Unclassified Vasculitis Research Articles

Epidemiology of ANCA vasculitis in Northern Spain.

The incidence of anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) shows disparate results due to variable classification criteria and heterogeneous-population series. We aimed to estimate the incidence of AAV in a well-defined population with standardized classification criteria. Population-based study of AAV patients diagnosed from January 2000 to December 2023 in Cantabria, Northern Spain. Patients were classified according to ACR/EULAR 2022 into granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or unclassified vasculitis if the criteria were not met. Eosinophilic granulomatosis with polyangiitis (EGPA) patients were not included. The annual incidence rates were estimated by cases over 1,000 000 (106) (95% CI) including overall AVV, type of AAV, sex, and year of diagnosis. A literature review was also performed. We included 152 (80/72 men; mean age; 70.6 ± 13.18 years) patients. They were classified as MPA (67; 44%), GPA (64; 42.2%), and unclassified vasculitis (21; 13.8%). Annual incidence was 13.4 (10-16.8)/106 [male 14.5 (10.5-18.5); female 12.1 (8.7-15.6)]. The Annual incidence of MPA was 5.9 (4-7.8)/106 and GPA 5.6 (3.9-7.3)/106. The mean Annual incidence increased from 6.1 (4.5-7.7)/106-16.5 (5.6-27.4)/106 in the last three years, particularly, in GPA from 2.3 (0.3-4.9)/106-8.2 (2-14.5)/106. The prevalence of AAV was 184.7 (181-188)/106. During a 20-year period we found that the incidence of AAV (GPA and MPA) in Northern Spain is higher than Southern Spain, but lower than Northern European countries. An increase in the incidence was observed in the last years.

COVID-19 Associated Vasculitis Confirmed by the Tissues RT-PCR: A Case Series Report

Several cases of skin and central nervous system vasculopathy associated with COVID-19 in children have been published, but the information is rather limited. Our study aimed to describe these cases of vasculitis associated with COVID-19 in children. In the retrospective-prospective case series study we included information regarding four children with COVID-19-associated vasculitis. In every case, we had a morphological description and the etiology was confirmed via real-time polymerase chain reaction during a tissue biopsy. The most involved systems were skin (4/4), respiratory (3/4), cardiovascular (2/4), nervous (1/4), eye (1/4), kidney (1/4), and inner year (1/4). All patients had increased inflammatory markers and thrombotic parameters (D-dimer). No patient met the criteria for multisystem inflammatory syndrome in children. Two patients met polyarteritis nodosa criteria, one met Henoch-Schonlein purpura criteria, and one met unclassified vasculitis criteria. All patients were treated with systemic glucocorticosteroids (two-pulse therapy). Non-biologic DMARDs were prescribed in all cases; 1/4 patients (25%) was treated with intravenous immunoglobuline, and 3/4 (75%) were treated with biologics (etanercept, tocilizumab, and adalimumab). Vasculitis associated with COVID-19 could be a life-threatening condition; SARS-CoV-2 might be a new trigger or etiological agent for vasculitis and other immune-mediated diseases. Further research and collection of similar cases are required.

Vasculitis and familial Mediterranean fever: Description of 22 French adults from the juvenile inflammatory rheumatism cohort.

The frequency of vasculitis may be increased in patients with Familial Mediterranean Fever (FMF), according to several studies. Our aim was to assess the characteristics of French adult patients with both diseases. Patients with vasculitis were selected from patients followed for FMF in the French JIR-cohort. Twenty-two patients were included [polyarteritis nodosa (PAN) n = 10, IgA vasculitis n = 8, unclassified vasculitis n = 2, granulomatosis with polyangiitis n = 1, and microscopic polyangiitis n = 1]. Pathogenic mutations in exon 10 were found in all 21 patients (96%) for which MEFV testing results were available, and 18 (82%) had two pathogenic mutations. Histology showed vasculitis in 59% of patients. Most patients with FMF-associated PAN were HBV-negative and had an inactive FMF before PAN onset, and 40% had a peri-renal or central nervous system bleeding. Most patients with FMF-associated IgA vasculitis had an active FMF before vasculitis onset, and 25% had digestive bleeding. Both patients with unclassified vasculitis had ischemic and/or hemorrhagic complications. This study confirms the predominance of PAN and IgA vasculitis in patients with FMF and the high frequency of bleeding in FMF-associated PAN. FMF should be considered in case of persistent symptoms and/or inflammatory syndrome despite vasculitis treatment in Mediterranean patients.

Clinical differences among patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive interstitial lung disease.

Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and idiopathic interstitial lung diseases (IIPs) are positive for myeloperoxidase (MPO)-ANCA. MPO-ANCA-positive vasculitis mainly comprises microscopic polyangiitis (MPA) and unclassifiable vasculitis. These diseases are frequently complicated by interstitial lung disease (ILD). Few studies have reported the clinical differences between the subtypes of MPO-ANCA-positive ILD. Therefore, this study aimed to examine the clinical findings and courses of MPO-ANCA-positive ILD. This retrospective study enrolled 100 patients with MPO-ANCA-positive ILD who were categorized into three groups: MPA (n = 44), unclassifiable vasculitis (n = 29), and IIP (n = 27). Our study compared the clinical findings and prognosis of these patients and analyzed the poor prognostic factors. Furthermore, we assessed the association between the patients with and without acute exacerbation of ILD (AE-ILD). Our study found clinical differences in serum markers, clinical symptoms, and treatment regimens among the three groups. ILD complications, as the main cause of death, differed among the three groups (P = 0.04). Patients with unclassifiable vasculitis showed higher survival rates than those with IIP (P = 0.046). Patients with AE-ILD showed fewer general symptoms (P = 0.02) and lower survival rates (P < 0.01) than those without AE-ILD. In multivariate analysis, AE-ILD development was a strong poor prognostic factor for MPO-ANCA-positive ILD. The subtypes of MPO-ANCA-positive ILD have different clinical features and prognoses. Patients who develop AE-ILD require careful evaluation of clinical courses. Key Points • In myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-positive interstitial lung disease (ILD), patients with unclassifiable vasculitis showed a better prognosis than those with idiopathic ILD.. • Development of acute exacerbation in ILD was a strong poor prognostic factor in patients with MPO-ANCA-positive ILD..

The Reclassification of Patients With Previously Diagnosed Eosinophilic Granulomatosis With Polyangiitis Based on the 2022 ACR/EULAR Criteria for Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

The American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) have proposed the 2022 classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). This study applied the 2022 ACR/EULAR criteria to Korean patients with previously diagnosed EGPA to investigate the concordance rate between the 2022 ACR/EULAR criteria and the old criteria for EGPA. In total, 51 patients with EGPA who met the 1990 ACR criteria, the 2007 European Medicines Agency algorithm, and the 2012 Chapel Hill Consensus Conference definitions were reclassified based on the 2022 ACR/EULAR criteria. Of 51 patients, 44 (86.3%) were reclassified as having EGPA according to the 2022 ACR/EULAR criteria. Among the 7 patients who failed to meet the 2022 ACR/EULAR criteria, 3 patients were reclassified as having microscopic polyangiitis (MPA) and 1 was reclassified as having granulomatosis with polyangiitis (GPA) based on the 2022 ACR/EULAR criteria; as well, 3 patients were reclassified as having unclassifiable vasculitis. Moreover, 6 patients who met the 2022 ACR/EULAR criteria for EGPA simultaneously met the criteria for MPA based on the 2022 ACR/EULAR criteria for MPA, and 1 who met the criteria for EGPA simultaneously met the criteria for GPA based on the 2022 ACR/EULAR criteria for GPA. The concordance rate between the 2022 ACR/EULAR criteria for EGPA and the old criteria was 86.3%. The most important factor in the failure to reclassify patients as having EGPA was the exclusion of nonfixed pulmonary infiltrates in the 1990 ACR criteria for EGPA. We cautiously suggest reconsidering nonfixed pulmonary infiltrates in cases reclassified as unclassifiable vasculitis. Further, additional classification strategies are needed for patients who simultaneously satisfy both antineutrophil cytoplasmic antibody-associated vasculitis subtypes.

Reclassification of previously diagnosed GPA patients using the 2022 ACR/EULAR classification criteria.

This study applied the 2022 criteria for granulomatosis with polyangiitis (GPA) proposed by the ACR and EULAR (the 2022 ACR/EULAR criteria) to Korean patients with previously diagnosed GPA to investigate the number of patients who could be reclassified as having GPA. Sixty-five patients with GPA, who met the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides and the 2007 European Medicines Agency algorithm for GPA, were included in this study. They were reclassified based on the 2022 ACR/EULAR criteria. Of the 65 patients, 48 patients (73.8%) were reclassified as having GPA. A patient could not be reclassified as having GPA if the patient did not have a total score of 5 despite granulomas on biopsy or clear GPA surrogate markers. Among the 17 patients unclassified as having GPA, 16 patients were reclassified as having MPA and one as having unclassifiable vasculitis, and furthermore, 94.1% of them harboured MPO-ANCA (or perinuclear (P)-ANCA). The concordance rate between the 2022 ACR/EULAR criteria for GPA and the previous criteria in patients with previously diagnosed GPA was 73.8%. Although the 2022 ACR/EULAR criteria are the product of the most advanced methodologic process, it should be noted that there were some consequences of distorting the CHCC definition, and further discussion is required, especially with respect to the weightage of the items.

Clinical Characteristics of Adult Patients with Systemic Vasculitis: Data of 1348 Patients from a Single Center.

To investigate the clinical characteristics of patients with systemic vasculitis in China by analyzing the data from a nationwide registry database, the Chinese Registry for Systemic Vasculitis (CRSV). The demographic data, clinical presentations, image and laboratory test results, disease activity assessment, treatment, and outcome of patients enrolled with the confirmed diagnosis of systemic vasculitis, including Takayasu's arteritis (TAK), ANCA-associated vasculitis (AAV), Behcet's syndrome (BD), Polyangitis nodosa (PAN), and unclassified systemic vasculitis (USV), were collected since July 2013 in the CRSV. The data during July 2013 and February 28 of 2020 were retrieved and analyzed. Up to February 2020, 3852 patients in total were registered in the CRSV. In Peking Union Medical College Hospital (PUMCH), 1348 patients were registered, including 730 patients with TAK, 343 with Behcet's disease (BD), 191 with AAV, 53 with USV, and 31 with PAN. More male patients were found in PAN (64.5%), BD (59.8%), and AAV (52.4%), while TAK was more prevalent in female patients (85.9%). The average age at disease diagnosis was 29.6 in TAK, 33.2 in BD, 28.6 in PAN, 39.4 in USV, and 48.1 in AAV. A significant difference was found between age at diagnosis of TAK and AAV. Gender comparisons revealed that the age at diagnosis of male patients with AAV was older than female patients. Hypertension (57.3%) and stroke (17.5%) were found to be more common in male patients with TAK, vascular involvement (27.3%) was found to be more common in male patients with BD, while neurological involvement (29.0%) was found to be more common in male patients with AAV than in females. This registry is the first in China and provides rich information about the clinical characteristics of Chinese patients with systemic vasculitis. There are significant differences in clinical presentations between different categories of systemic vasculitis.

Use of new diagnostic criteria for reclassification of polyarteritis nodosa

With the recognition of antineutrophil cytoplasmic antibodies (ANCA)-related vasculitis and widespread vaccination against viral hepatitis B, the prevalence of polyarteritis nodosa (PAN) varied considerably. In our study, patients diagnosed as polyarteritis nodasa (PAN)based on the 1990 American College of Rheumatology(ACR) criteria were reclassified using 2007 European Medicines Agency(EMA) algorithm modified by 2012 Chapel Hill Consensus Conference(CHCC) definitions, aiming to evaluate the new classification criteria for the diagnosis of PAN. A total of 113 PAN patients admitted to Peking Union Medical College Hospital from January 2002 to December 2018 were retrospectively analyzed, who were classified into three subtypes including 9 patients with cutaneous, 80 with classic and 24 Hepatitis B virus (HBV) associated PAN. All patients were reclassified according to 2007 EMA algorithm using CHCC 2012 definitions. As a result, 7 patients were diagnosed as microscopic polyangiitis(MPA) and 19 patients with unclassified vasculitis based on the new classification criteria. The diagnostic rate of PAN was gradually declined as the classification criteria of vasculitides was update. However, there are quite a few PAN patients in China, whom rheumatologists should pay attention to the early diagnosis and treatment.

Identification of Novel Adenosine Deaminase 2 Gene Variants and Varied Clinical Phenotype in Pediatric Vasculitis.

Individuals with deficiency of adenosine deaminase 2 (DADA2), a recently recognized autosomal recessive disease, present with various systemic vascular and inflammatory manifestations, often with young age at disease onset or with early onset of recurrent strokes. Their clinical features and histologic findings overlap with those of childhood-onset polyarteritis nodosa (PAN), a primary "idiopathic" systemic vasculitis. Despite similar clinical presentation, individuals with DADA2 may respond better to biologic therapy than to traditional immunosuppression. The aim of this study was to screen an international registry of children with systemic primary vasculitis for variants in ADA2. The coding exons of ADA2 were sequenced in 60 children and adolescents with a diagnosis of PAN, cutaneous PAN, or unclassifiable vasculitis (UCV), any chronic vasculitis with onset at age 5 years or younger, or history of stroke. The functional consequences of the identified variants were assessed by ADA2 enzyme assay and immunoblotting. Nine children with DADA2 (5 with PAN, 3 with UCV, and 1 with antineutrophil cytoplasmic antibody-associated vasculitis) were identified. Among them, 1 patient had no rare variants in the coding region of ADA2 and 8 had biallelic, rare variants (minor allele frequency <0.01) with a known association with DADA2 (p.Gly47Arg and p.Gly47Ala) or a novel association (p.Arg9Trp, p.Leu351Gln, and p.Ala357Thr). The clinical phenotype varied widely. These findings support previous observations indicating that DADA2 has extensive genotypic and phenotypic variability. Thus, screening ADA2 among children with vasculitic rash, UCV, PAN, or unexplained, early-onset central nervous system disease with systemic inflammation may enable an earlier diagnosis of DADA2.

Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes: French retrospective case-control study.

We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs). Data for 21 patients with trisomy 8-MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8-MDS/MPN without IADs. The median age of MDS/MPN patients with IADs was 67 [59-80]. The IADs were Behçet's-like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8-MDS/MPN cases without IADs, those with IADs were more often non-European (P=0.005) and had poor karyotype (P<0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8-associated MDS/MPN with and without IADs. The spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by Behçet's-like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.

CRDC: a Chinese rheumatology research platform.

This review introduces the history of development, organizational structure, funding resources, data collection, and quality control of the Chinese Rheumatism Data Center (CRDC) and summarizes the collection of data. In 2009, Peking Union Medical College Hospital (PUMCH), together with several rheumatism centers, established the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research Group (CSTAR) to collect data on Chinese patients for the study of SLE disease characteristics. In 2011, CSTAR was extended with the formation of the CRDC at PUMCH with direction from the National Health and Family Planning Commission of the PRC. The CRDC currently includes 300 registration sites and 50 regional sites that have successively begun to collect data on 12 rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, dermatomyositis, Takayasu arteritis, IgG4-related diseases, ANCA-associated vasculitis, gout, polyarteritis nodosa, unclassified systemic vasculitis, and Behcet disease. To date, 17,224 patients have been enrolled in the CRDC. Based on the SLE patients registered in the CRDC, papers investigating basic demographic characteristics and first symptom in Chinese SLE patients, risk factors of pulmonary hypertension, correlations between autoantibodies and clinical manifestations, and factors related to fetal loss have been published. The CRDC is a national registry that provides real-life data to improve clinical decision-making. At the same time, without additional work for the clinician, the CRDC is a powerful research database. The CRDC database provides sufficient information for Chinese clinical studies on rheumatology. Moreover, a mobile device application ensures convenient and efficient data collection without compromising data quality, thereby providing strong evidence-based data for the diagnosis and treatment of Chinese rheumatic patients.

Classification and characteristics of Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study.

IntroductionWe investigated the clinical and serological features of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan using data from a nationwide, prospective, inception cohort study.MethodsIn total, 156 Japanese patients with newly diagnosed AAV were classified according to the European Medicines Agency (EMEA) algorithm with exploratory surrogate markers for AAV-related non-granulomatous pulmonary lesions, predefined as alveolar haemorrhage and interstitial lung disease (ILD), and their clinical and serological features were evaluated.ResultsUsing the EMEA algorithm, we identified 14 patients (9.0%) with eosinophilic granulomatosis with polyangiitis (EGPA), 33 (21.2%) with granulomatosis with polyangiitis (GPA), 78 (50.0%) with microscopic polyangiitis and renal-limited vasculitis (MPA/RLV), and 31 (19.9%) with unclassifiable vasculitis. The average ages of patients with EGPA (male/female, 5/9), GPA (12/21), and MPA/RLV (35/43) and unclassifiable (9/22) were 58.0, 63.6, 71.1, and 70.6 years, respectively. Myeloperoxidase (MPO)-ANCA and proteinase-3 ANCA positivity was 50.0% and 0% for EGPA, 54.6% and 45.5% for GPA, 97.4% and 2.6% for MPA/RLV, and 93.5% and 3.2% for unclassifiable, respectively. According to the Birmingham Vasculitis Activity Score (BVAS), cutaneous (71.4%) and nervous system (92.9%) manifestations were prominent in EGPA and ear, nose, and throat manifestations (84.9%) and chest manifestations (66.7%) in GPA. Renal manifestations developed frequently in MPA/RLV (91.0%) and GPA (63.6%). The average serum creatinine levels were 0.71 mg/dL for EGPA, 1.51 mg/dL for GPA, 2.46 mg/dL for MPA/RLV, and 0.69 mg/dL for unclassifiable. The percentages of patients with ILD were 14.3% for EGPA, 9.0% for GPA, 47.4% for MPA/RLV, and 61.3% for unclassifiable. Patients with ILD (n = 61) had significantly lower BVAS (P = 0.019) with fewer ear, nose, and throat and cardiovascular manifestations than patients without ILD (n = 95).ConclusionsMPO-ANCA-positive MPA/RLV is the most common form of AAV in Japanese patients, and one-half of patients with GPA were positive for MPO-ANCA. ILD is an important clinical manifestation in Japanese patients with AAV. Unclassifiable vasculitis with MPO-ANCA positivity and ILD may represent a novel variant of MPA.Trial RegistrationThe University Hospital Medical Information Network Clinical Trials Registry: UMIN000001648. Registered 28 February 2009.

Uncommon presentations of primary systemic necrotizing vasculitides: the Great Masquerades

Systemic vasculitides are great masqueraders and at times their presenting manifestations can be very different from the usual recognized patterns. Such uncommon presentations of granulomatosis with polyangiitis (Wegener's granulomatosis), classical polyarteritis nodosa and unclassifiable vasculitides are described here with the relevant review of literature. All patients diagnosed as having systemic vasculitides and classified as having granulomatosis with polyangiitis (Wegener's granulomatosis), classic polyarteritis nodosa, microscopic polyangiitis and unclassifiable vasculitis according to EMEA consensus methodology and followed up prospectively from June 2007 to December, 2011 were included. Details of uncommon presentations of these disorders were identified. Seventy-nine patients with systemic vasculitides were seen under our rheumatology services during this period. These included 45 patients with granulomatosis with polyangiitis (Wegener's granulomatosis), 18 with classic polyarteritis nodosa, five with microscopic polyangiitis, four with Churg-Strauss syndrome and seven with unclassifiable vasculitis. The uncommon presentations of granulomatosis with polyangiitis were a tumefactive subcutaneous mass in the thigh; prostatomegaly with obstructive uropathy and advanced renal failure; and predominant gastrointestinal (GI) vasculitis with thrombocytopenia and coagulopathy at presentation. The uncommon manifestations of classic polyarteritis nodosa were secondary antiphospholipid antibody syndrome and Budd-Chiari syndrome. One patient with massive lower GI bleeding required surgical resection of the large bowel which showed isolated necrotizing granulomatous GI vasculitis. Single organ vasculitis of the GI tract was diagnosed. Systemic necrotizing vasculitides may present with uncommon manifestations and a high index of suspicion is required for early diagnosis and prompt treatment to prevent adverse outcomes.

FRI0226 Anca-associated vasculitis in a community-based teaching hospital in japan

BackgroundClinical phenotype of ANCA-associated vasculitis (AAV) is different between Japan and European countries with microscopic polyangiitis (MPA) predominating in Japan.1ObjectivesTo investigate the diagnosis and prognosis of AAV in a community-based...

Increased Sensitivity of the European Medicines Agency Algorithm for Classification of Childhood Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis (Wegener's; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative. Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference). MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA. EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.

A Half-Century of Autopsy Results

The objectives of this study were to clarify the details of pediatric vasculitic diseases on the basis of Japanese autopsy reports and determine whether there were cases of probable Kawasaki disease (KD) even before KD came to be widely recognized as a disease entity. Systemic vasculitis autopsy cases aged 15 years or less were selected from the total of 1,335,045 autopsy cases listed in the Annual of Pathological Autopsy Cases in Japan from 1958 through 2008. Those cases were classified into 14 disease groups and then analyzed with regard to various details. There were 380 autopsy cases of vasculitis in children (0.03% of the total autopsy cases). More than half were KD, and other diseases included unclassified vasculitis, polyarteritis nodosa, purpuric vasculitis, Takayasu arteritis, etc. The first recorded case of KD autopsy occurred in 1969. Up until 1976 there was a great difference in the number of autopsies between pediatric vasculitis and KD. However, after 1977 their numbers were in close agreement. The autopsy findings for 24 of 125 child vasculitis autopsies performed before 1976 and diagnosed as non-KD were consistent with KD. Although autopsies of pediatric vasculitis cases are extremely rare, the majority consists of KD. Moreover, it is likely that autopsy cases that were probably KD first appeared in the early 1960s.

Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood

To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4-17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0-49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.

Biologic therapy in primary systemic vasculitis of the young

To describe the biologic treatment regimens and report the efficacy and safety of biologic therapies in a multicentre series of children with primary systemic vasculitis (PSV). This was a retrospective descriptive case series of children with PSV treated with biologic therapy between February 2002 and November 2007. Primary retrospective outcome assessment measures were: daily corticosteroid dose; Birmingham Vasculitis Activity Score (BVAS); and adverse events (including infection rate). Twenty-five patients median age 8.8 (range 2.4-16) years; 11 male with active PSV (n = 6 with anti-neutrophil cytoplasmic antibody associated vasculitides, n = 11 with polyarteritis nodosa, n = 7 with unclassified vasculitis and n = 1 with Behçet's disease) were treated with biologic agents including infliximab (n = 7), rituximab (n = 6), etanercept (n = 4), adalimumab (n = 1) or multiple biologics sequentially (n = 7). Overall, there was a significant reduction in BVAS from a median of 8.5 (range 5-32) at start of therapy to 4 (range 0-19) at median 32 months follow-up (P = 0.003) accompanied by significant reduction in median daily prednisolone requirement from 1 (range 0.2-2) to 0.25 (range 0-1) mg/kg/day, P = 0.000. For those receiving multiple biologic agents sequentially, a similar clinical improvement was observed with corticosteroid sparing. Infections occurred in 24%, the most severe in those receiving infliximab. Our data provide retrospective evidence of efficacy of these agents, and highlight the associated infectious complications. Further multicentre standardization of treatment protocols and data collection to inform clinical trials of biologic therapy in systemic vasculitis of the young is required.

The significance of IgA class of antineutrophil cytoplasmic antibodies (ANCA) in childhood Henoch-Schönlein purpura.

Antineutrophil cytoplasmic antibodies (ANCA) have been identified in a wide variety of vasculitic disorders, but it is controversial whether ANCA are present in the sera of patients with HSP. This prospective study was designed to assess the place of ANCA, particularly their IgA subclass, in HSP. Thirty-five patients (18 boys, 17 girls) aged 9.4 +/- 4 (3-16) years with a clinical diagnosis of HSP based on American College of Rheumatology (ACR) criteria were enrolled. Thirteen patients (6 boys, 7 girls) aged 8.3 +/- 5.5 (2-21) years with other vasculitides, consisting of classic polyarteritis nodosa (PAN) (n = 2); cutaneous polyarteritis nodosa (n = 1); acute infantile hemorrhagic edema (n = 2); acute urticarial vasculitis (n = 2); hypocomplementemic vasculitis (n = 1); and unclassified vasculitis (n = 5) served as disease controls and 10 healthy children served as normal controls. Twenty-five HSP patients and 7 disease controls were re-evaluated in the resolution phase that was described as 4-6 weeks after all symptoms subsided and all medications were stopped. Blood samples for ANCA and IgA rheumatoid factor (RF) were studied by indirect immunofluorescence (IIF) and ELISA, respectively. IgG ANCA was significantly lower in percentage in HSP patients (2.8%) than in disease controls (40%) (p = 0.002). In contrast, IgA ANCA in cytoplasmic pattern was detected in a significantly higher percentage of HSP patients (82.3%) in the acute phase compared to those in the disease controls (38%) (p = 0.004). In the resolution phase, IgA ANCA was negative in 88% of the patients (p = 0.001 for acute vs resolution phases). Neither IgG nor IgA ANCA were seen in normal controls. No relationship was found between disease severity of HSP and IgA ANCA. Positive IgA rheumatoid factor was present in only two patients with HSP. In conclusion, our results suggest that IgA ANCA may be useful to confirm the diagnosis of HSP in children.

Cryptogenetic multifocal ulcerous stenosing enteritis: an atypical type of vasculitis or a disease mimicking vasculitis

BACKGROUND/AIMS Cryptogenetic multifocal ulcerous stenosing enteritis (CMUSE) is a rare disease whose origin is unknown. The aim of this study was to describe the clinical spectrum of CMUSE, to determine...