Pathogenic and therapeutic roles of cytokines in Kawasaki diseases.

Infancy and early childhood are the most common ages for acute pyretic Kawasaki disease (KD). Although the etiology remains a mystery, the current concept is that KD is caused by a contagious pathogen that infects the genetically vulnerable and induces an inflammatory mechanism aimed at cardiovascular organs. Resolving the inflammatory process and decreasing the incidence of coronary anomalies, namely coronary aneurysms, are two benefits of high-dose intravenous immunoglobulin (IVIG) administration. The etiology of KD has been linked to a large number of cytokines and treatment strategies to regulate these cytokines have been suggested. This review will focus on the critical role of cytokines in disease development and possible treatment approaches and potential clinical applications.

A CASE OF KAWASAKI DISEASE IN AN EIGHT-YEAR-OLD BOY.

Kawasaki disease is an acute systemic disease characterized by the predominant lesions of middle and small arteries, alongside destructive and proliferative vasculitis development. The aetiology is currently being discussed. Infectious factors are mostly preferred, in addition, autoimmune mechanisms and genetic heredity are considered. The diagnosis of Kawasaki disease is established by clinical signs; laboratory changes are usually taken into account as are ancillary criteria. The article discusses the clinical case of Kawasaki disease in an 8-year-old boy. Given the variety and inconsistency of the clinical symptoms (the child had four of the five mandatory criteria together with prolonged fever), there was a late diagnosis, namely on day 10 of the disease. Due to the high risk of cardiovascular complications in the differential diagnosis of children with fever lasting more than 3 days should be considered Kawasaki disease, followed by mandatory heart echocardiography during the first 10 days of the disease, especially if the fever is accompanied by the increase of acute phase reactants. When treating children with chronic fever without a specific source, the doctor should be wary of Kawasaki disease, as it can clinically simulate acute respiratory viral disease, the onset of diffuse connective tissue disease, and infectious endocarditis, and can have common features and require differential diagnostics with coronavirus associated multisystem inflammatory syndrome.

COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Similarities and differences between MIS-C and KD: a systematic review and meta-analysis.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome with some clinical manifestations similar to Kawasaki disease (KD), which is difficult to distinguish. OBJECTIVE: The study aimed to characterize the demographic characteristics, clinical characteristics, laboratory features, cardiac complications, and treatment of MIS-C compared with KD. STUDY DESIGN: Studies were selected by searching the PubMed, EMBASE and so on before February 28, 2022. Statistical analyses were performed using Review Manager 5.4 software and STATA 14.0. RESULTS: Fourteen studies with 2928 participants were included. MIS-C patients tended to be older and there was no significant difference in the sex ratio. In terms of clinical characteristics, MIS-C patients were more frequently represented with respiratory, gastrointestinal symptoms and shock. At the same time, they had a lower incidence of conjunctivitis than KD patients. MIS-C patients had lower lymphocyte counts, platelet (PLT) counts, erythrocyte sedimentation rates (ESRs), alanine transaminase (ALT), and albumin levels and had higher levels of aspartate transaminase (AST), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin, C-reactive protein (CRP), D-dimer, fibrinogen, ferritin, and creatinine. MIS-C patients had a higher incidence of left ventricle (LV) dysfunction, valvular regurgitation, pericardial effusion, myocarditis, and pericarditis. The incidence of coronary artery lesion (CAL) was lower in MIS-C patients [OR (95% CI): 0.52 (0.29, 0.93), p =0.03], while it was similar in the acute period. MIS-C patients had higher utilization of glucocorticoids (GCs) and lower utilization of intravenous immune globulin (IVIG). CONCLUSIONS: There were specific differences between MIS-C and KD, which might assist clinicians with the accurate recognition of MIS-C and further mechanistic research.

COVID-19 and multisystem inflammatory syndrome in children and adolescents.

As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions. However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown. We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19. We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill. These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development. TRANSLATIONS: For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section.

Case of adult-onset Kawasaki disease and multisystem inflammatory syndrome following SARS-CoV-2 vaccination.

Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS) are rare conditions that occur predominately in children. Recent reports document KD and MIS in adult patients following infection with SARS-CoV-2. Rarely, MIS is observed following vaccination against SARS-CoV-2, mostly in patients with prior SARS-CoV-2 infection. We report a case of KD in a man after a second SARS-CoV-2 vaccine dose, in absence of concurrent or prior SARS-CoV-2 infection. This patient also met criteria for probable MIS associated with vaccination. He tested negative for SARS-CoV-2 RNA via reverse transcriptase PCR, negative for SARS-CoV-2 nucleocapsid antibodies and demonstrated high levels SARS-CoV-2 spike protein antibodies, commonly used to assess vaccine response. Symptom improvement followed treatment with intravenous immunoglobulin, including desquamation of the hands and feet. As widespread vaccination against SARS-CoV-2 continues, increased vigilance and prompt intervention is necessary to limit the effects of postvaccination inflammatory syndromes.

Cyclosporine for the treatment of multisystem inflammatory syndrome in children with coronary artery aneurysms.

Multisystem inflammatory syndrome in children (MIS-C) is a newly described syndrome related to the COVID-19, resembling other known aetiologies, including Kawasaki disease. Cardiovascular involvement is common; left ventricle dysfunction and coronary artery aneurysm (CAA) are also observed. Many treatment guidelines recommend using intravenous immunoglobulin (IVIG) alone or with glucocorticoids as the first-line therapy. Biological agents, such as anakinra, are recommended for refractory cases, but the evidence is still accumulating. Moreover, the use of other treatment agents can be beneficial, especially when anakinra is unavailable. Here, we report the case of a 9-year-old girl who presented with MIS-C with CAAs. She received cyclosporine because two rounds of IVIG treatment were ineffective and the use of anakinra is not approved in Japan. Her cytokine profile showed that cyclosporine prevented exacerbation. The case highlights that cyclosporine therapy can be an option for the treatment of refractory MIS-C with CAA.

Clinical characteristics and treatments of multi-system inflammatory syndrome in children: a systematic review.

OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) can occur in association with coronavirus disease 2019 (COVID-19). It is not easy to differentiate MIS-C from severe COVID-19 or Kawasaki disease based on symptoms. The aim of this study was to describe the clinical and laboratory characteristics of MIS-C. PATIENTS AND METHODS: We searched PubMed/Medline for case series and reports of MIS-C published until June 20, 2020. From a total of nine articles involving 45 cases, various clinical and laboratory data were extracted. Each target case was evaluated by using different diagnostic criteria. RESULTS: The average age at onset of MIS-C was 8.6 years. In 80% of cases, the age of patients ranged from 5 to 15 years. Fever (100%) and shock (82%) were the most common presenting symptoms. Sixty percent of cases met the diagnostic criteria for typical or atypical Kawasaki disease. Biomarkers indicative of inflammation, coagulopathy, or cardiac injury were characteristically elevated as follows: ferritin (mean: 1,061 ng/mL), CRP (217 mg/L), ESR (69 mm/hr), IL-6 (214.8 pg/mL), TNFα (63.4 pg/mL), D-dimer (3,220 ng/mL), PT (15.5 s), troponin I (1,006 ng/L), and BNP (12,150 pg/mL). Intravenous immunoglobulin was administered in all target cases, and inotropic agents were commonly used as well. No case of death was observed. CONCLUSIONS: This study demonstrated that MIS-C is a serious condition that presents with fever, rash, as well as cardiovascular and gastrointestinal symptoms. Although it is challenging to differentiate MIS-C from Kawasaki disease or severe COVID-19, initiation of appropriate treatments through early diagnosis is warranted.

Childhood multisystem inflammatory syndrome associated with COVID-19 (MIS-C): Distinct from Kawasaki disease or part of the same spectrum?

One of the most challenging and intriguing phenomena observed during the COVID-19 pandemic has been the multisystem inflammatory syndrome in children (MIS-C). Patients with this condition present with some clinical features similar to those of Kawasaki disease (KD) and display signs and symptoms that are uncommon or rarely occur in this disorder, such as gastrointestinal complaints and myocarditis, often leading to myocardial failure and shock. In addition, patients' age is older than that of children with classic KD. Management is based on administering intravenous immunoglobulin, glucocorticoids, and anakinra in the most severe instances. It is still debated whether MIS-C and KD are different illnesses or represent a disease continuum.

Acute phase of Kawasaki disease: a review of national guideline recommendations.

Key aspects of the medical management of Kawasaki disease (KD) are not yet supported by a high evidence level, thus making room for individual recommendations. We performed a structured comparison of existing international KD guidelines to analyze potential differences in the implementation of evidence-based KD recommendations regarding diagnosis and therapy. To identify country-specific guidelines, we took a multilateral approach including a comprehensive PubMed literature, online research, and directly contacting national pediatric associations. We then ran a structured guidelines' analysis and evaluated the diagnostic and therapeutic differences in the context of evidence-based medicine. In this structured guideline analysis, we identified nine national and one European guidelines. According to them all, the diagnosis of KD still relies on its clinical presentation with no reliable biomarker recommended. First-line treatment consistently involves only intravenous immunoglobulin (IVIG) therapy. Recommendations in terms of acetylsalicylic acid, corticosteroids, and additional therapeutic options vary considerably. CONCLUSION: According to all guidelines, KD is diagnosed clinically with some variance in defining incomplete KD and being a non-responder to treatment. First-line treatment consistently includes IVIG. Recommendations for additional therapeutic strategies are more heterogeneous. WHAT IS KNOWN: • The diagnosis of KD relies on the clinical presentation, entailing challenges in timely diagnosis. • Other treatment options then IVIG are not supported by a high evidence level, making room for individual recommendations. WHAT IS NEW: • Definition of incomplete KD and being non-responsive to an initial treatment vary to some extent between the national guidelines. • Only IVIG is consistently proposed throughout all guidelines, further therapeutic recommendations vary between the national recommendations.

Kawasaki Disease with Peripheral and Facial Gangrene: A Case report and review of literature.

With the onset of the SARS-CoV-2 pandemic, Kawasaki Disease (KD) has come to the fore with its many atypical manifestations. Atypical clinical neurological, ophthalmological, musculoskeletal, gastrointestinal and pulmonary manifestations in a febrile child with raised markers should prompt the clinician to think of Kawasaki disease. Peripheral gangrene is a rare atypical manifestation of KD reported in infancy. We present a three-and-a-half-year-old boy with extensive gangrene all four limbs and face along with purpura fulminans. He was successfully treated with two doses of intravenous immunoglobulin (IVIG) and infliximab, with no residual gangrene. This case highlights that very severe forms of Kawasaki disease require IVIG, pulse steroids as well as infliximab for adequate control and complete resolution of the disease.

No Increase in Kawasaki Disease-Like Illnesses During the COVID-19 Pandemic Compared With 4 Previous Years: A Medical Records Review Analysis.

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection produces a wide variety of inflammatory responses in children, including multisystem inflammatory syndrome in children, which has similar clinical manifestations as Kawasaki disease (KD). METHODS: We performed a chart review of all patients with KD-like illnesses from January 1, 2016, to May 31, 2020, at a tertiary care children's hospital within a larger health system. Relevant symptoms, comorbid illnesses, laboratory results, imaging studies, treatment, and outcomes were reviewed. Descriptive analyses to compare features over time were performed. RESULTS: We identified 81 cases of KD-like illnesses from January 1, 2016, to May 31, 2020. Few clinical features, such as gallbladder involvement, were more prevalent in 2020 than in previous years. A few patients in 2020 required more intensive treatment with interleukin 1 receptor antagonist therapy. There were no other clear differences in incidence, laboratory parameters, number of doses of intravenous immunoglobulin, or outcomes over the years of the study. CONCLUSIONS: There was no difference in incidence, laboratory parameters, or number of doses of intravenous immunoglobulin required for treatment of KD-like illnesses during the COVID-19 pandemic when compared with previous years at our institution. Kawasaki disease-like illnesses, including multisystem inflammatory syndrome in children, may not have changed substantially during the COVID-19 pandemic.

Who Would Have Predicted Multisystem Inflammatory Syndrome in Children?

PURPOSE OF REVIEW: Multisystem inflammatory disease in children (MIS-C) is a novel post-infectious phenomenon following coronavirus disease-19 (COVID-19). Herein, we present an in-depth review of the latest MIS-C literature related to clinical findings, pathophysiology, imaging and laboratory studies, treatment algorithms, and disease outcomes. RECENT FINDINGS: With its non-specific presentation of fever, gastrointestinal symptoms, cardiovascular injury and shock, systemic inflammation, and Kawasaki disease (KD)-like features, MIS-C can be a diagnostic challenge, overlapping with KD and active COVID-19 infection. However, common laboratory features, imaging findings, and historical clues can lead to accurate diagnosis and allow for appropriate treatment with a variety of immunomodulatory therapies, including intravenous immunoglobulin (IVIG). Aggressive treatment of MIS-C leads to good outcomes. Longitudinal studies continue to illuminate long-term cardiac sequelae and recovery. MIS-C presents with fever, KD features, gastrointestinal symptoms, cardiac inflammation, and shock. Early recognition and prompt institution of IVIG and glucocorticoids provide for rapid improvement.

COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group.

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.

Infliximab treatment for refractory COVID-19-associated multisystem inflammatory syndrome in a Japanese child.

Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required.

COVID-19 associated Kawasaki-like multisystem inflammatory syndrome in an adult.

Recently, few reports have described a serious condition linked to SARS-CoV-2 that mimics Kawasaki disease called multisystem inflammatory syndrome, especially in children (MIS-C) and young adults. In this work, we report on a severe form of MIS in a young female adult previously infected by SARS-CoV-2. She was treated by plasmapheresis with albumin and steroids, however outcome was fatal. We discuss the pathogenesis of this rare and life threatening entity and suggest some therapeutic regimen. This syndrome should not be misdiagnosed with an infectious or a drug induced cutaneous rash in the current context of COVID-19 pandemic.

A 2-Month-Old with Kawasaki Disease with Coronary Artery Dilation in the Pre-COVID-19 Era.

BACKGROUND Kawasaki disease (KD) is an acute inflammatory vasculitis, which occurs mostly in childhood, predominantly between the ages of 6 months and 5 years. The incidence of coronary artery abnormalities associated with KD has decreased from 25% to 4% as a result of timely diagnosis and treatment with intravenous immunoglobulin (IVIG). Infants ≤6 months of age are the most likely to develop prolonged fever without the other clinical criteria for KD, and diagnosis can sometimes be challenging or delayed. They are therefore at particularly high risk of developing coronary artery abnormalities. CASE REPORT A 2-month-old male infant with no significant medical history initially presented with a history of nasal congestion, right conjunctivitis, red lips, and 1 loose stool in the pre-COVID-19 era. He was diagnosed with otitis media and was started on oral amoxicillin. By day 7 of fever, he had developed symptoms and signs and laboratory findings consistent with Kawasaki disease, which is rare in this age group. His echocardiogram showed dilated proximal left anterior descending and right coronary arteries. He was successfully treated, and his most recent echocardiogram, performed 17 months after his treatment, showed remarkable improvement in the coronary arteries. CONCLUSIONS Kawasaki disease in children less than 6 months of age is still rare, and the presentation can sometimes make the diagnosis somewhat challenging. Increased clinical suspicion is required for recognition in the youngest patients, as they are more likely to present with few features of KD. Early diagnosis and treatment are needed to prevent or minimize the risk of significant coronary artery abnormalities.

SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment.

This study was conducted to assess the clinical spectrum, management, and outcome of SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C). We reviewed medical records of children with MIS-C diagnosis seen at the Children's Hospital of Michigan in Detroit between April and June 2020. Thirty-three children were identified including 22 who required critical care (group 1) and 11 with less intense inflammation (group 2). Children in group 1 were older (median 7.0 years) than those in group 2 (median 2.0 years). Abdominal pain was present in 68% of patients in group 1. Hypotension or shock was present in 17/22 patients in group 1. Thirteen (39.4%) had Kawasaki disease (KD)-like manifestations. Five developed coronary artery dilatation; All resolved on follow-up. Intravenous immunoglobulin (IVIG) was given to all patients in group 1 and 7/11 in group 2. Second-line therapy was needed in 13/22 (group 1) for persisting inflammation or myocardial dysfunction; 12 received infliximab. All patients recovered.Conclusion: MIS-C clinical manifestations may overlap with KD; however, MIS-C is likely a distinct inflammatory process characterized by reversible myocardial dysfunction and rarely coronary artery dilatation. Supportive care, IVIG, and second-line therapy with infliximab were associated with a favorable outcome. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) manifestations include fever, gastrointestinal symptoms, shock, and occasional features of Kawasaki disease (KD). • Treatment includes immunomodulatory agents, most commonly IVIG and corticosteroids. What is New: • Spectrum of MIS-C varies from mild to severe inflammation and coronary artery dilatation occurred in 5/22 (23%) critically ill patients. • IVIG and infliximab therapy were associated with a favorable outcome including resolution of coronary dilatation; only 2/33 received corticosteroids.

Characterizing the differences between multisystem inflammatory syndrome in children and Kawasaki disease.

To characterize the new SARS-Co-V-2 related multisystem inflammatory syndrome in children (MIS-C) among Israeli children and to compare it with Kawasaki disease (KD). We compared, in two medical centers, the clinical and laboratory characteristics of MIS-C, KD and an intermediate group, which met the case definitions of both conditions. MIS-C patients were older, were more likely to be hypotensive, to have significant gastrointestinal symptoms, lymphopenia and thrombocytopenia and to have non-coronary abnormal findings in their echocardiogram. Lymphopenia was an independent predictor of MIS-C. Most of our MIS-C patients responded promptly to corticosteroid therapy. KD incidence in both centers was similar in 2019 and 2020. Although there is clinical overlap between KD and MIS-C, these are separate entities. Lymphopenia clearly differentiates between these entities. MIS-C patients may benefit from corticosteroids as first-line therapy.