In regard to rescue therapy for those patients with IVIG resistance, typically a second dose of IVIG is administered. There is significant variation across centers about the use of other agents, including corticosteroids and infliximab for rescue therapy. Formalized trials will be required to delineate optimal regimens for children with IVIG resistance.
Prognosis of KD
The vast majority of children with KD respond to a single dose of IVIG with rapid clinical improvement and reassuring echocardiography; these children have excellent prognoses. Published mortality rates are quite low, generally less than 1%, and deaths are typically due to rupture of inflamed, dilated coronary arteries within a month of disease onset or myocardial infarction from thrombosed coronary arteries occurring anywhere from a few months to years after disease onset.
The AHA has published specific guidelines for managing children with KD according to their relative risk of myocardial ischemia.2 Children who develop aneurysms require careful long-term monitoring by a pediatric cardiologist. Morbidity can be high in patients with significant cardiac sequelae from KD.
Long-Term Vascular Health
Important yet incompletely answered questions remain regarding those KD patients who never developed evidence of significant coronary artery involvement. Results have been conflicting regarding whether such patients have normal endothelial function or if they are at risk for accelerated atherosclerosis. A recent study offered some reassurance that children with normal coronary artery dimensions or mild ectasia throughout their disease course have similar indices of vascular health as healthy controls.16 However, questions of long-term vascular health in children with KD and normal coronary dimensions will be answered with large, prospective studies of middle-age individuals with a history of KD. Until such data become available, all children with a history of KD should be counseled regarding a heart healthy diet and lifestyle with avoidance of modifiable risk factors for heart disease.
Mary Beth Son, MD, is a specialist in rheumatology at Boston Children’s Hospital.
Key Points
- Kawasaki disease (KD) is an acute febrile illness of early childhood characterized pathologically by vasculitis of medium-size muscular arteries with a predilection for the coronary arteries.
- Because a diagnostic test for KD remains elusive, clinical criteria are relied upon to make the diagnosis.
- Timely diagnosis and treatment with intravenous gammaglobulin (IVIG) is necessary to prevent coronary artery abnormalities (CAA), because the prognosis of the disease is predicated entirely upon the degree of coronary artery involvement.
- Further research is required to delineate optimal treatment regimens for children at high risk for CAA and to determine the long-term risk of coronary artery disease for those children who never had overt coronary artery involvement.
References
- Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi = [Allergy]. 1967;16(3):178–222.
- Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110(17):2747–2771.
- Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113(22):2606–2612.
- Sano T, Kurotobi S, Matsuzaki K, et al. Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment. Eur J Pediatr. 2007;166(2):131–137.
- Egami K, Muta H, Ishii M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149(2):237–240.
- Sleeper LA, Minich LL, McCrindle BM, et al. Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr. 2011;158(5):831–835 e833.
- Yanagawa H, Nakamura Y, Yashiro M, et al. Incidence of Kawasaki disease in Japan: The nationwide surveys of 1999–2002. Pediatr Int. 2006;48(4):356–361.
- Onouchi Y, Gunji T, Burns JC, et al. ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet. 2008;40(1):35–42.
- Chang CJ, Kuo HC, Chang JS, et al. Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease susceptibility. PLoS One. 2013;8(8):e72037.
- Khor CC, Davila S, Breunis WB, et al. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. Nat Genet. 2011;43(12):1241–1246.
- Ha KS, Jang G, Lee J, et al. Incomplete clinical manifestation as a risk factor for coronary artery abnormalities in Kawasaki disease: A meta-analysis. Eur J Pediatr. 2013;172(3):343–349.
- Yellen ES, Gauvreau K, Takahashi M, et al. Performance of 2004 American Heart Association recommendations for treatment of Kawasaki disease. Pediatrics. 2010;125(2):e234–241.
- Hsieh KS, Weng KP, Lin CC, et al. Treatment of acute Kawasaki disease: Aspirin’s role in the febrile stage revisited. Pediatrics. 2004;114(6):e689–693.
- Newburger JW, Sleeper LA, McCrindle BW, et al. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. The N Engl J Med. 2007;356(7):663–675.
- Kobayashi T, Saji T, Otani T, et al. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): A randomised, open-label, blinded-endpoints trial. Lancet. 2012;379(9826):1613–1620.
- Selamet Tierney ES, Gal D, Gauvreau K, et al. Vascular health in Kawasaki disease. J Am Coll Cardiol. 2013;62(12):1114–1121.
