Abstract
Forty eight years ago Doctor Tomisaku Kawasaki firstly described a disease called “Acute febrile muco-cutaneous lymph node syndrome”, after labeled as Kawasaki disease (KD). It still remains a mysterious illness affecting coronaries in a quarter of untreated patients and is the most common cause of childhood-acquired heart disease in industrialized countries. Many gaps exist in our knowledge in the etiology and pathogenesis of KD. Numerous KD features still demand further efforts to achieve a better understanding of the disease. Some of these issues include coronaries’ injuries in children not fulfilling the classical diagnostic criteria, genetic predisposition, unpredictable ineffectiveness of current therapy in some cases, vascular dysfunction in patients not showing echocardiographic evidence of coronaries abnormalities in the acute phase and risk of potential premature atherosclerosis. The lack of specific laboratory tests for early identification of the atypical and incomplete cases, especially in infants, is one of the obstacles to treat early patients in order to reduce cardiovascular involvement. Transthoracic echocardiography remains the gold-standard for evaluation of coronaries in the acute phase and follow-up. In patients with severe vascular complications, more expensive and invasive investigations, such as coronary CT angiography and MRI, may be required. As children with KD grow-up, the acknowledgment and treatment of the potential sequelae become critical, requiring rheumatologists, cardiologists and infectious disease specialists cooperate to develop guidelines for a proper evaluation and management of patients. Deep education is recommended for physicians and other professionals about how to recognize the long-term impact of systemic problems related to KD.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Burns JC (2002) Commentary: translation of Dr. Tomisaku Kawasaki’s original report of fifty patients in 1967. Pediatr Infect Dis J 21:993–1005
Kawasaki T, Kosaki T, Okawa S, Shigematsu I, Yanagawa H (1974) A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 54:271–276
Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR (2002) Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 360:1197–1202
Kato H, Koike S, Yamamoto M, Ito Y, Yano E (1975) Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome. J Pediatr 86:892–898
Harnden A, Alves B, Sheikh A (2002) Rising incidence of Kawasaki disease in England: analysis of hospital admission data. BMJ 324:1424–1425
Nakamura Y, Yashiro M, Uehara R, Sadakane A, Tsuboi S, Aoyama Y et al (2012) Epidemiologic features of Kawasaki disease in Japan: results of the 2009–2010 nationwide survey. J Epidemiol 22:216–221
Rowley AH, Baker SC, Shulman ST, Fox LM, Takahashi K, Garcia FL et al (2005) Cytoplasmic inclusion bodies are detected by synthetic antibody in ciliated bronchial epithelium during acute Kawasaki disease. J Infect Dis 192:1757–1766
Hirao J, Hibi S, Andoh T, Ichimura T (1997) High levels of circulating interleukin- 4 and interleukin-10 in Kawasaki disease. Int Arch Allergy Immunol 112:152–156
Chan WC, Duong TT, Yeung RS (2001) Presence of IFN-gamma does not indicate its necessity for induction of coronary arteritis in an animal model of Kawasaki disease. J Immunol 173:3492–3503
Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC et al (2004) Diagnosis, treatment, and long- term management of Kawasaki disease. Circulation 110:2747–2771
Yeo Y, Kim T, Ha K, Jang G, Lee J, Lee K, Son C, Lee J (2009) Incomplete Kawasaki disease in patients younger than 1 year of age: a possible inherent risk factor. Eur J Pediatr 168:157–162
Sonobe T, Kiyosawa N, Tsuchiya K, Aso S, Imada Y, Imai Y et al (2007) Prevalence of coronary artery abnormality in incomplete Kawasaki disease. Pediatr Int 49:421–426
Genizi J, Miron D, Spiegel R, Fink D, Horovitz Y (2003) Kawasaki disease in very young infants: high prevalence of atypical presentation and coronary arteritis. Clin Pediatr (Phila) 42:263–267
Falcini F, Ozen S, Magni-Manzoni S, Candelli M, Ricci L, Martini G et al (2012) Discrimination between incomplete and atypical Kawasaki syndrome versus other febrile diseases in childhood: results from an international registry-based survey. Clin Exp Rheumatol 30:799–804
Huang MY, Gupta-Malhotra M, Huang JJ, Syu FK, Huang TY (2010) Acute-phase reactants and a supplemental diagnostic aid for Kawasaki disease. Pediatr Cardiol 31:1209–1213
Tacke CE, Romeih S, Kuipers IM, Spijkerboer AM, Groenink M, Kuijpers TW (2013) Evaluation of cardiac function by magnetic resonance imaging during the follow-up of patients with Kawasaki disease. Circ Cardiovasc Imaging 6:67–73
Dietz SM, Tacke CE, Kuipers IM, Viegman A, de Winter RJ, Burns C et al (2015) Cardiovascular imaging in children and adults following Kawasaki disease. Insight Imaging 6:697–705
Eleftheriou D, Levin M, ShingadiaD TR, Klein NJ, Brogan PA (2014) Management of Kawasaki disease. Arch Dis Child 99:74–83
Newburger JW, Sleeper LA, McCrindle BW, McCrindle DW, Minich LU, Gersony W et al (2007) Randomized trial of pulse corticosteroid therapy for primary treatment of Kawasaki disease. N Eng J Med 356:663–675
Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR et al (2008) Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 153:117–121
Kobayashi T, Saji T, Otani T, Kobayashi T, Saji T, Otani T (2012) 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 379:1613–1620
Chen S, Dong Y, Yin Y, Krucoff MW (2013) Intravenous immunoglobulin plus corticosteroid to prevent coronary artery abnormalities in Kawasaki disease: a meta-analysis. Heart 99:76–82
Sato S, Kawashima H, Kashiwagi Y, Oshika A (2013) Inflammatory cytokines as predictors of resistance to intravenous immunoglobulin therapy in Kawasaki disease patients. Int J Rheum Dis 16:168–172
Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD et al (2005) Infliximab treatment for refractory Kawasaki syndrome. J Pediatr 146:662–667
Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS et al (2008) Infliximabtreatment of intravenous immunoglobulin-resistant kawasaki disease. J Pediatr 153:833–838
Son MB, Gauvreau K, Burns JC, Corinaldesi E, Tremoulet AH, Watson VE et al (2011) Infliximab for intravenous immunoglobulin resistance in Kawasaki disease: a retrospective study. J Pediatr 158:644–649
Hirono K, Kemmotsu Y, Wittkowski H, Foell D, Saito K, Ibuki K et al (2009) Infliximab reduces the cytokine-mediated inflammation but does not suppress cellular infiltration of the vessel wall in refractory Kawasaki disease. Pediatr Res 65:696–701
Levin M, Burgner D (2014) Treatment of Kawasaki disease with anti-TNF antibodies. Lancet 383:1700–1703
Sonoda K, Mori M, Hokosaki T, Yokota S (2014) Infliximab plus plasma exchange rescue therapy in Kawasaki disease. J Pediatr 164:1128–1132
Davies S, Gold-von SG (2013) Should Infliximab be used as an adjuvant to IVIG in the treatment of children with Kawasaki disease who are at high risk for resistance to conventional therapy? Pediatr Cardiol 34:1756
Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T et al (2006) Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation 113:2606–2612
Sleeper LA, Minich LL, McCrindle BM, Lee JS, Mason W, Colan SD, Atz AM et al (2011) Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr 158:831–835
Cohen S, Tacke CE, Straver B, Meijer N, Kuipers IM, Kuijpers TW (2012) A child with severe relapsing Kawasaki disease rescued by IL-1 receptor blockade and extracorporeal membrane oxygenation. Ann Rheum Dis 71:2059–2061
Shafferman A, Birmingham JD, Randy QC (2014) High dose anakinra for treatment of severe neonatal Kawasaki disease: a case report. Pediatr Rheumatol Online 12:26
Miura M, Katada Y, Ishihara J (2004) Time interval of measles vaccination in patients with Kawasaki disease treated with additional intravenous immunoglobulin. Eur J Pediatr 163:25–29
Tacke CE, Smits GP, van der Klis FRM, Kuipers IM, Zaaijer HL, Kuijpers TW (2014) Reduced serologic response to mumps, measles, and rubella vaccination in patients treated with intravenous immunoglobulin for Kawasaki disease. Allergy Clin Immunol 131:1701
Cheung YF, Yung TC, Tam SC, Ho MH, Chau AK (2004) Novel and traditional cardiovascular risk factors in children after Kawasaki disease: implications for premature atherosclerosis. J Am Coll Cardiol 43:120–124
Noto N, Okada T, Karasawa K, Ayusawa M, Sumitomo N, Harada K et al (2009) Age-related acceleration of endothelial dysfunction and subclinical atherosclerosis in subjects with coronary artery lesions after Kawasaki disease. Pediatr Cardiol 30:262–268
Masi L, Franceschelli F, Leoncini G (2013) Can Fibroblast growth factor (FGF)-23 circulating levels suggest coronary artery abnormalities in children with Kawasaki disease? Clin Exper Rheumatol 31:149–153
Falcini F, Rigante D, Masi L, Covino M, Franceschetti F, Leoncincini G, Tarantino G, MatucciCerinic M, Brandi ML (2013) Fibroblast growth factor (FGF23) gene polymorphism in children with Kawasaki syndrome (KS) and susceptibility to cardiac abnormalities. Italian J Pediatr 39:69–74
Stagi S, Rigante D, Lepri G, MatucciCerinic M, Falcini F, (2016) Severe Vitamin D deficiency in patients with Kawasaki a potential role in the risk to develop heart vascular abnormalities?.Clin Rheumatol 35(7):1865–1872
Manlhiot C, Niedra E, McCrindle BW (2013) Long-term management of Kawasaki disease: implications for the adult patient. Pediatr Neonatol 54:12–21
JCS Joint Working Group (2014) Guidelines for diagnosis and management of cardiovascular Sequelae in Kawasaki disease (JCS 2013). Dig VersionCirc J 78:2521–2562
Levin M, Burns JC, Gordon JB (2014) Warfarin plus Aspirin or Aspirin alone for patient with giant coronary artery Aneurysms secondary to Kawasaki disease? Cardiology 129:174–177
Saij T, Ayusawa M, Miura M, Gobayashi T, Suzuki H, Mori M et al (2014) Guidelines for medical treatment of acute Kawasaki disease: report of the research committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version). Pediatr Int 56:135–158
Maric LS, Knezovic I, Papic N, Mise B, Roglic S, Markovinovic L et al (2014) Risk factors for coronary artery abnormalities in childrenwith Kawasaki disease: a 10‑year experience. RheumatolInt. Epubahead of print
Ishikawa T, Iwashima S (2013) Endothelial dysfunction in children within 5 years after onset of Kawasaki disease. Pediatrics 163(4):1117–1121
Rizk SR, El Said G, Daniels LB, Burns JC, El Said H, Sorour KA et al (2015) Acute myocardial ischemia in adults secondary to missed Kawasaki disease in childhood. Am J Cardiol 115:423–427
Onouchi Y (2012) Genetics of Kawasaki disease. Circul J 76:1581–1586
Burgner D, Davila S, Breunis WB, Ng SB, Li Y, Bonnard C, Ling L et al (2009) A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease. PLoS Genet 5:e1000319
Onouchi Y, Ozaki K, Burns JC, Shimizu C, Terai M, Hamada H et al (2012) A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet 44:517–521
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Falcini, F., Lepri, G. (2016). Kawasaki Disease: Past, Present and Future. In: Dammacco, F., Ribatti, D., Vacca, A. (eds) Systemic Vasculitides: Current Status and Perspectives. Springer, Cham. https://doi.org/10.1007/978-3-319-40136-2_15
Download citation
DOI: https://doi.org/10.1007/978-3-319-40136-2_15
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-40134-8
Online ISBN: 978-3-319-40136-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)