Kawasaki disease: Complications
- Robert Sundel, MD
Robert Sundel, MD
- Section Editor — Pediatric Rheumatology
- Associate Professor of Pediatrics
- Harvard Medical School
- Section Editors
- Marisa Klein-Gitelman, MD, MPH
Marisa Klein-Gitelman, MD, MPH
- Section Editor — Pediatric Rheumatology
- Chief, Division of Rheumatology
- Ann & Robert H. Lurie Children's Hospital of Chicago
- Professor of Pediatrics
- Northwestern University Feinberg School of Medicine
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Kawasaki disease (KD, also called mucocutaneous lymph node syndrome) is one of the most common vasculitides of childhood . KD also occurs rarely in adults. It is typically a self-limited condition, with fever and manifestations of acute inflammation lasting for an average of 12 days without therapy . However, complications such as coronary artery (CA) aneurysms, depressed myocardial contractility and heart failure, myocardial infarction, arrhythmias, and peripheral arterial occlusion may develop and lead to significant morbidity and mortality (table 1). Noncardiac complications may also affect children with KD.
The complications of KD are discussed in this topic review, with long-term cardiovascular sequelae of KD reviewed in greater detail separately. The epidemiology, etiology, clinical manifestations, diagnosis, and treatment of KD, refractory KD, and incomplete (atypical) KD are also presented separately. (See "Cardiovascular sequelae of Kawasaki disease" and "Kawasaki disease: Epidemiology and etiology" and "Kawasaki disease: Clinical features and diagnosis" and "Kawasaki disease: Initial treatment and prognosis" and "Refractory Kawasaki disease" and "Incomplete (atypical) Kawasaki disease".)
KD shock syndrome (KDSS), defined as sustained systolic hypotension (decrease in blood pressure greater than 20 percent from baseline) or clinical signs of poor perfusion, is a potentially life-threatening complication of KD [3,4]. It may be accompanied by multiple organ dysfunction syndrome (MODS), with MODS seen in 8 of 11 patients with KD and shock in one series . It is important to distinguish patients with KDSS from those with other causes of severe hypoperfusion since aggressive use of intravenous immune globulin (IVIG), which is essential for the successful control of KDSS, is not typically used in other types of shock. The presence of anemia and thrombocytosis is more common in KDSS as opposed to thrombocytopenia in toxic shock syndrome (TSS) and septic shock. The features that are most suggestive of KDSS, however, are younger age (mean age approximately three years in KDSS versus nine years for TSS)  and the presence of echocardiographic abnormalities, particularly valvulitis and coronary artery (CA) lesions. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis", section on 'Multiple organ dysfunction syndrome' and "Initial evaluation of shock in children" and "Initial management of shock in children".)
In one case series from a single institution, 13 of 187 consecutive patients with KD (7 percent) presented with KDSS between 2003 and 2007 . All patients with KDSS received fluid resuscitation, and seven also received inotropic agents. Patients with shock syndrome were more likely than KD patients who were hemodynamically stable to have consumptive coagulopathy and cardiac abnormalities including impaired left ventricular systolic function, mitral regurgitation, and CA abnormalities. In addition, patients who presented with shock had higher C-reactive protein (CRP) levels than those with uncomplicated KD. Most importantly, children with KDSS were also less responsive to initial IVIG therapy and more commonly required additional treatment for their KD.
KD may cause both coronary artery (CA) dilatation as well as myocardial abnormalities. The most significant effects of KD involve pathologic changes in the coronary arteries. Acute, necrotizing arteritis, subacute and persistent arterial inflammation, and luminal myofibroblastic proliferation appear to affect most if not all children with KD . Depending on their severity, these processes may result in formation of aneurysms (defined as dilatation of coronary arteries to more than 4 mm internal diameter), ectasia (representing less severe yet still abnormal CA diameters), functional vasodilatory abnormalities despite a normal arterial diameter, and stenosis of the vascular lumen . (See "Cardiovascular sequelae of Kawasaki disease".)
- Burns JC, Glodé MP. Kawasaki syndrome. Lancet 2004; 364:533.
- 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; 110:2747.
- Kanegaye JT, Wilder MS, Molkara D, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics 2009; 123:e783.
- Yim D, Ramsay J, Kothari D, Burgner D. Coronary artery dilatation in toxic shock-like syndrome: the Kawasaki disease shock syndrome. Pediatr Cardiol 2010; 31:1232.
- Gatterre P, Oualha M, Dupic L, et al. Kawasaki disease: an unexpected etiology of shock and multiple organ dysfunction syndrome. Intensive Care Med 2012; 38:872.
- Lin YJ, Cheng MC, Lo MH, Chien SJ. Early Differentiation of Kawasaki Disease Shock Syndrome and Toxic Shock Syndrome in a Pediatric Intensive Care Unit. Pediatr Infect Dis J 2015; 34:1163.
- Orenstein JM, Shulman ST, Fox LM, et al. Three linked vasculopathic processes characterize Kawasaki disease: a light and transmission electron microscopic study. PLoS One 2012; 7:e38998.
- Manlhiot C, Niedra E, McCrindle BW. Long-term management of Kawasaki disease: implications for the adult patient. Pediatr Neonatol 2013; 54:12.
- Son MB, Gauvreau K, Ma L, et al. Treatment of Kawasaki disease: analysis of 27 US pediatric hospitals from 2001 to 2006. Pediatrics 2009; 124:1.
- Curtis N, Levin M. Kawasaki disease thirty years on. Curr Opin Pediatr 1998; 10:24.
- McCrindle BW, Li JS, Minich LL, et al. Coronary artery involvement in children with Kawasaki disease: risk factors from analysis of serial normalized measurements. Circulation 2007; 116:174.
- Baer AZ, Rubin LG, Shapiro CA, et al. Prevalence of coronary artery lesions on the initial echocardiogram in Kawasaki syndrome. Arch Pediatr Adolesc Med 2006; 160:686.
- Nakamura Y, Yashiro M, Uehara R, et al. Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease. Pediatr Int 2004; 46:33.
- Koren G, Lavi S, Rose V, Rowe R. Kawasaki disease: review of risk factors for coronary aneurysms. J Pediatr 1986; 108:388.
- Beiser AS, Takahashi M, Baker AL, et al. A predictive instrument for coronary artery aneurysms in Kawasaki disease. US Multicenter Kawasaki Disease Study Group. Am J Cardiol 1998; 81:1116.
- Belay ED, Maddox RA, Holman RC, et al. Kawasaki syndrome and risk factors for coronary artery abnormalities: United States, 1994-2003. Pediatr Infect Dis J 2006; 25:245.
- Stockheim JA, Innocentini N, Shulman ST. Kawasaki disease in older children and adolescents. J Pediatr 2000; 137:250.
- Momenah T, Sanatani S, Potts J, et al. Kawasaki disease in the older child. Pediatrics 1998; 102:e7.
- Muta H, Ishii M, Sakaue T, et al. Older age is a risk factor for the development of cardiovascular sequelae in Kawasaki disease. Pediatrics 2004; 114:751.
- Uehara R, Belay ED, Maddox RA, et al. Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan. Pediatr Infect Dis J 2008; 27:155.
- Manlhiot C, Yeung RS, Clarizia NA, et al. Kawasaki disease at the extremes of the age spectrum. Pediatrics 2009; 124:e410.
- Newburger JW, Sanders SP, Burns JC, et al. Left ventricular contractility and function in Kawasaki syndrome. Effect of intravenous gamma-globulin. Circulation 1989; 79:1237.
- Yonesaka S, Takahashi T, Matubara T, et al. Histopathological study on Kawasaki disease with special reference to the relation between the myocardial sequelae and regional wall motion abnormalities of the left ventricle. Jpn Circ J 1992; 56:352.
- Muise A, Tallett SE, Silverman ED. Are children with Kawasaki disease and prolonged fever at risk for macrophage activation syndrome? Pediatrics 2003; 112:e495.
- al-Eid W, al-Jefri A, Bahabri S, al-Mayouf S. Hemophagocytosis complicating Kawasaki disease. Pediatr Hematol Oncol 2000; 17:323.
- Palazzi DL, McClain KL, Kaplan SL. Hemophagocytic syndrome after Kawasaki disease. Pediatr Infect Dis J 2003; 22:663.
- Ohga S, Ooshima A, Fukushige J, Ueda K. Histiocytic haemophagocytosis in a patient with Kawasaki disease: changes in the hypercytokinaemic state. Eur J Pediatr 1995; 154:539.
- Latino GA, Manlhiot C, Yeung RS, et al. Macrophage activation syndrome in the acute phase of Kawasaki disease. J Pediatr Hematol Oncol 2010; 32:527.
- Hendricks M, Pillay S, Davidson A, et al. Kawasaki disease preceding haemophagocytic lymphohistiocytosis: challenges for developing world practitioners. Pediatr Blood Cancer 2010; 54:1023.
- Suresh N, Sankar J. Macrophage activation syndrome: a rare complication of incomplete Kawasaki disease. Ann Trop Paediatr 2010; 30:61.
- Chen Y, Shang S, Zhang C, et al. Hemophagocytic lymphohistiocytosis at initiation of kawasaki disease and their differential diagnosis. Pediatr Hematol Oncol 2010; 27:244.
- Simonini G, Pagnini I, Innocenti L, et al. Macrophage activation syndrome/Hemophagocytic Lymphohistiocytosis and Kawasaki disease. Pediatr Blood Cancer 2010; 55:592.
- Koh KN, Im HJ, Chung NG, et al. Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party. Eur J Haematol 2015; 94:51.
- Wang W, Gong F, Zhu W, et al. Macrophage activation syndrome in Kawasaki disease: more common than we thought? Semin Arthritis Rheum 2015; 44:405.
- Jordan MB, Allen CE, Weitzman S, et al. How I treat hemophagocytic lymphohistiocytosis. Blood 2011; 118:4041.
- Davì S, Minoia F, Pistorio A, et al. Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Arthritis Rheumatol 2014; 66:2871.
- Amano S, Hazama F, Hamashima Y. Pathology of Kawasaki disease: II. Distribution and incidence of the vascular lesions. Jpn Circ J 1979; 43:741.
- Tomita S, Chung K, Mas M, et al. Peripheral gangrene associated with Kawasaki disease. Clin Infect Dis 1992; 14:121.
- Veiga PA, Pieroni D, Baier W, Feld LG. Association of Kawasaki disease and interstitial nephritis. Pediatr Nephrol 1992; 6:421.
- Ferriero DM, Wolfsdorf JI. Hemolytic uremic syndrome associated with Kawasaki disease. Pediatrics 1981; 68:405.
- Salcedo JR, Greenberg L, Kapur S. Renal histology of mucocutaneous lymph node syndrome (Kawasaki disease). Clin Nephrol 1988; 29:47.
- Zulian F, Falcini F, Zancan L, et al. Acute surgical abdomen as presenting manifestation of Kawasaki disease. J Pediatr 2003; 142:731.
- Mele T, Evans M. Intestinal obstruction as a complication of Kawasaki disease. J Pediatr Surg 1996; 31:985.
- Akikusa JD, Laxer RM, Friedman JN. Intestinal pseudoobstruction in Kawasaki disease. Pediatrics 2004; 113:e504.
- Lin YL, Chang TJ, Lu KC, et al. Surgical treatment of Kawasaki disease with intestinal pseudo-obstruction. Indian J Pediatr 2011; 78:237.
- Hussain RN, Ruiz G. Kawasaki disease presenting with intussusception: a case report. Ital J Pediatr 2010; 36:7.
- Prokic D, Ristic G, Paunovic Z, Pasic S. Pancreatitis and atypical Kawasaki disease. Pediatr Rheumatol Online J 2010; 8:8.
- Cherry R, Naon H, Cohen H, et al. Common bile duct stenosis and pancreatitis in Kawasaki disease: two cases and a review of the literature. Pediatr Infect Dis J 2010; 29:571.
- Carlton-Conway D, Ahluwalia R, Henry L, et al. Behaviour sequelae following acute Kawasaki disease. BMC Pediatr 2005; 5:14.
- Baker AL, Gauvreau K, Newburger JW, et al. Physical and psychosocial health in children who have had Kawasaki disease. Pediatrics 2003; 111:579.
- Magalhães CM, Magalhães Alves NR, Oliveira KM, et al. Sensorineural hearing loss: an underdiagnosed complication of Kawasaki disease. J Clin Rheumatol 2010; 16:322.
- Knott PD, Orloff LA, Harris JP, et al. Sensorineural hearing loss and Kawasaki disease: a prospective study. Am J Otolaryngol 2001; 22:343.
- CARDIAC COMPLICATIONS
- Coronary artery abnormalities
- - Risk factors for coronary artery aneurysms
- Depressed myocardial contractility
- MACROPHAGE ACTIVATION SYNDROME
- NONCORONARY VASCULAR INVOLVEMENT
- Urinary abnormalities and renal disease
- Gastrointestinal abnormalities
- Central nervous system
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS