Why does Kawasaki disease particularly involve the coronary arteries?

Why Kawasaki Disease Particularly Involves the Coronary Arteries

Kawasaki disease specifically targets medium-sized muscular arteries throughout the body, but the coronary arteries are particularly vulnerable due to their size, structure, and the synchronized inflammatory cascade that causes severe damage to all arterial wall layers, leading to aneurysm formation in 15-25% of untreated children. 1, 2

Anatomical Predilection for Medium-Sized Muscular Arteries

The fundamental reason coronary arteries are affected relates to vessel size and structure:

• KD vasculopathy primarily targets medium-sized muscular arteries, with the coronary arteries being the prototypical example of this vessel type in young children 1, 2
• The coronary arteries possess the specific structural characteristics (muscular media layer, elastic lamina) that make them susceptible to the three-phase inflammatory process of KD 1
• While KD causes systemic inflammation in all medium-sized arteries throughout the body, the coronary arteries are most clinically significant due to their critical role in cardiac perfusion 1, 3

The Three-Phase Pathological Process

The American Heart Association has identified why coronary damage is so severe and specific:

• Necrotizing arteritis occurs as a synchronized neutrophilic process that destroys all layers of the arterial wall (intima, media, and elastica) within the first 2 weeks after fever onset 1, 4
• Subacute/chronic vasculitis begins simultaneously in the first 2 weeks and can persist for months to years, characterized by marked accumulation of monocytes/macrophages that cause ongoing arterial damage 1, 4, 2
• Luminal myofibroblastic proliferation (LMP) represents a unique medial smooth muscle cell-derived process that begins early and has the potential to cause progressive arterial stenosis over time 1, 4

Why Coronary Arteries Are Most Vulnerable

Several factors explain the particular vulnerability of coronary vessels:

• The inflammation spreads completely around the circumference of the artery in a synchronized fashion, resulting in severe damage to all structural components simultaneously 2
• Coronary arteritis begins 6-8 days after KD onset, and inflammation of all arterial layers rapidly ensues, causing the vessel to dilate as structural integrity is lost 2
• The loss of intima, media, and elastica in severely affected vessels cannot be regenerated—only a rim of adventitia remains in giant aneurysms 1
• Lesions in all affected arteries are relatively synchronous as they evolve from acute to chronic injury, but coronary arteries bear the highest hemodynamic stress 2

Systemic Nature Despite Coronary Prominence

While coronary involvement is most clinically significant, the disease is truly systemic:

• Medium-sized arteries throughout the body can develop aneurysms, including subclavian, brachial, axillary, iliac, femoral, splanchnic, and mesenteric vessels 1
• The coronary arteries are simply the most critical vessels affected, making their involvement life-threatening through risk of thrombosis, myocardial infarction, and sudden death 1, 5
• Abdominal aortography and subclavian arteriography are recommended during coronary angiography to identify these other arterial aneurysms 1

Clinical Implications of Coronary Specificity

The particular involvement of coronary arteries drives management priorities:

• Peak mortality occurs 15-45 days after fever onset when established coronary vasculitis coincides with marked platelet elevation and hypercoagulable state 6
• Giant aneurysms (≥8 mm diameter or Z score ≥10) do not truly "resolve" or "regress"—they develop successive layers of thrombi with organization and calcification 1, 4
• Myocardial infarction can occur from acute thrombosis, progressive thrombosis, or stenosis caused by luminal myofibroblastic proliferation 1, 4
• IVIG treatment within 10 days of fever onset reduces coronary artery aneurysm risk from 15-25% to approximately 4.7% 4, 5

Pathophysiological Mechanisms

The underlying mechanisms explain why medium-sized muscular arteries are targeted:

• Aberrant activation of monocytes/macrophages is thought to be central to vascular lesion formation in KD 2
• The intense inflammatory process involves activation of IL-1, IL-6, and TNF signaling pathways that specifically damage arterial walls 3
• An infectious trigger (likely a novel RNA virus) in genetically susceptible children initiates the cascade, with identified susceptibility genes including ITPKC, CD40, BLK, and Fcγ receptors 4, 7