Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease

Objectives: Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are <5 years old. Intravenous immunoglobulin (IVIG) is the standard therapy for KD. However, many patients with KD still show poor response to initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Methods: Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG‐responsive and IVIG‐resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. Results: A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8–562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C‐reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Conclusion: Pre‐IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD.     

Immunoglobulin Failure and Retreatment in Kawasaki Disease

Several cases of Kawasaki disease (KD) were unresponsive to the initial treatment with intravenous immunoglobulin (IVIG). We retrospectively analyzed all children admitted with KD to determine the occurrence and variables associated with the initial IVIG treatment failure. All patients who fulfilled the criteria for KD and were treated with a single dose (2 g/kg) of IVIG between January 1995 and August 2001 were enrolled. An analysis of the patients who had initially failed to respond to IVIG was performed. A total of 120 patients were enrolled during the study period. There were 68 boys (56.7%). Fourteen patients (11.6%) were found to be unresponsive to initial IVIG treatment. Patients who were anemic (Hb<10 G/DL), HAD A HIGH NEUTROPHIL COUNT (> 75%), a high band count, and low albumin were at risk of failure to respond to a single dose of IVIG. We found no correlation among age, gender, days since starting IVIG treatment, and erythrocyte sedimentation rate (ESR) with failure of the initial IVIG treatment. There were 12 patients (10%) who developed coronary artery aneurysms. The failure of a single dose of IVIG treatment occured in up to 11.6% of our Kawasaki patients. We found that low hemoglobin (<10 G/DL), HIGH NEUTROPHIL COUNT (> 75%), high band count, and a low albumin were associated with the requirement for retreatment with a second dose of IVIG.     

Intravenous immune globulin plus corticosteroids in refractory Kawasaki disease

Background: The aim of the present study was to investigate the efficacy of i.v. immune globulin (IVIG) therapy combined with corticosteroids for additional treatment of acute Kawasaki disease (KD) unresponsive to initial IVIG treatment. Methods: In 50 prospective KD patients, six IVIG non‐responders without clinical improvement within 24–48 h after completion of initial IVIG, received 2 g/kg IVIG concurrently with 2 mg/kg i.v. prednisolone sodium succinate (PSL) until normalization of C‐reactive protein level. Treatment was then changed to oral PSL, which was tapered over time. Clinical and coronary artery lesion (CAL) outcomes were compared with those of 13 IVIG non‐responders who received additional heterogeneous therapies in 125 retrospective KD patients. In addition, the scoring system of Kobayashi et al. for prediction of non‐responsiveness to initial IVIG treatment was retrospectively verified in 175 KD subjects, consisting of 50 prospective and 125 retrospective patients in order to evaluate the efficacy of the re‐treatment regimen. Results: Incidence of CAL in the study patients was lower than in the control patients, although differences were not significant both in the acute stage (within 1 month: 1/6, 16.7% vs 7/13, 53.8%; P= 0.177) and in the convalescent stage (after 1 month: 0/6, 0.0% vs 4/13, 30.8%; P= 0.255). According to the non‐responder prediction system, the scores of six study and 13 control patients before initial IVIG treatment were similar (7.2 ± 1.9 vs 5.3 ± 3.1; P= 0.200). No serious adverse effects related to each treatment were noted in patients of either group. Conclusions: Additional IVIG combined with concurrent PSL appears to be safe and worth evaluation for the treatment of acute KD unresponsive to initial IVIG treatment.     

Serum levels of neutrophil activation cytokines in Kawasaki disease

BACKGROUND: The aim of the present study was to investigate whether neutrophils are early effector cells for vascular endothelial damage in the acute phase of Kawasaki disease (KD) by examining serial changes in neutrophil counts and serum levels of neutrophil activation cytokines, such as granulocyte colony stimulating factor (G-CSF) and interleukin (IL)-8. METHODS: From October 1994 to June 1998, a total of 52 patients with KD were included in the study. Thirty-three patients had some infectious diseases, while 20 healthy children served as control subjects. Serial changes in neutrophils were counted by the optimal Wright-Giemsa staining method and serum levels of IL-8 and G-CSF in patients with KD were measured by an enzyme-linked immunosorbent assay system. RESULTS: Serum G-CSF levels both before and after intravenous immunoglobulin therapy (IVIG; P<0.05) and neutrophil counts after IVIG (P<0.005) were higher in KD patients with coronary arterial lesions (CAL) than those without CAL. However, serum IL-8 levels before and after IVIG showed no significant differences in these two groups. CONCLUSIONS: These data suggest that neutrophils may be important as early effector cells for vascular endothelial damage and that G-CSF may play a more important role than IL-8 in KD.     

Steroid Pulse Therapy for Children With Intravenous Immunoglobulin Therapy–Resistant Kawasaki Disease: A Prospective Study

Patients with Kawasaki disease (KD) who did not respond to the initial IVIG are known to have higher risk for developing coronary arterial lesions (CALs). Our aim is to clarify whether patients with initial IVIG resistant KD may benefit from methylprednisolone pulse therapy (MPT) in comparison with re- treatment of IVIG (2nd IVIG). A total of 237 patients (median age: 2 years 2 months; range 1 months–10 years) with KD were initially treated with IVIG (2 g/kg). Among them, 41 patients (22 %) were assessed as IVIG resistance: these patients were allocated to either group A receiving MPT (n = 14) or group B receiving the 2nd IVIG (n = 27). Patients with resistant to the additional therapy (MPT or 2nd IVIG) were received second IVIG (group A) or MPT (group B). Changes in leukocyte count, C-reactive protein and albumin before and after an additional therapy were significantly greater in group A than those in group B. However, the prevalence of CALs did not differ between the groups (36 % in group A and 26 % in group B, p > 0.05). There was no significant difference in the medical cost between the groups (median cost: 92,032 JPY in group A and 97,331 JPY in group B). MPT does not reduce the risk of development to CAL and does not seem to be beneficial as single agent therapy for IVIG resistant KD.     

Association of lower eosinophil-related T helper 2 (Th2) cytokines with coronary artery lesions in Kawasaki disease

Kawasaki disease (KD) is a systemic febrile vasculitis particular coronary artery involvement. Eosinophilia has been found in our and other studies in KD. This study further investigates whether eosinophil-related T helper 2 (Th2) cytokines or the activation marker (eosinophil cationic protein – ECP) is involved in KD with coronary artery lesions (CAL). A total of 95 KD patients were enrolled for this study. Plasma samples were subjected to the measurement of interleukin (IL)-4, IL-5, and eotaxin by Luminex-Bedalyte multiplex beadmates system and to the measurement of ECP by fluoroimmunoassay. Patients with KD had higher eosinophils than controls. Eosinophil-related mediators: IL-4, IL-5, eotaxin, and ECP levels were also higher in KD patients than controls before intravenous immunoglobulin (IVIG) treatment. After IVIG treatment, ECP decreased but IL-4, IL-5, and eotaxin increased significantly. The higher the IL-5 and eosinophil levels after IVIG treatment, the lower rate of CAL was found. Changes of eosinophils after IVIG treatment were positively correlated to changes of IL-5 levels but not ECP levels. An increase of eosinophils and IL-5, but not ECP levels after IVIG treatment, was inversely correlated with CAL formation in KD.     

血清sIL-2RIL-6与hs-CRP水平的测定在川崎病早期诊断中的临床意义

目的：研究表明川崎病(Kawasakidisease,KD)异常的免疫激活可导致免疫性血管炎。该研究的目的在于探讨川崎病患儿血清可溶性白细胞介素2受体(soubleinterleukin-2receptors,sIL-2R)及白细胞介素-6(in-terleukin-6,IL-6)水平在川崎病早期诊断中的临床意义。方法：收集实验组32例川崎病患儿急性期静脉注射丙种球蛋白(intravenousgammaglobulin,IVIG)前、后及对照组20例外周静脉血,ELISA双抗体法测定血清sIL-2R,IL-6含量,同时检测血清超敏C-反应蛋白(high-sensitiveC-reactiveprotein,hs-CRP)含量。结果：川崎病患儿急性期用IVIG前及用IVIG后血清sIL-2R和hs-CRP含量均较正常儿童显著增高(P<0.05);IVIG用前较用后血清sIL-2R和hs-CRP含量同样有显著增高(P<0.05);IVIG前川崎病患儿血清IL-6水平较正常儿童显著增高(P<0.05)。川崎病患儿血清sIL-2R与hs-CRP水平呈正相关(r=0.60,P<0.01);IVIG前血清IL-6与hs-CRP水平呈正相关(r=0.68,P<0.01)。结论：sIL-2R,IL-6与hs-CRP在川崎病血管炎的病理过程中显著激活,血清sIL-2R与IL-6及hs-CRP水平增高有助于川崎病早期诊断,评估患儿免疫状况。     

Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan

BACKGROUND: Some Kawasaki disease (KD) patients do not respond to initial treatment with intravenous immunoglobulin (IVIG). The purpose of this study was to determine potential risk factors associated with IVIG nonresponse among KD patients in Japan. METHODS: Data were obtained from questionnaires used for the 18th nationwide KD survey of patients who visited hospitals in Japan from 2003 through 2004. Data for patients who met the case definition for KD and received 2 g/kg single infusion IVIG as the initial treatment within 10 days of illness were analyzed. IVIG nonresponders were defined as patients who needed secondary treatment after initial IVIG administration. RESULTS: Among 15,940 KD patients in Japan during 2003-2004, 6330 patients received 2 g/kg single infusion IVIG within 10 days of illness onset. IVIG nonresponders accounted for 20.3% of them (n = 1286). Male sex [odds ratio (OR), 1.21, 95% confidence interval (CI), 1.06-1.37], receipt of the initial IVIG before the fifth day of illness (OR: 1.89, 95% CI: 1.66-2.15), and having recurrent KD (OR: 1.38, 95% CI: 1.00-1.90) were significantly associated with IVIG nonresponse. In addition, IVIG nonresponders had significantly higher risks for coronary artery aneurysms (OR: 10.38, 95% CI: 6.98-15.45) or giant coronary artery aneurysms (OR: 54.06, 95% CI: 12.84-227.65). CONCLUSIONS: Physicians should consider potential IVIG nonresponse among recurrent KD patients or KD patients diagnosed and treated before the fifth day of illness, particularly if they are boys and have laboratory values associated with nonresponse such as low platelet count, and elevated alanine aminotransferase and C-reactive protein. Some of these patients may benefit from administration of the alternative secondary treatment early during the illness along with the initial IVIG treatment.     

Prediction of the Risk of Coronary Arterial Lesions in Kawasaki Disease by Brain Natriuretic Peptide

Kawasaki disease (KD) is an acute systemic vasculitis associated with the development of coronary arterial lesions (CALs) occurring in 3–5% of children treated by intravenous immune globulin (IVIG). However, a considerable number of patients who are not responding to IVIG are at much higher risk. Although studies have explored potential biomarkers to predict patients with KD who are at risk of CAL, no useful single marker exists. We hypothesized that the serum concentrations of the N-terminal moiety of brain natriuretic peptide (NT-proBNP) can be useful to predict CAL. Forty-three children with KD (29 males and 14 females) were enrolled in this study. Despite IVIG, 6 of the 43 patients developed CAL. There were, however, no significant differences in variables between children with CAL and those without CAL: These include age, gender, day of the illness, leukocyte count, and the serum levels of sodium, C-reactive protein, and albumin. The serum NT-proBNP level was significantly higher in children with CAL than those without CAL (2,611 ± 1,699 vs. 1,073 ± 1,427 pg/ml; P = 0.03): the cutoff value of 1,000 pg/ml to predict CAL produced a specificity of 0.68, sensitivity of 0.83, and an odds ratio as high as 10.4. In conclusion, NT-proBNP is increased in KD patients who are developing CAL, and patients with an elevated serum NT-proBNP >1,000 pg/ml have a risk of CAL ~10 times higher than that of patients with a modest increase.     

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目的探讨首次丙种球蛋白静脉注射(IVIG)无反应性川崎病(KD)的发生率及危险因素,及其再治疗方法的选择。方法总结2000—2004年北京45家医院KD患儿的临床资料,IVIG无反应性定义为首次IVIG治疗36h后体温仍超过38·5℃。结果1107例患儿纳入研究对象,1092例有急性期治疗资料,1052例(96·3%)接受IVIG治疗,135例对首次IVIG治疗无反应,发生率12·8%(135/1052)。Logistic回归分析发现血沉、GPT、WBC、发病至用IVIG的时间、血浆白蛋白及IVIG治疗剂量,是IVIG无反应性的独立危险因素(P<0·05)。对IVIG无反应者8例给第2剂2g/kg IVIG,5例热退;114例给1g/kg剂量IVIG治疗,35例(30·7%)热退;11例给400~600mg/kg IVIG,1例(9·1%)热退;2例给糖皮质激素,2例均热退。4种再治疗方法间比较,差异有统计学意义(P=0·015)。第2剂2g/kg IVIG治疗较其它再治疗所需进一步IVIG或激素治疗次数少,体温恢复快。结论约12·8%KD患儿对初次IVIG治疗无反应。血沉、WBC和GPT、血浆白蛋白、IVIG使用方法及起病至用IVIG的时间,是IVIG无反应的独立危险因素。对初次IVIG无反应患儿推荐使用第2剂2g/kgIVIG,对2次2g/kgIVIG治疗仍无效者可以选用糖皮质激素治疗。     

静脉丙种球蛋白无反应性川崎病的治疗及危险因素分析

目的探讨首次丙种球蛋白静脉注射(IVIG)无反应性川崎病(KD)的发生率及危险因素,及其再治疗方法的选择。 方法总结2000—2004年北京45家医院KD患儿的临床资料,IVIG无反应性定义为首次IVIG治疗36h后体温仍超过38.5℃。 结果1107例患儿纳入研究对象,1092例有急性期治疗资料,1052例(96.3%)接受IVIG治疗,135例对首次IVIG治疗无反应,发生率12.8%(135/1052)。Logistic回归分析发现血沉、GPT、WBC、发病至用IVIG的时间、血浆白蛋白及IVIG治疗剂量,是IVIG无反应性的独立危险因素(P<0.05)。对IVIG无反应者8例给第2剂2g/kg IVIG,5例热退;114例给1g/kg剂量IVIG治疗,35例(30.7%)热退;11例给400~600mg/kg IVIG,1例(9.1%)热退;2例给糖皮质激素,2例均热退。4种再治疗方法间比较,差异有统计学意义(P=0.015)。第2剂2g/kg IVIG治疗较其它再治疗所需进一步IVIG或激素治疗次数少,体温恢复快。 结论约12.8%KD患儿对初次IVIG治疗无反应。血沉、WBC和GPT、血浆白蛋白、IVIG使用方法及起病至用IVIG的时间,是IVIG无反应的独立危险因素。对初次IVIG无反应患儿推荐使用第2剂2g/kgIVIG,对2次2g/kg IVIG治疗仍无效者可以选用糖皮质激素治疗。     

N-terminal Pro-Brain Natriuretic Peptide (NT proBNP) as a Predictive Indicator of Initial Intravenous Immunoglobulin Treatment Failure in Children With Kawasaki Disease: A Retrospective Study

Intravenous immunoglobulin (IVIG) administered in the acute stage of Kawasaki disease (KD) is the standard therapy. Few reports describe nonresponders to initial treatment with IVIG in KD, which remains the most consistent risk factor for coronary artery lesions (CALs). This study aimed to investigate whether the serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a predictive indicator for identifying patients with KD at higher risk of IVIG treatment failure. In this study, 135 patients with a diagnosis of KD admitted for IVIG treatment were retrospectively enrolled for analysis. Of these 135 patients, 22 were nonresponders who received additional rescue therapy because they had an elevated body temperature 36 h after completion of initial IVIG treatment. The NT-proBNP concentration was significantly higher in the nonresponder group (2,465.36 ± 3,293.24 pg/mL) than in the responder group (942.38 ± 1,293.48 pg/mL) (p < 0.05). The optimal sensitivity and specificity cutoff point for predicted nonresponders was 1,093.00 pg/mL or higher. The sensitivity and specificity for prediction of IVIG response were respectively 70.0 and 76.5 %. The findings show that NT-proBNP is a helpful marker in determining patients at risk for not responding to initial IVIG treatment. The authors suggest that patients with an NT-proBNP level of 1,093.00 pg/dL or higher are likely to fail initial IVIG and may require further rescue therapy.     

Immunoglobulin preparations affect hyponatremia in Kawasaki disease

Hyponatremia frequently occurs in Kawasaki disease (KD). The aim of this study was to investigate the effect of Na content of the intravenous immunoglobulin (IVIG) preparation on serum Na levels in KD. Seventy-eight subjects, of whom 27 had hyponatremia, were split up into two groups: group A receiving IVIG preparations containing high Na (0.9%) and group B receiving IVIG preparations containing trace Na. While the data before IVIG therapy revealed no significant differences in the median serum Na between the groups, an administration of IVIG preparations increased the serum levels of Na in group A (P < 0.01) but not in group B (P > 0.05). Furthermore, the median serum Na level was significantly higher in group A than that in group B (139.0 vs 137.0 mEq/L, respectively, P < 0.01). No significant difference was found in the prevalence of coronary artery lesions between the groups. In conclusion, we should keep it in mind that the IVIG products without Na have an adverse affect on hyponatremia in KD though their efficacy seems to be equivalent to those containing high Na.     

Syndrome of inappropriate anti‐diuretic hormone in Kawasaki disease

Background: The pathogenesis of hyponatremia in acute Kawasaki disease (KD) remains unclear. A recent case report of KD complicated by syndrome of inappropriate anti‐diuretic hormone (SIADH) led us to determine the prevalence of SIADH in acute KD patients. Methods: Subjects were 39 Japanese KD patients (2–84 months of age, 25 males and 14 females) treated with intravenous immunoglobulin (IVIG), 2 g/kg/day and oral aspirin. SIADH was defined when hyponatremic patients (serum sodium concentration <135 mEq/L) had decreased serum osmolality <280 mOsm/kg H₂O, elevated urine sodium concentration >20 mEq/L and elevated urine osmolality >100 mOsm/kg H₂O without dysfunctions of renal, thyroid or adrenal gland. We also studied the relation between clinical course of SIADH and the amount of infused fluid during IVIG. Results: Before IVIG, 27 patients (69%) had hyponatremia and 11 (28% of total; 41% of hyponatremic patients) had SIADH while after IVIG, 13 (33%) hyponatremia and four (10%; 31% of hyponatremic patients) SIADH. Among 11 patients with SIADH before IVIG, SIADH improved in 10 after IVIG, but hyponatremia persisted in five. Significant correlation was observed between serum sodium concentration after IVIG and infusion amount in SIADH patients (r=?0.64, P= 0.03), but not in non‐SIADH patients. Conclusions: This is the first report to show that SIADH is common as a cause of hyponatremia in acute KD and hence careful management of water and sodium is warranted.     

Steroid pulse therapy for Kawasaki disease unresponsive to additional immunoglobulin therapy

BACKGROUND:

The optimal management of Kawasaki disease (KD) unresponsive to intravenous immunoglobulin (IVIG) therapy remains unclear.

OBJECTIVE:

To prospectively evaluate the efficacy and safety of intravenous methylprednisolone pulse (IVMP) therapy in KD cases unresponsive to additional IVIG.

METHODS:

KD patients who initially received IVIG (2 g/kg/24 h) and acetylsalicylic acid within nine days after disease onset were studied. Patients who did not respond received additional IVIG (2 g/kg/24 h), and those who still did not respond were given IVMP (30 mg/kg/day) for three days, followed by oral prednisolone. The response to treatment, echocardiographic findings and adverse effects were evaluated.

RESULTS:

Among 412 KD cases, 74 (18.0%) were treated with additional IVIG; 21 (28.4%) of the latter cases subsequently received IVMP followed by prednisolone. All cases became afebrile soon after IVMP infusion and did not have a high-grade fever during treatment with prednisolone for two to six weeks. Four weeks after disease onset, coronary artery lesions (CAL) were diagnosed according to the Japanese Ministry of Health and Welfare or the American Heart Association criteria in two of the 21 cases treated with IVMP plus prednisolone; among all 412 cases, three (0.7%) and eight (1.9%) had CAL according to each criteria, respectively. All CAL regressed completely one year after disease onset. Adverse effects of IVMP, such as hypothermia and sinus bradycardia, resolved spontaneously.

CONCLUSIONS:

In KD patients unresponsive to additional IVIG, IVMP promptly induced defervescence, and subsequent oral prednisolone suppressed recurrence of fever. IVMP followed by prednisolone therapy may prevent CAL, without severe adverse effects.     

免疫球蛋白无应答川崎病再次免疫球蛋白、英夫利昔单抗和激素治疗队列研究

背景 IVIG无应答KD患儿的治疗方案包括再次IVIG、英夫利昔单抗(IFX)和激素(IMP),目前不同治疗方案的疗效评价不一.目的 IVIG无应答KD患儿再次IVIG、IFX和IMP治疗效果比较.研究设计队列研究.方法 以IVIG无应答KD患儿为队列人群,再次治疗和补救治疗(再次治疗无反应)在江西省儿童医院(我院)中...     

A multicenter prospective randomized trial of corticosteroids in primary therapy for Kawasaki disease: clinical course and coronary artery outcome

OBJECTIVE: To investigate the role of corticosteroids in the initial treatment of Kawasaki disease (KD). STUDY DESIGN: Between September 2000 and March 2005, we randomly assigned 178 KD patients from 12 hospitals to either an intravenous immunoglobulin (IVIG) group (n = 88; 1 g/kg for 2 consecutive days) or an IVIG plus corticosteroid (IVIG+PSL) group (n = 90). The primary endpoint was coronary artery abnormality (CAA) before a 1-month echocardiographic assessment. Secondary endpoints included duration of fever, time to normalization of serum C-reactive protein (CRP), and initial treatment failure requiring additional therapy. Analyses were based on intention to treat. RESULTS: Baseline characteristics of groups were similar. Fewer IVIG+PSL patients than IVIG patients had a CAA before 1 month (2.2% vs 11.4%; P = .017). The duration of fever was shorter (P < .001) and CRP decreased more rapidly in the IVIG+PSL group than in the IVIG group (P = .001). Moreover, initial treatment failure was less frequent (5.6% vs 18.2%; P = .010) in the IVIG+PSL group. All patients assigned to the IVIG+PSL group completed treatment without major side effects. CONCLUSIONS: A combination of corticosteroids and IVIG improved clinical course and coronary artery outcome without causing untoward effects in children with acute KD.     

儿童免疫相关性疾病的常规免疫学指标研究

目的比较特发性血小板减少性紫癜(ITP)、过敏性紫癜(HSP)及皮肤黏膜淋巴结综合征(KD)的常规免疫学指标变化及静脉注射免疫球蛋白(IVIG)的应用。方法用流式细胞仪测T细胞亚群,免疫比浊法测免疫球蛋白(Ig)及补体。常规加IVIG治疗。结果ITP患儿CD3 CD4 T细胞降低并IgG升高;HSP患儿IgA升高伴CD3 T细胞增高。KD患儿CD3 CD8 T细胞降低。IVIG可明显改善3种疾病临床症状,尤其有助KD患儿冠状动脉损害发生率减少。结论T细胞亚群、lg 应作为ITP、HSP及KD的常规检查项目。早期应用IVIG对改善预后及缩短病程有重要意义。     

Adjunct cyclosporine therapy for refractory Kawasaki disease in a very young infant

Herein we describe the case of a 6‐week‐old boy who developed complete Kawasaki disease (KD). The cytokine profile and activation of monocytes and subsequent T cells matched the typical feature of refractory KD. The patient received a total of three courses of i.v. immunoglobulin (IVIG), but did not achieve clinical relief. Adjunctive therapy with oral cyclosporine A (CsA) led to prompt defervescence. This was continued for 7 days without serious adverse events. Coronary artery dilatations regressed within 3 months of follow up. KD infants <3 months of age are at higher risk of coronary artery aneurysm than the older ones. To our knowledge, oral CsA treatment has not been reported in such young infants with KD. The diagnosis and treatment of very young infants with KD are challenging. Adjunctive use of CsA in IVIG treatment could be effective for refractory KD in infants <3 months of age.     

Time interval of measles vaccination in patients with Kawasaki disease treated with additional intravenous immune globulin

A standard treatment with a dose of 2 g/kg of intravenous immune globulin (IVIG) is sometimes ineffective in some patients with Kawasaki disease (KD), who are commonly treated with additional IVIG. An interval of 6 to 7 months in Japan and 11 months in the United States is recommended before vaccination against measles after IVIG treatment for KD, but it is not known how long after treatment with additional IVIG. We studied the persistence of measles antibody titers in six episodes of KD in five patients without history of measles infection or vaccination, 4 to 28 months of age, after additional infusion of IVIG. The total dose was 4 g/kg in five episodes and 6 g/kg in one episode. Enzyme immunoassay antibody titers against measles were still positive (400) in all patients tested 3 months after additional infusion of IVIG and positive in one patient and equivocal (200 and <400) in three patients after 6 months, but negative (<200) in all after 9 months following infusion. Neutralization test antibody titers against measles were still positive (1:4) in all patients 3 months after additional infusion of IVIG, but only one after 6 months, and negative (<1:4) in all after 9 months following infusion. Conclusion: we suggest that an appropriate interval between infusion of 4 g/kg of intravenous immune globulin and measles vaccination be 9 months. The 11-month interval recommended in the United States for 2 g/kg may be longer than necessary.Abbreviations EIA enzyme immunoassay - HI hemagglutination inhibition - IVIG intravenous immune globulin - KD Kawasaki disease - NT neutralization test