AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Kawasaki disease (KD), also known as Kawasaki syndrome, was first described in Japan in 1967 by the pediatrician Dr Tomisaku Kawasaki. Since its original description, KD has been reported worldwide in children of all ethnic origins. Originally, KD was believed to be an acute, self-limiting febrile disease with an excellent prognosis; however, subsequent reports indicated that nearly 2% of patients with KD died from the illness, usually as a result of secondary cardiac sequelae.

Pathophysiology

Kawasaki disease is a systemic vasculitis of unknown etiology that affects the small- and medium-sized blood vessels of the body, in particular, the coronary arteries.

Frequency

United States

The yearly incidence of endemic KD in the United States is 67 cases per 100,000 children who are younger than 5 years. Approximately 3,000 hospitalizations occur annually in the United States as a result of KD. Seasonal peaks occur in the spring and winter with a relative paucity of cases in the summer months.

International

The incidence in Europe is comparable to that of the United States. In Japan, where KD has the highest incidence, an estimated 5,000-6,000 cases occur annually.

Race

• The incidence of KD remains the highest in children of Japanese descent, although the disease has now been reported in children of all ethnic origins.
• In the United States, KD occurs most often in children of Asian ancestry, followed by African Americans. The lowest incidence is in whites.

Sex

The male-to-female ratio is approximately 1.5:1.

Age

• Eighty percent of KD cases occur in children younger than 4 years, with most cases in the United States presenting in children aged 1-2 years.
• In Japan, the highest incidence occurs in persons aged 6-12 months. Cases in children older than 14 years are rare.

CLINICAL

Section 3 of 10  

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

History

• The most characteristic clinical sign required to establish a diagnosis of KD is a fever that persists for 5 days or more. Fever is the initial sign of the illness in many patients, generally following a waxing and waning pattern and lasting for 11 days on average.
• In addition to fever, at least 4 of the following 5 criteria should be satisfied for diagnosis:
• • Changes of the peripheral extremities include initial reddening or edema of the palms and soles, followed by membranous desquamation of the finger and toe tips or transverse grooves across the fingernails and toenails (Beau lines)
  • A polymorphous, primarily truncal, exanthem
  • Oropharyngeal changes including erythema, fissuring, and crusting of the lips, strawberry tongue, and diffuse mucosal injection of the oropharynx
  • Bilateral, nonexudative, painless bulbar conjunctival injection
  • Acute nonpurulent cervical lymphadenopathy with lymph node diameter greater than 1.5 cm
• KD is triphasic in nature with an acute, subacute, and convalescent phase.

Physical

• The acute phase lasts from 1-2 weeks and is characterized by a prolonged elevated temperature, often poorly responsive to antipyretics.
• The patient also manifests many or all of the above criteria.
• • More than 90% of children with KD develop an exanthem in the first few days of their illness, usually on the trunk and proximal extremities.
  • Lymphadenopathy is the least common sign, present in only 50-70% of patients.
• The subacute phase follows the acute phase, lasting 3-4 weeks. Many of the clinical symptoms begin to resolve, including the fever and rash.
• The final convalescent phase is marked by complete resolution of clinical signs of the illness, usually within 3 months of presentation.
• The most common ophthalmologic finding is bilateral conjunctival injection. Iridocyclitis, superficial punctate keratitis, vitreous opacities, papilledema, and subconjunctival hemorrhage also may occur.
• • Bilateral conjunctival erythema is one of the classical diagnostic criteria for KD, present in more than 90% of children with KD.
  • Mostly confined to the bulbar region
  • Nonexudative
  • Chemosis, follicles, and papillae are characteristically absent.
• A study by Blatt et al found that pediatricians seldom consider the eye redness significant enough to warrant ophthalmologic consultation. The authors suggested that only hospitalized children who exhibited signs of fever, conjunctival injection, and oral lesions would benefit from ophthalmologic examination.
• Burns et al found evidence of uveitis in 83% of children who were diagnosed with KD in the first week of their illness.
• • The anterior uveitis is usually mild and bilateral, sometimes associated with keratic precipitates.
  • The anterior uveitis peaks about a week after fever onset. It generally resolves within 2-8 weeks after disease onset without any of the common sequelae that often are seen with many other infectious causes of uveitis.
• Ohno et al found a significant incidence of superficial punctate keratitis (22%) in his study of patients with KD. Other findings noted in the study included papilledema (12%), vitreous opacities (12%), and subconjunctival hemorrhage (6%).
• Ryan and Walton described a case of a 10-month-old male infant in whom bilateral scarring of the superior and inferior fornices developed in association with KD.
• Less common posterior segment manifestations usually are limited to case reports. One such report by Font et al describes bilateral inner retinal ischemia due to thrombotic occlusion as a result of systemic vasculitis.
• A recent case documents periorbital vasculitis in an 8-month-old infant with KD, a previously unreported manifestation of KD.

Causes

• The etiology remains unclear, although epidemiological data support an infectious cause. Thus far, the unknown agent generally is believed to be ubiquitous in the environment, causing noticeable disease only in those individuals with some as yet undiscovered genetic predisposition for the illness.
• Based upon epidemiologic data, person-to-person transmission of the disease is unlikely.
• Several organisms have been investigated as the possible etiologic agents, as follows: mite-associated bacteria, tick-borne diseases, Rickettsia species, Propionibacterium acnes, and several viruses such as Epstein-Barr virus and retroviruses.
• Several investigators have noted the similarities of KD and toxic shock syndrome (TSS), a toxin-mediated disorder caused by a strain of Staphylococcus aureus and the streptococcal species.
• • The toxins elaborated by these strains are proposed to act as superantigens, molecules that elicit a more widespread immune response (eg, T-cell activation) in comparison to conventional antigens.
  • Some researchers believe that TSS and KD are different manifestations of the same disease.
• Other researchers believe that KD is caused by a unique bacterial toxin.
• Epidemiological studies suggest a controversial association of KD with recent carpet shampooing, flooding, and locations near bodies of water. These data have produced a water-borne vector hypothesis.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Adenovirus
Adverse drug reaction
Enterovirus
Epstein-Barr virus
Infantile polyarteritis nodosa
Influenza virus
Juvenile rheumatoid arthritis
Leptospirosis
Measles
Mercury toxicity (acrodynia)
Rheumatic fever
Scarlet fever
Staphylococcal or streptococcal TSS
Staphylococcal scalded skin syndrome
Systemic lupus erythematosus
Tick typhus
Yersinia pseudotuberculosis sepsis

WORKUP

Section 5 of 10  

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

Lab Studies

• Patients may develop an elevated white blood cell count with a predominance of neutrophils in the first few days of the illness.
• A normocytic, normochromic anemia may be present.
• Thrombocytosis occurs, peaking in the first month of the illness.
• Liver transaminase level elevation is common as is an elevated bilirubin and alkaline phosphatase.
• Acute phase reactants (classically erythrocyte sedimentation rate [ESR] and C-reactive protein) are increased for as many as 3 months after disease onset.

Imaging Studies

• Two-dimensional echocardiogram commonly is used to assess cardiac function and anatomy.
• Current guidelines suggest a baseline echo within 7 days of the disease onset, then a repeat echo 6-8 weeks later when coronary vascular abnormalities are more likely to be detected.

Other Tests

• Electrocardiographic (ECG) abnormalities such as left ventricular hypertrophy, abnormal Q waves, and a prolonged PR interval also commonly are noted. However, a normal ECG does not preclude a diagnosis of KD.

Procedures

• Coronary arteriography sometimes is used, if there are persistent irregularities on echo, or if the anatomy is difficult to define by echo.

TREATMENT

Section 6 of 10  

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

Medical Care

A thorough discussion of systemic care of KD is beyond the scope of this article. Nevertheless, the mainstays of systemic treatment are intravenous immunoglobulin (IVIG) and acetylsalicylic acid (aspirin); the goal is to reduce vascular inflammation. Consultation with a pediatrician, a pediatric intensivist or a pediatric cardiologist is essential to delivery of community standard care.

• Treat KD uveitis with topical corticosteroids such as prednisolone acetate, loteprednol etabonate, or dexamethasone, as well as topical cycloplegics.
• Although it generally resolves within days of IVIG therapy, conjunctival inflammation also may be treated with topical corticosteroids.
• Keratitis is treated with supportive care using topical tear replacement, preservative-free tears, ophthalmic ointments, and avoidance of irritants, tap water, rubbing behavior, and excessive use of topical preserved drops.

Consultations

• Consultation with a pediatrician is mandatory for current KD treatment options.
• A pediatric cardiology consult also is recommended.
• Consider the input of a pediatric infectious disease specialist.

MEDICATION

Section 7 of 10  

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

A single dose of IVIG at 2 g/kg given over 12 h is current treatment recommendation. In addition, aspirin is given at a dose of 80-100 mg/kg/d, divided into 4 doses. Systemic corticosteroid use remains controversial. Some believe that this treatment increases risk of cardiac sequelae. Pediatric consultation is necessary for current dosing guidelines and recommendations.

Drug Category: Immune globulins

A sterile, freeze-dried preparation of highly purified immunoglobulin G (IgG) derived from large pools of human plasma.

Drug Category: Antiplatelet and anti-inflammatory drugs

Acetylsalicylic acid is a potent inhibitor of both prostaglandin synthesis and platelet aggregation.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

FOLLOW-UP

Section 8 of 10  

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

Further Outpatient Care

• A follow-up echo is strongly urged to avoid a delayed diagnosis of the potentially devastating complications of coronary artery aneurysms and thrombosis.

Prognosis

• Although children appear ill during the first 2-3 weeks, complete recovery without sequelae is generally the rule.
• Recurrences are rare (0.06% of all cases).

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• KD is uncommon, while bilateral conjunctivitis is extremely common. The astute primary care physician, emergency room specialist, urgent care physician, or ophthalmologist should scrutinize cases of bilateral ocular redness associated with persistent fever, rash, and lymphadenopathy, particularly in the pediatric, Asian demographic groups most at risk. Referral to the appropriate pediatric subspecialist will ascertain community standard care in selected cases.

REFERENCES

Section 10 of 10

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

• American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease. Diagnostic guidelines for Kawasaki disease. Am J Dis Child. Nov 1990;144(11):1218-9. [Medline].
• Blatt AN, Vogler L, Tychsen L. Incomplete presentations in a series of 37 children with Kawasaki disease: the role of the pediatric ophthalmologist. J Pediatr Ophthalmol Strabismus. Mar-Apr 1996;33(2):114-9. [Medline].
• Burns JC, Joffe L, Sargent RA, Glode MP. Anterior uveitis associated with Kawasaki syndrome. Pediatr Infect Dis. May-Jun 1985;4(3):258-61. [Medline].
• Curtis N. What is the cause of Kawasaki disease? In: Infectious Diseases. 1994;8(3):71-76.
• Fatica NS, Ichida F, Engle MA, Lesser ML. Rug shampoo and Kawasaki disease. Pediatrics. Aug 1989;84(2):231-4. [Medline].
• Felz MW, Patni A, Brooks SE, Tesser RA. Periorbital vasculitis complicating Kawasaki syndrome in an infant. Pediatrics. Jun 1998;101(6):E9. [Medline].
• Font RL, Mehta RS, Streusand SB, et al. Bilateral retinal ischemia in Kawasaki disease. Postmortem findings and electron microscopic observations. Ophthalmology. May 1983;90(5):569-77. [Medline].
• Fujiwara H, Hamashima Y. Pathology of the heart in Kawasaki disease. Pediatrics. Jan 1978;61(1):100-7. [Medline].
• Germain BF, Moroney JD, Guggino GS, et al. Anterior uveitis in Kawasaki disease. J Pediatr. Nov 1980;97(5):780-1. [Medline].
• Jacob JL, Polomeno RC, Chad Z, Lapointe N. Ocular manifestations of Kawasaki disease (mucocutaneous lymph node syndrome). Can J Ophthalmol. Oct 1982;17(5):199-202. [Medline].
• Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi. Mar 1967;16(3):178-222. [Medline].
• Leung DY, Schlievert PM, Meissner HC. The immunopathogenesis and management of Kawasaki syndrome. Arthritis Rheum. Sep 1998;41(9):1538-47. [Medline].
• Ohno S, Miyajima T, Higuchi M, et al. Ocular manifestations of Kawasaki''s disease (mucocutaneous lymph node syndrome). Am J Ophthalmol. Jun 1982;93(6):713-7. [Medline].
• Rauch AM. Kawasaki syndrome: critical review of U.S. epidemiology. Prog Clin Biol Res. 1987;250:33-44. [Medline].
• Rauch AM. Kawasaki syndrome: review of new epidemiologic and laboratory developments. Pediatr Infect Dis J. Nov 1987;6(11):1016-21. [Medline].
• Richards SC, Apple DJ. Kawasaki's disease. In: The Eye in Systemic Disease. 1992;284-287.
• Ryan EH, Walton DS. Conjunctival scarring in Kawasaki disease: a new finding?. J Pediatr Ophthalmol Strabismus. May-Jun 1983;20(3):106-8. [Medline].
• Smith LB, Newburger JW, Burns JC. Kawasaki syndrome and the eye. Pediatr Infect Dis J. Feb 1989;8(2):116-8. [Medline].
• Yanagawa H, Nakamura Y, Yashiro M, et al. A nationwide incidence survey of Kawasaki disease in 1985-1986 in Japan. J Infect Dis. Dec 1988;158(6):1296-301. [Medline].

Article Last Updated: Sep 25, 2006