Controversies in diagnosis and management of Kawasaki disease

Table 1 American Heart Association guidelines for diagnosis of Kawasaki disease (2017)[13]

Classic KD is diagnosed with fever persisting for least 5 d
At least four of the five principal clinical features:
Changes in lips and oral cavity: Erythema, lips cracking, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
Changes in extremities
Acute: Erythema of palms, soles; edema of hands, feet
Subacute: Periungual peeling of fingers and toes in weeks 2 and 3
Polymorphous exanthema (diffuse maculopapular, urticarial, erythroderma, erythema-multiforme like, not vesicular or bullous)
Bilateral bulbar conjunctival injection without exudates
Cervical lymphadenopathy (> 1.5 cm diameter), usually unilateral
A careful history may reveal that ≥ 1 principal clinical features were present during the illness but resolved by the time of presentation
Exclusion of other diseases with similar findings (e.g., scarlet fever, viral infections like measles, adenovirus, enterovirus, Stevens-Johnson syndrome, toxic shock syndrome, drug hypersensitivity reactions, systemic juvenile idiopathic arthritis)

KD: Kawasaki disease.

Table 2 Kawasaki Disease Research Committee guidelines (Japanese Ministry of Health guidelines) for diagnosis of Kawasaki disease (2002)[14]

Five of the following six criteria
Fever persisting ≥ 5 d
Bilateral conjunctival congestion
Changes of lips and oral cavity
Polymorphous exanthema
Changes of peripheral extremities
Acute non-purulent cervical lymphadenopathy

Table 3 Salient differences between American Heart Association 2004 and 2017 criteria[1,13]

Duration of fever	In the presence of ≥ 4 principal clinical features, particularly when redness and swelling of the hands and feet are present, KD can be diagnosed even with 4 d of fever
History	Presence of one or more principal clinical manifestations of disease that can be revealed on history but have disappeared by the time of presentation, have been considered important for diagnosis
KD shock syndrome	KDSS has been given special consideration in the 2017 revised guidelines because in the presence of shock the diagnosis of KD is often not considered
KD in infants	Clinicians should have a lower threshold for diagnosis of KD in this age group
Incomplete KD	Algorithm for incomplete KD has been simplified
KD and infections	The issue of infections and KD has been detailed at length. Diagnosis of KD must not be excluded even in the presence of a documented infection when typical clinical features of KD are present
Bacterial lymphadenitis	Ultrasonography and computed tomography findings in differentiating the 2 conditions- bacterial lymphadenitis is often single and has a hypoechoic core on ultrasonography, while lymphadenopathy in KD is usually multiple and is associated with retropharyngeal edema or phlegmon
2D-echocardigraphy	The limitations of echocardiography and other diagnostic modalities have been highlighted. Z-score (by Manlihot et al) for severity classification of coronary artery abnormalities has been adapted

KD: Kawasaki disease; KDSS: Kawasaki disease shock syndrome.

Table 4 Coronary artery abnormalities severity classification in different guidelines

Criteria	Description
JMH criteria[14]	Aneurysm definition
	< 5 yr - ID > 3 mm
	≥ 5 yr - ID > 4 mm
Updated JMH (2008)[93]	Small aneurysm (dilatation with ID < 4 mm or if child is ≥ 5 yr of age, ID ≤ 1.5 times that of an adjacent segment)
	Medium aneurysm (dilatation with ID > 4 mm but ≤ 8 mm or if child is ≥ 5 yr of age, ID 1.5 to 4 times that of an adjacent segment)
	Large aneurysm (dilatation with ID > 8 mm or if child is ≥ 5 yr of age, ID > 4 times that of an adjacent segment)
AHA 2004 criteria[1]	Aneurysm ID z score > 2.5 (as per body surface area adjusted z scores)
	Small: < 5 mm
	Medium: 5 to 8 mm
	Giant aneurysm: > 8 mm based on absolute diameter
AHA 2017 criteria (Manlhiot et al)[13,68]	No involvement (Z score < 2)
	Dilation only (Z score 2 to < 2.5; or if initially < 2, a decrease in Z score during follow-up ≥ 1 thereby suggesting that coronary artery was dilated during acute stage though diameter was within normal standards and the diameter has regressed on follow-up)
	Small aneurysm (Z score ≥ 2.5 to < 5)
	Medium aneurysm (Z score ≥ 5 to < 10, and absolute dimension < 8 mm)
	Large or giant aneurysm (≥ 10, or absolute dimension ≥ 8 mm)

ID: Internal diameter; AHA: American Heart Association; JMH: Japanese Ministry of Health.