Is Macrophage Activation Syndrome in Kawasaki Disease Underrecognized?

Kawasaki disease (KD) is an acute vasculitis of unknown etiology that predominantly affects children < 5 years of age. It is now the leading cause of acquired heart disease in the pediatric age group in developed countries1. The diagnosis of classic KD is based on the presence of ≥ 5 days of fever and the demonstration of ≥ 4 of 5 principal clinical features: erythematous rash, bilateral nonexudative conjunctival injection, changes in the lips and oral cavity, erythema and edema in the hands and feet, and cervical lymphadenopathy, usually unilateral2. However, many children with KD, especially infants, present with fewer than 4 of the principal clinical findings (so-called incomplete KD), and may experience significant delays in diagnosis. The main complication of KD is the development of coronary artery aneurysms, which occur in around 25% of untreated cases. High-dose intravenous immunoglobulin (IVIG) administration in the acute phase of the illness has been shown to reduce the prevalence of coronary artery abnormalities to 3–6%1,3. However, about 10% to 20% of patients develop persistent or recurrent fever after primary therapy with IVIG and are termed IVIG resistant4. Several studies have shown that patients who are refractory to initial IVIG are at increased risk of developing coronary artery abnormalities5. A number of therapeutic approaches have been proposed for children who have failed to respond to initial therapy, including IVIG retreatment, corticosteroids, infliximab, cyclosporine, anakinra, plasma exchange, and cytotoxic agents1. Macrophage activation syndrome (MAS) is a life-threatening complication of rheumatic disorders that is part of the spectrum of secondary hemophagocytic lymphohistiocytosis (HLH)6. Although the pathophysiology of MAS is incompletely understood, it is thought to result from a dysfunctional immune response, which causes uncontrolled activation of the monocyte/macrophage system and … Address correspondence to Prof. A. Ravelli, Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genoa, Italy. Email: angeloravelli{at}gaslini.org.