Initial Intravenous γ‐Globulin Treatment Failure in Iranian Children with Kawasaki Disease

Kashef, Sara; Safari, Mojgan; Amin, Reza

doi:10.1016/s1607-551x(09)70141-x

Cited by 10 publications

(8 citation statements)

References 16 publications

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“…In published series of IVIG-resistance, the rates vary from a low of 9.4% in Iran to a high of 23% in the United States (3,4,6,17,18). …”

Section: Discussionmentioning

confidence: 99%

“…Treatment with a single dose of intravenous immunoglobulin (IVIG) and high-dose aspirin results in resolution of fever in most patients and significantly reduces the rate of coronary artery aneurysms (1). Despite this success, 10-20% of children will have persistent or recrudescent fever after their first infusion of IVIG (2)(3)(4)(5). These patients are at increased risk of developing coronary artery abnormalities (5,6).…”

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confidence: 99%

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Resistance to Intravenous Immunoglobulin in Children with Kawasaki Disease

Tremoulet

Best

Song

et al. 2008

The Journal of Pediatrics

354

295

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Objectives-To explore the increased incidence of intravenous immunoglobulin (IVIG) resistance among San Diego County Kawasaki disease (KD) patients in 2006 and to evaluate a scoring system to predict IVIG-resistant patients with KD.Study design-We performed a retrospective review of patients with KD treated within 10 days of fever onset. Using multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system. 2006, 38.3 % of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher % bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and γ-glutamyl transferase (GGT). They also had lower platelet counts and age-adjusted hemoglobin (zHgb) concentrations and were more likely to have aneurysms (p=0.0008). A scoring system developed to predict IVIG-resistant patients using illness day, % bands, GGT, and zHgb, had a sensitivity of 73.3% and specificity of 61.9%. Results-InConclusions-An unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Keywords Conflict of Interests:The authors have no conflicts of interest to report. Kawasaki disease (KD), the leading cause of pediatric acquired heart disease in the United States and Japan, is an acute, systemic vasculitis. Treatment with a single dose of intravenous immunoglobulin (IVIG) and high-dose aspirin results in resolution of fever in most patients and significantly reduces the rate of coronary artery aneurysms (1). Despite this success, 10-20% of children will have persistent or recrudescent fever after their first infusion of IVIG (2-5). These patients are at increased risk of developing coronary artery abnormalities (5,6). Additional therapies used in these patients include retreatment with IVIG, immunomodulatory agents such as infliximab, high dose methylprednisolone, cyclophosphamide, and plasmapheresis. (7-11). Identification of patients who are likely to be IVIG-resistant would allow the use of additional therapies early in the course of their illness when prevention of coronary artery damage might still be possible. NIH Public AccessA number of recent studies from Asia have identified demographic and laboratory characteristics, including age...

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“…In published series of IVIG-resistance, the rates vary from a low of 9.4% in Iran to a high of 23% in the United States (3,4,6,17,18). …”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Resistance to Intravenous Immunoglobulin in Children with Kawasaki Disease

Tremoulet

Best

Song

et al. 2008

The Journal of Pediatrics

354

295

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“…Furthermore, rates of IVIG non-responders or CAL formation differ among reports from different ethnic groups. [5][6][7][8]19,20 Thus, some host genetic factors must influence the clinical severity of KD. Many researchers who recognize this issue have repeatedly examined the association of candidate genetic variations with CAL formation and IVIG unresponsiveness.…”

Section: Discussionmentioning

confidence: 99%

ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease

et al. 2011

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Functional single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) (rs28493229) and caspase-3 (CASP3) (rs113420705; formerly rs72689236) are associated with susceptibility to Kawasaki's disease (KD). To evaluate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) unresponsiveness, we investigated 204 Japanese KD patients who received a single IVIG dose of 2 g kg(-1) (n=70) or 1 g kg(-1) daily for 2 days (n=134). The susceptibility allele of both SNPs showed a trend of overrepresentation in IVIG non-responders and, in combined analysis of these SNPs, patients with at least 1 susceptible allele at both loci had a higher risk for IVIG unresponsiveness (P=0.0014). In 335 prospectively collected KD patients who were treated with IVIG (2 g kg(-1)), this 2-locus model showed a more significant association with resistance to initial and additional IVIG (P=0.011) compared with individual SNPs. We observed a significant association when all KD patients with coronary artery lesions were analyzed with the 2-locus model (P=0.0031). Our findings strongly suggest the existence of genetic factors affecting patients' responses to treatment and the risk for cardiac complications, and provide clues toward understanding the pathophysiology of KD inflammation.

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“…Despite initial IVIG treatment, 6.8%-38.3% of patients are unresponsive to it [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and are at a higher risk for coronary artery lesions [30][31][32][33]37] . A study based on the United States national database showed that the resistance rate to initial IVIG therapy was 16.3% (hospital range 8.0%-26.8%) [36] .…”

Section: Unresponsive To Ivig Treatmentmentioning

confidence: 99%

Use of corticosteroids during acute phase of Kawasaki disease

Yu¹

2015

WJCP

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In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary.

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Initial Intravenous γ‐Globulin Treatment Failure in Iranian Children with Kawasaki Disease

Cited by 10 publications

References 16 publications

Resistance to Intravenous Immunoglobulin in Children with Kawasaki Disease

Resistance to Intravenous Immunoglobulin in Children with Kawasaki Disease

ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease

Use of corticosteroids during acute phase of Kawasaki disease

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