Small Vessel Vasculitis Research Articles

Eosinophilic granulomatosis with polyangiitis is characterized as a small vessel vasculitis with the propensity to have a myriad of presentations due to the targeting of several different organ systems. More often than not, it is the pulmonary system that is affected. However, other reported presentations have included involvement of the skin, cardiovascular system, neurological system, renal, musculoskeletal, and even gastrointestinal tract in sequential order of increasing rarity. In most of these reported cases, only one or a couple of systems are involved. Here, the authors present a case of eosinophilic granulomatosis with polyangiitis that has peculiar and ominous involvement of both the neurological and gastrointestinal systems, lending to its extreme rarity as well as severity. A 69-year-old Eastern European female patient was diagnosed with eosinophilic granulomatosis with polyangiitis exhibiting extensive multisystem involvement. Her case included a rare documented instance of hemorrhagic shock secondary to ileal gastrointestinal bleeding, occurring concurrently with multiple cerebral vascular infarctions. This case highlights the complexity and severity of eosinophilic granulomatosis with polyangiitis when it involves multiple organ systems simultaneously. It emphasizes the importance of recognizing eosinophilic granulomatosis with polyangiitis as a differential diagnosis in patients presenting with multisystem disease and unexplained eosinophilia. The report also underscores the need for aggressive management strategies and vigilance in diagnosing rare manifestations such as gastrointestinal hemorrhage and recurrent cerebral ischemic strokes.

Immunoglobulin A vasculitis (IgAV) is a common immune complex-mediated systemic small vessel vasculitis in children. Gastrointestinal (GI) involvement significantly impacts early prognosis and may precede the appearance of purpura, complicating timely diagnosis. We retrospectively analyzed 195 cases of children diagnosed with IgAV from June 2019 to April 2024, among whom 62 cases had GI involvement. Clinical and laboratory data were collected. Children in the IgAV GI involvement group exhibited lower rates of arthritis/arthralgia and significantly higher levels of neutrophil-to-lymphocyte ratio (NLR) (P = .002, OR = 1.455), platelet count (P = .020, OR = 1.005), and uric acid (P = .017, OR = 1.005), with lower immunoglobulin G (IgG) (P = .004, OR = .818) levels. Multivariate analysis identified NLR, platelet count, uric acid, and IgG as independent predictors. The combined model showed good discrimination (area under the curve [AUC] = 0.753) and high specificity (93.2%). Elevated NLR, platelet count, uric acid, and reduced IgG are independent risk factors for GI involvement in pediatric IgAV and may facilitate early risk stratification.

Purpose: To describe a case of retinal vasculitis as a presenting sign of atypical neurosarcoidosis with occult central nervous system involvement. Methods: A case report and literature review are presented, highlighting the role of the ophthalmic examination and the importance of early neurologic workup for diagnosis and treatment. Results: A 27-year-old woman presented with monocular blurry vision, central scotoma, and headache. Ophthalmic examination demonstrated retinal vasculitis bilaterally, and systemic steroid treatment was initiated. Further neurologic workup with brain magnetic resonance imaging revealed multiple enhancing foci, consistent with features of inflammation. The neurologic disease was recalcitrant, showing no response to multiple steroid-sparing therapies over 2 years. Further workup was pursued, including a brain biopsy showing noncaseating granulomas with small-vessel vasculitis. The ophthalmic and neurologic presentation was consistent with a diagnosis of atypical neurosarcoidosis. Clinical resolution was ultimately achieved after treatment with infliximab. Conclusions: Retinal vasculitis should have a low threshold for initiating early neurologic workup to assess central nervous system involvement.

Antineutrophil Cytoplasmic Antibody (ANCA)-associated Vasculitis (AAV) is a life-threatening systemic autoimmune disease. Break of tolerance against either proteinase 3 or myeloperoxidase is key to the disease etiology. Innate and adaptive immune cells cooperate and contribute to the inflammatory necrotizing small-vessel vasculitis. AAV can affect every organ and frequently affects the kidneys. Necrotizing crescentic glomerulonephritis is associated with worse patient outcome. Anti-inflammatory and immunosuppressive treatments are effective in inducing acute vasculitis remission but are associated with treatment-related morbidity and mortality. In 2024, Kidney Disease: Improving Global Outcomes (KDIGO) provided an update of the Clinical Practice Guideline for the Management of AAV patients with kidney manifestation. A major aspect of the update is the consequent reduction of glucocorticoid exposure to diminish glucocorticoid toxicity. The C5a receptor blocker avacopan allows significant reduction of the cumulative glucocorticoids during AAV induction treatment, while increasing sustained remission and improving the glomerular filtration rate. Therefore, avacopan is now considered in the guideline as an alternative to glucocorticoids. Other topics covered by the KDIGO experts are the use of cyclophosphamide and rituximab or combinations thereof in patients with severe kidney involvement for inducing AAV remission. Moreover, considerations for the use of plasma exchange are provided.

Abstract Disclosure: C. Ng: None. N. Samad: None. A. Trinh: None. F. Milat: None. P. Wong: None. Thalassemia bone disease is a common and severe complication of β-thalassemia major (TM), resulting from marrow expansion, hormonal deficiency including hypogonadism, iron toxicity and increased bone turnover. These factors contribute to reduced bone mineral density (BMD) and increased susceptibility to minimal trauma fracture (MTF). Optimal transfusions/iron chelation therapy, management of hormone deficiencies and antiresorptive therapies are the cornerstone of management. There are currently no reports examining the efficacy of the anabolic Romosozumab in TM. We report the use of Romosozumab in 2 patients with TM and severe osteoporosis. A 65-year-old male with TM on deferoxamine chelation, also had small vessel vasculitis requiring high doses of corticosteroids. He had severe osteoporosis, with a T-score of -4.0 at lumbar spine and a 12% loss of BMD over 2 years. Despite 5 years of zoledronic acid (ZA) treatment, there was ongoing decline in BMD at both lumbar spine and hip and he sustained a new L3 fracture. Following 12 months of Romosozumab, there was a significant improvement in BMD of 42% at the lumbar spine, 12% at the femoral neck and 12% at the total hip with T-scores of -1.5, -1.5 and -1.4 at those sites respectively. He tolerated Romosozumab well and is currently undergoing consolidation treatment with ZA. A 58-year-old Jehovah’s Witness male with TM, osteoporosis and multiple fractures had been treated with various osteoporosis therapies over 20 years, including bisphosphonates, strontium ranelate and denosumab. However, this patient continued to suffer MTF and progressive declines in BMD. Even after switching from 6-monthly to 3-monthly denosumab, his bone turnover markers remained elevated (C-telopeptide: 470ng/L; normal range 150-800ng/L) and he sustained supracondylar femoral and humeral fractures following a fall. Romosozumab was then initiated and was well tolerated. He achieved an increase in procollagen type 1 propeptide (P1NP) from 34μg/L to 130μg/L at 3-4 months (normal range 15-70 µg/L). A follow-up DXA scan after 12 months of treatment demonstrated a 6% improvement in BMD at the right hip (T-score: -2.9) and stability at the lumbar spine. This is the first case series of Romosozumab in the treatment of osteoporosis in patients with TM. The observed BMD gains were significant despite previous prolonged exposure to anti-resorptive therapy, and thus represents a promising treatment option in patients with TM and osteoporosis. A clinical trial to confirm these benefits is required. Presentation: Saturday, July 12, 2025

Point-of-Care Risk Factors for Systemic Disease in Patients With Small Vessel Vasculitis of the Skin

Abstract Background and Aims IgA vasculitis (IgAV) is a small-vessel vasculitis with predominant IgA deposits that involves the skin, the joints, the gastrointestinal tract and the kidneys, causing glomerulonephritis pathologically indistinguishable from IgA nephropathy [1]. Adults are less frequently affected than children but more often experience a relapsing/refractory course with severe kidney involvement [2]. As the treatment of this condition remains controversial, especially for adults, we have been working on developing recommendations for the management of adult-onset IgAV. Here, we report on the progress of this initiative with a focus on kidney involvement. Method The European IgA Vasculitis Study Group (EUGAVAS) is a multidisciplinary group of experts in the field of IgAV established in 2023. Members were initially asked to vote on key questions using a Delphi approach and questions that achieved a level of agreement ≥70% drove a systematic literature review (SLR) on Medline/Pubmed, Cochrane and Embase databases. Small working groups of 4–5 members drafted recommendation statements based on the SLR results and, where required, expert opinion. The preliminary statements were then discussed and amended by the whole group and are currently being voted on in the second Delphi round. The initiative was endorsed by the European Vasculitis Society (EUVAS). Results EUGAVAS consists of 38 experts, including 11 nephrologists, 10 internists/rheumatologists, four dermatologists, four pediatricians, four fellows, two pathologists, one representative IgAV patient, one vasculitis nurse, and one methodologist. Following the first Delphi round, 14 out of 16 key questions were retained. The SLR identified 335 relevant publications out of 3,784 abstracts reviewed (1,058 excluded as duplicates). The group agreed that the level of evidence available in the literature was insufficient to establish guidelines and drafted recommendation statements. Of the 14 preliminary statements, three focus on diagnosis and classification, three on disease staging, six on treatment, including general and organ-specific principles, and two on disease assessment and patient follow-up. Four statements are specifically dedicated to kidney involvement and discuss: 1) definition of kidney involvement and role of baseline prognostic factors; 2) indications to kidney biopsy and histological classification; 3) goals of treatment and options according to severity of kidney involvement; 4) role of nephroprotective measures. Kidney involvement is also discussed in other statements on definition of response and remission, use of biologic therapies, such as rituximab, and frequency and modality of patient follow-up. Conclusion A set of recommendations on management of adult-onset IgAV has been developed following a standardized approach and will soon be available for communication. The result of this initiative may help clinicians, especially nephrologists, manage patients with this condition and improve their prognosis.

Henoch-Schönlein purpura (HSP) also known as IgA vasculitis is a systemic small vessel vasculitis mainly affecting the skin, kidneys, joints, and gastrointestinal tract. However, the disease can affect any organ system of the body. The classic tetrad of presentation in Henoch-Schönlein purpura includes palpable purpura, joints pain, abdominal pain sometimes associated with bleeding, and renal disease. Pulmonary and pleural involvement in HSP is a rare manifestation and occurs more commonly in adults than in children. We report the case of a 67-year-old woman with diabetesand HSP complicated by pulmonary haemorrhage and pleural effusion. She was managed initially with pulse Methylprednisolone and Cyclophosphamide followed by a course of oral steroids. An excellent outcome was achieved. Keywords: Henoch-Schönlein purpura, IgA vasculitis, Pleural effusion, Pulmonary haemorrhage, Case Report.

HighlightsWhat are the main findings?•In this five-year, single-centre South-Indian pediatric cohort of Henoch–Schönlein purpura (HSP; n = 41), palpable purpura was universal, most often on the lower limbs (~95%), with frequent joint involvement (73.1%) and abdominal pain (61.0%) at presentation. Renal involvement occurred in 17% and was observed only in children aged ≥6 years, typically as microscopic haematuria with proteinuria (ISKDC II–III in the two biopsied cases). Rash relapse was uncommon (7.3%) and clustered with joint and abdominal symptoms at baseline; no relapsed child had nephritis, suggesting that the biology of cutaneous recurrence and renal morbidity may differ.•Management reflected severity (NSAIDs 71.6%, corticosteroids 31.7%, dapsone 24.4%), and renal outcomes were favourable at a mean 18.9-month follow-up (one child on long-term antihypertensives; no progression to end-stage renal disease). Clinically, these data support age-targeted urine and BP surveillance from ≥6 years. It also indicates that relapse risk tracks with systemic (joint/abdominal) features rather than renal disease.What is the implication of the main finding?•Age ≥6 years should be treated as a pragmatic bedside flag for nephritis risk in HSP. Prioritize early and frequent surveillance (urine dipstick and blood pressure weekly for the first month, then monthly up to 6 months).•Concurrent joint and abdominal symptoms at onset identify children at higher risk of cutaneous relapse rather than renal disease; plan relapse-focused follow-up and counselling accordingly.•Routine inflammatory markers (ESR/CRP) were not predictive of nephritis and should not replace targeted clinical monitoring.Background/Objectives: Henoch–Schönlein purpura (HSP), or IgA vasculitis, is the most common small-vessel vasculitis in children, yet Indian cohort data remain limited. We aimed to describe the clinical profile, renal involvement, treatment patterns, relapse, and outcomes of pediatric HSP at a tertiary centre in South India. Methods: We conducted a retrospective review of children <18 years diagnosed with HSP (January 2013–October 2018) using EULAR/PRINTO/PRES criteria. Demographics, clinical features, laboratory parameters, treatments, and outcomes were abstracted from records and analyzed in SPSS (descriptive statistics; Chi-square/Fisher’s exact and t/non-parametric tests as appropriate). Subgroup comparisons included renal vs. non-renal disease and age <6 vs. ≥6 years. An exploratory analysis examined predictors of nephritis. Results: Of 43 children identified, 2 were excluded (misclassified as systemic lupus erythematosus); 41 were analyzed. Mean age was 8.5 years (range 3–17), male: female 1.4:1. A preceding febrile illness or upper respiratory tract infection was noted in 41.4% and 17%, respectively. Palpable purpura was universal; joint involvement 73.1%, abdominal pain 61.0%, vomiting 41.5%. Renal involvement 17% occurred only in children ≥6 years; exploratory testing supported a strong age-linked signal for nephritis. Laboratory abnormalities included anemia (48.7%), thrombocytosis (19.5%), and elevated ESR (51.2%). Skin biopsy (n = 29) showed IgA and complement deposition; renal biopsy (n = 2) showed ISKDC grades II–III. Treatments included NSAIDs 71.6%, corticosteroids 31.7%, and dapsone 24.4% (used for severe systemic/persistent cutaneous disease). Rash relapse 7.3% clustered with joint plus abdominal symptoms and was not observed among children with nephritis. At a mean 18.9-month follow-up, one child required long-term antihypertensives; no child progressed to end-stage renal disease. Conclusions: Pediatric HSP in this South-Indian cohort followed a largely self-limited course with favourable renal outcomes. Age ≥6 years flagged higher renal risk, supporting age-targeted urine and blood-pressure surveillance, while relapse appeared to follow a non-renal trajectory (joint/abdominal clustering). Steroid and dapsone use reflected clinical severity rather than relapse risk. Findings align with Indian series and suggest lower renal morbidity than some East-Asian reports, adding region-specific evidence to guide monitoring and counselling.

Pregnancy outcomes in patients with systemic vasculitis in the USA from 2007 to 2022: an administrative claims-based study.

IntroductionPrimary angiitis of the CNS (PACNS) is a rare inflammatory disorder affecting blood vessels of the brain and spinal cord causing acute stroke. This study aimed to describe clinical, biochemical, imaging and histopathological findings of a retrospective single-center PACNS cohort in comparison to a cohort of secondary angiitis of CNS (SACNS).MethodsAll consecutive patients diagnosed with PACNS or SACNS between 2000 and 2023 were identified using our institutional database. Univariate comparison between both groups and multivariate analysis for independent predictors was performed, as well as Receiving Operating Characteristic analysis for white blood cell count predictive of PACNS. Kaplan–Meier curves were used for evaluating survival outcomes.ResultsWe identified 20 patients in each group. PACNS patients presented more frequently with seizures (40% vs. 5%, p = 0.02) and pseudotumoral lesions (45% vs. 10%, p = 0.014). In PACNS patients, median serum WBC count at diagnosis was lower (8.4×103/mm3 [6.4–9.9] vs. 11.2×103/mm3 [9–13.6] p = 0.027) and [18F]FDG-PET/CT (p = 0.001) was negative in all cases. No significant differences were observed for lumbar puncture profiles and diffusion weighted imaging patterns. Small-vessel vasculitis with a lymphocytic pattern was the most represented histologic phenotype in both groups. Serum WBC count ≤9.93 ×103/mm3 was the only independent predictor of PACNS using multivariate analysis [OR 95%CI 5.107, (1.177–22.159)]. Both groups did not differ in terms of mortality, relapse and clinical outcome.ConclusionIn our study, PACNS patients presented more often with pseudotumoral lesions, seizures and small-vessel involvement and lymphocytic histologic pattern. WBC count ≤9.93×103/mm3 was an independent predictor of PACNS diagnosis.

Evaluation of the concordance between clinical diagnosis and biopsy in cutaneous vasculitis.

Cutaneous small vessel vasculitis (CSVV) is an immune-mediated inflammatory disorder affecting the small dermal vessels and is often linked to autoimmune diseases, infections, or malignancies. Renal cell carcinoma (RCC), a common urologic malignancy, rarely presents with CSVV as a paraneoplastic manifestation. This case describes a 68-year-old woman with a history of left radical nephrectomy for clear cell RCC who presented with persistent flank pain and progressive purpuric, painful lesions on her lower limbs. Imaging revealed recurrent metastatic disease in the left retroperitoneum with inferior vena cava (IVC) involvement and a hypermetabolic right supraclavicular lymph node. Skin biopsy demonstrated neutrophilic infiltration and features of leukocytoclastic vasculitis, while immunohistochemistry confirmed the paraneoplastic nature of the vasculitis with positivity for IgM, vimentin, and cytokeratin. Initiation of sunitinib therapy resulted in significant improvement of the cutaneous lesions and tumor regression, followed by successful tumor debulking and IVC reconstruction. This case underscores the importance of considering paraneoplastic vasculitis in the differential diagnosis of new or atypical skin manifestations in patients with a history of RCC. Timely recognition and targeted therapy can improve outcomes and provide valuable insights into the broader systemic impact of malignancies like RCC.

Introduction:Leukocytoclastic vasculitis (LCV) is a small-vessel vasculitis characterized by immune complex deposition presenting with palpable purpura and petechiae. While commonly associated with systemic conditions such as infections and autoimmune diseases, LCV can be triggered less commonly by hematologic malignancies. Plasma cell disorders may lead to LCV through immune dysregulation and abnormal immunoglobulin production.1 The association between plasma cell dyscrasias and LCV emphasizes the importance of thorough evaluation in patients presenting with vasculitis, specifically those with underlying immunologic conditions. Case:A 60-year-old man with a history of monoclonal gammopathy of undetermined significance (MGUS) and systemic lupus erythematosus (SLE) with cutaneous features presented with petechiae, weight loss, and sixth months of constitutional symptoms. A punch biopsy confirmed LCV. Imaging revealed mesenteric and paraspinal nodules, and biopsy identified plasmacytoma. Laboratory evaluation showed elevated immunoglobulins (IgG 6000 mg/dL, IgA 2000 mg/dL) and markers of immune dysregulation. The patient’s course was complicated by septic shock, necessitating intensive care. Despite this, he stabilized and initiated dermatology-directed treatment for cutaneous lesions. Subsequent autologous hematopoietic stem cell transplantation and chemotherapy led to improvement in both systemic and cutaneous disease. Conclusion:This case highlights LCV as a paraneoplastic syndrome and a potential harbinger of plasma cell malignancy. Notably, resolution of LCV was achieved following definitive treatment of the underlying malignancy, emphasizing the importance of systemic therapy. Recognition of LCV as a manifestation of hematologic malignancy necessitates thorough evaluation, particularly in patients with pre-existing plasma cell disorders.

Lymphocytic and granulomatous cutaneous small-vessel vasculitis after polyadenosine diphosphate-ribose polymerase inhibitor therapy.

Behçet's disease (BD) is a chronic, relapsing, systemic vasculitis that can involve both arteries and veins. Ocular involvement, including non-granulomatous panuveitis and occlusive retinal vasculitis, is common and a significant cause of morbidity. Erenumab is a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor approved for migraine prevention Although it is generally well tolerated, recent concerns have emerged regarding its vasoconstrictive potential in patients with underlying vascular disorders. We report a case of a 44-year-old woman with a history of BD, well-managed with azathioprine and methotrexate, who developed painless, bilateral subacute visual loss eleven days after receiving her second monthly dose of erenumab. This occurred during a BD flare marked by oral ulcers and severe migraine. Despite corticosteroid treatment, visual acuity did not improve. Erenumab was discontinued, but at her following visit four weeks later, vision remained impaired and visual fields showed blind spot enlargement and nonspecific defects. We hypothesize that the patient's visual loss was due to secondary ischemia from BD-associated small-vessel vasculitis, potentially exacerbated by CGRP receptor blockade from erenumab, which may have impaired compensatory vasodilation in the optic nerve or retinal circulation. This case represents the first report of permanent bilateral visual impairment associated with CGRP antagonist use in a patient with BD. Recent FDA labeling updates for CGRP-targeting agents now caution against use in patients with preexisting vascular disease, including risk of hypertension and Raynaud's phenomenon. This case underscores the need for heightened caution when prescribing CGRP inhibitors to patients with systemic vasculitic disorders and highlights the importance of further investigation to better define the safety profile of these agents in individuals with underlying vascular disease.

ObjectivesImmunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis characterized by perivascular IgA deposition and neutrophil activation. Elafin, an anti-inflammatory and anti-protease protein expressed by epithelial and select immune cells, may play a role in modulating vascular inflammation. We evaluated serum elafin levels in pediatric patients with IgAV during active stage and remission, and investigated their associations with disease activity, organ involvement, and systemic inflammatory markers.MethodsThis single-center prospective case-control study included 51 pediatric patients diagnosed with IgAV and 54 age- and sex-matched healthy controls. Paired data were obtained from the same IgAV patients during the remission phase, allowing intra-individual comparisons. Serum elafin levels were quantified using enzyme-linked immunosorbent assay (ELISA). Inflammatory parameters, including complete blood counts, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), were assessed in all participants.ResultsSerum elafin levels were significantly elevated in patients with IgAV (45.43 ± 11.11 ng/dL; range: 34.02–69.28) compared to healthy controls (27.44 ± 12.66 ng/dL; range: 0.01–41.84) (p < 0.001), with the highest concentrations observed during active disease stage (p < 0.001). Patients with visceral involvement (gastrointestinal, renal, or scrotal) exhibited significantly higher elafin levels (p < 0.05), whereas no significant association was found with isolated skin or joint involvement. Serum elafin levels demonstrated positive correlations with the ESR (p = 0.001, r = 0.418), CRP (p < 0.001, r = 0.547), neutrophil-to-lymphocyte ratio (p = 0.002, r = 0.355), and systemic immune-inflammation index (p = 0.003, r = 0.347). Receiver operating characteristic curve analysis identified an optimal serum elafin cut-off value of 35.38 ng/dL for distinguishing active IgAV, yielding a sensitivity of 86.2% and specificity of 77.8%.ConclusionSerum elafin levels were significantly elevated during the active stage of IgAV and may serve as a potential biomarker for disease activity, particularly in patients with visceral involvement.

Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease characterized by necrotizing small-vessel vasculitis, commonly involving the head and neck region, facial palsy is an uncommon head and neck presentation of GPA, and bilateral facial palsy is exceedingly rare. We present the case of a patient who presented with bilateral acute facial paralysis with final diagnosis of GPA to raise awareness of this rare presentation of GPA. retrospective chart review. We present a case of a 52-year-old female, who presented with right-sided facial paralysis started 6 weeks earlier and left sided facial nerve paralysis started 5 days before presentation. In addition, patient suffered from severe bilateral mixed hearing loss and otorrhea. Physical exam revealed polypoid tissue occluding the ear canal and purulent otorrhea. Computed tomography showed completely opacified mastoids bilaterally without bony erosion, and without evidence of cholesteatoma on magnetic resonance imaging. No evidence of nasal, respiratory, or renal involvement was detected. Extensive lab work was within normal limits, besides elevated C-reactive protein and positive serine-proteinase 3 (PR3). Patient underwent left mastoidectomy with facial nerve decompression. The left middle ear space and mastoid were filled with dense granulation tissue. The facial nerve was decompressed and found to be intact to nerve stimulation. Pathology report was positive to PR3, confirming the diagnosis of GPA. She was started on rituximab and prednisone, and 6 weeks after surgery, the patient had improved otalgia, as well as significant improvement in left FN function to HB II, with right FN function at HBV. In the existing literature, there are 14 cases of bilateral facial palsy as a presentation of GPA, however, this presentation is the first in the existing literature without evidence of systemic involvement. This highlights that the absence of other systemic involvement and negative initial autoimmune workup does not exclude GPA as the etiology of facial palsy. Continued re-evaluation of systemic involvement and biopsies of middle ear contents is crucial in diagnosis.

INTRODUCTION IGA VASCULITIS IGAV, FORMERLY HENOCH-SCHÖNLEIN PURPURA IS A SYSTEMIC SMALL-VESSEL VASCULITIS THE AETIOLOGY OF IGAV IS MULTIFACTORIAL, INVOLVING ENVIRONMENTAL TRIGGERS IN GENETICALLY SUSCEPTIBLE INDIVIDUALS EVOLVING SOCIOECONOMIC AND ENVIRONMENTAL FACTORS MAY BE ALTERING THE CONTEMPORARY AETIOLOGICAL AND PRECIPITANT SPECTRUM OF IGAV PROSPECTIVE OBSERVATIONAL STUDIES ARE THEREFORE CRUCIAL FOR ELUCIDATING DISEASE MANAGEMENT, PROGNOSTIC FACTORS AND LONG-TERM OUTCOMES ALTHOUGH NUMEROUS STUDIES EXIST ON PAEDIATRIC IGAV, PROSPECTIVE COHORT DATA REMAIN LIMITED THIS MULTICENTRE PROSPECTIVE OBSERVATIONAL STUDY AIMS TO CHARACTERISE THE NATURAL HISTORY, AETIOLOGICAL/PRECIPITANT SPECTRUM, INCIDENCE AND OUTCOMES OF GASTROINTESTINAL AND RENAL INVOLVEMENT, FACTORS INFLUENCING THERAPEUTIC EFFICACY AND THE PREDICTIVE VALUE OF BIOMARKERS FOR DISEASE ACTIVITY: METHODS AND ANALYSIS: We will recruit 478 paediatric patients with newly diagnosed IgAV across multiple centres. Participants will undergo prospective longitudinal assessment at disease onset and at 1, 3, 6 and 12 months postdiagnosis. Standardised evaluations will include clinical manifestations, physical examinations, laboratory parameters and patient-reported outcomes. The data will be analysed statistically with SPSS software (V.27.0), adopting a significance threshold of p<0.05 and using 95% CIs for statistical inference. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (2024-K0480), the Ethics Committee of the First People's Hospital of Yulin (YLSY-IRB-SR-2025060), the Medical Research Ethics Committee of the Liuzhou Workers' Hospital (KY2024356) and the Ethics Committee of the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region (No. (2025-1)003) and written informed consent was obtained from all the parents or guardians of the patients involved. It will be disseminated by publication of peer-reviewed manuscripts and presentation in abstract form at national and international scientific meetings. TRIAL REGISTRATION NUMBER: ChiCTR2500099716.

We review the current standards of treatment and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management of anti-glomerular basement membrane (anti-GBM) disease. Anti-GBM disease is a unique form of small vessel vasculitis affecting the glomerular and pulmonary capillaries. It is caused by autoantibodies directed against the α3 chain of type IV collagen, leading to rapidly progressive glomerulonephritis with pulmonary haemorrhage in ∼50% of cases. Diagnosis relies on clinical features, kidney biopsy showing linear IgG deposition along the glomerular basement membrane, and/or detection of circulating anti-GBM antibodies. Historically, untreated disease was rapidly fatal, but the introduction of plasma exchange combined with cyclophosphamide and glucocorticoids has significantly improved outcomes, particularly in patients who are not dialysis-dependent at presentation. Dialysis-dependent patients have a lower likelihood of renal recovery, and treatment decisions must consider biopsy findings, clinical severity, and potential contraindications to standard immunosuppression. Unlike ANCA-associated vasculitis, relapses are rare in classic anti-GBM disease, and long-term maintenance immunosuppression is not routinely required. However, 'double positive' patients (anti-GBM and ANCA) have a higher relapse risk and require maintenance immunosuppressive treatment. Atypical anti-GBM presentations, including seronegative cases, are now better recognized but their optimal management remains unclear. Future research should define the use of oral versus intravenous cyclophosphamide in anti-GBM disease, clarify the role of rituximab, and determine the place of emerging therapies such as imlifidase. Advances in risk stratification and ongoing trials are expected to inform treatment individualisation and to improve treatment approaches for this aggressive autoimmune disease.