Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate

OBJECTIVE: To estimate the prevalences of polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), and Churg-Strauss syndrome (CSS). METHODS: Cases were collected in Seine-St. Denis County, a northeastern suburb of Paris, which has 1,093,515 adults (> or =15 years), 28% of whom are of non-European ancestry. The study period encompassed the entire calendar year 2000. Cases were identified by general practitioners, the departments of all the public hospitals and 2 large private clinics, and the National Health Insurance System. The Chapel Hill nomenclature was used to define MPA, and American College of Rheumatology criteria to define WG and CSS; PAN was diagnosed based on clinical laboratory, histological and/or angiographic findings. Three-source capture-recapture analysis was performed to correct for incomplete case ascertainment. RESULTS: A total of 75 cases were retained and capture-recapture analysis estimated that 23.8 cases had been missed by any 1 of the 3 sources. Accordingly, prevalences per 1,000,000 adults (95% confidence interval [95% CI]) were estimated to be 30.7 (95% CI 21-40) for PAN, 25.1 (95% CI 16-34) for MPA, 23.7 (95% CI 16-31) for WG, and 10.7 (95% CI 5-17) for CSS. The overall prevalence was 2.0 times higher for subjects of European ancestry than for non-Europeans (P = 0.01). CONCLUSIONS: This study provides the first prevalence estimates for these 4 vasculitides for a multiethnic, urban population. The significantly higher prevalence observed for Europeans may infer a genetic susceptibility of Caucasians. Compared with previous estimates based mostly on rural populations, the higher frequency of PAN and the lower frequency of WG might suggest specific environmental etiologic factors.     

Prevalences of polyarteritis nodosa,microscopic polyangiitis,Wegener's granulomatosis,and Churg‐Strauss syndrome in a French urban multiethnic population in 2000: A capture–recapture estimate

Objective

To estimate the prevalences of polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), and Churg‐Strauss syndrome (CSS).

Methods

Cases were collected in Seine–St. Denis County, a northeastern suburb of Paris, which has 1,093,515 adults (≥15 years), 28% of whom are of non‐European ancestry. The study period encompassed the entire calendar year 2000. Cases were identified by general practitioners, the departments of all the public hospitals and 2 large private clinics, and the National Health Insurance System. The Chapel Hill nomenclature was used to define MPA, and American College of Rheumatology criteria to define WG and CSS; PAN was diagnosed based on clinical laboratory, histological and/or angiographic findings. Three‐source capture–recapture analysis was performed to correct for incomplete case ascertainment.

Results

A total of 75 cases were retained and capture–recapture analysis estimated that 23.8 cases had been missed by any 1 of the 3 sources. Accordingly, prevalences per 1,000,000 adults (95% confidence interval [95% CI]) were estimated to be 30.7 (95% CI 21–40) for PAN, 25.1 (95% CI 16–34) for MPA, 23.7 (95% CI 16–31) for WG, and 10.7 (95% CI 5–17) for CSS. The overall prevalence was 2.0 times higher for subjects of European ancestry than for non‐Europeans (P = 0.01).

Conclusions

This study provides the first prevalence estimates for these 4 vasculitides for a multiethnic, urban population. The significantly higher prevalence observed for Europeans may infer a genetic susceptibility of Caucasians. Compared with previous estimates based mostly on rural populations, the higher frequency of PAN and the lower frequency of WG might suggest specific environmental etiologic factors.

     

The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort

The 1996 Five-Factor Score (FFS) for systemic necrotizing vasculitides (polyarteritis nodosa [PAN], microscopic polyangiitis [MPA], and Churg-Strauss syndrome [CSS]) is used to evaluate prognosis at diagnosis. In the current study we revisited the FFS, this time including Wegener granulomatosis (WG).We analyzed clinical, laboratory, and immunologic manifestations present at diagnosis of systemic necrotizing vasculitides for 1108 consecutive patients registered in the French Vasculitis Study Group database. All patients met the American College of Rheumatology and Chapel Hill nomenclature criteria. Univariable and multivariable analyses yielded the 2009 FFS for the 4 systemic necrotizing vasculitides.Overall mortality was 19.8% (219/1108); mortality for each of the SNV is listed in descending order: MPA (60/218, 27.5%), PAN (86/349, 24.6%), CSS (32/230, 13.9%), and WG (41/311, 13.2%) (p < 0.001). The following factors were significantly associated with higher 5-year mortality: age >65 years, cardiac symptoms, gastrointestinal involvement, and renal insufficiency (stabilized peak creatinine ≥150 μmol/L). All were disease-specific (p < 0.001); the presence of each was accorded +1 point. Ear, nose, and throat (ENT) symptoms, affecting patients with WG and CSS, were associated with a lower relative risk of death, and their absence was scored +1 point (p < 0.001). Only renal insufficiency was retained (not proteinuria or microscopic hematuria) as impinging on outcome. According to the 2009 FFS, 5-year mortality rates for scores of 0, 1, and ≥2 were 9%, 21% (p < 0.005), and 40% (p < 0.0001), respectively.The revised FFS for the 4 systemic necrotizing vasculitides now comprises 4 factors associated with poorer prognosis and 1 with better outcome. The retained items demonstrate that visceral involvement weighs heavily on outcome. The better WG prognosis for patients with ENT manifestations, even for patients with other visceral involvement, compared with the prognosis for those without ENT manifestations, probably reflects WG phenotype heterogeneity.     

Evaluation of the Sørensen diagnostic criteria in the classification of systemic vasculitis

OBJECTIVES: To evaluate the use of the diagnostic criteria for Wegener's granulomatosis (WG) and microscopic polyangiitis (mPA) proposed by S?rensen et al. in the classification of primary systemic vasculitis (PSV). METHODS: We applied to our cohort of PSV patients the American College of Rheumatology (ACR) criteria for WG, Churg-Strauss syndrome (CSS) and polyarteritis nodosa (PAN), the Chapel Hill Consensus Conference (CHCC) definitions for WG, mPA and CSS, the Hammersmith criteria for CSS and the S?rensen criteria for WG and mPA. RESULTS: Ninety-nine PSV cases were identified. Fifty-six fulfilled criteria for WG (ACR), 60 for PAN (ACR) and 15 for CSS (ACR). Four fulfilled the Hammersmith criteria for CSS. Thirty-nine were defined as mPA (CHCC). Fifty-three patients fulfilled the S?rensen criteria for WG and three for mPA. Five of six patients classified as WG (ACR) who did not meet the S?rensen criteria were excluded by eosinophilia. Six patients who did not fulfil WG (ACR) met the S?rensen criteria for WG. CONCLUSION: The classification of systemic vasculitis is complicated and many cases fulfil more than one set of criteria. The S?rensen criteria for WG is limited by its exclusion of eosinophilia despite reports of an association. We recommend that tissue eosinophilia or peripheral eosinophilia of <1.5x10(9)/l should not exclude a diagnosis of WG. With this modification, the S?rensen criteria for WG may be a useful method of classification, especially in confirming the classification of WG in patients who fulfil both WG (ACR) and mPA (CHCC). Few patients fulfilled the S?rensen criteria for mPA which suggests that they are not of value in classification.     

Detection of coronary artery lesions and myocardial necrosis by magnetic resonance in systemic necrotizing vasculitides

Objective

Myocardium and coronary arteries can occasionally be affected in patients with systemic necrotizing vasculitides; however, such involvement has not been systematically assessed using cardiovascular magnetic resonance imaging (MRI).

Methods

Magnetic resonance angiography and contrast‐enhanced MRI were applied for the assessment of coronary arteries (the left anterior descending [LAD], left circumflex [LCx], and right coronary artery [RCA]) and myocardium, respectively, in 39 patients with vasculitis who were asymptomatic for cardiac disease (16 with microscopic polyangiitis [MPA], 11 with Wegener's granulomatosis [WG], 9 with Churg‐Strauss syndrome [CSS], and 3 with polyarteritis nodosa [PAN]). Data were compared with age‐matched disease‐control patients with rheumatoid arthritis (n = 20) or systemic lupus erythematosus (n = 13), and with healthy control individuals with normal coronaries (n = 40).

Results

Patients with MPA, WG, and PAN (but not with CSS) were found to display significantly increased maximal diameters of coronary arteries compared with healthy controls (for MPA and WG; P < 0.001 for LAD and RCA, and P < 0.01 for LCx) and with both disease‐control groups (for only MPA; P < 0.01 for LAD and RCA, and P < 0.05 for LCx). Fusiform coronary aneurysms were detected in patients with MPA (4/16) and PAN (2/3), whereas coronary ectasias were evident in patients with MPA (14/16) and WG (2/11). The presence of myocardial necrosis (by assessment of late gadolinium‐enhanced images) was identified only in patients with MPA (2/16) and CSS (3/8 studied).

Conclusion

Cardiovascular MRI assessment of patients with systemic vasculitis revealed coronary ectatic disease in the majority of patients with MPA and PAN, as well as in several patients with WG. Myocardial necrosis can be detected in MPA and CSS.     

CD146在血管炎患者外周血白细胞表达的意义初探

目的探讨血管炎患者外周血白细胞CD146表达与临床活动性间的关系。方法流式细胞术检测39例活动期系统性血管炎患者[显微镜下多血管炎（MPA）13例,韦格纳肉芽肿（WG）9例,变应性肉芽肿性血管炎（CSS）2例,大动脉炎（TA）9例,白塞病（BD）4例,结节性多动脉炎（PAN）2例]及24例系统性红斑狼疮（SLE）患者外周血白细胞CD146表达,其中18例（MPA5例,WG4例,CSS2例,SLE4例,PAN2例,TA1例）患者经糖皮质激素和环磷酰胺治疗后于病情好转时再次检测。结果（1）与健康者相比,血管炎患者活动期中性粒细胞、淋巴细胞CD146表达增多,尤以中性粒细胞最多,差异均有统计学意义（P〈0．05）。（2）中性粒细胞CD146表达与淋巴细胞、单核细胞CD146表达相关（r值分别为0．66、0．853,P=0．000）,与病程、年龄、血沉、C反应蛋白、抗中性粒细胞胞浆抗体（ANCA）、PR3-ANCA、MPO-ANCA、血肌酐、伯明翰血管炎活动指数（BVAS）、系统性红斑狼疮疾病活动指数（SLEDAI）等无明显相关（r值分别为-0．108、-0．059、-0．073、-0．103、0．012、-0．5、-0．232、0．001、-0．08、0．089,P〉0．5）。（3）18例患者经治疗后好转期中性粒细胞、淋巴细胞CD146表达多数呈逐渐减少的趋势（P〈0．05）。结论CD 146在血管炎患者活动期外周血白细胞尤其是中性粒细胞中表达明显升高,随着糖皮质激素和免疫抑制剂治疗病情好转后呈下降或转阴趋势,其在血管炎发病机制中的意义有待深入研究。     

Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides

OBJECTIVE: To assess circulating immunoregulatory cytokines and soluble surface markers of T and B cell activation in the plasma of patients with Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MPA) during active and inactive disease, in order to establish their value in discriminating between disease entities and as markers of disease activity. METHODS: Plasma levels of IL-4, IL-5, IL-10, IL-12, IL-13, IFN-gamma and soluble CD23, CD26 and CD30 were determined by enzyme-linked immunosorbent assay in patients with WG (n = 21), CSS (n = 19) and MPA (n = 14) during active disease and remission. RESULTS: Concerning cytokines, no differences were observed for IFN-gamma, IL-4, IL-5 and IL-13. Plasma levels of IL-12 were decreased in all subgroups of patients. On the contrary, IL-10 levels were significantly elevated only in patients with CSS. Levels of sCD30 were significantly increased in patients with active generalized WG and CSS, but not in those with MPA and localized WG, correlating with the disease extent and activity. sCD26 levels were markedly decreased in patients with generalized WG, CSS and MPA and increased towards remission. sCD23 levels were slightly, but not significantly increased in CSS and generalized WG. CONCLUSION: Regarding the investigated immunoregulatory cytokines (Th1/Th2 type), only the measurement of plasma levels of IL-10 discriminated CSS from WG and MPA. The reported data could indicate a similar status of T cell activation in generalized WG and CSS, and possibly a shift in peripheral immunity towards a more humoral dominated immune response. The differences observed between patients with the localized and generalized forms of WG seem to reflect the clinically known biphasic course of this disease.     

No difference in the incidences of vasculitides between north and south Germany: first results of the German vasculitis register

OBJECTIVE: To register all newly diagnosed patients with primary systemic vasculitis (PSV) in two large regions in north and south Germany. METHODS: Between 1 January 1998 and 31 December 1999, all newly diagnosed cases of PSV, as defined by the Chapel Hill Consensus Conference 1992, were identified in two large mixed rural/urban regions in north and south Germany with a combined population of 4,880,543, for a population-based prospective study. The following sources were used: (i) all departments of every hospital, including their out-patient clinics; (ii) all departments of pathology; and (iii) all reference immunological laboratories serving the catchment area. All cases were re-evaluated by the authors. RESULTS: Over the whole period, 473 individuals were registered as having a new PSV. The incidence rates for all PSV were 54 cases per 1,000,000 inhabitants in the north and 48 in the south in 1998, and 48 and 41 respectively in 1999. People 50 yr and older had a three- to five-fold higher risk of getting PSVs than those under 50 yr. The incidences of antineutrophil cytoplasmic antibody (ANCA)-associated PSVs [Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS)] remained stable in both regions, at about 9.5 per 1,000,000 annually. The incidence of WG was two to three times greater than those of MPA and CSS. There was no difference in incidence rates between north and south Germany. CONCLUSION: First results from a population-based vasculitis register serving nearly 5,000,000 inhabitants in north and south Germany revealed no regional differences in the incidence of all PSVs between north and south. The incidence rates of ANCA-associated PSVs, such as WG and MPA, were lower than those in the UK and Norway but higher than that in Spain.     

Improved differentiation between Churg-Strauss syndrome and Wegener's granulomatosis by an artificial neural network

OBJECTIVE: To examine the operating characteristics of the American College of Rheumatology (ACR) classification criteria for Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG), and to develop and validate improved criteria for distinguishing CSS from WG. METHODS: The ACR classification criteria for WG and CSS were applied to 40 consecutive CSS patients age- and sex-matched with 40 patients with WG. Forty-three clinical, laboratory, and biopsy parameters were assessed. Artificial neural networks (ANNs) were trained and tested with all 43 parameters (set A) and with 15 solely clinical parameters documented at the initial manifestation of the disease (set B). The ANNs were trained with data from the first 27 CSS and 27 WG patients and validated with data from the next 13 consecutive CSS and 13 WG patients. To compare the ANNs with established methods, traditional format and classification tree criteria were generated using the same data sets. RESULTS: Fourteen of 40 CSS patients fulfilled the ACR criteria for WG, while 4 WG patients met the ACR criteria for CSS. The ANN, in contrast, reliably distinguished all CSS cases from WG cases (parameter set A, accuracy 100%). For parameter set B, the ANN achieved an accuracy of 100% in the training phase and 96% for validation. The newly formulated traditional format and classification tree criteria reached an accuracy of 81% and 88%, respectively. CONCLUSION: The ACR criteria for WG do not reliably differentiate between CSS and WG (specificity 65%). An ANN, however, could be trained to correctly allocate all but 1 patient on the basis of clinical data. Indeed, the ANN applied in this study proved superior to established methods of classification. We suggest that an ANN may be effectively applied in the classification of systemic vasculitides.     

Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies

BACKGROUND: The classification of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN) for epidemiology studies is confusing. The existing schemes such as American College of Rheumatology (ACR) criteria, Chapel Hill Consensus Conference (CHCC) definitions and Lanham criteria produce overlapping and conflicting classifications, making it difficult to compare incidence figures. Aim: To develop a consensus method of using these criteria and definitions for epidemiological studies to permit comparison without confounding by classification. METHODS: A stepwise algorithm was developed by consensus between a group of doctors interested in the epidemiology of vasculitis. The aim was to categorise patients with Wegener's granulomatosis, microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and PAN into single clinically relevant categories. The ACR and Lanham criteria for CSS, and ACR criteria for Wegener's granulomatosis were applied first, as these were considered to be the most specific. Surrogate markers for Wegener's granulomatosis were included to distinguish Wegener's granulomatosis from MPA. MPA was classified using the CHCC definition and surrogate markers for renal vasculitis. Finally, PAN was classified using the CHCC definition. The algorithm was validated by application to 20 cases from each centre and 99 from a single centre, followed by a paper case exercise. RESULTS: A four-step algorithm was devised. It successfully categorises patients into a single classification. There was good correlation between observers in the paper case exercise (91.5%; unweighted kappa = 0.886). CONCLUSION: The algorithm achieves its aim of reliably classifying patients into a single category. The use of the algorithm in epidemiology studies should permit comparison between geographical areas.     

Effect of classification on the incidence of polyarteritis nodosa and microscopic polyangiitis

Objective. Polyarteritis nodosa (PAN) has been used as a generic term for systemic vasculitis. The distinction between classic PAN and microscopic polyangiitis (MPA) has not always been made. The aims of this study were to compare the American College of Rheumatology (ACR) criteria for PAN with the Chapel Hill Consensus Conference (CHCC) definitions of classic PAN and MPA, and to estimate the annual incidence of PAN and MPA. Methods. The 1990 ACR criteria and CHCC definitions for systemic vasculitis were applied to an unselected cohort of 130 patients with systemic vasculitis attending a single district hospital in the UK between February 1, 1988 and January 31, 1994. Results. Eight patients who met the ACR criteria for PAN and who also met the CHCC definition of MPA but not classic PAN were identified. A further 5 patients met the CHCC definition of MPA but not the ACR criteria for any other type of systemic vasculitis. No patient who met the CHCC definition of classic PAN was identified. The annual incidence of MPA was calculated to be 3.6/million (95% confidence interval 1.7–6.9), and the annual incidence of PAN (ACR criteria) was 2.4/million (95% confidence interval 0.9–5.3). Conclusion. Classic PAN as defined by the CHCC is rare, because small vessel involvement is excluded from this definition.     

Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients

OBJECTIVE: To determine the long-term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg-Strauss syndrome (CSS), to compare the long-term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae. METHODS: Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five-Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis. RESULTS: The mean (+/- SD) followup of the entire population was 88.3 +/- 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)-related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non-HBV-related PAN who were given first-line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores > or =2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001). CONCLUSION: Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV-related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first-line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.     

Improved differentiation between Churg‐Strauss syndrome and Wegener's granulomatosis by an artificial neural network

Objective

To examine the operating characteristics of the American College of Rheumatology (ACR) classification criteria for Churg‐Strauss syndrome (CSS) and Wegener's granulomatosis (WG), and to develop and validate improved criteria for distinguishing CSS from WG.

Methods

The ACR classification criteria for WG and CSS were applied to 40 consecutive CSS patients age‐ and sex‐matched with 40 patients with WG. Forty‐three clinical, laboratory, and biopsy parameters were assessed. Artificial neural networks (ANNs) were trained and tested with all 43 parameters (set A) and with 15 solely clinical parameters documented at the initial manifestation of the disease (set B). The ANNs were trained with data from the first 27 CSS and 27 WG patients and validated with data from the next 13 consecutive CSS and 13 WG patients. To compare the ANNs with established methods, traditional format and classification tree criteria were generated using the same data sets.

Results

Fourteen of 40 CSS patients fulfilled the ACR criteria for WG, while 4 WG patients met the ACR criteria for CSS. The ANN, in contrast, reliably distinguished all CSS cases from WG cases (parameter set A, accuracy 100%). For parameter set B, the ANN achieved an accuracy of 100% in the training phase and 96% for validation. The newly formulated traditional format and classification tree criteria reached an accuracy of 81% and 88%, respectively.

Conclusion

The ACR criteria for WG do not reliably differentiate between CSS and WG (specificity 65%). An ANN, however, could be trained to correctly allocate all but 1 patient on the basis of clinical data. Indeed, the ANN applied in this study proved superior to established methods of classification. We suggest that an ANN may be effectively applied in the classification of systemic vasculitides.

     

Microscopic polyangiitis (microscopic polyarteritis) with late emergence of generalised Wegener's granulomatosis.

OBJECTIVES: Recent proposals for the nomenclature of systemic vasculitis have focused on a distinction between (classic) polyarteritis nodosa (PAN) and microscopic polyangiitis or polyarteritis (MPA). Thus, MPA may cause necrotising vasculitis of medium sized or small arteries but, unlike PAN, involvement of "microscopic" vessels must always be present in the former. This study aimed to show that the term "MPA" may represent a source of misinterpretation and to help illustrate difficulties of applying diagnostic criteria/definitions for conditions of unknown aetiology or variable clinical presentation and course. METHODS: Among 1250 consecutive patients screened for antineutrophil cytoplasmic antibodies (ANCA), 59 had been found to have idiopathic necrotising and crescentic glomerulonephritis plus ANCA while five had been found to have isolated pulmonary haemorrhage with biopsy verified necrotising alveolar capillaritis plus ANCA. None of these patients had clinical or histological evidence of Wegener's granulomatosis (WG) or evidence of biopsy verified vasculitis involving vessels other than glomerular or pulmonary capillaries at the time of presentation. RESULTS: Six of the 64 patients who met definition criteria for MPA at the time of initial diagnoses had entered into complete clinical remission upon appropriate corticosteroid and cyclophosphamide treatment between two weeks and three months, though subsequently (20 to 72 months; mean time: 42.3 months) developed characteristic clinical and histological features of overt WG. CONCLUSIONS: Microscopic polyangiitis/polyarteritis may be a dynamic condition with clinical and histopathological features evolving over time to other forms of small vessel vasculitis, mainly WG, thereby meaning that follow up would be necessary not only to control a given patient but also to make a final diagnosis. This follow up should be for a long time as there may be a long interval between initial presentation and subsequent development of WG lesions.     

Re-evaluation of 129 patients with systemic necrotizing vasculitides by using classification algorithm according to consensus methodology

Recently, a new classification algorithm (CA) for systemic necrotizing vasculitides was proposed by Watts et al. (Annals Rheum Dis 66:222–227, 2007) by using the American College of Rheumatology (ACR), Chapel Hill Consensus Criteria (CHCC) and Sorensen surrogate markers (So). We aimed to validate CA in our patients. One hundred twenty-nine patients followed up in our vasculitis clinic were reclassified according to CA in different categories (ACR or Lanham criteria in “1” for Churg–Strauss Syndrome (CSS); ACR in “2a”; CHCC-Wegener's granulomatosis (WG) in “2b”; CHCC-microscopic polyangiitis (MPA), So-WG in “2c”; So-WG, proteinase 3 (PR3) or myeloperoxidase antineutrophil cytoplasmic antibody (MPO ANCA) serology in “2d” for WG; clinical features and histology compatible with small vessel vasculitis without So-WG in “3a”; So-MPA, PR3 or MPO ANCA serology in “3b” for MPA; CHCC-classic-polyarteritis nodosa (c-PAN) or typical angiographic features in “4” for c-PAN; unclassifiable in “5”). Kappa statistic was used to analyse the agreement of the criteria that formed the algorithm. All of 12 CSS, 91% of 69 WG, 78% of 18 MPA and 93% of 26 c-PAN patients remained in their previous diagnosis. WG patients were placed in 2a (83%), 2c (3%), 2d (14%) categories. Four WG (6%) and four MPA (22%) patients were categorized as MPA (in 3a (75%), 3b (25%)) and WG (in 2c (75%), 2d (25%)), respectively. Three of four unclassified patients could be classified as c-PAN (two) and MPA (one). Significant agreement was demonstrated only for ACR and So criteria in WG (κ = 0.62, p < 0.001). The majority of our patients stayed on their previous diagnosis in “CA”. Our findings suggest that this algorithm is helpful and practical for epidemiological studies. Poor correlation of defined criteria was thought to be related to the fact that each criteria mainly consist of different characteristics of vasculitides such as clinical, histopathological and serological features.     

Epidemiology of ankylosing spondylitis in Northwest Greece, 1983-2002

OBJECTIVE: To investigate the incidence and the prevalence of ankylosing spondylitis (AS) in a defined area of northwest Greece with a total population of about 500,000 inhabitants. METHODS: AS cases were recorded from (i) in- and out-patients referred to the rheumatology clinics of the Ioannina university hospital and the Ioannina general hospital, and (ii) patients referred to private rheumatologists practising in the study area. An incident case was defined as any patient with AS, diagnosed during the period between 1 January 1983 and 31 December 2002 who were resident in the study area for at least 1 yr before the diagnosis. A prevalent case was defined as any patient with AS who was a resident of the study area on 31 December 2002. Diagnosis was based on the modified New York criteria for AS. Population data were based on the 1981, 1991 and 2001 National Censuses. RESULTS: A total of 113 cases were diagnosed among the population of the area studied during the period 1983-2002. Men constituted a 4.65-fold higher number of patients than women, and had a significantly higher mean age at diagnosis. All patients presented bilateral sacroiliitis, 40 patients (35.9%) had peripheral joint involvement and 15 patients presented extra-articular manifestations (13.27%). HLA-B27 antigen was found in 80.5% of our patients. The age-adjusted mean annual incidence rate for the population aged > or =16 yr was 1.5 cases per 10(5) inhabitants [95% confidence interval (CI) 0.4-2.5], and the age-adjusted prevalence rate on 31 December 2002 was 29.5 cases per 10(5) inhabitants (95% CI 25.9-33.1). The incidence rates were higher in the age group 35-44 yr for men and in the age group 25-34 yr for women. CONCLUSION: The incidence and prevalence of AS in the area studied were significantly lower than in other white populations and higher than in the Japanese population.     

Stable incidence of primary systemic vasculitides over five years: results from the German vasculitis register

OBJECTIVE: To register all newly diagnosed patients with primary systemic vasculitides (PSV) in a large region in northern Germany. METHODS: Between January 1, 1998 and December 31, 2002 all newly diagnosed cases of PSV were identified in a large mixed rural/urban northern German region consisting of 2,777,275 habitants in a population-based prospective study. The following sources were used: departments of all hospitals, including their outpatient clinics; all departments of pathology; and the reference immunologic labs serving the catchment area. RESULTS: During 5 years, 642 PSV patients were identified. The incidence rates for all PSV were between 40 and 54 cases per 1 million and per year. People at age 50 years and older had a 3-5-fold higher risk of developing PSV compared with those younger than 50 years. The incidence rates of antineutrophil cytoplasmic antibody (ANCA)-associated PSV (Wegener's granulomatosis [WG], microscopic polyangiitis [MPA], Churg-Strauss syndrome [CSS]) were between 9.5 and 16/million/year. WG occured 2-3 times more frequently than MPA or CSS. CONCLUSION: Results of a population-based vasculitis register over 5 years for the incidence of PSV among 2.78 million habitants in northern Germany revealed a stable incidence for all PSV. Compared with other European studies coming from small regions or referral centers, the incidence rates for ANCA-associated PSV were the same as in Norway, lower than those in United Kingdom, but higher than those in Spain.     

Antineutrophil cytoplasmic antibody–associated vasculitides: Could geographic patterns be explained by ambient ultraviolet radiation?

Objective

This ecological study describes and quantifies the association between ambient ultraviolet (UV) radiation levels, including daily winter vitamin D effective UV radiation levels and the incidence of the 3 antineutrophil cytoplasmic antibody–associated vasculitides (AAVs): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg‐Strauss syndrome (CSS). Latitudinal variation in occurrence of the AAVs, especially WG, has been previously reported. For other autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, inverse associations with latitude are hypothesized to indicate a causative role for low UV radiation exposure, possibly acting via vitamin D status.

Methods

Published epidemiologic studies provided data on incident cases, total population of study regions, age‐specific incidence rates, and study location. From these data and online age‐specific population data, we calculated crude incidence rates, the expected number of cases (to control for possible age confounding), and measures of ambient UV radiation. Negative binomial regression models were used to calculate the incidence rate ratio (IRR) for a 1,000 joules/m² increase in ambient UV radiation.

Results

The incidence of WG and CSS increased with increasing latitude and decreasing ambient UV radiation, with a stronger and more consistent effect across different UV radiation measures for WG, e.g., for average daily ambient clear sky erythemal UV radiation (WG: IRR 0.64 [95% confidence interval (95% CI) 0.44–0.94], P = 0.02; CSS: IRR 0.67 [95% CI 0.43–1.05], P = 0.08; MPA: IRR 1.16 [95% CI 0.92–1.47], P = 0.22). There was no apparent latitudinal variation in MPA incidence.

Conclusion

Our findings are consistent with a protective immunomodulatory effect of ambient UV radiation on the onset of WG and CSS. We discuss possible mechanisms, including the effect of vitamin D on the immune system.