AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Follow-up
• Miscellaneous
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Background

Kawasaki disease (KD) is an acute febrile vasculitic syndrome of early childhood. While at the Tokyo Red Cross Medical Center in Japan, Tomisaku Kawasaki reported 50 children in 1961-1967 who presented with fever, rash, conjunctival injection, cervical lymphadenitis, inflammation of the lips and oral cavity, and erythema and edema of the hands and feet. Children younger than 2 years died when they were improving or after they had seemingly recovered. Postmortem examinations revealed complete thrombotic occlusion of coronary artery aneurysms (CAAs) with myocardial infarction (MI) as the immediate cause of death. In 1976, Melish et al first reported Kawasaki disease in the United States in a group of 12 children from Honolulu examined from 1971-1973¹.

KD is now recognized worldwide. Cardiac involvement occurs in 20-25% of patients, and the mortality rate is 0.1-2%. KD is the leading cause of acquired heart disease in children in the developed world and may be a risk factor for adult ischemic heart disease.

In the United States, KD has now surpassed acute rheumatic fever as the leading cause of acquired heart disease in children².

Pathophysiology

The etiology of KD is unknown. Increasing evidence supports an infectious etiology for KD; however, whether the inflammatory response results from a conventional antigen or a superantigen continues to be debated. Recent immunohistochemical findings suggest that many vascular growth factors then play a role in the formation of the coronary artery lesions. The activated suppressor/cytotoxic T cells increase, and the CD8⁺ suppressor T cells decrease. Serum levels of interleukin (IL)–1, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and IL-6 are elevated. Involvement of the coronary vessels mimics infantile polyarteritis nodosa, but antibody profiles differ.

Most of the pathology of the disease is induced by a medium vessel arterial vasculitis. Initially, neutrophils are present in great numbers, but the infiltrate rapidly switches to mononuclear cells, T lymphocytes, and immunoglobulin A (IgA)–producing plasma cells. Inflammation involves all 3 layers of vessels. Eosinophils are preferentially accumulated in microvessels.

Dergun et al, Newburger et al, and Burns et al described families with multiple members affected with KD to increase awareness of the familial occurrence of KD among practitioners who care for these patients^{3, 2, 4}. They retrospectively reviewed medical records at 2 medical centers and data collected from remote families with KD who contacted the Kawasaki Syndrome Research Program at the University of California, San Diego.

The researchers studied 18 families with multiple affected members. Nine families had 2 affected siblings. In San Diego, 3 (0.7%) of 424 families with KD had cases involving siblings. Nine families were identified with KD in 2 generations or in multiple affected members, yielding a total of 24 children with KD. No clear pattern of inheritance could be deduced from these pedigrees. Therefore, multiple polymorphic alleles likely influence KD susceptibility. The authors concluded physicians should counsel affected families and make them aware of the potential increased risk of KD among family members.

Frequency

United States

Epidemics primarily occur in the late winter and spring, at 2- to 3-year intervals. Approximately 3000 children with KD are hospitalized annually in the United States. Regional incidence rates are reported to range from 67.2 cases per 100,000 children younger than 5 years in large, urban, multiethnic populations (eg, Los Angeles, Calif) to 9.8 cases per 100,000 children younger than 5 years in populations in states such as Georgia.

International

Approximately 5000-6000 cases are reported each year in Japan. The incidence in 2000 was 134.2 cases per 100,000 children younger than 5 years. Several epidemics have occurred in Japan during the years 1979, 1982, and 1985. No epidemics have occurred since that time.

Marked spatial and temporal patterns were noted in both the seasonality and deviations from the average number of KD cases in Japan. Seasonality was bimodal, with peaks in January and June and/or July and a nadir in October. This pattern was consistent throughout Japan during the entire 14-year period. Very high or low numbers of cases were reported in certain years, but the overall variability was consistent throughout the entire country. Temporal clustering of KD cases was detected with nationwide outbreaks⁵.

Yanagawa et al (2006) reviewed the epidemiology of KD in Japan⁶. From 1999-2002, 18,604 boys and 13,662 girls with KD were reported. The average annual incidence was 137.7 per 100,000 children younger than 5 years. The male-to-female ratio was 1.3:1. The incidence peaked at age 9-11 months, and the proportion of patients younger than 1 year was 26%. Most cases occurred in January. Acute-stage cardiac lesions and cardiac sequelae occurred more often in children younger than 1 year and older than 4 years. The following symptoms were reported (listed in decreasing incidence):

• Fever that persisted for 5 or more days

• Conjunctival congestion

• Changes in lips and oral cavity

• Polymorphous exanthema

• Changes of extremities

• Cervical lymphadenopathy

Mortality/Morbidity

The mortality rate is reported to be 0.1-2%. Approximately 20-25% of untreated patients develop cardiac problems, including CAAs, acute MI secondary to true coronary artery obstruction, myocarditis, congestive heart failure (CHF), pericarditis with pericardial effusion, mitral or aortic insufficiency, and dysrhythmias. Aneurysms develop in less than 5-10% of patients treated with intravenous gamma globulin before the 10th day of illness. Approximately 5% may have aortic or mitral regurgitation due to valvulitis, transient papillary muscle dysfunction, or MI. Arthritis persists in some children. KD appears to be a rare cause of adult cardiac dysfunction.

Race

The prevalence of KD is highest among Japanese. Rates are intermediate among blacks, Polynesians, and Filipinos and are lowest among whites.

Sex

KD is more common in males than in females, with a male-to-female ratio of 1.3-1.6:1. Arthritis appears more common in girls than in boys.

Age

Approximately 90-95% of cases occur in children younger than 10 years. In the United States, the incidence peaks in children aged 18-24 months. In Japan, the incidence peaks in children aged 6-12 months. The earliest reported case in Japan occurred in a 20-day-old newborn. KD in adults is rare. Kawasakilike syndromes have been reported in adults infected with human immunodeficiency virus (HIV).

CLINICAL

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History

Kawasaki disease (KD) has 3 stages, as follows:

• Acute stage (1-11 d)
• • High fever (temperature >104°F)
  
  
  • Irritability
  
  
  • Nonexudative bilateral conjunctivitis (90%)
  
  
  • Anterior uveitis (70%)
  
  
  • Perianal erythema (70%)
  
  
  • Acral erythema and edema that impede ambulation
  
  
  • Strawberry tongue and lip fissures
  
  
  • Hepatic, renal, and GI dysfunction
  
  
  • Myocarditis and pericarditis
  
  
  • Lymphadenopathy (75%), generally a single, enlarged, nonsuppurative cervical node measuring approximately 1.5 cm


• Subacute stage (11-30 d)
• • Persistent irritability, anorexia, and conjunctival injection
  
  
  • Decreased temperature
  
  
  • Thrombocytosis
  
  
  • Acral desquamation
  
  
  • Aneurysm forms


• Convalescent or chronic phase (>30 d)
  
  
  • Expansion of aneurysm
  
  
  • Possible MI
  
  
  • A tendency for smaller aneurysms to resolve on their own (60% of cases)

Physical

• Patients with classic KD must have 5 of the following symptoms (fever is an absolute criterion):
  
  
  • Fever, lasting more than 5 days and refractory to appropriate antibiotic therapy
  
  
  • Polymorphous erythematous rash
  
  
  • Nonpurulent bilateral conjunctival injection
  
  
  • Oropharyngeal changes, including diffuse hyperemia, strawberry tongue, and lip changes (eg, swelling, fissuring, erythema, bleeding)
  
  
  • Peripheral extremity changes, including erythema, edema, induration, and desquamation
  
  
  • Nonpurulent cervical lymphadenopathy


• Other findings may include the following:
  
  
  • General - Irritability
  
  
  • Cardiac - Coronary aneurysms, pericardial effusion, myocarditis, CHF
  
  
  • Neurologic - Stiff neck secondary to aseptic meningitis, facial palsy, cerebral infarction
  
  
  • Renal - Sterile pyuria, proteinuria, nephritis, acute renal failure
  
  
  • Musculoskeletal - Joint involvement (arthralgias or arthritis)
  
  
  • Pulmonary - Pleural effusion, infiltrates
  
  
  • GI - Abdominal pain, diarrhea, hepatitis, obstructive jaundice, hydrops, pancreatitis, gall bladder distention
  
  
  • Tissues - Meatitis, vulvitis, urethritis
  
  
  • Ophthalmologic - Conjunctivitis, uveitis
  
  
  • Dermatologic - Peripheral extremity gangrene, pustules, erythema multiforme–like lesions, perianal desquamation, macules, papules, measleslike rash, scarlet fever–like erythema, and induration at the site of bacille Calmette-Guérin (BCG) inoculation (commonly observed in Japan); pustulovesicular skin eruption in a child with probable KD; Beau lines associated with KD after the disease resolves


• Up to 10-45% of published cases have incomplete or atypical clinical presentations. The 2 most commonly missing findings include cervical lymphadenopathy and polymorphous rash.



• Mucous-membrane changes are the most common manifestations of KD, occurring in more than 90% of patients with either typical or atypical forms of the disease.

Causes

The etiology of KD remains unknown. At present, most of the epidemiologic and immunologic evidence indicates that the causative agent is probably infectious. This idea of an infectious etiology is supported by the age of the patients affected, the periodic epidemics, the wavelike and geographic spread of illness during the epidemic, and the self-limited nature of the illness. Furthermore, 1.4% of cases in Japan involve siblings. The overall clinical presentation of patients with KD is similar to that of patients with a viral or superantigenic disease.

The failure to isolate one pathogen highlights the likelihood that the cause of KD is multifactorial and that genetic and immunologic factors, and possibly a vector, influence the disease. Superantigens and cytotoxic T cells appear to be involved. Passive maternal immunity might account for the failure of most cases to develop before the patient is aged 4 months.

KD has been linked to various infections, including the following:

• Parvovirus B19


• Meningococcal septicemia


• Coxiella burnetii


• Bacterial toxin–mediated superantigens


• HIV


• Mycoplasma pneumoniae


• Adenovirus


• Klebsiella pneumoniae bacteremia


• Parainfluenza type 3 virus


• Rotavirus infection


• Measles


• Human lymphotropic virus infection

A case of KD with CAAs and Yersinia pseudotuberculosis infection has been reported. KD does not appear to be linked to Rickettsia conorii, Rickettsia typhi, C burnetii, or Ehrlichia phagocytophila group allergens, such as anionic detergents and house dust mites, and some chemicals (including heavy metals). KD is not associated with human herpesvirus 8, transfusion transmitted virus (TTV), GB virus C/hepatitis G virus, or Chlamydia pneumoniae infections.

Hypercoagulability does not occur during the acute stage of KD.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Scarlet fever
Staphylococcal scalded skin syndrome
Tick-borne diseases
Toxic epidermal necrolysis
Y pseudotuberculosis infection
Adenovirus infection
Drug reactions (eg, Stevens-Johnson syndrome)

WORKUP

Section 5 of 11  

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Lab Studies

• No specific laboratory test is used to diagnose Kawasaki disease (KD); however, certain abnormalities coincide with various stages.
  • Mild-to-moderate normochromic anemia is observed in the acute stage along with a moderate-to-high WBC count with a left shift, which is a predominant sign of immature and mature granulocytes.

  • Many levels of the acute-phase reactant markers, such as the erythrocyte sedimentation rate (ESR), C-reactive protein, and serum a-1-antitrypsin are elevated.

  • Culture results are all negative.
     
     
• Antineutrophil cytoplasmic antibodies, antiendothelial cell antibodies, antinuclear antibody, and rheumatoid factors: These levels are all within the reference range.

• Platelets
  • Thrombocytosis typically develops during the second or third week of illness, with an average of 700,000/μL.

  • Thrombocytopenia is associated with severe coronary artery disease and MI.

• Acute-phase reactants
  • ESR and C-reactive protein and alpha-1-antitrypsin levels are elevated.

  • Serum complement levels are within the reference range or elevated.

• Liver enzymes
  • Mild elevations in transaminase values are observed in 40% of patients; elevated alanine aminotransferase (ALT) levels can indicate a more serious course.

  • Bilirubin levels are elevated in 10% of patients.
     
• Urinalysis: Mild-to-moderate sterile pyuria of urethral origin and proteinuria may occur.

• Cardiac enzymes: Levels of cardiac enzymes (eg, creatine kinase [CK], creatine kinase-MB isozyme [CK-MB], cardiac troponin, and lactate dehydrogenase [LD-1 > LD-2]) are elevated during an MI.

• Rapid antigen test: Test results for adenovirus are negative. 

• Sittiwangkul et al (2006) reviewed the records of 70 patients with KD who were administered intravenous immunoglobulin (2 g/kg) at a hospital in Singapore from January 1995 to June 2004⁹. The study noted that initial treatment with intravenous immunoglobulin failed to elicit a response in 13% of these patients. The diagnosis in 2 patients with intravenous immunoglobulin–resistant KD was delayed and giant aneurysms developed. Patients with high ESRs were at an increased risk of intravenous immunoglobulin–resistant KD. Patients with intravenous immunoglobulin–resistant KD  had a higher prevalence of coronary artery lesions at the acute phase and 2 months after onset.

Imaging Studies

• Radiography
  
  
  • Perform chest radiography to rule out cardiomegaly or subclinical pneumonitis.
  
  
  • Chest radiography should be performed to assess baseline findings and to confirm a clinical suspicion of CHF.


• Echocardiography
  
  
  • This is the study of choice to evaluate for CAAs.
  
  
  • During the acute stage, obtaining a baseline echocardiogram is important to rule out CAAs and evidence of myocarditis, valvulitis, or pericardial effusion.
  
  
  • In children, ensure that pediatric cardiologists perform this study because they are familiar with coronary artery diameters.
  
  
  • Diffuse dilatation of coronary lumina can be observed in 50% of patients by the 10th day of illness.
  
  
  • Echocardiography should be repeated in the second or third week of illness and 1 month after all other laboratory results have normalized.
  
  
  • If the echocardiographic findings are abnormal at any point, refer the child to a pediatric cardiologist for a complete cardiac workup and follow-up care.
  
  


• Ultrasonography
  
  
  • Gall bladder ultrasonography may be necessary if liver or gall bladder dysfunction is suspected.
  
  
  • Obtain a scrotal sonogram in males to evaluate for epididymitis.
  
  
  • Although epididymitis is generally an inflammatory process that affects boys aged 9-14 years, it can be observed in younger boys with Henoch-Schönlein purpura and KD.
  
  


• Magnetic resonance angiography (MRA)
  
  
  • Free-breathing 3-dimensional (3D) coronary MRA accurately defines CAA in patients with KD.
  
  
  • This technique may provide a noninvasive alternative when the image quality of transthoracic echocardiography is insufficient, thereby reducing the need for serial radiographic coronary angiography in this patient group.
  
  

Other Tests

• Electrocardiography
  
  
  • Obtain an ECG to evaluate for various conduction abnormalities.
  
  
  • Children with KD may also have acute infarction.
  
  
  • Tachycardia, a prolonged PR interval, ST-T wave changes, and a decreased voltage of R waves may indicate myocarditis.
  
  
  • Q waves or ST–T wave changes may indicate an MI.

Procedures

• Lumbar puncture may reveal CSF pleocytosis.
• A select group of patients may require cardiac catheterization and angiography.

Histologic Findings

Biopsy samples are usually not collected from the skin in patients with KD. Weedon summarized the reported findings of KD, as follows¹⁰:

• Features are nonspecific.
  
  
• Lymphocytes and mononuclear cells manifest in a perivascular fashion.
  
  
• Edema of the papillary dermis may be present.
  
  
• Pustules with small intraepidermal and subcorneal abscesses unrelated to eccrine ducts may be present.
  
  
• One report noted subtle vascular alterations, subendothelial edema, focal endothelial cell necrosis, and vascular deposition of minute quantities of fibrinoid material.

More definite reports have noted the internal vascular changes of KD.

Destruction of vascular layers and infiltration of inflammatory cells in blood vessels are observed. Upon ultrastructural examination, myocardial changes reveal hypertrophy, various degrees of degeneration, proliferation and abnormality of mitochondria, infiltration of a small number of lymphocytes, and fibrosis. Coronary microvascular lesions are characterized by microvascular dilatation, endothelial cell injury, platelet aggregation with thrombosis, and stenotic lumen with thickened walls in the small arterioles.

TREATMENT

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Medical Care

The main goal of treatment is to prevent coronary artery disease and to relieve symptoms. Full doses of salicylates (aspirin) and intravenous gamma globulin are the mainstays of treatment. Baumer (2006) concluded that no quality randomized clinical trials have been performed and that current evidence is insufficient to support the use of salicylate in children with Kawasaki disease (KD) as part of their treatment regimen¹¹.

• Admit all patients to the hospital for intravenous gamma globulin administration and observation until fever is controlled.

• Closely monitor cardiovascular function.

• Patients with small aneurysms must take aspirin.

• Dipyridamole is indicated in patients with larger aneurysms.

• Patients taking long-term aspirin therapy should receive an influenza vaccination to protect against Reye syndrome.

Consultations

• Consult a pediatric or adult cardiologist for the following:
• • Children or adults with clinically significant coronary artery disease
  • Determining the appropriate timing of subsequent echocardiographic studies
  • Anticoagulation in patients with large aneurysms
  • Other studies to assess cardiac function, such as stress testing and coronary artery angiography

• Consult a pediatric or adult infectious disease specialist to rule out infectious disease as a cause of fever.

• Consult a pediatric or adult rheumatologist to rule out other causes of vasculitis and connective tissue diseases.

• Consult a pediatric dermatologist to rule out other conditions that can manifest with fever and a rash.

MEDICATION

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The pathophysiology of Kawasaki disease (KD) involves inflammation. The patient's own immune system probably causes the vasculitis that leads to morbidity and mortality in KD. Early and aggressive intervention improves outcome. Standard treatment includes aspirin and intravenous immunoglobulin (IVIG) to treat inflammation and to prevent consequences of coronary artery disease. Other anticoagulants or antiplatelet agents (eg, warfarin, dipyridamole) are occasionally used.

Between September 2000 and March 2005, 178 children with KD from 12 hospitals were randomized to receive either IVIG alone or IVIG with a corticosteroid. The study concluded that the latter group had an improved clinical course and decreased coronary artery complications without an increase of unacceptable adverse effects¹².

Treatment of IVIG-resistant KD with methotrexate has been reported to be effective.

Infliximab treatment for refractory KD was effective in a small study. Zulian et al  (2006) found infliximab to be useful in treating patients with refractory KD¹³. Stenbog et al (2006) also noted the effectiveness of TNF-alpha blockade in patients with complicated refractory K¹⁴.

Methylprednisolone pulse therapy used to treat massive lymphadenopathy in a child with IVIG-resistant KD has been effective.

Drug Category: Immunomodulatory agents

IVIG is a purified preparation of gamma globulin. It is derived from large pools of human plasma comprising 4 subclasses of antibodies, approximating the distribution of human serum.

Taniuchi et al evaluated a possible relationship between the effectiveness of gamma globulin treatment for patients with KD and the polymorphism of Fcgamma RIIa, IIIb, and IIIa¹⁵. Genomic DNA was extracted from whole blood collected from 56 patients with KD who received gamma globulin treatment. The genotypes for Fcgamma RIIIb-NA(1, 2), Fcgamma RIIa-H/R131, and FcgammaRIIIa-F/V158 were determined to investigate the association between these polymorphisms and the development of coronary lesions.

About 23% of patients with the HH allele for the Fcgamma RIIa polymorphism developed coronary artery lesions, compared with 60% with the HR and RR alleles. HR and RR alleles may be a predictor of the progression of coronary lesions in KD before the start of gamma globulin therapy.

A polymorphism in plasma platelet–activating factor acetylhydrolase is involved in resistance to immunoglobulin treatment in KD.

Drug Category: Nonsteroidal anti-inflammatory agents

These agents inhibit 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 disease have received aspirin for prolonged periods.

Drug Category: Antiplatelet agents

Besides aspirin, dipyridamole may be used to prevent microthrombus formation.

FOLLOW-UP

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Further Inpatient Care

• Admit patients to the hospital, administer IVIG, and observe them until their fever is controlled.


• Carefully monitor cardiovascular performance.


• Once the fever resolves, clinically significant CHF or myocardial dysfunction is unlikely.

Further Outpatient Care

• Reevaluate all patients within 1 week of hospital discharge.
• Schedule the patient for repeat echocardiography 21-28 days after the onset of fever.
• If baseline echocardiographic studies and those obtained at 3-4 weeks do not depict any evidence of coronary aneurysms, further echocardiography is usually unnecessary.
• Patients with no cardiac changes on echocardiography at any stage do not require activity restrictions or medications beyond 3 months after the initial illness.
• Ensure that a patient with CAAs or other cardiac abnormalities receives further care, as dictated by a cardiologist.

In/Out Patient Meds

• The mainstays of inpatient therapy include aspirin (100 mg/kg/d) and IVIG (400 mg/kg/d in 2-h infusions for 4 consecutive days).


• IVIG therapy can be administered alternatively as a 2-g/kg dose infused over 8-12 hours as a single dose.


• Aspirin (3-10 mg/kg/d divided 2-4 times daily) is continued until the fever, platelet levels, and ESR return to the reference range.

Transfer

• Transfer patients with suspected Kawasaki disease (KD) to a facility that has skilled clinicians and a pediatric or adult cardiologist to evaluate the echocardiogram.



• IVIG must be available for prompt administration.

Complications

• Cardiovascular
  
  
  • Clinically significant heart failure or myocardial dysfunction (unlikely to occur once fever is resolved)
  
  
  • Diffuse coronary artery ectasia and aneurysm formation, giant aneurysm (internal luminal diameter >8 mm)
  
  
  • MI
  
  
  • Myocarditis (common but rarely causes CHF)
  
  
  • Valvulitis, usually mitral (only occurs in 1% of patients and rarely requires valve replacement)
  
  
  • Pericarditis with small pericardial effusions (occurs in 25% of patients with acute illness)
  
  
  • Systemic arterial aneurysms
  
  
  • Rupture of CAA with hemopericardium


• Other complications
• • Extreme irritability, especially in younger infants
  
  
  • Aseptic meningitis
  
  
  • Arthritis
  
  
  • Mild hepatic dysfunction, jaundice (rare)
    
    
  • Gallbladder hydrops (diagnosed using ultrasonography, usually resolves without surgical intervention)
  
  
  • Diarrhea
  
  
  • Pneumonitis
  
  
  • Otitis media
  
  
  • Erythema and induration at the site of BCG inoculation (reported in Japan)
  
  
  • Peripheral extremity gangrene (extremely rare)
  
  
  • Bowel ischemia and necrosis

Prognosis

• With prompt treatment, the prognosis is good.
• The current mortality rate is 0.1-2%.

Patient Education

• The fact that most cases resolve must be communicated to the patient and family. The fact that KD can be fatal must also be communicated.
  
  
• Educate patients about the possibility of recurrence.
  • The recurrence rate is 4% in Japan but is less than 1% in North America.
    
    
  
  
  • Emphasize the need for continued care if cardiac problems are present because KD is a potentially fatal illness.
    
    
  
  
  • Advise the patient's family that aspirin therapy must be continued until discontinued by the physician.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Failure to diagnosis atypical cases of KD is a pitfall.


• Failure to make a diagnosis before the 10th day of illness so that IVIG can be administered to help prevent CAAs is a pitfall. If the diagnosis is suspected but cannot be confirmed, refer the patient to a center with experience in treating illness in a timely manner.


• Various infectious foci can mimic KD, including retropharyngeal abscess or cellulitis, peritonsillar abscess, orbital cellulitis, cervical lymphadenitis or deep neck infection, retropharyngeal phlegmon, and preseptal cellulitis.


• KD mimics measles and group A beta-hemolytic streptococcal infection; therefore, making a wrong diagnosis may lead to inappropriate treatment.


• When considering the rare diagnosis of mastoiditis, evaluate for other entities in the differential diagnosis before performing surgical intervention. However, if the patient is unstable or a threatened complication of mastoiditis is apparent, immediate mastoidectomy is required.

MULTIMEDIA

Section 10 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Patchy generalized macular erythema, which is also typical of some viral exanthems.
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Media type:  Photo

Media file 2:  Peeling and erythema of the fingertips.
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Media type:  Photo

Media file 3:  Strawberry tongue.
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Media type:  Photo

REFERENCES

Section 11 of 11

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1. Melish ME, Hicks RM, Larson EJ. Mucocutaneous lymph node syndrome in the United States. Am J Dis Child. Jun 1976;130(6):599-607. [Medline].
2. Newburger JW, Taubert KA, Shulman ST, et al. Summary and abstracts of the Seventh International Kawasaki Disease Symposium: December 4-7, 2001, Hakone, Japan. Pediatr Res. Jan 2003;53(1):153-7. [Medline]. [Full Text].
3. Dergun M, Kao A, Hauger SB, Newburger JW, Burns JC. Familial occurrence of Kawasaki syndrome in North America. Arch Pediatr Adolesc Med. Sep 2005;159(9):876-81. [Medline].
4. Burns JC, Cayan DR, Tong G, et al. Seasonality and temporal clustering of Kawasaki syndrome. Epidemiology. Mar 2005;16(2):220-5. [Medline].
5. Burns JC, Mason WH, Hauger SB, et al. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. May 2005;146(5):662-7. [Medline].
6. Yanagawa H, Nakamura Y, Yashiro M, Uehara R, Oki I, Kayaba K. Incidence of Kawasaki disease in Japan: the nationwide surveys of 1999-2002. Pediatr Int. Aug 2006;48(4):356-61. [Medline].
7. Royle JA, Williams K, Elliott E, et al. Kawasaki disease in Australia, 1993-95. Arch Dis Child. Jan 1998;78(1):33-9. [Medline].
8. Harnden A, Alves B, Sheikh A. Rising incidence of Kawasaki disease in England: analysis of hospital admission data. BMJ. Jun 15 2002;324(7351):1424-5. [Medline].
9. Sittiwangkul R, Pongprot Y, Silvilairat S, Phornphutkul C. Management and outcome of intravenous gammaglobulin-resistant Kawasaki disease. Singapore Med J. Sep 2006;47(9):780-4. [Medline].
10. Weedon R. Kawasaki Syndrome: The vasculopathic reaction pattern. In: Skin Pathology. 2002:238-9.
11. Baumer JH, Love SJ, Gupta A, et al. Salicylate for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2006;(4):CD004175. [Medline].
12. Inoue Y, Okada Y, Shinohara M, 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].
13. Zulian F, Zanon G, Martini G, Mescoli G, Milanesi O. Efficacy of infliximab in long-lasting refractory Kawasaki disease. Clin Exp Rheumatol. Jul-Aug 2006;24(4):453. [Medline].
14. Stenbog EV, Windelborg B, Horlyck A, Herlin T. The effect of TNFalpha blockade in complicated, refractory Kawasaki disease. Scand J Rheumatol. Jul-Aug 2006;35(4):318-21. [Medline].
15. Taniuchi S, Masuda M, Teraguchi M, et al. Polymorphism of Fcgamma RIIa may affect the efficacy of gamma-globulin therapy in Kawasaki disease. J Clin Immunol. Jul 2005;25(4):309-13. [Medline].
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Article Last Updated: May 25, 2007