Pathophysiology of Kawasaki Disease

Abstract

Kawasaki Disease (KD) vasculopathy, which most significantly affects the coronary arteries, is characterized by three linked pathological processes: necrotizing arteritis, subacute/chronic (SA/C) vasculitis, and luminal myofibroblastic proliferation (LMP). Necrotizing arteritis (NA), initiated at the endothelial luminal surface, leads to giant aneurysms that can rupture or thrombose. SA/C vasculitis begins in the adventitia and is closely associated with LMP. LMP consists of actively proliferating smooth muscle cell-derived myofibroblasts and their matrix products, and can result in progressive arterial luminal stenosis. All three processes begin in the first 2 weeks after fever onset. NA subsides in the first 2 weeks, while subacute/chronic vasculitis and LMP can persist for months or years. The clinical and epidemiological features of KD are best explained by infection with an as-yet-unidentified ubiquitous agent, likely a virus entering via the respiratory route. Recent advances in genomics and RNA sequencing are beginning to reveal specific immune response dysfunction in KD that could lead to new diagnostics and therapeutics for this important childhood illness.