PROFILE OF RESISTANCE TO IVIG TREATMENT IN PATIENT WITH KAWASAKI DISEASE AND CONCOMITANT INFECTION

Abstract BACKGROUND Kawasaki disease (KD) is a paediatric systemic vasculitis that can be associated with concomitant viral or bacterial infections. Patients with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. OBJECTIVES However, it is unknown how concomitant infection influences the response to IVIG treatment. The aim of this study was to determine the impact of concurrent infection on the prevalence of IVIG resistance and coronary outcome. DESIGN/METHODS Retrospective study of 154 children (mean age at diagnosis: 3.4 ± 2.8 years) diagnosed with KD, between 2008–2016 in a tertiary paediatric university hospital, of which 59 (38%) had concomitant infection. RESULTS Delay in diagnosis (>10 days of fever) was similar between patients with and without concomitant infection (7% vs 7%, p=0.89). Patients with concomitant infection were more likely to have fever 48 hours after initial treatment (36% vs 20%, p=0.05) and to be treated with a second dose of IVIG (33% vs 18%, p=0.04). Patients with infection had higher C-reactive protein at the time of diagnosis (148 vs 112 mg/L, p=0.04), which persisted after IVIG administration (111 vs 59 mg/L at 48 hours, p=0.003). However, there was no statistically significant difference in the prevalence of coronary artery (CA) complications (coronary artery Z-score > 2.5) between patients with and without concomitant infection (36% vs 39%, p=0.68). CONCLUSION Children with KD and concomitant infection are more likely to have persistent fever and elevated inflammatory markers after treatment requiring a second dose of IVIG. Nevertheless, this is not associated with an increased risk of CA complications. Larger scale studies are needed to help distinguish IVIG resistance from infection in children with persistent fever and guide management of this population. Table/Chart or graphic upload

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Coronary Aneurysm and IVIG Resistance Prediction in Kawasaki Disease

10.21203/rs.3.rs-56396/v1 ◽

2020 ◽

Author(s):

Yusuf Ziya Varlı ◽

Kazim Oztarhan

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Clinical Laboratory ◽

Systemic Vasculitis ◽

Cervical Lymphadenopathy ◽

Artery Aneurysm ◽

Ivig Treatment ◽

Left Circumflex Artery ◽

Ivig Resistance ◽

Significant Difference

Abstract Background: Kawasaki disease (KD) is the most common cause of coronary artery aneurysm (CAA) in children. This study aimed to determine the clinical characteristics, demographic features, frequency of coronary involvement, and resistance to intravenous immunoglobulin (IVIG) treatment in Turkey based on our data.Methods: Patients with KD were evaluated with demographic data, clinical, laboratory, and echocardiographic findings. Results: Between 2010–2019, a total of 259 patients (male/female: 1.67) were treated in our hospital, with 48 (%19) cases < 1 year of age. According to diagnostic criteria, 31% were diagnosed with typical KD and 69% with atypical (incomplete) KD. The frequency of clinical findings were as follows: changes in the lips and oral mucosa (79%); polymorphic rash (69%); conjunctivitis (65%); changes in the extremities (54%); and cervical lymphadenopathy (48%). There was no significant difference between typical and atypical KD in the frequency order. CAA development and IVIG resistance occurred in 11.6% and 12.3% of cases, respectively. IVIG resistance was more common in infants and hospitalization times were longer in this group. Coronary artery lesions existed in 45 patients; right coronary artery (RCA) alone (20%), left coronary artery (LCA) alone (44.5%), and RCA and LCA together were involved (35.5%). The left main coronary artery affected 20 patients, the left anterior descending artery (LAD) affected nine patients (45%), the left circumflex artery (LCx) affected two patients (10%), and the LAD and LCx together affected two patients (10%). None of the patients had myocardial infarctions or died during follow-up. Conclusion: KD is a systemic vasculitis common in pediatric infants in which coronary artery involvement affects prognosis. Due to IVIG resistance and increased coronary involvement accompanying this vasculitis, it is an important problem in countries where the disease is common. It is important to know the factors that increase the risk of coronary involvement and IVIG resistance development.

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HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease

Rheumatology ◽

10.1093/rheumatology/key356 ◽

2018 ◽

Vol 58 (5) ◽

pp. 770-775 ◽

Cited By ~ 6

Author(s):

Jong Gyun Ahn ◽

Yoonsun Bae ◽

Dongjik Shin ◽

Jiho Nam ◽

Kyu Yeun Kim ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Single Nucleotide Polymorphisms ◽

Odds Ratio ◽

Ivig Treatment ◽

Nucleotide Polymorphisms ◽

Coronary Artery Lesions ◽

Hmgb1 Level ◽

Single Nucleotide ◽

Ivig Resistance

Abstract Objectives Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that affects infants and young children. Recent reports of elevated serum high mobility group box 1 (HMGB1) level during the acute phase of KD and its relationship to poor response to IVIG treatment suggest a possible association of HMGB1 polymorphisms with KD. We investigated the association between the polymorphisms of the HMGB1 gene, KD susceptibility, coronary artery lesions, and KD response to IVIG treatment. Methods Whole genome sequencing of the HMGB1 gene was performed to identify causative variants. Two tagging single nucleotide polymorphisms of the HMGB1 gene were selected using linkage disequilibrium analysis. The tagging single nucleotide polymorphisms were genotyped using the TaqMan Allelic Discrimination assay in a total of 468 subjects (265 KD patients and 203 controls). Results The HMGB1 single nucleotide polymorphisms were not associated with KD susceptibility. However, in KD patients, there was a significant association of rs1412125 with coronary artery lesions formation in the recessive model (GG vs AA + GA: odds ratio = 4.98, 95% CI = 1.69–14.66, P = 0.005). In addition, rs1412125 was associated with IVIG resistance in the recessive (GG vs AA + GA: odds ratio = 4.11, 95% CI = 1.38–12.23, P = 0.017) and allelic models (G vs A: odds ratio = 1.80, 95% CI = 1.06–3.06, P = 0.027). Conclusion The rs1412125 in HMGB1 might be a risk factor for the development of coronary artery lesions and IVIG resistance in KD patients.

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Abstract O.07: The Clinical Risk Factors of Intravenous Immunoglobulin Resistance and Coronary Artery Lesion of Kawasaki Disease: Retrospective Analysis of 602 Cases

Circulation ◽

10.1161/circ.131.suppl_2.o07 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

lijian xie ◽

Cuizhen Zhou ◽

Renjian Wang ◽

Tingting Xiao ◽

Jie Shen ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Coronary Artery ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Clinical Evidence ◽

Clinical Risk Factors ◽

Ivig Treatment ◽

Ivig Resistance ◽

Sensitive Group

Introduction: The incidence of Kawasaki disease (KD) in China is increasing for years. The current coronary artery lesion (CAL) incidence is 5-10% in KD with intravenous immunoglobulin (IVIG) treatment. And the 10-20% KD patients still exhibit IVIG resistance. However, little clinical evidence on the occurrence of either CAL or IVIG resistance for big KD sample study in China during the past decade. Objective: In order to find clinical risk factors of CAL and IVIG resistance of KD in China. Methods: We retrospectively analyzed the clinical manifestations, laboratory results, treatment and complications of cardiac vascular of 602 KD cases from 2007 to 2012 admitted at Shanghai Children’s Hospital. The SAS 9.2 edition was used for statistical analysis. The mean ± standard deviation or the median were used for measurements. Case numbers and percentages were used for the count number. The t-test and the Mann-Whitney test were both used for mean comparisons. Single factor and multi-factor logistic regression analyses were used to analyze the risk factors. Results: 1. The KD gender male to female ratio was 1.85: 1. The KD median age was 2.0 years old (one month to 11.7 years old). 20.1% cases (121 of 602) exhibited CAL. There was no difference of CAL incidence between the gender (p=0.09). 2. The incidence of bright red cracked lips (p=0.001), peeling of the skin of the toes (p=0.021) and perianal skin peeling (p=0.031) are less in group with CAL. 3. Among the 602 cases, there were 525 cases that were sensitive to IVIG therapy. 100 of those cases had CAL with an incidence of 19.1%. Among the 26 IVIG resistance cases, there were 9 cases with CAL with an incidence of 34.6%, which was higher than the IVIG sensitive group (p=0.05). 4. ESR (p=0.014), CRP (p=0.017), PLT (p=0.003) and Hb (p=0.032) were much higher in the IVIG resistance group than the IVIG sensitive group, even though the IVIG resistance group started the IVIG treatment earlier (p=0.003). 5. Logistic regression analysis was conducted to show that GPT≥80IU/L was the independent risk factor of IVIG resistance, risk ratio was 2.945 (p=0.012) . Conclusion: This research suggests that risk factors of clinical evidence for IVIG resistance and CAL in KD.

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Effect of Early Intravenous Immunoglobulin Therapy in Kawasaki Disease: A Systematic Review and Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2020.593435 ◽

2020 ◽

Vol 8 ◽

Author(s):

Fan Yan ◽

Huayong Zhang ◽

Ruihua Xiong ◽

Xingfeng Cheng ◽

Yang Chen ◽

...

Keyword(s):

Systematic Review ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Meta Analysis ◽

The United States ◽

Cochrane Library ◽

Ivig Treatment ◽

Intravenous Immunoglobulin Therapy ◽

Increased Risk ◽

Significant Difference

Background: In the latest 2017 American Heart Association guidelines for Kawasaki disease (KD), there are no recommendations regarding the early administration of intravenous immunoglobulin (IVIG). Therefore, the purpose of this systematic review and meta-analysis was to investigate the effects of early IVIG therapy on KD.Methods: We searched databases including the PubMed, Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2019.Results: Fourteen studies involving a total of 70,396 patients were included. Early treatment with IVIG can lead to an increased risk of IVIG unresponsiveness [OR 2.24; 95% CI (1.76, 2.84); P = 0.000]. In contrast to the studies performed in Japan [OR 1.27; 95% CI (0.98, 1.64); P = 0.074] that found no significant difference in coronary artery lesions (CAL) development, studies conducted in China [OR 0.73; 95% CI (0.66, 0.80); P = 0.000] and the United States [OR 0.50; 95% CI (0.38, 0.66); P = 0.000] showed a reduced risk in the occurrence of CAL with early IVIG treatment.Conclusions: At present, the evidence does not support the treatment with IVIG in the early stage of the onset of KD. But, early IVIG treatment could be a protective factor against the development of CAL, which needs to be further clarified.

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Predicting IVIG resistance in UK Kawasaki disease

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-307397 ◽

2015 ◽

Vol 100 (4) ◽

pp. 366-368 ◽

Cited By ~ 51

Author(s):

Sarah Davies ◽

Natalina Sutton ◽

Sarah Blackstock ◽

Stuart Gormley ◽

Clive J Hoggart ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Corticosteroid Treatment ◽

C Reactive Protein ◽

Japanese Children ◽

Coronary Artery Abnormalities ◽

Reactive Protein ◽

Ivig Resistance ◽

Increased Risk

The Kobayashi score (KS) predicts intravenous immunoglobulin (IVIG) resistance in Japanese children with Kawasaki disease (KD) and has been used to select patients for early corticosteroid treatment. We tested the ability of the KS to predict IVIG resistance and coronary artery abnormalities (CAA) in 78 children treated for KD in our UK centre. 19/59 children were IVIG non-responsive. This was not predicted by a high KS (11/19 IVIG non-responders, compared with 26/40 responders, had a score ≥4; p=0.77). CAA were not predicted by KS (12/20 children with CAA vs 25/39 with normal echo had a score ≥4; p=0.78). Low albumin and haemoglobin, and high C-reactive protein were significantly associated with CAA. The KS does not predict IVIG resistance or CAA in our population. This highlights the need for biomarkers to identify children at increased risk of CAA, and to select patients for anti-inflammatory treatment in addition to IVIG.

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P2808Absorb bioresorbable scaffold vs. Xience metallic stent: outcomes in the AIDA trial stratified by SYNTAX score

European Heart Journal ◽

10.1093/eurheartj/ehz748.1120 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

R Y G Tijssen ◽

R P Kraak ◽

I M Van Dongen ◽

J Elias ◽

S H Hofma ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Clinical Outcomes ◽

Primary Endpoint ◽

Metallic Stent ◽

Target Vessel ◽

Increased Risk ◽

Significant Difference ◽

Absorb Bvs ◽

The Impact

Abstract Aims Extent of coronary artery disease (CAD) may affect outcomes after percutaneous coronary intervention (PCI). In this pre-specified subgroup analysis of the AIDA trial we evaluated the impact of SXscore on clinical outcomes Methods and results AIDA was a multicenter trial comparing Absorb with Xience. SX score was assessed using the baseline diagnostic angiograms. Each coronary lesion with diameter stenosis ≥50% in vessels ≥1.5 mm was scored. All lesion scores were combined to provide the overall SXscore. The angiographic SXscore calculations were performed by core laboratory analysts who were blinded for clinical events (Cardialysis B.V., Rotterdam, The Netherlands). Clinical outcomes were subsequently stratified according to SXscore tertiles: SXlow (SXcore ≤8), SXmid (SXscore >8 and ≤15) and SXhigh (>15). The primary endpoint of this AIDA-trial substudy was target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction and target vessel revascularization. The SXscore was prospectively calculated in 1661 of the 1845 patients (90%). The SXscore ranged from 1 to 57, with a mean±SD of 12.9±8.5 and a median of 11 (Q1-Q3 7–17). In this analysis the SXscore tertiles were defined as SXlow (SXcore ≤8) (n=589), SXmid (SXscore >8 and ≤15) (n=538), and SXhigh (>15) (n=534). Patients in the SXhigh group were older, had a more extensive medical history for previous revascularizations (both PCI and coronary artery bypass grafting), and were more likely to present with a ST-elevation myocardial infarction. At 2 follow-up the Kaplan-Meier estimates of TVF for the overall AIDA study population was 15.5% in the SXhigh tertile, 10.4% in the SXmid tertile and 4.7% in the SXlow tertile (hazard ratio (HR) 3.53 95% CI 2.28–5.45; P<0.001). The event rate of the primary endpoint of TVF was numerically lower in Absorb when compared to Xience (3.7% versus 5.6%; HR 0.64; 95% CI 0.29 - 1.40; p=0.257) in the SXlow tertile. Patients treated with Absorb and a SXscore >8 had significantly higher event rates as compared to patients with a SXscore ≤8. The rates of TVF in the Absorb BVS population are 15.5% (SXhigh), 11.4% (SXmid), and 3.7% (SXlow), with a significant difference between the SXlow versus SXmid (HR 3.27; 95% CI 1.61–6.68; p=0.001) and SXlow versus SXhigh (HR 4.57; 95% CI 2.29–9.10; p<0.001). Target Vessel Failure in Absorb BVS Conclusions This study demonstrates that implantation of the Absorb in patients with a SXscore ≤8 is associated with numerically lower TVF rates as compared to the Xience drug-eluting stent. The rate of scaffold thrombosis in this SXlow tertile, while still higher for Absorb, is more acceptable than in SXmid and SXhigh score tertiles. Higher SXscore (i.e. >8), both Sxmid and SXhigh, however, appears to be associated with markedly increased risk of device thrombosis, revascularization and myocardial infarction in patients treated with the Absorb. Acknowledgement/Funding The AIDA trial was financially supported by an unrestricted research grant from Abbott Vascular

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Desquamation in Kawasaki Disease and its Relationship with Coronary Artery Abnormalities

10.21203/rs.3.rs-18250/v1 ◽

2020 ◽

Author(s):

JIAHUEI YAN ◽

Wan-Shan Lo ◽

Mindy Ming-Huey Guo ◽

Ying-Hsien Huang ◽

Ling-Sai Chang ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Laboratory Data ◽

Ivig Treatment ◽

Low Grade ◽

High Grade ◽

Laboratory Findings ◽

Coronary Artery Abnormalities ◽

Significant Difference ◽

Hands And Feet

Abstract Background Desquamation of hands and feet is a common characteristic of Kawasaki disease (KD), and occurs in 68-98% of patients diagnosed with KD. In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. Method We retrospectively reviewed children with KD who had follow-up visits in Kaohsiung Chang Gung Memorial Hospital’s pediatric outpatient department (OPD) during 2018 and 2019. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment, and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. Results We enrolled a total 112 patients in the study, and 92 patients (82.1%) had hand or feet desquamation. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p=0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p=0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell count (p=0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p=0.016). We observed no significant difference in IVIG resistance between the groups. Conclusion This report is the first to demonstrate that the desquamation level of hands or feet in Kawasaki disease is associated with different coronary artery abnormalities and laboratory findings. Physicians should be cautious of CAA formation, particularly in patients with low-grade hand peeling.

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Desquamation In Kawasaki Disease And Its Relationship With Coronary Artery Abnormalities

10.21203/rs.3.rs-24866/v1 ◽

2020 ◽

Author(s):

JIAHUEI YAN ◽

Wan-Shan Lo ◽

Mindy Ming-Huey Guo ◽

Ying-Hsien Huang ◽

Ling-Sai Chang ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Laboratory Data ◽

Ivig Treatment ◽

Low Grade ◽

High Grade ◽

Laboratory Findings ◽

Coronary Artery Abnormalities ◽

Significant Difference ◽

Hands And Feet

Abstract Background Desquamation of hands and feet is a common characteristic of Kawasaki disease (KD), and occurs in 68-98% of patients diagnosed with KD. In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship.Method We retrospectively reviewed children with KD who had follow-up visits in Kaohsiung Chang Gung Memorial Hospital’s pediatric outpatient department (OPD) during 2018 and 2019. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment, and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet.Results We enrolled a total 112 patients in the study, and 92 patients (82.1%) had hand or feet desquamation. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p=0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p=0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell count (p=0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p=0.016). We observed no significant difference in IVIG resistance between the groups. Conclusion This report is the first to demonstrate that the desquamation level of hands or feet in Kawasaki disease is associated with different coronary artery abnormalities and laboratory findings. Physicians should be cautious of CAA formation, particularly in patients with low-grade hand peeling.

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Sonographic Gallbladder Abnormality Is Associated with Intravenous Immunoglobulin Resistance in Kawasaki Disease

The Scientific World JOURNAL ◽

10.1100/2012/485758 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 13

Author(s):

Chih-Jen Chen ◽

Fu-Chen Huang ◽

Mao-Meng Tiao ◽

Ying-Hsien Huang ◽

Li-Yan Lin ◽

...

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Clinical Features ◽

Demographic Data ◽

Laboratory Data ◽

Ivig Treatment ◽

Coronary Artery Lesions ◽

Abdominal Sonography ◽

Ivig Resistance ◽

Group B

Objective. Kawasaki disease (KD) is an acute systematic vasculitis in children which causes coronary arterial lesions and hydrops of gallbladder. Our objective is to correlate the clinical significance and influence on disease outcome of patients with gallbladder abnormalities in Kawasaki dissease.Methods. Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients with abdominal sonography were divided into 2 groups based on the absence (Group A,N=61) or presence (Group B,N=16) of gallbladder abnormalities (GBA), defined as hydrops or acalculous cholecystitis. Between the two groups, clinical features, demographic data (including admission days, coronary artery lesions, IVIG resistance), and laboratory data before/after IVIG treatment were collected for analysis.Results. The presence of sonographic gallbladder abnormalities is correlated with higher levels of serum CRP, GPT, and neutrophils. It also points to an increased number of IVIG resistance rates in group B. There was no significant statistical difference among clinical features, age, gender, admission days, or coronary artery lesions between the two groups.Conclusion. Sonographic gallbladder abnormalities are associated with higher CRP, GPT, neutrophil and IVIG resistance in KD. It can be used as a predictor of IVIG resistance in patients with KD.

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Malattia di Kawasaki: quale dose di immunoglobuline nei bambini grandi?

Medico e Bambino pagine elettr ◽

10.53126/mebxxiii231 ◽

2020 ◽

Vol 23 (9) ◽

pp. 231-233

Author(s):

Lorenzo Mambelli ◽

Alessandra Iacono ◽

Giovanna Rametta ◽

Federico Marchetti

Keyword(s):

Retrospective Study ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Treatment Effects ◽

Ivig Treatment ◽

Japanese Children ◽

Ivig Resistance ◽

Coronary Aneurysms ◽

Significant Difference ◽

Randomised Controlled

In a retrospective study conducted on a population of Japanese children with a weight ≥ 25 kg and with Kawasaki disease, no significant difference has been observed for the onset of coronary aneurysms, intravenous immunoglobulin (IVIg) resistance, duration of the hospitalisation and adverse treatment effects among the groups treated with 2 g/kg and 1 g/kg doses of IVIg. New randomised controlled studies are desirable to check the most appropriate IVIg dose for old children, also considering the cortisone treatment in association with the IVIg treatment firstly.

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