Systemic vasculitis: one year in review 2024.

Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

OBJECTIVES: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. METHODS: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. RESULTS: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CONCLUSION: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

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.

Epidemiology of systemic vasculitis.

PURPOSE OF REVIEW: Epidemiology of vasculitides exhibit geographic variation and data from some parts of the world are still scarce. Increased recognition of these rare diseases and improvement in diagnosis and patient care may lead to changes in their epidemiology. In this review, we aimed to highlight the most recent work on the epidemiology of systemic vasculitis. RECENT FINDINGS: New data from countries where information on the epidemiology of giant cell arteritis, Takayasu arteritis and Behçet syndrome were limited have revealed that these conditions are not as rare as previously believed. The incidence rates during the coronavirus disease 2019 pandemic highlight the link between Kawasaki disease and respiratory pathogens. The use of different classification criteria hampers the comparison of true incidence and prevalence rates in antineutophil cytoplasmic antibody (ANCA)-associated vasculitis and its subtypes between geographies and over time. SUMMARY: Recent studies have highlighted the epidemiology of vasculitides in different parts of the world and changing trends. Standardization of study design and disease definitions is needed to improve the reliability and comparability of the results.

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.

Different epidemiologic profiles of systemic vasculitis between Brazil and Peru-preliminary results in two referral centers from both countries.

Little is known about the epidemiology of systemic vasculitis in South American countries. The aim of this study is to compare the prevalence of systemic vasculitides in two vasculitis referral centers from Brazil and Peru. A cross-sectional study was performed and all patients above 18 years of age, with at least 6 months of follow-up and who met classification or diagnosis criteria for the most common forms of vasculitis, were included. A total of 562 patients with systemic vasculitis were analyzed, 345 (61.4%) from Brazil and 217 (38.6%) from Peru. The frequency of Behçet's disease (37.9% vs. 1.8%; p < 0.0001), Takayasu arteritis (TAK) (25.2% vs. 6.9%; p < 0.0001), and giant cell arteritis (9.8% vs. 0.9%; p < 0.0001) was higher in the Brazilian center than the Peruvian one. On the other hand, the frequency of microscopic polyangiitis (MPA) (67.3% vs. 2.8%; p < 0.0001) and renal-limited vasculitis (2.8% vs. 0.0%; p = 0.009) was higher in the Peruvian center. No differences were found concerning other forms of vasculitis. At diagnosis, Brazilian patients with TAK, granulomatosis with polyangiitis, and MPA were younger than Peruvian patients. Epidemiologic differences in the frequency of systemic vasculitis are observed between a vasculitis referral center from Brazil and another from Peru. Key Points • Significant differences are observed regarding the epidemiologic profile of systemic vasculitis between Brazil and Peru. • MPA is the predominant form of vasculitis in Peru while BD and TAK are the most frequent forms of vasculitis in Brazil. • The age at diagnosis of TAK, MPA, and GPA was lower in Brazilian patients than in Peruvian patients.

Cardiovascular events and the role of accelerated atherosclerosis in systemic vasculitis.

The spectrum of inflammatory blood vessel diseases includes both atherosclerosis and the primary systemic vasculitides. Although the inciting triggers differ, significant overlap exists in the mechanisms that contribute to sustained inflammation and vascular damage in both entities. With improvement in therapeutics to control acute vasculitis leading to longer survival, cardiovascular morbidity and mortality has emerged as the leading cause of death for vasculitis patients. Cardiovascular events likely occur as a consequence of vasculitis, vascular damage from prior inflammation causing a sustained procoagulant state, and accelerated atherosclerosis. In this review, we discuss the latest evidence regarding risk of cardiovascular events in patients with major forms of primary systemic vasculitis, and review the mechanisms by which accelerated atherosclerosis may occur.

Risk Factors for Severe Outcomes in Patients With Systemic Vasculitis and COVID-19: A Binational, Registry-Based Cohort Study.

OBJECTIVE: COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID-19. We undertook this study to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS: A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. RESULTS: The cohort included 65 patients with systemic vasculitis who developed COVID-19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1-14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9-38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. CONCLUSION: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision-making relating to the risk of severe COVID-19 in this vulnerable patient group.

Vasculitis Involving the Gastrointestinal System Is Often Incidental but Critically Important.

OBJECTIVES: This study was aimed to investigate the significance of unexpected vasculitis identified in gastrointestinal (GI) specimens by determining its prevalence and correlation with clinical outcomes. METHODS: GI specimens with histologic evidence of vasculitis were identified in our pathology database over a 10-year period (January 2008 to August 2018). Clinical history, treatment, and follow-up were reviewed. RESULTS: Of the 131,367 GI pathology cases received over the 10-year study period, 29 (0.02%) cases showed histologic evidence of GI vasculitis. The majority (69%, 20/29) were not clinically suspected. Of these, 20% (4/20) of patients were subsequently diagnosed with systemic vasculitis. During the mean follow-up period of 34.0 months, 24% (4/17) of the patients with this unexpected diagnosis died as the result of direct complications of GI vasculitis. We also found that 95% of cases with unexpected vasculitis in their GI pathology specimens were communicated in a timely manner to the ordering physicians, which necessitated the immediate initiation of additional workups in 85% of these patients. CONCLUSIONS: The GI involvement of vasculitis is rarely encountered by pathologists, but its diagnosis carries tremendous clinical significance with a high mortality rate. Therefore, timely communication is highly recommended for the early diagnosis and treatment of this disease.

Handgrip strength is a comorbidity marker in systemic necrotizing vasculitides and predicts the risk of fracture and serious adverse events.

OBJECTIVE: Sarcopenia has been associated with poor outcomes in various medical and surgical conditions. However, its impact in systemic necrotizing vasculitides (SNV) had never been characterized. We aimed to assess the prevalence, associated factors and prognostic impact of sarcopenia in SNV. METHODS: Patients with SNV were successively included in a prospective longitudinal study assessing comorbidities. At inclusion, we evaluated sarcopenia by assessing skeletal muscle mass index using DXA and muscle strength using handgrip strength. Vasculitis and treatments-related events were recorded and analysed using Cox models. RESULTS: One hundred and twenty patients were included. At inclusion, low handgrip strength (<30 kg for men and 20 kg for women) was identified in 28 (23%) patients, while no patient exhibited low skeletal muscle mass index (<7.23 kg/m2 for men and 5.67 kg/m2 for women). Low handgrip strength was associated with age (P <0.0001), type of vasculitis (P =0.01), vasculitis damage index (P =0.01), history of falls (P =0.0002), osteoporosis (P =0.04), low serum albumin (P =0.003) and prealbumin (P =0.0007), high CRP (P =0.001), high FRAX® tool (P =0.002) and low bone mineral density at femoral neck (P =0.0002). After median follow-up of 42 months, low handgrip strength was associated with higher risk of bone fracture [HR 4.25 (1.37-13.2), P =0.01] and serious adverse events [HR 2.80 (1.35-5.81), P =0.006]. CONCLUSION: Handgrip strength is associated in SNV with nutritional status and comorbidities such as bone disease, and seems to predict, as in other medical conditions, the risk of fracture and serious adverse events during follow-up. In contrast, assessment of skeletal muscle mass index in this population remains uncertain.

Association of serum high mobility group box 1 levels with disease activity and renal involvement in patients with systemic vasculitis.

High mobility group box 1 (HMGB1) is a kind of proinflammatory mediator that acts as an alarmin when released by dying, injured or activated cells. Previous studies have reported that HMGB1 are closely linked to antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The present study aimed to evaluate whether serum HMGB1 levels were associated with systemic vasculitis (VAs).The study population consisted of 51 patients with VAs, 46 patients with essential hypertension (EH) and 46 healthy controls (HC). Thirty-five patients with VAs had in active stage and 16 patients with VAs in an inactive stage. Furthermore, 31 patients with VAs had renal involvement, the other 20 patients were selected for without renal involvement. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. Associations between serum HMGB1 levels with clinical and laboratory parameters were analyzed.Serum HMGB1 levels in patients with VAs were significantly higher than in EH and HC (all P < .05), and no difference regarding serum HMGB1 levels could be found between EH and HC (P = .208). Serum HMGB1 levels in VAs patients with active stage were significantly higher than those in HC and VAs patients with inactive stage (all P < .05). Patients with renal involvement and non-renal involvement had increased HMGB1 levels compared with HC (all P < .05). In addition, serum HMGB1 levels were significantly higher in patients with renal involvement compared with non-renal involvement patients (P = .001). Correlation analysis showed that serum HMGB1 levels were positive significant correlated with the Birmingham Vasculitis Activity Score, hypersensitive C reactive protein (Hs-CRP), serum creatinine (Scr) and 24-hour proteinuria (all P < .05). Among the subsets of VAs, serum HMGB1 levels were significantly higher in AAV, polyarteritis nodosa (PAN) and takayasu arteritis (TA) than in HC (all P < .05). More interestingly, serum HMGB1 were significantly higher in patients with PAN compared with AAV and TA patients (all P < .05). Furthermore, there was positive correlation between serum HMGB1 levels and Hs-CRP, Scr, and 24-hour proteinuria in patients with PAN (all P < .05).Serum HMGB1 levels are increased in patients with VAs compared with HC and EH and can reflect the disease activity and renal involvement.

Takayasu arteritis: A distinct syndrome of large vessel vasculitis: A view point by late Professor Paul Bacon.

Takayasu arteritis (TA), despite being classified as a large vessel vasculitis, has distinct genetic, pathological and clinical features as compared to giant cell arteritis. It is a rare disease seen more commonly in Asian countries. The challenge lies in assessing the degree of inflammation in a narrowed vessel and immunosuppressive therapy improves inflammatory features but is unable to open up an occluded vessel. It may have a positive effect on retarding further occlusion. Like antineutrophil cytoplasmic antibody-associated vasculitis, TA needs a collaborative effort to do randomized controlled therapy to provide benefit to patients.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Cigarette smoking and risk of primary systemic vasculitis: a propensity score matching analysis.

Introduction: Considering limited data about the association between smoking and primary systemic vasculitides (PSV), present study aims to investigate smoking habit in PSV patients compared to healthy subjects as well as to examine the effect of smoking on clinical characteristics, disease activity and disease outcome in PSV patients. Methodology: We included 126 patients diagnosed with PSV and 210 age- and sex-matched healthy controls. Demographic and clinical information and smoking history of patients and healthy controls were obtained by direct interview and questionnaire. Individuals who had smoked at least 100 cigarettes in their lifetime before the first symptom of vasculitis were classified as smokers; those who had never smoked or smoked less than 100 cigarettes in their lifetime were categorized as never smokers. Disease activity was evaluated by Birmingham Vasculitis Activity Score (BVAS). Disease outcome was assessed by vasculitis damage index (VDI) and the number of patients with disease in remission. Propensity score matching analyses (PSM) for reducing the heterogeneity between studied groups and calculating the actual effect of smoking in PSV was performed. Results: No significant differences were observed in clinical manifestations and disease outcome of patients including VDI and the patients with disease in remission between ever and never smokers. However, disease activity according to BVAS in ever smokers was significantly higher than never smokers (P=0.020). PSM resulted in 82 patients with PSV, and 164 matched healthy persons with similar baseline characteristics. By multivariate logistic regression and after adjustment for age, sex, marital status and educational status, ever smoking was not significantly associated with an increased risk of PSV compared with never smoking. Discussion and conclusion: Our study indicated a significant association between disease activity and smoking as well as a non-significant association between the clinical manifestations and disease outcome of PSV with smoking in Azeri population. Although further studies are needed to confirm these preliminary results, it seems that smoking may not be a significant risk factor for PSV.

Update on the epidemiology, risk factors, and outcomes of systemic vasculitides.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and giant cell arteritis (GCA) are the most common primary systemic vasculitides of the adult population, while polymyalgia rheumatica (PMR) is a clinical syndrome often associated with GCA. Incidence and prevalence rates of AAV have been increasing in the last decades, whereas those of GCA and PMR have remained stable. The mutual interplay between environmental and genetic risk factors leading to the development of these diseases has been further analyzed in the last years. The role of infectious agents has repeatedly been studied with regard to Staphylococcus aureus, associated with relapse in granulomatosis with polyangiitis, and Herpes zoster, potentially contributing to GCA development. Remission of disease and prevention of disease-related complications are the most important outcomes for all systemic vasculitides. Although these goals are achieved in the majority of patients receiving modern therapies, the prevention of treatment-related complications, especially glucocorticoid side effects, is still an unmet need that is common to AAV, GCA, and PMR.

Brief Report: Risk of Childhood Rheumatic and Nonrheumatic Autoimmune Diseases in Children Born to Women With Systemic Lupus Erythematosus.

OBJECTIVE: Several autoimmune diseases have familial aggregation and, possibly, common genetic predispositions. In a large population-based study, we evaluated whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of rheumatic and nonrheumatic autoimmune diseases versus children born to mothers without SLE. METHODS: Using the Offspring of SLE Mothers Registry, we identified children born live to SLE mothers and their matched controls, and ascertained autoimmune diseases based on ≥1 hospitalization or ≥2 physician visits with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetric complications, calendar birth year, and sex of child. RESULTS: A total of 509 women with SLE had 719 children, while 5,824 matched controls had 8,493 children. The mean ± SD follow-up period was 9.1 ± 5.8 years. Children born to mothers with SLE had a similar frequency of rheumatic autoimmune diagnoses (0.14%; 95% confidence interval [95% CI] 0.01-0.90) versus controls (0.19% [95% CI 0.11-0.32]). There was a trend toward more nonrheumatic autoimmune diseases in SLE offspring (1.11% [95% CI 0.52-2.27]) versus controls (0.48% [95% CI 0.35-0.66]). In multivariate analyses, we did not see a clear increase in rheumatic autoimmune disease (odds ratio [OR] 0.71 [95% CI 0.11-4.82]), but children born to mothers with SLE had a substantially increased risk of nonrheumatic autoimmune disease versus controls (OR 2.30 [95% CI 1.06-5.03]). CONCLUSION: Although the vast majority of offspring have no autoimmune disease, children born to women with SLE may have an increased risk of nonrheumatic autoimmune diseases versus controls. Additional studies assessing offspring through to adulthood would be additionally enlightening.

Epidemiology of primary systemic vasculitis in children: a population-based study from southern Sweden.

OBJECTIVES: To estimate the annual incidence rate of paediatric primary systemic vasculitis (PSV) in a defined geographical area in southern Sweden. METHODS: Potential cases of PSV [IgA vasculitis (IgAV, Henoch-Schönlein purpura), Kawasaki disease (KD), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), polyarteritis nodosa (PAN), and Takayasu's arteritis (TAK)] were identified in a comprehensive regional healthcare register. The study area is Skåne, the southernmost county of Sweden (population 1.29 million; 21.4% aged <18 years). Case records for children (0-17 years) assigned a diagnosis code between M300 and M319 and/or D690 were reviewed to ascertain diagnosis. Only patients diagnosed between 2004 and 2014 were included. RESULTS: In total, 556 patients with PSV were identified. The annual incidence rate per million children (95% confidence interval) was estimated to be 200 (183-217) for all PSV, 175.5 for IgAV (160-191), 20.1 for KD (14.9-25.4), 1.4 (0-2.8) for each of GPA and MPA, 0.7 (0-1.7) for PAN, and 0.4 (0-1.1) for each of EGPA and TAK. Among children aged <10 years, 99.5% of cases were either IgAV or KD, both exhibiting a seasonal pattern paralleling infections. There were no deaths, but three cases of end-stage renal disease were noted, all in MPA. CONCLUSIONS: Vasculitis is relatively common during childhood. Mild cases associated with the infection season are most common in the youngest age groups, while during adolescence a substantial proportion has more severe forms of vasculitis.