Summary. Because death after acute systemic vasculitis is now disease. More damage occurred after presentation than after relapse. Lung and multi-system ...
Q J Med 1997; 90:391–399
Original papers QJM Damage occurs early in systemic vasculitis and is an index of outcome A .R. E XL EY1,3, D.M . CA RRUTHE RS3, R. A. L UQMANI 3,4, G. D. KITAS 3, C . GORDON3, B .A. JANS SE N3, C .O .S. SAVAGE2 and P. A. BA CON3 From the Birmingham Vasculitis Group, Departments of 1Immunology, 2Nephrology, and 3Rheumatology, The University of Birmingham, Edgbaston, and 4Department of Rheumatology, University of Edinburgh, Edinburgh, UK Received 20 March 1997
Summary Because death after acute systemic vasculitis is now uncommon, alternative measures of outcome are required. A significant component of patient morbidity is disease-related damage, which can be quantified by the Vasculitis Damage Index (64 items in 11 organ-based systems). We investigated serially the time-course of damage in 120 patients with systemic vasculitis, to determine the earliest indicators of outcome. High damage scores at 2 years after presentation were characteristic of fatal disease (OR 8.1–12.4). Significant damage occurred within 6 months of presentation, and was a feature of fatal
disease. More damage occurred after presentation than after relapse. Lung and multi-system damage were early indicators of poor outcome in severe non-fatal disease. Damage occurs early in systemic vasculitis, and is an indicator of poor outcome. This novel observation, together with evidence of persistent subclinical disease activity and the high frequency of relapse, suggests a need for new treatment strategies. Analogy with the management of acute leukaemia suggests a strategy of early diagnosis and intensive induction of remission, with early escalation of treatment for resistant disease.
Introduction The dramatic increase in survival in systemic vasculitis since the advent of cytotoxic therapy1–3 has significantly reduced the value of mortality as an index of outcome. Alternative measures of outcome address patient morbidity including disease activity, diseaserelated damage and functional outcome.4 Disease activity can be measured using the Birmingham Vasculitis Activity Score, which is a powerful clinical tool for guiding active treatment in systemic vasculitis.5 More than half the patients with systemic vasculitis suffer a relapse within 5 years of remission,6 and active or ‘grumbling’ disease can account for half the patient years of follow-up.7 Significant morbidity due
to disease or drug toxicity occurs in the majority of patients with systemic vasculitis, despite remission of active disease.7 Damage represents the accumulation of permanent scars due to disease or drug toxicity, and to quantify, this we developed and validated the Vasculitis Damage Index (VDI).8 The VDI is a powerful clinical tool which is comprehensive, credible, and more sensitive for recording the accumulation of damage in systemic vasculitis than other available indices.8 We applied the VDI in a cross-sectional study to examine systemic vasculitis from the novel perspective of damage in order to determine its relevance. For this purpose,
Address correspondence to Dr A.R. Exley, Department of Rheumatology, The Medical School, University of Birmingham, Birmingham B15 2TT © Oxford University Press 1997
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patients with fatal disease were chosen as the gold standard for severe disease. Fatal disease was characterized by high total VDI scores with multi-system damage including organ failure. In non-fatal vasculitis, multi-system damage identified a subgroup of patients with the characteristics of severe disease. At last observation the VDI was a powerful measure of disease severity (Exley AR, Bacon PA, Luqmani R, et al., manuscript submitted). Identification of early indicators of outcome and severe disease is critical for further progress in the management of systemic vasculitis. We therefore investigated the earliest features of severe disease in a serial study of 120 patients with systemic vasculitis. We compared damage following presentation with damage following relapse, then examined the relationship between early and late damage. These investigations highlighted five early clinical features of systemic vasculitis which we tested for their power to predict severe disease and poor outcome at last observation. These studies were applied both to all patients with vasculitis and to the subgroup of patients with Wegener’s granulomatosis, as an example of primary necrotizing systemic vasculitis.
spectively by case-note review of 20 cases of severe fatal vasculitis. Systemic vasculitis was diagnosed according to accepted criteria, and patients were then classified according to the ACR criteria.5,10–17 The Chapel Hill consensus definitions were used for microscopic polyangiitis18 and Wegener’s granulomatosis, which were further subdivided into classical (renal) and non-renal disease as described previously.19 Data from the interval after both presentation and first relapse were collected in 35 of the patients with non-fatal vasculitis (Table 1). The date of first symptoms attributable to vasculitis was recorded as the onset of disease. The date of presentation to any hospital was recorded as the common reference point. We compared the increase in damage scores in the 6 months after presentation (interval A) with the 6 months after relapse (interval B). The 100 cases with non-fatal vasculitis were grouped according to damage scored at 6 months after presentation. Group 1 included patients with damage limited to a single organ-based system, while group 2 patients had damage in more than one organ-based system. The same criteria were applied to the 49 cases of Wegener’s granulomatosis with non-fatal vasculitis (Table 2).
Methods Patients
Damage scores
This observational study was based on data from 100 patients with systemic vasculitis attending the Birmingham University Hospital Vasculitis Clinics July 1993–December 1995 during prospective follow-up studies9. Data was also collected retro-
There are 64 items of damage listed in the VDI, which also incorporates a glossary and guidelines for its application. All damage occurring since the onset of vasculitis is included. The total VDI score is the cumulative sum of items of damage scored.
Table 1
Non-fatal and severe fatal systemic vasculitis (120 patients)
All patients
Patients studied at presentation and first relapse
Diagnosis
Non-fatal:fatal disease (number)
Systemic rheumatoid vasculitis Polyarteritis nodosa Classical Wegener’s granulomatosis Non-renal Wegener’s granulomatosis Takayasu’s arteritis Behcet’s disease Churg-Strauss syndrome Microscopic polyangiitis All Age at presentation (years) Symptoms before presentation (years) Presentation to relapse (years) Presentation to last observation (years)
8:7 12:1 22:11 27:1 7:0 7:0 7:0 10:0 100:20 49 (34–60) vs. 62 (52–68)* 0.2 (0.1–1.0) vs. 0.1 (0.1–0.3)**
4 2 11 10 2 1 35 45 (29–57) 0.2 (0.1–0.5) 2.3 (1.5–4.2)
5.0 (2.6–8.9) vs. 2.4 (0.5–5.6)***
The table shows the demographic details for 120 patients with systemic vasculitis including 35 patients with non-fatal systemic vasculitis who were studied at both presentation and first relapse. Patients were classified according to standard criteria as described in Methods. Data are medians and interquartile ranges. *p
