Search Results (20)

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

Background: Kawasaki disease (KD) is a systemic vasculitis of medium arteries, particularly involving coronary arteries. Coronary artery lesions (CALs) is the most serious complication in the acute stage, potentially leading to ischemic cardiomyopathy, myocardial infarction and sudden death. Environmental factors and genetic background contribute to individual susceptibility to develop CALs. The aim of this study was to define the risk factors for CALs in an Italian cohort. Methods: Data of KD patients from 10 Italian sites were registered into a REDCap database where demographic and clinical data, laboratory findings and coronary status were recorded. KD was diagnosed according to AHA definition. We used multiple logistic regression analysis to identify independent risk factors for CALs. Results: A total of 517 patients were enrolled, mainly Caucasians (83.6%). Presentation was complete in 321 patients (62.8%) and IVIG responsiveness in 360 (70%). CALs developed in 136/517 (26.31%). Gender, age, ethnicity, clinical presentation, fever duration, non-coronary cardiac events, Hb, albumin and CRP were significantly different between patients with and without CALs, while seasonality was not. Male gender, age < 18 months, Asian ethnicity, incomplete presentation and fever > 10 days were independent risk factors for CALs. Conclusions: Age younger than 18 months, incomplete KD and longer fever duration are risk factors for CALs. Asian ethnicity also represents a risk factor in our Italian Cohort. Full article

Introduction: An aberrant immune response involving yet unidentified environmental and genetic factors plays a crucial role in triggering Kawasaki disease (KD). Aims: The aim of this study was to assess general and laboratory data at the onset of KD in a single-center cohort of children managed between 2003 and 2023 and retrospectively evaluate any potential relationship with the development of KD-related cardiovascular abnormalities (CVAs). Patients and methods: We took into account a total of 65 consecutive children with KD (42 males, median age: 22 months, age range: 2–88 months) followed at the Department of Life Sciences and Public Health in our University; demographic data, clinical signs, and laboratory variables at disease onset, before IVIG infusion, including C-reactive protein, hemoglobin, white blood cell (WBC) count, neutrophil count, platelet count, aminotransferases, natremia, albumin, total bilirubin, and 25-hydroxyvitamin D were evaluated. Results: Twenty-one children (32.3% of the whole cohort) were found to have echocardiographic evidence of CVAs. Univariate analysis showed that diagnosis of KD at <1 year or >5 years was associated with CVAs (p = 0.001 and p = 0.01, respectively); patients with CVAs had a longer fever duration and mostly presented atypical or incomplete presentations. Interestingly, all patients with CVAs had lower levels of vitamin D (less than 30 mg/dL, p = 0.0001) and both higher WBC and higher neutrophil counts than those without CVAs (p = 0.0001 and p = 0.01, respectively). Moreover, blood levels of albumin were significantly lower in KD patients with CVAs compared to those without (11/21, 52% versus 13/44, 30%, p = 0.02). Multiple logistic regression with correction for sex showed that serum vitamin D < 30 ng/mL, WBC count > 20.000/mm³, and age > 60 months at KD onset were the only independent factors statistically associated with CVAs. Conclusions: Hypovitaminosis D, WBC count over 20.000/mm³, and age above 5 years at KD onset emerged as independent factors statistically associated with the occurrence of CVAs. Full article

Kawasaki disease (KD) is an acute vasculitis that mainly affects children under 5 years of age, leading to coronary artery alterations (CAAs) in 25% of untreated patients. Macrophage activation syndrome (MAS) is a secondary hemophagocytic lymphohistiocytosis (HLH) that can complicate the acute, subacute, and chronic phases of KD. We retrospectively reviewed three cases of children affected by KD complicated with MAS hospitalized in two pediatric units in Emilia Romagna, a northern region of Italy. Case 1: a previously healthy 23-month-old female with full clinical criteria of KD and a hemorrhagic rash due to MAS during the acute phase of the illness. This patient responded promptly to a high dose of intravenous immune globulin (IVIG) and three pulses of high doses of methylprednisolone (MPD) with improvement in clinical signs and laboratory tests without the development of CAA at any phase of illness. Case 2: a previously healthy 10-month-old female with incomplete KD with persistent fever and maculopapular rash. This patient did not respond to IVIG and developed MAS during the subacute phase, characterized by persistent fever, hypertransaminasemia, hyperferritinemia, and hypofibrinogenemia after two high doses of IVIG and boluses of MPD. The patient responded to the addition of IL-1 blocker and anakinra and did not present CAA alterations during any phase of the illness. Case 3: a previously healthy 26-month-old male with incomplete KD with fever, maculopapular rash, cheilitis, and hyperemic conjunctivitis. This patient developed gallbladder hydrops and CAA in the acute phase and did not respond to two high doses of IVIG and a high dose of MPD. In the subacute phase, this patient was complicated with MAS and responded to intravenous anakinra. During the subacute phase, the patient developed transient aneurysms that regressed during the chronic phase. These cases reiterate that prompt diagnosis and aggressive immunomodulatory treatment can limit the most severe complications of MAS complicating KD. High doses of IVIG and MPD may result in a favorable outcome or more aggressive adjunctive treatment may be needed. Anakinra, cyclosporine, monoclonal antibodies, and plasmapheresis can be used as adjunctive treatment in the case of unresponsive MAS in KD. Notably, MAS, present during the subacute phase in cases 2 and 3, promptly responded to anakinra, an IL-1 blocker, without the use of cyclosporine. Our experience confirms that the IL-1 blocker can be considered an optimal choice after non-response to IVIG and MPD in KD complicating with MAS, avoiding over-treatment with cytotoxic drugs. Full article

The diagnosis of Kawasaki disease (KD) is challenging and often delayed mainly in case of young infants and in presence of an incomplete disease and atypical features. Facial nerve palsy is one of the rare neurologic symptoms of KD, associated with a higher incidence of coronary arteries lesions and may be an indicator of a more severe disease. Here, we describe a case of lower motor neuron facial nerve palsy complicating KD and perform an extensive literature review to better characterize clinical features and treatment of patients with KD-associated facial nerve palsy. The patient was diagnosed at the sixth day of disease and presented extensive coronary artery lesions. A prompt treatment with intravenous immunoglobulins, aspirin and steroids obtained a good clinical and laboratory response, with resolution of facial nerve palsy and improvement of coronary lesions. The incidence of facial nerve palsy is 0.9–1.3%; it is often unilateral, transient, more frequent on the left and seemingly associated with coronary impairment. Our literature review showed coronary artery involvement in the majority of reported cases (27/35, 77%) of KD with facial nerve palsy. Unexplained facial nerve palsy in young children with a prolonged febrile illness should prompt consideration of echocardiography to exclude KD and start the appropriate treatment. Full article

Recognition of macrophage activation syndrome (MAS) in patients with refractory Kawasaki disease (KD) can be challenging. This study aimed to investigate the incidence of MAS in patients with refractory KD and to compare the characteristics of refractory KD and MAS. Medical records of 468 patients diagnosed with KD from January 2010 to December 2019 were retrospectively reviewed. Of the 468 KD patients, 63 were enrolled in the study as a refractory KD group (n = 59) and an MAS group (n = 4). The incidence of MAS was 0.8% (4/468) in patients with KD and 6.3% (4/63) in patients with refractory KD. Compared to the refractory KD group, the MAS group had higher frequencies of incomplete KD, hepatosplenomegaly, third-line treatment, and MAS screening, and showed lower levels of albumin. No significant differences were found in other clinical and laboratory findings. In addition to four patients with MAS, five patients with refractory KD who received third-line treatment showed severe systemic inflammation and organ dysfunction, but only one in five patients underwent MAS screening, including ferritin levels. In conclusion, given the relatively high incidence of MAS in children with refractory KD and the similar phenotype between refractory KD and MAS, we propose that MAS screening should be included in routine laboratory tests for refractory KD. Full article

Viral infections are a key issue in modern medicine. SARS-CoV-2 infection confirms that we are not sufficiently prepared for these unforeseen infections. The COVID-19 pandemic has cultivated a great sense of fear and distrust in patients. If viral infections, in this case, SARS-CoV-2, overlap with another infection, the symptoms are prolonged and worsened, and complications may occur. Starting from an objective clinical finding of a patient they had in follow-up and treatment, the authors present the problems of the diseases the patient suffered from. These are described as reviews so that readers can get an idea of the clinical methods of expression and the therapeutic possibilities. Therefore, this article describes Lyme disease and post-treatment Lyme disease syndrome, SARS-CoV-2 infection, and multisystem inflammatory syndrome in children (MISC-C), as the patient suffered from an incomplete form of Kawasaki disease. During the treatment for Lyme disease, the patient also contracted the influenza type A virus. Although any of these diseases could have the potential for serious evolution, our patient still went through these infections relatively well. This can be explained by the fact that the patient had a slow immune response to the aforementioned infections, which allowed him to survive these diseases relatively easily, unlike other individuals who have an exaggerated immune response or who suffer from serious immune involvement, e.g., hepatitis B with a fulminant response. The case was presented chronologically, but at the same time, all particular infection manifestations were accurately described. For these reasons, the article is presented in the form of a review, exemplified by the case itself. Of the 52 cases of MISC-C found in the Pediatrics Clinic II of Cluj-Napoca, we present the case of a male patient who presented with Lyme disease, post-treatment Lyme disease syndrome, Kawasaki disease, and MISC-C incomplete form. Full article

Kawasaki disease (KD) is a febrile coronary vasculitis that affects younger children and includes complications such as coronary artery aneurysm. KD diagnoses are diagnosed based on clinical presentations, a process that still poses a challenge for front-line physicians. In the current study, we developed a novel predictor using the hemoglobin-for-age z-score (HbZ) and plasma hepcidin to differentiate Kawasaki disease (KD) from febrile children (FC). There were 104 FC and 115 KD subjects (89 typical KD; 26 incomplete KD) for this study, and data were collected on the biological parameters of hemoglobin and plasma hepcidin levels. A receiver operating characteristic curve (auROC), multiple logistics regression, and support vector machine analysis were all adopted to develop our prediction condition. We obtained both predictors, HbZ and plasma hepcidin, for distinguishing KD and FC. The auROC of the multivariate logistic regression of both parameters for FC and KD was 0.959 (95% confidence interval = 0.937–0.981), and the sensitivity and specificity were 85.2% and 95.9%, respectively. Furthermore, the auROC for FC and incomplete KD was 0.981, and the sensitivity and specificity were 92.3% and 95.2%, respectively. We further developed a model of support vector machine (SVM) classification with 83.3% sensitivity and 88.0% specificity in the training set, and the blind cohort performed well (78.4% sensitivity and 100% specificity). All data showed that sensitivity and specificity were 81.7% and 91.3%, respectively, by SVM. Overall, our findings demonstrate a novel predictor using a combination of HbZ and plasma hepcidin with a better discriminatory ability for differentiating from WBC and CRP between children with KD and other FC. Using this predictor can assist front-line physicians to recognize and then provide early treatment for KD. Full article

Diagnosis of Kawasaki disease in infants under 3 months of age is challenging. This study aimed to confirm the diagnostic efficacy of BCGitis in patients with Kawasaki disease aged <3 months. Overall, 473 children were enrolled; they were grouped by age into group 1 (≤3 months, n = 19) and group 2 (>3 months, n = 454). Data, including clinical features and laboratory results, were analyzed and compared between the groups. In group 1, 89% of patients showed Bacille Calmette-Guérin site reactivation. In group 1, total duration of fever and fever duration before initial treatment were significantly shorter than in group 2 (p = 0.001). The incidences of conjunctival injection, changes in extremities (erythema and edema), and cervical lymphadenopathy were significantly lower (p = 0.006, p = 0.040, and p < 0.001, respectively), and desquamation was higher in group 1 (p = 0.004). The incidences of incomplete Kawasaki disease, coronary artery complications, and resistance to intravenous immunoglobulin did not differ between the groups. Kawasaki disease should be suspected in infants aged <3 months with unexplained fever and BCGitis, even if the principal clinical symptoms are not fully presented. BCGitis in infantile Kawasaki disease is a useful sign and can help in the diagnosis of Kawasaki disease. Full article

Kawasaki disease (KD) is an acute febrile illness, principally affecting children under 5 years, due to a systemic vasculitis of obscure etiology. In 2017, the American Heart Association published the diagnostic criteria for KD in their scientific statement. Following the emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been an upsurge in the reports of KD as well as a novel multisystem inflammatory syndrome in children (MIS-C). Clinical manifestations of MIS-C are similar to KD and toxic-shock syndrome, making the clinical diagnosis challenging. Studies have shown promising results to differentiate KD from MIS-C using epidemiological, clinical, hematological, and immunological characteristics. Serological evidence may be negative in these patients at presentation, as MIS-C is a late manifestation of SARS-CoV-2 exposure. However, diagnosis and management challenges currently exist due to a gap in knowledge of these conditions. Further research is warranted to identify diagnostic tools to differentiate KD and MIS-C and optimize the therapeutic strategy, reducing morbidity and mortality related to these phenotypically similar diseases. This review aims to highlight the best available evidence for managing children with KD and MIS-C in the background of the ongoing COVID-19 pandemic. Full article

Background: We examined the characteristics of Kawasaki disease (KD) patients who presented with limited and faint principal clinical features. Methods: We retrospectively reviewed the clinical records of 62 KD patients who presented with limited and faint clinical features at admission. A clinical feature that was recognizable by even junior doctors was defined as a definite feature (d-Feature), and a feature that was faint and recognizable by only experienced doctors was defined as a faint feature (f-Feature). Results: At admission, 82% of patients presented with fever and ≤1 d-Feature. Two days later, the d-Features increased in number and diagnoses of KD were established in 32 patients with fever and ≥4 d-Features. In 30 patients with ≤3 d-Features, experienced doctors recognized f-Features and diagnosed KD in 22 patients because of fever and ≥4 features. Among eight patients with ≤3 features, experienced doctors diagnosed six patients as incomplete KD considering their faint abnormal echocardiographic findings. For the remaining two patients, experienced doctors decided to commence KD treatments considering the patients’ clinical course. Conclusions: Sufficient clinical experience is essential during the diagnosis of KD in patients presenting with limited and f-Features. Educational programs for junior doctors on how to recognize f-Features and evaluate faint abnormal coronary artery findings are necessary. Full article

Background: Kawasaki disease (KD) is a syndrome of unknown cause that results in high fever and coronary vasculitis in children. The incidence of KD increased in Taiwan over the past few decades. Taiwanese government executed domains of early screening, effective methods for isolation or quarantine, and digital technologies for identifying potential cases for the early elimination strategy for coronavirus disease 2019 (COVID-19) and public health interventions for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 pandemic, leading to an effective reduction of the risk of airway infections in children. The purpose of this study is to analyze whether those public health interventions reduce the incidence of KD in 2020. Methods: Patients with KD who visited Chang Gung Memorial Hospital (CGMH) between 1 January, 2018, and 31 December, 2020 were included for trend analysis. This is a retrospective case series study conducted at the CGMH, which consists of a network of seven hospital branches equipped with more than 10,000 beds in different areas of Taiwan. Results: Compared with the 2018 and 2019 databases, the incidence of KD decreased significantly by 30% and 31%, respectively (p < 0.05) in 2020, when public health interventions were comprehensively implemented in Taiwan. This result shows that the incidence of KD decreased during the COVID-19 pandemic in Taiwan without change of the presentation KD (typical or incomplete) and percentage of IVIG resistance in 2020. Conclusion: As public health interventions were carried out for the SARS-CoV-2 pandemic, the incidence of KD was significantly reduced in Taiwan. Is KD a preventable disease? Full article

We aimed to evaluate the utility of the serum ferritin level as an early screening test of Kawasaki disease with macrophage activation syndrome (KD-MAS). We analyzed the serum ferritin levels on the first day of admission and the clinical progress of patients diagnosed with complete or incomplete KD. Of the 158 patients, 5 were diagnosed with KD-MAS. Conjunctival injection was significantly more frequent in KD group (p = 0.035), although there were no significant differences in other clinical features. On the first day of admission, the serum ferritin level in the KD-MAS group was >500 ng/mL, which was higher than that in the KD group (p = 0.001). In the KD-MAS group, total bilirubin, triglyceride, and lactate dehydrogenase (LDH) were significantly higher, and erythrocyte sedimentation rate (ESR), total protein, albumin, and fibrinogen were significantly lower than the KD group (p < 0.05). Four patients were diagnosed with MAS within 7 days after admission, and 4 (80%) patients with KD-MAS survived. In conclusion, carrying out an early ferritin screening test is important in patients with principal clinical features that may suspect KD. We propose to include ferritin level in the primary laboratory test to differentiate between KD with and without MAS early. Full article

Background and Objectives: Most cases of Kawasaki disease (KD) occur between the ages of 6 months and 5 years. Differences in immunological reaction and CAL (coronary artery lesion) by the age subgroups classified according to the prevalence of KD and those particularly in the earlier life of KD should be investigated. Materials and Methods: The laboratory data of 223 infantile and 681 non-infantile KD cases from 2003 to 2018 at Korea University Hospital were retrospectively analyzed. Patients with KD were divided into infants and non-infants and further subdivided into four subgroups by age. The age-adjusted Z-values were compared among the subgroups. Febrile controls were identified as patients with fever for >5 days and who showed some of the KD symptoms. Results: IVIG (intravenous immunoglobulin) resistance at the age of 6 months or less was significantly lower than that at the ages of 7–12 months and 13–60 months (respectively, p < 0.05). The significant risk factors for CAL in total KD patients were age, incomplete KD, post-IVIG fever, IVIG resistance, convalescent Z-eosinophil, and subacute platelet (p < 0.05). The significant risk factors for CAL at the age of 6 months or less were IVIG resistance, acute Z-neutrophil, subacute Z-neutrophil, subacute NLR (neutrophil to lymphocyte ratio), and subacute platelet (respectively, p < 0.05). Conclusion: Younger age and incomplete presentation in KD can be independent risk factors for CAL. The immune reactions of KD at a younger age are more tolerated compared with those at older ages during the acute phase. The immune response at the age of 6 months or less showed immune tolerance in terms of incomplete presentation and IVIG responsiveness. The risk factors such as IVIG resistance, subacute platelet, subacute NLR, and acute or subacute Z-neutrophil at the age of 6 months or less can be very useful parameters to predict CAL in young, incomplete KD. Full article

The risk of ethnic Kawasaki disease (KD) has been proposed to be associated with blood mercury levels in American children. We investigated the blood levels of mercury in children with KD and their association with disease outcome. The mercury levels demonstrated a significantly negative correlation with sodium levels (p = 0.007). However, data failed to reach a significant difference after excluding the child with blood mercury exceeding the toxic value. The findings indicate that KD patients with lower sodium concentrations had a remarkably higher proportion of intravenous immunoglobulin (IVIG) resistance (p = 0.022). Our patients who had lower mercury levels (<0.5 μg/L) had more changes in bacille Calmette-Guerin. Mercury levels in 14/14 patients with coronary artery lesions and 4/4 patients with IVIG resistance were all measured to have values greater than 1 μg/L (while average values showed 0.92 μg/L in Asian American children). Mercury levels had no correlations with IVIG resistance or coronary artery lesion (CAL) formation (p > 0.05). CAL development was more common in the incomplete group than in the complete KD group (p = 0.019). In this first report about mercury levels in KD patients, we observed that the juvenile Taiwanese had higher mercury concentration in blood compared to other populations. Full article