Evaluation of the Sørensen diagnostic criteria in the classification of systemic vasculitis
S. E. Lane,
R. A. Watts,
T. H. W. Barker1 and
D. G. I. Scott
Departments of Rheumatology and
1 Histopathology, Norfolk and Norwich University Hospital, Norwich, UK
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Abstract
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Objectives. To evaluate the use of the diagnostic criteria for Wegener's granulomatosis (WG) and microscopic polyangiitis (mPA) proposed by Sørensen 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, ChurgStrauss 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 Sørensen 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 Sørensen criteria for WG and three for mPA. Five of six patients classified as WG (ACR) who did not meet the Sørensen criteria were excluded by eosinophilia. Six patients who did not fulfil WG (ACR) met the Sørensen criteria for WG.
Conclusion. The classification of systemic vasculitis is complicated and many cases fulfil more than one set of criteria. The Sørensen criteria for WG is limited by its exclusion of eosinophilia despite reports of an association. We recommend that tissue eosinophilia or peripheral eosinophilia of <1.5x109/l should not exclude a diagnosis of WG. With this modification, the Sørensen 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 Sørensen criteria for mPA which suggests that they are not of value in classification.
KEY WORDS: Classification, Systemic vasculitis, Wegener's granulomatosis, Eosinophilia.
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Introduction
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The classification of systemic vasculitis remains contentious. The two most widely used systemsthe 1990 American College of Rheumatology (ACR) criteria [1] and the 1994 Chapel Hill Consensus definitions (CHCC) [2]are imperfect in a number of ways. The ACR (1990) criteria were designed to provide a standard method of describing groups of patients for research and to distinguish one type of vasculitis from another, but not to distinguish vasculitis from other diseases. They do not include microscopic polyangiitis (mPA) as a disease entity, nor do they use antineutrophil cytoplasmic antibodies (ANCA) as a potential classification criterion. The CHCC aimed to reach a consensus on the names of the major non-infectious vasculitides and provided working definitions of 10 different types of vasculitis. They were not intended to be used as either classification or diagnostic criteria but are frequently applied in the absence of an alternative classification for mPA. Sørensen et al. [3] have recently proposed diagnostic criteria for Wegener's granulomatosis (WG) and mPA based upon the CHCC definitions. They proposed the following diagnostic criteria for WG: (i) biopsy or a surrogate parameter for granulomatous inflammation in the respiratory system; (ii) biopsy-verified necrotizing vasculitis in small to medium-sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA (ANCA with specificity for proteinase 3); and (iii) lack of eosinophilia in the blood and biopsy samples. The criteria for mPA were (i) biopsy-verified necrotizing vasculitis in small vessels and/or glomerulonephritis with few or no immune deposits; (ii) involvement of more than one organ system, as indicated by biopsy-verified vasculitis in small to medium-sized vessels or a surrogate parameter for glomerulonephritis; and (iii) lack of biopsy and a surrogate parameter for granulomatous inflammation in the respiratory tract. They derived their criteria from a retrospective study of patients seen in a tertiary referral centre.
We examined the potential value of their proposed definitions as classification criteria in an unselected cohort of patients with primary systemic vasculitis (PSV) collected prospectively over a 12-yr period from a defined population.
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Patients and methods
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The study was hospital-based in the former Norwich Health Authority (NHA), Norfolk (UK). The NHA provided administrative services to a group of 77 primary care practices covering a population of approximately 415 000. Patients were included in the study if they were registered with one of these practices.
Patients attending with a new clinical diagnosis of PSV between 1 January 1988 and 31 June 2000 were recorded prospectively and those registered with a general practitioner in the NHA were identified. In addition, the histopathology department records of renal and skin biopsies were searched for patients with a potential diagnosis of vasculitis and the hospital discharge diagnostic index (ICD-9 and ICD-10) was also searched for patients with a discharge diagnosis of vasculitis. The complete case records of all patients identified with systemic vasculitis were reviewed.
Patients with a documented episode of systemic vasculitis prior to 1988 were excluded and patients with giant cell arteritis, Takayasu arteritis, HenochSchönlein purpura, cutaneous leucocytoclastic angiitis, cryoglobulinaemic vasculitis and vasculitis secondary to connective tissue disease or rheumatoid arthritis were excluded.
The ACR (1990) criteria for polyarteritis nodosa (PAN) [4], WG [5] and ChurgStrauss syndrome (CSS) [6] and the Hammersmith criteria for CSS [7] were used to classify all patients and the CHCC definition for mPA, WG and CSS were also applied. The CHCC definitions were not designed to be applied as classification criteria and individuals were classified according to biopsy findings. According to CHCC nomenclature, mPA is a necrotizing vasculitis with few or no immune deposits, affecting small vessels (capillaries, venules or arterioles); necrotizing arteritis involving small and medium-sized arteries may be present; necrotizing glomerulonephritis is very common; and pulmonary capillaritis often occurs. Cases were classified as having mPA if one or more of these findings was noted on biopsy in a patient with clinical systemic vasculitis unless more specific appearances of WG and CSS were noted, in which case they were classified accordingly. The use of these definitions in this way is limited because not all patients had a biopsy and classical findings may not be evident on a particular biopsy sample. This explains why, in many cases, individuals classified as mPA using the CHCC method can also be classified as WG or CSS using the ACR definitions. The CHCC definitions as modified by Sørensen were applied to all patients [3]. A physician (RAW) not directly involved in patient care confirmed the diagnosis of vasculitis.
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Results
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Between 1988 and 2000 we identified 99 patients with PSV in the NHA population. In many cases patients could be classified by more than one set of criteria. Fifty-six patients fulfilled the ACR (1990) criteria for WG, 60 fulfilled the ACR (1990) criteria for PAN and 15 the ACR (1990) criteria for CSS. Four additional patients fulfilled the Hammersmith criteria for CSS and 39 were defined as mPA (CHCC).
Only 56 patients could be classified using the Sørensen classification criteria. Fifty-three patients fulfilled the Sørensen criteria for WG and three their criteria for mPA. Table 1
compares the ACR and CHCC classifications of patients with the Sørensen criteria.
Six patients who fulfilled the ACR criteria for WG did not meet the Sørensen definition. In five cases this was because of the presence of an eosinophilic infiltrate on renal biopsy. The clinical details of these patients are given in Table 2
. Case 3 also had a mild blood eosinophilia (<1.5x109/l) and case 4 had significant peripheral blood eosinophilia (7x109/l; normal range 00.4x109/l). The latter was also classifiable as CSS by the ACR and Hammersmith criteria but had classical nodules on X-ray.
Six additional patients fulfilled the Sørensen criteria for WG. One could be otherwise classified only as PAN (ACR), three as mPA (CHCC) and two as both mPA (CHCC) and PAN (ACR).
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Discussion
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The classification of PSV is complicated and many individuals fulfil more than one set of criteria. In particular, many cases who can be classified as PAN (ACR) also meet the criteria/definitions for WG, CSS and/or mPA. Of the 60 patients classified as PAN, 36 could also be classified as WG, nine as CSS and 29 as mPA. The original description of the PAN (ACR) criteria acknowledged this lack of specificity. In our series, 15 patients could be classified as both WG (ACR) and mPA (CHCC). It is important to be able to classify these patients as either one diagnosis or the other in a systematic, reproducible way, for example in casecontrol studies or therapeutic trials. The Sørensen criteria potentially provide an effective method to distinguish between these diagnoses using surrogate markers of granulomatous inflammation and PR3-classical ANCA. However, their usefulness is limited by the exclusion of a diagnosis of WG on the basis of blood or tissue eosinophilia without clear guidance on the level of eosinophilia. The presence of eosinophilia in WG has been recognized in the literature [8], and in our experience it is not an uncommon finding in biopsy specimens in cases of WG (ACR), although in these cases eosinophilia is less prominent than in CSS (Fig. 1
). Of the five patients in whom a diagnosis of WG was excluded on the basis of eosinophilia, only one could be classified as CSS by other means. Tissue or peripheral blood eosinophilia should not therefore be an absolute criterion for exclusion for WG. A peripheral blood eosinophil count of >1.5x109/l is suggestive of CSS, and the Hammersmith criteria for CSS [7] uses this level as one of the criteria for diagnosis. We suggest that a peripheral blood eosinophil count of <1.5x109 /l is compatible with a diagnosis of WG/mPA. The difficulties of classification of mPA (CHCC) and PAN (ACR) have been discussed previously [9]. The very small number of patients recognized as mPA by the Sørensen criteria suggests that these criteria are really of no added value in the classification of mPA, although we acknowledge that they were designed as diagnostic criteria.

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FIG. 1. (A) Kidney biopsy in WG demonstrating interstitial eosinophils. (B) Leucocytoclastic vasculitis with eosinophilic infiltrate in CSS.
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We therefore suggest that, with a modification of the acceptable level of eosinophilia, the Sørensen criteria provide an effective method of classifying WG, particularly in those individuals who meet definitions/criteria of both WG (ACR) and mPA (CHCC).
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Acknowledgments
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SEL was supported by the Arthritis Research Campaign. We are grateful to the physicians of the Norfolk and Norwich Hospital for referring patients to us.
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Notes
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Correspondence to: S. E. Lane, Department of Rheumatology, Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK. 
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References
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Submitted 27 July 2001;
Accepted 16 April 2002