subgroups: generalized/diffuse/severe, characterized by the involvement of one or more major organ(s), including progressive renal disease and/or extensive alveolar hemorrhage, and limited/localized/early systemic, which predominantly presents as isolated ear, nose, and throat diseases and is not directly life-threatening [23, 94–96]. Localized/limited forms account for up to 29% of GPA at diagnosis, particularly in women, who are slightly younger than those with diffuse GPA (41 years vs. 50 years of age at diagnosis). ANCAs are found in more than 90% of patients with systemic/diffuse/severe GPA but only in 50–78% of those with limited forms. However, transition from a localized to a systemic form and vice versa is possible during the disease. Strictly and persistently localized GPA is exceptional (<5% of patients in both German and French cohorts after 3 years of followup) [97, 98].

Pediatric GPA

GPA is rare in children. Clinical manifestations are similar to those for adults, but girls are more frequently affected than are boys, and nasal deformities and subglottic stenosis are more frequent [99, 100] (Table 8.4). Kidney damage is also frequent and often with a poorer prognosis than in adults. Venous thrombosis may also occur more frequently (in up to 16% of children with GPA). In contrast, neurological manifestations seem less frequent (18% of cases) [101]. However, the overall prognosis is similar but with signifcant morbidity from disease damage and treatment side effects.

Diagnosis

Diagnostic Approach

Classifcation criteria have been defned (Table 8.1 for adults and Table 8.4 for children), and new ones by the American College of Rheumatology and the European League Against Rheumatism have been published in 2021, which reinforce the role of PR3-ANCA. Conversely, and importantly, there are no diagnostic criteria [14]. However, diagnosis of GPA is relatively simple in patients with typical clinical features (Box 8.1) such as a combination of nasal crusting and erosive rhinitis, lung nodules, renal involvement with microscopic hematuria and proteinuria, skin purpura on lower limbs, and mononeuritis multiplex. Still, in practice, the diagnosis is often delayed by weeks or months because the frst manifestations are often not specifc (lingering rhinitis, for example) and are isolated for a while, before more suggestive manifestations of the disease develop. The presence of PR3-ANCAs will almost defnitively support the diagnosis, when it is clinically suspected, without the need for a biopsy. However, even in this setting, as well as in less obvious ones, a histological confrmation may be necessary. A renal biopsy in the setting of renal impairment may also provide prognostic information for renal recovery [61]. In addition, several mimickers that must be ruled out, including infections (endocarditis, which can be associated with positive ANCA testing or fungal infections affecting the ENT or lungs, causing granulomatous in ammation on biopsies) and cocaine-levamisole use, can also be associated with PR3ANCAs and/or MPO-ANCAs (or anti-elastase ANCAs, which are not routinely tested) [102].