Risk factors associated with persistent coronary artery lesions in children with Kawasaki Disease in an Italian cohort

Risk factors associated with persistent coronary artery lesions in children with Kawasaki Disease in an Italian cohort | 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 Risk factors associated with persistent coronary artery lesions in children with Kawasaki Disease in an Italian cohort Fiorentina Guida, Elisabetta Morana, Elena Tarì, Leonardo Frazzoni, and 18 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6243172/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 May, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose: Kawasaki disease (KD) can be complicated, mainly during the acute stage, by coronary artery lesions (CALs); their persistence, after the subacute stage, increases cardiovascular morbidity and life-threatening events lifelong. While several scores, based on Asians and Americans, have been proposed to predict the risk of CALs or non-response, less efforts have been aimed to identify risk factors associated with the persistence of CALs (pCALs). Our study aimed, firstly, to identify the risk factors for pCALs in Italian patients and, secondly, to assess the validity of an existing risk score, previously applied to a North-Americans. Methods: Data of KD patients from 11 Italian sites were registered into a centralized RedCap database. pCALs were defined as the persistence of CALs 8 weeks after the diagnosis. Clinical, demographic and laboratory features of patients with and without pCALs were analyzed and compared. Multiple logistic regression was used to identify independent risk factors for pCALs. A ROC analysis was conducted to assess the performance and reliability of the existing risk score model to predict the persistence of CALs. Results: 517 children were enrolled (Caucasian 87.4%) of which 52 developed pCALs. pCALs were more prevalent in males (12.03% p=0.06), Asian ethnicity (26.9%, p: 0.026), younger patients (61.5%, p: 0.05), incomplete clinical presentation (p=0.03), and associated with pathological features at abdominal ultrasound (p=0.04). Children with pCALs had higher WBC and CRP but lower Hb. Male gender (12.03% p=0.06), age younger than 6 months (61.5%, p: 0.05), Asian ethnicity (26.9%, p: 0.026), fever longer than 10 days, incomplete presentation(p=0.03), CRP >13 mg>dl were independent risk factors for pCALs. Children who developed pCALs, compared to those with acute CALs, were younger, mostly IVIG non-responders (34.6%, 18/52 versus 29.6%, 153/517; p<0.001) and late-treated. Additionally, Son's risk score demonstrated high predictive value in identifying children at greater risk for pCALs. Conclusions: Male gender, younger age, incomplete clinical presentation, Asian ethnicity, and elevated CRP levels are independent risk factors for pCALs in our Italian cohort. Notably, the risk score developed by Son et al. demonstrated its potential utility in identifying children who may benefit from closer follow-up and early adjunctive therapy to limit coronary damage and related morbidity in a predominantly Caucasian population. Kawasaki disease persistent coronary artery lesions risk score coronary artery aneurysms risk factors Figures Figure 1 What is known？ · Kawasaki disease can cause CALs, which increase cardiovascular risk if they persist. · Previous research has focused mainly on predicting CALs or treatment resistance, but little evidence is available on the risk factors for CALs persistence. What is new? · Our study identifies independent risk factors for pCALs in Italian children: male gender, younger age, incomplete presentation, Asian ethnicity and high CRP levels. · By applying the Son Risk Score to our population, we confirmed its predictive value in a predominantly Caucasian cohort and its reliability in identifying susceptibility to CALs persistence. Introduction Kawasaki disease (KD) is an acute febrile systemic vasculitis with an unclear etiology that primarily affects children under five years-old [ 1 , 2 ]. Its major complication is coronary involvement, where vasculopathic processes lead to vascular wall injury and subsequently dilation or aneurysms [ 3 ], increasing cardiovascular risk of the affected children in the short, medium [ 4 ], and long term [ 5 ]. The genetic background [ 6 ] affects the susceptibility to the disease [ 7 , 8 ], and its severity in Asian and other ethnic groups [ 9 – 15 ]. Other predisposing factors, such as environmental factors and infections, interplay with genetics, triggering the disease and favoring the development of coronary artery lesions (CALs) [ 16 – 18 ]. Identifying anamnestic, demographic, clinical, and laboratory variables associated with the risk of coronary involvement could lead to identifying children who might benefit from additional immunomodulatory therapy alongside intravenous immunoglobulins (IVIG) at an early stage, thereby reducing vascular damage and improving cardiovascular outcomes. Indeed, CALs develop in 5% of patients despite proper and timely treatment making KD the leading cause of acquired heart disease in children [ 19 ]. CALs typically develop within the first ten days after the onset of KD [ 20 ] and tend to normalize their diameter in up to 75% of cases within two years of the disease's diagnosis [ 20 , 21 ] despite vascular wall histological alteration occurring. So far, numerous studies have been conducted to identify risk factors that expose children with KD to developing CALs and their persistence over the first eight weeks of the diagnosis. Younger age, male gender, IVIG resistance or a delayed administration, a prolonged course of fever, multiple coronary involvement, along with blood test alterations, such as elevated C reactive protein (CRP), altered neutrophil-to-lymphocyte ratio, reduced hemoglobin level, and hypoalbuminemia, have been related to higher rate of CALs in the acute stage of KD [ 22 – 27 ]. In addition, subgroups of children with KD with different laboratory and clinical presentations have been associated with coronary involvement or IVIG resistance [ 28 , 29 ]. Moreover, different risk scores aimed at identifying the formation of CALs have been validated in the Asian population [ 30 – 32 ] but showed lower accuracy in other ethnicities [ 33 , 34 ]. The risk score published by Son et al. assessed the predictive value for coronary lesions in a North American multiethnic cohort using simple data, such as age, ethnicity, CRP, and initial coronary z-score [ 35 ]. It is thus necessary to identify risk factors associated with a higher likelihood of persisting after the subacute stage and to validate existing diagnostic tools across different geographical regions. This will enable patients to benefit from personalized treatments based on precise risk stratification. Materials and methods Data for this study were retrospectively and prospectively collected and entered into a REDcap database, from an Italian cohort composed of 11 recruiting centers [ 36 ] between January 1, 2000, and June 30, 2023. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of IRCCS AOU BO (Avec 340/2017/O/OssAOUBO approved on 1/16/2019). According to local regulations, the institutional review board granted the study approval at each enrolling site. Informed consent was obtained from all individual participants’ parents included in the study. The Data Coordinating Center (IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy) reviewed and analyzed all the data, ensuring patient eligibility, data completeness, and accuracy. The materials and methods have been previously detailed in a prior publication by our group [ 36 ]. Briefly, the diagnosis of KD, the clinical presentation (complete and incomplete form), the response to treatment with IVIG (IVIG- responders, IVIG non responders), and the timing of treatment related to the diagnosis (late or not treated) were based on the American Heart Association criteria [ 1 , 4 ]. Collected data included demographical and clinical features, blood tests (i.e., white blood cells (WBC), percentage of neutrophils (N%), percentage of lymphocytes (L%), hemoglobin levels (Hb), platelet count (PLT), serum glucose, hepatic and kidney function markers, CRP and erythrocyte sedimentation rate (ESR), serum albumin, and serum electrolyte levels), echocardiographic evaluation, and abdominal ultrasound (US) performed during the hospitalization if requested by the physician. The laboratory values were collected during the acute (from the onset to the 10th days after fever onset), subacute (from the 11th to the 20th days after fever onset), and chronic stage (from the 6th week after fever onset) for each patient. In addition, gastrointestinal (GI) involvement was defined as the presence of symptoms such as diarrhea, abdominal pain, or vomiting, along with abnormal abdominal US findings, including gallbladder hydrops, effusion in the pouch of Douglas, thickening of the intestinal wall, mesenteric adenopathies, or abdominal effusion. Echocardiography was performed during the acute, subacute, and chronic stages with the same modalities previously published [ 36 ]. CA involvement was then classified by Z-score as no involvement (Z < 2), dilation (Z 2 to < 2.5), small aneurysm (Z 2.5 to < 5), medium aneurysm (Z 5 to 10), according to the 2017 AHA guidelines [ 1 ]. Persistent coronary artery lesions (pCALs) were defined as the persistence of CA dilation or aneurysm 8 weeks after the diagnosis of KD. Transient coronary lesions (tCALs) were defined as CALs development by the 20th day of fever and resolved by 8 weeks after fever onset. Left main coronary artery (LMCA), left anterior descending coronary artery (LAD), circumflex (CX) and right coronary artery (RCA) were studied. Categorical variables were presented as absolute frequency and percentage, while non-normally distributed continuous variables were displayed as mean, standard deviation (SD), and/or interquartile range (IQR). Multivariate logistic regression was used to assess the risk factors for developing persistent coronary artery lesions (pCALs) in our population. Odds ratio and 95% confidence interval were obtained, and P < 0.05 was considered as statistically significant. The variables statistically related to a higher risk for developing pCALs were evaluated to elaborate a risk prediction model. A Receiver Operating Characteristic (ROC) analysis was conducted to assess the performance and reliability of Son’s risk prediction model [ 35 ] to predict the development of pCALs in the presented population. Statistical analysis was performed using STATA software version 16 (Stata Corp., College Station, TX). Results A total of 517 (boys 53.8%, mean age 44 months, SD 38.19) patients were included in the study and 52 patients (10%) developed pCALs. Demographical, clinical, therapeutical, laboratory, and radiological features of patients with and without pCALs are displayed in Table 1 . Table 1 Demographical clinical and laboratoristic features of patients with pCALs compared to those without pCALs pCALs No pCALs Demographical features N % N % p value OR IC (95%) Gender - Male - Female 38 14 74.5 27.5 278 187 53.8 36.2 0.043* Ethnicity - Asian - Caucasian - Afro-American - Other 7 40 3 2 13.7 78.4 5.9 3.9 19 412 15 19 3.7 79.7 2.9 3.7 0.019* Seasonality - Autumn - Summer - Winter - Spring 13 10 16 13 25.5 19.6 31.4 25.5 118 66 158 120 22.8 12.8 30.6 23.2 0.792 Clinical features N % N % p value OR IC (95%) Clinical presentation - Complete - Incomplete 25 26 49 51 295 164 57.1 31.7 0.033* Fever duration, mean days (SD) 13 (7.6) 8.6 (4.1) 10 days) 48 94.1 428 82.8 0.015* Conjunctivitis 30 58.8 213 41.2 0.103 Swelling of the hand and feet 20 39.2 148 28.6 0.333 Rash 32 62.7 221 42.7 0.155 Oral changes a 26 51 208 40.2 0.469 Cervical adenopathy b 15 29.4 154 29.8 0.533 GI group c 29 55.8 266 57.3 0.843 GI manifestations d 16 30.7 179 34.6 0.276 Liver involvement e 0 10 1.9 Abdominal ultrasound findings f 5 9.6 38 7.4 0.040* Pulmonary complications g 2 3.9 20 3.9 0.561 Perianal/diaper erythema 3 5.9 9 1.7 0.082 Osteomuscular involvement h 0 10 1.9 0.286 Aseptic meningitis 0 1 0.2 0.738 Facial nerve palsy 0 1 0.2 0.738 Macrophagic activation syndrome 0 1 0.2 0.738 Retropharyngeal edema/phlegmon 0 1 0.2 0.738 Treatment N % N % p value OR IC (95%) Standard treatment 46 88.5 444 96.7 0.023* OR: 1.08 95%CI: 0.46–2.48 Late treatment 12 23 51 11.1 0.076 OR: 2.67 95%CI: 1.32–5.41 Not treated 6 11 15 3.3 0.023* OR: 4.27 95%CI: 1.58–11.53 IVIG- responders 22 42.3 342 83.8 < 0.001* OR: 0.36 95%CI: 0.20–0.64 IVIG- non responders 18 34.6 102 23 < 0.001* OR: 2.09 95%CI: 1.13–3.84 a Oral changes: Erythema and cracking of lips (cheilitis); strawberry tongue; erythema of oral and pharyngeal mucosa; b Cervical adenopathy: defined as a swallowing of the cervical nodes bigger than 1.5 cm. c GI, Gastro-intestinal manifestations: diarrhea and/or abdominal pain and/or vomiting d GI, Gastro-intestinal group refers to any patient with one of the following: liver test anomalies (GOT and GPT), pathological findings at abdominal ultrasounds, GI signs or symptoms. e Liver involvement: liver test anomalies and/or jaundice f Abdominal ultrasound findings: gallbladder hydrops, effusion in the pouch of Douglas, swallowing of the intestinal wall, mesenterial adenopathies. abdominal effusion g Pulmonary complications: peribronchial interstitial inflammation h Osteomuscular involvement: joint pain and/or arthtritis GOT. glutamic oxaloacetic transaminase; GPT. glutamate-pyruvate transaminase; GGT. Gamma-glutamyltransferase; ESR. Erythrocyte sedimentation rate; CRP: C-reactive protein Compared to patients without pCALs, those with pCALs were younger (mean age: 25.3 months, SD 24.8; p 0.043) and predominantly male (38/52, 74.5%; p = 0.043), more likely to be Asian (7/52, 13.7%; p = 0.019), to have an incomplete clinical presentation (26/52, 51% vs 164/465, 31.7%, p 0.033) and fever lasting more than 10 days (48/52, 94.1% vs 428, 82.8%, p 0.001). They were more prone to present abdominal US anomalies (respectively 5/52, 9.6% vs 38/517, 7.4%, p 0.04), with a similar rate of GI manifestations when compared to children without pCALs (respectively 16/52, 31.4% vs 179/517, 34.6% p 0.276). Forty-six out of 52 (88%) who developed pCALs received IVIG, and 34/46 (73.9%) within the first 10 days of fever. Twenty-two out of 46 (47.8%) patients were IVIG responders, 18 patients (39.1%) were IVIG non-responders. Second line treatments were a second dose of IVIG infusion alone in 6/46 (13.05%), IVIG and steroids in 7/46 (15.2%), and biologics in 5/46 (10.9%), particularly anakinra in 4 (8.7%) patients and infliximab in 1 (2.2%). The lack of treatment with IVIG and IVIG-unresponsiveness were significantly associated with pCALs (respectively p 0.023; OR 4.27, 95% CI 1.58–11.53, and p < 0.001; OR 2.09, 95% CI 1.13–3.84). Table 2 shows laboratory tests of the patients with pCALs compared with tCALs, and without pCALs. Table 2 Comparison of laboratoristic data of patients with pCALs with tCALs (p value a ) and with those who never developed CALs (p value b ) tCALs p value a No pCALs p value b pCALs Red blood cells x 10 12 (/L) mean ± SD 4.239 ± 1.115 0.087 4.327 ± 1.104 0.030* 4.145 ± 1.676 Haemoglobin (g/dl) mean ± SD 10.9 ± 1.43 0.042* 11.15 ± 1.3 0.079 10.7 ± 1.2 Platelets (x 10 9 /L) mean ± SD 376.577 ± 177.540 0.844 372.397 ± 180.737 0.605 386.956 ± 187.281 GOT (UI/l) mean ± SD 62.116 ± 48.4 0.481 71.6 ± 40.4 0.726 62.3 ± 31.9 GPT (UI/l) mean ± SD 68.7 ± 48.83 0.323 77.7 ± 45.4 0.647 87.1 ± 62.8 GGT (UI/l) mean ± SD 52.148 ± 32.74 0.801 52.2 ± 33.67 0.441 70.2 ± 57.3 Albumin (g/dl) mean ± SD 3.475 ± 0.67 0.008* 3.4 ± 0.68 0.003* 3.1 ± 0.667 Sodium (mmol/l) mean ± SD 134.47 ± 3.2 0.837 134.5 ± 3.78 0.746 134.3 ± 2.7 ESR (mm/h) mean ± SD 62.08 ± 31.12 0.701 63.8 ± 32.7 0.630 60.2 ± 33.1 CRP (mg/dl) mean ± SD 11.01 ± 7.69 0.008* 9.3 ± 6.5 0.001* 12.7 ± 7.7 When compared with patients without pCALs, those with pCALs presented lower red blood cell count (p 0.030) and serum albumin (p 0.003) and higher CRP (p 0.001), and lower Hb and albumin (respectively p 0.042 and p 0.008) and higher CRP (p 0.008) when compared with patients with tCALs. In addition, in comparison to patients with tCALs (35), those with pCALs were younger (mean age: 25.3 months versus 36.5 months; p 0.043), IVIG- resistants (34.6%, 18/52 versus 29.6%, 153/517; p < 0.001); late treatment was more frequent in pCALs without reaching the statistical significance (11.5%, 6/52 versus 7.9% 41/135; p 0.076). Both groups experienced a similar incidence of GI involvement (16/52, 31.4% vs 84/135, 26%; p 0.868). pCALs were classified as dilation in 48.0% (25/52), small aneurysm in 26.9% (14/52), medium aneurysm in 17.3% (9/52), and giant aneurysm in 7.7% (4/52) of the population. When pCALs occurred in a single vessel, LAD was the most frequently affected (20/52, 38.4%), followed by the Cx (15/52, 28.8%), LMCA (13/52, 25%), and RCA (4/52, 7.7%). Multi-coronary injury (at least 2 vessels involved) occurred in 41/52 (78.8%) of patients: LAD was affected in 59.6% (31/52), LMCA in 51.9% (27/52), RCA in 40.4% (21/52), and Cx in 36.5% (19/52). All patients presented normal left ventricular systolic function, 7.6% (4/52) mild mitral regurgitation, and 3.8% (2/52) mild pericardial effusion. tCALs developed in 129/135 (95.5%) patients during the acute phase and 6/135 (4.4%) during the convalescent phase. CALs persisted in 52/135 (38.5%) and regressed in 83/135 (61.5%). The total number of CALs during acute and subacute stage was 111: LMCA was the most commonly affected vessels (44/111; 39.6%), followed by LAD (23/111; 20.7%), Cx (25/111; 22.5%), and finally proximal RCA (19/111; 17.1%). At 8 weeks after the diagnosis (Table 3 ), the regression rate followed the initial severity: 62.2% if the initial lesion was dilation, 32.4% if small aneurysms, 5.4% if medium aneurysms and none of initial large aneurysms. Table 3 8 week-regression rates of CALs developing during the acute and subacute stage Regression rate of tCALs based on initial severity and site LMCA LAD Cx RCA prox TOTAL Dilation 27 (61.4%) 14 (60.9%) 14 (56%) 14 (73.7%) 69 (62.2%) Small aneurysms 15 (34.1%) 8 (34.8%) 9 (36%) 4 (21.1%) 36 (32.4%) Medium aneurysms 2 (4.5%) 1 (4.3%) 2 (8%) 1 (5.3%) 6 (5.4%) Large aneurysms 0 0 0 0 0 TOTAL 44 (39.6%) 23 (20.7%) 25 (22.5%) 19 (17.1%) 111 A multivariate logistic regression was conducted to assess risk factors for developing pCALs. Male gender (p 0.043, OR 2.34, IC95% 1.02–5.34), age younger than 6 months (p 0.042, OR 0.37, IC95% 0.14–0.96), Asian ethnicity (p 0.019, OR 0.63, IC95%), fever lasting more than 10 days (p 0.015, OR1.56, IC95% 1.09–2.25), CRP higher than 13 mg/dl (p 0.033, OR 2.19, IC95% 1.06–4.52) were independent risk factors for pCALs, while Hb lower than 10.3 g/dl (p 0.079, OR 1.97, IC95% 0.92–4.2) was not statistically associated with higher incidence of pCALs. The cutoff of 10.3 g/dl was chosen as the lowest standard deviation for the definition of anemia in children aged from one to twelve years-old (37). A ROC analysis was performed to assess the performance of Son’s risk prediction model (35) to identify patients at risk for developing pCALs in our cohort. The area under the ROC curve (AUC) is 0.7915, suggesting the good discriminating power of the model (Fig. 1 ). Discussion Our study confirms that male gender, younger age, Asian ethnicity, incomplete clinical presentation, longer fever duration (particularly more than 10 days), abnormal abdominal US findings and IVIG-resistance are risk factors for the persistence of coronary lesions in an Italian mostly Caucasian cohort. At the laboratory tests, lower red blood cells, lower albumin, and higher CRP are associated with persistence of coronary damage. By the comparison of patients with pCALS and tCALs, the former were younger and more likely to be IVIG resistant and late treated, to have lower hemoglobin and albumin and higher CRP. Thus, younger age, no response to standard treatment, higher inflammatory marker and lower albumin are linked in general to coronary involvement either during acute and 8-weeks phases of KD, potentially supporting the role of a longer inflammation in younger subjects. In addition, IVIG-resistance was an independent risk factor, as age younger than 6 months, Asian ethnicity, fever duration more than 10 days and CRP greater than 13 mg/dl, according with data from multiethnic children with KD. Most studies tried to identify risk factors for CALs during the acute stage of KD [ 26 , 36 , 38 ] and fewer focused on the factors linked to the coronary damage over time [ 22 , 39 ]. Our findings show that IVIG resistance is linked with the occurrence of coronary damage not only during the acute stage of the disease [ 1 , 36 ], but also with its persistence after resolution of inflammation. This is crucial because IVIG resistance, associated with large CALs and male gender, was significantly linked with major cardiac adverse events in a multicentric Japanese study including over 1000 KD patients [ 40 ]. In our cohort, CALs persisted for 8 weeks after diagnosis in 38.2% of patients after the acute phase [ 36 ]. Coronary size is known to influence lesion progression [ 41 , 42 ]: small aneurysms typically regress, while 70–95% of medium and large-sized aneurysms tend to persist, with up to 20% progressing to stenosis. In addition, smaller CALs tend to regress earlier [ 43 ], usually within six months from the onset, especially in patients younger than one year of age. Our results show that smaller CALs, including dilations and small-sized aneurysms, regress after eight weeks in over 90% of cases, whereas large and giant coronary aneurysms do not. The lack of improvement of coronary size in case of large/giant aneurysms is different from what previously found in KD Japanese patients, who showed a regression rate of 28–36% of cases 10 years after the diagnosis [ 20 ]. It is important to highlight the different time points, as our data confirm the trend of size-based improvement and reflect an evolving condition, given that pathological mechanisms continue for years after diagnosis [ 3 ]. The most common sites of coronary involvement in decreasing frequency are reported to be the proximal LAD, proximal RCA, LMCA and CX [ 20 , 44 ]. In our population the distribution of pCALs is consistent with data from multiethnic and Asian population: LAD was the most affected coronary artery in case of single and multivessel involvement, followed by CX and LMCA; RCA, on the other hand, was more frequently involved when multicoronary injury occurred. The vast majority of CALs were dilation and small aneurysms, accounting for 74.8% of cases, while giant aneurysms persisted in 7.6% of patients. Blood tests linked to coronary damage mostly overlap for patients with aCALs and pCALs: lower values of red blood cells, Hb and albumin, and higher CRP levels were significantly associated with tCALs and pCALs, in line with other cohorts [ 36 , 45 , 46 ]. Moreover, a higher hemoglobin level was identified as an independent risk factor for CAL regression within three weeks of diagnosis [ 47 ] and is therefore included in a nomogram score to predict it. Our findings indicate that significant and persistent inflammation—characterized by elevated CRP levels, lower albumin, prolonged fever duration, and IVIG resistance—plays a crucial role in coronary damage. Previous studies have demonstrated an association between CRP [ 47 , 48 ] and IVIG unresponsiveness [ 29 , 49 ] with the development of CALs. Notably, CRP emerged as an independent risk factor for the persistence of CALs in our cohort. Furthermore, CRP levels > 13 mg/dL, which are included in the Son’s score, demonstrated a strong predictive value for injury persistence in our study population. Despite its link to IVIG resistance, pCALs were detected in over 40% of IVIG responders. Additionally, Asian ethnicity was identified as an independent risk factor, even though only 13.7% of the cohort was of Asian descent. This finding supports the hypothesis that coronary injury arises from a complex interplay of multiple factors, including genetic predisposition and unknown environmental triggers. The presence of abdominal US anomalies during the acute phase of the disease was significantly associated with pCALs. Notably, previous studies linked abdominal US anomalies to a more severe course of KD, including the development of CALs [ 29 ] and IVIG resistance [ 50 ]. Additionally, elevated fecal calprotectin levels and aCALs have been shown to predict CAL persistence [ 50 ]. However, in our population, the gastrointestinal (GI) group—including those with GI symptoms and/or liver laboratory abnormalities—did not exhibit a higher risk for pCALs. This finding aligns with data from a multiethnic population [ 28 ] but contrasts with a Chinese cohort that demonstrated an intermediate risk for CALs [ 50 ]. Similarly to our findings, both studies identified younger age at diagnosis as the highest risk factor for CALs compared to groups with liver involvement, severe inflammation, cervical lymphadenopathy, and elevated band neutrophils. Furthermore, gamma-glutamyl transferase levels were reported as an independent risk factor for CAL persistence in another Asian cohort [ 22 ]; however, we did not observe this association in our study. KD cardiovascular sequelae are related to coronary damage leading to stenosis and thrombosis, myocardial ischemia, and sudden death [ 19 , 51 ]. Multiple studies across different ethnic groups [ 21 , 35 , 39 , 51 – 54 ] have emphasized the significance of initial coronary size, which appears to be correlated with CAL persistence. Therefore, it is essential to develop and validate a predictive tool for pCALs in KD patients. Son et al. developed and validated a risk score model in a multiethnic US population, including initial coronary artery size and simple clinical and laboratory data, such as age, ethnicity and CRP [ 35 ]. The Update on Diagnosis and Management of KD stated that patients identified as “high-risk” by Son risk score could benefit from initial intensification treatment [ 2 ]. When tested in our population, Son’s Risk Score demonstrated strong predictive value for pCALs, suggesting its effectiveness in assessing the persistence of CALs in patients who could benefit from the intensification treatment. For instance, primary adjunctive treatment with Infliximab [ 55 ] or Anakinra [ 20 ] were shown the be associated with a greater likelihood of CALs regression in patients with coronary involvement at the initial evaluation. Conclusion In a predominantly Caucasian cohort, IVIG resistance, diagnosis of KD before six months of age, Asian ethnicity, and CRP levels exceeding 13 mg/dL were identified as independent risk factors for CAL persistence beyond eight weeks post-diagnosis. Abnormal abdominal ultrasound findings were associated with pCALs and should be assessed at diagnosis, particularly in boys with an incomplete clinical presentation, anemia, and low albumin levels. Notably, Son’s score enables the rapid identification of patients at risk for persistent coronary injury, allowing for early treatment intensification regardless of IVIG response, potentially reducing KD-related morbidity. Abbreviations AUC Area under the curve CA coronary artery CAL coronary artery lesion CRP C reactive protein Cx left circumflex branch ESR Erythrocyte sedimentation rate GGT Gamma-glutamyltransferase GOT glutamic oxaloacetic transaminase GPT glutamate-pyruvate transaminase IQR interquartile range KD Kawasaki Disease LAD Left anterior descending coronary artery LMCA left main coronary artery OR Odds Ratio pCALs persistent Coronary Artery Lesions RCA Right coronary artery ROC Receiver Operating Characteristic SD standard deviation Declarations The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The authors have no relevant financial or non-financial interests to disclose. All authors contributed to the study’s conception and design. Material preparation and data collection were performed by Marianna Fabi, Fiorentina Guida, Elisabetta Morana, Laura Andreozzi, Lucia Augusta Baselli, Martina Rossano, Ivana Bruno, Francesca Lami, Elena Corinaldesi, Cristina Cicero, Lorenzo Mambelli, Barbara Bigucci, Andrea Taddio, Michela Cappella, Paola Fernicola, and Marcello Lanari. Leonardo Frazzoni, and Rocco Maurizio Zagari performed data analysis. The first draft of the manuscript was written by Fiorentina Guida, Laura Andreozzi, and Marianna Fabi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of IRCCS AOU BO (Avec 340/2017/O/OssAOUBO approved on 1/16/2019). Informed consent was obtained from all individual participants included in the study. Data Availability Data for this study were retrospectively and prospectively collected and entered into a REDcap database, from an Italian cohort composed of 11 recruiting centers [36] between January 1, 2000, and June 30, 2023 References 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, Council on Epidemiology and Prevention (2017) American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. ;135(17):e927-e999. doi: 10.1161/CIR.0000000000000484. Epub 2017 Mar 29. Erratum in: Circulation. 2019;140(5):e181-e184. 10.1161/CIR.0000000000000703 . 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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-6243172","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":434021414,"identity":"d503ba28-1338-4cd6-a19b-c293dded0017","order_by":0,"name":"Fiorentina Guida","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero Universitaria di Bologna","correspondingAuthor":false,"prefix":"","firstName":"Fiorentina","middleName":"","lastName":"Guida","suffix":""},{"id":434021415,"identity":"24d7ba63-72f2-42a7-aedb-92014061415e","order_by":1,"name":"Elisabetta Morana","email":"data:image/png;base64,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","orcid":"","institution":"University of Bologna","correspondingAuthor":true,"prefix":"","firstName":"Elisabetta","middleName":"","lastName":"Morana","suffix":""},{"id":434021416,"identity":"ef0e2a0b-f047-467a-8579-e5a8b5d4abd9","order_by":2,"name":"Elena Tarì","email":"","orcid":"","institution":"University of Bologna","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Tarì","suffix":""},{"id":434021417,"identity":"9b1af656-b981-423b-8d59-1fd90912b3fb","order_by":3,"name":"Leonardo Frazzoni","email":"","orcid":"","institution":"UOC Gastroenterologia ed Endoscopia Digestiva Forlì-Cesena, AUSL della Romagna","correspondingAuthor":false,"prefix":"","firstName":"Leonardo","middleName":"","lastName":"Frazzoni","suffix":""},{"id":434021418,"identity":"4b462f4d-1ff2-46b3-9cef-53e986ac401d","order_by":4,"name":"Laura Andreozzi","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero Universitaria di Bologna","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Andreozzi","suffix":""},{"id":434021419,"identity":"bdcf69f7-76c7-497b-bf17-adbff8bd6866","order_by":5,"name":"Lucia Augusta Baselli","email":"","orcid":"","institution":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico","correspondingAuthor":false,"prefix":"","firstName":"Lucia","middleName":"Augusta","lastName":"Baselli","suffix":""},{"id":434021420,"identity":"736604a7-6a82-47c7-9658-be3910e6b997","order_by":6,"name":"Francesca Lami","email":"","orcid":"","institution":"University of Modena and Reggio Emilia","correspondingAuthor":false,"prefix":"","firstName":"Francesca","middleName":"","lastName":"Lami","suffix":""},{"id":434021421,"identity":"38ee6483-5b54-476e-b956-434b70441630","order_by":7,"name":"Elena Corinaldesi","email":"","orcid":"","institution":"Carpi Hospital","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Corinaldesi","suffix":""},{"id":434021422,"identity":"97e47971-1076-4dca-bbcc-f44cbf4d0728","order_by":8,"name":"Cristina Cicero","email":"","orcid":"","institution":"AUSL, Guglielmo da Saliceto Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Cicero","suffix":""},{"id":434021423,"identity":"4f886f2e-faaf-4f15-b4c4-04c6f35887c6","order_by":9,"name":"Lorenzo Mambelli","email":"","orcid":"","institution":"Santa Maria delle Croci Hospital, AUSL della Romagna","correspondingAuthor":false,"prefix":"","firstName":"Lorenzo","middleName":"","lastName":"Mambelli","suffix":""},{"id":434021424,"identity":"d749ee73-3af4-4663-8d64-40d6febb0c4a","order_by":10,"name":"Gianluca Vergine","email":"","orcid":"","institution":"Rimini Hospital, AUSL Romagna","correspondingAuthor":false,"prefix":"","firstName":"Gianluca","middleName":"","lastName":"Vergine","suffix":""},{"id":434021425,"identity":"4e4cbaec-b9fc-4385-a323-0e7160f10e2a","order_by":11,"name":"Andrea Taddio","email":"","orcid":"","institution":"IRCCS \"Burlo Garofolo, Trieste. University of Trieste","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Taddio","suffix":""},{"id":434021426,"identity":"55fbab06-23a3-4249-9aaf-441a6d249f6e","order_by":12,"name":"Michela Cappella","email":"","orcid":"","institution":"Santa Maria Nuova Hospital, Azienda Unità Sanitaria Locale (AUSL)-Scientific Institute for Research and Healthcare (IRCCS) of Reggio Emilia","correspondingAuthor":false,"prefix":"","firstName":"Michela","middleName":"","lastName":"Cappella","suffix":""},{"id":434021427,"identity":"b6510bb7-d506-401b-8d1b-94991a18d8f8","order_by":13,"name":"Barbara Bigucci","email":"","orcid":"","institution":"Rimini Hospital, AUSL Romagna","correspondingAuthor":false,"prefix":"","firstName":"Barbara","middleName":"","lastName":"Bigucci","suffix":""},{"id":434021428,"identity":"00bce99a-7489-4727-9367-e455947b0665","order_by":14,"name":"Ivana Bruno","email":"","orcid":"","institution":"Santa Maria delle Croci Hospital, AUSL della Romagna","correspondingAuthor":false,"prefix":"","firstName":"Ivana","middleName":"","lastName":"Bruno","suffix":""},{"id":434021429,"identity":"7c8e0f6e-08c6-452e-801c-c62b9a5677fa","order_by":15,"name":"Paola Fernicola","email":"","orcid":"","institution":"G.B. Morgagni Pierantoni Hospital, Azienda Unità Sanitaria Locale (AUSL) Romagna","correspondingAuthor":false,"prefix":"","firstName":"Paola","middleName":"","lastName":"Fernicola","suffix":""},{"id":434021430,"identity":"a1080bbe-b6ca-419d-b8c8-017be4983ab8","order_by":16,"name":"Ilaria Frabboni","email":"","orcid":"","institution":"University of Modena and Reggio Emilia","correspondingAuthor":false,"prefix":"","firstName":"Ilaria","middleName":"","lastName":"Frabboni","suffix":""},{"id":434021431,"identity":"c244895c-1d05-460d-a212-e2ff71579fca","order_by":17,"name":"Matteo Meli","email":"","orcid":"","institution":"AUSL Bologna, Ospedale Maggiore","correspondingAuthor":false,"prefix":"","firstName":"Matteo","middleName":"","lastName":"Meli","suffix":""},{"id":434021433,"identity":"be5211fd-9939-4e7a-a61f-cb01915ed850","order_by":18,"name":"Martina Rossano","email":"","orcid":"","institution":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico","correspondingAuthor":false,"prefix":"","firstName":"Martina","middleName":"","lastName":"Rossano","suffix":""},{"id":434021434,"identity":"dc753059-8022-4983-a958-a08c8913413e","order_by":19,"name":"Rocco Maurizio Zagari","email":"","orcid":"","institution":"University of Bologna","correspondingAuthor":false,"prefix":"","firstName":"Rocco","middleName":"Maurizio","lastName":"Zagari","suffix":""},{"id":434021436,"identity":"7e5b48dd-a1ac-4433-9176-21b2a848a579","order_by":20,"name":"Marcello Lanari","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero Universitaria di Bologna","correspondingAuthor":false,"prefix":"","firstName":"Marcello","middleName":"","lastName":"Lanari","suffix":""},{"id":434021437,"identity":"0cb6e740-b857-4ba3-8cee-e76f6dbb1698","order_by":21,"name":"Marianna Fabi","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero Universitaria di Bologna","correspondingAuthor":false,"prefix":"","firstName":"Marianna","middleName":"","lastName":"Fabi","suffix":""}],"badges":[],"createdAt":"2025-03-17 09:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6243172/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6243172/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-025-06162-0","type":"published","date":"2025-05-31T15:57:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79573500,"identity":"61245ccb-fde7-4ca6-b05c-ee1f2f55800c","added_by":"auto","created_at":"2025-03-31 11:06:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47164,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe application of Son’s risk score to predict the development of pCALs in the presented population\u003c/strong\u003e. The ROC curve evaluates the performance of Son’s risk prediction model (35) in predicting the development of pCALs. The X-axis represents the false positive rate (1 - Specificity), and the Y-axis represents the true positive rate (Sensitivity). The blue curve illustrates the model's ability to distinguish between positive and negative classes at various threshold settings. The green diagonal line signifies random classification. The area under the ROC curve (AUC) is 0.7915, indicating that the model has good discriminative power.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6243172/v1/fc5d785c1cdf02ca7af001bf.png"},{"id":83783127,"identity":"0192e8d0-91f2-459e-9795-98e7e65ecbd8","added_by":"auto","created_at":"2025-06-02 16:11:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1090545,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6243172/v1/7b85507c-6152-42d3-bade-52cde23474ae.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk factors associated with persistent coronary artery lesions in children with Kawasaki Disease in an Italian cohort","fulltext":[{"header":"What is known？","content":"\u003cp\u003e\u0026middot; Kawasaki disease can cause CALs, which increase cardiovascular risk if they persist.\u003c/p\u003e\n\u003cp\u003e\u0026middot; Previous research has focused mainly on predicting CALs or treatment resistance, but little evidence is available on the risk factors for CALs persistence.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is new?\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026middot; Our study identifies independent risk factors for pCALs in Italian children: male gender, younger age, incomplete presentation, Asian ethnicity and high CRP levels.\u003c/p\u003e\n\u003cp\u003e\u0026middot; By applying the Son Risk Score to our population, we confirmed its predictive value in a predominantly Caucasian cohort and its reliability in identifying susceptibility to CALs persistence.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eKawasaki disease (KD) is an acute febrile systemic vasculitis with an unclear etiology that primarily affects children under five years-old [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Its major complication is coronary involvement, where vasculopathic processes lead to vascular wall injury and subsequently dilation or aneurysms [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], increasing cardiovascular risk of the affected children in the short, medium [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and long term [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The genetic background [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] affects the susceptibility to the disease [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and its severity in Asian and other ethnic groups [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Other predisposing factors, such as environmental factors and infections, interplay with genetics, triggering the disease and favoring the development of coronary artery lesions (CALs) [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Identifying anamnestic, demographic, clinical, and laboratory variables associated with the risk of coronary involvement could lead to identifying children who might benefit from additional immunomodulatory therapy alongside intravenous immunoglobulins (IVIG) at an early stage, thereby reducing vascular damage and improving cardiovascular outcomes. Indeed, CALs develop in 5% of patients despite proper and timely treatment making KD the leading cause of acquired heart disease in children [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. CALs typically develop within the first ten days after the onset of KD [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and tend to normalize their diameter in up to 75% of cases within two years of the disease's diagnosis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] despite vascular wall histological alteration occurring.\u003c/p\u003e \u003cp\u003eSo far, numerous studies have been conducted to identify risk factors that expose children with KD to developing CALs and their persistence over the first eight weeks of the diagnosis. Younger age, male gender, IVIG resistance or a delayed administration, a prolonged course of fever, multiple coronary involvement, along with blood test alterations, such as elevated C reactive protein (CRP), altered neutrophil-to-lymphocyte ratio, reduced hemoglobin level, and hypoalbuminemia, have been related to higher rate of CALs in the acute stage of KD [\u003cspan additionalcitationids=\"CR23 CR24 CR25 CR26\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In addition, subgroups of children with KD with different laboratory and clinical presentations have been associated with coronary involvement or IVIG resistance [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMoreover, different risk scores aimed at identifying the formation of CALs have been validated in the Asian population [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] but showed lower accuracy in other ethnicities [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The risk score published by Son \u003cem\u003eet al.\u003c/em\u003e assessed the predictive value for coronary lesions in a North American multiethnic cohort using simple data, such as age, ethnicity, CRP, and initial coronary z-score [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. It is thus necessary to identify risk factors associated with a higher likelihood of persisting after the subacute stage and to validate existing diagnostic tools across different geographical regions. This will enable patients to benefit from personalized treatments based on precise risk stratification.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eData for this study were retrospectively and prospectively collected and entered into a REDcap database, from an Italian cohort composed of 11 recruiting centers [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] between January 1, 2000, and June 30, 2023.\u003c/p\u003e \u003cp\u003e This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of IRCCS AOU BO (Avec 340/2017/O/OssAOUBO approved on 1/16/2019). According to local regulations, the institutional review board granted the study approval at each enrolling site. Informed consent was obtained from all individual participants\u0026rsquo; parents included in the study.\u003c/p\u003e \u003cp\u003e The Data Coordinating Center (IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy) reviewed and analyzed all the data, ensuring patient eligibility, data completeness, and accuracy.\u003c/p\u003e \u003cp\u003eThe materials and methods have been previously detailed in a prior publication by our group [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Briefly, the diagnosis of KD, the clinical presentation (complete and incomplete form), the response to treatment with IVIG (IVIG- responders, IVIG non responders), and the timing of treatment related to the diagnosis (late or not treated) were based on the American Heart Association criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCollected data included demographical and clinical features, blood tests (i.e., white blood cells (WBC), percentage of neutrophils (N%), percentage of lymphocytes (L%), hemoglobin levels (Hb), platelet count (PLT), serum glucose, hepatic and kidney function markers, CRP and erythrocyte sedimentation rate (ESR), serum albumin, and serum electrolyte levels), echocardiographic evaluation, and abdominal ultrasound (US) performed during the hospitalization if requested by the physician. The laboratory values were collected during the acute (from the onset to the 10th days after fever onset), subacute (from the 11th to the 20th days after fever onset), and chronic stage (from the 6th week after fever onset) for each patient.\u003c/p\u003e \u003cp\u003eIn addition, gastrointestinal (GI) involvement was defined as the presence of symptoms such as diarrhea, abdominal pain, or vomiting, along with abnormal abdominal US findings, including gallbladder hydrops, effusion in the pouch of Douglas, thickening of the intestinal wall, mesenteric adenopathies, or abdominal effusion. Echocardiography was performed during the acute, subacute, and chronic stages with the same modalities previously published [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. CA involvement was then classified by Z-score as no involvement (Z\u0026thinsp;\u0026lt;\u0026thinsp;2), dilation (Z 2 to \u0026lt;\u0026thinsp;2.5), small aneurysm (Z 2.5 to \u0026lt;\u0026thinsp;5), medium aneurysm (Z 5 to \u0026lt;\u0026thinsp;10), and large aneurysm (Z\u0026thinsp;\u0026gt;\u0026thinsp;10), according to the 2017 AHA guidelines [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Persistent coronary artery lesions (pCALs) were defined as the persistence of CA dilation or aneurysm 8 weeks after the diagnosis of KD. Transient coronary lesions (tCALs) were defined as CALs development by the 20th day of fever and resolved by 8 weeks after fever onset. Left main coronary artery (LMCA), left anterior descending coronary artery (LAD), circumflex (CX) and right coronary artery (RCA) were studied.\u003c/p\u003e \u003cp\u003eCategorical variables were presented as absolute frequency and percentage, while non-normally distributed continuous variables were displayed as mean, standard deviation (SD), and/or interquartile range (IQR). Multivariate logistic regression was used to assess the risk factors for developing persistent coronary artery lesions (pCALs) in our population. Odds ratio and 95% confidence interval were obtained, and P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as statistically significant. The variables statistically related to a higher risk for developing pCALs were evaluated to elaborate a risk prediction model. A Receiver Operating Characteristic (ROC) analysis was conducted to assess the performance and reliability of Son\u0026rsquo;s risk prediction model [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] to predict the development of pCALs in the presented population. Statistical analysis was performed using STATA software version 16 (Stata Corp., College Station, TX).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 517 (boys 53.8%, mean age 44 months, SD 38.19) patients were included in the study and 52 patients (10%) developed pCALs.\u003c/p\u003e \u003cp\u003eDemographical, clinical, therapeutical, laboratory, and radiological features of patients with and without pCALs are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographical clinical and laboratoristic features of patients with pCALs compared to those without pCALs\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003epCALs\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNo pCALs\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDemographical features\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIC (95%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003cp\u003e- Male\u003c/p\u003e\n \u003cp\u003e- Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e74.5\u003c/p\u003e\n \u003cp\u003e27.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e278\u003c/p\u003e\n \u003cp\u003e187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e53.8\u003c/p\u003e\n \u003cp\u003e36.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.043*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEthnicity\u003c/p\u003e\n \u003cp\u003e- Asian\u003c/p\u003e\n \u003cp\u003e- Caucasian\u003c/p\u003e\n \u003cp\u003e- Afro-American\u003c/p\u003e\n \u003cp\u003e- Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e13.7\u003c/p\u003e\n \u003cp\u003e78.4\u003c/p\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003cp\u003e412\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003cp\u003e79.7\u003c/p\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.019*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSeasonality\u003c/p\u003e\n \u003cp\u003e- Autumn\u003c/p\u003e\n \u003cp\u003e- Summer\u003c/p\u003e\n \u003cp\u003e- Winter\u003c/p\u003e\n \u003cp\u003e- Spring\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e25.5\u003c/p\u003e\n \u003cp\u003e19.6\u003c/p\u003e\n \u003cp\u003e31.4\u003c/p\u003e\n \u003cp\u003e25.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003cp\u003e158\u003c/p\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e22.8\u003c/p\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003cp\u003e30.6\u003c/p\u003e\n \u003cp\u003e23.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical features\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC (95%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical presentation\u003c/p\u003e\n \u003cp\u003e- Complete\u003c/p\u003e\n \u003cp\u003e- Incomplete\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e295\u003c/p\u003e\n \u003cp\u003e164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e57.1\u003c/p\u003e\n \u003cp\u003e31.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0.033*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFever duration, mean days (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePersistent fever (\u0026gt;\u0026thinsp;10 days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e428\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.015*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConjunctivitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSwelling of the hand and feet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.333\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e221\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOral changes\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCervical adenopathy\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.533\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGI group\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGI manifestations\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLiver involvement\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbdominal ultrasound findings\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.040*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePulmonary complications\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePerianal/diaper erythema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteomuscular involvement\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAseptic meningitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFacial nerve palsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMacrophagic activation syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetropharyngeal edema/phlegmon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC (95%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStandard treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.023*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR: 1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95%CI: 0.46\u0026ndash;2.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLate treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR: 2.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95%CI: 1.32\u0026ndash;5.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.023*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR: 4.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95%CI: 1.58\u0026ndash;11.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIVIG- responders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR: 0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95%CI: 0.20\u0026ndash;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIVIG- non responders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOR: 2.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95%CI: 1.13\u0026ndash;3.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eOral changes: Erythema and cracking of lips (cheilitis); strawberry tongue; erythema of oral and pharyngeal mucosa;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003eCervical adenopathy: defined as a swallowing of the cervical nodes bigger than 1.5 cm.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ec\u003c/sup\u003eGI, Gastro-intestinal manifestations: diarrhea and/or abdominal pain and/or vomiting\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ed\u003c/sup\u003eGI, Gastro-intestinal group refers to any patient with one of the following: liver test anomalies (GOT and GPT), pathological findings at abdominal ultrasounds, GI signs or symptoms.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ee\u003c/sup\u003eLiver involvement: liver test anomalies and/or jaundice\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ef\u003c/sup\u003eAbdominal ultrasound findings: gallbladder hydrops, effusion in the pouch of Douglas, swallowing of the intestinal wall, mesenterial adenopathies. abdominal effusion\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eg\u003c/sup\u003ePulmonary complications: peribronchial interstitial inflammation\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eh\u003c/sup\u003eOsteomuscular involvement: joint pain and/or arthtritis\u003c/p\u003e\n\u003cp\u003eGOT. glutamic oxaloacetic transaminase; GPT. glutamate-pyruvate transaminase; GGT. Gamma-glutamyltransferase; ESR. Erythrocyte sedimentation rate; CRP: C-reactive protein\u003c/p\u003e\n \u003cp\u003eCompared to patients without pCALs, those with pCALs were younger (mean age: 25.3 months, SD 24.8; p 0.043) and predominantly male (38/52, 74.5%; p\u0026thinsp;=\u0026thinsp;0.043), more likely to be Asian (7/52, 13.7%; p\u0026thinsp;=\u0026thinsp;0.019), to have an incomplete clinical presentation (26/52, 51% \u003cem\u003evs\u003c/em\u003e 164/465, 31.7%, p 0.033) and fever lasting more than 10 days (48/52, 94.1% \u003cem\u003evs\u003c/em\u003e 428, 82.8%, p 0.001). They were more prone to present abdominal US anomalies (respectively 5/52, 9.6% \u003cem\u003evs\u003c/em\u003e 38/517, 7.4%, p 0.04), with a similar rate of GI manifestations when compared to children without pCALs (respectively 16/52, 31.4% \u003cem\u003evs\u003c/em\u003e 179/517, 34.6% p 0.276).\u003c/p\u003e \u003cp\u003eForty-six out of 52 (88%) who developed pCALs received IVIG, and 34/46 (73.9%) within the first 10 days of fever. Twenty-two out of 46 (47.8%) patients were IVIG responders, 18 patients (39.1%) were IVIG non-responders. Second line treatments were a second dose of IVIG infusion alone in 6/46 (13.05%), IVIG and steroids in 7/46 (15.2%), and biologics in 5/46 (10.9%), particularly anakinra in 4 (8.7%) patients and infliximab in 1 (2.2%). The lack of treatment with IVIG and IVIG-unresponsiveness were significantly associated with pCALs (respectively p 0.023; OR 4.27, 95% CI 1.58\u0026ndash;11.53, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; OR 2.09, 95% CI 1.13\u0026ndash;3.84). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows laboratory tests of the patients with pCALs compared with tCALs, and without pCALs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of laboratoristic data of patients with pCALs with tCALs (p value\u003csup\u003ea\u003c/sup\u003e) and with those who never developed CALs (p value\u003csup\u003eb\u003c/sup\u003e)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003etCALs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo pCALs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003epCALs\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed blood cells x 10\u003csup\u003e12\u003c/sup\u003e (/L) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.239\u0026thinsp;\u0026plusmn;\u0026thinsp;1.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.327\u0026thinsp;\u0026plusmn;\u0026thinsp;1.104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.030*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e4.145\u0026thinsp;\u0026plusmn;\u0026thinsp;1.676\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dl) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.042*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e11.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e10.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (x 10\u003csup\u003e9\u003c/sup\u003e/L) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e376.577\u0026thinsp;\u0026plusmn;\u0026thinsp;177.540\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.844\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e372.397\u0026thinsp;\u0026plusmn;\u0026thinsp;180.737\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.605\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e386.956\u0026thinsp;\u0026plusmn;\u0026thinsp;187.281\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGOT (UI/l) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e62.116\u0026thinsp;\u0026plusmn;\u0026thinsp;48.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.481\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e71.6\u0026thinsp;\u0026plusmn;\u0026thinsp;40.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.726\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e62.3\u0026thinsp;\u0026plusmn;\u0026thinsp;31.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGPT (UI/l) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e68.7\u0026thinsp;\u0026plusmn;\u0026thinsp;48.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e77.7\u0026thinsp;\u0026plusmn;\u0026thinsp;45.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e87.1\u0026thinsp;\u0026plusmn;\u0026thinsp;62.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGGT (UI/l) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e52.148\u0026thinsp;\u0026plusmn;\u0026thinsp;32.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e52.2\u0026thinsp;\u0026plusmn;\u0026thinsp;33.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.441\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e70.2\u0026thinsp;\u0026plusmn;\u0026thinsp;57.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dl) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.475\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.008*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.667\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSodium (mmol/l) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e134.47\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.837\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e134.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.746\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e134.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR (mm/h) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e62.08\u0026thinsp;\u0026plusmn;\u0026thinsp;31.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.701\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e63.8\u0026thinsp;\u0026plusmn;\u0026thinsp;32.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;33.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/dl) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.01\u0026thinsp;\u0026plusmn;\u0026thinsp;7.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.008*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e12.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWhen compared with patients without pCALs, those with pCALs presented lower red blood cell count (p 0.030) and serum albumin (p 0.003) and higher CRP (p 0.001), and lower Hb and albumin (respectively p 0.042 and p 0.008) and higher CRP (p 0.008) when compared with patients with tCALs.\u003c/p\u003e \u003cp\u003eIn addition, in comparison to patients with tCALs (35), those with pCALs were younger (mean age: 25.3 months \u003cem\u003eversus\u003c/em\u003e 36.5 months; p 0.043), IVIG- resistants (34.6%, 18/52 \u003cem\u003eversus\u003c/em\u003e 29.6%, 153/517; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001); late treatment was more frequent in pCALs without reaching the statistical significance (11.5%, 6/52 \u003cem\u003eversus\u003c/em\u003e 7.9% 41/135; p 0.076). Both groups experienced a similar incidence of GI involvement (16/52, 31.4% vs 84/135, 26%; p 0.868).\u003c/p\u003e \u003cp\u003epCALs were classified as dilation in 48.0% (25/52), small aneurysm in 26.9% (14/52), medium aneurysm in 17.3% (9/52), and giant aneurysm in 7.7% (4/52) of the population. When pCALs occurred in a single vessel, LAD was the most frequently affected (20/52, 38.4%), followed by the Cx (15/52, 28.8%), LMCA (13/52, 25%), and RCA (4/52, 7.7%). Multi-coronary injury (at least 2 vessels involved) occurred in 41/52 (78.8%) of patients: LAD was affected in 59.6% (31/52), LMCA in 51.9% (27/52), RCA in 40.4% (21/52), and Cx in 36.5% (19/52). All patients presented normal left ventricular systolic function, 7.6% (4/52) mild mitral regurgitation, and 3.8% (2/52) mild pericardial effusion.\u003c/p\u003e \u003cp\u003etCALs developed in 129/135 (95.5%) patients during the acute phase and 6/135 (4.4%) during the convalescent phase. CALs persisted in 52/135 (38.5%) and regressed in 83/135 (61.5%).\u003c/p\u003e \u003cp\u003eThe total number of CALs during acute and subacute stage was 111: LMCA was the most commonly affected vessels (44/111; 39.6%), followed by LAD (23/111; 20.7%), Cx (25/111; 22.5%), and finally proximal RCA (19/111; 17.1%). At 8 weeks after the diagnosis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), the regression rate followed the initial severity: 62.2% if the initial lesion was dilation, 32.4% if small aneurysms, 5.4% if medium aneurysms and none of initial large aneurysms.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e8 week-regression rates of CALs developing during the acute and subacute stage\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eRegression rate of tCALs based on initial severity and site\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eLMCA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eLAD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eCx\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eRCA prox\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eTOTAL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDilation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (61.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (60.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (73.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e69 (62.2%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmall aneurysms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (34.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (21.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e36 (32.4%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedium aneurysms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e6 (5.4%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLarge aneurysms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTOTAL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e44 (39.6%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e23 (20.7%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e25 (22.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e19 (17.1%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e111\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA multivariate logistic regression was conducted to assess risk factors for developing pCALs. Male gender (p 0.043, OR 2.34, IC95% 1.02\u0026ndash;5.34), age younger than 6 months (p 0.042, OR 0.37, IC95% 0.14\u0026ndash;0.96), Asian ethnicity (p 0.019, OR 0.63, IC95%), fever lasting more than 10 days (p 0.015, OR1.56, IC95% 1.09\u0026ndash;2.25), CRP higher than 13 mg/dl (p 0.033, OR 2.19, IC95% 1.06\u0026ndash;4.52) were independent risk factors for pCALs, while Hb lower than 10.3 g/dl (p 0.079, OR 1.97, IC95% 0.92\u0026ndash;4.2) was not statistically associated with higher incidence of pCALs. The cutoff of 10.3 g/dl was chosen as the lowest standard deviation for the definition of anemia in children aged from one to twelve years-old (37).\u003c/p\u003e \u003cp\u003eA ROC analysis was performed to assess the performance of Son\u0026rsquo;s risk prediction model (35) to identify patients at risk for developing pCALs in our cohort. The area under the ROC curve (AUC) is 0.7915, suggesting the good discriminating power of the model (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study confirms that male gender, younger age, Asian ethnicity, incomplete clinical presentation, longer fever duration (particularly more than 10 days), abnormal abdominal US findings and IVIG-resistance are risk factors for the persistence of coronary lesions in an Italian mostly Caucasian cohort. At the laboratory tests, lower red blood cells, lower albumin, and higher CRP are associated with persistence of coronary damage. By the comparison of patients with pCALS and tCALs, the former were younger and more likely to be IVIG resistant and late treated, to have lower hemoglobin and albumin and higher CRP.\u003c/p\u003e \u003cp\u003eThus, younger age, no response to standard treatment, higher inflammatory marker and lower albumin are linked in general to coronary involvement either during acute and 8-weeks phases of KD, potentially supporting the role of a longer inflammation in younger subjects.\u003c/p\u003e \u003cp\u003eIn addition, IVIG-resistance was an independent risk factor, as age younger than 6 months, Asian ethnicity, fever duration more than 10 days and CRP greater than 13 mg/dl, according with data from multiethnic children with KD.\u003c/p\u003e \u003cp\u003eMost studies tried to identify risk factors for CALs during the acute stage of KD [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] and fewer focused on the factors linked to the coronary damage over time [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Our findings show that IVIG resistance is linked with the occurrence of coronary damage not only during the acute stage of the disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], but also with its persistence after resolution of inflammation. This is crucial because IVIG resistance, associated with large CALs and male gender, was significantly linked with major cardiac adverse events in a multicentric Japanese study including over 1000 KD patients [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our cohort, CALs persisted for 8 weeks after diagnosis in 38.2% of patients after the acute phase [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Coronary size is known to influence lesion progression [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]: small aneurysms typically regress, while 70\u0026ndash;95% of medium and large-sized aneurysms tend to persist, with up to 20% progressing to stenosis. In addition, smaller CALs tend to regress earlier [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], usually within six months from the onset, especially in patients younger than one year of age.\u003c/p\u003e \u003cp\u003eOur results show that smaller CALs, including dilations and small-sized aneurysms, regress after eight weeks in over 90% of cases, whereas large and giant coronary aneurysms do not. The lack of improvement of coronary size in case of large/giant aneurysms is different from what previously found in KD Japanese patients, who showed a regression rate of 28\u0026ndash;36% of cases 10 years after the diagnosis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. It is important to highlight the different time points, as our data confirm the trend of size-based improvement and reflect an evolving condition, given that pathological mechanisms continue for years after diagnosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe most common sites of coronary involvement in decreasing frequency are reported to be the proximal LAD, proximal RCA, LMCA and CX [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. In our population the distribution of pCALs is consistent with data from multiethnic and Asian population: LAD was the most affected coronary artery in case of single and multivessel involvement, followed by CX and LMCA; RCA, on the other hand, was more frequently involved when multicoronary injury occurred. The vast majority of CALs were dilation and small aneurysms, accounting for 74.8% of cases, while giant aneurysms persisted in 7.6% of patients.\u003c/p\u003e \u003cp\u003eBlood tests linked to coronary damage mostly overlap for patients with aCALs and pCALs: lower values of red blood cells, Hb and albumin, and higher CRP levels were significantly associated with tCALs and pCALs, in line with other cohorts [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Moreover, a higher hemoglobin level was identified as an independent risk factor for CAL regression within three weeks of diagnosis [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e] and is therefore included in a nomogram score to predict it.\u003c/p\u003e \u003cp\u003eOur findings indicate that significant and persistent inflammation\u0026mdash;characterized by elevated CRP levels, lower albumin, prolonged fever duration, and IVIG resistance\u0026mdash;plays a crucial role in coronary damage. Previous studies have demonstrated an association between CRP [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] and IVIG unresponsiveness [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e] with the development of CALs. Notably, CRP emerged as an independent risk factor for the persistence of CALs in our cohort. Furthermore, CRP levels\u0026thinsp;\u0026gt;\u0026thinsp;13 mg/dL, which are included in the Son\u0026rsquo;s score, demonstrated a strong predictive value for injury persistence in our study population.\u003c/p\u003e \u003cp\u003eDespite its link to IVIG resistance, pCALs were detected in over 40% of IVIG responders. Additionally, Asian ethnicity was identified as an independent risk factor, even though only 13.7% of the cohort was of Asian descent. This finding supports the hypothesis that coronary injury arises from a complex interplay of multiple factors, including genetic predisposition and unknown environmental triggers.\u003c/p\u003e \u003cp\u003eThe presence of abdominal US anomalies during the acute phase of the disease was significantly associated with pCALs. Notably, previous studies linked abdominal US anomalies to a more severe course of KD, including the development of CALs [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and IVIG resistance [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Additionally, elevated fecal calprotectin levels and aCALs have been shown to predict CAL persistence [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, in our population, the gastrointestinal (GI) group\u0026mdash;including those with GI symptoms and/or liver laboratory abnormalities\u0026mdash;did not exhibit a higher risk for pCALs. This finding aligns with data from a multiethnic population [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] but contrasts with a Chinese cohort that demonstrated an intermediate risk for CALs [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSimilarly to our findings, both studies identified younger age at diagnosis as the highest risk factor for CALs compared to groups with liver involvement, severe inflammation, cervical lymphadenopathy, and elevated band neutrophils. Furthermore, gamma-glutamyl transferase levels were reported as an independent risk factor for CAL persistence in another Asian cohort [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]; however, we did not observe this association in our study.\u003c/p\u003e \u003cp\u003eKD cardiovascular \u003cem\u003esequelae\u003c/em\u003e are related to coronary damage leading to stenosis and thrombosis, myocardial ischemia, and sudden death [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Multiple studies across different ethnic groups [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan additionalcitationids=\"CR52 CR53\" citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e] have emphasized the significance of initial coronary size, which appears to be correlated with CAL persistence. Therefore, it is essential to develop and validate a predictive tool for pCALs in KD patients. Son et al. developed and validated a risk score model in a multiethnic US population, including initial coronary artery size and simple clinical and laboratory data, such as age, ethnicity and CRP [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The Update on Diagnosis and Management of KD stated that patients identified as \u0026ldquo;high-risk\u0026rdquo; by Son risk score could benefit from initial intensification treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. When tested in our population, Son\u0026rsquo;s Risk Score demonstrated strong predictive value for pCALs, suggesting its effectiveness in assessing the persistence of CALs in patients who could benefit from the intensification treatment. For instance, primary adjunctive treatment with Infliximab [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e] or Anakinra [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] were shown the be associated with a greater likelihood of CALs regression in patients with coronary involvement at the initial evaluation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn a predominantly Caucasian cohort, IVIG resistance, diagnosis of KD before six months of age, Asian ethnicity, and CRP levels exceeding 13 mg/dL were identified as independent risk factors for CAL persistence beyond eight weeks post-diagnosis. Abnormal abdominal ultrasound findings were associated with pCALs and should be assessed at diagnosis, particularly in boys with an incomplete clinical presentation, anemia, and low albumin levels. Notably, Son\u0026rsquo;s score enables the rapid identification of patients at risk for persistent coronary injury, allowing for early treatment intensification regardless of IVIG response, potentially reducing KD-related morbidity.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv id=\"AGS1\" class=\"AbbreviationGroupSection\"\u003e \u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eArea under the curve\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoronary artery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoronary artery lesion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCx\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft circumflex branch\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eErythrocyte sedimentation rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGGT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGamma-glutamyltransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGOT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eglutamic oxaloacetic transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGPT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eglutamate-pyruvate transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKawasaki Disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeft anterior descending coronary artery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLMCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft main coronary artery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003epCALs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epersistent Coronary Artery Lesions\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRCA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRight coronary artery\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReceiver Operating Characteristic\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003estandard deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study\u0026rsquo;s conception and design. Material preparation and data collection were performed by Marianna Fabi, Fiorentina Guida, Elisabetta Morana, Laura Andreozzi,\u0026nbsp;Lucia Augusta Baselli, Martina Rossano, Ivana Bruno, Francesca Lami, Elena Corinaldesi, Cristina Cicero, Lorenzo Mambelli, Barbara Bigucci, Andrea Taddio, Michela Cappella, Paola Fernicola, and Marcello Lanari.\u0026nbsp;Leonardo Frazzoni, and Rocco Maurizio Zagari performed data analysis. The first draft of the manuscript was written by Fiorentina Guida, Laura Andreozzi, and Marianna Fabi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of IRCCS AOU BO (Avec 340/2017/O/OssAOUBO approved on 1/16/2019). Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData for this study were retrospectively and prospectively collected and entered into a REDcap database, from an Italian cohort composed of 11 recruiting centers [36] between January 1, 2000, and June 30, 2023\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\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, Council on Epidemiology and Prevention (2017) American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and. 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PMID: 28734587\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDominguez SR, Anderson MS, El-Adawy M, Glod\u0026eacute; MP (2012) Preventing coronary artery abnormalities: a need for earlier diagnosis and treatment of Kawasaki disease. Pediatr Infect Dis J 31(12):1217\u0026ndash;1220. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/INF.0b013e318266bcf9\u003c/span\u003e\u003cspan address=\"10.1097/INF.0b013e318266bcf9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiyata K, Bainto EV, Sun X, Jain S, Dummer KB, Burns JC, Tremoulet AH (2023) Infliximab for intensification of primary therapy for patients with Kawasaki disease and coronary artery aneurysms at diagnosis. Arch Dis Child 108(10):833\u0026ndash;838. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/archdischild-2023-325639\u003c/span\u003e\u003cspan address=\"10.1136/archdischild-2023-325639\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003eEpub 2023 May 31. PMID: 37258054; PMCID: PMC10511975\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Kawasaki disease, persistent coronary artery lesions, risk score, coronary artery aneurysms, risk factors","lastPublishedDoi":"10.21203/rs.3.rs-6243172/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6243172/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eKawasaki disease (KD) can be complicated, mainly during the acute stage, by coronary artery lesions (CALs); their persistence, after the subacute stage, increases cardiovascular morbidity and life-threatening events lifelong. While several scores, based on Asians and Americans, have been proposed to predict the risk of CALs or non-response, less efforts have been aimed to identify risk factors associated with the persistence of CALs (pCALs). Our study aimed, firstly, to identify the risk factors for pCALs in Italian patients and, secondly, to assess the validity of an existing risk score, previously applied to a North-Americans.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eData of KD patients from 11 Italian sites were registered into a centralized RedCap database. pCALs were defined as the persistence of CALs 8 weeks after the diagnosis. Clinical, demographic and laboratory features of patients with and without pCALs were analyzed and compared. Multiple logistic regression was used to identify independent risk factors for pCALs. A ROC analysis was conducted to assess the performance and reliability of the existing risk score model to predict the persistence of CALs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e517 children were enrolled (Caucasian 87.4%) of which 52 developed pCALs. pCALs were more prevalent in males (12.03% p=0.06), Asian ethnicity (26.9%, p: 0.026), younger patients (61.5%, p: 0.05), incomplete clinical presentation (p=0.03), and associated with pathological features at abdominal ultrasound (p=0.04). Children with pCALs had higher WBC and CRP but lower Hb.\u003c/p\u003e\n\u003cp\u003eMale gender (12.03% p=0.06), age younger than 6 months (61.5%, p: 0.05), Asian ethnicity (26.9%, p: 0.026), fever longer than 10 days, incomplete presentation(p=0.03), CRP \u0026gt;13 mg\u0026gt;dl were independent risk factors for pCALs. Children who developed pCALs, compared to those with acute CALs, were younger, mostly IVIG non-responders (34.6%, 18/52 versus 29.6%, 153/517; p\u0026lt;0.001) and late-treated. Additionally, Son's risk score demonstrated high predictive value in identifying children at greater risk for pCALs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eMale gender, younger age, incomplete clinical presentation, Asian ethnicity, and elevated CRP levels are independent risk factors for pCALs in our Italian cohort. Notably, the risk score developed by Son et al. demonstrated its potential utility in identifying children who may benefit from closer follow-up and early adjunctive therapy to limit coronary damage and related morbidity in a predominantly Caucasian population.\u003c/p\u003e","manuscriptTitle":"Risk factors associated with persistent coronary artery lesions in children with Kawasaki Disease in an Italian cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 11:06:37","doi":"10.21203/rs.3.rs-6243172/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-10T19:06:32+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-10T00:54:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"337447425573516287001630560792526215182","date":"2025-03-21T16:43:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-21T13:46:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317251526631234004040963810143059659215","date":"2025-03-21T13:22:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-19T13:47:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-19T06:58:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-19T02:42:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2025-03-17T09:22:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9aa17284-444b-44f8-8af6-dbbcbff458f4","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-02T16:07:41+00:00","versionOfRecord":{"articleIdentity":"rs-6243172","link":"https://doi.org/10.1007/s00431-025-06162-0","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2025-05-31 15:57:24","publishedOnDateReadable":"May 31st, 2025"},"versionCreatedAt":"2025-03-31 11:06:37","video":"","vorDoi":"10.1007/s00431-025-06162-0","vorDoiUrl":"https://doi.org/10.1007/s00431-025-06162-0","workflowStages":[]},"version":"v1","identity":"rs-6243172","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6243172","identity":"rs-6243172","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}