Coronary Aneurysm and IVIG Resistance Prediction in Kawasaki Disease

Coronary Aneurysm and IVIG Resistance Prediction in Kawasaki Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Coronary Aneurysm and IVIG Resistance Prediction in Kawasaki Disease Yusuf Ziya Varlı, Kazim Oztarhan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-56396/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version 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. Pediatrics Rheumatology Kawasaki disease prolonged fever coronary aneurysm IVIG resistance Background Kawasaki disease (KD) is an acute febrile systemic vasculitis of childhood that is characterized by fever, bilateral non-exudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rashes, and cervical lymphadenopathy. [1-3] KD generally in children < 5 years of age, and if left untreated it has been reported that 15%–25% of patients with KD develop coronary artery lesions ([CALs], aneurysms, or ectasia). [3] KD can cause myocarditis, arrhythmias, and myocardial infarction in the acute phase, and sudden cardiac death due to coronary artery aneurysms and stenosis in the subacute and chronic phases. KD is an important health problem, and early diagnosis and treatment significantly reduce the risk of complications, morbidity, and mortality with coronary artery disease. [1-4] Laboratory tests, although non-specific, provide support for a diagnosis of KD in patients with non-classic, but suggestive clinical features. Clinical experience suggests that KD is unlikely if the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count are normal after day 7 of illness. In addition, a low white blood cell count and lymphocyte predominance suggest an alternative diagnosis. [2] The efficacy of intravenous immunoglobulin (IVIG) administered in the acute phase of KD has been well-established to reduce the prevalence of coronary artery abnormalities. Patients who laboratory evidence of inflammation who fail to respond to a second infusion of IVIG, steroids, or infliximab require additional therapy to control inflammation. [2-4] In this study we determined the clinical characteristics, laboratory findings, demographic features, frequency of coronary involvement, and resistance to IVIG treatment in Turkey based on the data from our hospital. Methods The diagnosis of KD is of two types (classical type/complete KD and incomplete KD/atypical KD). [2] The diagnosis of typical KD is based on the presence of ≥ 5 days of fever and the presence of ≥ 4 of 5 principal clinical features. [2] The diagnosis of incomplete (atypical) KD should be considered in any infant or child with prolonged unexplained fever, < 4 of the principal clinical findings, and compatible laboratory or echocardiographic findings. [2] Gender, age at diagnosis, presence of diagnostic criteria, number of days with fever, and personal and family histories were recorded. Twenty-six cases with missing file data or with a diagnosis difference other than KD were excluded from the study at the beginning. The patients were subjected to echocardiographic examination at the time of diagnosis and in the subacute period for the presence of coronary artery involvement and the risk of complications. Myocardial wall mobility, ejection fraction values (%), and the diameters of coronary arteries were measured; Z scores were calculated according to American Heart Association (AHA) guidelines. [2] According to the Z score calculation, the following definitions were applied: dilation, 2 < Z score < 2.5 or if initially < 2 and a decrease in Z score during follow-up ≥1; small aneurysm, 2.5 ≤ Z score < 5; moderate aneurysm, 5 ≤ Z score < 10; and large or giant aneurysm, Z score was defined as ≥ 10. [2] IVIG and aspirin were given in appropriate doses to all patients hospitalized with a diagnosis of KD according to AHA criteria as the standard primary treatment. [2] IVIG resistance is defined as recurrent or permanent fever development at least 36 h after the end of the IVIG infusion in 10%–20% of patients with KD. [2,5,6] The cases were grouped in terms of coronary artery aneurysms (CAAs) development and responses to IVIG treatment. The gender of the patients, the age at the time of diagnosis, the presence of diagnostic criteria, the number of days with fever, and the personal and family histories were recorded. Retrospective statistical comparisons were made between the groups. All data were obtained from clinical and laboratory findings recorded at the time of diagnosis, echocardiographic examinations obtained at diagnosis, and follow-up. Twenty-six patients with missing file data or with a diagnosis other than KD were excluded from the study at the beginning. Laboratory findings included hemogram parameters, ESR, acute phase reactants (CRP, procalcitonin [PCT], and ferritin), electrolytes (Na, K, Cl, Ca, Mg, and P), kidney and liver function tests (ALT, AST, GGT, LDH, albumin, ALP, total and direct bilirubin, urea, creatinine, and uric acid), lipid profiles (total cholesterol, LDL, HDL, and triglycerides), coagulation values (PT, aPTT, and INR), urinalyses, and hemoculture results. Data were analyzed using (SPSS Statistics for Macintosh, version 24.0; IBM Corp., Armonk, NY, USA). Categorical variables were summarized using frequencies (percentage [%]). The mean ± standard deviation was used for continuous variables. Normality was assessed for continuous data using the Kolmogorov–Smirnov test. An independent samples t-test was used for continuous variables. Categorical variables were compared using a chi-squared test. A p-value < 0.05 was taken as an indicator of statistical significance. Results and significance values are summarized in the relevant tables. Results Two hundred fifty-nine patients (males, 162, females 97; male-to-female ratio, 1.67) were treated in our hospital, with 48 of patients (19%) < 1 year of age. The age range was 3 months–9.8 years. The average number of days before admission to the hospital was 6.7. Of the patients, 90.7% received outpatient antibiotic therapy prior to hospitalization. CAA development and IVIG resistance were noted in 11.6% and 12.3% of patients, respectively. Coronary ectasia/dilatation was detected in 15 patients (6% [2 < Z score < 2.5]), and the coronaries were completely normal in 214 patients (83%). According to the diagnostic criteria, 31% of patients were treated as typical KD and 69% as 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%). The frequencies of clinical findings in diagnostic types are summarized in Table 1. CALs were demonstrated in 45 patients; the right coronary artery (RCA) alone (20%), the left coronary artery (LCA) alone (44.5%), and the RCA and LCA were involved together (35.5%). The left main coronary artery (LMCA) 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%). Of the patients with coronary artery involvement, 53.3% were < 1 year of age and 83.3% were < 5 years of age. IVIG resistance was detected in 35.6% of patients with CAAs. All patients were treated with standard primary therapy, IVIG, and aspirin. Aspirin was discontinued in 29 patients (11%) because salicylic acid poisoning developed. Two patients were given pulsed steroid therapy, eight patients needed intensive care, and one patient was treated with plasmapheresis. Table 2 and 3 summarize the clinical and demographic data of the patients with respect to their responsiveness to IVIG treatment and the development of CAAs. It was observed that the frequency of CAA development increased in IVIG-resistant patients, and similarly, the frequency of IVIG resistance increased in those who developed CAAs. This association was statistically significant (p < 0.001). There was a statistically significant difference between the age groups with both CAA development and IVIG resistance using a chi-square test and no significant difference existed as a function of gender. When IVIG resistant and sensitive patients are compared (Table 3) 91.6% of IVIG-resistant patients were < 5 years of age. Hospitalization time and coronary artery involvement increased and were statistically significant. Laboratory findings were analyzed by grouping in Table 4. according to coronary involvement and in Table 5 according to IVIG responsiveness. In Table 4, the laboratory findings of patients with KD were compared according to the presence of coronary artery involvement. When the laboratory findings of patients with coronary artery involvement were examined, it was found that the hematocrit, total protein, and albumin levels decreased, and the leukocyte count, platelet count, and CRP, troponin T, and N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels increased. In Table 5, the laboratory findings of patients with IVIG resistance were compared with patients who were sensitive to IVIG. In patients with IVIG resistance, the leukocyte and platelet counts, CRP, and ALT, troponin T, and NT-proBNP levels were increased, while the hematocrit and sodium levels were decreased. Discussion A CAA is the most important complication of KD. CAAs develop in 15%–25% of untreated patients; this rate decreases to 5% with treatment within the first 10 days. [3] Early diagnosis and treatment is very important because it directly affects mortality. To provide early intervention for CALs caused by KD, we analyzed the clinical characteristics of typical and incomplete KD patients. In this study there was no significant difference between the frequency of clinical findings in patients diagnosed with typical and atypical KD. The most common findings in both groups were mucosal involvement in the mouth, polymorphic exanthema, and non-exudative conjunctive injection. The most common clinical finding (80%) in some studies was non-exudative conjunctive injection followed by polymorphic exanthema and mucosal involvement in the mouth. [7] Asian patients with changes in the oral mucosa, cervical lymphadenopathy, swelling of the extremities, and polymorphous rashes were more likely to be IVIG-resistant, but in non-Asian patients there was no significant difference among these symptoms and IVIG resistance. [17] In the population in our study, we did not note any significant difference between IVIG resistance and the risk of developing coronary lesions and clinical findings. The prevalence of coronary artery abnormalities in a clinical trial of initial treatment was 23% 4 weeks after enrollment, which reduced to 8% with 4 infusions of low-dose IVIG. In a subsequent trial of single high-dose IVIG, this was further reduced to approximately 4%. [8,9] In our study, CAAs were detected in 11.6% of patients. There is no conclusive data regarding the incidence of the disease and complications due to the lack of large-scale research in South Korea with a sufficient number of cases. Several different risk scores are used to predict IVIG resistance and CALs. Shin et al. [10] reported that among the risk scoring systems, the Kobayashi risk score demonstrated significant differences between IVIG resistance and responder groups in Korean patients with KD. Many researchers have scrutinized the clinical data and laboratory parameters at onset predicting the risk of CAA. [11,12] Risk factors for CAA are duration of fever > 2 weeks, platelet count, increased acute phase reactants, and age < 5 years. Demonstration of CALs by echocardiography is important for prognostication. Damage to coronary arteries is a substantial risk for a significant percentage of children with KD, most often for those with resistance to IVIG. Maximal efforts should be made to visualize all major coronary artery segments. In order of highest-to-lowest frequency of occurrence, typical sites of CAAs include the proximal LAD and proximal RCA, followed by the LMCA, LCx, distal RCA, and the junction between the RCA and posterior descending coronary artery. Enlargement of the LMCA caused by KD does not involve the orifice and rarely occurs without associated dilation of the LAD, the LCx, or both arteries. [2] In our study CALs existed in 45 patients; the RCA alone (20%), the LCA alone (44.5%), and the RCA and LCA were involved together (35.5%). The LMCA affected 20 patients, the LAD affected nine patients, the LCx affected two patients, and LAD and LCx together affected two patients. IVIG resistance was more common in infants and the hospitalization times were longer in this group. The coronary involvement rate in our patients was 17.3%. This rate was 12.8% in the IVIG-responsive group and 50% in the IVIG-resistant group. KD has no specific diagnostic laboratory markers. Recent studies have investigated factors for predicting resistance to IVIG and CALs. These data include the duration of fever, polymorphonuclear neutrophil (PMN) cell count, hemoglobin level, platelet count, and CRP, transaminase, total bilirubin, and NT-proBNP, albumin, and sodium levels. [13] In our study, when the laboratory findings of the group in which coronary artery aneurysms were detected in KD, the leukocyte and platelet counts, and CRP, troponin T, and NT-proBNP levels were significantly increased and the albumin level was decreased. Several previous studies demonstrated that a higher PMN percentage, and NT-proBNP, total bilirubin, CRP, aspartate aminotransferase, and alanine aminotransferase levels were considered predictive factors for patients with KD resistance to IVIG treatment. [13-16] In our study a statistically significant decrease in the sodium level was observed in IVIG-resistant patients. The cause of hyponatremia is still unknown in patients with KD. Lim et al. [17] found that there was a strong negative correlation between the level of serum sodium and inflammatory factors, including CRP and interleukin-6 (IL-6) in children with KD. The most probable pathophysiologic mechanism underlying hyponatremia is non-osmotic secretion of antidiuretic hormone (ADH). Several studies have confirmed that the release of ADH is promoted by IL-6 and tumor necrosis factor-α (TNF-α) during inflammation. [18] IL-6, TNF-α, and other cytokines participate in inflammation among KD patients in the acute phase, [19] suggesting that hyponatremia may be associated with inappropriate release of ADH. The marked increase in plasma IL-6 and TNF-α in IVIG-resistant infants compared with IVIG-responsive patients [20,21] may explain the significant hyponatremia in IVIG non-responders. In our study it was observed that hyponatremia and hypoalbuminemia were correlated with an increase in acute phase reactants in IVIG-resistant patients. In addition to KD, studies involving patients with inflammatory diseases, such as pneumonia, urinary tract infections, and lupus erythematosus, also demonstrated that hyponatremia is an important marker for severity and prognosis. [22,23] The mechanisms underlying hypoalbuminemia consist of the following: increased vascular permeability leading to leakage of albumin, [24,25] liver dysfunction resulting in decreased albumin synthesis; and a lack of essential amino acids due to low nutrient intake or malnutrition, resulting in reduced albumin synthesis. [26] In our study thyrombocytosis was detected in patients with CAL and IVIG resistance. This increase was statistically significant in CAL patients. Although some studies recognized both thrombocytopenia and significant thrombocytosis as predictors of CAA or IVIG resistance; however, the majority of studies showed no association. [27,28] The mechanism underlying thrombocytosis is unclear. It has been suggested that the elevated thrombopoietin level caused by acute inflammatory responses can lead to thrombocytopoiesis. [29] In our study IVIG resistance was detected in 12.4% of the patients. When the group developing coronary artery aneurysms was examined, we found that aneurysms developed more frequently in < 1 year and the risk of developing IVIG resistance and length of hospital stay were significantly increased. Several studies have reported that the frequency of developing CAA increases in 5 years. [5,6] Based on a meta-analysis, when patients who were IVIG-resistant and -responsive were compared, the hemoglobin level, leukocyte and platelet counts, and ESR were statistically significant. [30] In our study the increased risk of IVIG resistance was shown to be statistically significant, especially in the group < 5 years of age. When the laboratory findings of our IVIG-resistant patients were examined, a significant increase existed in the leukocyte count (marked neutrophil increase), platelet count, and CRP, ALT, troponin T and NT-proBNP levels, while the hematocrit and sodium levels were significantly decreased. Although IVIG is the established treatment for acute KD, [2,3] in some studies < 10% of patients with KD were resistant to this treatment. Patients resistant to IVIG were at a higher risk of developing CALs than patients responding to IVIG. [15,16] Considering the frequency of IVIG resistance by age group, a significant increase in risk occurred in infants (p <0.001). In our study the risk of developing IVIG resistance increased as age decreased. Indeed, there are several studies with similar results. [30-33] Conclusion As a result, KD patients in Turkey, in terms of development-related coronary complications, have a higher risk. It is important to identify factors that increase the risk of coronary complications and IVIG resistance in KD. Because the risk of CAA is always higher in IVIG-resistant patients, predicting IVIG resistance may play a role in reducing the development of CAA. Abbreviations AHA: American Heart Association CAA: coronary artery aneurysm CALs: coronary artery lesions CRP: C-reactive protein ESR: erythrocyte sedimentation rate IVIG: intravenous immunoglobulin KD: Kawasaki disease LAD: left anterior descending artery LCA: left coronary artery LCx: left circumflex artery LMCA: left main coronary artery RCA: right coronary artery Declarations Ethics approval and consent to participate The study protocol was approved by the University of Health Science, Kanuni Sultan Suleyman Research and Training Hospital Human Investigation Committee (HIC) (protocol number 48865165-302.14.01). Consent for publication Not applicable. Availability of data and materials The datasets analysed during the current study are available from the corresponding author on reasonable request. Competing interests Both authors declare that they have no competing interests. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Authors' contributions KO: carried out the management of the research and the cardiological evaluation of the patients, encouraged Dr. Varli, reviewed and revised the article, supervised the project. YZV: Researched the literature, performed statistical analysis of the data of the cases and contributed to the writing of the article. All authors were contributors to the writing of the manuscript and formation of tables. All authors read and approved the final manuscript. Acknowledgements The authors acknowledge the contributions of Assoc. Prof. Nuray Aktay Ayaz from the Department of Pediatric Rheumatology. References Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children.] Arerugi. 1967;16:178–2. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017;135:e927–9. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA. Diagnosis, treatment, and longterm management of Kawasaki disease. A statement for health professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Circulation. 2004;110:2747–71. Moffett BS, Syblik D, Denfield S, Altman C, Tejtel-Sexson K. Epidemiology of immunoglobulin resistant Kawasaki disease: results from a large, national database. Pediatr Cardiol. 2015;36:374–8. Newburger JW, Sleeper LA, McCrindle BW, Minich LL, et al. Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007;356:663–75. Bar-Meir M, Kalisky I, Schwartz A, Somekh E, Tasher D, Israeli Kawasaki Group. Prediction of resistance to intravenous immunoglobulin in children with kawasaki disease. J Pediatric Infect Dis Soc. 2018;7:25–9. Morales-Quispe JA, Espinola-Zavaleta N, Caballero-Caballero R, García-López JJ, Rodríguez-Quezada JM, Betanzos-Rodríguez E. Clinical evolution and cardiovascular complications in children with Kawasaki disease. Rev Med Inst Mex Seguro Soc. 2011;49:295–300. Newburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, Glode MP, Mason WH, Reddy V, Sanders SP, Shulman ST, Wiggins JW, Hicks RV, Fulton DR, Lewis AB, Leung DYM, Colton T, Rosen FS, Melish ME. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986;315:341–7. Newburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, Colan SD, Duffy CE, Fulton DR, Glode MP, Mason WH, Meissner HC, Rowley AH, Shulman ST, Reddy V, Sundel RP, Wiggins JW, Colton T, Melish ME, Rosen FS. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. New Engl J Med. 1991;324:1633–9. Shin J, Lee H, Eun L. Verification of current risk scores for Kawasaki disease in Korean children. J Korean Med Sci. 2017;32:1991–6. Daniels SR, Specker B, Capannari TE, Schwartz DC, Burke MJ, Kaplan S. Correlates of coronary artery aneurysm formation in patients with Kawasaki disease. Am J Dis Child. 1987;141:205–7. Koren G, Lavi S, Rose V, Rowe R. Kawasaki disease: Review of risk factors for coronary aneurysms. J Pediatr. 1986;108:388–92. Woo HO. Predictive risk factors of coronary artery aneurysms in Kawasaki disease. Korean J Pediatr. 2019;62:124– Nakamura Y, Yashiro M, Uehara R, Sadakane A, Tsuboi S, Aoyama Y, Kotani K, Tsogzolbaatar EO, Yanagawa H. Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey. J Epidemiol. 2012;22:216–21. Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, Martin DD, Newburger JW, Burns JC. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008; 153:117–21. Muta H, Ishii M, Furui J, Nakamura Y, Matsuishi T. Risk factors associated with the need for additional intravenous gamma-globulin therapy for Kawasaki disease. Acta Paediatr. 2006;95:189–93. Lim GW, Lee M, Kim HS, Hong YM, Sohn S. Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion in kawasaki disease. Korean Circ J. 2010;40:507–13. Kim JH, Park JH, Eisenhut M, Yu JW, Shin JI. Inflammasome activation by cell volume regulation and inflammation-associated hyponatremia: a vicious cycle. Med Hypotheses. 2016;93:117–21. Agarwal S, Agrawal DK. Kawasaki disease: etiopathogenesis and novel treatment strategies. Expert Rev Clin Immunol. 2017;13:247–58. Hu P, Jiang GM, Wu Y, Huang BY, Liu SY, Zhang DD, Xu Y, Wu YF, Xia X, Wei W, Hu B. TNF-alpha is superior to conventional inflammatory mediators in forecasting IVIG nonresponse and coronary arteritis in Chinese children with Kawasaki disease. Clin Chim Acta. 2017;471:76–80. Wu Y, Liu FF, Xu Y, Wang JJ, Samadli S, Wu YF, Liu HH, Chen WX, Luo HH, Zhang DD, Wei W, Hu P. Interleukin-6 is prone to be a candidate biomarker for predicting incomplete and IVIG nonresponsive Kawasaki disease rather than coronary artery aneurysm. Clin Exp Med. 2019;19:173–81. Park SW, Shin SM, Jeong M, Cho DH, Lee KH, Eisenhut M, Kronbichler A, Moritz M, Il Shin J. Hyponatremia in children with respiratory infections: a cross-sectional analysis of a cohort of 3938 patients. Sci Rep. 2018;8:164–94. Il Shin J, Park SJ, Suh CH, Lee GH, Hur MW, Han SY, Kim DS, Kim JH. Hyponatremia in patients with systemic lupus erythematosus. Sci Rep. 2016;6:255– Kuo HC, Liang CD, Wang CL, Yu HR, Hwang KP, Yang KD. Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease. Acta Paediatr. 2010;99:1578–83. Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: pathogenesis and clinical significance. JPEN J Parenter Enteral Nutr. 2019;43:181–93. Arques S. Human serum albumin in cardiovascular diseases. Eur J Intern Med. 2018;52:8–12. Maric LS, Knezovic I, Papic N, Mise B, Roglic S, Markovinovic L, Tesovic G. Risk factors for coronary artery abnormalities in children with Kawasaki disease: a 10-year experience. Rheumatol Int. 2015;35:1053– Berdej-Szczot E, Małecka-Tendera E, Gawlik T, Firek-Pędras M, Szydłowski L, Gawlik A. Risk factors of immunoglobulin resistance and coronary complications in children with Kawasaki disease. Kardiol Pol. 2017;75:261– Ishiguro A, Ishikita T, Shimbo T, Matsubara K, Baba K, Hayashi Y, Naritaka S, Nakahata T. Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease. Thromb Haemost. 1998;79:1096– Li X, Chen Y, Tang Y, Ding Y, Xu Q, Sun L, Qian W, Qian G, Qin L, Lv H. Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases. Eur J Pediatr. 2018;177:1279–92. Rigante D, Andreozzi L, Fastiggi M, Bracci B, Natale MF, Esposito S. Critical Overview of the Risk Scoring Systems to Predict Non-Responsiveness to Intravenous Immunoglobulin in Kawasaki Syndrome. Int J Mol Sci. 2016;17:278. Fabi M, Andreozzi L, Corinaldesi E, Bodnar T, Lami F, Cicero C, Tchana B, Landini C, Sprocati M, Bigucci B, Balsamo C, Valin PS, Fazzio GD, Iughetti L, Valletta E, Marchetti F, Donti A, Lanari M. Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort. Eur J Pediatr. 2019;178:315–22. Tang Y, Yan W, Sun L, Huang J, Qian W, Ding Y, Lv H. Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an East China population. Clin Rheumatol. 2016;35:2771–6. Tables Table 1 . Frequency diagnostic criteria met in patients Clinical Findings Total (n:259) Typical KD (n:80) Incomplete KD (n:179) (%) (%) (%) Changes of the lips and oral mucosa Conjunctival congestion Cervical lymphadenopathy Rash Peripheral-extremity changes 206 (79.5%) 168 (64.9%) 124 (47.9%) 179 (69.1%) 140 (54.1%) 75 (93.8%) 70 (87.5%) 57 (71.3%) 72 (90%) 58 (72.5%) 131 (73.2%) 98 (54.7%) 67 (37.4%) 107 (59.8%) 82 (45.8%) KD: Kawasaki Disease Table 2 . Demographic data of patients in the development of coronary artery aneurysm Variable Development of coronary aneurysm P value Normal (n = 229) CAA (n = 30) Gender Male Female 0.194 a 140 (61.1%) 89 (38.9%) 22 (73.3%) 8 (26.7%) Age range 2.94 (0.11–9.9) d 0.71 (0.19–9.78) d <0.001 b Total fever days 6 (1–20) d 6 (2–15) d 0.896 b Age group <1 year 1≤ and <5 years old ≥5 years old <0.001 c 32 (14%) 141 (61.6%) 56 (24.5%) 16 (53.3%) 9 (30%) 5 (16.7%) Hospitalization time (days) 10 (3–35) d 13 (6–35) d 0.003 b IVIG resistance frequency 16 (75%) 16 (35.6%) <0.001 a Type of diagnosis 0.341 a Typical KD 73 (91.3%) 7 (8.8%) Incomplete KD 156 (87.2%) 23 (12.8%) a Pearson chi-square test was used b Mann-Whitney U test was used c significant difference was observed in the < 1 year of age group d "Median" and "lowest - highest values" in parentheses were specified for non-normally distributed data CAA: Coronary artery aneurysm; IVIG: intravenous immunoglobulin Table 3 . Demographic data of patients in response to IVIG treatment Variable IVIG responsiveness P value Responders (n = 227) Non-responders (n = 32) Gender Male Female 0.701 a 141 (62.1%) 86 (37.9%) 21 (65.6%) 11 (34.4%) Age range 3.06 (0.16–9.9) d 1.12 (0.11–9.78) d 0.002 b Total fever days 5 (1–20) d 6 (1–20) d 0.028 b Age group <1 year of age 1≤ and <5 years of age ≥5 years of age <0.001 c 33 (14.5%) 136 (59.9%) 58 (25.6%) 15 (46.9%) 14 (43.8%) 3 (9.4%) Hospitalization time (days) 10 (3–35) d 14 (5–35) d 0.005 b Coronary involvement 29 (12.8%) 16 (50%) <0.001 a Type of diagnosis 0.718 a Typical KD 71 (88.8%) 9 (11.3%) Incomplete KD 156 (87.2%) 23 (12.8%) a Pearson chi-square test was used b Mann-Whitney U test was used c significant difference was observed in the < 1 year age group d "Median" and "lowest - highest values" in parentheses were specified for non-normally distributed data IVIG: intravenous immunoglobulin Table 4 . Central tendency and variability measures of laboratory data according to coronary involvement Variable Normal Coronary involvement P value (n = 214) (n = 45) Sedimentation 67.35 (27.47) c 66.64 (28.86) 0.880 a WBC 13 000 (1 000– 49 570) d 14 950 (5 290– 36 800) d 0.002 b NEU (%) 61.74 (16.88) c 59.70 (19.12) c 0.504 a Hematocrit 32.19 (4.14) c 30.65 (4.47) c 0.032 a PLT 374 000 (51 000–2 099 000) d 482 000 (162 000–1 395 000) d 0.001 b C-reactive protein 67.9 (1–417.4) d 93.5 (3.1–369) d 0.044 b Total protein 7.1 (1.16) c 6.53 (0.8) c 0.001 a Albumin 3.68 (0.51) c 3.49 (0.46) c 0.037 a AST 34 (4–628) d 38 (15.3–1 230) d 0.642 b ALT 24 (4–705) d 26 (8–704) d 0.307 b Na 135.03 (3.25) c 135.33 (3.23) c 0.591 a K 4.46 (0.59) c 4.76 (0.75) c 0.020 a Urea 18 (1–95) d 14 (1–57) d 0.003 b Creatinine 0.3 (0.09–1.03) d 0.27 (0.13–0.8) d 0.006 b Troponin T 0.003 (0.003–0.03) d 0.007 (0.003–0.127) d 0.034 b NT-proBNP 241 (55–35 000) d 1 248 (196–35 000) d 0.016 b a Independent sample t-test was used for parametric testing b Mann-Whitney U test was used for non-parametric testing c "Average" and "standard deviation" values in parentheses were specified for normally distributed data d "Median" and "lowest - highest values" in parentheses were specified for non-normally distributed data ALT: alanine transaminase; AST: aspartate aminotransferase; K: potassium; Na: sodium; NEU (%): neutrophil/leukocyte ratio; PLT: platelet count; NT-proBNP: N-terminal-pro-brain natriuretic peptide; WBC: White blood cell Table 5 . Central tendency and variability measures of laboratory data according to IVIG resistance Variable Responders Non-responders P value (n = 227) (n = 32) Sedimentation 66.9 (27.18) c 69.44 (30.97) 0.629 a WBC 13 000 (1 000–49 570) d 18 000 (6 320–33 230) d <0.001 b NEU (%) 60.62 (17.27) c 65.07 (17.55) c 0.190 a Hematocrit 32.15 (4.23) c 30.38 (4.07) c 0.029 a PLT 399 000 (51 000–2 099 000) d 409 500 (195 000–1 356 000) d 0.621 b C-reactive protein 67 (1–417.4) d 107.2 (4.8–369) d 0.015 b Total protein 7.03 (1.16) c 6.63 (0.89) c 0.183 a Albumin 3.65 (0.51) c 3.53 (0.45) c 0.298 a AST 34 (11–604) d 38.5 (4–1 230) d 0.245 b ALT 24 (4–527) d 35 (5–705) d 0.033 b Na 135.35 (3.18) c 133.83 (3.29) c 0.010 a K 4.48 (0.61) c 4.72 (0.73) c 0.051 a Urea 18 (1–95) d 16.5 (5–57) d 0.895 b Creatinine 0.3 (0.09–1.03) d 0.25 (0.16–0.8) d 0.030 b Troponin T 0.005 (0.003–0.17) d 0.068 (0.008–0.127) d 0.026 b NT-proBNP 329 (55–35 000) d 19 792 (4584–35 000) d 0.014 b a Independent sample t-test was used for parametric testing b Mann-Whitney U test was used for non-parametric testing c "Average" and "standard deviation" values in parentheses were specified for normally distributed data d "Median" and "lowest - highest values" in parentheses were specified for non-normally distributed data ALT: alanine transaminase; AST: aspartate aminotransferase; K: potassium; Na: sodium; NEU (%): neutrophil/leukocyte ratio; PLT: platelet count; NT-proBNP: N-terminal-pro-brain natriuretic peptide; WBC: White blood cell Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-56396","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":1387831,"identity":"c1466757-90ce-4305-ac56-d6f99c7c6782","order_by":0,"name":"Yusuf Ziya Varlı","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAnklEQVRIiWNgGAWjYJCCAwwMNqRrSSPdosMkqDW4kf7wME/N+Wj52Q2MHz7mEKUlIeEwz7HbuRvuHGCWnLmNOC0HDs5gA2qRSGBj5iVOS2LDwRn/zuXOn0G8lmSGAx/bDuQ23CBWi+SZZ0Atfcm5G24kNhPnF77j6Y8/JHyzAzos+eCHj8RoUTgAZzI2EKEeCOSJVDcKRsEoGAUjGQAA+Xw+M0MTjuMAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-9648-3796","institution":"Istanbul Egitim ve Arastirma Hastanesi","correspondingAuthor":true,"prefix":"","firstName":"Yusuf","middleName":"Ziya","lastName":"Varlı","suffix":""},{"id":1387832,"identity":"0999ab49-2640-46ea-ba81-18608a1d5453","order_by":1,"name":"Kazim Oztarhan","email":"","orcid":"","institution":"Department of Pediatric Cardiology, Kanuni sultan Suleyman Research and Training Hospital, University of Health Science, Istanbul","correspondingAuthor":false,"prefix":"","firstName":"Kazim","middleName":"","lastName":"Oztarhan","suffix":""}],"badges":[],"createdAt":"2020-08-09 12:06:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-56396/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-56396/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13574670,"identity":"63ba1f34-7b75-49a5-a5bd-fc85fb023837","added_by":"auto","created_at":"2021-09-17 03:59:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":453025,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-56396/v1/0702acae-5748-4f94-9ada-779d2bc69607.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eCoronary Aneurysm and IVIG Resistance Prediction in Kawasaki Disease\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eKawasaki disease (KD) is an acute febrile systemic vasculitis of childhood that is characterized by fever, bilateral non-exudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rashes, and cervical lymphadenopathy.\u003cstrong\u003e\u003csup\u003e[1-3]\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKD generally in children \u0026lt; 5 years of age, and if left untreated it has been reported that 15%\u0026ndash;25% of patients with KD develop coronary artery lesions ([CALs], aneurysms, or ectasia).\u003cstrong\u003e\u003csup\u003e[3]\u003c/sup\u003e\u003c/strong\u003e KD can cause myocarditis, arrhythmias, and myocardial infarction in the acute phase, and sudden cardiac death due to coronary artery aneurysms and stenosis in the subacute and chronic phases. KD is an important health problem, and early diagnosis and treatment significantly reduce the risk of complications, morbidity, and mortality with coronary artery disease.\u003cstrong\u003e\u003csup\u003e[1-4]\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLaboratory tests, although non-specific, provide support for a diagnosis of KD in patients with non-classic, but suggestive clinical features. Clinical experience suggests that KD is unlikely if the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelet count are normal after day 7 of illness. In addition, a low white blood cell count and lymphocyte predominance suggest an alternative diagnosis.\u003cstrong\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe efficacy of intravenous immunoglobulin (IVIG) administered in the acute phase of KD has been well-established to reduce the prevalence of coronary artery abnormalities. Patients who laboratory evidence of inflammation who fail to respond to a second infusion of IVIG, steroids, or infliximab require additional therapy to control inflammation.\u003cstrong\u003e\u003csup\u003e[2-4]\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study we determined the clinical characteristics, laboratory findings, demographic features, frequency of coronary involvement, and resistance to IVIG treatment in Turkey based on the data from our hospital.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe diagnosis of KD is of two types (classical type/complete KD and incomplete KD/atypical KD).\u003cstrong\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003c/strong\u003e The diagnosis of typical KD is based on the presence of \u0026ge; 5 days of fever and the presence of \u0026ge; 4 of 5 principal clinical features.\u003cstrong\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003c/strong\u003e The diagnosis of incomplete (atypical) KD should be considered in any infant or child with prolonged unexplained fever, \u0026lt; 4 of the principal clinical findings, and compatible laboratory or echocardiographic findings.\u003cstrong\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGender, age at diagnosis, presence of diagnostic criteria, number of days with fever, and personal and family histories were recorded. Twenty-six cases with missing file data or with a diagnosis difference other than KD were excluded from the study at the beginning.\u003c/p\u003e\n\u003cp\u003eThe patients were subjected to echocardiographic examination at the time of diagnosis and in the subacute period for the presence of coronary artery involvement and the risk of complications. Myocardial wall mobility, ejection fraction values (%), and the diameters of coronary arteries were measured; Z scores were calculated according to American Heart Association (AHA) guidelines.\u003cstrong\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to the Z score calculation, the following definitions were applied: dilation, 2 \u0026lt; Z score \u0026lt; 2.5 or if initially \u0026lt; 2 and a decrease in Z score during follow-up \u0026ge;1; small aneurysm, 2.5 \u0026le; Z score \u0026lt; 5; moderate aneurysm, 5 \u0026le; Z score \u0026lt; 10; and large or giant aneurysm, Z score was defined as \u0026ge; 10.\u003csup\u003e[2]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIVIG and aspirin were given in appropriate doses to all patients hospitalized with a diagnosis of KD according to AHA criteria as the standard primary treatment.\u003cstrong\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003c/strong\u003e IVIG resistance is defined as recurrent or permanent fever development at least 36 h after the end of the IVIG infusion in 10%\u0026ndash;20% of patients with KD.\u003cstrong\u003e\u003csup\u003e[2,5,6]\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe cases were grouped in terms of coronary artery aneurysms (CAAs) development and responses to IVIG treatment. The gender of the patients, the age at the time of diagnosis, the presence of diagnostic criteria, the number of days with fever, and the personal and family histories were recorded. Retrospective statistical comparisons were made between the groups.\u003c/p\u003e\n\u003cp\u003eAll data were obtained from clinical and laboratory findings recorded at the time of diagnosis, echocardiographic examinations obtained at diagnosis, and follow-up. Twenty-six patients with missing file data or with a diagnosis other than KD were excluded from the study at the beginning.\u003c/p\u003e\n\u003cp\u003eLaboratory findings included hemogram parameters, ESR, acute phase reactants (CRP, procalcitonin [PCT], and ferritin), electrolytes (Na, K, Cl, Ca, Mg, and P), kidney and liver function tests (ALT, AST, GGT, LDH, albumin, ALP, total and direct bilirubin, urea, creatinine, and uric acid), lipid profiles (total cholesterol, LDL, HDL, and triglycerides), coagulation values (PT, aPTT, and INR), urinalyses, and hemoculture results.\u003c/p\u003e\n\u003cp\u003eData were analyzed using (SPSS Statistics for Macintosh, version 24.0; IBM Corp., Armonk, NY, USA). Categorical variables were summarized using frequencies (percentage [%]). The mean \u0026plusmn; standard deviation was used for continuous variables. Normality was assessed for continuous data using the Kolmogorov\u0026ndash;Smirnov test. An independent samples t-test was used for continuous variables. Categorical variables were compared using a chi-squared test. A p-value \u0026lt; 0.05 was taken as an indicator of statistical significance. Results and significance values are summarized in the relevant tables.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTwo hundred fifty-nine patients (males, 162, females 97; male-to-female ratio, 1.67) were treated in our hospital, with 48 of patients (19%) \u0026lt; 1 year of age. The age range was 3 months\u0026ndash;9.8 years. The average number of days before admission to the hospital was 6.7. Of the patients, 90.7% received outpatient antibiotic therapy prior to hospitalization. CAA development and IVIG resistance were noted in 11.6% and 12.3% of patients, respectively. Coronary ectasia/dilatation was detected in 15 patients (6% [2 \u0026lt; Z score \u0026lt; 2.5]), and the coronaries were completely normal in 214 patients (83%). According to the diagnostic criteria, 31% of patients were treated as typical KD and 69% as 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%). The frequencies of clinical findings in diagnostic types are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003eCALs were demonstrated in 45 patients; the right coronary artery (RCA) alone (20%), the left coronary artery (LCA) alone (44.5%), and the RCA and LCA were involved together (35.5%). The left main coronary artery (LMCA) 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%). Of the patients with coronary artery involvement, 53.3% were \u0026lt; 1 year of age and 83.3% were \u0026lt; 5 years of age. IVIG resistance was detected in 35.6% of patients with CAAs.\u003c/p\u003e\n\u003cp\u003eAll patients were treated with standard primary therapy, IVIG, and aspirin. Aspirin was discontinued in 29 patients (11%) because salicylic acid poisoning developed. Two patients were given pulsed steroid therapy, eight patients needed intensive care, and one patient was treated with plasmapheresis.\u003c/p\u003e\n\u003cp\u003eTable 2 and 3 summarize the clinical and demographic data of the patients with respect to their responsiveness to IVIG treatment and the development of CAAs. It was observed that the frequency of CAA development increased in IVIG-resistant patients, and similarly, the frequency of IVIG resistance increased in those who developed CAAs. This association was statistically significant (p \u0026lt; 0.001). There was a statistically significant difference between the age groups with both CAA development and IVIG resistance using a chi-square test and no significant difference existed as a function of gender.\u003c/p\u003e\n\u003cp\u003eWhen IVIG resistant and sensitive patients are compared (Table 3) 91.6% of IVIG-resistant patients were \u0026lt; 5 years of age. Hospitalization time and coronary artery involvement increased and were statistically significant.\u003c/p\u003e\n\u003cp\u003eLaboratory findings were analyzed by grouping in Table 4. according to coronary involvement and in Table 5 according to IVIG responsiveness. In Table 4, the laboratory findings of patients with KD were compared according to the presence of coronary artery involvement. When the laboratory findings of patients with coronary artery involvement were examined, it was found that the hematocrit, total protein, and albumin levels decreased, and the leukocyte count, platelet count, and CRP, troponin T, and N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels increased.\u003c/p\u003e\n\u003cp\u003eIn Table 5, the laboratory findings of patients with IVIG resistance were compared with patients who were sensitive to IVIG. In patients with IVIG resistance, the leukocyte and platelet counts, CRP, and ALT, troponin T, and NT-proBNP levels were increased, while the hematocrit and sodium levels were decreased.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA CAA is the most important complication of KD. CAAs develop in 15%\u0026ndash;25% of untreated patients; this rate decreases to 5% with treatment within the first 10 days.\u003csup\u003e[3] \u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eEarly diagnosis and treatment is very important because it directly affects mortality. To provide early intervention for CALs caused by KD, we analyzed the clinical characteristics of typical and incomplete KD patients. In this study there was no significant difference between the frequency of clinical findings in patients diagnosed with typical and atypical KD. The most common findings in both groups were mucosal involvement in the mouth, polymorphic exanthema, and non-exudative conjunctive injection. The most common clinical finding (80%) in some studies was non-exudative conjunctive injection followed by polymorphic exanthema and mucosal involvement in the mouth.\u003csup\u003e[7]\u003c/sup\u003e Asian patients with changes in the oral mucosa, cervical lymphadenopathy, swelling of the extremities, and polymorphous rashes were more likely to be IVIG-resistant, but in non-Asian patients there was no significant difference among these symptoms and IVIG resistance.\u003csup\u003e[17]\u003c/sup\u003e In the population in our study, we did not note any significant difference between IVIG resistance and the risk of developing coronary lesions and clinical findings.\u003c/p\u003e\n\u003cp\u003eThe prevalence of coronary artery abnormalities in a clinical trial of initial treatment was 23% 4 weeks after enrollment, which reduced to 8% with 4 infusions of low-dose IVIG. In a subsequent trial of single high-dose IVIG, this was further reduced to approximately 4%.\u003csup\u003e[8,9]\u003c/sup\u003e In our study, CAAs were detected in 11.6% of patients. There is no conclusive data regarding the incidence of the disease and complications due to the lack of large-scale research in South Korea with a sufficient number of cases. Several different risk scores are used to predict IVIG resistance and CALs. Shin et al.\u003csup\u003e[10]\u003c/sup\u003e reported that among the risk scoring systems, the Kobayashi risk score demonstrated significant differences between IVIG resistance and responder groups in Korean patients with KD.\u003c/p\u003e\n\u003cp\u003eMany researchers have scrutinized the clinical data and laboratory parameters at onset predicting the risk of CAA.\u003csup\u003e[11,12]\u003c/sup\u003e Risk factors for CAA are duration of fever \u0026gt; 2 weeks, platelet count, increased acute phase reactants, and age \u0026lt; 5 years.\u003c/p\u003e\n\u003cp\u003eDemonstration of CALs by echocardiography is important for prognostication. Damage to coronary arteries is a substantial risk for a significant percentage of children with KD, most often for those with resistance to IVIG.\u003c/p\u003e\n\u003cp\u003eMaximal efforts should be made to visualize all major coronary artery segments. In order of highest-to-lowest frequency of occurrence, typical sites of CAAs include the proximal LAD and proximal RCA, followed by the LMCA, LCx, distal RCA, and the junction between the RCA and posterior descending coronary artery. Enlargement of the LMCA caused by KD does not involve the orifice and rarely occurs without associated dilation of the LAD, the LCx, or both arteries.\u003csup\u003e[2]\u003c/sup\u003e In our study CALs existed in 45 patients; the RCA alone (20%), the LCA alone (44.5%), and the RCA and LCA were involved together (35.5%). The LMCA affected 20 patients, the LAD affected nine patients, the LCx affected two patients, and LAD and LCx together affected two patients. IVIG resistance was more common in infants and the hospitalization times were longer in this group. The coronary involvement rate in our patients was 17.3%. This rate was 12.8% in the IVIG-responsive group and 50% in the IVIG-resistant group.\u003c/p\u003e\n\u003cp\u003eKD has no specific diagnostic laboratory markers. Recent studies have investigated factors for predicting resistance to IVIG and CALs. These data include the duration of fever, polymorphonuclear neutrophil (PMN) cell count, hemoglobin level, platelet count, and CRP, transaminase, total bilirubin, and NT-proBNP, albumin, and sodium levels.\u003csup\u003e[13]\u003c/sup\u003e In our study, when the laboratory findings of the group in which coronary artery aneurysms were detected in KD, the leukocyte and platelet counts, and CRP, troponin T, and NT-proBNP levels were significantly increased and the albumin level was decreased.\u003c/p\u003e\n\u003cp\u003eSeveral previous studies demonstrated that a higher PMN percentage, and NT-proBNP, total bilirubin, CRP, aspartate aminotransferase, and alanine aminotransferase levels were considered predictive factors for patients with KD resistance to IVIG treatment.\u003csup\u003e[13-16]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn our study a statistically significant decrease in the sodium level was observed in IVIG-resistant patients. The cause of hyponatremia is still unknown in patients with KD. Lim et al.\u003csup\u003e[17]\u003c/sup\u003e found that there was a strong negative correlation between the level of serum sodium and inflammatory factors, including CRP and interleukin-6 (IL-6) in children with KD. The most probable pathophysiologic mechanism underlying hyponatremia is non-osmotic secretion of antidiuretic hormone (ADH). Several studies have confirmed that the release of ADH is promoted by IL-6 and tumor necrosis factor-\u0026alpha; (TNF-\u0026alpha;) during inflammation.\u003csup\u003e[18]\u003c/sup\u003e IL-6, TNF-\u0026alpha;, and other cytokines participate in inflammation among KD patients in the acute phase,\u003csup\u003e[19]\u003c/sup\u003e suggesting that hyponatremia may be associated with inappropriate release of ADH. The marked increase in plasma IL-6 and TNF-\u0026alpha; in IVIG-resistant infants compared with IVIG-responsive patients\u003csup\u003e[20,21]\u003c/sup\u003e may explain the significant hyponatremia in IVIG non-responders. In our study it was observed that hyponatremia and hypoalbuminemia were correlated with an increase in acute phase reactants in IVIG-resistant patients. In addition to KD, studies involving patients with inflammatory diseases, such as pneumonia, urinary tract infections, and lupus erythematosus, also demonstrated that hyponatremia is an important marker for severity and prognosis.\u003csup\u003e[22,23]\u003c/sup\u003e The mechanisms underlying hypoalbuminemia consist of the following: increased vascular permeability leading to leakage of albumin,\u003csup\u003e[24,25]\u003c/sup\u003e liver dysfunction resulting in decreased albumin synthesis; and a lack of essential amino acids due to low nutrient intake or malnutrition, resulting in reduced albumin synthesis.\u003csup\u003e[26]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn our study thyrombocytosis was detected in patients with CAL and IVIG resistance. This increase was statistically significant in CAL patients. Although some studies recognized both thrombocytopenia and significant thrombocytosis as predictors of CAA or IVIG resistance; however, the majority of studies showed no association.\u003csup\u003e[27,28]\u003c/sup\u003e The mechanism underlying thrombocytosis is unclear. It has been suggested that the elevated thrombopoietin level caused by acute inflammatory responses can lead to thrombocytopoiesis.\u003csup\u003e[29]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn our study IVIG resistance was detected in 12.4% of the patients. When the group developing coronary artery aneurysms was examined, we found that aneurysms developed more frequently in \u0026lt; 1 year and the risk of developing IVIG resistance and length of hospital stay were significantly increased. Several studies have reported that the frequency of developing CAA increases in \u0026lt; 1 year and \u0026gt; 5 years.\u003csup\u003e[5,6]\u003c/sup\u003e Based on a meta-analysis, when patients who were IVIG-resistant and -responsive were compared, the hemoglobin level, leukocyte and platelet counts, and ESR were statistically significant.\u003csup\u003e[30]\u003c/sup\u003e In our study the increased risk of IVIG resistance was shown to be statistically significant, especially in the group \u0026lt; 5 years of age. When the laboratory findings of our IVIG-resistant patients were examined, a significant increase existed in the leukocyte count (marked neutrophil increase), platelet count, and CRP, ALT, troponin T and NT-proBNP levels, while the hematocrit and sodium levels were significantly decreased.\u003c/p\u003e\n\u003cp\u003eAlthough IVIG is the established treatment for acute KD,\u003csup\u003e[2,3]\u003c/sup\u003e in some studies \u0026lt; 10% of patients with KD were resistant to this treatment. Patients resistant to IVIG were at a higher risk of developing CALs than patients responding to IVIG.\u003csup\u003e[15,16]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eConsidering the frequency of IVIG resistance by age group, a significant increase in risk occurred in infants (p \u0026lt;0.001). In our study the risk of developing IVIG resistance increased as age decreased. Indeed, there are several studies with similar results.\u003csup\u003e[30-33]\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAs a result, KD patients in Turkey, in terms of development-related coronary complications, have a higher risk. It is important to identify factors that increase the risk of coronary complications and IVIG resistance in KD. Because the risk of CAA is always higher in IVIG-resistant patients, predicting IVIG resistance may play a role in reducing the development of CAA.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAHA: American Heart Association\u003c/p\u003e\n\u003cp\u003eCAA: coronary artery aneurysm\u003c/p\u003e\n\u003cp\u003eCALs: coronary artery lesions\u003c/p\u003e\n\u003cp\u003eCRP: C-reactive protein\u003c/p\u003e\n\u003cp\u003eESR: erythrocyte sedimentation rate\u003c/p\u003e\n\u003cp\u003eIVIG: intravenous immunoglobulin\u003c/p\u003e\n\u003cp\u003eKD: Kawasaki disease\u003c/p\u003e\n\u003cp\u003eLAD: left anterior descending artery\u003c/p\u003e\n\u003cp\u003eLCA: left coronary artery\u003c/p\u003e\n\u003cp\u003eLCx: left circumflex artery\u003c/p\u003e\n\u003cp\u003eLMCA: left main coronary artery\u003c/p\u003e\n\u003cp\u003eRCA: right coronary artery\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the University of Health Science, Kanuni Sultan Suleyman Research and Training Hospital Human Investigation Committee (HIC) (protocol number 48865165-302.14.01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKO: carried out the management of the research and the cardiological evaluation of the patients, encouraged Dr. Varli, reviewed and revised the article, supervised the project. YZV: Researched the literature, performed statistical analysis of the data of the cases and contributed to the writing of the article. All authors were contributors to the writing of the manuscript and formation of tables. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the contributions of Assoc. Prof. Nuray Aktay Ayaz from the Department of Pediatric Rheumatology.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children.] Arerugi. 1967;16:178\u0026ndash;2.\u003c/li\u003e\n\u003cli\u003eMcCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017;135:e927\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eNewburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, Shulman ST, Bolger AF, Ferrieri P, Baltimore RS, Wilson WR, Baddour LM, Levison ME, Pallasch TJ, Falace DA, Taubert KA. Diagnosis, treatment, and longterm management of Kawasaki disease. A statement for health professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Circulation. 2004;110:2747\u0026ndash;71.\u003c/li\u003e\n\u003cli\u003eMoffett BS, Syblik D, Denfield S, Altman C, Tejtel-Sexson K. Epidemiology of immunoglobulin resistant Kawasaki disease: results from a large, national database. Pediatr Cardiol. 2015;36:374\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eNewburger JW, Sleeper LA, McCrindle BW, Minich LL, et al. Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007;356:663\u0026ndash;75.\u003c/li\u003e\n\u003cli\u003eBar-Meir M, Kalisky I, Schwartz A, Somekh E, Tasher D, Israeli Kawasaki Group. Prediction of resistance to intravenous immunoglobulin in children with kawasaki disease. J Pediatric Infect Dis Soc. 2018;7:25\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eMorales-Quispe JA, Espinola-Zavaleta N, Caballero-Caballero R, Garc\u0026iacute;a-L\u0026oacute;pez JJ, Rodr\u0026iacute;guez-Quezada JM, Betanzos-Rodr\u0026iacute;guez E. Clinical evolution and cardiovascular complications in children with Kawasaki disease.\u0026nbsp;Rev Med Inst Mex Seguro Soc. 2011;49:295\u0026ndash;300.\u003c/li\u003e\n\u003cli\u003eNewburger JW, Takahashi M, Burns JC, Beiser AS, Chung KJ, Duffy CE, Glode MP, Mason WH, Reddy V, Sanders SP, Shulman ST, Wiggins JW, Hicks RV, Fulton DR, Lewis AB, Leung DYM, Colton T, Rosen FS, Melish ME. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986;315:341\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eNewburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, Colan SD, Duffy CE, Fulton DR, Glode MP, Mason WH, Meissner HC, Rowley AH, Shulman ST, Reddy V, Sundel RP, Wiggins JW, Colton T, Melish ME, Rosen FS. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. New Engl J Med. 1991;324:1633\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eShin J, Lee H, Eun L. Verification of current risk scores for Kawasaki disease in Korean children. J Korean Med Sci. 2017;32:1991\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eDaniels SR, Specker B, Capannari TE, Schwartz DC, Burke MJ, Kaplan S. Correlates of coronary artery aneurysm formation in patients with Kawasaki disease. Am J Dis Child. 1987;141:205\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eKoren G, Lavi S, Rose V, Rowe R. Kawasaki disease: Review of risk factors for coronary aneurysms. J Pediatr. 1986;108:388\u0026ndash;92.\u003c/li\u003e\n\u003cli\u003eWoo HO. Predictive risk factors of coronary artery aneurysms in Kawasaki disease. Korean J Pediatr. 2019;62:124\u0026ndash;\u003c/li\u003e\n\u003cli\u003eNakamura Y, Yashiro M, Uehara R, Sadakane A, Tsuboi S, Aoyama Y, Kotani K, Tsogzolbaatar EO, Yanagawa H. Epidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey. J Epidemiol. 2012;22:216\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eTremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, Martin DD, Newburger JW, Burns JC. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008; 153:117\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eMuta H, Ishii M, Furui J, Nakamura Y, Matsuishi T. Risk factors associated with the need for additional intravenous gamma-globulin therapy for Kawasaki disease. Acta Paediatr. 2006;95:189\u0026ndash;93.\u003c/li\u003e\n\u003cli\u003eLim GW, Lee M, Kim HS, Hong YM, Sohn S. Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion in kawasaki disease. Korean Circ J. 2010;40:507\u0026ndash;13.\u003c/li\u003e\n\u003cli\u003eKim JH, Park JH, Eisenhut M, Yu JW, Shin JI.\u0026nbsp;Inflammasome activation by cell volume regulation and inflammation-associated hyponatremia: a vicious cycle. Med Hypotheses. 2016;93:117\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eAgarwal S, Agrawal DK.\u0026nbsp;Kawasaki disease: etiopathogenesis and novel treatment strategies.\u0026nbsp;Expert Rev Clin Immunol. 2017;13:247\u0026ndash;58.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eHu P, Jiang GM, Wu Y, Huang BY, Liu SY, Zhang DD, Xu Y, Wu YF, Xia X, Wei W, Hu B. TNF-alpha is superior to conventional inflammatory mediators in forecasting IVIG nonresponse and coronary arteritis in Chinese children with Kawasaki disease.\u0026nbsp;Clin Chim Acta. 2017;471:76\u0026ndash;80.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eWu Y, Liu FF, Xu Y, Wang JJ, Samadli S, Wu YF, Liu HH, Chen WX, Luo HH, Zhang DD, Wei W, Hu P.\u0026nbsp;Interleukin-6 is prone to be a candidate biomarker for predicting incomplete and IVIG nonresponsive Kawasaki disease rather than coronary artery aneurysm.\u0026nbsp;Clin Exp Med. 2019;19:173\u0026ndash;81.\u003c/li\u003e\n\u003cli\u003ePark SW, Shin SM, Jeong M, Cho DH, Lee KH, Eisenhut M, Kronbichler A, Moritz M, Il Shin J. Hyponatremia in children with respiratory infections: a cross-sectional analysis of a cohort of 3938 patients. Sci Rep. 2018;8:164\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eIl Shin J, Park SJ, Suh CH, Lee GH, Hur MW, Han SY, Kim DS, Kim JH. Hyponatremia in patients with systemic lupus erythematosus.\u0026nbsp;Sci Rep. 2016;6:255\u0026ndash;\u003c/li\u003e\n\u003cli\u003eKuo HC, Liang CD, Wang CL, Yu HR, Hwang KP, Yang KD. Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease.\u0026nbsp;Acta Paediatr.\u0026nbsp;2010;99:1578\u0026ndash;83.\u003c/li\u003e\n\u003cli\u003eSoeters PB, Wolfe RR, Shenkin A.\u0026nbsp;Hypoalbuminemia: pathogenesis and clinical significance.\u0026nbsp;JPEN J Parenter Enteral Nutr.\u0026nbsp;2019;43:181\u0026ndash;93.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eArques S.\u0026nbsp;Human serum albumin in cardiovascular diseases.\u0026nbsp;Eur J Intern Med.\u0026nbsp;2018;52:8\u0026ndash;12.\u0026nbsp;\u003c/li\u003e\n\u003cli\u003eMaric LS, Knezovic I, Papic N, Mise B, Roglic S, Markovinovic L, Tesovic G. Risk factors for coronary artery abnormalities in children with Kawasaki disease: a 10-year experience. Rheumatol Int. 2015;35:1053\u0026ndash;\u003c/li\u003e\n\u003cli\u003eBerdej-Szczot E, Małecka-Tendera E, Gawlik T, Firek-Pędras M, Szydłowski L, Gawlik A. Risk factors of immunoglobulin resistance and coronary complications in children with Kawasaki disease. Kardiol Pol. 2017;75:261\u0026ndash;\u003c/li\u003e\n\u003cli\u003eIshiguro A, Ishikita T, Shimbo T, Matsubara K, Baba K, Hayashi Y, Naritaka S, Nakahata T. Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease. Thromb Haemost. 1998;79:1096\u0026ndash;\u003c/li\u003e\n\u003cli\u003eLi X, Chen Y, Tang Y, Ding Y, Xu Q, Sun L, Qian W, Qian G, Qin L, Lv H. Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases. Eur J Pediatr. 2018;177:1279\u0026ndash;92.\u003c/li\u003e\n\u003cli\u003eRigante D, Andreozzi L, Fastiggi M, Bracci B, Natale MF, Esposito S. Critical Overview of the Risk Scoring Systems to Predict Non-Responsiveness to Intravenous Immunoglobulin in Kawasaki Syndrome. Int J Mol Sci. 2016;17:278.\u003c/li\u003e\n\u003cli\u003eFabi M, Andreozzi L, Corinaldesi E, Bodnar T, Lami F, Cicero C, Tchana B, Landini C, Sprocati M, Bigucci B, Balsamo C, Valin PS, Fazzio GD, Iughetti L, Valletta E, Marchetti F, Donti A, Lanari M. Inability of Asian risk scoring systems to predict intravenous immunoglobulin resistance and coronary lesions in Kawasaki disease in an Italian cohort. Eur J Pediatr. 2019;178:315\u0026ndash;22.\u003c/li\u003e\n\u003cli\u003eTang Y, Yan W, Sun L, Huang J, Qian W, Ding Y, Lv H. Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an East China population. Clin Rheumatol. 2016;35:2771\u0026ndash;6.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable \u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003eFrequency diagnostic criteria met in patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"624\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"281\"\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Findings\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(n:259)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003eTypical KD\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(n:80)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"144\"\u003e\n\u003cp\u003e\u003cstrong\u003eIncomplete KD\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(n:179)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"144\"\u003e\n\u003cp\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"281\"\u003e\n\u003cp\u003eChanges of the lips and oral mucosa\u003c/p\u003e\n\u003cp\u003eConjunctival congestion\u003c/p\u003e\n\u003cp\u003eCervical lymphadenopathy\u003c/p\u003e\n\u003cp\u003eRash\u003c/p\u003e\n\u003cp\u003ePeripheral-extremity changes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003e206 (79.5%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e168 (64.9%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e124 (47.9%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e179 (69.1%)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e140 (54.1%)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e75 (93.8%)\u003c/p\u003e\n\u003cp\u003e70 (87.5%)\u003c/p\u003e\n\u003cp\u003e57 (71.3%)\u003c/p\u003e\n\u003cp\u003e72 (90%)\u003c/p\u003e\n\u003cp\u003e58 (72.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"144\"\u003e\n\u003cp\u003e131 (73.2%)\u003c/p\u003e\n\u003cp\u003e98 (54.7%)\u003c/p\u003e\n\u003cp\u003e67 (37.4%)\u003c/p\u003e\n\u003cp\u003e107 (59.8%)\u003c/p\u003e\n\u003cp\u003e82 (45.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eKD: Kawasaki Disease\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable \u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e. Demographic data of patients in the development of coronary artery aneurysm\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"360\"\u003e\n\u003cp\u003e\u003cstrong\u003eDevelopment of coronary aneurysm\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eNormal (n = 229)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eCAA (n = 30)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"180\"\u003e\n\u003cp\u003eGender\u003c/p\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"360\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"85\"\u003e\n\u003cp\u003e0.194\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e140 (61.1%)\u003c/p\u003e\n\u003cp\u003e89 (38.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e22 (73.3%)\u003c/p\u003e\n\u003cp\u003e8 (26.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eAge range\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e2.94 (0.11\u0026ndash;9.9)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e0.71 (0.19\u0026ndash;9.78)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eTotal fever days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e6 (1\u0026ndash;20)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e6 (2\u0026ndash;15)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e0.896\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"180\"\u003e\n\u003cp\u003eAge group\u003c/p\u003e\n\u003cp\u003e\u0026lt;1 year\u003c/p\u003e\n\u003cp\u003e1\u0026le; and \u0026lt;5 years old\u003c/p\u003e\n\u003cp\u003e\u0026ge;5 years old\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"360\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e32 (14%)\u003c/p\u003e\n\u003cp\u003e141 (61.6%)\u003c/p\u003e\n\u003cp\u003e56 (24.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e16 (53.3%)\u003c/p\u003e\n\u003cp\u003e9 (30%)\u003c/p\u003e\n\u003cp\u003e5 (16.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eHospitalization time (days)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e10 (3\u0026ndash;35)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e13 (6\u0026ndash;35)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.003\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eIVIG resistance frequency\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e16 (75%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e16 (35.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eType of diagnosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"3\" width=\"85\"\u003e\n\u003cp\u003e0.341\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eTypical KD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e73 (91.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e7 (8.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eIncomplete KD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e156 (87.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e23 (12.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"625\"\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ea \u003c/sup\u003e\u003c/em\u003e\u003cem\u003ePearson chi-square test was used\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003eb \u003c/sup\u003e\u003c/em\u003e\u003cem\u003eMann-Whitney U test was used\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ec \u003c/sup\u003e\u003c/em\u003e\u003cem\u003esignificant difference was observed in the \u0026lt; 1 year of age group \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ed \u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\"Median\" and \"lowest - highest values\" in parentheses were specified for non-normally distributed data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCAA: Coronary artery aneurysm; IVIG: intravenous immunoglobulin\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable \u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003cstrong\u003e. \u003c/strong\u003e\u003cstrong\u003eDemographic data of patients in response to IVIG treatment\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"625\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"360\"\u003e\n\u003cp\u003e\u003cstrong\u003eIVIG responsiveness\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eResponders (n = 227)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e\u003cstrong\u003eNon-responders (n = 32)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"180\"\u003e\n\u003cp\u003eGender\u003c/p\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"360\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"85\"\u003e\n\u003cp\u003e0.701\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e141 (62.1%)\u003c/p\u003e\n\u003cp\u003e86 (37.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e21 (65.6%)\u003c/p\u003e\n\u003cp\u003e11 (34.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eAge range\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e3.06 (0.16\u0026ndash;9.9)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e1.12 (0.11\u0026ndash;9.78)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.002\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eTotal fever days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e5 (1\u0026ndash;20)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e6 (1\u0026ndash;20)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.028\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"180\"\u003e\n\u003cp\u003eAge group\u003c/p\u003e\n\u003cp\u003e\u0026lt;1 year of age\u003c/p\u003e\n\u003cp\u003e1\u0026le; and \u0026lt;5 years of age\u003c/p\u003e\n\u003cp\u003e\u0026ge;5 years of age\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"360\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ec\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e33 (14.5%)\u003c/p\u003e\n\u003cp\u003e136 (59.9%)\u003c/p\u003e\n\u003cp\u003e58 (25.6%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e15 (46.9%)\u003c/p\u003e\n\u003cp\u003e14 (43.8%)\u003c/p\u003e\n\u003cp\u003e3 (9.4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eHospitalization time (days)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e10 (3\u0026ndash;35)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e14 (5\u0026ndash;35)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.005\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eCoronary involvement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e29 (12.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e16 (50%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eType of diagnosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd rowspan=\"3\" width=\"85\"\u003e\n\u003cp\u003e0.718\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eTypical KD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e71 (88.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e9 (11.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003eIncomplete KD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e156 (87.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"180\"\u003e\n\u003cp\u003e23 (12.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"625\"\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ea \u003c/sup\u003e\u003c/em\u003e\u003cem\u003ePearson chi-square test was used\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003eb \u003c/sup\u003e\u003c/em\u003e\u003cem\u003eMann-Whitney U test was used\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ec \u003c/sup\u003e\u003c/em\u003e\u003cem\u003esignificant difference was observed in the \u0026lt; 1 year age group \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ed \u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\"Median\" and \"lowest - highest values\" in parentheses were specified for non-normally distributed data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIVIG: intravenous immunoglobulin\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable \u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003cstrong\u003e. \u003c/strong\u003e\u003cstrong\u003eCentral tendency and variability measures of laboratory data according to coronary involvement\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"616\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"142\"\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e\u003cstrong\u003eCoronary involvement\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e\u003cstrong\u003e(n = 214)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e\u003cstrong\u003e(n = 45)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eSedimentation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e67.35 (27.47)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e66.64 (28.86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e0.880\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e13 000 (1 000\u0026ndash; 49 570)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e14 950 (5 290\u0026ndash; 36 800)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.002\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eNEU (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e61.74 (16.88)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e59.70 (19.12)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e0.504\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eHematocrit\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e32.19 (4.14)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e30.65 (4.47)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.032\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003ePLT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e374 000 (51 000\u0026ndash;2 099 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e482 000 (162 000\u0026ndash;1 395 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.001\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eC-reactive protein\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e67.9 (1\u0026ndash;417.4)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e93.5 (3.1\u0026ndash;369)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.044\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eTotal protein\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e7.1 (1.16)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e6.53 (0.8)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.001\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eAlbumin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e3.68 (0.51)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e3.49 (0.46)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.037\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eAST\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e34 (4\u0026ndash;628)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e38 (15.3\u0026ndash;1 230)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e0.642\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eALT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e24 (4\u0026ndash;705)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e26 (8\u0026ndash;704)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e0.307\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eNa\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e135.03 (3.25)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e135.33 (3.23)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e0.591\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e4.46 (0.59)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e4.76 (0.75)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.020\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eUrea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e18 (1\u0026ndash;95)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e14 (1\u0026ndash;57)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.003\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eCreatinine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e0.3 (0.09\u0026ndash;1.03)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e0.27 (0.13\u0026ndash;0.8)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.006\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eTroponin T\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e0.003 (0.003\u0026ndash;0.03)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e0.007 (0.003\u0026ndash;0.127)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.034\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"142\"\u003e\n\u003cp\u003eNT-proBNP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"160\"\u003e\n\u003cp\u003e241 (55\u0026ndash;35 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e1 248 (196\u0026ndash;35 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"128\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.016\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"616\"\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ea \u003c/sup\u003e\u003c/em\u003e\u003cem\u003eIndependent sample t-test was used for parametric testing\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003eb \u003c/sup\u003e\u003c/em\u003e\u003cem\u003eMann-Whitney U test was used for non-parametric testing\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ec \u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\"Average\" and \"standard deviation\" values in parentheses were specified for normally distributed data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ed \u003c/sup\u003e\u003c/em\u003e\u003cem\u003e\"Median\" and \"lowest - highest values\" in parentheses were specified for non-normally distributed data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eALT: alanine transaminase; AST: aspartate aminotransferase; K: potassium; Na: sodium; NEU (%): neutrophil/leukocyte ratio; PLT: platelet count; NT-proBNP: N-terminal-pro-brain natriuretic peptide; WBC: White blood cell\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable \u003c/strong\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003cstrong\u003e. Central tendency and variability measures of laboratory data according to IVIG resistance\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" width=\"648\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e\u003cstrong\u003eResponders\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e\u003cstrong\u003eNon-responders\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e value\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e\u003cstrong\u003e(n = 227)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e\u003cstrong\u003e(n = 32)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eSedimentation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e66.9 (27.18)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e69.44 (30.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.629\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e13 000 (1 000\u0026ndash;49 570)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e18 000 (6 320\u0026ndash;33 230)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eNEU (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e60.62 (17.27)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e65.07 (17.55)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.190\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eHematocrit\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e32.15 (4.23)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e30.38 (4.07)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.029\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003ePLT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e399 000 (51 000\u0026ndash;2 099 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e409 500 (195 000\u0026ndash;1 356 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.621\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eC-reactive protein\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e67 (1\u0026ndash;417.4)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e107.2 (4.8\u0026ndash;369)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.015\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eTotal protein\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e7.03 (1.16)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e6.63 (0.89)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.183\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eAlbumin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e3.65 (0.51)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e3.53 (0.45)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.298\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eAST\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e34 (11\u0026ndash;604)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e38.5 (4\u0026ndash;1 230)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.245\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eALT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e24 (4\u0026ndash;527)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e35 (5\u0026ndash;705)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.033\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eNa\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e135.35 (3.18)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e133.83 (3.29)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.010\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eK\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e4.48 (0.61)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e4.72 (0.73)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.051\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eUrea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e18 (1\u0026ndash;95)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e16.5 (5\u0026ndash;57)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e0.895\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eCreatinine\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e0.3 (0.09\u0026ndash;1.03)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e0.25 (0.16\u0026ndash;0.8)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.030\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eTroponin T\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e0.005 (0.003\u0026ndash;0.17)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e0.068 (0.008\u0026ndash;0.127)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.026\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003eNT-proBNP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"183\"\u003e\n\u003cp\u003e329 (55\u0026ndash;35 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"195\"\u003e\n\u003cp\u003e19 792 (4584\u0026ndash;35 000)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"134\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.014\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" width=\"648\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003ea \u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cem\u003eIndependent sample t-test was used for parametric testing\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003eb\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e Mann-Whitney U test was used for non-parametric testing\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e \"Average\" and \"standard deviation\" values in parentheses were specified for normally distributed data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003ed\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e \"Median\" and \"lowest - highest values\" in parentheses were specified for non-normally distributed data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eALT: alanine transaminase; AST: aspartate aminotransferase; K: potassium; Na: sodium; NEU (%): neutrophil/leukocyte ratio; PLT: platelet count; NT-proBNP: N-terminal-pro-brain natriuretic peptide; WBC: White blood cell\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Kawasaki disease, prolonged fever, coronary aneurysm, IVIG resistance","lastPublishedDoi":"10.21203/rs.3.rs-56396/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-56396/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e 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.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003ePatients with KD were evaluated with demographic data, clinical, laboratory, and echocardiographic findings. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Between 2010–2019, a total of 259 patients (male/female: 1.67) were treated in our hospital, with 48 (%19) cases \u0026lt; 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. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e 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.\u003c/p\u003e","manuscriptTitle":"Coronary Aneurysm and IVIG Resistance Prediction in Kawasaki Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-08-13 21:43:19","doi":"10.21203/rs.3.rs-56396/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8337ad91-006e-4403-adca-1278902633cb","owner":[],"postedDate":"August 13th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":288435,"name":"Pediatrics"},{"id":288436,"name":"Rheumatology"}],"tags":[],"updatedAt":"2021-02-03T11:38:20+00:00","versionOfRecord":[],"versionCreatedAt":"2020-08-13 21:43:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-56396","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-56396","identity":"rs-56396","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}