Latent Class Analysis to Explore Subtypes of EGPA: Focusing on Respiratory Involvement and Inflammation Markers.

Antineutrophil Cytoplasmic Antibodies and Organ-Specific Manifestations in Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis

Background:Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder, characterised by asthma, eosinophilia, and small-to-medium size vessel vasculitis. Clinical manifestations of EGPA differ based on the presence or absence...

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.

Since testing for antineutrophil cytoplasmic antibodies (ANCA) became available for routine evaluation, no large homogeneous cohort of patients with the Churg-Strauss syndrome has been studied. To define the clinical and biological characteristics of newly diagnosed Churg-Strauss syndrome, according to the presence or absence of ANCA. Cross-sectional analysis of manifestations of participants who were enrolled in treatment trials between December 1995 and December 2002. Multicenter study in 63 clinical centers in France, Belgium, Latvia, and the United Kingdom, coordinated by the French Vasculitis Study Group. 112 patients with Churg-Strauss syndrome that was recently diagnosed on the basis of current classifications. The authors compared principal demographic, clinical, and laboratory features according to ANCA status at diagnosis. The authors detected ANCA in 43 (38%) patients. Positive ANCA status at diagnosis was associated with renal involvement, peripheral neuropathy, and biopsy-proven vasculitis, whereas negative ANCA status was associated with heart disease and fever. The authors assessed ANCA by immunofluorescence, but they did not assess ANCA centrally or systematically retest if ANCA was undetected at diagnosis. Phenotypically, ANCA-positive and ANCA-negative Churg-Strauss syndrome might differ. The association of ANCA positivity with clinical symptoms that indicate inflammation and necrosis of small vessels might characterize a predominantly vasculitic pattern of the Churg-Strauss syndrome.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings.

IntroductionEosinophilic granulomatosis with polyangiitis (EGPA) is part of antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitides. In EGPA small-vessel vasculitis is associated with eosinophilia and asthma. About 40% of EGPA patients are ANCA-positive, suggesting a role for B cells in the pathogenesis of EGPA. B cell-depleting therapy with rituximab (RTX) can be effective in ANCA-positive EGPA, but very few patients have been published to date. The role of RTX in the treatment of ANCA-negative EGPA is unclear.MethodsWe report a single-center cohort of patients with eosinophilic granulomatosis with polyangiitis. Of these patients, nine (six ANCA-positive, three ANCA-negative) had been treated with RTX for relapsing or refractory disease on standard immunosuppressive treatment. In a retrospective analysis, data on treatment response, frequency of relapses, adverse events, and peripheral B-cell reconstitution were evaluated. Furthermore, serum immunoglobulin concentrations, ANCA status, and peripheral B cell subpopulations were assessed after RTX treatment.ResultsAll patients had high disease activity before RTX treatment. At presentation 3 months after RTX therapy, all ANCA-positive and ANCA-negative patients had responded to RTX, with one patient being in complete remission, and eight patients being in partial remission. After a mean follow-up of 9 months, C-reactive protein concentrations had normalized, eosinophils had significantly decreased, and prednisone had been tapered in all patients. In all patients, RTX therapy was combined with a standard immunosuppressive therapy. Within the 9-month observation period, no relapse was recorded. Three patients were preemptively retreated with RTX, and during the median follow-up time of 3 years, no relapse occurred in these patients. During the follow-up of 13 patient-years, five minor but no major infections were recorded.ConclusionsIn our analysis on nine patients with EGPA resistant to standard therapy, rituximab proved to be an efficient and safe treatment for ANCA-positive and ANCA-negative patients. Preemptive retreatment with RTX, combined with standard maintenance immunosuppressants, resulted in a sustained treatment response. Prospective, randomized trials evaluating the use of RTX in EGPA are warranted.

BackgroundPatient-based registries can help advance research on rare diseases such as eosinophilic granulomatosis with polyangiitis (EGPA), a complex multiorgan form of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.ObjectiveThe aim of this study is to compare patient-reported and physician-reported data on manifestations, treatments, and outcomes for patients with EGPA.MethodsWe completed a comparative analysis of patients ≥18 years with EGPA in Canada and the United States from the following 2 cohorts: (1) The Vasculitis Patient-Powered Research Network (VPPRN), a self-enrolled secure portal with patient-entered data updated quarterly (2014-2019) and (2) the Vasculitis Clinical Research Consortium (VCRC) observational studies, a physician-entered database (2003-2019) of patients who fulfilled the 1990 American College of Rheumatology classification criteria for EGPA. The studied parameters included demographic characteristics, clinical manifestations, ANCA status, treatments, and relapses.ResultsData from 195 patients with a validated diagnosis of EGPA in the VPPRN and 354 patients enrolled in the VCRC were analyzed. Compared to the VCRC cohort, the patients in the VPPRN cohort were more likely to be female (135/195, 69.2% compared to 209/354, 59%; P=.02) and younger at diagnosis (47.3 compared to 50.0 years; P=.03); both cohorts reported similar frequencies of asthma (177/184, 96.2% in the VPPRN cohort compared to 329/354, 92.9% in the VCRC cohort; P=.13) and cardiac manifestations (44/153, 28.8% compared to 75/354, 21.2%; P=.06), but the VPPRN cohort reported less frequent lung manifestations other than asthma and more frequent disease manifestations in all other organ systems. The ANCA positivity was 48.9% (64/131) in the VPPRN patients compared to 38.9% (123/316; P=.05) in the VCRC cohort. Relapsing disease after study enrollment was reported in 32.3% (63/195) of patients in the VPPRN compared to 35.7% (99/277) of patients in the VCRC. Most therapies (GC, cyclophosphamide, mepolizumab) were used at similar frequencies in both groups, except for rituximab with VPPRN patients reporting more use than the VCRC cohort (47/195, 24.1% compared to 29/277, 10.5%; P<.001).ConclusionsOverall, patients and physicians report manifestations of EGPA at similar frequencies. However, observed differences between patient and physician reports imply the potential occurrence of selection biases. These results support the use of patient-reported data in EGPA but also the need for careful consideration of disease-specific definitions for the study of EGPA and how patient- and physician-reported data are collected.Trial RegistrationClinicalTrials.gov NCT00315380, https://clinicaltrials.gov/ct2/show/NCT00315380; ClinicalTrials.gov NCT01241305, https://clinicaltrials.gov/ct2/show/NCT01241305

Objectives: Previous studies have suggested differences in vasculitic and eosinophilic phenotypes based on anti-neutrophil cytoplasmic antibody (ANCA) positivity in eosinophilic granulomatosis with polyangiitis (EGPA). However, their relevance under the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria remains unclear. We aimed to evaluate the clinical features and outcomes of EGPA according to myeloperoxidase (MPO)-ANCA status in a Korean cohort. Methods: We conducted a retrospective cohort study that included 57 patients with EGPA without proteinase 3-ANCA positivity who fulfilled the 2022 ACR/EULAR classification criteria. Patients were classified into MPO-ANCA-positive (n = 25) and MPO-ANCA-negative (n = 32) groups. Clinical manifestations, laboratory findings, and outcomes, including all-cause mortality, relapse, end-stage kidney disease (ESKD), cerebrovascular accident (CVA), and acute coronary syndrome (ACS), were compared between the two groups. Results: MPO-ANCA-positive patients exhibited higher Five-Factor Scores (1.0 [0.0–1.0] vs. 0.0 [0.0–1.0], p = 0.038), lower Short Form 36 Physical Component Summary scores (35.0 [19.7–56.3] vs. 52.5 [43.5–69.7], p = 0.048), and elevated systemic inflammation markers (higher erythrocyte sedimentation rate: 58.0 [16.0–97.5] mm/hr vs. 25.5 [7.0–63.8] mm/hr, p = 0.026). Constitutional symptoms were more frequent among MPO-ANCA-positive patients (n = 14 [56.0%] vs. n = 3 [9.4%], p < 0.001), whereas no significant differences were found in vasculitic or eosinophilic manifestations. Kaplan–Meier analysis revealed no differences in the overall (p = 0.36), relapse-free (p = 0.80), ESKD-free (p = 0.87), CVA-free (p = 0.26), or ACS-free (p = 0.94) survival rates between the two groups. Conclusions: In Korean patients with EGPA classified under the 2022 ACR/EULAR classification criteria, MPO-ANCA positivity, as compared to ANCA-negative status, was associated with a higher disease burden and poorer quality of life but not with distinct vasculitic or eosinophilic manifestations and adverse outcomes.

Objective To investigate the value of antineutrophil cytoplasmic antibody (ANCA) in clinical phenotype of eosinophilic granulomatosis with polyangiitis (EGPA). Methods The clinical data of 64 patients with EGPA from Peking Union Medical College Hospital between 2007 to 2016 were retrospectively analyzed, and the patients were followed up. Characteristics of patients with ANCA positive and ANCA negative were compared by independent-samples t test, Mann-Whitney U test and Chi-square test. Results Among 64 patients with EGPA, 12(19%) were serum ANCA positive and 52(81%) were negative. The incidence of fever (77% vs 35%, χ2=9.403, P=0.002) and renal involvement, including proteinuria (67% vs 25%, χ2=7.678, P=0.006), hematuria (58% vs 8%, χ2=17.57, P<0.01), renal inadequacy (33% vs 4%, χ2=9.978, P=0.002) , and the BVAS score higher than 15 (92% vs 60%, χ2=4.440, P=0.035) in ANCA positive group were higher than ANCA negative group, while the presence of allergic rhinitis (17% vs 56%, χ2=5.969, P=0.015), mucocutaneous lesion (33% vs 65%, χ2=4.152, P=0.042) and cardiac involvement (8% vs 44%, χ2=3.361, P=0.021) in the ANCA-positive group was lower when compared with ANCA-negative patients. The positive ratio of rheumatoid factor (RF) (100% vs 42%, χ2=7.723, P=0.006), and the level of erythrocyte sedimentation rate (ESR) (50 vs 35.5 mm/1 h, P=0.034) in ANCA-positive group were higher than in ANCA negative group. There was no significant difference in pathological characteristics between the two groups. According to the treatment and prognosis, there were no significant differences between the two groups in the usage and dosage of steroids and immunosuppressant, the remission rate and recurrence rate of the disease, and the death rate due to the primary disease. Conclusion The clinical manifestations of EGPA are complicate. Whether ANCA is positive or not may be related to the clinical phenotypes. More attention should be paid to renal involvement in ANCA positive patients while cardiac involvement in ANCA negative patients. Key words: Polyangiitis; Phenotype; Churg-Strauss syndrome; Antineutrophil cytoplasmic antibody

BackgroundAtherosclerosis and its complications are one the leading cause of death in patients with anti-neutrophil cytoplasmic antibodies (ANCA)- associated vasculitis (AAVs), despite the recent remarkable improvements in prognosis. The mechanism...

CARDIAC MANIFESTATIONS OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystemic vasculitis which was previously called Churg-Strauss syndrome or allergic granulomatosis. It has an unknown pathogenesis, possibly autoimmune in nature. As it has a low incidence, there is only scant published literature. This case report is valuable to dermatologists, since skin involvement is one of the most common features of the vasculitic phase. This report represents one of the possible presentations of EGPA according to the antineutrophil cytoplasmic antibody status – which in our case was negative, with a low prognostic Five-Factor Score – that was successfully treated with oral steroids and azathioprine as a steroid-sparing agent. Our objective was to add a case report to the scarce existing literature in order to learn more about therapeutic options for EGPA. This case report demonstrates that oral steroids, as induction treatment, and azathioprine, as maintenance treatment, are effective in elderly patients with EGPA without involvement of any other organs. Nevertheless, additional studies are necessary to achieve appropriate management.

Background:In the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), neutrophils play a crucial role, serving as both the target cells attacked by ANCA and the main participating cells in...

Background:The activation of neutrophils via anti-neutrophil cytoplasmic antibodies (ANCA), degranulation and formation of extracellular traps (NETs) are central processes in the pathogenesis of ANCA-associated vasculitis. As a result of increased...

Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists