Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment

Abstract

Clinical, laboratory, and echocardiographic data were retrospectively analyzed in 112 patients with acute Kawasaki disease who received high-dose (2 g/kg) intravenous gamma-globulin (IVIG) treatment within 2 days and were compared for those who were responsive and non-responsive to initial IVIG treatment. Coronary arteries adjusted for body surface area (BSA) were evaluated quantitatively by comparison with the mean dimensions for 85 normal control subjects. The incidence of coronary abnormalities was higher in IVIG-non-responsive patients as compared to IVIG-responsive patients (71% versus 5%, p<0.0001). Univariate analysis of pre-IVIG data showed that the neutrophil count and serum levels of C-reactive protein (CRP), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH) were significantly higher in IVIG-non-responsive versus responsive patients. Multivariate analysis selected CRP (p=0.009), TB (p<0.001), and AST (p=0.002) as independent predictors of non-responsiveness to initial IVIG treatment. By defining predictive values, patients with at least two of three predictors (CRP>or=7.0 mg, TB>or=0.9 mg, or AST>or=200 IU/L) are considered to be non-responsive to IVIG for acute Kawasaki disease. Alternatively, more intense initial therapy may be a promising therapeutic strategy for patients who are predicted to be IVIG-non-responsive.

Immunoglobulin Resistance in Kawasaki Disease

“…Kawasaki disease children who are resistant or refractory to initial immunoglobulin therapy with recrudescence of fever are thought to be a ''hyperinflammatory phenotype'' and are considered to be at a higher risk for coronary artery aneurysms 3,[16][17][18][19] and other complications. 20,21 Several factors have been reported to be associated with refractory cases, including younger age, 22 male gender, 23 earlier presentation, 3 initial treatment before day 4 of fever, lower platelets, 3,22 lower hemoglobin, 3,24 higher white blood cell 25 and bands counts, 3 elevated C-reactive protein 3,19,22,24,26,27 and erythrocyte sedimentation rate, 18 elevated lactate dehydrogenase, 19,24 abnormal liver function, 3,19,22,23,26,27 lower serum albumin 23,28,29 and certain biomarkers, 30-33 among others.…”

Responsiveness to intravenous immunoglobulins and occurrence of coronary artery abnormalities in a single-center cohort of Italian patients with Kawasaki syndrome

“…Egami et al showed that resistance to IVIG treatment can be predicted evaluating age, illness days, platelet count, serum transaminase level and CRP [13]. A multivariate analysis by Sano et al in 112 patients with KS, who received IVIG within 2 days, selected high CRP, total bilirubin and aspartate aminotransferase as independent predictors of low rate of response to initial IVIG treatment, finding that patients with at least two increased predictors of the three might result unresponsive to IVIG [14]. Failure of a single IVIG dose might occur in up to 11.6% of KS patients, especially if displaying low hemoglobin, high neutrophil count and low albumin [15].…”

The Relationship Between Severity of Kawasaki Disease and History of Ischemic Heart Disease in the Parents

“…In a study by Sano T, patients who were non-responsive to intravenous immunoglobu- lin (IVIG) had higher CRP and aspartate aminotransferase (AST). Total bilirubin and Body surface area adjusted coronary dimensions were statistically more in diameter in non-responsive group (25). Kubayashi et al proved that sodium ≤ 133 mM/L, neutrophils > 80%, days of illness at initial treatment ≤ four days, AST, age in months ≤ two, platelet count < 300,000/µL and CRP ≥ 10 mg/dL were independent predictors of non-responsive-IVIG, but not for coronary complications (26).…”

“…Kubayashi et al proved that sodium ≤ 133 mM/L, neutrophils > 80%, days of illness at initial treatment ≤ four days, AST, age in months ≤ two, platelet count < 300,000/µL and CRP ≥ 10 mg/dL were independent predictors of non-responsive-IVIG, but not for coronary complications (26). The retrospective study which looked at risk factors for refractory KD in Japan resulted that in 20% of cases who did not respond to initial IVIG therapy, risk factors associated with the need for retreatment were initial treatment on/before the fifth day of illness, recurrent episodes of KD and male gender) (25). A scoring system by Nakano H. et al used age, CRP and platelet count to predict and determine the patients with higher chance for coronary problems (27).…”