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PubMed2006

Treatment of ANCA-associated systemic vasculitis.

The antineutrophil cytoplasmic antibodies (ANCA)-associated small vessel vasculitides include Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis (MPA), and the renal limited form of MPA, also known as pauci-immune or idiopathic crescentic glomerulonephritis. ANCA are probably necessary but not sufficient for disease pathogenicity. Classical induction and maintenance therapy of these conditions with corticosteroids and long-term cyclophosphamide is associated with occasional relapse and major toxicities. Therefore, treatment regimens being investigated include induction with methotrexate or, especially for patients with more aggressive disease accompanied by renal insufficiency, therapies that include either pulses of methylprednisolone or plasma exchanges. Nontraditional options for maintenance therapy may include step-down treatment with azathioprine or mycophenolate mofetil. For patients with Wegener's granulomatosis, studies have shown a reduced occurrence of flares with the use of co-trimoxazole. Finally, although a carefully randomized controlled trial with etanercept demonstrated that this tumor necrosis factor (TNF)-blocking agent was not superior to conventional maintenance therapy, a biologic agent with a different mechanism of action, rituximab, may prove a satisfactory alternative.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1990

Systemic vasculitis in the 1980s--is there an increasing incidence of Wegener's granulomatosis and microscopic polyarteritis?

Thirty-six cases of Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA) presenting to the nephrology service in Leicester between 1980 and 1989 were reviewed. Apart from the diagnostic respiratory tract lesions seen in WG, cases of MPA and WG could not be distinguished by age and sex, range and severity of organ involvement, response to treatment (oral prednisolone and cyclophosphamide), mortality or renal outcome. The combined incidence of WG and MPA in 1980-86 was 1.5/million/year. Following the introduction in January 1987 of an assay for anti-neutrophil cytoplasmic antibody (ANCA), the incidence of WG and MPA increased in 1987-89 to 6.1/million/year (p less than 0.0001). Cases seen during these two periods did not differ by any clinical parameter except that later cases had less severe renal disease at referral and improved renal outcome. Median serum creatinine was significantly lower at presentation in 1987-89 (p less than 0.02). Of those surviving 3 months from presentation only 1/20 in 1987-89 had end stage renal failure compared with 4/10 in 1980-86 (p less than 0.02). These findings may reflect increasing diagnostic awareness of WG and MPA among physicians since the introduction of ANCA.

Adult↗
PubMed1989

Serum cytokine changes in systemic vasculitis.

Cytokines are known to alter a number of vascular tissue cell functions. The aim of this retrospective study was to determine serum cytokine levels in patients with vasculitis and to analyse the possible relation to the severity of the disease. Tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1)beta, IL-2, interferon (IFN)- and IFN-gamma were assayed in 33 patients with polyarteritis nodosa (PAN) or Churg and Strauss angiitis (CSA), and three with Wegener granulomatosis (WG). Serum cytokine changes were observed in most patients with active disease, i.e. before treatment was started. In the majority of patients with PAN or CSA, there was a marked increase in serum IFN-alpha and IL-2 levels, while TNF-alpha and IL-beta levels were moderately elevated. Serum IFN-gamma remained undetectable in all but one of these patients. In patients with WG, serum IFN-alpha and IL-2 levels were also elevated, whereas IL-1 beta, IFN-gamma and TNF alpha levels remained within normal limits. In paired samples of patients with PAN, IFN-alpha and IL-2 levels were significantly higher before than after treatment. These preliminary data suggest that a particular pattern of cytokine changes is associated with vasculitis and that cytokines might be involved in the pathogenesis of PAN/CSA and WG. Prospective studies are warranted to determine whether cytokines could be considered for the monitoring of disease activity and therapy.

Biological Factors↗
PubMed1989

[Anti-cytoplasmic antibodies of neutrophil granulocytes in systemic vasculitis].

Autoantibodies to the cytoplasmic components of neutrophil polymorphonuclear granulocytes (ACPA) were searched for by indirect immunofluorescence on ethanol-fixed smears from normal white blood cells in 248 sera from patients with Wegener's granulomatosis, Kawasaki disease and various other vasculitides, connective tissue diseases, nephropathies and infiltrative pulmonary diseases. Apart from a weak positivity in a few Kawasaki disease sera, ACPA were found in Wegener's granulomatosis (and micropolyarteritis) only, with a correlation between ACPA titers and disease activity. These results confirm the value of ACPA in the diagnosis and evaluation of activity of Wegener's granulomatosis.

Antibodies↗