• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.817-820
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• 2003

Purpose : Intravenous immunoglobulin(IVIG) has been used as an immunomodulatory treatment for several immune-mediated diseases. The early effect of high-dose IVIG on biochemical profiles including lipids and proteins was evaluated in patients with Kawasaki disease(KD). Methods : Twelve children with KD(nine boys) were treated with IVIG of 2 g/kg over 12 hours. Serial sera were collected from the patients four times : before IVIG treatment and two hours, 24 hours and seven days after IVIG treatment. The samples were frozen at $-20^{\circ}C$ before biochemical analysis. Results : A significant decrease in albumin concentration was found two hours h and 24 hours after IVIG treatment, but this recovered to the pretreatment level after seven days. Total cholesterol and triglyceride increased slightly after seven day. A significant decrease in HDL-cholesterol and C-reactive protein was seen two hours and 24 hours after IVIG treatment. Conclusion : High-dose IVIG affects immediate changes in protein profiles and HDL-cholesterol in KD. Changes in HDL-cholesterol induced by IVIG may be the result of changes in systemic protein metabolism.

• Pediatric Infection and Vaccine
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• v.15 no.2
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• pp.180-187
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• 2008

Purpose : We wanted to determine the characteristics of patients with Kawasaki disease (KD) who were unresponsive to intravenous immunoglobulin (IVIG). Methods : The patients with KD were divided into two groups: the IVIG responsive group (25 cases) and the IVIG unresponsive group (14 cases). We analyzed various parameters before and after the administration of IVIG, including the complete blood cell count with the differential count (%), the erythrocyte segmentation rate (ESR), the C-reactive protein (CRP) level and the protein and lipid profiles. Results : The IVIG unresponsive group had a prolonged duration of fever and a higher incidence of CAL compared to the IVIG responsive group (P<0.001, respectively). Before IVIG infusion, the neutrophil differential, the ESR and the CRP values were higher (P<0.001), and the total protein and albumin values were lower in the IVIG unresponsive group (P=0.01) compared to the IVIG responsive group. After IVIG infusion, there were no significant changes in the WBC count and CRP levels in the IVIG unresponsive group. The reduction of the HDL-cholesterol levels by IVIG was more significant in the unresponsive group (P=0.02). Conclusion : A more severe and prolonged inflammatory response occurred in the IVIG unresponsive group at an early stage, and this finding can be detected by such inflammatory parameters as the neutrophil count and the CRP and HDL-cholesterol levels after IVIG infusion.

• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.204-208
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• 2008

Purpose : The aim of this study was to investigate the incidence and course of neutropenia following intravenous immunoglobulin (IVIG) therapy in children with idiopathic thrombocytopenic purpura (ITP). Methods : From January 2001 to June 2006, fifty-four patients with ITP were enrolled in this study. Forty-two of 54 patients were treated with IVIG, while the other 12 were treated with anti-D immunoglobulin (Anti-D Ig). Post-treatment absolute neutrophil counts (ANC) were compared between patients who received IVIG and those who received Anti-D Ig. Comparison of post-treatment ANC between patients who treated with two different IVIG regimens (400 mg/kg/day for 5 days and 1 g/kg/day for 2 days) was also performed. Results : Pretreatment ANC were not significantly different between the two treatment groups. After treatment with IVIG, 32 out of 42 patients (76.2%) showed more than 50% decrease of ANC from the baseline. On the other hand, only 2 out of 12 patients (16.7%) showed more than 50% decrease of ANC from the baseline after treatment Anti-D Ig. No significant difference was observed in the decline of ANC between the first IVIG treatment (42 patients) and repeated IVIG treatment groups (7 patients). There was no statistical difference in post-treatment ANC between patients who treated with two different IVIG regimens. The neutropenia induced by IVIG had resolved spontaneously in 38 out of 39 patients (97%) after several days. Conclusion : Neutropenia following IVIG administration may not be an uncommon finding in children with ITP. It seems to be transient and self limited.

• Clinical and Experimental Pediatrics
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• v.48 no.11
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• pp.1187-1192
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• 2005

Purpose : The purpose of this study is to determine the effectiveness of intravenous immunoglobuin (IVIG) administration in fullterm neonates having clinically suspected neonatal sepsis. Methods : Forty full-term neonates admitted to the neonatal intensive care unit with clinically suspected neonatal sepsis, who had at least two positive diagnostic criteria were enrolled. Twenty neonates were enrolled into the IVIG arm and 20 in the placebo arm. Neonates with a gestational age of less than 36 weeks and those with any major congenital malformation were excluded. The neonates were randomized to receive 1 g/kg of IVIG or equivalent amount of normal saline. The treatments including antibiotics and supportive care were administered. Results : The neonates in the therapy and placebo groups were comparable in terms of birth weight, gestational age, sex distribution, duration of antibiotics therapy and admission, elevation of serum IgG level, mortality rate, change of CBC, and serum level of acute phase reactants etc. Conclusion : Serum IgG values increased significantly 5 days after administration of IVIG in the IVIG-treated group and decreased significantly 5 days after administration of normal saline in the placebo group. However, there was no significant difference in the duration of antibiotics therapy and admission, or of mortality between the IVIG-treated and placebo groups. No adverse reactions to the IVIG infusions were noted during the study. Our preliminary observations suggest that the administration of 1 g/kg IVIG to neonates had some effect on augmentation of humural immune status in neonates with clinically suspected sepsis. But further study is needed to verify the benefit of IVIG infusion to neonatal sepsis.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.886-893
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• 2005

Purpose : Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin(IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor(VEGF)-induced tube formation of endothelial cells in vitro on Matrigel assay. Methods : Human umbilical vein endothelial cells(HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents : VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. Results : IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. Conclusion : We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.

• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.306-312
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• 1993

To evaluate the meaning of anti-HCV detection in patients treated with IVIG, serum levels of aspartate aminotranstferase(AST), alanine aminotransterase(ALT), HCV Ab titer were measured after treatment with IVIG in 36 patients diagnised of Kawasaki disease or neonatal sepsis. Also polymerase chain reaction (PCR) for the detection of HCV was done in 8 patients with persistent HCV Ab positivity at 3 months after IVIG treatment. The results were as follows 1) HCV Ab was positive in all 36 patients at 1 week after IVIG treatment, but in only 8 cases it was positive at 3 months after IVIG treatment. 2) AST, ALT were elevated in 9 cases at 1 week after IVIG treatment, but they were normalized in all cases at 3 months after IVIG treatment. 3) PCR for the detection of HCV was done in 8 patients with persistent HCV Ab positivity at 3 months after IVIG treatment, but HCV was not isolated in any cases. These results suggested that detection of anti-HCV was merely transitory phenominon of HCV Ab transmission, did not show any evidence of HCV infection due to HCV transmission.

• Pediatric Infection and Vaccine
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• v.5 no.1
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• pp.147-151
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• 1998

On the treatment of Kawasaki disease, approximately 10% of children treated with IVIG have persistent or recrudescent fever despite IVIG treatment. We had experienced two children with Kawasaki disease who did not respond after multiple dosages of IVIG. They were treated within the first 10 days of onset of fever and were given oral aspirin (100mg/kg/day) and IVIG(2gm/kg) in a single infusion for 8 to 10 hours. The first child had not resolution of symptoms after three intravenous doses of IVIG(total 4gm/kg). And then treated with high dose methylprednisolone(30mg/kg) for 2 to 3 hours intravenously without symptoms improvement. On fifth hospital days, he was retreated with IVIG (2gm/kg) again with ultimate resolution of symptoms. The second child had resolution of symptoms after three intravenous doses of IVIG(total 4gm/kg). No adverse events were associated with the administration of IVIG or steroid. We reported two cases of IVIG non-responded Kawasaki disease with a brief review of the related literatures.

• Clinical and Experimental Pediatrics
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• v.50 no.10
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• pp.1005-1010
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• 2007

Purpose : To determine the optimal time of high dose intravenous immune globulin (IVIG) treatment, we analysed the clinical characteristics and progress of a group of Kawasaki disease patients who had early treatment with IVIG. Method : A retrospective study was conducted of 188 patients with Kawasaki disease who were admitted to Yeungnam University Medical Center from January 2000 to December 2005. All patients were treated with a high dose IVIG and high dose aspirin for the initial acute phase treatment. The early treatment group consisted of 94 patients who received treatment before 5 days of fever, and the conventional group consisted of 94 patients who were treated on or after day 5. The patients' sex, age, laboratory findings, total duration of fever, duration of fever after initial IVIG, need for additional IVIG and coronary artery status were noted. Result : There were no significant differences between the two groups in sex ratio and age. No significant differences were noted in the level of WBC count, ESR, CRP, serum albumin, LDH, total duration of fever and coronary abnormality. But the value of ALT($151.8{\pm}17.3$ vs. $81.9{\pm}13.4$, P=0.002), duration of fever after initial IVIG ($3.8{\pm}0.5days$ vs. $2.1{\pm}0.2days$, P=0.003), and rate of additional IVIG (15.9% vs. 6.3%, P=0.037) were significantly higher in the early treatment group. There was no significant difference in initial dose of IVIG, but dosage of aspirin was lower in early treatment group (P=0.037). Conclusion : There is no evidence that early treatment of IVIG has greater efficacy in preventing cardiac sequelae than conventional treatment. In addition, early treatment is likely to result in a greater requirement for additional IVIG treatment.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.133-137
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• 1998

Purpose : To investigate renal toxicity of high-dose intravenous immunoglobulin(IVIG) in children with Kawasaki disease and idiopathic thrombocytopenic purpura. Methods : 23 children with Kawasaki disease and 7 children with idiopathic thrombocytopenic purpura who were treated with high-dose IVIG(2 g/kg) were evaluated for the change of urine output, blood urea nitrogen(BUN), serum creatinine(Scr), creatinine clearance(Ccr), tubular reabsorption of phosphorus(TRP), fractional excretion of sodium(FENa), 24hour urine ${\beta}_2$-microglobulin/creatinine(${\beta}_{2}MG/cr$) ratio and urine microalbumin/creatinine(MA/cr) ratio at post-IVIG 1 and 3 day. Results : There was no significant change of urine output, BUN, Scr, Ccr, TRP, 24hour urine ${\beta}_{2}MG/cr$ and MA/cr ratio after high-dose IVIG treatment. Transient increase of FENa at post-IVIG 1 day was the only significant change. Conclusion : There was no significant renal toxicity of high-dose IVIG in children with Kawasaki disease and idiopathic thrombocytopenic purpura who had normal renal function.

• Clinical and Experimental Pediatrics
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• v.48 no.4
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• pp.416-424
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• 2005

Purpose : To find the risk factors associated with coronory artery lesions, non-responsiveness to intravenous immunoglobulin(IVIG) treatment, and recurrences in Kawasaki disease patients. Methods : We retrospectively analyzed 1,000 Kawasaki disease patients who were admitted to Yonsei University Medical Center from September 1990 to December 2003. We compared between responder and non-responder groups to IVIG treatment as well as between relapsed and non-relapsed groups, and as to the relapsed group, we also compared variables between patients in their first and second attack states. Finally, factors associated with longer-fever duration from disease onset were evaluated. Results : Longer fever durations before and after IVIG treatment, male sex, lower Hgb and Hct level, higher WBC count and segmented WBC proportion, and higher CRP and Harada's score were related with coronary artery lesions. Non-responsiveness was related to higher WBC count, segmented WBC proportion, CRP, SGPT, Harada's score, and pyuria. Moderate-to-severe coronary artery dilatations and recurrences were more commonly seen among the non-responder group. No significant predictive factors for recurrence were found. In the relapsed group, lower WBC count, CRP, and shorter fever duration from disease onset were observed in their second attack state. Fever duration from disease onset showed positive correlation with WBC count, CRP, and Harada's score and negative correlation with Hgb levels. Conclusion : Higher WBC count, CRP, and higher Harada's score were related to both higher incidences of coronary artery lesions and non-responsiveness to IVIG treatment, and these factors were also related with longer fever duration. Non-responders to IVIG treatment showed higher recurrence rate and more moderate-to-severe coronary artery dilatations than responders.