Double-seropositive anti-glomerular basement membrane (GBM) disease, characterized by the presence of both anti-GBM and anti-neutrophil cytoplasmic autoantibodies (ANCAs), is extremely rare in children. Double-seropositive patients represent a hybrid phenotype combining the severe acute kidney injury of isolated anti-GBM disease with the relapse risk and subsequent need for maintenance treatment of ANCA-associated vasculitis. Here we present the case of an 11-year-old girl presenting with rapidly progressive glomerulonephritis leading to kidney failure and warranting kidney replacement therapy. Anti-GBM antibodies and myeloperoxidase-ANCAs were both detected in serum. Kidney histopathology revealed over 90% crescents. Despite the aggressive presentation, treatment with high-dose corticosteroids, plasmapheresis, and rituximab led to recovery of kidney function and dialysis discontinuation. Our case suggests that rituximab, without cyclophosphamide, may represent a promising therapeutic approach in children with double-seropositive anti-GBM disease, even in severe presentations.

Autoimmune glomerulonephritis (GN) emerges when self-reactive humoral and cellular immunity converge in the kidney. Combined immunofluorescence and electron microscopy aids in classifying GN; however, more stratification strategies are required for personalized therapy. We aimed to review biopsy-anchored clinicopathologic classification and pathophysiology of GN-associated disorders based on immunofluorescence and electron microscopy. Additionally, we sought to integrate mechanistic insights from multiomics and spatial profiling that resolve the composition and spatial organization of the cellular "neighborhoods" that drive injury and repair across IgA vasculitis/nephropathy, lupus nephritis, antiglomerular basement membrane disease, and antineutrophil cytoplasmic antibody-associated vasculitis. Although inciting antigens, immune complexes, and deposition patterns vary among entities, downstream injury pathways overlap. The convergent programs include complement activation, including locally produced renal complement, Fc receptor-driven myeloid effector functions, neutrophil extracellular traps with nucleic-acid sensing, the reprogramming of monocytes/macrophages, interleukin (IL)-23/IL-17, and type 1 interferon-primed cytotoxicity of T cells, and epithelial stress responses in podocytes and parietal epithelial cells. Despite diverse triggers, autoimmune GNs share targetable injury pathways. Integrating biopsy-defined immune deposits and the accompanying inflammatory context with spatial, single-cell, and proteomic readouts enables mechanistic subtyping and pathway-aligned therapy. Tailoring treatment to individual dominant injury programs may improve renal outcomes and reduce adverse effects.

Idiopathic and granulomatosis with polyangiitis (GPA)-related subglottic stenosis (SGS) are considered distinct immune-mediated inflammatory disorders. Limited data exist on serum inflammatory markers, specifically C-Reactive Protein (CRP), for SGS diagnosis, differentiation, and prognostication. The study objective was the characterization of CRP levels in idiopathic (iSGS) and GPA-SGS to assess CRP's ability to distinguish SGS subtypes and predict SGS progression and recurrence. Retrospective review of patients with idiopathic or GPA-SGS from 2007 to 2024 at a single institution. Surgery-free interval (SFI) was calculated as the time between surgical interventions. Statistical analysis included independent t-tests, chi-squared, and univariate linear regression. 59 iSGS and 47 GPA-SGS patients were included. CRP was elevated in 36% of iSGS and 49% of GPA-SGS patients (0.0.6 mg/dL). Mean maximum CRP was 2.7 mg/dL lower in iSGS compared to anti-neutrophil cytoplasmic antibody (ANCA)-positive GPA-SGS (p = 0.035). The maximum CRP in iSGS was 3.6 mg/dL, while 10 (21%) GPA patients had CRPs greater than 3.6 mg/dL (max = 31 mg/dL). ANCA-negative GPA-SGS mean CRP was not significantly different than iSGS or ANCA-positive GPA-SGS. CRP and SFI did not correlate on univariate linear analysis. Mild elevation of CRP is common in SGS patients. High CRP levels are more frequent in GPA-SGS, potentially aiding clinical differentiation of etiologies. However, CRP at presentation does not appear to correlate with disease recurrence in iSGS or GPA-related SGS, limiting its value as a biomarker and prognostic tool.

"Eiffel-by-night" sign in hypertrophic pachymeningitis: Clinical and radiological correlates.

Takayasu arteritis (TAK) is a granulomatous large-vessel vasculitis typically affecting young adult females. Pediatric cases are rare, and infantile onset is exceptional. Management relies on immunosuppression, with surgery reserved for severe complications. We describe a now 5.5-year-old boy diagnosed with TAK at six months of age, presenting with hypertensive encephalopathy and kidney dysfunction. Despite treatment with corticosteroids and anti-TNFα, his kidney function deteriorated, leading to kidney failure and dialysis. At nearly three years of age, he underwent abdominal aorto-aortic bypass and bilateral nephrectomy due to progressive vascular narrowing and refractory hypertension. At age four, he successfully received a deceased-donor kidney transplant. Eighteen months post-transplant, he maintains excellent graft function and shows no signs of TAK recurrence. This case underscores the complexity of diagnosing and managing infantile TAK with multiorgan involvement. To our knowledge, he is among the youngest reported TAK patients to undergo successful kidney transplantation following major vascular surgery. His course demonstrates the potential for long-term remission and safe transplantation under standard immunosuppression, without continued anti-TNFα therapy. The literature is sparse regarding kidney failure and transplantation in TAK, particularly in infants. This case highlights key management dilemmas in infantile TAK, including clinical diagnosis, timing of surgery and transplantation, choice of immunosuppression, and long-term monitoring. It emphasizes the importance of a multidisciplinary approach and the need for collaborative research to address knowledge gaps in this rare but complex condition.

Functional classification of antineutrophil cytoplasmic antibody (ANCA) and its relation with clinical parameters of ANCA-associated vasculitis.

Avacopan, a complement component 5a (C5a) receptor antagonist, is an emerging therapeutic agent for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. However, its intrinsic efficacy remains unclear. A 74-year-old woman with granulomatosis with polyangiitis (GPA) presenting as a pulmonary mass, sinusitis, otitis media with hearing loss, and mononeuritis multiplex is reported. Initial remission was achieved with prednisolone and cyclophosphamide followed by maintenance with low-dose prednisolone and azathioprine. After 3 years, she relapsed with recurrent blood-stained sputum and enlargement of the pulmonary lesion despite negative ANCA titers. Infection and malignancy were excluded. Avacopan (60 mg/day) was introduced with low-dose prednisolone and azathioprine. Over 12 months, the pulmonary mass regressed, and blood-stained sputum improved, enabling complete withdrawal of prednisolone after 20 months. This case suggests a potential direct effect of avacopan on pulmonary inflammatory lesions in GPA and highlights the importance of long-term treatment evaluation. Cite this article as: Nakagomi D, Kubota S, Kobayashi Y, Hanai S. Regression of a refractory pulmonary lesion in granulomatosis with polyangiitis following the addition of avacopan. Eur J Rheumatol. 2026, 13, 0062, doi:10.5152/eurjrheum.2026.25062.

To examine contemporary trends in mortality due to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in Europe. We utilised publicly available data from Eurostat on deaths recorded with GPA or MPA as the underlying cause of death for the period 2011-2021. Crude and standardised mortality rates (SMRs) were calculated for each country and linear regression used to determine changes in mortality rates over time. Crude mortality rate was also stratified by age and sex. To investigate the association between geography and mortality rate, the SMR for each country was displayed on a choropleth map and plotted against the country's latitude. Our analysis of 29 European countries showed a stable mortality rate due to GPA and MPA between 2011-2021, but rising age at death median age-band 70-74 at the start and 75-79 at the end of the study period. There were differences between countries with the highest mortality rate in Denmark (SMR 31.03 per 10 million) and the lowest in Romania (SMR 0.77 per 10 million). Mortality rates were higher in adults aged over 80 years and there were more deaths in men compared with women. A latitudinal gradient in SMR was seen in GPA but not MPA, with the highest mortality rates in Scandinavia. Despite major advances in disease management, our results show that deaths due to GPA and MPA were stable over the last decade, indicating an ongoing need to improve the treatment of these diseases.

Rituximab (RTX) is a standard maintenance therapy for ANCA-associated vasculitis. Its efficacy in Japan remains unclear, where microscopic polyangiitis (MPA) predominates and clinical characteristics differ from Western-dominated RCT populations. Japanese patients with MPA or granulomatosis with polyangiitis (GPA) enrolled in a nationwide registry were included. Exposure was RTX use during maintenance therapy. The primary endpoint was major relapse-free survival at 104 weeks. The secondary endpoint was any relapse-free survival (major or minor) at 104 weeks. Baseline differences were adjusted using inverse probability of treatment weighting (IPTW) based on key demographic and disease-related covariates. A total of 389 patients were analyzed, with 85 in the RTX group. The RTX group included a higher proportion of GPA cases (37/85 vs. 74/304), resulting in baseline imbalance. After IPTW, no major relapses were observed in the RTX group, whereas the major relapse-free survival at 104 weeks was 94.8% in the non-RTX group. The RTX group showed significantly higher any relapse-free survival at 104 weeks (95.4% vs. 83.3%; HR for any relapse, 0.27; 95% CI, 0.09-0.74; p = 0.02). Our findings suggest that RTX may be an effective option for remission maintenance in Japanese patients with MPA or GPA.

Granulomatosis with polyangiitis (GPA), a subtype of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), is a systemic inflammatory disease that typically affects the respiratory tract and kidneys. However, atypical pancreatic manifestations have been reported, which may present clinically as acute pancreatitis or exocrine insufficiency, and radiologically as pancreatic enlargement or pseudotumour.A female in her 40s presented with nasal crusting and epistaxis. She subsequently developed fever, weight loss, haemoptysis, bilateral pulmonary nodules and a pancreatic tail mass. Pancreatic biopsy revealed caseating granulomatous inflammation, and antitubercular therapy was commenced.On developing haematuria and proteinuria, proteinase 3-ANCA testing and renal biopsy confirmed AAV. Treatment with rituximab and high-dose corticosteroids led to clinical improvement and radiological regression of both pulmonary and pancreatic lesions, consistent with systemic GPA involvement.This case highlights the importance of considering systemic inflammatory disease, alongside infective and malignant aetiologies, when evaluating pancreatic masses or focal pancreatitis with constitutional symptoms and multiorgan involvement.

Granulomatosis with polyangiitis (GPA) is traditionally regarded as a neutrophil-driven necrotizing vasculitis. However, the potential involvement of eosinophilic inflammation has not been fully elucidated. We investigated the contribution of eosinophilic inflammation to the pathogenesis of GPA, with a particular focus on eosinophil extracellular trap formation (EETosis). This retrospective study included 52 patients, including 25 with active GPA and 27 in remission. We recorded enzyme-linked immunosorbent assay-based serum concentrations of eosinophil-derived proteins (galectin-10, eosinophil cationic protein [ECP], eosinophil-derived neurotoxin [EDN]), neutrophil-derived proteins (myeloperoxidase [MPO]), and a marker for extracellular traps (citrullinated histone H3 [CitH3]) for these patients. EETosis in tissue samples of patients were examined by immunofluorescence staining. Serum-induced EETosis was evaluated in vitro. Serum concentration of galectin-10, ECP, EDN, CitH3, and C-reactive protein, and antineutrophil cytoplasmic antibodies-titre of patients with active GPA were significantly higher than those in remission. Galectin-10 had the strongest correlation with the Birmingham Vasculitis Activity Score (r=0.778, P<0.001). Increased galectin-10 levels were identified to be associated with the active stage after adjustment for glucocorticoid dose and eosinophil count. Receiver operating characteristic analyses of galectin-10 to discriminate between active and remission phases revealed an area under the curve of 0.923, with 85.2% sensitivity and 91.1% specificity. GPA lung tissue showed lytic eosinophils and EETosis. Additionally, serum from active GPA patients induced EETosis in vitro whereas that from remission patients did not. Eosinophil activation and EETosis may contribute to the disease activity of GPA, highlighting a previously underrecognized component of its pathogenesis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have consistent nephroprotective effects across diverse patient populations, including those with glomerular disease without diabetes mellitus. These somehow unexpected benefits cannot be solely explained by glycosuria and intrarenal hemodynamic effects. Experimental evidence largely supports the effects of SGLT2 inhibitors on several pathways, many of them outside the kidneys. This review explores the mechanisms underlying these benefits, focusing on those of importance in primary and secondary glomerulonephritis. In addition to glucose homeostasis, SGLT2 inhibitors exert local and systemic effects that mimic nutrient deprivation, impacting inflammation, immunity, autophagy, hypoxia responses, ferroptosis, lipotoxicity, and energy metabolism. Sodium-glucose cotransporter 2 inhibitors modulate inflammatory pathways through suppression of cytokines and NLR family pyrin domain containing 3 inflammasome activity, mechanisms relevant to immunoglobulin A glomerulonephritis, lupus nephritis, and anti-neutrophil cytoplasmic antibody-associated vasculitis. They also influence immune cell metabolism, inhibit T-cell activation, and potentially modulate B-cell and macrophage polarization. There is evidence that autophagy may show a dual role in glomerular disease. It could activate innate and adaptive immunity, so triggering the disease, or may protect podocytes, so reducing proteinuria and the risk of progression. Sodium-glucose cotransporter 2 inhibition also modulates the hypoxia inducible factor axis and reduces ferroptosis, possibly contributing to attenuate hypoxia-induced kidney damage. The upregulation of ketogenesis and activation of nutrient-sensing pathways (adenosine monophosphate-activated protein kinase-activated protein kinase, sirtuins, and mammalian target of rapamycin) further supports their role in metabolic reprogramming. Finally, they contribute to preserve gerosuppressor functions by increasing kidney Klotho, a protein with anti-aging, and-inflammatory, and antifibrotic effects, and liver betaine. Although direct clinical evidence on the specific molecular pathways targeted by SGLT2 inhibitors in glomerulonephritis remains limited, preclinical data and emerging human observations suggest SGLT2 inhibitors may offer therapeutic advantages beyond non-specific kidney-cardiovascular protection.

ABSTRACT Background Ureaplasma spp. are a rare cause of invasive disease outside of the neonatal period. Recent studies have shown that immunosuppression with B-cell depleting therapies, such as rituximab or obinutuzumab, can increase the risk of invasive infection. We present a case in which a patient receiving B-cell depleting therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis and pauci-immune nephritis was diagnosed with disseminated, invasive Ureaplasma infection. Case Summary A 17-year-old female with documented B-cell depletion presented to the emergency department from the pediatric infectious disease clinic with persistent shoulder pain. Within the first month of admission, the patient developed multifocal abscesses with joint involvement and an echodensity resembling a possible vegetation, all of which were unresponsive to broad-spectrum antibiotics. A broad-spectrum polymerase chain reaction test detected Ureaplasma urealyticum in aspirated joint fluid from multiple anatomic sites. Clinical improvement occurred after initiation of combination therapy with intravenous doxycycline and levofloxacin. Conclusion We describe a patient with documented iatrogenic B cell depletion presenting with a disseminated, multifocal invasive Ureaplasma infection including osteoarthritis, cellulitis, and soft tissue abscess. Following a 6-week course of levofloxacin, the patient’s C-reactive protein, fever, and pain resolved without further evidence of disease. This case report highlights the importance of considering disseminated, invasive Ureaplasma spp. when evaluating B-cell depleted patients with challenging multifocal symptom complexes. In addition, this case report highlights the critical role of molecular diagnosis in identifying this fastidious pathogen.

Beyond Classification: An Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Case

Interstitial Lung Disease (ILD) can occur in association with ANCA-associated Vasculitis (AAV-ILD) or as an isolated entity with positive ANCA (ANCA-ILD). However, data on the epidemiology and outcomes of these conditions remain limited. A European multicentre retrospective study encompassed patients with AAV-ILD or ANCA-ILD. Baseline and subsequent chest CT studies were centrally reviewed. Primary outcomes included forced vital capacity (FVC) decline, respiratory failure, and mortality. 162 patients (MPO-ANCA 85%); 123 (76%) had AAV-ILD and 39 (24%) ANCA-ILD. At baseline, Usual Interstitial Pneumonia (UIP) was the most frequent radiologic pattern (57%), while half had a radiological fibrosis grade >10%. Kidney involvement was present in 73%, most commonly Berden focal class. UIP and Non-specific interstitial pneumonia (NSIP) patterns showed greater annual FVC decline than other patterns (UIP: -1.99%, NSIP: -3.76%, [p=0.35] others: +0.36%). An adjusted mixed-effects model indicated that rituximab was associated with mean FVC % improvement at 12 months (+6.02%; p=0.07). Radiologic progression occurred in ~50%, mainly in younger patients with higher fibrosis severity grade. Respiratory failure (19%) was associated with fibrosis severity (grade 4: HR 4.7; p=0.029) and baseline FVC% (HR 0.95; p=0.002). Over a median 4.2-year follow-up, 48% died. Age (HR 1.08; p=0.04) and baseline FVC% (HR 0.97; p=0.05) were independent predictors of mortality. At baseline, higher fibrosis severity, UIP, and lower FVC% were associated with worse outcomes. Immunosuppressives, such as rituximab, may help preserve lung function. The need for early identification and individualized treatment in ILD associated with AAV or ANCA is underscored.

Overactivation of the complement system plays a role in the pathophysiology of several serious kidney diseases, such as immunoglobulin A nephropathy, complement 3 glomerulopathy, atypical hemolytic uremic syndrome, and antineutrophil cytoplasmic antibody-associated vasculitis. A key focus of recent research has been developing complement inhibitors to target the underlying disease mechanisms of these diseases and thereby improve patient outcomes. Currently, five complement inhibitors are approved by the United States Food and Drug Administration as effective for the treatment of kidney diseases: eculizumab, ravulizumab, avacopan, iptacopan, and pegcetacoplan. However, some of these therapies may increase the risk of serious, potentially life-threatening infections, particularly from encapsulated organisms including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b. Health care providers must recognize this risk and implement preventive measures when prescribing complement inhibitors. This review summarizes the infectious risks associated with complement inhibitors and highlights key clinical considerations for their safe and effective use in the treatment of kidney diseases. It is intended to serve as an accessible resource for providers utilizing these agents in clinical practice.

This case report demonstrates a paediatric patient with antineutrophil cytoplasmic antibody-associated vasculitis, most consistent with a diagnosis of granulomatosis with polyangiitis (GPA), who presented with extensive airway involvement. It highlights that, although rare, the potential occurrence of GPA can be clinically challenging.

Cytomegalovirus-induced severe enterocolitis associated with ANCA-associated vasculitis and diffuse alveolar haemorrhage in a child: a diagnostic and therapeutic dilemma.

ANCA are a key biomarker for ANCA-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Although indirect immunofluorescence (IIF) has traditionally been the reference technique, its diagnostic value in contemporary real-world practice remains uncertain. The aim of this study was to evaluate the diagnostic performance of IIF ANCA testing in routine clinical practice. We conducted a retrospective study of all patients with an ANCA request at a tertiary hospital over a 4-year period. All IIF-positive sera were subsequently tested for anti-PR3 and anti-MPO antibodies by chemiluminescent immunoassay (CLIA). Clinical data, test indication and final diagnoses were retrieved from electronic medical records. We included 5157 patients and IIF was positive in 653 (12.7%): perinuclear ANCA (P-ANCA) in 17.9%, cytoplasmic ANCA (C-ANCA) in 13.3% and atypical ANCA (A-ANCA) in 68.8%. CLIA was negative in 97.3% of A-ANCA. AAV was diagnosed in 47 patients, and 42 (89.4%) had positive IIF. For GPA and MPA, IIF showed a sensitivity of 93% and specificity of 88%, with a very high negative predictive value (NPV) (99.9%) but low positive predictive value (PPV) (6.1%). Specificity improved to 96.8% when restricted to typical patterns (C-ANCA or P-ANCA) and to 99.6% when combined with positive CLIA results >20 IU/ml. Almost all AAV cases were diagnosed in patients with high pre-test probability (such as renal disease, lung infiltrates or peripheral neuropathies) and interstitial lung disease was the most frequent non-AAV diagnosis in IIF-positive patients. ANCA IIF retains good diagnostic efficiency and a very high NPV for GPA and MPA, but has low PPV, particularly when tested for nonspecific symptoms.

Introduction: Primary central nervous system vasculitis (PCNSV) is a rare, heterogenous and polymorphic disorder affecting the blood vessels of the CNS. It is a diagnosis of exclusion with no disease specific clinical features, serological or imaging findings. Historically, the presence of hemorrhages was considered rare in PCNSV. However, with the advent of susceptibility weighted imaging (SWI) sequences of MRI, the presence of microhemorrhages has been found to be common despite macrohemorrhages being uncommon. Hypothesis: The presence of microhemorrhages in the cerebellar tonsils on SWI sequences of MRI brain in a patient with an unexplained neurological deficit are indicative of PCNSV. Methods: We retrospectively evaluated our biopsy proven PCNSV patients and patients with hypertensive cerebellar hemorrhage who underwent an MRI (1.5T or 3T) between 2020-2024. All clinic-radiological and histopathological details of these patients were entered into a predesigned proforma. A senior neuroradiologist evaluated the MRI scans for the presence of tonsillar microhemorrhages. Results: Twenty-nine patients of PCNSV (15- granulomatous vasculitis; 14 – lymphocytic vasculitis) and 44 patients with hypertensive cerebellar ICH fulfilled the study criteria. The clinical characteristics of the patients are mentioned in table 1. All PCNSV patients (100%) were found to have tonsillar microhemorrhages along with supratentorial and infratentorial lesions (T2/ FLAIR/ SWI) and 27/29 (93.1%) revealed punctate or linear enhancement of these tonsillar lesions (Figure 1). There was no difference in the microhemorrhage pattern between granulomatous and lymphocytic vasculitis subtypes of PCNSV. In comparison, only 9/44 (20.4%) patients with cerebellar hemorrhage had tonsillar microhemorrhages. Amongst them, all of them had pontine microhemorrhages while 6/9 (66.7%) and 5/9 (55.5%) had concomitant midbrain and medullary microhemorrhages respectively. Most patients with concomitant pontine microhemorrhages had no cerebellar tonsil involvement. Conclusions: Cerebellar tonsillar microhemorrhages in PCNSV may be a marker of its intrinsic microangiopathy. The presence of cerebellar tonsillar microhemorrhages in patients with an unexplained neurological deficit may be an imaging marker for diagnosing PCNSV.