We read with interest the recent report by the Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group on differences between what they defined as “limited” and “severe” forms of WG with regard to clinical features, antineutrophil cytoplasmic antibody (ANCA) serology, and biopsy findings (1). In his original report on 3 patients with a previously unrecognized new disease entity, Friedrich Wegener concentrated on vasculitic features, but soon he stressed the importance of granuloma formation in what became known as Wegener’s granulomatosis in the 1950s (2). Later, a study by Fienberg suggested that WG may start as granulomatous disease in the respiratory tract, and that vasculitis may evolve subsequently (3).

Meanwhile, numerous clinical and experimental studies have demonstrated that interaction of ANCA with neutrophils leads to endothelial damage, subsequent vasculitis, and leukocyte recruitment, but the relationship between vasculitic and granulomatous lesions needs to be further clarified (for review, see ref. 4). As has been noted in earlier studies (5), the WGET Research Group detected ANCA (by immunofluorescence) and anti–proteinase 3 antibodies (PR3 ANCA)(by enzyme-linked immunosorbent assay) less frequently in patients with limited disease than in patients with generalized WG (1). This may reflect true differences of disease stage, but further methodical improvements, such as use of capture ELISA or detection of ANCA directed against the pro form of PR3, may be more sensitive in the early stages of the disease and to changes in disease activity (6). Carrington and Liebow introduced the term limited WG to characterize predominant involvement of the lungs in the absence of kidney involvement (7). Some patients may present with isolated meningocerebral inflammation or ophthalmic involvement without renal manifestations and the absence of ANCA (8). The European Vasculitis Study Group (EUVAS) refined the term limited WG by determining 2 subgroups previously subsumed under the category of limited forms. The determination of subgroups was based on clinical and pathologic considerations in order to define disease stages. Localized WG was defined as WG restricted to the upper and/or lower respiratory tract. Early systemic WG included any organ involvement except renal, or imminent vital organ failure. Finally, generalized WG included renal involvement and/or imminent organ failure. Two other subgroups, namely, severe renal and refractory disease, were defined to cover the spectrum of disease and to enroll patients into appropriate stage-adopted treatment trials (9). It is obvious that the WGET Research Group’s definition of limited WG as the absence of an immediate threat necessitating aggressive therapy, and that of severe WG as all other patients (1), differs from the EUVAS definitions and may cause confusion. Whereas the EUVAS defined disease stages (9), the WGET Research Group defined 2 groups of patients according to disease activity at the time of enrollment