Use of corticosteroids during acute phase of Kawasaki disease

Table 1 Re-treatment with corticosteroids or additional intravenous immunoglobulin in Kawasaki disease patients unresponsive to initial intravenous immunoglobulin

Ref.	No. of patientswith KD	Definition ofunresponsiveness:BT, obs period, other	No. of patientsunresponsive to initial IVIG	Stageof CS Tx	Regimen	No. of patients re-Tx	Tx day after fever onset1	No. of patientswith response	No. of patientswith CAA	No. of patients with adverse effects
[22]	411	36 h after IVIG	63	2nd line	IVMP 30 mg/kg per day, 3 d	44	7 (6-8)	34	5	Hypertension 5, hypothermia 3, bradycardia 3, transient paralysis 1
					Followed Pd
					IVIG 1-2 g/kg	19	8 (5-11)	12	2
[40]	NA	≥ 37.5 °C, 48 h after IVIG	22	2nd line	IVMP 30 mg/kg per day, 3 d	11	NA	NA	2	Hypertension 10, hypothermia 1, bradycardia 9, hyperglycemia 6, aPTT↓ 3
					IVIG 2 g/kg	11	NA	NA	3
[23]	164	≥ 37.5 °C, 36-48 h after IVIG	27	2nd line	IVMP 30 mg/kg per day, 3 d	13	7 ± 1.3	NA	0	Bradycardia 2
		CRP↓ ≤ 50%
					IVIG 2 g/kg	14	8 ± 2.4	NA	3
[24]	237	≥ 38 °C, 36 h after IVIG	41	2nd line	IVMP 30 mg/kg per day, 3 d	14	7 (7-9)	7	5	Gastrointestinal bleeding 1
		37.5 °C-38 °C and CRP↓ ≤ 50%			Followed Pd
					IVIG 2 g/kg	27	8 (5-14)	21	7
[25]	262	≥ 37.5 °C, 48 h after IVIG	35	3rd line	IVMP 20 mg/kg per day, 3 d	9	NA	NA	7	NA
		CRP↓ ≤ 50%
					IVIG 1 g/kg	8	NA	NA	5
[26]	412	48 h after IVIG	74	3rd line	IVMP 30 mg/kg per day, 3 d	21	8 (IQR 8-9)	21	2	Hypertension 17, hypothermia 3, bradycardia 17, hyperglycemia 7, serum Na↓ 4
					Followed Pd

¹Median (range), median (IQR), or mean ± SD. IVIG: Intravenous immunoglobulin; KD: Kawasaki disease; BT: Body temperature; obs: Observation; Tx: Treatment; CS: Corticosteroids; CAA: Coronary artery aneurysm; NA: Not available; IVMP: Intravenous methylprednisolone pulse; Pd: Oral prednisolone; IQR: Interquartile range.

Table 2 Risk scoring systems for the selection of patients expected to have unresponsiveness to initial intravenous immunoglobulin treatment

	Cut-off	Points
Kobayashi score (≥ 4-5 points)[51,54,55]
Age	≤ 12 mo	1
Days of illness at initial treatment	≤ 4	2
Platelet count	≤ 300 × 103/mm3	1
Neutrophil	≥ 80%	2
CRP	≥ 10 mg/dL	1
AST	≥ 100 IU/L	2
Sodium	≤ 133 mmol/L	2
Egami score (≥ 3 points)[52]
Age	≤ 6 mo	1
Days of illness at initial treatment	≤ 4	1
Platelet count	≤ 300 × 103/mm3	1
CRP	≥ 8 mg/dL	1
ALT	≥ 80 IU/L	2
Sano score (≥ 2 points)[53]
CRP	≥ 7 mg/dL	1
AST	≥ 200 IU/L	1
Total bilirubin	≥ 0.9 mg/dL	1

IVIG: Intravenous immunoglobulin; CRP: C-reactive protein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 3 Clinical and laboratory variables associated with the unresponsiveness to initial intravenous immunoglobulin treatment

	Risk factors	Ref.
Age	≤ 6-12 mo	[51,52,58]
Sex	Male	[33,61]
Duration of fever	Long duration	[58,69]
Days of illness at initial treatment	≤ 4	[31,33,51,52,58,60,71]
Recurrent Kawasaki disease	Recurrent case	[33]
Principal features/symptoms	Early appearance	[72]
	Polymorphous exanthema	[60]
	Lymphadenopathy	[32]
Other physical findings	Changes around anus	[60]
Brand of IVIG	β-propiolactone	[65,66]
Neutrophil	≥ 80%, or increased	[51,58,60,69,72]
Band form	≥ 20%, or increased	[31,34]
Hemoglobin	Anemia by age, < 10 g/dL	[31,59]
Eosinophil count	High level – good response	[68]
Platelet count	≤ 300 × 103/mm3, or decreased	[51,52,58,72]
	≥ 530 × 103/mm3	[32]
ESR	≥ 75 mm/h, or increased	[32,37]
CRP	≥ 7-10 mg/dL, or increased	[51-53,58-60,69]
Albumin	Lower than normal	[34,61,67]
ALT	≥ 80-84 IU/L	[52,62]
AST	≥ 100-200 IU/L, or increased	[51,53,61,72]
Total bilirubin	≥ 0.9 mg/dL, or increased	[53,62,72]
γGlutamyl transferase	≥ 60 IU/L	[31]
Lactate dehydrogenase	> 590 IU/L	[59]
Sodium	≤ 133 mmol/L	[51]
Imaging studies	Sonographic GB abnormalities	[70]

IVIG: Intravenous immunoglobulin; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; NT-proBNP: N-terminal fragment of B-type natriuretic peptide; GB: Gall bladder.