Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin. Optimal dosage and differences in therapeutic efficacy of IGIV in Kawasaki disease. Intravenous gamma-globulin for Kawasaki disease. Intravenously administered immunoglobulin in the treatment of childhood Guillain-Barré syndrome: a randomized trial. Selective high dose gamma-globulin treatment in Kawasaki disease: assessment of clinical aspects and cost effectiveness. High-dose gammaglobulin therapy for Kawasaki disease. A multicenter, randomized, controlled trial of intravenous gamma globulin therapy in children with acute Kawasaki disease. Comparison of intravenous immunoglobulin and plasma exchange in treatment of mechanically ventilated children with Guillain Barré syndrome: a randomized study. Randomized comparison of ganciclovir plus intravenous immune globulin (IVIG) with IVIG alone for prevention of primary cytomegalovirus disease in children receiving liver transplants.
Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay. In an initial study, three groups of patients with Kawasaki disease received either aspirin alone or alkylated immunoglobulin G intravenous preparation (IGIV) 200 mg/kg daily x 3 days + aspirin, or 400 mg/kg alkylated IGIV daily x 3 days + aspirin. In a second study, three groups of patients were treated with either 100, 200 or 400 mg/kg of native IGIV in combination with aspirin daily for 5 days. While the regimen of 200 mg/kg native IGIV daily x 5 days was found to be effective, the incidence of coronary artery lesions (CAL) was even less on a regimen of 400 mg/kg daily x 5 days. It is therefore suggested that a better therapeutic effect can be achieved with a 400 mg/kg dose of native IGIV. Based on the results from these two studies, it is assumed that native IGIV is more effective in inhibiting CAL formation and persistence than the chemically modified preparation in which the biological activity of the Fc region in the immunoglobulin G molecule is altered. We studied the effect of gamma-globulin (IVGG) and aspirin (ASA) on the development of the coronary artery lesions (CAL) of Kawasaki disease (KD) in three different protocols. Within 29 days of the onset of KD the echocardiographic evidence of CAL had developed in 39-42% of the patients in the ASA group, but only in 13.7-20.8% of the patients treated with IVGG (200 or 400 mg/kg X 5). In long-term follow-up observation of CAL of these patients the evidence of CAL in both the ASA and the IVGG group regressed gradually; however, the residual rate of CAL was significantly low in the IVGG group at all times up to 24 months after onset. These facts suggest that when using IVGG for KD, we should select a dose of intact gamma-globulin, 1,000 mg/kg or more in total, to prevent the occurrence of CAL. We have demonstrated not only a significant reduction in the occurrence of CAL in patients treated with IVGG but a reduction in the residual rate of CAL for two years as compared with those treated by ASA. To determine the optimal treatment for childhood Guillain-Barré syndrome (GBS).
                We performed a randomized, multicenter study of GBS according to international diagnostic criteria. In study 1 (early treatment), children able to walk unaided for 5 meters were randomized for 1 g/kg intravenously administered immunoglobulin (IVIG) over 2 days or no treatment. The primary outcome measure was the degree of disability at nadir. In study 2 (treatment for severe GBS), children unable to walk 5 meters unaided were randomized for 1 g/kg IVIG over 2 days or 0.4 g/kg IVIG over 5 days. The primary outcome measure was the number of days needed to regain the ability to walk unaided. Children randomized for no treatment in study 1 could enter study 2 if loss of unaided walking occurred.
                Ninety-five children with GBS were registered in 40 months. Twenty-one children were randomized in study 1 and 51 in study 2 (5 after deterioration in study 1). Twenty-eight children were not randomized for various reasons. Eleven of 21 patients in study 1 lost the ability to walk unassisted and 6 were bedridden, with no statistically significant difference between the children initially randomized for treatment versus no treatment. Recovery occurred faster in the group randomized for early treatment. In study 2, recovery did not differ significantly between the children treated for 2 days versus 5 days (median time to unaided walking: 19 days vs 13 days). Secondary transient deterioration in the disability score occurred more frequently in the group with the 2-day regimen than in the group treated for 5 days (5 of 23 patients vs 0 of 23 patients). Multivariate analysis with Cox regression showed that disease severity at the nadir was the only prognostic factor for recovery.
                Treatment with IVIG before loss of unaided walking did not give rise to a less severe course, but recovery occurred somewhat faster. However, given the small number of patients, the power of this conclusion is low. For treatment after loss of unaided walking, there was no significant difference in the effectiveness of 2 g/kg IVIG administered over 2 days versus 5 days. Early "relapses" occurred more frequently after the shorter treatment regimen. High-dose intravenous gamma-globulin (IVGG) plus aspirin (ASA) treatment is effective in preventing coronary artery complications in acute Kawasaki disease (KD). However, gamma-globulin is very expensive, especially in Japan. Furthermore the indication for IVGG treatment and the optimal dose of gamma-globulin remain controversial.
                To examine these two issues, we used Harada's scoring system to investigate whether a single 2 g/kg dose therapy has any advantage over the 5 day 400 mg/kg per day therapy.
                We studied 203 patients with KD who had no coronary artery complications on admission. Of these, 145 patients scored 4 or more on Harada score within the first 9 days of illness and were treated with IVGG treatment. Using a random number table, 72 patients were selected to receive a single 2 g/kg dose (2 g group), while the remaining 73 patients were treated with 400 mg/kg per day for 5 consecutive days (400 mg group). Those who had a Harada score of three or less received no IVGG (non-IVGG group) treatment (58 patients).
                The incidence rate of coronary artery complications in the 2 g group was significantly lower than in the 400 mg group. The duration of high fever, positive duration of C-reactive protein and the number of hospital days in the 2 g group were each significantly shorter than in the 400 mg group. The total medical expense in the 2 g group was significantly lower than in the 400 mg group. There were no coronary artery complications in the non-IVGG group.
                It was found to be clinically more effective and more cost effective to select a patient by Harada's scoring system and, where a score of four or more was obtained, to administer a single 2 g/kg intravenous dose of gamma-globulin for acute KD. To evaluate the effectiveness of gammaglobulin in decreasing the incidence of coronary artery lesions in Kawasaki disease, a randomized controlled study in 136 patients was conducted using high doses of gammaglobulin 400 mg/kg/d for 3 days plus aspirin 30 mg/kg/d (gammaglobulin group) and aspirin alone at the same dosage (aspirin group). The total febrile period and the duration of fever after treatment were significantly shorter in the gammaglobulin group than in the aspirin group (P less than 0.001). The incidence of coronary artery lesions and of coronary artery aneurysms was significantly lower in the gammaglobulin group than in the aspirin group up to 30 days after the onset of Kawasaki disease (P less than 0.01 and P less than 0.05, respectively). In 16 of 69 patients given gammaglobulin, fever persisted for longer than 3 days, and there was a higher incidence of coronary artery lesions among them. The effectiveness of high doses of gammaglobulin in preventing coronary artery lesions has been demonstrated, but the indications and the optimal dose of gammaglobulin remain to be determined. We studied the effect of intravenous, polyethyleneglycol-treated, human immunoglobulin, administered at 200 mg/kg per day (group A: n = 147; male 86, female 61; age < 1 year, 50) or 400 mg/kg per day (group B: n = 152; male 87, female 65; age < 1 year, 52) for five consecutive days and compared it with freeze-dried, sulfonated human immunoglobulin [group C: n = 152; male 87, female 65; age < 1 year, 51), administered at 200 mg/kg per day for five consecutive days, on the prevention of coronary artery abnormalities in Kawasaki disease. Echocardiograms were interpreted blindly and independently. Proportions of 87.1%, 95.4%, and 82.3% in groups A, B, and C, respectively, had no coronary artery abnormalities. The confidence limits of difference between the proportions of groups A and C, groups B and C, and groups B and A were -4.4% and 10.4%, 7.8% and 15.9%, and 4.0% and 10.8%, respectively. Duration of fever and serum immunoglobulin G (IgG) levels were correlated with the prevalence of coronary artery abnormalities. We concluded that intravenous, polyethyleneglycol-treated, human immunoglobulin and freeze-dried, sulfonated human immunoglobulin had clinically equivalent effects on coronary artery abnormalities, and that five daily doses of 400 mg/kg of intravenous, polyethyleneglycol-treated, human immunoglobulin is more effective than that of 200 mg/kg gamma globulin. Respiratory failure is a life threatening complication of Guillain Barré syndrome (GBS). There is no consensus on the specific treatment for this subset of children with GBS.
                This was a prospective randomized study to compare the outcome of intravenous immunoglobulin (IVIG) and plasma exchange (PE) treatment in children with GBS requiring mechanical ventilation. Forty-one children with GBS requiring endotracheal mechanical ventilation (MV) within 14 days from disease onset were included. The ages of the children ranged from 49 to 143 months.Randomly, 20 children received a five-day course of IVIG (0.4 g/kg/day) and 21 children received a five-day course of one volume PE daily. Lumbar puncture (LP) was performed in 36 patients (18 in each group).
                Both groups had comparable age (p = 0.764), weight (p = 0.764), duration of illness prior to MV (p = 0.854), preceding diarrhea (p = 0.751), cranial nerve involvement (p = 0.756), muscle power using Medical Research Council (MRC) sum score (p = 0.266) and cerebrospinal fluid (CSF) protein (p = 0.606).Children in the PE group had a shorter period of MV (median 11 days, IQR 11.0 to 13.0) compared to IVIG group (median 13 days, IQR 11.3 to 14.5) with p = 0.037.Those in the PE group had a tendency for a shorter Pediatric Intensive Care Unit (PICU) stay (p = 0.094).A total of 20/21 (95.2%) and 18/20 (90%) children in the PE and IVIG groups respectively could walk unaided within four weeks after PICU discharge (p = 0.606).There was a negative correlation between CSF protein and duration of mechanical ventilation in the PE group (p = 0.037), but not in the IVIG group (p = 0.132).
                In children with GBS requiring MV, PE is superior to IVIG regarding the duration of MV but not PICU stay or the short term neurological outcome.The negative correlation between CSF protein values and duration of MV in PE group requires further evaluation of its clinical usefulness.
                Clinicaltrials.gov Identifier NCT01306578. A randomized placebo-controlled trial was conducted to determine the benefit of ganciclovir (5 mg/[kg x d]) for 30 days in addition to intravenous immune globulin (IVIG) for 16 weeks for prevention of primary cytomegalovirus (CMV) disease in children receiving liver transplants. Patients were monitored for 6 months after transplantation. The two groups of patients (recipients of 29 ganciclovir plus IVIG and 27 recipients of IVIG alone) were similar in terms of age, sex, and underlying disease. The incidence of CMV disease among the ganciclovir plus IVIG recipients and the IVIG alone recipients was 17% and 26%, respectively, and the time to disease in these recipients was 46 days and 32 days, respectively. There was no difference between groups in terms of survival; episodes of rejection, bacteremia, or fungemia; use of immunosuppressive agents; and incidence of leukopenia or thrombocytopenia. These results suggest that a 4-week course of ganciclovir with IVIG is not more effective than IVIG alone for prevention of primary CMV disease. Since short-term prophylaxis with ganciclovir may delay the onset of CMV disease, further studies with a longer course of ganciclovir prophylaxis are warranted.
Children fulfilling the diagnostic criteria for Kawasaki disease should be treated with IVIG (2 gm/kg single dose) within 10 days of onset of symptoms.