Primary renal vasculitis in Norfolkincreasing incidence or increasing recognition?
Suzanne E. Lane1,
David G. I. Scott1,
Alex Heaton2 and
Richard A. Watts1,3
1 Department of Rheumatology,
2 Department of Nephrology, Norfolk and Norwich Healthcare NHS Trust, Norwich and
3 Ipswich Hospital NHS Trust, Ipswich, UK
Correspondence and offprint requests to:
Dr S. E. Lane, Department of Rheumatology, Norfolk and Norwich Healthcare NHS Trust, Brunswick Rd, Norwich, NR1 3SR, UK.
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Abstract
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Background. The incidence of renal vasculitis has previously been estimated using histological definitions or only a single clinical diagnosis, e.g. Wegener's Granulomatosis (WG). Our hospital is the single referral centre for the former Norwich Health Authority (NHA) which encompasses a stable, homogenous, well-defined and studied population. We estimated the overall incidence of primary renal vasculitis and the incidence within individual clinical disease classifications.
Methods. All cases of primary renal vasculitis diagnosed within the NHA over 66 months (19921997) were identified by review of renal biopsies, the Norfolk Vasculitis Register, hospital discharge summaries and plasmapheresis records. Patients were classified using the 1990 American College of Rheumatology criteria for Polyarteritis Nodosa (PAN), Churg Strauss Syndrome (CSS) and HenochSchonlein Purpura; the Chapel Hill Consensus Conference Definitions for Microscopic Polyangiitis (mPA) and the Lanham criteria for CSS. Incidence figures were calculated using the NHA adult population of 413747 (1994). Ninety-five per cent confidence intervals (C.I.) were calculated using the poisson distribution.
Results. The overall annual incidence for primary renal vasculitis was 18/million (C.I. 12.924.4). The annual incidence of renal involvement of individual diseases was as follows: WG 7.9/million (95% C.I. 4.712.5); mPA 7.5/million (95% C.I. 4.412.0); PAN 7.0/million (95% C.I. 4.011.4); HSP 3.1/million (95% C.I. 1.26.3); CSS 1.3/million (95% C.I. 0.33.9).
Conclusions. The annual incidence for primary renal vasculitis overall and the individual subtypes in Norfolk is much higher than previous European estimates. This may reflect an increasing incidence in primary renal vasculitis with time or underestimation in previous studies. However the incidence of renal vasculitis in our population is markedly lower than reported in Kuwait. There may therefore be true variation in incidence between populations which could have implications for the aetiology of primary vasculitis.
Keywords: classification; epidemiology; pauci-immune glomerulonephritis; vasculitis
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Introduction
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Vasculitis is an important treatable cause of renal impairment that leads to significant morbidity and mortality. Little data is available on the incidence of renal vasculitis. Early reports are difficult to interpret due to confusing definitions and the absence of accepted criteria. In 1990 the American College of Rheumatology (ACR) proposed criteria for individual diseases using clinical and histological features [14]. The Chapel Hill Consensus Conference (CHCC) in 1994 proposed definitions to take account of vessel size [5]. Using these criteria and definitions, epidemiological study has been possible and recent data suggests that these diseases are relatively rare, may be increasing with time, and may occur more commonly in the elderly population than originally suspected [6,7].
No study has considered the overall incidence of renal vasculitis using these criteria. Previous studies have considered individual disease subtypes e.g. Wegener's Granulomatosis (WG) or crescentic necrotizing glomerulonephritis (GN) and rapidly progressive GN (RPGN) [6,812].
The area covered by the former Norwich Health Authority (NHA), an administrative grouping of 77 primary care practices, has been used successfully to study the epidemiology of primary systemic vasculitis and rheumatoid arthritis [13,14]. It is suitable for epidemiological study because it has a stable, well-defined adult population of about 415000, served by a single district general hospital which provides a renal service to the NHA and also surrounding areas. There is little referral out of district and these patients can be identified because of good communication between hospital specialities, adjacent health districts and primary care. A prospective register of all patients diagnosed with vasculitis at the central hospital was established in 1988.
The aim of this study was to estimate the annual incidence in adults (>15 years old) resident in the NHA of clinical primary systemic vasculitis with renal involvement.
The annual incidence was obtained in those who fulfilled accepted classification criteria for each of the following: WG; Microscopic polyangiitis (mPA); Churg Strauss syndrome (CSS); Polyarteritis Nodosa (PAN); and adult HenochSchonlein purpura (HSP). In addition an overall annual incidence figure was obtained for all patients with a primary renal vasculitis (definition follows).
As the use of the classifications and definitions is continuing to evolve, detailed data of patients who fulfil more than one criteria is provided and ANCA data available is included to ensure that results may be reliably compared to future studies.
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Methods
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Definitions
For the purpose of this study we defined primary renal vasculitis as one of the following.(i) A patient who fulfilled criteria for one of the primary systemic vasculitides and had either a renal biopsy appearance compatible with vasculitis where there was no other identifiable cause for these changes or renal impairment attributable to vasculitis;
(ii) A patient who did not fulfil classification criteria but had a renal biopsy highly suggestive of vasculitis with no other identifiable cause and who was treated clinically as having vasculitis.
Renal impairment was considered to be caused by vasculitis when an elevation of serum creatinine (above the laboratory normal range) coincided with a clinical flare of vasculitis and where there was no alternative identifiable cause.
The following disease classifications were used:
Wegener's Granulomatosis (WG) ACR (1990) criteria [1]
Polyarteritis Nodosa (PAN) ACR (1990) criteria [2]
Microscopic polyangiitis (mPA) CHCC (1994) definition [5]
Churg Strauss Syndrome (CSS) ACR (1990) [3] and/or Lanham 1984 [15]
HenochSchonlein Purpura (HSP) ACR (1990) criteria [4].
Patients with secondary vasculitis due to an identifiable underlying disorder, for example rheumatoid arthritis, systemic lupus erythematosus or cryoglobulinaemia, were excluded.
Patient identification
Patients with primary systemic vasculitis were identified in the following ways to ensure that as far as possible no cases were missed.
(i) Records of all renal biopsies performed at the Norfolk and Norwich Hospital over 66 months (19921997) were reviewed and those with appearances suggestive of vasculitis were evaluated. Although necrotizing GN with or without crescent formation or arteritis is the classical appearance of vasculitis on biopsy, various biopsy appearances can occur. Therefore biopsies were included for review where there was evidence of focal segmental proliferative GN, necrosis, crescents, mesangial proliferation, a pauci-immune appearance on immunofluorescence, arteritis or granuloma formation. Any biopsy that was reported as suspicious of vasculitis was also included for further assessment. Biopsies after January 1995 were readily identifiable through the pathology computerized records. Prior to this date patients who had had a renal biopsy were identified from ultrasound records, then biopsy results obtained through pathology computerized records or by case note review. Table 1
illustrates the diagnoses of patients included and excluded from the study by biopsy review.
(ii) The prospective Vasculitis Register was used to identify patients known to have primary vasculitis diagnosed during the study period [7].
(iii) Hospital records of patients' discharge summaries were searched for any patients coded as having a renal biopsy or a diagnosis of a primary or renal vasculitis.
(iv) Between 1994 and 1997 records of patients who received plasmapheresis were available and were reviewed to identify any vasculitis patients too unwell to have a biopsy. No additional patients were identified in this way.
Case note review
The case notes of all patients identified were reviewed with respect to diagnosis, biopsy appearance and renal function. In each case the underlying diagnosis of the patient was established and those found to have vasculitis were classified as above using a form adapted from the Birmingham Vasculitis Activity Score form [16]. Some patients fulfilled criteria for more than one disease classification.
Eighty one patients (61 resident in NHA) were classified as having a primary systemic vasculitis between 1992 and 1997 following case note review. Sixty one of these patients (47 in NHA) were already known to the vasculitis register. Fifteen patients not on the vasculitis register were found by renal biopsy review (nine in NHA) and a further five patients (all in NHA) were found on review of hospital discharge letters.
Nine patients (four in NHA) were identified who were felt to have primary renal vasculitis but did not fulfil classification criteria (Table 2
). Two were already known to the register, six were found by renal biopsy review (three in NHA) and one by records review (NHA).
Data analysis
Incidence figures were calculated for patients resident in the former NHA. Residency in the NHA was established according to the location of the patient's general practitioner at the time of diagnosis. We used the NHA although it is no longer in existence as this population has been studied by the Norfolk Arthritis Register and well-established population details are available [13]. All patients resident in the former NHA continue to be referred to our single District General Hospital.
The annual incidence of renal vasculitis for each disease classification and the overall annual incidence of adult primary renal vasculitis was calculated using the adult population of 413747 (1994). This was the population of patients over the age of 15 registered with the 77 general practitioners that comprised the former NHA. The adult population in 1994 consisted of 199682 males and 214056 females. The population was 99% caucasian and split between urban and rural areas. Where a patient fulfilled criteria for more than one disease classification they were included in the calculation for each disease. Ninety-five per cent confidence intervals (C.I.) were calculated using the poisson distribution for the number of cases observed.
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Results
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The classification of patients with primary systemic vasculitis who attended the Norfolk and Norwich Hospital 19921997 is shown in Table 3
. Each category is subdivided to show the sex ratio, residency in the NHA and renal involvement. Four additional patients classified as CSS had renal impairment but this could be attributed to ovarian carcinoma, gentamicin administration, chronic renal failure due to both hypertension and insulin dependent diabetes mellitus, and renal impairment in a critically ill patient within 24 h of death rather than vasculitis per se. One patient diagnosed as mPA was found to have subacute bacterial endocarditis at post-mortem and was therefore excluded. Renal impairment in all other cases could be attributed to vasculitis. One patient diagnosed with WG with renal impairment and a biopsy compatible with IgA nephropathy was included.
For the individual diseases the annual incidence for patients with renal involvement in each disease was as follows: WG 7.9/million (95% C.I. 4.712.5); mPA 7.5/million (95% C.I. 4.412.0); PAN 7.0/million (95% C.I. 4.011.4); HSP 3.1/million (95% C.I. 1.26.3); CSS 1.3/million (95% C.I. 0.33.9). Incidence by sex is shown in Table 4
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In total 41 patients living in the NHA with renal vasculitis fulfilled at least one classification criteria for primary systemic vasculitis. An additional four patients in the NHA failed to fulfil classification criteria but had clinical features of vasculitis, compatible renal biopsies and responded appropriately to treatment. An estimate for the annual incidence of primary renal vasculitis for our population was therefore 18.0/million (95% C.I. 12.924.4).
The percentage of patients with renal involvement for each disease derived from all patients studied was as follows: mPA 92% (23/25); PAN 87% (20/23); WG 79% (26/33); HSP 64% (7/11); and CSS 20% (3/15). There was no significant difference in the percentage of male or female patients. Details of ANCA results for all patients is shown in Table 5
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Discussion
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Our annual incidence figure for primary renal vasculitis, 18.0/million/year is higher than previous European studies. In Leicester, England, Andrews et al. reviewed the incidence of mPA and WG between 19801986 [6]. Classification of WG used criteria similar to the ACR 1990 criteria and a diagnosis of mPA required clinical evidence of vasculitis in more than one organ system and histological evidence of small vessel vasculitis at least one site in the absence of specific respiratory or histological features of WG. There were 36 cases in their population of 1.3 million. All cases had renal involvement, 35 with focal segmental necrotizing GN and one with a scarred end-stage kidney. The combined annual incidence for mPA and WG was 1.5/million.
In Lund, Sweden, Westman et al. reported 56 cases of WG, fulfilling ACR criteria and 67 cases of mPA, using CHCC definitions, in their population of 1.2 million between 1971 and 1993 [8]. All cases had renal involvement. The annual incidence for WG and mPA respectively was therefore 2.1/million and 2.5/million. The combined annual incidence for mPA and WG was 4.6/million.
Thirty one patients in our population with renal vasculitis fulfilled classification criteria for WG and/or mPA. The annual incidence for renal involvement in WG and mPA combined in the NHA was 13.6/million (95% C.I. 9.319.3) which is much higher than those reported by either the Leicester or Lund groups.
A survey of the Italian Registry of Renal Biopsies in patients over 18 years of age revealed an annual incidence for 1993 of 1.6/million for necrotizing vasculitis and 1.3/million for HSP, lower than our figure for adult HSP of 3.1/million/year [9].
Other studies have considered histological and laboratory definitions of renal vasculitis. Andrassy et al. investigated the incidence of crescentic GN and RPGN in Heidelberg, Germany, between 1984 and 1989 [10]. There were 33 cases of biopsy proven crescentic GN and five cases of RPGN on clinical definitions during the study period in their population of 930000, giving a combined annual incidence of 7.0/million. This study included patients with SLE, Goodpastures and IgA nephropathy in addition to WG, HSP and mPA. In Huddinge, Sweden, Pettersson et al. found 71 new cases of pauci-immune necrotizing and crescentic GN between 1986 and 1992 in their adult population of 1.2 million, giving a mean annual incidence of 8/million. It was noted that the annual incidence doubled from 6/million in 1986 to 12/million in 1992 [11]. Both papers suggest that the incidence of renal vasculitis may be increasing. Conversely a 10-year retrospective study from 1986 to 1996 in Wessex, England, found the annual incidence of biopsy proven RPGN to be 3.5/million and this was stable throughout the period [12]. Although different definitions have been used, the annual incidence we report is probably genuinely higher than that reported in the other studies, particularly as secondary vasculitis was included in some calculations and specifically excluded in ours.
One study does however find much higher incidence figures than our population. El-Reshaid et al. studied renal disease associated with mPA and classical PAN using the CHCC definition in the Kuwaiti population [17]. The local population comprised of 60% heterogeneous expatriates so the remaining 40% of Kuwaiti nationals alone was used to determine incidence figures. An annual incidence of 45/million was found for mPA, classic PAN and patients with angiography compatible with PAN but who failed to fulfil criteria. The annual incidence was 65/million for males and 33/million/year for females.
Our annual incidence figure of 7.5/million for renal disease in mPA is much lower than that of the Kuwaiti study. It is interesting to note that there were no cases of classic PAN using CHCC definitions in our population during the study period. Our incidence figure is likely to be a slight underestimate as some patients may have had only mild changes on their renal biopsy and would therefore not have been detected by renal biopsy review. Some patients may have also been missed if they had been too unwell to have a renal biopsy or if the biopsy was unsuccessful. However this difference in incidence would be slight and a large discrepancy in incidence remains between the two populations.
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Conclusions
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The overall annual incidence figure for primary renal vasculitis in Norfolk is 18.0/million, 7.9/million for WG and 7.5/million for mPA which are all higher than previous European reports. These differences could reflect true variation between populations, be due to underestimation in previous studies or indicate that the incidence of renal vasculitis is increasing with time.
The incidence of renal vasculitis in Norfolk is much lower than in Kuwait. Further study of different populations using comparable classification criteria will provide important information of the variation of these diseases in time and space and may lead to a greater understanding of their aetiology.
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References
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-
Leavitt R, Fauci A, Bloch D et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's Granulomatosis. Arthritis Rheum 1990; 33: 11011117[ISI][Medline]
-
Lightfoot R, Michel A, Bloch D et al. The American College of Rheumatology 1990 classification of polyarteritis nodosa. Arthritis Rheum 1990; 33: 10881093[ISI][Medline]
-
Masi A, Hunder G, Lie J et al. The American College of Rheumatology 1990 criteria for the classification of Churg Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990; 33: 10941100[ISI][Medline]
-
Mills J, Michel A, Bloch D et al. The American College of Rheumatology 1990 criteria for the classification of Henoch Schonlein purpura. Arthritis Rheum 199; 33: 11141121[ISI][Medline]
-
Jeanette J, Falk R, Andrassy K et al. Nomenclature of Systemic Vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37: 187192[ISI][Medline]
-
Andrews M, Edmunds M, Campbell A, Walls J, Feehally J. Systemic vasculitis in the 1980sis there an increasing incidence of Wegener's Granulomatosis and microscopic polyarteritis? J Royal Coll Physicians 1990; 24: 284288[ISI]
-
Watts RA, Carruthers DM, Scott DGI. Epidemiology of systemic vasculitis: changing incidence or definition? Semin Arth Rheum 1995; 25: 2834[ISI]
-
Westman K, Bygren P, Olsson H et al. Relapse rate, renal survival and cancer morbidity in patients with Wegener's Granulomatosus or microscopic polyangiitis with renal involvement. J Am Soc Nephrol 1998; 9: 842852[Abstract]
-
Schena F and the Italian Group of Renal Immunopathology. Survey of the Italian Registry of Renal Biopsies. Frequency of the renal diseases for seven consecutive years. Nephrol Dial Transplant 1997; 12: 418426[Abstract]
-
Andrassy K, Kuster S, Waldherr R, Ritz E. Rapidly Progressive Glomerulonephritis: analysis of prevalence and clinical course. Nephron 1991; 59: 206212[ISI][Medline]
-
Pettersson E, Sundelin B, Heigl Z. Incidence and outcome of pauciimmune necrotizing and crescentic glomerulonephritis in adults. Clin Nephrol 1995; 43: 141149[ISI][Medline]
-
Hedger N, Stevens J, Drey N, Roderick P. Does ANCA negative vasculitis differ from ANCA positive? A ten year retrospective study in Wessex, 1998. The Renal Association Autumn Meeting Abstract [Suppl]: 71
-
Watts R, Scott DGI. Classification and epidemiology of the vasculitides. In: Yazici H, Husby G eds. Bailliere's Clinical Rheumatology. Bailliere Tindall, London: 1997; 11: 191217
-
Symmons D, Barret E, Bankhead C et al. The incidence of Rheumatoid arthritis in the United Kingdom: results from the Norfolk Arthritis Register. Br J Rheum 1994; 33: 7357395[ISI][Medline]
-
Lanham J, Elkon K, Pusey C et al. Systemic Vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss Syndrome 1984. Medicine (Baltimore) 1984; 63: 6581[ISI][Medline]
-
Exley AR, Bacon PA, Luqmani RA et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. Q J Med 1994; 87: 671678[Abstract]
-
El-Reshaid K, Kapoor M, El Resshaid W et al. The Spectrum of renal disease associated with microscopic polyangiitis and classic polyarteritis nodosa in Kuwait. Nephrol Dial Transplant 1997; 12: 18741882[Abstract]
Received for publication: 11. 1.99
Accepted in revised form: 29. 7.99