GPA, MPA, histopathology,
• MeSH
• ANCA-asociované vaskulitidy * diagnóza   patologie   MeSH
• Churgův-Straussové syndrom * diagnóza   patologie   MeSH
• dospělí MeSH
• granulomatóza s polyangiitidou * diagnóza   patologie   MeSH
• lidé MeSH
• mikroskopická polyangiitida * diagnóza   patologie   MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protilátky proti cytoplazmě neutrofilů MeSH

BACKGROUND: Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. METHODS: Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. RESULTS: From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. CONCLUSIONS: In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

• Klíčová slova
• ANCA-associated vasculitis, MMF, granulomatosis with polyangiitis, microscopic polyangiitis, mycophenolate mofetil,
• MeSH
• ANCA-asociované vaskulitidy * farmakoterapie   MeSH
• imunosupresiva terapeutické užití   MeSH
• indukce remise MeSH
• kyselina mykofenolová terapeutické užití   MeSH
• lidé MeSH
• mikroskopická polyangiitida * MeSH
• peroxidasa MeSH
• protilátky proti cytoplazmě neutrofilů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• imunosupresiva MeSH
• kyselina mykofenolová MeSH
• peroxidasa MeSH
• protilátky proti cytoplazmě neutrofilů MeSH