Anti-LAMP-2 Antibody Seropositivity in Children with Primary Systemic Vasculitis Affecting Medium- and Large-Sized Vessels.

Chronic primary systemic vasculitis (PSV) comprises a group of heterogeneous diseases that are broadly classified by affected blood vessel size, clinical traits and the presence (or absence) of anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) and myeloperoxidase (MPO). In small vessel vasculitis (SVV), ANCA are not present in all patients, and they are rarely detected in patients with vasculitis involving medium (MVV) and large (LVV) blood vessels. Some studies have demonstrated that lysosome-associated membrane protein-2 (LAMP-2/CD107b) is a target of ANCA in SVV, but its presence and prognostic value in childhood MVV and LVV is not known. This study utilized retrospective sera and clinical data obtained from 90 children and adolescents with chronic PSV affecting small (SVV, n = 53), medium (MVV, n = 16), and large (LVV, n = 21) blood vessels. LAMP-2-ANCA were measured in time-of-diagnosis sera using a custom electrochemiluminescence assay. The threshold for seropositivity was established in a comparator cohort of patients with systemic autoinflammatory disease. The proportion of LAMP-2-ANCA-seropositive individuals and sera concentrations of LAMP-2-ANCA were assessed for associations with overall and organ-specific disease activity at diagnosis and one-year follow up. This study demonstrated a greater time-of-diagnosis prevalence and sera concentration of LAMP-2-ANCA in MVV (52.9% seropositive) and LVV (76.2%) compared to SVV (45.3%). Further, LAMP-2-ANCA-seropositive individuals had significantly lower overall, but not organ-specific, disease activity at diagnosis. This did not, however, result in a greater reduction in disease activity or the likelihood of achieving inactive disease one-year after diagnosis. The results of this study demonstrate particularly high prevalence and concentration of LAMP-2-ANCA in chronic PSV that affects large blood vessels and is seronegative for traditional ANCA. Our findings invite reconsideration of roles for autoantigens other than MPO and PR3 in pediatric vasculitis, particularly in medium- and large-sized blood vessels.

Evaluating the risk of ischemic stroke at a young age in patients with autoimmune inflammatory rheumatic diseases: a population-based cohort study in Taiwan.

Background: Recent studies have demonstrated an increased incidence of ischemic stroke among patients with certain autoimmune inflammatory rheumatic diseases (AIIRDs). However, the associations between young stroke and AIIRDs have not been fully investigated. This study aimed to evaluate the risk of ischemic stroke among young patients with AIIRDs. Methods: The National Health Insurance Research Database in Taiwan was utilized to establish cohorts of patients with AIIRDs diagnosed between 2004 and 2015, who were compared with 1,000,000 control participants. Cox proportional hazards regression models were used to calculate the hazard ratio of ischemic stroke and young ischemic stroke for individual AIIRDs after adjustment for relative risk factors. Results: During the study period, a total of 64,120 patients with AIIRDss and 1,000,000 control patients were identified. The overall mean follow-up time was 5.33 years. There were 223 (0.8%) and 1,923 (0.3%) young ischemic stroke-related hospitalizations among patients with AIIRDs and controls, respectively. The incidence rate of young ischemic stroke was 0.08 in patients with rheumatoid arthritis, 0.08 in patients with Sjögren's syndrome, 0.26 in patients with systemic lupus erythematosus, 0.17 in patients with idiopathic inflammatory myositis, 0.24 in patients with systemic sclerosis, 0.05 in patients with Behçet's disease, and 0.44 in patients with systemic vasculitis, versus 0.05 per 100 person-years in the general population. The adjusted hazard ratios for young ischemic stroke were 1.07 (95% CI 0.70-1.43) for rheumatoid arthritis, 1.39 (95% CI 0.94-2.06) for Sjögren's syndrome, 5.79 (95% CI 4.68-7.17) for systemic lupus erythematosus, 2.07 for idiopathic inflammatory myositis (95% CI 0.98-4.38), 2.79 for systemic sclerosis (95% CI 1.38-5.63), 0.82 for Behçet's disease (95% CI 0.26-2.55), and 4.15 (95% CI 1.96-8.82) for systemic vasculitis. Conclusions: Patients younger than 50 years with systemic lupus erythematosus, systemic sclerosis, or systemic vasculitis have a significantly elevated risk of developing ischemic stroke. Further research is needed to elucidate the pathogenesis of accelerated atherosclerosis in these AIIRDs.

Clinical characteristics and risk factors of cardiac involvement in pediatric immunoglobulin A vasculitis: A 7-year retrospective study from a single tertiary medical center.

Immunoglobulin A vasculitis(IgAV) is the most common form of systemic vasculitis affecting children. To date, cardiac involvement in pediatric IgAV has not been fully investigated and its prevalence may be underestimated. This study aims to reveal the clinical and laboratory characteristics of cardiac involvement in pediatric IgAV and further determine its risk factors. A total of 1451 children with IgAV were recruited between January 2016 and December 2022. According to the severity of cardiac involvement, the patients were divided into the myocarditis/suspected myocarditis group, cardiac abnormalities group, and non-cardiac involvement group. Demographic, clinical, and laboratory characteristics were retrospectively extracted from the individual data collected in the medical records. Among the 1451 pediatric IgAV patients, 179 (12.3%) were identified with cardiac involvement, including 154 (10.6%) with cardiac abnormalities and 25 (1.7%) with myocarditis/suspected myocarditis. Cardiac involvement in pediatric IgAV mainly manifested as elevated cardiac biomarker levels (n = 162), electrocardiogram abnormalities (n = 46), and echocardiogram/chest X-ray abnormalities (n = 15); however, cardiac-related symptoms were only observed in 15.1% of patients with cardiac involvement. Multivariate analysis demonstrated that interval from disease onset to diagnosis > 7 days (OR, 2.157; 95% CI, 1.523-3.057; p < 0.001), IgAV with multi-organ involvement (OR, 1.806; 95% CI, 1.242-2.627; p = 0.002), and elevated D-dimer levels (OR, 1.939; 95% CI, 1.259-2.985; p < 0.001) were independent risk factors for cardiac involvement in pediatric IgAV. The length of hospital stay was significantly longer in the myocarditis/suspected myocarditis group compared with the other two groups (p < 0.05).     Conclusion: This study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7 days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV. What is Known: • Immunoglobulin A vasculitis (IgAV) is the most common form of systemic vasculitis affecting children and adolescents, which exhibits diverse clinical manifestations. Cases of severe IgAV complicated by cardiac involvement have been anecdotally reported. What is New: • The present study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7 days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV.

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.

Risk of Hypertensive Disorders and Preterm Birth in Pregnant Women With Systemic Vasculitides: A Nationwide Population-Based Cohort Study.

OBJECTIVE: Even though systemic vasculitides (SVs) affect primarily patients over 50 years of age, they can occur among women of childbearing age. Preterm birth (PTB) and hypertensive disorders are frequent complications of pregnancy in SVs. This study aims to evaluate the risk of hypertensive disorders and PTB among pregnant women with SVs, and to identify associated risk factors. METHOD: Using the French health insurance data warehouse, we conducted a nationwide cohort study including all pregnancies between 2013 and 2018 in women with SVs. Theses pregnancies were matched to pregnancies among women without SVs. We estimated risk of hypertensive disorders and PTB risk during pregnancy among women with SVs and investigated associated risk factors using a nested case-control design. RESULTS: Among 3,155,723 pregnancies, we identified 646 pregnancies in women with SVs, matched to 3,230 controls. SVs were significantly associated with hypertensive disorders (odds ratio [OR] 1.7, 95% confidence interval [95% CI] 1.3-2.2) and PTB (OR 1.8, 95% CI 1.4-2.3). Chronic renal failure before pregnancy, history of or treated arterial hypertension, the occurrence of vasculitides flare during pregnancy, and the subgroup of SVs were independently associated with the occurrence of hypertensive disorders. Maternal age at delivery, chronic renal failure before conception, and the occurrence of vasculitides flare during pregnancy were independently associated with the occurrence of PTB. CONCLUSION: About one of seven pregnancies in women with SVs is associated with hypertensive disorders or preterm birth. The occurrence of vasculitides flare was associated with these complications. Our findings support the importance of prepregnancy counseling to ensure disease stability.

[Severe systemic vasculitis induced by ibrutinib]. / Vascularite systémique sévère induite par l'ibrutinib.

INTRODUCTION: The specific cutaneous toxicity of Bruton's tyrosine kinase inhibitors is poorly described. We report a case of severe systemic vasculitis induced by ibrutinib. OBSERVATION: A 73-year-old woman with chronic lymphocytic leukemia was treated with ibrutinib. Eighteen months after treatment onset, ulceronecrotic lesions on toes and tongue occurred. Skin biopsy found vasculitis of small and medium vessels. Biologic tests were negative. This vasculitis was refractory to systemic corticosteroid therapy and azathioprine. Ibrutinib was stopped on the hypothesis of drug-induced vasculitis. Skin lesions improved after discontinuation of ibrutinib. CONCLUSION: The mechanism of action of ibrutinib does not explain the occurrence of vasculitis and an immunoallergic mechanism is suspected.

Primary Systemic Vasculitides as a Cause of Group IV Pulmonary Hypertension.

The primary systemic vasculitides are rare diseases characterized by vessel wall inflammation. Isolated pulmonary vasculitis, large-vessel vasculitis, and Behçet's disease are mimickers of chronic thromboembolic pulmonary hypertension (CTEPH); group IV pulmonary hypertension (PH) can occur as a devastating complication in the course of these diseases. Pulmonary endarterectomy, balloon angioplasty, anticoagulation and pulmonary vasodilator agents are the main treatment options for CTEPH. There is no specific recommendation for the treatment of patients having group IV PH due to primary systemic vasculitides. We reviewed herein data about group IV PH due to primary systemic vasculitides.

Systemic vasculitis and headache.

PURPOSE OF REVIEW: Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system or so called neurovasculitides, lead to pervasive injury and disability making these disorder of paramount importance to clinicians. RECENT FINDINGS: Headache is an important clue to vasculitic involvement of central nervous system (CNS) vessels. CNS vasculitis may be primary, in which only intracranial vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. A suspicion of vasculitis based on the history, clinical examination, or laboratory studies warrants prompt evaluation and treatment to forestall progression and avert cerebral ischemia or infarction. There has been remarkable progress in the pathogenesis, diagnosis, and treatment of primary adult and pediatric CNS vasculitides predicated on achievements in primary systemic forms. SUMMARY: Vasculitis can be diagnosed with certainty after intensive evaluation that includes tissue confirmation whenever possible. Clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, tempered by the recognition of anticipated medication side effects.

New-onset systemic vasculitis following SARS-CoV-2 infection and vaccination: the trigger, phenotype, and outcome.

The global health crisis caused by the COVID-19 pandemic overwhelmed the capacity of healthcare systems to cope with the rapidly spreading infection and its associated complications. Among these complications, autoimmune phenomena such as systemic vasculitis emerged as a significant challenge. Both the SARS-CoV-2 virus and the vaccines developed to combat it appeared to induce clinical manifestations resembling various types of systemic vasculitis, affecting large, medium, and small vessels. These virus- or vaccine-induced vasculitides exhibited a distinct natural history and course from de novo vasculitis, as they were more responsive to steroid therapy and some mild cases even resolved spontaneously. Notably, there have been no confirmed cases of SARS-CoV-2 infection or vaccination triggering variable vessel vasculitis like Behcet's disease or Kawasaki disease. IgA vasculitis, which is predominantly a pediatric condition, was more prevalent in adults after COVID-19 infection and they had a favorable outcome with glucocorticoid treatment. The impact of immunosuppression, especially B-cell-depleting agents, on the immunogenicity of the vaccine was evident, but there was no significant increase in the incidence of SARS-CoV-2 infection in these patients compared to the general population. Considering their relatively benign course, these post-COVID or post-vaccine vasculitides seem to be amenable to 0.8 to 1 mg/kg prednisolone or equivalent, which could be gradually tapered. The need for immunosuppression and the duration of steroid therapy should be determined on an individual basis. While the world still reels from the perils of a deadly pandemic, the aftermath continues to haunt. Our narrative review aims to explore the effects of COVID and the vaccine on systemic vasculitis, as well as the effect of disease and immunosuppression on the immunogenicity of the COVID vaccine.

Patient-reported outcomes in vasculitis.

Systemic vasculitis encompasses a group of multisystem disorders; both the diseases and the treatment strategies can have a significant impact on a patient's health-related quality of life (HRQoL). Using patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) to evaluate the patient's view of their condition, treatments, and healthcare journey is essential to the patient-centered care approach. In this paper, we discuss the use of generic, disease-specific, and treatment-specific PROMs and PREMs in systemic vasculitis and future research goals.

Dermatological Lesions of Cholesterol Embolisation Syndrome and Kaposi Sarcoma Mimic Primary Systemic Vasculitis: Case report study.

Primary systemic vasculitis can present with a wide spectrum of manifestations ranging from systemic non-specific features such as fever, malaise, arthralgia and myalgia to specific organ damage. We describe two cases of cholesterol embolisation syndrome and Kaposi sarcoma mimicking primary systemic vasculitis, both of which were characterised by features such as livedo reticularis, blue toe syndrome, a brown purpuric skin rash and positive perinuclear anti-neutrophil cytoplasmic antibodies associated with Kaposi sarcoma. Establishing the right diagnosis was challenging and thus this report aimed to highlight the possible ways to distinguish them from primary systemic vasculitis.

Central Nervous System Vasculitis: Primary Angiitis of the Central Nervous System and Central Nervous System Manifestations of Systemic Vasculitis.

Central nervous system vasculitis (CNSV) is a group of disorders leading to inflammatory vasculopathy within the brain, spinal cord, and leptomeninges. CNSV is divided into primary angiitis of the central nervous system (PACNS) and secondary CNSV based on the underlying etiology. PACNS is a rare inflammatory disorder with poorly understood pathophysiology and heterogeneous and highly variable clinical features. The diagnosis depends on a combination of clinical and laboratory variables, multimodal imaging, and histopathological examination as well as exclusion of mimics. Several systemic vasculitides, infectious etiologies and connective tissue disorders have been shown to cause secondary CNSV and require prompt recognition.

Systemic Vasculitis and Its Association with the Eye.

Vasculitis is a group of diseases characterized by the inflammation of the blood vessel walls. They are classified according to the size of the main vessel involved: large vessel, medium vessel, and small vessel vasculitis. Ophthalmic manifestations are quite common in most of these diseases. Episcleritis and scleritis are the most prevalent manifestation of vasculitis. However, there are certain ocular features characteristic of specific vasculitis entities. Given the severity and potential life-threat of these diseases, knowledge of the ocular manifestations is mandatory for the ophthalmologists.

Cardiac Involvement in Systemic and Local Vasculitides: The Value of Noninvasive Multimodality Imaging.

Despite significant advances in managing systemic vasculitides, cardiovascular morbidity, and mortality are still of primary concern. Advances in noninvasive imaging have broadened our understanding of the clinical heterogeneity of cardiac involvement in vasculitides. Common cardiovascular complications in primary or secondary vasculitides are; coronary artery aneurysms, acute coronary syndromes, myocarditis, pericarditis, endocarditis, and valvular dysfunction. Echocardiography, cardiac magnetic resonance , positron emission tomography, and computed tomography angiography are essential in identifying cardiac involvement and guiding treatment. Here, we present our experiences of cardiac involvement in systemic vasculitides, covering most aspects of common cardiac complications based on a multi-modality approach to challenging (real-world) cases. As many cardiac manifestations are clinically silent, heart function should be systemically assessed by a multimodality imaging-based approach, including ECG, serial echocardiograms with strain imaging and 3D, and cardiac magnetic resonance to detect early signs of cardiac manifestations. This enables timely intervention and optimal medical treatment, which is essential for a better prognosis. There is a need for better and closer collaboration in clinical practice and research fields between cardiologists and rheumatologists.

Multicentre case-control study evaluating the safety of anti-SARS-CoV-2 vaccines in a cohort of patients with systemic vasculitis.

OBJECTIVES: Data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis (SV), are limited. The aim of this study was to evaluate the occurrence of a disease flare and the appearance of adverse events (AEs) following administration of anti-SARS-CoV-2 vaccine in a multicentre cohort of patients with SV. METHODS: Patients with SV and healthy controls (HC) from two different Italian rheumatology centres were asked to complete a questionnaire assessing disease flares occurrence, defined as new onset of clinical manifestations related to vasculitis needing an implementation of therapy, and local/systemic AEs appearance following anti SARS-CoV-2 vaccination. RESULTS: 107 patients with SV (57 ANCA-associated) and 107 HC were enrolled. A disease flare occurred in only one patient (0.93%) with microscopic polyangiitis after the first dose of an mRNA vaccine. After both the first and the second vaccine dose administration, no significant differences in AEs between patients with SV and HC were observed; no serious AEs were reported as well. CONCLUSIONS: These data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.

Systemic vasculitis: one year in review 2023.

Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.

The epidemiology of pathologically confirmed clinically isolated aortitis: a North American population-based study.

OBJECTIVES: Clinically isolated aortitis (CIA) refers to inflammation of the aorta without signs of systemic vasculitis or infection. Population-based data on the epidemiology of CIA in North America is lacking. We aimed to investigate the epidemiology of pathologically confirmed CIA. METHODS: Residents of Olmsted County, Minnesota were screened for thoracic aortic aneurysm procedures with current procedural terminology codes between January 1, 2000, and December 31, 2021, using the resources of the Rochester Epidemiology Project. The medical records of all patients were manually reviewed. CIA was defined as histopathologically confirmed active aortitis diagnosed by evaluation of aortic tissue obtained during thoracic aortic aneurysm surgery in the absence of any infection, rheumatic disease, or systemic vasculitis. Incidence rates were age and sex adjusted to the 2020 United States total population. RESULTS: Eight incident cases of CIA were diagnosed during the study period; 6 (75%) of them were female. Median (IQR) age at diagnosis of CIA was 78.3 (70.2-78.9) years; all were diagnosed following ascending aortic aneurysm repair. The overall age and sex adjusted annual incidence rate of CIA was 8.9 (95% CI, 2.7-15.1) per 1,000,000 individuals over age 50 years. The median (IQR) duration of follow-up was 8.7 (1.2-12.0) years. The overall mortality compared to the age and sex matched general population did not differ (standardised mortality ratio: 1.58; 95% CI, 0.51-3.68). CONCLUSIONS: This is the first population-based epidemiologic study of pathologically confirmed CIA in North America. CIA predominantly affects women in their eighth decade and is quite rare.

Another side of lupus: A case report of lupus presenting with cutaneous vasculitis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune complex disease that affects any organ, characterized by immune complex formation and autoantibody production. Lupus vasculitis begins at a young age. These patients generally have a longer disease duration. Ninety percent of cases in lupus-associated vasculitis present with cutaneous vasculitis. Disease activity, severity, organ involvement, response to treatment and drug toxicity determine the frequency of outpatient control in lupus. Depression and anxiety are observed more frequently in SLE than in the normal population. Our case, it is an example of the patient's disruption of controls due to psychological trauma and that lupus can cause serious cutaneous vasculitis. In addition, psychiatric evaluation of lupus cases from the time of diagnosis may have a positive effect on the prognosis.

Identification of new risk loci shared across systemic vasculitides points towards potential target genes for drug repurposing.

OBJECTIVES: The number of susceptibility loci currently associated with vasculitis is lower than in other immune-mediated diseases due in part to small cohort sizes, a consequence of the low prevalence of vasculitides. This study aimed to identify new genetic risk loci for the main systemic vasculitides through a comprehensive analysis of their genetic overlap. METHODS: Genome-wide data from 8467 patients with any of the main forms of vasculitis and 29 795 healthy controls were meta-analysed using ASSET. Pleiotropic variants were functionally annotated and linked to their target genes. Prioritised genes were queried in DrugBank to identify potentially repositionable drugs for the treatment of vasculitis. RESULTS: Sixteen variants were independently associated with two or more vasculitides, 15 of them representing new shared risk loci. Two of these pleiotropic signals, located close to CTLA4 and CPLX1, emerged as novel genetic risk loci in vasculitis. Most of these polymorphisms appeared to affect vasculitis by regulating gene expression. In this regard, for some of these common signals, potential causal genes were prioritised based on functional annotation, including CTLA4, RNF145, IL12B, IL5, IRF1, IFNGR1, PTK2B, TRIM35, EGR2 and ETS2, each of which has key roles in inflammation. In addition, drug repositioning analysis showed that several drugs, including abatacept and ustekinumab, could be potentially repurposed in the management of the analysed vasculitides. CONCLUSIONS: We identified new shared risk loci with functional impact in vasculitis and pinpointed potential causal genes, some of which could represent promising targets for the treatment of vasculitis.