The usefulness of neutrophil-to-lymphocyte ratio in predicting coronary artery dilation with Kawasaki disease / 中华实用儿科临床杂志

Objective To assess the neutrophil-to-lymphocyte ratio (NLR) to predict coronary artery dilation in patients with Kawasaki disease (KD).Methods The blood routine were collected from all patients with KD before intravenous immunoglobulin(IVIG) treatment and after 2 days of IVIG treatment.NLR was calculated through dividing the neutrophil count by the lymphocyte.Multivariate Logistic analysis and receiver-operating characteristic (ROC) curve were used to determine the value of NLR predicting coronary artery dilation and the risk factors of coronary artery dilation in KD.Results Of the 404 cases with KD,50 cases were coronary artery dilation.Compared with the patients without coronary artery dilatation,patients with coronary artery dilatation were more inclined to occur in males (76.0％ vs.51.7％,x2 =10.45,P ＜0.01) at younger ages[(26.5 ±7.1) months vs.(31.3 ±8.4) months,t =3.85,P ＜ 0.01],while the days of fever pre-IVIG treatment [(6.9 ± 1.6) d vs.(5.5 ± 1.2) d,t =7.38,P ＜ 0.01] and after IVIG treatment [(4.7 ± 1.3) d vs.(2.1 ± 0.9) d,t =17.97,P ＜ 0.01] as well as total fever days [(10.2 ± 3.7) d vs.(7.5 ± 2.5) d,t =6.68,P ＜ 0.01] were all longer.Meanwhile,before IVIG treatment,patients with coronary artery dilatation had higher leukocytes [(18.6 ± 5.2) × 109/L vs.(15.4 ± 4.4) × 109/L,t =4.70,P ＜0.01],NLR value (4.5 ±0.8 vs.3.1 ± 0.4,t =19.82,P ＜0.01),neutrophil [(13.7 ±6.3) × 109/L vs.(10.2 ± 4.3) × 109/L,t =5.05,P＜0.01] and C-reactive protein(CRP) [(108.4 ±26.9) mg/Lvs.(99.5 ±32.3) mg/L,t =1.86,P ＜ 0.05],and the differences were statistically significant.However,between coronary artery dilatation group and non-coronary artery dilatation group,the lymphocyte number,platelet and erythrocyte sedimentation rate were not significantly different before IVIG treatment (all P ＞ 0.05).And the WBC [(10.4 ± 5.2) × 109/L vs.(8.3 ± 4.6) × 109/L,t=3.04,P＜0.01],NLR value (2.1 ±0.7 vs.1.2 ±0.5,t =13.87,P ＜0.01),nentrophil [(8.2 ± 1.7) × 109/L vs.(5.3 ± 1.2) × 109/L,t =16.37,P ＜0.01],platelet (PLT) [(492.4 ± 68.3) × 109/L vs.(445.6 ± 82.4) ×109/L,t=3.84,P＜0.01],CRP [(46.2±28.8) mg/L vs.(19.5±10.8) mg/L,t=12.47,P＜0.01],ESR[(45.9 ±28.6) mm/1 h vs.(28.2 ± 15.7) mm/1 h,t =6.63,P ＜0.01] of patients with coronary artery dilatation after IVIG treatment were also higher than the patients without coronary artery dilatation,and all of the differences were statistically significant.The ROC curve result revealed that the best NLR cut-off value during the acute febrile phase for predicting coronary artery dilation was 4.51,and the area under the curve was 0.82 (95％ CI 0.75-0.89) with sensitivity and specificity of 0.78 and 0.80,respectively.At the same time the best NLR cut-off values in 2 days after IVIG for predicting coronary artery dilation was 1.46,and the area under the curve was 0.85 (95％ CI 0.79-0.92) with sensitivity and specificity of 0.84 and 0.79,respectively.Multivariate Logistic analysis revealed that the days of fever before and after IVIG treatment,total fever days,NLR before and after IVIG treatment,as well as WBC and CRP after treatment with IVIG were all independent predictive factors of coronary artery dilation development.Conclusion The NLR could be used to predict coronary artery dilation development in patients with KD.

Factors Predicting Response to Splenectomy in Patient with Immune Thrombocytopenia Purpura

OBJECTIVE: Splenectomy has been proposed to be the standard therapy for patients with steroid refractory immune thrombocytopenic purpura (ITP). This study aimed to describe valuable factors predicting the effect of splenectomy in patients with ITP. METHODS: A total of 51 adult patients who underwent splenectomy for steroid refractory ITP were evaluated their medical records retrospectively. The response to the treatment was classified on the basis of the platelet count. RESULTS: The responding group included 35 patients (68.8%), the partial-responding group included 4 patients (7.8%), and non-responding group was 12 patients (23.5%). On univariate analysis, the response of splenectomy correlated with only the intravenous immune globulin (IVIG) response (66.7%, P=0.006), but hemolysis, autoantibody, a presence of accessory spleen, the response of steroid were not significantly associated with the effect of splenectomy. On multivariate analysis, the response of IVIG and the amount of platelet transfusion were independent variables of the response of splenectomy. CONCLUSION: Patients with ITP who have good responses to IVIG are likely to have a good or favorable responses to splenectomy.

Clinical characteristics and progress of Kawasaki disease patients who had early treatment with intravenous immune globulin / 소아과

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+/-17.3 vs. 81.9+/-13.4, P=0.002), duration of fever after initial IVIG (3.8+/-0.5 days vs. 2.1+/-0.2 days, 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.

Coronary Complication according to Retreatment of Immune Globulin in Kawasaki Disease

PURPOSE: Recently most of patients with Kawasaki disease (KD) get treatment within several days of illness. But, some patients still suffer from coronary complication (CC) despite early initial treatment with intravenous immune globulin (IVIG) and even the additional therapy. We investigated the risk factors of CC in non-responders to initial therapy who needed additional IVIG infusion among patients with KD. METHODS: Forty five non-responders to initial IVIG who got additional IVIG infusion were reviewed from 1996 to 2007. We devided patients into two groups with CC (group A, n=17) or without CC (group B, n=28). Clinical characteristics, timing of additional IVIG infusion and laboratory results were reviewed. And we investigated the differences between the two groups and tried to find risk factors of CC. RESULTS: In comparison between the two groups, CC, clinical characteristics and timing of IVIG infusion were not different between two groups. But, total febrile days were significantly longer and peak platelets counts were significantly higher in group A (P=0.006, P=0.013). On the logistic regression analysis, total febrile days longer than 10.5 days was the only risk factor of CC in these patients. CONCLUSION: Our results showed that patients with CC inspite of repeated IVIG therapy had longer fever duration. So, additional therapy besides re-treatment with IVIG aiming at shortening total duration of fever seems to be important in refractory KD to prevent CC.

Manifestation of Coronary Artery Lesions after Immunoglobulin Re-treatment in Initial Immunoglobulin-resistant Kawasaki Disease / 소아과

PURPOSE: To evaluate the predictable factors for why initial intravenous immune globulin(IVIG) therapy failed and the outcome of coronary lesions after additional IVIG retreated in initial IVIG-resistant Kawasaki disease(KD). METHODS: Retrospective studies were performed on 284 cases of KD treated with one episode of high-dose IVIG and 63 cases with additional IVIG retreatment at this hospital from January 2000 to June 2003. 2D echocardiogram was done at admission, two months later and every two or three months when coronary lesion had improved more than two months later. RESULTS: In 69(24.3%) of 284 cases with post-first course of IVIG therapy, 19(43.2%) of 63 cases with additional IVIG retreatment, coronary abnormality had been shown by initial 2D-echocardiogram examined at acute stage. In five(1.8%) of 284 patients with post-first course of IVIG therapy, and in three(4.8%) of 63 cases with additional IVIG retreatment, coronary lesions still remained at follow-up echocardiogram. Even though there was a tendency of increased coronary lesions in the group with additional IVIG retreatment, there was no significant differences in the incidence of coronary lesions between the two groups. There were no significant differences in age, sex, and other clinical findings between the two groups. CONCLUSION: Combination therapy with high doses of IVIG and aspirin is generally effective as a standard treatment for KD but not always. Coronary lesion did not increased despite additional IVIG therapy for initial IVIG-resistant KD. There was no predictable factor for initial IVIG-resistant KD.

High-dose Intravenous Immune Globulin Retreatment in Kawasaki Disease

PURPOSE: To determine clinical features, laboratory findings and cardiac abnormalities of high- dose immune globulin(IVIG) retreatment in patients with Kawasaki disease, and to report effectiveness of retreatment. METHODS: Retrospective study of 174 children diagnosed with Kawasaki disease at Ewha Mokdong hospital from March, 1999 to July, 2001. RESULTS: Twenty(11.5%) of 174 patients were retreated with high-dose IVIG. After this, only two patients(1.1%) did not respond to IVIG retreatment. Patients with failure to respond to initial IVIG did not differ from the patients who responded to a single course of IVIG in sex, age, days of fever at initial IVIG and clinical characteristics. Compared with responders with single IVIG treatment, the patients who were retreated had significantly lower albumin(3.7 vs 3.4 g/dL, P< 0.05), higher ALT(118.2 vs 229.3 U/L, P<0.05) and CRP(8.9 vs 13.3 mg/dL, P<0.05). On echocardiography, patients who recieved IVIG retreatment were significantly more likely to have caronary abnormalities(45.0% vs 13.6%, P<0.05). CONCLUSION: Retratment with IVIG for persistent or recurrent fever was safe and effective.

Experience of High-Dose Intravenous Immune Globulin Therapy for Neonatal Immune Hemolytic Jaundice due to ABO Incompatibility

PURPOSE: Neonatal immune hemolytic jaundice due to blood group incompatibility is important to treat properly because of an early rise and a high peak of serum bilirubin level and a risk of kernicterus. The conventional therapeutic modalities for neonatal immune hemolytic jaundice due to blood group incompatibility are phototherapy and exchange transfusion. We evaluated the effect of intravenous immune globulin (IVIG) therapy on hyperbilirubinemia due to ABO incompatibility. METHODS: This study included 6 infants with hyperbilirubinemia due to ABO incompatibility who were admitted to the nursery of Eulji Medical Center, Nowon Hospital, from January 2000 to February 2001. All 6 infants had a positive direct Coombs test. Their serum bilirubin levels were above 12 mg/dl within 24hours of age and above 20 mg/dl after 24hours of age. They were treated with intensive phototherapy and IVIG. RESULTS: We classified the effective group when a decline in serum bilirubin level was more than 2 mg/dl in 3-4 hours after IVIG therapy, and the ineffective group when there was a decline in serum bilirubin level less than 2 mg/dl, a re-rise after the initial response to IVIG, or a decline after the combined therapy with intensive phototherapy and IVIG equal or less than that after intensive phototherapy alone. In the effective group (n=2), the average decline in serum bilirebin level was 4.1 mg/dl in 3-4 hours and 8.1 mg/dl in 12-16 hours after IVIG therapy, while in the ineffective group (n=4), the average decline was 1.9 mg/dl and 2.7 mg/dl, respectively. Five among 6 infants were treated with IVIG therapy and 1 infant was treated with exchange transfusion. No serious side effect was detected during and after IVIG therapy. CONCLUSION: We demonstrated the effectiveness of IVIG therapy in 2 infants out of six who were treated with intensive phototherapy and IVIG for hyperbilirubinemia due to ABO incompatibility. IVIG therapy could be considered if hyperbilirubinemia due to ABO incompatibility does not respond to intensive phototherapy alone. Further prospective and randomized studies would be needed.

Predictive Values of High Dose Immune Globulin G or Oral Prednisone Therapy for the Splenectomy Response in Patients with Chronic Idiopathic Thrombocytopenic Purpura / 대한소아혈액종양학회지

PURPOSE: The aim of this study is to investigate the usefulness of responsiveness to high dose intravenous immune globulin G (IVIG) or oral prednisone therapy as preoperative predictors for splenectomy response in patients with chronic idiopathic thrombocytopenic purpura (ITP). METHODS: We reviewed retrospectively the charts of 23 patients who were admitted to Yonsei Medical Center, Wonju Christian Hospital, Ajou Medical College Hospital and Pochon CHA General Hospital under the diagnosis of chronic ITP and plenectomized from January 1990 to April 1999, below the age of 20. All of the patients had been treated with high dose IVIG and, or oral prednisone. The responses to the treatments were classified according to Berchtold and McMillan's criteria (1) complete response (CR) 50 103/L. RESULTS: Of 23 patients, 12 boys and 11 girls, the mean age at operation was 12.4 years (5.4~19.4 years), the mean duration from diagnosis to splenectomy was 47 months (6~173 months) and mean follow up was 33 months (3~95 months). Of the 6 patients with responses to oral prednisone, 5 had responses to splenectomy and of the 12 patients with reponses to IVIG, 10 had responses to splenectomy at 3 months. All of 14 patients with no response to oral prednisone and 4 patients with no response to IVIG were responsed to splenectomy at 3 months. Four patients relapsed during follow up and there was no serious complication following splenectomy. CONCLUSION: We concluded that a positive response to oral prednisone or IVIG may be associated with a positive response to subsequent splenectomy and splenectomy is an effective and safe treatment.

Effect of High-dose Intrevenous Immune Globulin in the Treatment of Neonatal Immune Hemolytic Jaundice Unresponsive to Phototherapy / 대한주산의학회잡지

OBJECTIVE: Immune hemolytic jaundice is caused by the destruction of antibody-sensitized erythrocytes and is associated with antibody-dependent cellular cytotoxic effects mediated by Fc receptor-bearing cells of the reticuloendothelial system. Intravenous immune globulin(IVIG) may have exerted its effect through Fc receptor blockade. We studied the effect of high-dose intravenous immune globulin(HDIVIG) in neonatal hemolytic jaundice unresponsive to phototherapy. METHODS: We selected only those with Coombs test(+) immune hemolytic jaundice who had admittcd at the NICU of the Dcpartment of Pediatzics of Dongsan Medical Center, Keimyung University between January 1995 and December 1998. They were unresponsive to phototherapy. Ten newborn infants(9 ABO incomplatibilities, l minor group incompatabillity due to anti-E) received HDIVIG therapy combined with phototherapy. IVIG was given as a dose of lg/kg for 6 hours, and serial hemoglobin, reticulocyte count, and bilirubin levels were evaluated. If the serum bilirubin level went up and reached the level above 22mg/dl, we conducted exchange transfusion for the patient. RESULTS: HDIVIG induced a significant decrease of serum billirubin levels in 8(80%, group I, HDIVIG responsive poup) of 10 cases and only 2 cases(group II, HDIVIG unreponsive group) required exchange tnnsfusions. No side effect was observed after HDIVIG therapy. CONCLUSION: We suggest HDIVIG may be effective in the treatment of phototherapy-resistant hyperbilirubinemia due to blood group incompatibility. More studies are needed to confirm the optimal dosage and therapeutic indication of HDIVIG in the therapy of neonatal immune hemolytic jaundice.

Treatment of Intravenous Immune-Globulin Resistant Kawasaki Disease with Corticosteroids

PURPOSE: To evaluate the efficacy of steroid therapy on prevention of development and progression of coronary artery aneurysm in intravenous immune globulin (IVIG)-resistant Kawasaki disease, we treated three children with high dose of intravenous methylprednisolone followed by low dose oral prednisolone. METHODS: We selected three children with Kawasaki disease who did not repond or who initially responded but soon developed recrudescent fever after retreatment of IVIG (total 4gm/kg). These three patients were treated with high dose methylprednisolone (10mg/kg) intravenously and followed by low dose prednisolone (1mg/kg) orally for 7 days. Echocardiographic evalutions were performed within 8 days of admission (before steroid therapy), at discharge and 1 month after discharge. RESULTS: All three patients showed rapid normalization of clinical symptoms and did not developed significant coronry artery abnormalities. No adverse reaction was observed. CONCLUSIONS: Steroid therapy (mini pulse methylprednisolone and prednisolone therapy) is valuable for patients with Kawasaki disease resistant to intravenous immune globulin therapy.

Effects of intravenous immune globulin on the peripheral lymphocyte phenotypes in Kawasaki disease

The effect of intravenous immune globulin (IVIG) on the lymphocyte phenotypes in acute Kawasaki disease (KD) was studied in a random trial of IVIG-and-aspirin versus aspirin-alone. Before therapy, patients in each treatment group had an increased percentage of B cells, and a decreased percentage of T cells, CD4 T cells, CD8 T cells and CD5+ B cells. There was no significant difference in immunologic parameters between the two groups measured before therapy. Patients treated with IVIG-and-aspirin had by the fourth day developed a highly-significant increase in T cells, CD4 T cells and CD8 T cells and a decrease in B cells. Despite the decrease of B cells, there were significant increases in CD5+ B cells in both treatment groups. However, the degree of increase in the IVIG-and-aspirin treated group was significantly more noticeable than that in the aspirin-alone treated group. These findings indicate that treatment with IVIG restores the T- and B- cell abnormalities, especially CD5+ B-cell abnormalities found in patients with acute KD.

Effects of intravenous immune globulin on the peripheral lymphocyte phenotypes in Kawasaki disease

The effect of intravenous immune globulin (IVIG) on the lymphocyte phenotypes in acute Kawasaki disease (KD) was studied in a random trial of IVIG-and-aspirin versus aspirin-alone. Before therapy, patients in each treatment group had an increased percentage of B cells, and a decreased percentage of T cells, CD4 T cells, CD8 T cells and CD5+ B cells. There was no significant difference in immunologic parameters between the two groups measured before therapy. Patients treated with IVIG-and-aspirin had by the fourth day developed a highly-significant increase in T cells, CD4 T cells and CD8 T cells and a decrease in B cells. Despite the decrease of B cells, there were significant increases in CD5+ B cells in both treatment groups. However, the degree of increase in the IVIG-and-aspirin treated group was significantly more noticeable than that in the aspirin-alone treated group. These findings indicate that treatment with IVIG restores the T- and B- cell abnormalities, especially CD5+ B-cell abnormalities found in patients with acute KD.

Study on the Restraining Factors in the Intravenous Immune Globulin(IVIG)Bacterial Endotoxin Test / 中国药房

OBJECTIVE:To study the restraining factors in the intravenous immune globulin(IVIG.)bacterial endotoxin test.METHODS:A series tests were designed;the sensitivity of limulus was checked and the limit of endotoxin was validated;the effects of vehicle and pH value on the IVIG endotoxin test results were observed so as to find out the chief restraining factors of this test method.RESULTS:Lower pH value has an inhibition effect on the in IVIG bacterial endotoxin test.CONCLUSION:Bacterial endotoxin test can replace the rabbit testing method in the pyrogen test of IVIG.When the condition of lower pH is changed.