Wegener's granulomatosis. New aspects of the disease course, immunodiagnostic procedures, and stage-adapted treatment.

Wegener's granulomatosis (WG) has been diagnosed more frequently in the past few years. The etiology is still unclear; the pathogenesis is only vaguely understood. The association between HLA-DR2 and/or B8 and WG indicates that there is a genetic predisposition. Without treatment WG is said to run a rapid malignant course; with immunosuppressive treatment, however, long-term remission has been reported in about 90% of the cases. More recently several new aspects of WG have been worked out. From the clinical point of view it is particularly important to point out that there are two phases the disease can run through: in more than one third of the cases WG begins with an initial stage that can last for many years without causing any life-threatening complications, but which can at any time turn into the classic disseminated disease. From the immunological point of view it is important to mention that there are new autoantibodies directed against intracytoplasmic antigens of leukocytes with the acronym ACPA. ACPA (synonym: ANCA) are found in greater than 95% of the cases of WG that are in the acute generalized phase, but also in the active initial phase in greater than 60% of the cases. There is a close correlation between ACPA titre and the disease activity: after remission has been induced there is a clear drop in titre, while the titre rises again during relapse, but remains unchanged during superinfection. Thus we must adapt the treatment to the stage the disease is in and accept that ACPA will help to monitor the therapeutical procedure. In our experience, continuous cyclophosphamide-cortisone treatment must still be considered to be the treatment of choice for the acute generalized stage. When the progression of the disease has been stopped, cyclophosphamide can be administered monthly as a bolus for 6 more months. Thereafter we switch to trimethoprim/sulfamethoxazol (T/S) for 12 more months. Furthermore, we must assume that the initial phase of the disease (loco-regional disease) can be treated less aggressively: e.g., with T/S and/or prednisolone.