[Vasculitides and anti-GBM disease]

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV)-granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA)-as well as anti-glomerular basement membrane disease (anti-GBM disease) are systemic small-vessel vasculitides with high mortality. Diagnosis relies on serology/laboratory testing, organ screening, and exclusion of differential diagnoses. Biopsy must not delay therapy initiation in fulminant cases. In GPA and MPA, loss of T‑ and B‑cell tolerance and ANCA-mediated activation of neutrophils are pivotal. Diagnostic hallmarks include myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA. Kidney biopsy reveals pauci-immune necrotizing and extracapillary proliferative glomerulonephritis. Remission induction consists of glucocorticoids (GC) combined with rituximab (RTX) or cyclophosphamide (CYC). Maintenance therapy is preferably performed with RTX. EGPA is defined by eosinophilic tissue infiltration, often accompanied by asthma and nasal polyposis; ANCAs are present in 30-40%. Diagnostic evaluation includes blood count, inflammatory markers, immunoglobuline E (IgE), ANCA, and ENT, pulmonary, and cardiac evaluation. Nonorgan-threatening disease is treated with GC, whereas relapsing disease is managed with interleukin (IL)-5 pathway inhibitors. Organ- or life-threatening manifestations require GC plus CYC or RTX, followed by IL‑5 pathway inhibitors for maintenance therapy. Anti-GBM is driven by autoantibodies against type IV collagen and presents with a nephritic syndrome and/or alveolar hemorrhage. Within 24 h, diagnostic evaluation should include testing for anti-GBM antibodies and ANCA, thoracic imaging, exclusion of infection, and a kidney biopsy demonstrating linear IgG deposits. Treatment consists of plasmapheresis combined with GC and CYC, with RTX as an alternative. Maintenance therapy is not required unless concomitant ANCA positivity is present.