Kawasaki disease in infants and young children

21 March 2019

When one mentions Kawasaki Disease, the first thought that appears is often that of the eponymous motorcycle.

In actual fact, Kawasaki disease is an acute self-limited vasculitis of unknown aetiology that occurs predominantly in infants and young children. It was first described in Japan by Tomisaku Kawasaki in 1967.

In untreated children, coronary artery aneurysms or ectasia can develop in up to 25% and may lead to myocardial infarction, sudden death or ischaemic heart disease. Even when treated appropriately with high dose IV immunoglobulin, ~5% of children can still develop coronary dilatation, usually transient and 1% giant aneurysms.

Epidemiology

In developed countries, Kawasaki disease has surpassed acute rheumatic fever as the leading cause of acquired heart disease in children. It occurs in children of all races, with the highest incidence in the Far East.

Japan has the highest incidence of Kawasaki disease in the world; the frequency of this disease is 10 to 20 times higher than in Western countries. Between 1999 – 2002, the annual incidence in Japan was found to be 137.7 per 100,000 children under 5 years of age. In 2010, the incidence in Japan rose to 239.6 per 100,000 children under 5 years old. Between 2003 - 2005, Park et al noted that South Korea which has the second highest incidence, had 105 cases per 100,000 children under 5 years. Studies in Beijing 2000 – 2004 showed an annual incidence of 40.9 – 55.1 per 100,000 children under 5 years.

Approximately 80% of cases occur in children from 6 months to 5 years of age. However, there are cases from as young as one month old and as old as 10 yearsof age. The extremes of ages may have a poorer outcome due to late or missed diagnosis. Kawasaki disease has very rarely been reported in adolescents and adults. Fewer than 60 cases in adults have been reported in the literature from different geographic locations.

Kawasaki disease is slightly more common in boys than girls. The boy to girl ratio is 1.5 to 1. In Japan, the recurrence rate is approximately 4%.The proportion of cases with a positive family history is ~1%

Aetiology

The aetiology is unknown. Clinical and epidemiological features suggest an infectious cause ie age distribution and tendency to occur in time-space clusters. However, conventional bacterial/viral cultures and serological methods have failed to identify an infectious cause. It is possible that Kawasaki disease results from an immunologic response that is triggered by any of several different microbial agents.

One of the hypotheses is that this agent produces clinically apparent disease only in certain genetically susceptible individuals, particularly Asians. There is little evidence of person-to-person transmission, hence this hypothesis assumes that most infected children experience asymptomatic infection with only a small fraction developing disease. A genetic predilection to Kawasaki disease has long been suspected. Siblings of affected patients have 10-20 times higher probability of developing this disease.

Pathology

Although the coronary arteries are virtually always involved in autopsy cases, Kawasaki disease is a generalized systemic vasculitis. In severe cases, aneurysms may occur in the coeliac, mesenteric, axillary, femoral, iliac and renal arteries. The media of affected vessels demonstrate oedematous dissociation of the smooth muscle cells. Active inflammation is replaced over several weeks to months by progressive fibrosis with scar formation.

Diagnosis

In the absence of a specific diagnostic test, the diagnosis of Kawasaki disease is still based on clinical criteria. The clinical criteria are as follows:

• Fever for 5 days or more associated with 4 of the following 5 criteria
  • Changes of the extremities
    Acute: Erythema of palms and soles and oedema of hands and feet
    Sub-acute: Periungual peeling of fingers and toes in weeks 2 and 3
  • Polymorphous rash
  • Bilateral nonpurulent conjunctival injection
  • Changes in the lips and oral cavity: Erythema, lips cracking, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
  • Cervical lymphadenopathy (>1.5cm diameter), usually unilateral

Typically not all of the clinical criteria are present together at a single point of time and watchful waiting is often necessary to clinch the diagnosis. “Incomplete” or atypical cases of Kawasaki disease may pose a diagnostic dilemma. However, patients with fever of ≥5 days and <4 principal criteria can be diagnosed as having Kawasaki disease when coronary artery involvement is detected by echo.

The other common features can include irritability, abdominal pain, diarrhea and vomiting, arthritis or arthralgia and jaundice.

Differential diagnosis:-

• Viral infections (eg measles, adenovirus, enterovirus)
• Scarlet fever
• Bacterial cervical lymphadenitis
• Drug hypersensitivity reactions
• Steven Johnson syndrome
• Juvenile chronic arthritis
• Leptospirosis

Common pitfalls in diagnosis

Children may present with just fever and unilateral cervical lymph node swelling and therefore diagnosed as bacterial cervical lymphadenitis. The rash and mucosal changes that occur subsequently may be brushed off as an allergic reaction to the antibiotics given. Similarly an infant who presents with pyuria may be treated for urinary tract infection and the rashes and other signs attributed to an allergic reaction to antibiotics. Children who present with fever, rash, irritability and white cells in the cerebrospinal fluid may be misdiagnosed as viral meningitis. This is particularly so if the child is out of the normal age range of 6 months to 5 years of age. Therefore, a high index of suspicion is required in every child with prolonged fever and a few of the clinical criteria.

References:

1. 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; 2747-2771
2. 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. 2006 Aug. 48(4):356-61.
3. Park YW, Han JW, Park IS, Kim CH, Cha SH, Ma JS, et al. Kawasaki disease in Korea, 2003-2005. Pediatr Infect Dis J. 2007 Sep. 26(9):821-3.
4. Pediatr Infect Dis J 2007 May;26(5):449-51 Du ZD, Zhao D, Du J, Zhang YL, Lin Y, Liu C, et al. Epidemiologic study on Kawasaki disease Beijing from 2000 through 2004.
5. Illustrated Textbook of Paediatrics by Tom Lissauer and Graham Clayden, published by Mosby, 1st edition 1996

 

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