ANCA produce tissue damage by activating cytokine-primed neutrophils and monocytesThese activated neutrophils adhere to endothelial cells, releasing proteolytic granule contents and proinflammatory cytokines
The release of inflammatory cytokines causes the downstream release of reactive oxygen species and oxidative damage, which further activates the endothelium causing more inflammation…In short, ANCAs activate neutrophil
Focal glomerulonephritis with crescent formation on renal biopsy specimen, characteristic of Wegener granulomatosis.
Lung biopsy specimen from a patient with Wegener granulomatosis showing evidence of vasculitis and inflammation
CYCLOPS trial - Pulse IV vs. daily PO
MEPEX trial –Plasmapharesis vs IV methylprednisolone BOTH WITH PO prednisone and cyclophosphamide (not the best trial)
CYCAZAREM- Azathioprine vs. Cycophosphamide in maintenance. Same efficacy, MANY fewer complications. So we use Azathioprine. Another study compared MTX & AZA. Same relapse rate. Same side effect rate, just different side effects.
Pathogenetic model proposed for Churg–Strauss syndrome, based on available experimental evidence. Hypothetical allergens or antigens may be uptaken by antigen-presenting cells and presented to CD4+ T cells, leading to T-cell activation and expansion. Antigen-presenting cells (which can be of different cell types, for example, dendritic cells, monocyte macrophages, and eosinophils) have a restricted HLA repertoire and often express HLA-DRB4. Once activated, CD4+ T cells secrete IFN-γ, which promotes granulomatous inflammation, and also drive eosinophil activation and expansion through the secretion of IL-4, IL-5, and IL-13, or by means of the CD95–CD95L pathway. Eosinophils mediate tissue damage mainly by secreting granule proteins such as ECP and MBP. Endothelial cells may also contribute to tissue infiltration by eosinophils by releasing eotaxin-3, a chemokine with strong chemotactic activity on eosinophils. B cells are also likely to play a pathogenetic role: activated on antigen encountering and 'helped' by T-helper 2 cytokines such as IL-4 and IL-13, they may become mature plasma cells and then produce different autoantibodies, including ANCA, which may in turn mediate vasculitis. ANCA, anti-neutrophil cytoplasmic antibodies; CD95L, CD95 ligand; ECP, eosinophilic cationic protein; IFN-γ, interferon-γ; IL(-4, -5, -13), interleukin(-4, -5, -13); MBP, major basic protein; TCR, T-cell receptor.
The most common radiological manifestations consist of transient, patchy, nonsegmental areas of consolidation without predilection for any lung zone.[24-26] The areas of consolidation can be symmetric or asymmetric and may have a peripheral distribution similar to that seen in chronic eosinophilic pneumonia[25,26] (Fig. 5). Less common manifestations include small or large nodules, unilateral or bilateral pleural effusions, and hilar lymphadenopathy.
Skin & Kidney
Type IV collagen
Alpha 3, alpha 4, alpha 5 form a triple helical molecule (the promotor) which then dimerize to form a Hexamer of type IV collagen.
Fig 1 A hypothetical structure of α3 chain type IV collagen. Linear structure of human α3 chain type IV collagen composed of three distinct domains: a cysteine rich N-terminal 7S domain, a central triple helical domain with multiple small interruptions and a globular C-terminal non-collagenous (NC1) domain.