VEGF (Vascular Endothelial Growth Factor)
Central pathogenic driver — mediates vascular permeability, edema, organomegaly, neuropathy
- Expression
- Markedly elevated (5-10x normal)
- Evidence level
- established
- Targeted by
- Bevacizumab (disappointing results; insufficient alone)
Role in pathogenesis
VEGF is the central cytokine driving POEMS manifestations. Serum levels are typically 5-10 fold above normal and correlate with disease activity. VEGF drives increased vascular permeability causing edema, ascites, pleural effusion, papilledema, and contributes to peripheral nerve demyelination via increased endoneural pressure. Paradoxically, single-cell analysis shows VEGF is NOT produced by the clonal plasma cells themselves — IL-6 from clones induces VEGF production in surrounding cells.