Microscopic Polyangiitis

This report assesses the observed risk of PML in patients treated with the anti-CD20 monoclonal antibody rituximab in the regulatory authority-approved autoimmune indications rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). This was a cumulative analysis of confirmed PML cases in patients receiving rituximab for RA or GPA/MPA from both spontaneous reports and clinical trial sources, as captured in the manufacturer global company safety and clinical databases. Overall reporting rates were calculated and patient case details were summarized. As of 17 November 2015, there were nine confirmed PML cases among patients who had received rituximab for RA and two for GPA. Corresponding estimated reporting rates were 2.56 per 100,000 patients with RA (estimated exposure ≈ 351,396 patients) and < 1 per 10,000 patients with GPA/MPA (estimated exposure 40,000-50,000 patients). In all cases, patients had ≥ 1 potential risk factor for PML independent of rituximab treatment. In the RA population, the estimated reporting rate of PML generally remained stable and low since 2009 despite increasing rituximab exposure. There was no pattern of latency from time of rituximab initiation to PML development and no association of PML with the number of rituximab courses. Global post-marketing safety and clinical trial data demonstrated that the occurrence of PML is very rare among rituximab-treated patients with RA or GPA/MPA and has remained stable over time.

ObjectiveAlthough a possible association among myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA), microscopic polyangiitis (MPA), and idiopathic pulmonary fibrosis (IPF) has been suggested, the clinical significance of MPO-ANCA in idiopathic interstitial pneumonias (IIPs), including IPF and non-IPF, remains unclear. We aimed to investigate the frequency of MPO-ANCA positivity, as well as MPA incidence and risk factors for development in patients initially diagnosed with IIP.MethodsWe retrospectively analysed 305 consecutive patients who were initially diagnosed as IIP and had MPO-ANCA results available.ResultsOf the 305 patients, 26 (8.5%) were MPO-ANCA-positive. Baseline characteristics were similar between the MPO-ANCA-positive and -negative patients. The cumulative 5-year MPA incidence was 24.3% in the MPO-ANCA-positive patients and 0% in the -negative patients (P ConclusionMPO-ANCA positivity was uncommon, but was associated with subsequent MPA development in patients initially diagnosed with IIP, including both IPF and non-IPF cases. The study suggested that attention should be paid to MPA development in MPO-ANCA-positive IIP patients with UIP pattern on HRCT and those without treatment for IIP.

BackgroundThe data from cohorts of childhood-onset granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) remain scarce and heterogeneous. We aimed to analyse the features at presentation, therapeutic approaches and the disease course of these rare diseases.MethodsElectronic searches of Medline and the Cochrane Central Register of Controlled trials database were conducted. We also checked the reference lists of the studies included and other systematic reviews, to identify additional reports. We included all cohorts, cross-sectional studies or registries reporting features at presentation or outcomes in patients with a diagnosis of childhood-onset GPA or MPA (age ResultsWe reviewed 570 full texts and identified 14 studies on GPA and 8 on MPA. Childhood-onset GPA and MPA occurred predominantly in female subjects during adolescence. For GPA, ear-nose-throat (ENT) disease (pooled prevalence 82 % [95 % CI 78-87]), constitutional symptoms (73 % [95 % CI 55-88]), renal (65 % [95 % CI 49-79]), and lower respiratory tract (61 % [95 % CI 48-74]) manifestations were the most frequently reported at presentation. Renal disease was a hallmark of MPA (94 % [95 % CI 89-97]). ANCA were detected in >90 % of children with GPA or MPA. Combined corticosteroids and cyclophosphamide was the most frequently used first remission-inducing treatment for GPA (76 % [95 % CI 69-82]) and MPA (62 % [95 % CI 20-96]). Relapses occurred more frequently in GPA (67-100 %) than in MPA (25-50 %). The leading causes of death were the disease itself, and infections.ConclusionsChildhood-onset MPA and GPA remain severe diseases with frequent relapses and a high cumulative morbidity. Survival and disease-free survival need to be improved.

ObjectiveTo analyze the diagnostic pathway of patients with ANCA-associated vasculitis (AAV) and to identify factors associated with the time to diagnosis, including the role of referring and previously consulted medical specialties.MethodsThis retrospective single-center study analyzed patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) who received their diagnosis between 2014 and 2024. Data were extracted from medical records. Time to diagnosis was defined as the period between first AAV-related symptoms and confirmed diagnosis. Factors associated with diagnostic delay were analyzed using multivariate Cox regression. Temporal differences between subtypes were visualized using Kaplan-Meier curves.ResultsA total of 216 patients were included (GPA n = 128; MPA n = 70; EGPA n = 18). Median time to diagnosis was numerically longest in EGPA (455 days [IQR 144-924]) compared with GPA (120 days [IQR 61334]) and MPA (153 days [IQR 90-366]). Renal involvement was statistically associated with a shorter time to diagnosis (HR 1.65, 95% CI 1.18-2.31, p = 0.004), whereas prior consultations with dermatologists (HR 0.41, p = 0.004), pulmonologists (HR 0.58, p = 0.003), and rheumatologists (HR 0.63, p = 0.003) showed longer delays. Higher BVAS and CRP levels statistically correlated with shorter diagnostic intervals.ConclusionThe diagnostic delay in AAV varies by disease subtype and clinical presentation. EGPA shows the numerically longest time to diagnosis, while renal involvement seems to facilitate earlier diagnosis. Enhanced awareness among non is essential to reduce diagnostic delay and prevent organ damage, although outcome measures were not assessed in our study. Key Points • Diagnostic delay in ANCA-associated vasculitis varies between disease subtypes, organ involvement, and consulted specialties. • EGPA shows the numerically longest diagnostic delay, whereas renal involvement seems to facilitate earlier diagnosis. • Earlier recognition of AAV across specialties may reduce diagnostic delay and prevent organ damage.