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Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109/liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77–91%) and the specificity was 99% (95% CI 98–100%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research.

Additional file 1: Supplementary Table 1. Demographic and clinical features of SSc patients recruited for the in vitro T or B cell-depletion. Supplementary Table 2. Overview on medications given to all individual SSc patients with SSc treated with or without immunosuppressive drugs in the present and previous study [5]. Supplementary Figure 1. Efficiency of depletion of human T or B cells from PBMC. Levels of CD3+ T cells (A), CD4+ T cells (B), CD8+ T cells (C), and CD20+ B cells (D) were determined by FACS analysis and presented as % of total human leukocytes in PBMC. Statistical significance of comparison was determined using the paired t test. Supplementary Figure 2. Levels of human leukocytes in peripheral blood of recipient mice. Mice were transferred with whole PBMC, T-cell depleted, or B-cell depleted PBMC, and peripheral blood was taken at the 6th week (A, B) and 12th week (C, D) after the transfer. Subsequently, human CD45+ leukocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells and CD20+ B cells were identified by flow cytometry. Levels of human leukocytes are presented as percentage of total leukocytes including murine and human leukocytes in murine blood. Comparison on levels of human leukocytes indicated between mice transferred with whole PBMC (n = 7) and mice transferred with T-cell depleted PBMC (n = 7) (A) and between mice transferred with whole PBMC (n = 10) and mice transferred with B-cell depleted PBMC (n = 10) (B) by week by the 6th week after the transfer. Comparison on levels of human leukocytes indicated between mice transferred with whole PBMC (n = 4) and mice transferred with T-cell depleted PBMC (n = 4) (C) and between mice transferred with whole PBMC (n = 16) and mice transferred with B-cell depleted PBMC (n = 6) (D) by week by the 12th week after the transfer. P values reflect comparisons between mice transferred with whole PBMC and mice transferred with T- or B-cell depleted PBMC. Statistical significance was determined using the Wilcoxon matched pairs test. Supplementary Figure 3. Presence of ANA in sera of PBMC-transferred mice. Antinuclear antibody (ANA) pattern of murine sera were detected using (HEp-2) cell-based immunofluorescence staining (EUROPattern Suite, Euroimmun, Germany). Two out of 7 mice which received whole PBMC from SSc patients scored positive for ANA, and their ANA patterns were consistent with those of two corresponding SSc patients. By contrast, mice which received T cell-depleted or B cell-depleted PBMC isolated from the 2 SSc patients were ANA negative. Representative micrographs of the ANA test for mice received whole PBMC, T cell-depleted PBMC (PBMC T-/-) or B cell-depleted PBMC (PBMC B-/-) are shown. Supplementary Figure 4. Matrix of Spearman’s correlation coefficients between immunological and histopathological variables. Severity of inflammation in the lung, kidney and liver as well as levels of circulating human CD45+ leukocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells and CD20+ B cells at 6th week after the cell transfer, and levels of total IgG, anti-AT1R IgG and anti-ETAR IgG in sera obtained after the sacrifice of mice were used for the analysis. Samples were tested for normal distribution by using Shapiro-Wilk normality test. Since most variables were not normally distributed, Spearman correlation was applied for the analysis. A color-coded correlation scale is provided on the right of the plot. Blue and ellipses represent negative and positive correlations, respectively, and darker color tones representd larger correlation coefficient magnitudes. Statistically significant differences are indicated by asterisks (*p

Vorgeschichte: Übernahme einer 41-jährigen Patientin aus einem auswärtigen Krankenhaus bei pulmonalen Rezidiv einer 2 Jahre zuvor diagnostizierten Granulomatose mit Polyangiitis (GPA) mit rasch progredienten bipulmonalen Konsolidierungen und beginnender Kavernenbildung mit Einschmelzung[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

Einleitung: Ziel des Gemeinsamen Vaskulitis Registers im deutschsprachigen Raum (GeVas) ist es, alle Patienten mit einer neu diagnostizierten Vaskulitis oder einer Therapieumstellung bei einem Rezidiv in einem prospektiven, multizentrischen und pseudonymisierten Register zu erfassen und so den Langzeitverlauf[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

Einleitung: Durch Zusammenbruch des Immunprivilegs in der Arterienwand kommt es zu Aktivierung, Proliferation und Polarisierung von Th1- und Th17-Zellen, und damit zu vermehrter Produktion von Interferon-gamma und Interleukin 17 (IL-17) [ref:1]. Die Hypothese, dass IL-17A eine Schlüsselrolle[zum vollständigen Text gelangen Sie über die oben angegebene URL], 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Background: Systemic sclerosis (SSc) is characterized by endothelial dysfunction, vasculopathy, inflammation, fibrosis and – as a distinctive feature – thickening of the skin (scleroderma) through accumulation of collagen. Vascular injury is the underlying cause of Raynaud’s phenomenon,[for full text, please go to the a.m. URL], 46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Background: Cross-talk of platelets and leukocytes is involved in immune-mediated pathologies. In granulomatosis with polyangiitis (GPA), a systemic autoimmune vasculitis, increased platelet counts and platelet markers correlate with disease activity. Here we provide evidence that platelets are directly[for full text, please go to the a.m. URL], 46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.

Background: Cell death and dysregulation of dead cell clearance play a crucial role in the initiation of chronic inflammatory diseases and autoimmunity. The cardinal pathological features of granulomatosis with polyangiitis are necrotizing granulomatous inflammation and necrotizing autoimmune vasculitis.[for full text, please go to the a.m. URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)