IVIG Resistance Research Articles

Kawasaki Disease Diagnosis and Treatment in over 1000 Patients: A Continuum of Dysregulated Inflammatory Responses.

Kawasaki disease (KD) is a pediatric vasculitis, leading to coronary artery aneurysms (CAAs) in ~4-14%. Attention to the etiology and course of KD was generated by the close mimic of a SARS-CoV-2-induced phenotype, called multisystem inflammatory syndrome in children (MIS-C). A total of 1179 cases were collected from 2012 with ~50% of cases retrospectively included. Clinical characteristics were described and risk factors for CAA (persistence) were investigated. Phenotypic patterns of the prospectively included KD patients were evaluated. These patterns were also compared to the seronegative KD and seropositive MIS-C cases identified during the SARS-CoV-2 pandemic. KD mostly affected boys and children < 5 years. IVIG resistance, CAAs, and giant CAAs occurred in 24.5%, 21.4%, and 6.6%, respectively. Giant CAAs were significantly more likely to normalize to a normal Z score in patients that were younger than 2.5 years old at the time of initial giant CAA (χ2 test p = 0.02). In our prospective (SARS-CoV-2-seronegative) KD series, there was a diminishing male predominance over time, whereas the proportions of incomplete presentations (p < 0.001) and patients with circulatory shock (p = 0.04) increased since the COVID-19 pandemic. Pre- and post-pandemic KD cases presented with different levels of C-reactive protein, thrombocyte counts, and hemoglobin levels over the years. Compared to pandemic KD, SARS-CoV-2-seropositive MIS-C patients were older (p < 0.001), and more often required intensive care admission (p < 0.001), with a gradual decrease over time between 2020 and 2022 (p = 0.04). KD carried a substantial risk of CAA development in contrast to MIS-C. the phenotypic changes seen over the last twelve years of our prospective follow-up study suggest a spectrum of hyperinflammatory states with potentially different triggering events within this clinical entity.

Explorative case control study on the associations of serum vitamin D3, folic acid and vitamin B12 levels on Kawasaki disease and coronary artery lesions.

Kawasaki Disease (KD) is a pediatric vasculitic disorder characterized by systemic small vasculitis, notably coronary arteritis, with unclear pathogenesis. This explorative case-control study investigated the association between folic acid (FA), vitamin D3 (VD3), and vitamin B12 (VB12) levels and the different types of Kawasaki Disease, as well as the incidence of coronary artery lesions (CALs). In this explorative case control study, 365 KD children admitted to our hospital from January 1, 2022 to June 30, 2023 were included as the KD group. Simultaneously, 365 healthy children who received physical examination during the same period were included as the control group. The KD group was divided into typical KD group and incomplete KD group (IKD group), CALs group and non-CALS group, and IVIG sensitive group and IVIG resistant group. The children with CALs were divided into small tumor group, medium tumor group and large tumor group. Serum levels of FA, VB12, and VD3 were compared across all groups. Serum levels of FA and VD3 were significantly decreased in both the KD and CALs groups (p < 0.05), and both factors were identified as independent risk factors for KD and CALs. Similarly, reduced serum VD3 levels were observed in the IKD and IVIG-resistant groups (p < 0.05), with VD3 also being an independent risk factor for both IKD and IVIG resistance. Additionally, lower serum FA levels were noted in the group with large aneurysms (p < 0.05), establishing FA as an independent risk factor for aneurysm size. Serum levels of folic FA and vitamin VD3 were significantly reduced in children with KD. Furthermore, these reductions were more pronounced in children with IKD and CALs. This pattern suggests that lower FA and VD3 levels may increase the risk of more severe coronary lesions in KD patients. Therefore, monitoring these biomarkers could provide valuable insights for early clinical diagnosis and intervention.

Incidence of coronary artery lesions in children with recurrent Kawasaki disease

ABSTRACT Objective Coronary artery lesions (CALs) are a major complication of Kawasaki disease (KD); however, data on CAL incidence and risk factors in recurrent KD are limited. Methods Ninety-seven children with recurrent KD were retrospectively enrolled from 2013 to 2022, and CAL incidence was tracked during admission, discharge, and during follow-up. Results Initially, 27.8% had CAL at admission and discharge, declining to 7.2% at 12 months post-discharge. Most patients (66 of 97, 68.0%) did not exhibit CAL at any of the time points, 7 cases presented CAL at all time points, indicating a persistent CAL. The remaining 20 cases presented CAL at admission but recovered at discharge or during follow-up. Notably, transient CALs had presented at discharge, or during the follow-up, but finally resolved at 12 months after discharge. Notably, prior IVIG resistance and increased prothrombin time seemed associated with CAL in recurrent KD, suggesting they could help identify patients needing close monitoring. Conclusion The study highlights decreasing CAL incidence over time in recurrent KD but with diverse patterns, emphasizing the importance of monitoring and further investigations to confirm these findings.

Retrospective evaluation of 130 cases with kawasaki disease follow-up in a tertiary care center in Turkey between 1999 and 2019: a 20-year experience

ABSTRACT Objectives Kawasaki disease (KD), which is a medium vessel vasculitis, is common in Asian countries and is the most common cause of childhood-acquired heart diseases in developed countries. However, disease course and epidemiological data are limited in non-Asian developing countries like ours. We aimed to evaluate the clinical features and prognosis of patients with KD in our country and ethnicity, one of the referee centers of our country. Methods Patients with KD in our center for the last 20 years in the pre-COVID-19 pandemic era were included in the study. The clinical and laboratory findings, treatments, and follow-up findings were reviewed retrospectively in different age groups. Results Of the 130 patients, 82 (63%) were male. The median age at diagnosis was 2.97 years (2 months-11.5 years). Thirty-six (27.7%) patients were diagnosed with incomplete KD, and there was no significant laboratory difference between incomplete KD and complete KD patients. Thirty-three (25.3%) patients had coronary artery lesions (CAL), and it persisted in only 3 of 33 patients. One of 15 patients with IVIG resistance had CAL. The independent risk factors were days of illness at initial IVIG administration for CAL (p = 0.013, OR [95%CI] = 1.20 [1.04–1.38]) and low hemoglobin (p = 0.003, OR [95%CI] = 0.51 [0.33–0.79]) and low sodium for IVIG resistance (p = 0.012, OR [95%CI] = 0.81[0.69–0.95]). Conclusions The rate of CAL is approximately three times higher in our results than in the Japanese data in recent years. We showed that the time of IVIG administration is the most critical factor for preventing CAL. Wide-ranging studies are needed to decently predict the disease process according to the age and region of patients.

457 - A case of atypical Kawasaki Disease with elevated serum IL-18 and ferritin levels & potential IVIG resistance

457 - A case of atypical Kawasaki Disease with elevated serum IL-18 and ferritin levels & potential IVIG resistance

Development of a prediction model for progression of coronary artery lesions in Kawasaki disease.

This study aimed to identify risk factors for the progression of coronary artery lesions (CALs) in children with Kawasaki disease (KD) and to develop a nomogram prediction model. This is a retrospective case-control study in which the participants were categorized into three groups based on the changes of the maximum Z score (Zmax) of coronary arteries at the 1-month follow-up compared with the baseline Zmax: CALs-progressed, CALs-improved, and CALs-unchanged. Of total 387 patients, 65 (27%), 319 (73%), and 3 (0.7%) patients were categorized into CALs-progressed group, CALs-improved group, and CALs-unchanged group, respectively. Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, C-reactive protein, albumin, and soluble interleukin-2 receptor (odds ratio: 7.19, 1.51, 2.32, 1.52, 0.86, and 1.46, respectively; all P-values < 0.01). The nomogram prediction model including these six independent risk factors yielded an area under the curve (AUC) of 0.80 (95% confidence interval, 0.74 to 0.86). The accuracy of this model reached 81.7% after the Monte-Carlo Bootstrapping 1000 repetitions. The nomogram prediction model can identify children at high risk for the progression of CALs at early stages. Six independent factors associated with CALs progression were identified, including initial IVIG resistance, baseline Zmax, the number of coronary arteries involved, CRP, ALB, and sIL-2R. The prediction model we constructed can identify children at high risk for the progression of CALs at early stages and help clinicians make individualized treatment plans. Prospective, multi-centered studies with larger sample sizes are warranted to validate the power of this prediction model in children with KD.

Comparative effectiveness of two intravenous immunoglobulin products in children with Kawasaki disease, a nationwide cohort study

Kawasaki Disease (KD) is the most common acquired pediatric heart disease in the developed world. Rapid infusion of high-dose intravenous immunoglobulin is the standard therapy. Different manufacturing processes of IVIG may influence their efficacy. This study aims to conduct a head to head comparison of two IVIGs, TBSF and Privigen, from a nationwide perspective. The main data source was the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 3368 KD cases involving children under 2 years of age were enrolled from January 2015 to November 2020. The primary endpoint was IVIG resistance, which we defined as the total amount exceeding 26 g in one admission. The secondary endpoints encompassed two distinct criteria: coronary involvement, which was defined as the prolonged use of aspirin or anti-coagulation agents between 180 and 360 days after the index date, and recurrence, which was defined as readmission for IVIG therapy occurring more than 30 days after previous KD index day and continuing until the end of the follow-up period. Privigen demonstrated a lower IVIG resistance rate at 9.4% in comparison to TBSF, which exhibited a rate of 9.7% (odds ratio 0.72, 95% CI 0.52–0.99). Privigen had a lower odds of coronary involvement (odds ratio 0.38, 95% CI 0.18–0.82). There is no difference in recurrence rate (odds ratio 0.60, 95% CI 0.22–1.68). Privigen might have a lower rate of IVIG resistance and reduced coronary artery involvement. The discrepancy may be due to the concentration, the stabilizers, or the source of plasma. Further investigation is needed to compare the effectiveness of different IVIGs in the large randomized controlled clinical trial.

Serum IL-41 might be a biomarker for IVIG resistance and coronary artery lesions in Kawasaki disease.

This study aimed to evaluate serum IL-41 levels in IVIG resistance and CALs, and to elucidate the relationship between IL-41 and Kawasaki disease (KD)-related clinical parameters. 93 children with KD were collected. Baseline clinical data were obtained by physical examination. Serum IL-41 levels were detected with an enzyme-linked immunosorbent assay. The correlations between IL-41 and the clinical parameter of KD were performed by Spearman correlation coefficient. Receiver operating characteristic curve analysis was performed to assess the predictive ability of IL-41 for IVIG resistance and CALs. Serum IL-41 levels were significantly increased in the IVIG resistance group compared with the response group, and serum IL-41 levels in the CALs group were higher than those in the non-CALs group. Serum IL-41 levels were positively correlated with erythrocyte sedimentation rate, C-reactive protein and C-reactive protein/albumin ratio, but negatively correlated with albumin. Serum IL-41 levels was an independent risk factor for CALs, and total fever days and neutrophil-to-lymphocyte ratio (NLR) were independent predictors for IVIG resistance. The area under the curve (AUC) value for serum IL-41 to predict IVIG resistance was 0.73, yielding a sensitivity of 54.55% and a specificity of 81.71%. The AUC of serum IL-41 was 0.712, with a sensitivity of 63.16% and a specificity of 72.97% for predicting CALs. IL-41 was not inferior to NLR in predicting IVIG resistance (z=0.282, p=0.7783). Serum IL-41 was increased in IVIG resistance and CALs. Serum IL-41 might be a new potential biomarker for IVIG resistance and CALs.

A Proposed Scoring System for IVIG Resistance in Kawasaki Disease

A Proposed Scoring System for IVIG Resistance in Kawasaki Disease

Kawasaki disease and multisystem inflammatory syndrome in children. Differences, and similarities in a pediatric center in Mexico

To evaluate the differences and similarities in clinical picture, laboratory findings and outcomes between children's with Kawasaki Disease (KD) versus multisystem inflammatory syndrome (MIS-C). We conducted a retrospective, comparative study from children with Kawasaki Disease (KD) hospi-talized in Sinaloa Pediatric Hospital from January 1, 2004, to March 31, 2020, and patients with multisystem inflammatory syndrome (MIS-C) according with World Health Organization (WHO) case definition criteria be-tween May 1, 2020 and May 31, 2021. Demographic characteristics, epidemiological data, clinical features, laboratory findings, type of treatment and clinical outcomes were compared among both groups. Eighty-one patients were included (62 patients with KD and 19 with MIS-C). several clinical and lab-oratory differences were found among these two entities. Median age was lower in KD vs. MIS-C (25 vs 79 months). Those finding more frequent in KD were male gender (64.5 vs. 47.4%), Mucocutaneous features (93.5 vs. 63.2%): Oral changes (83.9 vs. 63.2%) and extremity changes (77.4 vs. 57.9%); complete form of KD was (75.8 vs. 47.4%), Coronary artery aneurysm (16.1 vs. 11.8%). Secondly, findings that were more frequent in MIS-C than KD were Gastrointestinal involvement (89.4 vs. 9.6%), shock (57.9 vs. 3.2%), neurological symp-toms (63.1 vs. 11.2%), kidney involvement (52.6 vs. 16.1%), heart disease in general (52.9% vs 29%): Myocardial dysfunction (23.5 vs. 11.3%) and pericardial effusion (17.6 vs. 2.9%). Lymphocyte count (2.07 + 2.03 vs. 4.28 + 3.01/mm3), platelet count (197.89 + 187.51 vs. 420.37 + 200.08/mm3); serum albumin (2.29 + 0.65 vs. 3.33 + 0.06g/dL), and CPR (21.4 + 11.23 vs. 14.26 + 12.37 mg/dL). KD vs. MIS-C types of Treatment: IVIG (96.8 vs. 94.7%), systemic steroids (4.82 vs. 94.7%), IVIG resistance (19.4 vs. 15.8). Finally, mortality in KD was 0% and 5.3% in MIS-C. Similarities were found in both groups such as fever, rash, and conjunctivitis. Nevertheless, signifi-cant differences such as severity of clinical presentation with multi-organ involvement and worst inflammato-ry response were found more frequently in MIS-C group than KD group, requiring more fluid replacement, use of inotropic agents and higher steroids dosages. Also, mortality rate was higher in patients with MIS-C thanpatients with KD. Similar results have been observed in other studies where both disorders were compared.

Predictive value of albumin for intravenous immunoglobulin resistance in a large cohort of Kawasaki disease patients

BackgroundIntravenous immunoglobulin (IVIG) has been the mainstay of treatment for Kawasaki disease (KD) over the past decades. However, 10–20% of KD patients are resistant to IVIG treatment which puts those patients at high risk of coronary artery lesions (CALs). Therefore, it is important to predict whether patients will be resistant to IVIG before the treatment. This study aimed to investigate the risk factors for IVIG non-responsive patients with KD.MethodsThis study enrolled patients diagnosed with KD and divided them into two groups, IVIG responders and IVIG non-responders. We compared the differences in demographics and clinical data between the two groups. Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis.ResultsIn total, 907 KD patients were reviewed, with 841 IVIG responders and 66 IVIG non-responders. Patients in IVIG responders were younger than IVIG non-responders. The length of hospitalization of the IVIG non-responders was significantly longer than IVIG responders. The neutrophils%, C-reaction protein (CRP), and CRP/albumin ratio in IVIG responders were significantly lower than in IVIG non-responders (P < 0.05). The lymphocyte% and Albumin in IVIG responders were significantly higher than in IVIG non-responders. Multivariable logistic regression analysis demonstrated that albumin (OR = 0.881, 95% CI, 0.781 to 0.994, p-value = 0.039) was an independent risk factor for predicting IVIG resistance. The area under the ROC curve was 0.644, with a cut-off of ≤ 33.4 g/L determined by Youden’s index. The sensitivity and specificity in predicting IVIG resistance were 40.91% and 83.47%, respectively.ConclusionAlbumin can serve as a potential predicting marker for IVIG resistance in KD. A lower albumin level may be useful for identifying KD patients with a high risk of IVIG resistance to guide further therapy strategies.

Kawasaki disease in Malaysia: Biochemical profile, characterization, diagnosis and treatment.

Kawasaki disease (KD) is an acute idiopathic systemic vasculitis with a self- limiting course that predominantly affects children under 5 years old, particularly in the East Asian countries. Nevertheless, to date, the data on KD in Malaysia are limited. This study aimed to evaluate the epidemiology, clinical features, treatment, and outcomes of KD among the pediatric patients admitted to Hospital Canselor Tunku Muhriz (HCTM), Kuala Lumpur, Malaysia. A retrospective cohort study of 66,500 pediatric patients presented at HCTM from the year 2004 to 2021 was conducted. 62 KD cases out of 66,500 pediatric admissions were reported, with a male-to-female ratio of 1.58 to 1. Majority of KD patients (95.0%) were younger than 5 years old. Prior infection was reported in 5 KD patients (8.1%). Apart from the classical features, manifestations of various organ systems including cardiovascular (16.1%), gastrointestinal (43.5%), neurological (1.61%), musculoskeletal (1.61%), and genitourinary (17.7%) systems were observed. There was a significant association between sterile pyuria and coronary artery aneurysm (CAA) (p < 0.05). Interestingly, abnormal liver parameters (p < 0.05) and incomplete KD (p < 0.05) were significantly related to IVIG resistance. The presence of family history, immunological disorder, and previous infection in our KD patients suggested that there is a possibility of genetic, immunological, and infectious roles in the pathophysiology of KD. IVIG resistance is more likely to occur in KD patients with hepatic dysfunction or incomplete KD presentation. These findings highlighted the significant contribution of laboratory parameters to the prognosis of KD, prompting more in-depth research on the KD scoring systems and their relevance in this country.

The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population.

BackgroundKawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported.MethodsA total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance.ResultsBoth of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06–3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10–2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62–4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37–3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22–2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24–2.27, p = 0.0008).ConclusionOur findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.

Retrospective Cohort Study of Clinical Profile and IVIg Resistance in Children with Incomplete Kawasaki Disease in a Tertiary Care Center

Retrospective Cohort Study of Clinical Profile and IVIg Resistance in Children with Incomplete Kawasaki Disease in a Tertiary Care Center

Predicting IVIG resistance in Kawasaki disease with machine learning models augmented with synthetic sampling

Predicting IVIG resistance in Kawasaki disease with machine learning models augmented with synthetic sampling

Ultrasound evaluation of endothelial dysfunction in immunoglobulin-resistant children with acute Kawasaki disease.

Given the evidence that brachial artery flow-mediated dilation (FMD) is declined in children later after the onset of Kawasaki disease (KD), we hypothesized that indicators that detect the situation of the endothelium are useful parameters that can accurately reflect subclinical dysfunction in resistant patients and assist in differentiating patients with KD at a higher risk of IVIG resistance, which may be valuable in better understanding how to protect patients from endothelial and thrombotic complications. Fifty IVIG-resistant KD children, 120 IVIG-responsive KD children, 35 febrile children with acute upper respiratory infection, and 50 healthy controls were recruited, and indicators reflecting endothelial inflammation, including flow-mediated dilation (FMD), were measured. Receiver operating characteristic (ROC) curve analysis was utilized to determine the threshold values of these indicators of IVIG resistance. Multiple logistic regression analysis was performed to determine whether FMD was an independent predictor of IVIG-resistant patients. In comparison with the lab data, PCT, Na + , and FMD exhibited AUCs of 0.727, 0.653, and 0.698 (P < 0.05), respectively, in predicting IVIG resistance in KD through ROC analysis. PCT > 1.69ng/ml, Na + < 133.2mmol/l, and FMD < 5.79% were independent predictors of IVIG resistance in KD (OR 4.257, 3.516, 3.563, 95% CI 1.549 ~ 11.700, 1.277 ~ 9.680, 1.299 ~ 9.772, P < 0.05). More severe endothelial dysfunction, especially lower FMD, was present in IVIG-resistant patients than in IVIG-responsive patients. It is a helpful diagnostic tool that provides supportive criteria to detect KD patients at a higher risk of IVIG resistance when FMD < 5.79% in children. Key Points • IVIG-resistant KD patients have more severe endothelial dysfunction than IVIG-sensitive patients. • FMD < 5.79% may indicate an increased risk of IVIG resistance in children with Kawasaki disease.

A Sri Lankan infant with immunoglobulin resistant incomplete Kawasaki disease with a vesicular psoriasiform rash, hypertension and late onset small joint arthritis: a case report

BackgroundKawasaki disease (KD) is a medium and small vessel vasculitis which usually has a good response to immunoglobulin therapy (IVIG). We present a case of incomplete KD with IVIG resistance associated with an unusual combination of vesicular guttate-psoriasiform rash, hypertension and late onset small joint arthritis.Case presentationA four-month-old male infant from Sri Lanka presented with high fever, conjunctival redness, pedal oedema and skin rash. He was found to have hypertension since admission with a high white cell count and high inflammatory markers. There was poor response to intravenous antibiotics and subsequent 2D echocardiogram revealed coronary artery aneurysms suggestive of KD. In the third week of illness he developed a vesiculo-papular rash involving face, trunk and limbs – which on biopsy revealed features of guttate psoriasis.Fever spikes continued and the coronary arteries showed progressive dilatation despite timely intravenous immunoglobulin administered on day 6 and methylprednisolone administered on day 10-13. Therapeutic response by means of reduction of fever was seen only after initiation of intravenous infliximab on day 28 of illness for which the fever responded within 24 hours. He developed a small joint arthritis of hands and feet on day 40 of illness which responded only after initiating methotrexate therapy. The hypertension persisted for 4 months after the onset of the illness before complete resolution.ConclusionThis case report depicts an unusual presentation of KD with a vesicular guttate-psoriasiform eruption, hypertension and late onset small joint arthritis. It highlights that clinicians should be aware of the fact that KD could present with such atypical manifestations and could develop unusual complications.

Predictive role of sampling-time specific prognostic nutritional index cut-off values for intravenous immunoglobulin resistance and cardiovascular complications in Kawasaki disease

BackgroundIntravenous immunoglobulin (IVIG) resistance and cardiovascular complications prediction are pivotal topic of interests in Kawasaki disease (KD). The prognostic nutritional index (PNI) has been proposed to be valuable in predicting the severity of inflammatory status and prognosis in clinical circumstances, with limited data in KD. Therefore, we prospectively investigated the role of sampling-time specific PNI cut-off values in predicting initial IVIG resistance as well as cardiovascular complications in patients with KD for the first time. MethodsA total of 755 patients with KD were prospectively recruited between January 2015 and December 2019. Patients with KD were subgrouped based on the presence of IVIG resistance or cardiovascular complications. The clinical and laboratory parameters were compared. Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was further applied to assess the predictive values of PNI in IVIG resistance and cardiovascular complications. ResultsThe lower level of PNI was identified as independent risk factors for initial IVIG resistance and cardiovascular complications. The discriminating cut-off values of the PNI for IVIG resistance, all cardiovascular complications, CALs, KDSS and myocarditis were 47.8, 52.2, 38.6, 48.2 and 52.0, with the corresponding sensitivities of 0.573, 0.679, 0.174, 0.750, 0.851, and specificities of 0.753, 0.549, 0.957, 0.679 and 0.576, respectively. After sampling time stratification, the sensitivities and specificities of the PNI obtained at the sixth day from fever onset for prediction of both IVIG resistance (0.778, 0.787) and all cardiovascular complications (0.667, 0.753) remarkably improved. ConclusionPNI may serve as a promising predictor for KDSS in patients with KD. PNI obtained at sixth day from fever onset possess good predictive power for both IVIG resistance and all cardiovascular complications in KD.

Etanercept with IVIg for acute Kawasaki disease: a long-term follow-up on the EATAK trial.

The Etanercept as Adjunctive Treatment for Acute Kawasaki Disease, a phase-3 clinical trial, showed that etanercept reduced the prevalence of IVIg resistance in acute Kawasaki disease. In patients who presented with coronary artery involvement, it reduced the maximal size and short-term progression of coronary artery dilation. Following up with this patient group, we evaluated the potential long-term benefit of etanercept for coronary disease. Patients were followed for at least 1 year after the trial. The size of dilated arteries (z-score ≥ 2.5) was measured at each follow-up visit. The z-score and size change from baseline were evaluated at each visit and compared between patients who received etanercept versus placebo at the initial trial. Forty patients who received etanercept (22) or placebo (18) in the Etanercept as Adjunctive Treatment for Acute Kawasaki Disease trial were included. All patients showed a persistent decrease in coronary artery size measurement: 23.3 versus 5.9% at the 6-month visit, 24 versus 13.1% at the 1-year visit, and 20.8 versus 19.3% at the ≥ 2-year visit for etanercept or placebo, respectively, with similar results for decrease in coronary artery z-scores. In a multivariate analysis, correcting for patients' growth, a greater size reduction for patients on the etanercept arm versus placebo was proved significant for the 6-month (p = 0.005) and the 1-year visits (p = 0.019) with a similar end outcome at the ≥ 2-year visit. Primary adjunctive therapy with etanercept for children with acute Kawasaki disease does not change the end outcome of coronary artery disease but may promote earlier resolution of artery dilation.

Sterile Pyuria in Kawasaki Disease: A Large Prospective Cohort Study

BackgroundKawasaki disease (KD) is an acute systemic vasculitis and is becoming the leading cause of acquired cardiac disease in Children. Sterile pyuria is a known complication of KD. However, its associations with the inflammatory reaction severity, IVIG resistance as well as coronary artery lesions (CALs) in KD remain elusive.AimsWe aimed to analyze the clinical profiles of sterile pyuria in KD, to determine whether sterile pyuria is an indicator of the disease severity in patients with KD, and to assess the associations between sterile pyuria and IVIG resistance as well as CALs.MethodsWe prospectively collected data from 702 patients with KD between January 2015 and June 2020. Profiles of patients with sterile pyuria (group A, n = 63) were compared to those of patients without sterile pyuria (group B, n = 639). The associations between sterile pyuria and IVIG resistance as well as CALs in KD were further determined by univariate and/or multivariate logistic regression analysis.ResultsSterile pyuria was observed in 9.0% of patients with KD, without predominance in age spectrum and gender. The levels of neutrophil percentages, alanine transaminase, total bilirubin, blood urea nitrogen, creatinine, the incidence of initial IVIG resistance, and rate of moderate/giant coronary artery aneurysms (CAAs) were significantly higher in group A than that in group B. Sterile pyuria was identified as an independent risk factor for initial IVIG resistance, yielding high specificity (92.7%) and low sensitivity (18.5%). However, sterile pyuria was not associated with repeated IVIG resistance and persistence of CALs in KD.ConclusionThe incidence of sterile pyuria is relatively low in KD patients. Patients with sterile pyuria in KD exhibited a more severe inflammatory burden and were more likely to develop the initial IVIG resistance and moderate/giant CAAs. The overall prognosis of KD patients with sterile pyuria was satisfactory.