Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease often leading to rapidly progressive glomerulonephritis. Oxidative stress plays a critical role in the development and progression of ANCA-associated glomerulonephritis (AAGN), but the underlying mechanisms remain poorly understood. Targeting genes related to oxidative stress may provide novel insights and supplementary therapeutic benefits for AAGN. In the current study, we obtained differentially expressed genes from AAGN-related microarray datasets in the Gene Expression Omnibus database, and oxidative stress-related genes (OSRGs) from the GeneCards and Gene Ontology databases to identify differentially expressed OSRGs. Then, by integrating weighted gene co-expression network analysis, and machine learning algorithms, we identified four upregulated hub OSRGs (all p < 0.01) with strong diagnostic potential (all AUC > 0.9)-CD44, ITGB2, MICB, and RAC2 - in the AAGN glomerular training dataset GSE104948 and validation dataset GSE108109, along with two hub OSRGs (all p < 0.05) with better diagnostic potential (all AUC > 0.7) - upregulated gene VCAM1 and downregulated gene VEGFA-in the AAGN tubulointerstitial training dataset GSE104954 and validation dataset GSE108112. The GSEA analysis suggested that these hub genes may play a role in inflammatory and immune response processes. Moreover, we constructed regulatory networks and identified drugs that potentially target these hub genes. It's to be noted that RAC2 and ITGB2 were associated with cyclophosphamide in the AAGN glomerular compartment, while VCAM1 and VEGFA were associated with dexamethasone in the tubulointerstitial compartment. This study offers novel insights into immune-associated OSRGs within the glomerular and tubulointerstitial compartments of AAGN which may serve as innovative targets for diagnosing and treating AAGN.

The primary purpose of our study was to perform a comprehensive systematic review, aiming to bring out the association between gut microbiota, Henoch-Schönlein Purpura (HSP) and Henoch-Schönlein nephritis (HSPN) patients.

A systematic review was performed using five electronic databases, including Medline (through PubMed), Scopus, Embase, Cochrane, and Web of Science, from inspection up to March 21, 2024, to detect the studies that assessed the gut microbiota variation in Henoch-Schönlein Purpura (HSP) and Henoch-Schönlein nephritis (HSPN) patients.

Microbial diversity, richness, and composition in HSP patients are decreased compared to the healthy control group. In addition, HSP patients display a different microbiota structure and show a significant difference in taxonomic abundance between HSP and health control, which differs from one level to another. At the phylum level, Bacteroidetes, Fusobacteria, and Blastocladiomycota were more abundant; at the class level, Bacteroidetes were more abundant; at the order level, Bacteroidetes were more abundant in the HSP group-stage and site of HSP involvement effect on microbiota. Gastrointestinal tract involvement is characterized by increased abundance of Streptococcus and Fusobacteria and a decrease in Faecalibacterium. Kidney involvement is characterized by increased abundance of Streptococcus spp, which can be used as an indicator of disease severity. Escherichia-Shigella can be used as a diagnostic for the recurrence of HSP because its abundance is higher than primary HSP.

Gut microbiota can be utilized to assess the severity, recurrence, and site of HSP infection by analyzing the diversity, richness, and abundance of specific microorganisms associated with the condition.

There is no consensus-based treatment for adult-onset immunoglobulin A vasculitis with nephritis (IgAV nephritis). Tonsillectomy is a treatment option for primary IgA nephropathy, which has similar histopathological features and pathogenesis to IgAV nephritis. The present case series aimed to describe the clinical course of patients with IgAV nephritis who underwent tonsillectomy in our institution. Adult patients with biopsy-proven IgAV nephritis who received tonsillectomy from 2015 to 2022 were systematically reviewed at six hospitals in Japan. Hematuria, proteinuria and slope of the estimated glomerular filtration rate (eGFR) were evaluated before and after tonsillectomy. Patients with IgAV nephritis who underwent tonsillectomy was identified in 12 of 2626 kidney biopsies performed during the study period. The median observation periods before and after tonsillectomy were 20.7 and 48.6 months, respectively. The following drugs were administered concurrent with tonsillectomy: corticosteroids (n = 8), mizoribin (n = 1), and rituximab (n = 1). Three patients were not treated with corticosteroids or immunosuppressants. During post-tonsillectomy observation, 5 patients showed remission of hematuria. Of the 10 patients whose proteinuria was not at a remission level prior to tonsillectomy, 7 showed remission of proteinuria after tonsillectomy. The eGFR slope was attenuated in 9 patients after tonsillectomy relative to before tonsillectomy. This study suggests that some patients may benefit from tonsillectomy in the treatment of IgAV nephritis. The efficacy of tonsillectomy or combination therapy with immunosuppression for IgAV nephritis requires further case series to clarify the clinicopathologic picture of patients associated with a response to tonsillectomy.

Primary Angiitis of Central Nervous System (PACNS) is a rare disease featured by transmural inflammation in vessels pertaining to brain, leptomeninges and spinal cord. It is a rare disease and the involvement of the spinal cord represents a rarer and not yet completely investigated subtype.

We performed a systematic search of the available literature on Pubmed and Embase, adding backward and forward citations, in order to retrieve the reported cases of PACNS i9nvolvimeng the spinal cord without time limitations. The main aim is to retrieve information about clinical and demographic features, pathological and neuroradiological findings on brain and spinal cord, and, finally, treatment and outcome.  RESULTS: The search provided 33 papers (mainly individual case reports) and 38 patients, with a large age frame (from 12 to 70 years of age), mainly adults. Among these ones 36/38 received a pathological diagnosis and granulomatous pattern was the main reported one. The description of spinal cord involvement in MRI is variable form extensive tumefactive lesions to spinal roots prominent involvement. The mortality is high (29% at the end of the individual follow-up).   DISCUSSION: As in non-spinal involvement, the main limitation of the retrieved cases is the inhomogeneity of the diagnostic and therapeutic pathway with underusing and underreporting of neuroradiolgoical techniques relevant for the diagnosis according with the available diagnostic criteria. Spinal cord involvement confirms its rarity, but it has been associated to a high disability and mortality and the diagnosis of PACNS has therapeutic consequences.  CONCLUSIONS: Spinal cord involvement is present in a minority of PACNS cases with a variety of neuroradiological and pathological findings. The standardization of the diagnostic pathway could help to improve the quality of information in prospective studies.

To describe the characteristics and outcome of patients with the association of large vessel vasculitis (LVV, Takayasu arteritis [TA] or GCA) and IBD.

An observational, multicentre, retrospective case-control study. Cases were LVV-IBD patients from European countries, whereas controls had isolated LVV (iLVV).

A total of 39 TA-IBD and 12 GCA-IBD cases were enrolled, compared with 52 isolated GCA (iGCA) and 93 isolated TA (iTA) controls. LVV occurred after IBD in 56% in TA-IBD and 75% in GCA-IBD, with a median interval of 1 year (interquartile range [IQR] 1-7) in TA-IBD and 8.6 years (IQR 1-17.7) in GCA-IBD. Crohn's disease was more common in TA-IBD (67%), whereas ulcerative colitis was more common in GCA-IBD (58%). Compared with iTA, TA-IBD were significantly younger at diagnosis of TA (median age 27 vs 37 years, P < 0.001) and had more upper limb claudication (36% vs 12%, P = 0.006). GCA-IBD patients had more frequent arterial thickening or stenosis than controls (75% vs 30%, respectively, P = 0.044) and tended to more frequently involve gastrointestinal arteries (20% vs 0%, respectively, P = 0.06). LVV occurred in IBD patients despite treatment with glucocorticoids (36%), azathioprine (25%) or TNF-alpha blockers (29%). The presence of the IBD was not associated with a higher LVV relapse rate in multivariate analysis (adjusted hazard ratio [aHR] 0.62 [0.13-2.83] for GCA and aHR 0.92 [0.44-1.89] for TA).

This study identifies specific clinical and imaging characteristics of LVV-IBD patients, in particular a more severe vascular presentation of GCA-IBD patients compared with iGCA patients.

IgG4-related disease (IgG4-RD) is a systemic, chronic immune-mediated inflammatory disorder that, similar to sarcoidosis, can affect various organs and tissues. IgG4-related periaortitis (PAo)/retroperitoneal fibrosis (RPF) is among the five major manifestations of IgG4-RD. Despite introduction of the ACR and EULAR classification criteria for IgG4-RD in 2019, diagnosing IgG4-related PAo/RPF and periarteritis (PA) remains challenging because obtaining biopsies from these lesions is difficult. Additionally, while glucocorticoids are highly effective in treating IgG4-RD, managing aortic or arterial lesions poses unique challenges.

This brief review discusses the utility of Japanese organ-specific diagnostic criteria for IgG4-related PAo/RPF and PA, along with recent advances in treatment strategies including management of organ-specific issues related to these lesions.

First, we analyzed 99 patients with IgG4-related PAo/RPF and PA based on expert diagnoses to propose organ-specific diagnostic criteria. Next, we retrospectively analyzed an additional 110 patients with IgG4-related PAo/RPF and PA, as well as 73 mimickers with clinical features requiring differentiation from true IgG4-RD to validate the proposed criteria.

Histopathological specimens were obtained from only 33 patients (20 periaortic, 5 coronary arteries, 4 iliac arteries, 1 mesenteric artery, and 5 retroperitoneal lesions not involving arteries). Among these, 71.4 % showed storiform fibrosis, and 71.4 % displayed obliterative phlebitis. The mean number of IgG4-positive plasma cells exceeded 10 per high-power field in all specimens, and the IgG4/IgG-positive cell ratio exceeded 40 % in 32 specimens (91.4 %). Radiographic findings were essential for diagnosing IgG4-related PAo/RPF and PA, supported by elevated serum IgG4 levels and the presence of characteristic involvement of other organs affected by IgG4-RD. Validation analysis confirmed that incorporating "imaging findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-Pao/PA/RPF lesions" improved sensitivity from 68.4 % to 77.2 %, with only a minimal reduction in specificity (from 97.4 % to 94.7 %).

Diagnosing IgG4-related PAo/RPF and PA remains challenging even when using the latest diagnostic or classification criteria, compared to diagnosing IgG4-RD involving other major organs, such as lacrimal and salivary glands, pancreas, and kidneys. In addition, when treating patients with IgG4-related PAo/RPF and PA, organ-specific factors must be considered when developing treatment strategies.

The adjusted Global Antiphospholipid Syndrome (APS) Score (aGAPSS) was developed for assessing the probability of thrombotic events in APS patients. This study investigated whether the aGAPSS at diagnosis was associated with poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

This study included 170 AAV patients who had the results of APS-related antibodies at diagnosis but were not diagnosed with APS. All-cause mortality, end-stage kidney disease (ESKD), cerebrovascular accident, and acute coronary syndrome were considered poor AAV outcomes. The aGAPSS comprises five items, with 5, 4, 4, 3, and 1 points assigned to anticardiolipin antibodies, anti-β2-glycoprotein 1 antibodies, lupus anticoagulants, hyperlipidaemia, and arterial hypertension at AAV diagnosis, respectively.

The median age of the 170 patients [93 microscopic polyangiitis (MPA), 44 granulomatosis with polyangiitis (GPA), and 33 eosinophilic GPA (EGPA)] was 63.0 years. The optimal cut-off of the aGAPSS at diagnosis for ESKD during follow-up was set as two using the receiver operating characteristic curve. AAV patients with an aGAPSS ≥2 at diagnosis exhibited a significantly reduced ESKD-free survival rate compared to those with an aGAPSS <2 at diagnosis (p=0.045). Additionally, MPA and GPA patients, excluding EGPA patients for whom the median aGAPSS at diagnosis was close to 0, also showed similar patterns to the results among the 170 patients with AAV (p=0.021).

This study is the first to demonstrate that the aGAPSS at diagnosis was significantly associated with ESKD during follow-up in AAV patients without APS.

To clarify the differences in clinical phenotypes, therapeutic patterns, and outcomes of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) across geographic regions using a multinational cohort.

Data were collected from patients with newly diagnosed or relapsing GPA or MPA in Europe, Japan and the USA from January to July 2020. The composite outcome of kidney failure and/or death within 52 weeks after treatment was evaluated, and the hazard ratios across the regions were estimated using the Cox proportional hazard model. Heterogeneities of the effects were investigated via thorough subgroup analyses.

Among the 254 eligible patients (Europe, 137; Japan, 73; USA, 44), those in Japan were older and had higher proportions of MPO-ANCA positivity and lung involvement compared with Europe and the USA. The estimated glomerular filtration rate at diagnosis varied across regions, with the highest dialysis requirement in the USA. Cyclophosphamide and rituximab use were, respectively, 57% and 63% in Europe, 29% and 40% in Japan, and 34% and 86% in the USA. Within 52 weeks, 8%, 10% and 18% developed kidney failure, while 9%, 7% and 7% died in Europe, Japan, and the USA, respectively; and the composite outcome occurred in 15%, 14% and 23% of patients. The hazard ratios for kidney failure and/or death were comparable across regions; however, they varied among certain subgroups.

Although the kidney failure-free survival was comparable across continents, regional differences existed in clinical phenotypes and therapeutic patterns.

To describe the clinical profile and compare the long-term outcomes of patients with systemic polyarteritis nodosa (S-PAN) treated with various treatment regimens at our centre in the last two decades.

Data regarding clinical presentation, treatment allocation, relapses and outcomes of patients fulfilling American College of Rheumatology (ACR) 1990 criteria for PAN in the last two decades were recorded from electronic medical records. Relapse-free survival and predictors were analysed using Kaplan-Meier survival statistics and regression analysis.

Altogether, 53 patients, including two with hepatitis B infection, were included. Cutaneous lesions and peripheral neuropathy were the commonest manifestations. Most patients (64.2%) presented with a five-factor score (FFS) of 0. Disease-attributable hypertension and peripheral gangrene were the most common manifestations of severe disease. During a median follow-up period of 53.5 months in 49 patients who had a follow up, 43 (87.8%) attained complete response while 3 (6.1%) had a partial response. Among 46 patients who had follow up of more than 3 months, 19 (41.3%) patients relapsed at a median duration of 82 (interquartile range 36.3-127.7) months. The relapse-free survival in patients who received induction with mycophenolate (n = 26) was comparable to that with cyclophosphamide (n = 21) [adjusted hazard ratio (HR): 0.68]. Smoking history was an independent predictor of relapse (HR = 6.28, P = 0.013) while age was protective (HR = 0.94, P = 0.015). Overall, fatality was observed in 5 (10%) patients. FFS and BVAS at 3 months were among the predictors of mortality.

In our cohort of S-PAN, relapses were observed in 41.3% of patients. Mycophenolate was similar to cyclophosphamide in maintaining relapse-free survival. Only 10% fatality was recorded. FFS and BVAS at 3 months were predictors of mortality.

To define the prevalence, distribution and characteristics of patients with VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammation, somatic) syndrome who have confirmed vasculitis.

Patients with VEXAS syndrome, verified by positive UBA1 mutation, were included. Chart review was performed to identify patient characteristics and outcomes. Vasculitis diagnosis was based on either histopathology showing vascular inflammation or non-invasive angiography findings. Summary statistics were calculated.

Eighty-nine patients met inclusion criteria. All were male with a median age of onset of 66.9 years (interquartile range 60.1, 72.7). Median (interquartile range) follow-up was 3.8 (2.2-5.5) years, during which 21 patients (23.6%) had evidence of vasculitis. Vasculitis subtypes included small vessel vasculitis (19.1%), cutaneous medium vessel vasculitis (2.2%) and large vessel vasculitis (2.2%). No patient had more than one vessel size involved. Histopathology in small vessel vasculitis patients was consistent with cutaneous leukocytoclastic vasculitis in the majority, though one patient had leukocytoclastic peritubular capillaritis on renal biopsy. Cranial symptoms (headache, vision changes or jaw pain) were noted in 18.0%. Two additional patients not experiencing cranial symptoms exhibited large vessel involvement with confirmed carotid thickening on non-invasive angiography; one of these had a positive temporal artery biopsy.

VEXAS syndrome manifests as a variable vessel vasculitis in a quarter of patients, with cutaneous small and medium vessel involvement being particularly common. Some patients may have positive ANCA serologies or even renal vasculitis leading to misdiagnosis. Cranial symptoms are common and may mimic GCA, though documented large vessel inflammation is rare.

A 52-year-old man presented with severe abdominal pain, elevated C-reactive protein (CRP) levels, and characteristic skin findings, leading to a diagnosis of immunoglobulin A (IgA) vasculitis with gastrointestinal (GI) involvement. Initial evaluation, including contrast-enhanced computed tomography (CT) and esophagogastroduodenoscopy (EGD), revealed marked inflammation of the duodenum and a punched-out ulcer, both of which showed partial improvement with conservative treatment. However, the patient developed worsening abdominal pain, arthralgia, and purpura, accompanied by reduced plasma factor XIII activity (47%). Factor XIII substitution therapy was initiated as a monotherapy, resulting in immediate symptom relief and significant endoscopic improvement of the duodenal ulcer. This case highlights the potential of factor XIII monotherapy as an effective treatment option for adult IgA vasculitis with severe GI manifestations.

The aim of this study was to report the annual and age-specific incidence of AAV and PAN in the adult population of Norfolk County, UK.

Individuals newly diagnosed with AAV or PAN between 1 January 2011 and 31 December 2020 residing in the postal areas of NR1-NR30 were included. Patients were classified according to the European Medicines Agency algorithm. Population data were available from the Office of National Statistics, UK.

A total of 164 patients were diagnosed with AAV or PAN over 4.7 million person-years. The annual incidence (95% CI) of AAV was 34.3 (29.2, 40)/million person-years. The annual incidence (95% CI) of granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis was 18.9 (15.2, 23.3), 12.8 (9.7, 16.4) and 2.6 (1.3, 4.5)/million person-years, respectively. The annual incidence (95% CI) for PAN was 0.6 (0.1, 1.9)/million person-years. The age-specific incidence of granulomatosis with polyangiitis and microscopic polyangiitis rose with each decade of life and was highest in the 8th decade for granulomatosis with polyangiitis [53.2 (95% CI 36.2, 75.6) per million] and in the 9th decade for microscopic polyangiitis [48.4 (95% CI 27.1, 79.8) per million].

The incidence of AAV, specifically that of granulomatosis with polyangiitis and of microscopic polyangiitis, is slowly rising over time. It is most notable among the elderly population, among whom the incidence rates for granulomatosis with polyangiitis and microscopic polyangiitis peak. There may be a 4-year incidence cycle, which needs confirmation in a longer study.

Patients with anti-neutrophil cytoplasmic antibody (ANCA)-positive interstitial lung disease (ILD) but without evidence of systemic vasculitis have been reported in studies and are classified as isolated ANCA-positive idiopathic interstitial pneumonia (IIP). However, the clinical significance of ANCA, particularly myeloperoxidase (MPO) -ANCA in IIP remains poorly understood. This study aims to investigate the differences between ANCA-positive and ANCA-negative IIP patients and further explore the impact of MPO-ANCA on clinical manifestations and prognostic outcomes.

We reviewed 408 ILD patients with available ANCA results from January 2012 to September 2021. 61 patients diagnosed with microscopic polyangiitis-associated ILD were not included in the analysis. A comparative analysis was performed between 61 isolated ANCA-positive IIP patients (ANCA-IIP group) and 286 ANCA-negative IIP patients (IIP group). We further conducted subgroup analyses based on the status of MPO-ANCA.

Baseline clinical characteristics, pulmonary function tests, radiological features and all-cause mortality were similar between ANCA-IIP and IIP groups. When comparing the MPO-ANCA-IIP group with the IIP group and the non-MPO-ANCA-IIP group separately, a higher proportion of fibrotic features was observed on imaging (P = 0.004 vs IIP group; P = 0.031 vs non-MPO-ANCA-IIP group). After one year of treatment, the MPO-ANCA-IIP group showed a significantly greater decline in pulmonary function parameters compared to both the IIP group and the non-MPO-ANCA-IIP group. The frequency of pulmonary function decline was significantly higher in the MPO-ANCA-IIP group compared to the non-MPO-ANCA-IIP group (P = 0.026). Additionally, MPO-ANCA was not found to be statistically associated with mortality among patients with IIP.

ANCA-IIP patients had similar clinical characteristics and prognoses with IIP patients. MPO-ANCA-IIP patients had more prominent fibrosis on imaging and a greater decline in pulmonary function following treatment. Special attention should be paid to MPO-ANCA positivity during the diagnosis and treatment of IIP patients.

ClinicalTrials.gov: NCT04413149, May 2020.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of antineutrophil cytoplasmic antibody-associated vasculitis characterized by inflammation of small- and medium-sized vessels, causing symptoms in multiple organs. The symptoms and daily life problems reported by patients with EGPA themselves are largely unknown. We conducted a cross-sectional survey to investigate the reality of EGPA-related symptoms in patients with EGPA.

Specialists and specialized facilities with experience in treating patients with EGPA cooperated in the survey; specialists from 28 facilities across Japan participated. Patients diagnosed with EGPA by their physician and treated for ≥ 1 year who agreed to answer the online questions were enrolled and completed the survey between March and June 2024. Patients answered questions about their general symptoms, asthma symptoms, and quality of life.

We analyzed valid responses from 200 patients (61.0% female/38.5% male/0.5% prefer not to answer) with EGPA. The mean age was 57.9 years and 34.5% were ≥ 65 years old. Patients were treated at rheumatology departments (48.0%), respiratory/allergy departments (48.0%), and other departments (4.0%). Basic treatments included oral glucocorticoids (63.0%) and anti-interleukin-5/receptor α biologics (61.0%). Symptoms in > 50.0% of patients (past month) were pain/numbness (73.5%), fatigue/malaise (68.0%), asthmatic symptoms (56.0%), nasal/paranasal symptoms (55.0%), and joint/muscle pain (54.5%). Pain/numbness was considered the most painful symptom (29.5%). Nearly all patients experienced symptoms affecting two or more organs/systems. Patients reported that EGPA symptoms had detrimental impacts on physical and mental health; 67.0% of patients thought they were not understood by others because their disease is invisible, and symptoms frequently affected their daily life (61.5%), work (53.0%), sleep (49.5%), and social life (36.5%).

This is the largest survey of patients with EGPA. We have revealed the reality of patients' perceptions of EGPA-related symptoms. These results are expected to contribute to improvement in patient-centered EGPA management.

jRCT1050230186.

Objectives: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises rare systemic vasculitides that can present with cognitive dysfunction. However, data on the screening and characterization of cognitive dysfunction in AAV remain limited. Methods: Cognitive complaints in AAV patients were screened using self-report questionnaires. Objective cognitive impairment was assessed with a standardized neurocognitive test battery. Results were compared with clinical evaluations, brain MRI findings, treatment history, and neuropsychiatric symptoms. All test results were standardized for the overall population. Results: Twelve patients (five women, seven men) with a median [IQR] age of 68 [59-71] and a median [IQR] disease duration of 92 months [55-127] were included. None of the patients showed evidence of vasculitis activity on brain MRI. Cognition was assessed using a standardized neurocognitive test battery in all patients except one. Four patients (36%) were found to have cognitive impairment, defined as three or more altered tests. The most affected functions were attentional and executive, with the d2-R (4/4), Rey-Osterrieth Complex Figure Delayed Recall (3/4), and Trail Making Test Part B (3/4) showing the most frequent deficiencies. Objective cognitive disorders were not associated with self-reported cognitive complaints. No significant association was found between cognitive impairment and vasculitis activity or sequelae, corticosteroid and immunosuppressive treatments, or neuropsychiatric symptoms. Conclusions: This study highlights the presence of cognitive impairments in AAV, predominantly affecting attentional and executive functions, which may reflect vascular involvement. Early and tailored approaches to cognitive screening and management are essential to improve patient care and quality of life.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis with hypereosinophilia that is preceded by asthma and chronic rhinosinusitis with nasal polyps. Since multiple organs may be involved in this disease, early treatment is required. In this regard, glucocorticoid (GC) therapy is often initiated before a definitive diagnosis is made. A biopsy of an injured organ is useful for a diagnosis but is not performed in all cases due to its invasiveness and, at times, diagnostic accuracy. Therefore, a comprehensive diagnosis is often made based on symptoms and clinical course of disease. However, it is sometimes difficult to distinguish EGPA from other hypereosinophilic diseases or vasculitides. In recent years, in addition to GC and immunosuppressive agents, anti-interleukin (IL)-5/IL-5 receptor alpha (IL-5Rα) antibodies targeting eosinophils have become increasingly important in the treatment of EGPA. However, accumulating data suggest that such anti-IL-5/IL-5Rα antibody therapy may have effects beyond those observed in eosinophils. This paper outlines the clinical features, diagnosis, pathogenesis, and current treatment of EGPA, a hypereosinophilic disease.

Cogan Syndrome (CS) is a rare autoimmune systemic vasculitis affecting the inner ear and the eye with systemic manifestations affecting mainly young adults. The clinical presentation is historically classified in two subtypes. Typical CS associated interstitial keratitis with audio-vestibular symptoms with a 2-year maximum delay between these 2-organ involvements. Atypical CS subgroup associated inflammatory ocular disease in the absence of interstitial keratitis, audio-vestibular impairment, and systemic manifestations in a delay longer than 2 years between different organ manifestations. Neither diagnostic criteria nor specific biomarkers could lead to definite diagnosis. Cogan syndrome is a diagnosis of exclusion after a meticulous appropriate investigation to rule out other conditions. Disease prognosis is related to the risk of deafness and/or blindness as well as complications related to systemic vasculitis. Early recognition of this condition and early intervention can minimize disabling and irreversible damage. Treatment of CS is challenging, and the only available data comes from case reports and series. The aim of this review is to describe the clinical spectrum and outcome of CS through a summary of published case series, the differential diagnosis, and the therapeutic approaches with a special focus on the recent novel therapeutic options in the biological era.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) present heterogeneous neurological symptoms that are often misdiagnosed, contributing to delays in identification and prompt treatment. Few studies in Latin America have described the frequency of neurological involvement in AVV; none have explicitly described the characteristics of nervous system involvement.

This case-control study examined patient records for AVV treated at a university hospital in Colombia between 2005 and 2023. Patients with and without neurological manifestations were compared and a survival analysis was performed.

Forty-eight cases and seventy-nine controls were included. The median age was 58 years, 57.5 % were female. The diagnosis was made in 67.7 % of cases during the hospital stay, and in-hospital mortality was 14 %. Nervous system involvement was more frequent in undifferentiated AAV (100 %), followed by eosinophilic granulomatosis with polyangiitis (75 %), microscopic polyangiitis (33.3 %), and granulomatosis with polyangiitis (25.9 %). The most common neurological manifestations were peripheral neuropathy (50 %), patient-reported symptoms of sensory dysfunction (43.7 %), and cranial neuropathy (39.6 %); headache was frequent among patients with neurological involvement. Patients with neurological manifestations presented a lower median creatinine at admission and a lower proportion of patients with a five-factor score > 2. No differences in one-year all-cause mortality were observed.

This study presents an exhaustive clinical characterization of the neurological profile of patients with AAV from a single center in Latin America. Patients with nervous system involvement showed less severe renal involvement and a lower proportion of 5-year risk of mortality scores; one-year all-cause mortality was similar between groups.

Behçet's syndrome (BS) is a systemic vasculitis that affects vessels of all calibers. It has several defining characteristics, such as its tendency for remission over time and a typical geographical distribution. Clinically, the association of venous thrombosis with arterial aneurysms, inflammatory parenchymal brain involvement, the classic pattern of posterior uveitis with retinal vasculitis, and the well-known triad of bipolar ulcers and erythema nodosum are distinctive features of this condition. Despite some advances in the pathogenesis of BS and the use of biological drugs that have improved prognosis, certain aspects remain controversial, such as the role of the pathergy test or the determination of HLA-B*51 in the diagnosis of the disease, or the actual value of anticoagulation in patients with BS and vascular thrombosis.

Many monogenic autoinflammatory diseases, including DADA2 (deficiency of adenosine deaminase 2), HA20 (haploinsufficiency of A20), SAVI (STING-associated vasculopathy with onset in infancy), COPA syndrome, LAVLI (LYN kinase-associated vasculopathy and liver fibrosis) and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, present predominantly with vasculitis and constitute a substantial subgroup of vasculitic conditions associated with a 'probable aetiology'. The spectrum of monogenic vasculitis encompasses all sizes and types of blood vessel, ranging from large vessels to medium-size and small vessels, and from the arterial side to the venous side of the vasculature. Monogenic vasculitis typically starts early in life during infancy or childhood; VEXAS syndrome, which presents in late adulthood, is an exception. The activation of myeloid cells via inflammasome and nuclear factor-κB pathways, type I interferon-enhanced autoimmune mechanisms and/or dysregulated adaptive immune responses have an important role in the development of immune-mediated endothelial dysfunction and vascular damage. Genetic testing is essential for the diagnosis of underlying monogenic autoinflammatory diseases; however, the penetrance of genetic variants can vary. Increased awareness and recognition of distinctive clinical findings could facilitate earlier diagnosis and allow for more-targeted treatments.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (ANCA-vasculitis) is an autoimmune disease characterized by inflammation and necrosis of small or medium vessels. In the past, the role of the complement in the pathogenesis of ANCA-vasculitis has been underestimated, due to the paucity of the complement at sites of injured glomeruli. Following evidence from animal models of the major role of the complement in pathogenesis of ANCA-vasculitis, the complement has again attracted interest. Immunohistology analysis of pauci-immune glomerulonephritis-ANCA glomerulonephritis (ANCA-GN)-reveals the presence of complement products and membrane attack complex, suggesting their involvement in the disease process. Researchers emphasize the complement classical or lectin pathway as a contributor to the development of ANCA-vasculitis. The era of targeted therapies to suspend the complement activation as a therapy for ANCA-vasculitis has arrived, and thus, the comprehension of its role is very important. This review summarizes recent insights on the important role of complement activation in the development of ANCA-vasculitis as well as the emerging therapeutic possibilities that target complement components for the treatment of this condition.

In this study, we aimed to evaluate the factors affecting the development of damage and mortality in patients with AAV treated at our tertiary referral center. This retrospective study included data on patients with AAV who fulfilled the Chapel Hill Consensus Conference (CHCC) criteria. Patients were divided into c-ANCA/PR3( +) and p-ANCA/MPO ( +) groups based on ANCA immunofluorescence and/or ELISA results, and relapse, damage, and mortality data were compared across the groups. Data from 254 patients (n = 136, 53.5% female) were included in the analysis. Clinical diagnosis was GPA in 186 (73.2%) and MPA in 68 (26.8%) patients. During the follow-up, 217 of 242 (89.7%) patients developed damage, and the median VDI score of the cohort was 2 (IQR: 2). VDI scores were higher in the first period (1997-2011) than in the second period (2011-2021) in the entire cohort (p = 0.012) and in patients with GPA compared with MPA (p = 0.034). Five-year and overall survival rates were 88.1% and 80.3% in the entire cohort; 87.8% and 81% in c-ANCA/PR3 ( +); 86.2% and 76% in p-ANCA/MPO ( +) (Log-Rank: p = 0.35); 91% and 84.5% in GPA; 81% and 67.2% in MPA patients (Log-Rank: p < 0.001). Development of malignancy, severe infection, and active/persistent disease after the induction phase were associated with higher mortality in patients with AAV. In our AAV cohort, permanent organ damage was detected in the majority of the patients. Although the median VDI score decreased over time, mortality did not change.

ANCA-associated vasculitis (AAV) is a rare and potentially fatal autoimmune disorder characterized by pauci-immune necrotizing vasculitis affecting small- to medium-sized blood vessels. The pathogenic role of ANCAs in AAV is supported by both clinical and experimental evidence, and when used in the proper clinical setting, ANCA testing is highly specific for AAV. Testing with both indirect immunofluorescence assay and enzyme immunoassay may increase sensitivity for AAV; however, testing with a high-quality enzyme immunoassay may be used alone. Nonvasculitic conditions and drugs can cause ANCA positivity without manifestations of AAV. We review ANCA testing itself, performance characteristics and specific conditions for the laboratory test, and various conditions when ANCA testing is useful in diagnosis, disease monitoring, and selecting treatment.

Age-associated B cells (ABCs) are a distinct subset of B cells. This B-cell population expands in the elderly but is also abnormally expanded in patients with autoimmune diseases like systemic lupus erythematosus (SLE). ABC differentiation requires unique signaling stimuli, including BCR stimulation, TLR7 and TLR9 signaling, and the action of cytokines. The role of ABCs in the pathogenesis and treatment strategies of SLE has been a research hotspot in recent years. Possible pathogenic mechanisms include the production of autoantibodies and cytokines, as well as stimulation of spontaneous germinal center. Specifically targeting ABCs is a promising strategy for treating SLE. This article reviews the role of ABCs in SLE. Understanding the origin and differentiation of ABCs and their role in SLE will facilitate the discovery of novel drug targets for the treatment of SLE.

Systemic vasculitis, common forms of which include anti-neutrophil cytoplasmic antibody-associated small-vessel vasculitis, large-vessel vasculitis and Behçet syndrome, are frequently complicated by arterial or venous thrombotic events (AVTEs). Newly identified entities such as DADA2 (deficiency of adenosine deaminase 2) and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, which are driven by genetic mutations, also exhibit vasculitic features and are associated with a high risk of AVTEs. AVTEs in systemic vasculitis, including monogenic forms of vasculitis, are due to the complex interaction of inflammation and coagulation. New insights into the pathogenetic mechanisms implicate endothelial dysfunction, immune complex deposition and the interplay of pro-inflammatory cytokines with prothrombotic factors, which collectively promote thrombus formation. AVTEs impose a substantial disease burden, complicate diagnosis and negatively affect prognosis by increasing the risk of morbidity and mortality. Early diagnosis and treatment are crucial to prevent lasting damage. Management strategies should target both thrombosis and underlying inflammation. Antithrombotic therapies, including low-dose aspirin, or oral anticoagulants should be used on the basis of individual thrombotic risk assessment. Immunosuppressive therapy is the cornerstone of treatment for arterial and venous thrombosis, particularly in Behçet syndrome, in which vascular inflammation has a crucial role in thrombotic complications.

The immunological response and adverse effects of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients receiving coronavirus disease-2019 (COVID-19) vaccines remain unclear. We aimed to evaluate the effects of these vaccines on AAV disease activity.

We reviewed the medical records of 52 patients with AAV who had received at least second doses of the COVID-19 vaccine and evaluated their immunogenicity by measuring the anti-spike (S) antibody (Ab) titer levels using the Roche Elecsys® immunoassay. Responses to the Birmingham Vasculitis Activity Score (BVAS) tool and 36-Item Short Form Survey before and after vaccination were obtained to assess AAV disease activity. Vaccine reactivity was measured using a standardized questionnaire.

We enrolled 52 patients with AAV. No differences were found between those who received second and third doses of vaccination in terms of AAV type, disease activity, vaccine type, or the use of immunosuppressive agents, including steroids. The median anti-S Ab titer was 3967.0 after third doses compared to 419.0 after second doses (p=0.001). Except for mycophenolate mofetil (MMF), when immunosuppressants were administered in conjunction with steroids, the Ab titer was higher after the third vaccination than that after the second dose. The BVAS remained unchanged before and after second and third doses. No life-threatening adverse events were reported.

Although COVID-19 vaccine may not produce sufficient antibodies in patients taking MMF, the vaccine did not exacerbate disease activity or cause severe side effects. Therefore, COVID-19 vaccines should be considered in patients with AAV.

This study aimed to evaluate the utility of ANCA specificity as a primary criterion for classifying AAV subtypes to simplify the diagnostic process without compromising accuracy.

A retrospective cohort study was conducted involving 310 patients diagnosed with AAV between January 2015 and December 2023 across three tertiary care centers affiliated with Peking University. Patients were reclassified using three methods: the European Medicines Agency (EMA) algorithm, the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria, and ANCA specificity-based classification. Concordance between classification systems was assessed using Cohen's kappa coefficients.

ANCA specificity-based classification demonstrated substantial to almost perfect agreement with the 2022 ACR/EULAR criteria for MPA/MPO-AAV (kappa = 0.806) and GPA/PR3-AAV (kappa = 0.663). Many patients initially classified as GPA under the EMA algorithm were reclassified as MPA when using ANCA specificity. EGPA classification remained consistent across all methods (kappa = 0.725 between EMA and ACR/EULAR), suggesting that ANCA specificity is less critical for EGPA. The use of ANCA specificity simplified the classification process, aligning closely with the underlying pathophysiology of AAV subtypes.

ANCA specificity serves as a valuable adjunct in the classification of AAV, particularly for distinguishing between MPA and GPA. Utilizing ANCA serotypes can simplify the diagnostic process, potentially facilitating earlier diagnosis and targeted treatment. For EGPA, traditional classification criteria remain effective. Incorporating ANCA specificity into clinical practice may enhance diagnostic accuracy and improve patient outcomes in AAV management. Key Points • ANCA-based classification aligns strongly with the 2022 ACR/EULAR criteria for MPA and GPA, providing a simplified diagnostic approach. • Adopting this approach can streamline the classification process, reduce invasive procedures, and enable earlier diagnosis while maintaining high concordance with established systems.

The aim of the study was to investigate urinary and serum tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as potential biomarkers in a longitudinal cohort of patients with ANCA-associated vasculitis (AAV).

Patients with active AAV were included in the study. The Birmingham Vasculitis Score 2003 (BVAS) was used for assessment of disease activity and C-reactive protein (CRP), creatinine, albuminuria, and serum (s) and urinary (u) TWEAK levels were measured at baseline and 6-month follow-up. sTWEAK was measured in population-based controls for comparison. Kidney biopsies from AAV patients were stained for TWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14) using immunohistochemistry (IHC).

sTWEAK was measured in 74 patients and uTWEAK in 69 patients, 42 of whom had kidney involvement. uTWEAK-to-creatinine ratio (uTWEAK/Cr) was significantly higher at baseline compared with follow-up (median 7.21 vs 4.94 ng/mmol, P < .0001). Patients with kidney involvement had higher uTWEAK/Cr levels compared with those without (P = .03). A correlation was found between uTWEAK/Cr and BVAS (P = .006), albuminuria (P = .022) and crescentic changes (P = .03). sTWEAK levels were higher in patients at inclusion than at follow-up (P = .009) but no difference was found when comparing patients and controls, nor did sTWEAK correlate with BVAS. IHC staining showed a clear expression of TWEAK but a fainter pattern of Fn14 in kidney biopsies from AAV patients.

uTWEAK/Cr correlated with BVAS, albuminuria and number of crescents in active AAV and may be a useful biomarker in assessing disease activity in patients with AAV, whereas sTWEAK level is not.

Data on the presentation and management of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in private practice are limited.

We sought to characterize the profiles and disease burden of patients with EGPA in a real-world private practice setting.

This was a retrospective, noninterventional, longitudinal study (GSK ID: 217426) of US Allergy Partners network data. For patients with a diagnosis of EGPA, confirmed by 2 or more EGPA clinical features, index was defined as their first visit with an Allergy Partners physician (January 2007-June 2021); postindex lasted until loss of follow-up or study end (December 2021). Patient characteristics at index, physician characteristics at any time, symptoms, treatment characteristics, and clinical outcomes postindex were assessed.

Of 52 patients (median follow-up, 3.7 years), 75% were diagnosed with EGPA outside the Allergy Partners network. Each patient received care from a median (Q1-Q3) of 4.0 (3.0-5.0) physician specialties. Most had asthma (92%), rhinitis (75%), and sinusitis (62%) and experienced a mean ± SD of 18.1 ± 4.3 distinct self-reported symptoms. Most (85%) used oral corticosteroids, with 73% (32 of 44) on daily doses of more than 12 mg; 60% used mepolizumab. Overall, 75% of patients (39 of 52) achieved a response (improved/controlled symptoms); 46% (24 of 52) achieved controlled status after worsened, unchanged, or active symptoms, and of these 38% (9 of 24) relapsed.

The complex private practice presentation of EGPA, with heterogeneous patient response to standard treatments, highlights a significant disease burden and continued need for optimized treatment strategies within a multidisciplinary team approach.

Takayasu arteritis is a rare form of large-vessel vasculitis primarily affecting the aorta and its major branches, with a higher prevalence in young women. This inflammatory disease can lead to significant complications, including ischemic stroke and transient ischemic attacks, though large-vessel occlusion stroke is an uncommon initial manifestation. Diagnosis relies heavily on vascular imaging, and treatment typically involves high-dose glucocorticoids, revascularization procedures, and close monitoring for restenosis, which occurs frequently after interventions.

This case report describes a 38-year-old North African woman who presented with acute left-sided hemiparesis and visual disturbances due to large-vessel occlusion involving the common carotid artery and middle cerebral artery. Mechanical thrombectomy and stenting were performed successfully, resulting in complete recanalization without complications. The patient was later diagnosed with Takayasu arteritis, and this was managed with high-dose corticosteroids. During a 2-year follow-up, no complications such as restenosis or re-occlusion were observed, and the patient remained in good health.

This case is notable for the successful use of dual mechanical thrombectomy and stenting in the acute management of stroke in Takayasu arteritis without short- or long-term complications, a rare outcome not commonly reported in the literature. It highlights the potential efficacy of this approach in carefully selected patients, suggesting that postoperative immunosuppressive therapy may reduce the incidence of restenosis.

This study aimed to evaluate the density of tubulointerstitial macrophages with renal outcomes in patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody associated glomerulonephritis (MPO-ANCA-associated GN).

This study analysed patients with MPO-ANCA-associated GN who had renal biopsies at Jinling Hospital. It looked at the density of CD68+ macrophages in the tubulointerstitium and examined correlations with serum creatinine levels, urinary protein levels, treatment regimen and renal histologic class. The study used KM curves to show the impact of these factors on renal prognosis and conducted multivariate analyses with Cox proportional hazards regression models.

A total of 172 patients with MPO-ANCA-associated GN (median age: 50 y, 43.6% male) were included. Stratification of the cohort into tertiles was based on tubulointerstitial macrophage density. Significant differences in serum creatinine levels, induction treatment regimen, the rates of end-stage kidney disease, and renal histologic class were observed between the three groups. Correlation analysis showed that induction treatment regimen and renal histologic class were correlated with tubulointerstitial macrophage density. Kaplan-Meier curves illustrated patients with a lower presence of CD68+ macrophages in the tubulointerstitium experienced significantly better renal survival compared with those with a higher presence. The higher levels of CD68+ macrophage infiltration were significantly associated with adverse renal outcomes. This association persisted after adjusting for potential confounders including baseline serum creatinine, histopathological class, and induction therapy modalities.

The results of our study provide insight into the prognostic significance of macrophage infiltration in the tubulointerstitium in MPO-ANCA-associated GN.

Diseases that develop necrotizing vasculitis of cutaneous muscular arteries include cutaneous arteritis (CA) and polyarteritis nodosa (PAN). It is difficult to distinguish them based on skin biopsy findings alone. This study demonstrated that artificial intelligence (AI) can discriminate them based on skin biopsy findings and revealed where AI focuses on the image. Ninety-three hematoxylin-and-eosin images of CA and 19 PAN images were used. Among them, 85 CA and 17 PAN images were used to train AI; thereafter, AI was challenged to classify the remaining images. The same test images were evaluated by 26 pathologists with different years of experience. AI accuracy was 75.2 %, whereas that of pathologists was 42.8 %. Gradient-weighted class activation mapping (Grad-CAM) indicated that AI focused on connective tissues around the affected vessels rather than the affected vessels. Twenty-two of the 26 pathologists were randomly divided into two groups of 11 each, one of which referred to Grad-CAM images and was challenged in the second-round test of images different from the first round. The accuracy significantly improved after referring to Grad-CAM images, whereas it was equivalent to the first round without referring to Grad-CAM images. In the survey after the second-round test, pathologists who referred to Grad-CAM images suggested that inflammation and fibrosis in the surrounding connective tissues in PAN might be abundant compared to CA. AI may be useful for histological differentiation between CA and PAN and can help pathologists improve the ability of discriminating CA and PAN based on histological findings of skin biopsy specimens.

Although previous studies have reported poor outcomes in older-onset (≥ 75 years old) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with younger-onset AAV, the distinct cause of poor prognosis remains unclear. This study aimed to investigate the clinical features, therapies, and outcomes of older patients with granulomatosis with polyangiitis (GPA) and patients with microscopic polyangiitis (MPA) compared to younger-onset patients.

This two-center retrospective cohort study enrolled 70 newly-onset Japanese patients with AAV (GPA and MPA) from the Fukushima Medical University Hospital and Ohta-Nishinouchi Hospital in Fukushima, Japan, between 2004 and 2019. Clinical records were retrospectively reviewed, and clinical features and outcomes (1-year and 3-year survival by the Kaplan-Meier method) were compared between older and younger GPA/MPA groups, respectively.

Clinical features of the older GPA/MPA group were similar to those of the younger GPA/MPA group; however, the older GPA group showed severe inflammation and the older MPA group had an increased frequency of renal involvement and fever. The 1-year survival in the older MPA group was significantly lower than that in the younger MPA group. Immunosuppressive therapy including cyclophosphamide, rituximab, and other immunosuppressive agents was important to sustain the survival of patients with GPA/MPA.

Older patients with GPA/MPA may have specific clinical features; careful observation is needed during the treatment of older patients with MPA. Immunosuppressive therapy may improve the prognosis of patients with AAV.

This article provides gastroenterologists with an overview of small bowel involvement in systemic vasculitis. Though various vasculitides can impact the small bowel, we highlight those with a more frequent and clinically significant GI involvement.

Recent advances, including increased accessibility to cross-sectional imaging, capsule endoscopy and device-assisted enteroscopy, have improved detection of gastrointestinal manifestations in systemic vasculitis. Studies have also explored the genetic and inflammatory pathways involved in these diseases, although high-quality evidence on diagnosis and treatment remains limited, leading to reliance on expert consensus.

Small bowel involvement is common in Behçet's disease and small vessel vasculitis, presenting with symptoms ranging from mild to severe, including massive bleeding, ischemia, and perforation, often indicating a poorer prognosis. Diagnosis is challenging, but in patients with a known or suspected history of vasculitis, it should prompt contrast-enhanced abdominal imaging and endoscopic evaluation. Treatment decisions should be made collaboratively by a multidisciplinary team, with immunosuppressive therapy remaining the cornerstone.