Diagnostics and therapy of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides.

Granulumatosis with polyangiitis (wegener's)/GPA microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS) are primary systemic vasculitides which predominantly affect small vessels, showing a high association with a positive C/PR3-ANCA in GPA and P/MPO-ANCA in MPA, so called ANCA-associated vasculitides (AAV). The diagnostic work-up relies on an interdisciplinary approach including imaging techniques and laboratory tests in order to assess disease stage and extent. The golden standard remains the histological proof of a necrotizing, pauci-immune small vessel vasculitis, in GPA additionally non-caseating granuloma is found mainly in the respiratory tract. Treatment is adapted to disease stage and extent and relies on a combination of a cytotoxic plus a tapering regimen of glucocorticosteroids. Induction of remission in "early systemic" disease without organ- and life-threatening organ manifestations and a near normal kidney function can be achieved with methotrexate. In the generalized phase with significant renal dysfunction cyclophosphamide is the mainstay of therapy, in rapidly progressive glomerulonephritis with an imminent dialysis indication plasmapheresis is performed additionally. When remission is achieved, usually after 3-6 months of induction treatment, cyclophosphamide is switched to azathioprine as maintenance of remission drug. Alternative therapies are methotrexate provided the kidney function is normal or Leflunomide in the long-term follow-up the relapse rate in ANCA-associated vasculitis is approximately 50% in 5 years, irrespective of the drug used for maintenance treatment. The relapse rate is significantly higher in GPA than in MPA and CSS.

[Treatment of ANCA-associated vascularitides]. / Traitement des vascularites systémiques associées aux ANCA.

Treatment for ANCA-associated vasculitides is now well defined, but must be adjusted for each patient according to the type of vasculitis, its precise form (e.g., limited versus systemic Wegener's granulomatosis) and severity, and patients' characteristics, such as age and renal function. The therapeutic decision must also take into account the risk of adverse events inherent to each treatment. The efficacy of adequate induction treatment has been demonstrated: more than 80% of patients now achieve remission. Relapse rates nonetheless remain high, especially in Wegener's granulomatosis. Patients with microscopic polyangiitis or Churg-Strauss syndrome with no poor prognostic factors can be treated with corticosteroids alone, with immunosuppressants added only in case of treatment failure. Patients with Wegener's granulomatosis or microscopic polyangiitis or Churg-Strauss syndrome and one or more poor prognostic factors must receive a combination of corticosteroids and immunosuppressants, mainly intravenous pulsed cyclophosphamide. Plasma exchange is indicated as an adjuvant therapy for patients with severe renal involvement. Once remission is achieved, maintenance therapy can replace cyclophosphamide by a less toxic immunosuppressive drug, such as azathioprine or methotrexate. For these latter patients, the optimal duration of induction therapy remains to be determined, but should not be shorter than 18 months. Conversely, there is no need to prescribe high-dose corticosteroids for months. Prednisone must be started at 1 mg/kg/d then rapidly tapered so that patients are not receiving more than 15 mg/d after 3-4 months of therapy. Biological therapies also appear to have a place in the therapeutic armamentarium for ANCA-associated systemic vasculitides, at least for patients whose disease is refractory to conventional therapy. However, the precise indications for anti-TNFalpha or anti-CD20 monoclonal antibodies and their optimal regimens (doses and durations) have not yet been defined. Anti-IL5, interferon-alpha and anti-IgE monoclonal antibodies might also be useful for Churg-Strauss syndrome. These biologics must be prescribed extremely cautiously and only in trial settings, especially in view of the adverse effects, few but severe, recently been reported with them.