Reduced-dose versus high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: predefined 2-year follow-up study.

OBJECTIVES: The LoVAS trial reported non-inferiority in remission induction rates between the reduced-dose and conventional high-dose glucocorticoid regimens plus rituximab for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 6 months; however, maintenance glucocorticoid requirements and long-term outcomes are unknown. METHODS: A total of 140 patients with new-onset ANCA-associated vasculitis without severe glomerulonephritis or alveolar haemorrhage were randomised to receive reduced-dose prednisolone (0.5 mg/kg/day) plus rituximab (375 mg/m2/week×4) or high-dose prednisolone (1 mg/kg/day) plus rituximab. After achieving remission, patients received the rituximab maintenance therapy (1 g/6 months). RESULTS: A total of 134 patients were analysed. Among patients who achieved remission with the protocolised treatments, the majority of patients in the reduced-dose group (89.7%) and 15.5% in the high-dose group discontinued prednisolone (median time to withdrawal, 150 and 375 days, respectively). During 24-month trial period, two patients in the reduced-dose group (2.8%) died, while five patients in the high-dose group (7.6%) died (p=0.225). Relapse occurred in nine patients in the reduced-dose group (13.0%) (two major and seven minor) and five in the high-dose group (7.6%) (two major and three minor) (p=0.311). Serious adverse events (SAEs) were less frequent in the reduced-dose group (36 events in 19 patients, 27.5%) than in the high-dose group (54 events in 30 patients, 46.2%) (p=0.025). CONCLUSION: At 24 months, frequencies of relapse did not differ between the groups, and SAEs were less frequent in the reduced-dose group due to the lower event rate in the 6-month induction phase. The bias to myeloperoxidase-ANCA positivity (85.8%) in the trial population should be noted. TRIAL REGISTRATION NUMBER: NCT02198248.

Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA-associated vasculitis: a propensity score analysis of the real-world nationwide database.

OBJECTIVES: Life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) and/or alveolar haemorrhage (AH) has a poor prognosis. Rituximab (RTX) is as effective as cyclophosphamide (CY) in remission induction therapy; however, the effectiveness and safety of RTX have not been established in life-threatening AAV. This study aimed to investigate the short-term effectiveness and safety of RTX in life-threatening AAV with RPGN and/or AH. METHODS: Between April 2018 and March 2020, cases treated with systemic glucocorticoids and RTX or intravenous CY (IVCY) was extracted from a Japanese nationwide inpatient database. Effectiveness was evaluated by in-hospital mortality and severe renal dysfunction requiring haemodialysis (HD) at discharge. Safety was evaluated by the in-hospital incidence of infections. The propensity score (PS) for RTX was estimated. Multivariable Cox and logistic regression with adjustment for PS were conducted to estimate the association of RTX with outcomes. RESULTS: From 16 001 612 hospitalised records, 687 life-threatening AAV cases were extracted. No significant difference in in-hospital mortality (adjusted HR 1.06; 95% CI 0.62 to 1.80) was found between the groups. Although the RTX group had a lower risk of fungal infections (adjusted OR (aOR) 0.45; 95% CI 0.23 to 0.84) and pneumocystis pneumonia (aOR 0.58; 95% CI 0.32 to 1.00), they might have an increased risk of severe renal dysfunction requiring HD at discharge (aOR 2.58; 95% CI 1.02 to 6.91). CONCLUSIONS: In life-threatening AAV, RTX has similar short-term effectiveness on mortality to IVCY. Although RTX might have a lower risk of fungal infections and pneumocystis pneumonia, the short-term renal prognosis might be inferior to IVCY.

Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study.

OBJECTIVE: Relapsing polychondritis (RP) is a systemic inflammatory disease of unknown aetiology. The objective of this study was to examine the contribution of rare genetic variations to RP. METHODS: We performed a case-control exome-wide rare variant association analysis that included 66 unrelated European American cases with RP and 2923 healthy controls (HC). Gene-level collapsing analysis was performed using Firth's logistics regression. Exploratory pathway analysis was performed using three different methods: Gene Set Enrichment Analysis, sequence kernel association test and higher criticism test. Plasma DCBLD2 levels were measured in patients with RP and HC using ELISA. RESULTS: In the collapsing analysis, RP was associated with a significantly higher burden of ultra-rare damaging variants in the DCBLD2 gene (7.6% vs 0.1%, unadjusted OR=79.8, p=2.93×10-7). Plasma DCBLD2 protein levels were significantly higher in RP than in HC (median 4.06 ng/µL vs 0.05 ng/µL, p<0.001). The pathway analysis revealed a statistically significant enrichment of genes in the tumour necrosis factor signalling pathway driven by rare damaging variants in RELB, RELA and REL using higher criticism test weighted by eigenvector centrality. CONCLUSIONS: This study identified specific rare variants in the DCBLD2 gene as a putative genetic risk factor for RP. These findings should be validated in additional patients with RP and supported by future functional experiments.

Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials.

OBJECTIVE: To compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively). METHODS: The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84. RESULTS: 277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25). CONCLUSIONS: According to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.

OBJECTIVES: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK. METHODS: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments. RESULTS: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients. CONCLUSIONS: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.

Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial.

OBJECTIVE: To compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis. METHODS: We conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing at least 2 years of fixed-schedule rituximab. In the B cell arm, rituximab was reinfused upon B cell repopulation; in the ANCA arm, rituximab was reinfused upon significant rise in ANCA level. Evaluations were conducted every 3 months. The primary endpoint was clinical relapse, defined as a modified BVAS/WG >0 by 36 months. Secondary endpoints included serious adverse events (SAEs) and rituximab exposure. RESULTS: 115 patients were enrolled. Median follow-up time was 4.1 years (IQR 2.5-5.0). By Kaplan-Meier analysis, 4.1% (95% CI 1.0 to 15.6) of patients had a clinical relapse in the B cell arm, compared with 20.5% (95% CI 11.9 to 34.1) in the ANCA arm, at 3 years after study entry (log-rank p=0.045). Total SAEs, including infectious SAEs, and deaths did not differ. The number of SAEs due to COVID-19 was higher in the B cell arm (p=0.049). In the B cell arm, patients received a mean of 3.6 (SD 2.4) infusions (3.6 g) per person over the median study follow-up time of 4.1 years, compared with 0.5 (SD 1.4) infusions (0.5 g) per patient in the ANCA arm (p<0.001). CONCLUSIONS: Rituximab dosed for B cell repopulation results in fewer clinical relapses than when dosed for a rise in ANCA level in maintenance of remission for ANCA vasculitis. Overall safety was equivalent; SAEs due to COVID-19 and rituximab exposure were higher with the B cell strategy. TRIAL REGISTRATION NUMBER: NCT02749292.

Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways.

OBJECTIVES: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients. METHODS: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed. Synovial tissue specimens from patients with inflammatory arthritis and aorta tissue were used as disease control samples. Senescent cells and their histological origin were identified with specific cellular markers; IL-6 and MMP-9 were investigated as components of the senescent associated secretory phenotype by triple costaining. GCA or PMR artery culture supernatants were applied to fibroblasts, HUVECs and monocytes with or without IL-6R blocking agent to explore the induction of IL-6-associated cellular senescence. RESULTS: Senescent cells were present in GCA arteries at higher proportion compared with PMR (9.50% vs 2.66%, respectively, p<0.0001) and were mainly originated from fibroblasts, macrophages and endothelial cells. IL-6 was expressed by senescent fibroblasts, and macrophages while MMP-9 by senescent fibroblasts only. IL-6(+) senescent cells were associated with the extension of vascular inflammation (transmural inflammation vs adventitia limited disease: 10.02% vs 4.37%, respectively, p<0.0001). GCA but not PMR artery culture supernatant could induce IL-6-associated senescence that was partially inhibited by IL-6R blockade. CONCLUSIONS: Senescent cells with inflammatory phenotype are present in GCA arteries and are associated with the tissue inflammatory bulk, suggesting a potential implication in disease pathogenesis.

Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial.

OBJECTIVES: To evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial. METHODS: Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included the Glucocorticoid Toxicity Index, estimated glomerular filtration rate, urinary albumin to creatinine ratio, health-related quality of life and safety. RESULTS: Of the 330 patients who received study medication, 214 (64.8%) received rituximab (once weekly for 4 weeks), with a mean age of 59.8 years; 163 (76.2%) had renal vasculitis and 125 (58.4%) were newly diagnosed. Remission at week 26 and sustained remission at week 52 were achieved by 83/107 (77.6%) and 76/107 (71.0%) patients in the avacopan group and 81/107 (75.7%) and 60/107 (56.1%) in the prednisone taper group, respectively. The relapse rate, recovery of renal function, speed of reduction in albuminuria and glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 34.6% and 39.3% of patients in the avacopan and prednisone taper groups, respectively. CONCLUSIONS: These data suggest that in patients with ANCA-associated vasculitis receiving rituximab, efficacy of treatment with avacopan compared with a prednisone taper was similar at week 26 and greater at week 52, with a favourable safety profile. In addition, avacopan was associated with improved renal outcomes and lower glucocorticoid toxicity. These results demonstrate the efficacy and safety of avacopan in patients receiving background induction therapy with rituximab. TRIAL REGISTRATION NUMBER: NCT02994927.

EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update.

BACKGROUND: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

Data quality and patient characteristics in European ANCA-associated vasculitis registries: data retrieval by federated querying.

OBJECTIVES: This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV) registries. METHODS: Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis. RESULTS: A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively. CONCLUSIONS: In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.

Validation of a new glucocorticoid-specific Patient-Reported Outcome Questionnaire (the Steroid PRO).

OBJECTIVES: Glucocorticoids used in the treatment of inflammatory rheumatic conditions can impact on health-related quality of life. An underpinning qualitative study developed a long-list of candidate items for a treatment-specific patient-reported outcome (PRO) measure. The objective of this paper is to determine scale structure and psychometric properties of the Steroid PRO. METHODS: A cross-sectional survey of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. Initial survey collected demographics, clinical information, 40 Steroid PRO candidate items and EuroQol-5 Dimensions- 5 levels (EQ-5D-5L). Follow-up, 3-5 days later, collected Steroid PRO candidate items and a condition-change ('transition') question. Analysis included Rasch measurement model, exploratory factor analysis (EFA), and hypothesis testing for discriminative validity, convergence validity and test-retest reliability. RESULTS: Total responses 946: UK n=743 (79%); USA n=139 (15%); Australia/New Zealand n=64 (7%); mean age 57.6 (SD=13.6); 833 (88%) women. Participants with inflammatory arthritis n=197 (21%), connective tissue disease and/or vasculitis n=402 (42%), giant cell arteritis and/or polymyalgia rheumatica n=347 (37%). Twenty-five items were removed due to lack of fit to Rasch model. Of the remaining items, EFA suggested four subscales: Social impact (4 items); Impact on appearance (3 items); Psychological impact (5 items); Treatment concerns (3 items). Rasch modelling supported a four-subscale structure and total score, confirming construct validity and reliability. Hypothesis testing confirmed discriminant and convergence validity. Intraclass correlation coefficient (total score) was 0.809 demonstrating excellent (test-retest) reliability. CONCLUSIONS: The Steroid PRO is a 15-item, valid and reliable scale for measuring the impact of glucocorticoid therapy in people with rheumatic diseases.

Endothelial dysfunction and complement activation are independently associated with disease duration in patients with systemic vasculitis.

OBJECTIVES: Systemic vasculitis is a heterogenous group of autoimmune diseases characterized by enhanced cardiovascular mortality. Endothelial dysfunction is associated with accelerated vascular damage, representing a core pathophysiologic mechanism contributing to excess CV risk. Recent studies have also shown that complement activation holds significant role in the pathogenesis of Anti-Neutrophilic Cytoplasmic Autoantibody (ANCA) -associated vasculitis (AAV). Given the potential crosstalk between the endothelium and complement, we aimed to assess, for the first time simultaneously, easily accessible biomarkers of endothelial dysfunction and complement activation in SV. METHODS: We measured circulating endothelial microvesicles (EMVs) and soluble complement components representative of alternative, classical and terminal activation (C5b-9, C1q, Bb fragments, respectively) in a meticulously selected group of patients with systemic vasculitis, but without cardiovascular disease. Individuals free from systemic diseases, who were matched with patients for cardiovascular risk factors(hypertension, diabetes, smoking, dyslipidemia), comprised the control group. RESULTS: We studied 60 individuals (30 in each group). Patients with systemic vasculitis had elevated EMVs, higher levels of C5b-9 [536.4(463.4) vs 1200.94457.3), p = 0.003] and C1q [136.2(146.5 vs 204.2(232.9), p = 0.0129], compared to controls [232.0 (243.5) vs 139.3(52.1), p < 0.001]. In multivariate analysis both EMVs and C5b-9 were independently associated with disease duration (p = 0.005 and p = 0.004 respectively), yet not with disease activity. CONCLUSION: Patients with systemic vasculitis exhibit impaired endothelial function and complement activation, both assessed by easily accessible biomarkers, even in the absence of cardiovascular disease manifestations. EMVs and soluble complement components such as C5b-9 and C1q could be used as early biomarkers of endothelial dysfunction and complement activation, respectively, in clinical practice during the course of SV, yet their predictive value in terms of future cardiovascular disease warrants further verification in appropriately designed studies.

Shifting perspectives in coronary involvement of polyarteritis nodosa: case of 3-vessel occlusion treated with 4-vessel CABG and review of literature.

BACKGROUND: Polyarteritis Nodosa (PAN) is a systemic vasculitis (SV) historically thought to spare the coronary arteries. Coronary angiography and contemporary imaging reveal coronary stenosis and dilation, which are associated with significant morbidity and mortality. Coronary arteries in PAN are burdened with accelerated atherosclerosis from generalized inflammation adding to an inherent arteritic process. Traditional atherosclerotic risk factors fail to approximate risk. Few reports document coronary pathology and optimal therapy has been guarded. METHODS: Database publication query of English literature from 1990-2022. RESULTS: Severity of coronary involvement eludes laboratory monitoring, but coronary disease associates with several clinical symptoms. Framingham risk factors inadequately approximate disease burden. Separating atherosclerosis from arteritis requires advanced angiographic methods. Therapy includes anticoagulation, immunosuppression and revascularization. PCI has been the mainstay, though stenting is confounded by vagarious alteration in luminal diameter and reports of neointimization soon after placement. CONCLUSIONS: When graft selection avoids the vascular territory of SV's, CABG offers definitive therapy. We have contributed report of a novel CABG configuration in addition to reviewing, updating and discussing the literature. Accumulating evidence suggests discrete clinical symptoms warrant suspicion for coronary involvement.

Enthesitis as an initial presentation of vascular Behçet's syndrome: a case-based review.

Enthesitis is a characteristic manifestation of spondyloarthropathy (SpA). Historically, Behçet's syndrome (BS) was classified within SpA. Although they are now classified separately, the association between BS and SpA remains controversial. The concept of MHC-I (major histocompatibility complex class I)-opathy has been proposed based on the overlap in immunopathological mechanisms among diseases associated with human leukocyte antigen (HLA) class I. Enthesitis is a frequent complication in patients with BS who also have acne and arthritis. However, information regarding enthesitis in patients with BS without arthritis (BS-WA) is limited. Herein, we report a case of vascular BS complicated by enthesitis. In this case, heel pain was the dominant symptom at presentation. Laboratory tests revealed chlamydia antibody positivity, leading to a tentative diagnosis of reactive arthritis. Despite treatment, C-reactive protein (CRP) levels remained elevated. Imaging revealed numerous aneurysmal lesions in the large vessels. Based on these findings and other symptoms, patient was diagnosed with vascular BS. He tested positive for HLA-B15 and HLA-B46, which are associated with peripheral SpA. Subsequent remission induction therapy for BS was effective and the patient was discharged without complications. Our case and a literature review suggest that there exists a subgroup of BS-WA with a complication of enthesitis, possibly belonging to the spectrum of MHC-I-opathies. It is important to consider BS as a differential diagnosis in patients presenting with enthesitis and to conduct a precise medical history review regarding the symptoms of BS.

Clinical and anamnestic features of patients with systemic vasculitis: a single-center retrospective study.

Systemic vasculitides are the most complex and problematic autoimmune rheumatic diseases characterized by affections of large, medium, or small vessels. Although the immunopathogenesis of vasculitides is thoroughly studied, the epidemiology and etiology are poorly explored. The main triggers of vasculitides are environmental, genetic, and various infectious factors. Diagnosis of vasculitides is complicated due to the non-specific nature of their symptoms. Vasculitides affect various organ systems with abrupt or slow (weeks-months) development of symptoms. This study aims to analyze the demographic and clinical-anamnestic characteristics of patients with systemic vasculitides in a single centre before and during the COVID-19 pandemic in Kazakhstan. A single-centre retrospective study of medical records of 80 patients above 18 years was conducted in the Almaty City Rheumatology Center. Medical records of 24 males (30%) and 56 females (70%) with systemic vasculitides, diagnosed from January 2019 to December 2021, were analyzed. Age, gender, damaged organ systems, disability, concomitant diseases, disease experience, laboratory data, and other variables were recorded. The records of hospitalized patients with systemic vasculitides were analyzed. Of 80 patients registered in 2019-2021, the most common were those with IgA vasculitis (n = 32, 40%), Takayasu arteritis (n = 17, 21.25%), and granulomatosis with polyangiitis (n = 12, 15%). Behçet disease was diagnosed less frequently (n = 9, 11.25%). Patients with systemic vasculitides had pre-obesity (n = 19), class 1 obesity (n = 13), and class 2 obesity (n = 2). Musculoskeletal affections were present in 52 patients (65%). Gastrointestinal, cutaneous, and cardiovascular affections were recorded in 45 (56.3%), 37 (46.3%), and 39 (48.8%) cases, respectively. Only 8 patients (10%) had affections of the nervous system. Most patients had elevated C-reactive protein (n = 29, 36.3%) and leukocytosis (n = 33, 41.3%). One-third of patients with vasculitides had a history of abortions. Musculoskeletal, cutaneous, gastrointestinal, and cardiovascular affections are common in patients with systemic vasculitides. Obesity is a frequent comorbidity in vasculitides. Comorbidities and abortions complicate the disease course and its management.

An Update on Noninfectious Retinal Vasculitis.

BACKGROUND: Retinal vasculitis (RV) signifies the inflammation of various retinal vessels. Noninfectious RV differs from infectious RV with regard to its pathogenesis and treatment. It can have varied clinical presentations and may be associated with systemic vasculitic diseases. SUMMARY: Noninfectious RV can be caused due to type-III hypersensitivity reactions, increased expression of intracellular adhesion molecules, and genetic susceptibility. Noninfectious RV is primarily classified on the basis of the type of retinal vessels involved. It can be further classified as an occlusive or nonocclusive. RV can be a major association of systemic diseases like Behcet's disease, sarcoidosis and systemic lupus erythematosus. Newer modalities, like ultra-widefield fundus fluorescein angiography, can help in the management of RV. Effective treatment of noninfectious RV requires anti-inflammatory and immunosuppressive therapy. The patients may require treatment with high-dose corticosteroids and biological agents. Anti-vascular endothelial growth factor injections and laser photocoagulation may be indicated to treat the occlusive disease. Prompt treatment may prevent complications like vitreous hemorrhage, neovascular glaucoma, and tractional retinal detachment. The treatment more often requires a multidisciplinary approach. KEY MESSAGES: This review provides a comprehensive update on the various causes of noninfectious RV, including both systemic and isolated ocular conditions. It also details various complications and management strategies for this condition.

[Laboratory diagnostics for vasculitis beyond antineutrophil cytoplasmatic autoantibodies]. / Labordiagnostik bei Vaskulitiden jenseits von antineutrophilen zytoplasmatischen Autoantikörpern.

The diagnosis of systemic vasculitis (SV) is a major clinical challenge due to the very different forms of presentation and requires an interdisciplinary approach. Targeted laboratory diagnostics support making the diagnosis, differential diagnosis and classification and are also a key component in the detection of active organ manifestations and treatment complications. The basic laboratory tests include the erythrocyte sedimentation rate (ESR), C­reactive protein (CRP), blood count, serum creatinine, urinalysis, specific autoantibodies, complement, immunoglobulins, cryoglobulins and hepatitis B and C serology. Antineutrophil cytoplasmic autoantibodies (ANCA), antiglomerular basement membrane antibodies (anti-GBM antibodies) and anti-C1q antibodies are valuable laboratory markers for the diagnosis of the various forms of small vessel vasculitis. There are no specific laboratory tests for the diagnosis of medium and large vessel vasculitis. Despite advances in our understanding of the pathogenesis of vasculitis, no biomarkers have yet been identified that can be reliably used to guide treatment or that are useful in distinguishing vasculitis from other inflammatory diseases such as infections or treatment complications.

The primary systemic vasculitis associated optic neuritis: a retrospective analysis in a single center over 10 years.

OBJECTIVES: To investigate the clinical and image characteristics of primary systemic vasculitis-associated optic neuritis patients. METHODS: This is a retrospective study. The patients clinically diagnosed with primary system vasculitis-induced optic neuritis were recruited from March 2013 to December 2023. All cases received orbital magnetic resonance imaging scans were analyzed. The ocular findings, systemic manifestations, laboratory data and prognosis were reviewed retrospectively. In addition, the related literature was reviewed. RESULTS: Fourteen patients (21 eyes), including 10 men and 4 women, were enrolled in this study. The ages ranged from 30 to 86 years in this cohort. Orbits MRI detects the enlargement and/or enhancement of the optic nerve. Cases 1-5 reported a confirmed diagnosis of Takayasu's arteritis, and cases 6-8 had giant cell arteritis. Cases 9-13 were antineutrophil cytoplasmic antibody-associated vasculitis. Case 14 was Cogan's syndrome. Mult organs and tissues, such as the kidneys, heart, paranasal sinuses, meninges, and respiratory system, were involved. In all of the 14 involved patients, the disease onset was either during the fall or winter season. There were no or only slight improvements in visual activity after conventional therapies. CONCLUSIONS: The autoantibodies' attack on the optic nerve, ischemic damage, or destruction of the blood-brain barrier may be the potential pathogenesis of vasculitis-associated optic neuritis. Even with prompt and aggressive clinical interventions, the prognosis remains unsatisfactory.

Systemic vasculitis involving the kidney: the nephropathologist's point of view.

Kidneys are often targets of systemic vasculitis (SVs), being affected in many different forms and representing a possible sentinel of an underlying multi-organ condition. Renal biopsy still remains the gold standard for the identification, characterization and classification of these diseases, solving complex differential diagnosis thanks to the combined application of light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM). Due to the progressively increasing complexity of renal vasculitis classification systems (e.g. pauci-immune vs immune complex related forms), a clinico-pathological approach is mandatory and adequate technical and interpretative expertise in nephropathology is required to ensure the best standard of care for our patients. In this complex background, the present review aims at summarising the current knowledge and challenges in the world of renal vasculitis, unveiling the potential role of the introduction of digital pathology in this setting, from the creation of hub-spoke networks to the future application of artificial intelligence (AI) tools to aid in the diagnostic and scoring/classification process.

ANCA-associated systemic vasculitis initially mimicking peripheral neuropathy in an elderly woman.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV) is a rare systemic immunological condition that predominantly impacts small arteries, veins, and capillaries, often leading to kidney damage and pulmonary injury. It is important to note that individuals primarily presenting with peripheral neuropathy (PN) are uncommon in AASV, which can result in significant misdiagnosis or undiagnosed cases. The severity and location of PN can vary among patients. In this article, we present a case of an AASV patient initially showing signs of PN. This case highlights the significance of considering AASV as a potential cause of unexplained neurological symptoms. Timely identification and proper treatment are essential for improving the survival rate and functional prognosis of AASV patients.