eMedicine Specialties > Emergency Medicine > Pediatric

Pediatrics, Kawasaki Disease

Steven J Parrillo, DO, FACOEP, FACEP, Associate Professor, Emergency Medicine, Jefferson Medical College and Philadelphia College of Osteopathic Medicine; Medical Director, Department of Emergency Medicine, Einstein Elkins Park; Chair, Emergency Management Committee, Albert Einstein Healthcare Network; Medical Director, Disaster Medicine and Management Masters Program, Philadelphia University
Catherine V Parrillo, DO, FACOP, FAAP, Clinical Assistant Professor, Department of Pediatrics, Philadelphia College of Osteopathic Medicine

Updated: Oct 28, 2009

Introduction

Background

Kawasaki disease (KD) (ie, Kawasaki syndrome [KS]) is a febrile illness of childhood. It is a self-limited acute vasculitic syndrome of unknown etiology, first described by Tomisaku Kawasaki in 1967. At that time, he reported 50 children from 1961-1967 who presented with a distinctive clinical illness characterized by fever and rash, which was then thought to be a benign childhood illness.

Several years later, fatalities occurred in Japan among children younger than 2 years. The fatalities occurred when patients were improving or had recovered. Postmortem examinations revealed complete thrombotic occlusion of coronary artery aneurysms with a myocardial infarction (MI) as the immediate cause of death. It soon became evident that, when studied by echocardiography (ECHO), 20-25% of untreated children developed cardiovascular sequelae ranging from asymptomatic coronary artery ectasis or aneurysm formation to giant coronary artery aneurysms with thrombosis, MI, and sudden death. Even today, 15-25% of untreated patients develop coronary artery aneurysms. (The increase from older quotes of 5% is largely based on revised echocardiographic criteria for aneurysmal dilatation).

Although inflammatory infiltrates have been shown in the myocardium, pancreas, kidney, and biliary tract, no significant sequelae persist in those nonvascular tissues. A single report of pulmonary involvement has appeared in the literature. Gallbladder vasculitis (hydrops) is a significant, though uncommon complication.

Kawasaki syndrome has now surpassed rheumatic fever as the leading cause of acquired heart disease in the United States among children younger than 5 years.

In recent years, much attention has been given to incomplete cases of Kawasaki disease.

Pathophysiology

The etiology of Kawasaki disease remains unknown, although many suspect an infectious etiology. Indicators suggesting an infectious etiology include the occurrence of periodic epidemics with geographic spread; the self-limited nature; the winter and summer presentations; and the characteristic fever, adenopathy, and eye signs.

Some now believe that many factors (viruses, staphylococci "super antigens") are capable of triggering a final common pathway that results in immune activation. All effective therapies are directed at this immune activity.¹ Other proposed infectious agents include Parvovirus B19, Yersinia, and cytomegalovirus.¹

The frequency of Kawasaki disease in Asian populations has led several authors to suggest a genetic predisposition to genetic polymorphisms.^2,3

Treadwell et al have suggested that an association exists between Kawasaki disease and the use of a humidifier in the room of a child with an antecedent respiratory illness.⁴ Others have noted association with freshly cleaned carpets and living near a body of water.⁵  

Frequency

United States

Epidemics occur primarily in late winter and spring with 3-year intervals, lending some credence to the possibility of an infectious etiology. Kawasaki disease is most commonly observed in children from the middle and upper-middle classes. The estimated number of children hospitalized annually in the United States is about 3000, though more than 4000 admissions occurred in 2006, some of which were incomplete cases. The highest incidence in the United States is in Hawaii at 17 per 100,000 children younger than 5 years.⁶

International

Outside the United States, the disease is most frequently observed in Japan, Taiwan, and Korea. The prevalence of Kawasaki disease increased from 1967 to the mid 1980s and has leveled out at 5000-6000 cases per year. Several epidemics occurred in Japan during the years 1979, 1982, and 1985. The current Japanese incidence is approximately 112 cases per 100,000 population.

The occurrence rate in the United Kingdom doubled in the last decade.⁶

Mortality/Morbidity

• The development of coronary artery aneurysms (CAA) with consequences such as thrombosis or rupture determines the degree of disability. Acute MI has been reported secondary to true coronary artery obstruction. These aneurysms tend to develop approximately 1-2 weeks after onset of symptoms. 
• Myocarditis, congestive heart failure, pericarditis with pericardial effusion, mitral or aortic insufficiency, and dysrhythmias may be observed early in the disease. Decreased left ventricular function is present in approximately 50% of all patients with Kawasaki syndrome. Additionally, arthritis persists in some children.
• The risk of aneurysm is increased in patients who have fever for more than 16 days, who have recurrence of fever after an afebrile period of at least 48 hours, are male, who have cardiomegaly, and especially who are younger than 1 year. Some laboratory values at presentation may also predict a greater likelihood of aneurysm development including hematocrit <35%, thrombocytopenia (<350,000), elevated C-reactive protein (CRP), albumin <3.5g/dL, and WBC >12,000. Incomplete Kawasaki may also be an independent predictor of CAA development.⁷ The most important predictor is total duration of fever longer than 8 days.⁸
• Researchers are beginning to look at the possibility that patients with aneurysms may have an increased risk of premature coronary atherosclerotic disease.
• Until recently, the long-term outcome of pediatric coronary artery bypass performed in these children was unknown. Kitamura et al followed 114 children and adolescents for as long as 25 years after bypass. Survival rates were 95%, though some had either percutaneous coronary intervention or repeat CABG. Only 5 deaths occurred in the group.⁹

Race

Kawasaki disease is more common in the Japanese-American population. Worldwide, it is most common in all Asian populations.

Sex

Kawasaki disease is more common in males than in females, with a male-to-female ratio of 1.5:1.

Age

Eighty-five percent of children with Kawasaki disease are younger than 5 years.¹

In the United States, the peak prevalence is in children aged 18-24 months. The Japanese patient population is younger than the patient population in the United States; Kawasaki disease is most frequently observed in infants aged 6-12 months, with equal numbers in the first and second year of life.

Pannaraj et al noted that Kawasaki disease may occur at the extremes of age range, meaning infants younger than 6 months or children older than 5 years and that pediatricians and infectious diseases specialists frequently fail to consider the diagnosis.¹⁰

Infants aged 6 months or younger may have maternal antibody protection, but incomplete cases — and some of the poorest outcomes — have been reported in that age group.⁸

Manlhiot et al suggest that children at the extremes of the age spectrum, those younger than 6 months and those older than 9 years, are more likely to have a suboptimal outcome.¹¹

Clinical

History

Most children present because of concern of a prolonged fever. Diagnosis requires fever of at least 5 days duration (though many believe that the diagnosis can be made earlier in otherwise classic presentations). Parents may note that the fever began abruptly. Antibiotic therapy may have been initiated for other diagnoses, but fever persists. The affected child is usually more irritable than would be expected by the degree of fever.

Key historical clues include the following:

• Fever
  • At least 5 days in duration
  • Often abrupt in onset
  • Unresponsive to antibiotic therapy, if given
• Irritability - Out of proportion to the degree of fever or other signs (Note that a lumbar puncture to rule out meningitis may demonstrate a pleocytosis).

Physical

Diagnosis and clinical features of Kawasaki disease

• The diagnosis of classic Kawasaki disease requires fever (>39°C) of at least 5 days' duration and the presence of 4 of the following:
  • Changes in extremities including erythema, edema, and desquamation. This may limit movement and cause the child to refuse to bear weight. Desquamation of the fingers and toes begins in the periungual region, may involve the palms and soles, and is usually observed 1-2 weeks after the onset of fever. (Occurrence is approximately 75%.)

Peeling and erythema of the fingertips.

• Bulbar conjunctivitis (not associated with exudates) is almost always bilateral. (Occurrence is approximately 85%.)
• Polymorphous rash (not vesicular) is usually generalized but may be limited to the groin or lower extremities. (Occurrence is approximately 80%.)
• Cervical lymphadenopathy is usually greater than 1.5 cm and unilateral; it is the least common of all clinical features in US cases, though it is more common in Asia. (US occurrence is approximately 40%.)
• Changes in the lips and oral cavity include pharyngeal erythema, dry/fissured or swollen lips, and strawberry tongue. (Occurrence is approximately 90%.)

Pediatrics, Kawasaki disease. Note the appearance of the hand and lips. Photo courtesy of Sam Richardson, MD.

• Clinical features
  • The onset is usually abrupt with a high sustained fever that is unresponsive to antibiotic therapy and lasts for 1 week or longer. In addition, other typical features may be present.
  • Lips become erythematous and fissured. Bleeding may be noted.
  • The tongue is described as a strawberry tongue because of the diffuse erythema and prominent papillae.

Strawberry tongue.

• The neck may be stiff enough to consider meningitis, especially since many such patients are very irritable. Aseptic meningitis (pleocytosis) may be present in one half of all patients.
• The primary cardiac involvement is the development of coronary artery aneurysms. Myocarditis and pericarditis with or without effusion may also occur in the acute stage.
• Other clinical features of the disease may include urethritis, orchitis, arthritis/arthralgia, abdominal pain, vomiting/diarrhea (one third of patients), sterile pyuria (one third of patients), hepatitis, and gallbladder distention.
• Although rare in the United States, reactions of erythema, induration, and ulcerations may occur at the inoculation site of children who have received the BCG vaccine.

Incomplete cases also occur. (Clinical features are typical, just not present in the numbers required for fully manifested cases. For that reason, the term "incomplete KD" is used rather than "atypical KD"). In this setting, usually in children younger than 6 months of age, fever plus only 3 features establishes the diagnosis. The rationale is that treatment is safe and effective and that failure to diagnose Kawasaki disease may have a significant negative impact on outcome. The American Academy of Pediatrics (AAP)/American Heart Association (AHA) published criteria for the diagnosis in incomplete Kawasaki disease in 2004 in both Pediatrics and Circulation.¹² Those articles include a helpful algorithm summarized as follows:

• When fever plus 2 or 3 of the typical features are present for 5 days or more, and patient characteristics suggest possible Kawasaki disease, a C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) should be obtained.
  • If CRP level is less than 3 mg/dL and ESR is more than 40 mm/h, the child is monitored and actions taken as appropriate.
  • If CRP is greater than or equal to 3 mg/dL and ESR is greater than or equal to 40 mm/h, supplemental laboratory studies should be performed. Those studies include albumin, alanine aminotransferase (ALT), platelets, WBC count, and urine (for pyuria). Abnormal limits include the following:
    • Albumin <3 g
    • Anemia for age
    • Elevated ALT level
    • Platelets >450,000 (after 7 d)
    • WBC count >12,000
    • Presence of pyuria
  • If 3 or more supplemental laboratory criteria are positive, a diagnosis of Kawasaki disease is made. The child should have an echocardiogram and be treated.
  • If fewer than 3 supplemental laboratory criteria are positive, cardiac echocardiogram should be performed. If negative but fever persists, a repeat echocardiogram may be performed. If the echocardiogram is negative and the fever abates, Kawasaki disease is unlikely. If the echocardiogram is positive, the child is treated for Kawasaki disease.

Newberger questioned the suitability of laboratory findings as evidence of inflammation, noting that in some cases, the clinical criteria are not all present on any given day. Conversely, some patients with an inflammatory disorder did not meet the clinical case definition but developed coronary artery abnormalities consistent with Kawasaki disease.⁶

Hinze et al reported a case of Kawasaki disease in a 3-month-old boy manifested by typical signs and coronary artery aneurysms but without fever. He commented on the difficulty in making the diagnosis in young infants.¹³

Case reports of other unusual presentations have been published including GI bleeding, lupuslike illness in a recurrent case, arthritis, and rhabdomyolysis. Such presentations appear to be very uncommon.¹

Three phases occur, as follows. Some authors add a fourth "chronic" phase.

• Acute febrile phase - 1-2 weeks
  • The temperature is elevated (>104°F).
  • The child is irritable.
  • Bilateral conjunctivitis and rash are present.
  • The hands and feet develop the erythema and edema that cause the child to refuse to walk. Note that this finding may be the last to develop. Lack of extremity findings may cause consideration of incomplete Kawasaki disease.
  • The tongue and oral mucosa become red and cracked.
  • Hepatic dysfunction may develop.
  • Cardiac complications noted in the first stage include myocarditis and pericarditis.
• Subacute phase - Begins when fever and other signs have abated. This phase should end by the 4th week.
  • This is characterized by persistent irritability, anorexia, and conjunctival injection.
  • Fever resolution begins this stage. However, persistent fever beyond 2-3 weeks may be an indication of recrudescent Kawasaki disease. (See Recrudescent Kawasaki disease below).
  • If fever persists, the outcome is less favorable because of a greater risk of cardiac complications.
  • Thrombocytosis develops, and the platelet count may exceed 1 million/mm³.
  • Desquamation of the fingertips and toes begins at this time.
  • Aneurysm formation may occur during this stage.
  • Children are at greatest risk of sudden death during this phase.
• Convalescent phase - Approximately 4-6 weeks
  • This phase begins when all signs of illness have disappeared and continues until acute-phase reactants (ESR, CRP level) have returned to normal.
  • The most significant clinical finding that persists through this phase is the presence of coronary artery aneurysms.
• Chronic phase
  • This stage is only of clinical importance in patients who have developed cardiac complications.
  • Its duration is of lifetime significance because the aneurysm formed in childhood may rupture in adulthood.
  • In some cases of aneurysms rupturing in adult life, careful reviews of past medical histories have revealed febrile childhood illnesses of unknown etiology.

Causes

The etiology of Kawasaki disease remains unknown. Multiple theories exist, including an infectious etiology, an immunological abnormality, and even the possibility of a link with carpet shampoo. Clinical and epidemiologic features support an infectious etiology, but many authorities believe that an autoimmune component also exists. As noted above, many believe there is a predisposition in the Asian population.

One group of authors has suggested a link with tumor necrosis factor-alpha (TNF-alpha).

The US Food and Drug Administration (FDA) required the makers of RotaTeq rotavirus vaccine to report in the package insert that a total of 9 cases of Kawasaki disease had occurred in children who had received the vaccine. However, most believe that there is no connection between the vaccine and the disease and that the incidence of Kawasaki disease is no greater that in the nonimmunized population.¹⁵

One case report in the literature documents a 35-day-old infant who developed Kawasaki disease after his second hepatitis B vaccination.¹⁶

Differential Diagnoses

Workup

Laboratory Studies

• No specific laboratory test exists for Kawasaki disease; however, certain abnormalities coincide with various stages.
• A mild-to-moderate normochromic anemia is observed in the acute stage along with a moderate to alarmingly elevated WBC count with a left shift. 
  • Many of the acute-phase reactant markers, such as the ESR, CRP level, and serum alpha1-antitrypsin level are elevated. Most authors mention only ESR and CRP.
  • Culture results are all negative.
• During the subacute stage, platelet count elevation is the outstanding marker.
  • It begins to rise in the second week and continues to rise during the third week.
  • Levels as high as 2 million have been observed.
  • The acute reactive markers remain elevated.
• In the convalescent stage, the levels of platelets and other markers begin to return to values within the reference range. Laboratory values may require 6-8 weeks to normalize.
• Liver function studies and serum lipase measurement may be indicated in selected cases.

Imaging Studies

• An echocardiogram is the study of choice in Kawasaki disease to demonstrate coronary artery aneurysms in both fully manifested and suspected incomplete cases.
• Coronary angiography or percutaneous coronary intervention (PCI) may be required in some with coronary artery aneurysms (CAA).
• During the acute stage, a baseline echocardiogram is important.
  • The echocardiogram should be repeated in the second or third week and again 1 month after all other laboratory results have normalized.
  • Many centers perform a 1-year echocardiogram, even when the first ones show no aneurysm.
  • If the echocardiogram results are abnormal at any point, the child should be referred to a pediatric cardiologist for a complete cardiac workup and follow-up care.
• Ultrasonography of the gallbladder may be necessary if any suggestion of liver or gallbladder dysfunction is present.
• A chest radiograph should be obtained to assess baseline findings and to confirm clinical suspicion of congestive heart failure.

Other Tests

• An electrocardiogram (ECG) indicates the presence of various conduction abnormalities. Additionally, children with Kawasaki syndrome may suffer acute infarction.
• Exercise stress testing may play a role later in life.¹
• One study used multislice spiral CT to assess coronary artery abnormalities in 16 adolescents and young adults with Kawasaki disease. Although the numbers were small, CT was 100% sensitive in the detection of coronary artery aneurysms but only 87.5% sensitive for the detection of significant stenosis or occlusion. False-positive results occurred secondary to severe calcification in 5 arteries and cardiac motion artifact in 2. Specificity was therefore 92.5%.¹⁷
• In another small study, electron beam computed tomography (EBCT) was used to determine if coronary artery calcifications could be used as a marker of future coronary artery events. The authors felt that this study may be useful for risk stratification in long-term management of patients with Kawasaki disease.¹⁸

Procedures

• A select group may require cardiac catheterization.
• Coronary artery bypass grafting may be required.

Treatment

Prehospital Care

No specific prehospital care exists for Kawasaki disease. Paramedics should assess the need for intravenous access and rhythm monitoring.

Emergency Department Care

• Any young child who presents to the emergency department (ED) with symptoms of early or acute-stage Kawasaki disease should be evaluated to rule out sepsis or meningitis.
• Although the diagnosis may seem obvious, other life-threatening diseases must be ruled out.
• The ED physician must consider the possibility that a child has an incomplete case and proceed with the evaluation listed above.
• Intravenous access and cardiac monitoring should be established.
• Depending on the institution, anti-inflammatory therapy may need to begin in the ED.
• Arrangements for admission must take into consideration the potential for multiple problems. This is not a routine pediatric illness. Accordingly, transferring the patient to a pediatric referral center may be prudent.

Consultations

• Pediatrics
  • Consultation with a pediatric cardiologist may be required if coronary artery aneurysms are identified or if other cardiac complications develop.
  • Pediatric cardiothoracic surgery assistance may be needed in the pediatric ICU for those patients who need bypass surgery.

Medication

The medical management of Kawasaki disease primarily involves the use of gamma globulin. Although some have suggested that aspirin is no longer needed, most use high-dose aspirin for a variable period of time, followed by lower-dose aspirin for its antiplatelet effects. Of note, a 2008 Cochrane Database of Systematic Reviews article concluded that "there is insufficient evidence to indicate whether children with Kawasaki disease should continue to receive salicylate as part of their treatment regimen."¹⁹

Some controversy exists about the ideal timing to begin gamma globulin, but this is not an issue that concerns emergency physicians. It is given most often from days 5-7.

Although data are limited, authors of several case reports have suggested a possible role for thrombolysis in those with acute MI as a consequence of thrombus formation in aneurysms.²⁰ At this time, it seems unlikely that the emergency physician will administer this therapy.

Some have suggested that there is, or may be, a role for corticosteroids. Most have pointed out that not only is there no good data to support a benefit in terms of outcome but also that current therapy with IVIG and aspirin is safe and effective.^21,22,23 In a meta-analysis of 4 studies and 447 patients, Athappan et al concluded that the addition of steroids to standard therapy (IVIG + aspirin) decreased the rate of re-treatment but did not decrease the incidence of coronary aneurysms or adverse events.²³

Ibuprofen antagonizes aspirin's antiplatelet activity and should be avoided.

Because these children will take aspirin for a variable period of time, vaccination against influenza and varicella must be ensured.

Studies that involved plasma exchange or cyclophosphamide have shown variable results. Both are used in cases of refractory disease.¹

Gamma globulins

These agents can be used to assist in the treatment of inflammation resulting from autoimmune disorders. Much of the pathophysiology in KD involves inflammation. Early and aggressive intervention improves outcome.

Immune globulin, intravenous (Carimune, Gammagard S/D, Gammar-P, Gamunex, Polygam S/D)

Generally recommended as the first drug to be used, but it is not usually the sole therapy. Neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).

Dosing

Adult

Not established

Pediatric

A single dose of 2 g/kg IV infused over 12 h is the most common regimen; alternatively, 1 g/kg/d for 2 d
Less often, a regimen calls for 400 mg/kg/d IV qd for 4 d
Repeat course of therapy may be indicated in those who do not have an adequate response to initial treatment

Interactions

Globulin preparation may interfere with immune response to live-virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)

Contraindications

Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies; severe thrombocytopenia or coagulation disorders

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Flushing of the face, chills, nausea, dyspnea, and tachycardia are the most common adverse effects; less common adverse effects include chest tightness, dizziness, fever, headache, and diaphoresis
Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion)
Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes mellitus, volume depletion, and preexisting kidney disease; laboratory findings associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Anti-inflammatory agents

These agents systemically interfere with events leading to inflammation. Aspirin is indicated for antiplatelet effect.

Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Adequate anti-inflammatory therapy requires that aspirin be combined with gamma globulin.
Children with coronary artery aneurysms receive aspirin for prolonged periods. First-line therapy with intravenous immunoglobulin. PO absorption of aspirin may decrease in Kawasaki disease to <50% (compared to typical bioavailability of 85-90%). This altered bioavailability may explain why higher doses required to achieve a salicylate serum concentration >20 mg/dL.

Dosing

Adult

Not established

Pediatric

80-100 mg/kg/d PO divided qid for 2 wk initial; 3-5 mg/kg PO qd for 6-8 wk maintenance; may use high-dose regimen for 2 days, then switch to the low dose for the remainder of the treatment period; currently no good literature support one regimen over the other
Coronary artery abnormalities: 3-5 mg/kg PO qd long term (with or without dipyridamole)

Interactions

Coadministration with ibuprofen may decrease antiplatelet effect; efficacy may also decrease when coadministered with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs

Contraindications

Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; use in children (<16 y) with influenza because of association of aspirin with Reye syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants; caution in asthma; dose is on the borderline of that causing salicylate toxicity, therefore, monitor for toxicity (ie, vomiting, hyperpnea, lethargy, liver dysfunction); monitor salicylate level and maintain at 18-28 mg/dL

Follow-up

Further Inpatient Care

• Although some authors advocate a 23-hour observation period, most patients with Kawasaki disease are formally admitted to a pediatric or pediatric cardiology service for aggressive supportive and anti-inflammatory therapy.

Further Outpatient Care

• Careful follow-up care is necessary in the child who has developed cardiac complications.
  • A pediatric cardiologist should provide follow-up care for the child.
  • The long-term implications for coronary artery disease are unknown at this time.

Inpatient & Outpatient Medications

• The pediatrician or cardiologist who provides the long-term care monitors aspirin therapy and decides whether or not to use warfarin or heparin.
• Tumor necrosis factor-alpha blockade with infliximab has been advocated by some in cases of refractory Kawasaki disease (KD).²⁴

Transfer

• Because of the potential life threats, patients with Kawasaki disease must be admitted to a hospital with a pediatric service.
• Some authorities recommend transferring those patients with documented coronary artery aneurysms to a tertiary pediatric facility.

Deterrence/Prevention

• Because the etiology of Kawasaki disease is unknown, there is no method of deterrence. Therapy is directed at prevention of coronary artery aneurysm formation.

Complications

• The primary complications of Kawasaki disease involve the development and rupture of coronary artery aneurysms. Giant aneurysms may occur and may be resistant to Kawasaki disease therapy. Some recommend coronary artery bypass grafting using arterial grafts that can grow with the child. Transplant has been performed in some children who had large aneurysms in vessels not amenable to bypass.
• Dehydration may result from fever and anorexia.
• Hyponatremia secondary to SIADH has been reported in a very young infant.
• Joint inflammation in the acute phase may limit mobility.
• Pancreatitis, hydrops (vasculitis) of the gallbladder, hepatitis, meningitis, and orchitis may complicate care.
• Endovascular ultrasonography has shown that some resolved aneurysms are associated with marked intimal thickening.

Prognosis

• Those patients who do not develop coronary artery aneurysms recover fully. Recurrence is unusual, occurring in only 1-3% of all cases.
• The severity of aneurysms determines the prognosis in the remainder. More than half of all aneurysms resolve by the 2-year mark. Endovascular ultrasonography has shown that, even when aneurysms resolve, marked intimal thickening is present. Vessel flow may be abnormal.
• Some believe that giant aneurysms are likely to thrombose or become stenotic. Studies are ongoing.
• Coronary artery bypass grafting has been required in some children with severe perfusion deficits. Follow-up of children and adolescents 20-25 years post CABG has shown a 95% survival rate, though some have had to have repeat CABG or PCI.⁹

Patient Education

• Parents and other caregivers must understand the need for close pediatric and cardiology follow-up until the disease has fully resolved.

Miscellaneous

Medicolegal Pitfalls

• Failure to diagnose the disease is the primary medical/legal pitfall.
• Failure to consider the possibility of incomplete Kawasaki disease could lead to delayed (or missed) diagnosis and treatment with a consequent increased likelihood of coronary artery aneurysms development.

Multimedia

Media file 1: Pediatrics, Kawasaki disease. Note the appearance of the hand and lips. Photo courtesy of Sam Richardson, MD.

Media file 2: Peeling and erythema of the fingertips.

Media file 3: Strawberry tongue.

References

1. Pinna GS, Kafetzis DA, Tselkas OI, Skevaki CL. Kawasaki disease: an overview. Curr Opin Infect Dis. Jun 2008;21(3):263-70. [Medline].

2. Caquard M, Parlier G, Siret D. [Family observation of Kawasaki disease: 2 cases in sister and brother]. Arch Pediatr. May 2006;13(5):453-5. [Medline].

3. Burns JC, Shimizu C, Gonzalez E, Kulkarni H, Patel S, Shike H. Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. J Infect Dis. Jul 15 2005;192(2):344-9. [Medline].

4. Treadwell TA, Maddox RA, Holman RC, Belay ED, Shahriari A, Anderson MS, et al. Investigation of Kawasaki syndrome risk factors in Colorado. Pediatr Infect Dis J. Oct 2002;21(10):976-8. [Medline].

5. Burns JC, Glodé MP. Kawasaki syndrome. Lancet. Aug 7-13 2004;364(9433):533-44. [Medline].

6. Newburger JW, Fulton DR. Kawasaki disease. Curr Opin Pediatr. Oct 2004;16(5):508-14. [Medline].

7. Yeo Y, Kim T, Ha K, Jang G, Lee J, Lee K. Incomplete Kawasaki disease in patients younger than 1 year of age: a possible inherent risk factor. Eur J Pediatr. Feb 2009;168(2):157-62. [Medline].

8. Kim T, Choi W, Woo CW, Choi B, Lee J, Lee K. Predictive risk factors for coronary artery abnormalities in Kawasaki disease. Eur J Pediatr. May 2007;166(5):421-5. [Medline].

9. Kitamura S, Tsuda E, Kobayashi J, Nakajima H, Yoshikawa Y, Yagihara T. Twenty-five-year outcome of pediatric coronary artery bypass surgery for Kawasaki disease. Circulation. Jul 7 2009;120(1):60-8. [Medline].

10. Pannaraj PS, Turner CL, Bastian JF, Burns JC. Failure to diagnose Kawasaki disease at the extremes of the pediatric age range. Pediatr Infect Dis J. Aug 2004;23(8):789-91. [Medline].

11. Manlhiot C, Yeung RS, Clarizia NA, Chahal N, McCrindle BW. Kawasaki Disease at the Extremes of the Age Spectrum. Pediatrics. Aug 24 2009;[Medline].

12. [Guideline] Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, 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. Oct 26 2004;110(17):2747-71. [Medline].

13. Hinze CH, Graham TB, Sutherell JS. Kawasaki disease without fever. Pediatr Infect Dis J. Sep 4 2009;[Medline].

14. Mine K, Takaya J, Hasui M, et al. A case of Kawasaki disease associated with syndrome of inapproriate secretion of antidiuretic hormone. Acta Paediatr. 2003;22:663-66.

15. Hua W, Izurieta HS, Slade B, Belay ED, Haber P, Tiernan R, et al. Kawasaki Disease After Vaccination: Reports to the Vaccine Adverse Event Reporting System 1990-2007. Pediatr Infect Dis J. Sep 12 2009;[Medline].

16. Miron D, Fink D, Hashkes PJ. Kawasaki disease in an infant following immunisation with hepatitis B vaccine. Clin Rheumatol. Dec 2003;22(6):461-3. [Medline].

17. Kanamaru H, Sato Y, Takayama T, Ayusawa M, Karasawa K, Sumitomo N, et al. Assessment of coronary artery abnormalities by multislice spiral computed tomography in adolescents and young adults with Kawasaki disease. Am J Cardiol. Feb 15 2005;95(4):522-5. [Medline].

18. Dadlani GH, Gingell RL, Orie JD, Roland JM, Najdzionek J, Lipsitz SR, et al. Coronary artery calcifications in the long-term follow-up of Kawasaki disease. Am Heart J. Nov 2005;150(5):1016. [Medline].

19. Baumer JH, Love SJ, Gupta A, Haines LC, Maconochie I, Dua JS. Salicylate for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2006;(4):CD004175. [Medline].

20. Krendel S, Pollack P, Hanly J. Tissue plasminogen activator in pediatric myocardial infarction. Ann Emerg Med. May 2000;35(5):502-5. [Medline].

21. [Best Evidence] Inoue Y, Okada Y, Shinohara M, Kobayashi T, Kobayashi T, Tomomasa T, et al. A multicenter prospective randomized trial of corticosteroids in primary therapy for Kawasaki disease: clinical course and coronary artery outcome. J Pediatr. Sep 2006;149(3):336-341. [Medline].

22. Shulman ST. Is there a role for corticosteroids in Kawasaki disease?. J Pediatr. Jun 2003;142(6):601-3. [Medline].

23. Athappan G, Gale S, Ponniah T. Corticosteroid therapy for primary treatment of Kawasaki disease - weight of evidence: a meta-analysis and systematic review of the literature. Cardiovasc J Afr. Jul-Aug 2009;20(4):233-6. [Medline].

24. Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. May 2005;146(5):662-7. [Medline].

25. Burns JC. Revisiting steroids in the primary treatment of acute Kawasaki disease. J Pediatr. Sep 2006;149(3):291-2. [Medline].

26. Burns JC. The riddle of Kawasaki disease. N Engl J Med. Feb 15 2007;356(7):659-61. [Medline].

27. Chantepie A, Mauran P, Lusson JR, Vaillant MC, Bozio A. [Cardiovascular complications of Kawasaki syndrome: results of a French multicenter study]. Arch Pediatr. Jul 2001;8(7):713-9. [Medline].

28. Daniels SR. Steroid treatment for Kawasaki disease. J Pediatrics. Sept 2006;149 (3):336.

29. Morgan GJ, MacLeod C, Jenkins J, Stewart C, Craig B. IVIG, aspirin, and Kawasaki disease. J Pediatr. Aug 2003;143(2):280-1; author reply 281. [Medline].

30. Nomura Y, Masuda K, Yoshinaga M, Takei S, Miyata K. Possible relationship between streptococcal pyrogenic exotoxin A and Kawasaki syndrome in patients older than six months of age. Pediatr Infect Dis J. Sep 2003;22(9):794-8. [Medline].

31. Rowley AH, Shulman ST. Kawasaki syndrome. Pediatr Clin North Am. Apr 1999;46(2):313-29. [Medline].

32. Saulsbury FT. Comparison of high-dose and low-dose aspirin plus intravenous immunoglobulin in the treatment of Kawasaki syndrome. Clin Pediatr (Phila). Oct 2002;41(8):597-601. [Medline].

33. Schratz LM, Meyer RA, Schwartz DC. Serial intracoronary ultrasound in children: feasibility, reproducibility, limitations, and safety. J Am Soc Echocardiogr. Aug 2002;15(8):782-90. [Medline].

34. Selamet Tierney ES, Newburger JW. Are patients with Kawasaki disease at risk for premature atherosclerosis?. J Pediatr. Sep 2007;151(3):225-8. [Medline].

35. Sundel RP, Baker AL, Fulton DR, Newburger JW. Corticosteroids in the initial treatment of Kawasaki disease: report of a randomized trial. J Pediatr. Jun 2003;142(6):611-6. [Medline].

36. Weinstein M. Inflammation at a previous inoculation site: an unusual presentation of Kawasaki disease. CMAJ. Feb 14 2006;174(4):459-60. [Medline].

Keywords

Kawasaki disease, Kawasaki disease symptoms, Kawasaki disease treatment, Kawasaki's disease, Kawasaki disease in children, incomplete Kawasaki disease, Kawasaki syndrome, myocardial infarction, myocarditis, acute vasculitic syndrome, coronary artery aneurysms, sudden death

Contributor Information and Disclosures

Author

Steven J Parrillo, DO, FACOEP, FACEP, Associate Professor, Emergency Medicine, Jefferson Medical College and Philadelphia College of Osteopathic Medicine; Medical Director, Department of Emergency Medicine, Einstein Elkins Park; Chair, Emergency Management Committee, Albert Einstein Healthcare Network; Medical Director, Disaster Medicine and Management Masters Program, Philadelphia University
Steven J Parrillo, DO, FACOEP, FACEP is a member of the following medical societies: American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, American Osteopathic Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Catherine V Parrillo, DO, FACOP, FAAP, Clinical Assistant Professor, Department of Pediatrics, Philadelphia College of Osteopathic Medicine
Catherine V Parrillo, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey Glenn Bowman, MD, MS, Consulting Staff, Highfield MRI, Columbus, Ohio
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center
Grace M Young, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Emergency Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Richard G Bachur, MD, Associate Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston
Richard G Bachur, MD is a member of the following medical societies: American Academy of Pediatrics, Society for Academic Emergency Medicine, and Society for Pediatric Research
Disclosure: Nothing to disclose.

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