Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort

Abstract Background Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 present similarly with mucocutaneous symptoms and fever. Both syndromes can progress to shock. Successful treatments for MIS-C are largely based on proven KD management. As more patients with MIS-C are treated, protocols are adjusted. Infectious Diseases (ID) specialists are often early consultants in these cases. Understanding differences in how body systems are affected in MIS-C versus KD is essential for management. Figure 1. Cardiac changes among patients with Kawasaki Disease shock syndrome (KDSS) and Muti-system Inflammatory Syndrome (MIS-C) Methods This is a single hospital comparison of 25 cases of MIS-C with mucocutaneous presentation and symptoms of shock and 25 consecutive cases of KD Shock Syndrome (KDSS). Cases were compared for demographics, symptoms, cardiac abnormalities, medical treatments, and cardiac recovery. Results Patients with MIS-C develop symptoms of shock including sustained hypotension and tachycardia at 3 times the rate of patients with KD (45% vs 13%; p< 0.001). On echocardiogram, left ventricular myocardial dysfunction, assessed by ejection fraction, is more commonly noted in cases of MIS-C than KDSS (fig 1). About half of patients with MIS-C show left ventricular myocardial dysfunction initially with normalization by 6 months post-presentation in the majority (96%). Conclusion Cardiac changes and shock events related to KD and MIS-C are thought to be caused by differing inflammatory mediators. By comparing these two syndromes, we can determine ways to manage each optimally. MIS-C often results in left ventricular myocardial dysfunction, which is rarer in KD cases. Fluid resuscitation with multiple fluid boluses followed by inotropes to treat hypotension in cases of in MIS-C puts increased strain on the already weakened myocardium. Early intravenous immunoglobulin (IVIG) administration, even in the presence of mild hypotension, can simultaneously provide the patient with additional fluid and decrease the underlying inflammatory process. This prompt treatment might reduce the need for pressor support while protecting the myocardium from further damage. As early consultants in MIS-C, ID providers should be educated regarding the unique cardiac challenges of MIS-C and avoid delay in IVIG treatment and cardiologist and intensivist consultation. Disclosures All Authors: No reported disclosures

Download Full-text

KAWASAKI DISEASE IN INFANTS LESS THAN ONE YEAR OF AGE: AN ITALIAN COHORT FROM A SINGLE CENTER

10.21203/rs.2.10643/v3 ◽

2019 ◽

Author(s):

Greta Mastrangelo ◽

Rolando Cimaz ◽

Giovan Battista Calabri ◽

Gabriele Simonini ◽

Donatella Lasagni ◽

...

Keyword(s):

Kawasaki Disease ◽

Severe Disease ◽

Disease Onset ◽

Retrospective Chart Review ◽

Ivig Treatment ◽

New Finding ◽

Mucosal Changes ◽

One Year ◽

Few Data ◽

Italian Cohort

Abstract Background and aims Few data are currently available for Kawasaki disease (KD) below 12 months especially in Caucasians. This study aims to analyze clinical and laboratory features of KD among an Italian cohort of infants. Methods A retrospective chart review of KD children aged less than one year at time of disease onset between January 2008-December 2017 was performed. Clinical data, laboratory parameters, instrumental findings, treatment and outcome were collected in a customized database. Results Among 113 KD patients, 32 (28.3%) were younger than 1 year. Nineteen patients aged below 6 months, and three below 3 months. The median age was 5.7 ±2.7 months. The mean time to diagnosis was 7±3 days and was longer in the incomplete forms (8 ± 4 vs 6 ± 1 days). Conjunctival injection was present in 26 patients (81.2%); rash in 25 (78.1%); extremity changes in 18 (56.2%); mucosal changes in 13 (40.6%,) and lymphadenopathy only in 7 (21.8%). Mucosal changes were the least common features in incomplete forms (18.2%). Twenty-two patients (68.7%) had incomplete KD. Nineteen (59.4%) had cardiac involvement, of whom 13 (59.0%) had incomplete form. ESR, PCR and platelet values were higher in complete KD; especially, ESR resulted significantly higher in complete forms (80 ± 25.7 mm/h vs 50 ± 28.6 mm/h; p = 0.01). Conversely, AST level was statistically significant higher in patients with incomplete forms (95.4 ± 132.7 UI/L vs 29.8 ± 13.2 UI/L; p = 0.03). All patients received IVIG. Response was reported in 26/32 patients; 6 cases needed a second dose of IVIG and one required a dose of anakinra. Conclusion In our cohort, incomplete disease was commonly found, resulting in delayed diagnoses and poor cardiac prognosis. Infants with incomplete KD seem to have a more severe disease and a greater predilection for coronary involvement than those with complete KD. AST was significantly higher in incomplete forms, thus AST levels might be a new finding in incomplete forms’ diagnosis. Eventually, we highlight a higher resistance to IVIG treatment. To our knowledge this is the first study involving an Italian cohort of patients with KD below 12 months.

Download Full-text

KAWASAKI DISEASE IN INFANTS LESS THAN ONE YEAR OF AGE: AN ITALIAN COHORT FROM A SINGLE CENTER

10.21203/rs.2.10643/v1 ◽

2019 ◽

Author(s):

Greta Mastrangelo ◽

Rolando Cimaz ◽

Giovan Battista Calabri ◽

Gabriele Simonini ◽

Donatella Lasagni ◽

...

Keyword(s):

Kawasaki Disease ◽

Severe Disease ◽

Disease Onset ◽

Retrospective Chart Review ◽

Ivig Treatment ◽

New Finding ◽

Mucosal Changes ◽

One Year ◽

Few Data ◽

Italian Cohort

Abstract Background and aims Few data are currently available for Kawasaki disease (KD) below 12 months especially in Caucasians. This study aims to analyze clinical and laboratory features of KD among an Italian cohort of infants. Methods A retrospective chart review of KD children aged less than one year at time of disease onset between January 2008-December 2017 was performed. Clinical data, laboratory parameters, instrumental findings, treatment and outcome were collected in a customized database. Results Among 113 KD patients, 32 (28.3%) were younger than 1 year. Nineteen patients aged below 6 months, and three below 3 months. The median age was 5.7 ±2.7 months. The mean time to diagnosis was 7±3 days and was longer in the incomplete forms (8 ± 4 vs 6 ± 1 days). Conjunctival injection was present in 26 patients (81.2%); rash in 25 (78.1%); extremity changes in 18 (56.2%); mucosal changes in 13 (40.6%,) and lymphadenopathy only in 7 (21.8%). Mucosal changes were the least common features in incomplete forms (18.2%). Twenty-two patients (68.7%) had incomplete KD. Nineteen (59.4%) had cardiac involvement, of whom 13 (59.0%) had incomplete form. ESR, PCR and platelet values were higher in complete KD; especially, ESR resulted significantly higher in complete forms (80 ± 25.7 mm/h vs 50 ± 28.6 mm/h; p = 0.01). Conversely, AST level was statistically significant higher in patients with incomplete forms (95.4 ± 132.7 UI/L vs 29.8 ± 13.2 UI/L; p = 0.03). All patients received IVIG. Response was reported in 26/32 patients; 6 cases needed a second dose of IVIG and one required a dose of anakinra. Conclusion In our cohort, incomplete disease was commonly found, resulting in delayed diagnoses and poor cardiac prognosis. Infants with incomplete KD seem to have a more severe disease and a greater predilection for coronary involvement than those with complete KD. AST was significantly higher in incomplete forms, thus AST levels might be a new finding in incomplete forms’ diagnosis. Eventually, we highlight a higher resistance to IVIG treatment. To our knowledge this is the first study involving an Italian cohort of patients with KD below 12 months.

Download Full-text

Kawasaki Disease In Infants Less Than One Year Of Age: An Italian Cohort From A Single Center

10.21203/rs.2.10643/v4 ◽

2019 ◽

Author(s):

Greta Mastrangelo ◽

Rolando Cimaz ◽

Giovan Battista Calabri ◽

Gabriele Simonini ◽

Donatella Lasagni ◽

...

Keyword(s):

Kawasaki Disease ◽

Severe Disease ◽

Disease Onset ◽

Retrospective Chart Review ◽

Ivig Treatment ◽

New Finding ◽

Mucosal Changes ◽

One Year ◽

Few Data ◽

Italian Cohort

Abstract Background and aims Few data are currently available for Kawasaki disease (KD) below 12 months especially in Caucasians. This study aims to analyze clinical and laboratory features of KD among an Italian cohort of infants. Methods A retrospective chart review of KD children aged less than one year at time of disease onset between January 2008-December 2017 was performed. Clinical data, laboratory parameters, instrumental findings, treatment and outcome were collected in a customized database. Results Among 113 KD patients, 32 (28.3%) were younger than 1 year. Nineteen patients aged below 6 months, and three below 3 months. The median age was 5.7 ±2.7 months. The mean time to diagnosis was 7±3 days and was longer in the incomplete forms (8 ± 4 vs 6 ± 1 days). Conjunctival injection was present in 26 patients (81.2%); rash in 25 (78.1%); extremity changes in 18 (56.2%); mucosal changes in 13 (40.6%,) and lymphadenopathy only in 7 (21.8%). Mucosal changes were the least common features in incomplete forms (18.2%). Twenty-two patients (68.7%) had incomplete KD. Nineteen (59.4%) had cardiac involvement, of whom 13 (59.0%) had incomplete form. ESR, PCR and platelet values were higher in complete KD; especially, ESR resulted significantly higher in complete forms (80 ± 25.7 mm/h vs 50 ± 28.6 mm/h; p = 0.01). Conversely, AST level was statistically significant higher in patients with incomplete forms (95.4 ± 132.7 UI/L vs 29.8 ± 13.2 UI/L; p = 0.03). All patients received IVIG. Response was reported in 26/32 patients; 6 cases needed a second dose of IVIG and one required a dose of anakinra. Conclusion In our cohort, incomplete disease was commonly found, resulting in delayed diagnoses and poor cardiac prognosis. Infants with incomplete KD seem to have a more severe disease and a greater predilection for coronary involvement than those with complete KD. AST was significantly higher in incomplete forms, thus AST levels might be a new finding in incomplete forms’ diagnosis. Eventually, we highlight a higher resistance to IVIG treatment. To our knowledge this is the first study involving an Italian cohort of patients with KD below 12 months.

Download Full-text

Case Report: Changes in Cytokine Kinetics During the Course of Disease in a Japanese Patient With Multisystem Inflammatory Syndrome in Children

Frontiers in Pediatrics ◽

10.3389/fped.2021.702318 ◽

2021 ◽

Vol 9 ◽

Author(s):

Satoshi Takasago ◽

Aiko Sakai ◽

Masaya Sugiyama ◽

Masashi Mizokami ◽

Hiromichi Hamada ◽

...

Keyword(s):

Kawasaki Disease ◽

Acute Myocarditis ◽

Severe Disease ◽

Gastrointestinal Symptoms ◽

Disease Status ◽

Classical Trajectory ◽

Course Of Disease ◽

Old Japanese ◽

Cervical Swelling ◽

Inflammatory Syndrome

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that is reportedly linked to coronavirus disease 2019. Affected patients present with gastrointestinal symptoms and cardiovascular dysfunction, in addition to Kawasaki disease-like features, suggesting the potential for overlapping disease mechanisms. Kawasaki disease has been reported among individuals of East Asian ethnicities, whereas there is minimal clinical literature regarding the occurrence of MIS-C among individuals of Asian ethnicities. A few reports thus far have described changes in cytokine kinetics during the course of disease in patients with MIS-C. We followed the temporal cytokine kinetics in a 9-year-old Japanese girl who exhibited a classical trajectory of MIS-C. The patient exhibited right cervical swelling and pain, abdominal pain, vomiting, and lip reddening, which developed 31 days after she was diagnosed with severe acute respiratory syndrome coronavirus-2 infection. The patient was diagnosed with Kawasaki disease on her fifth day of illness; because she fulfilled the criteria for MIS-C, she was also diagnosed with this disease on her fifth day of illness. Her fever rapidly resolved upon administration of intravenous immunoglobulin, aspirin, and prednisolone. On the patient's sixth day of illness, she developed acute myocarditis, which was treated with two diuretics and one vasodilator; the myocarditis ameliorated within a few days. Analyses of temporal kinetics for 71 serum cytokines revealed several patterns of cytokine changes that were consistent with the patient's clinical course of disease. Importantly, there was a clear distinction between cytokines that did and did not decrease rapidly following post-treatment fever resolution. These findings may be useful for the assessment of disease status and selection of therapy in patients with similar symptoms; they may also provide insights for basic and clinical research regarding MIS-C.

Download Full-text

Multisystem inflammatory syndrome in Indian adolescents associated with SARS-CoV-2 infection: a case report

The Egyptian Journal of Internal Medicine ◽

10.1186/s43162-021-00085-6 ◽

2021 ◽

Vol 33 (1) ◽

Author(s):

Rahul D. Bhiwgade ◽

M. C. Nischitha ◽

Bhushan Shahare ◽

Shobhna Bitey

Keyword(s):

Kawasaki Disease ◽

Severe Disease ◽

Late Presentation ◽

Case Presentation ◽

Empiric Antibiotics ◽

Non Invasive ◽

Indian Adolescents ◽

Atypical Kawasaki Disease ◽

Polymerase Chain ◽

Inflammatory Syndrome

Abstract Background Adolescents with coronavirus disease 2019 (COVID-19) associated multisystem inflammatory syndrome (MIS) can present with shock and myocardial injury and mimic Kawasaki disease. Case presentation We describe 4 previously well adolescents (age 13–14 years), presenting with clinical features of MIS in children (MIS-C). All patients had nearly similar clinical presentation. Hematological investigations revealed elevated inflammatory markers, anemia, thrombocytopenia, and decreased neutrophil:lymphocyte ratio. All patients were negative on real-time polymerase chain reaction against severe acute respiratory syndrome coronavirus 2, but had elevated immunoglobulin G titers. Two patients had atypical Kawasaki disease. Three patients had severe disease with hypotensive shock and required intensive care with fluids and inotropes. Two patients required non-invasive respiratory support for dyspnea and one patient had biventricular dysfunction. All received empiric antibiotics, low-molecular weight heparin, steroids, and intravenous immunoglobulin. One patient succumbed, while others recovered well. Conclusions MIS-C may be a late presentation in adolescent with COVID-19. Individualized treatment with empiric antibiotics, immunomodulation, and thromboprophylaxis can result in significantly better outcome.

Download Full-text

Defining Kawasaki Disease and Pediatric Multi-Inflammatory Syndrome During SARS-CoV-2 Epidemic in Italy: Results From A National, Multicenter Survey.

10.21203/rs.3.rs-106975/v1 ◽

2020 ◽

Author(s):

Marco Cattalini ◽

Sara Della Paolera ◽

Fiammetta Zunica ◽

Claudia Bracaglia ◽

Manuela Giangreco ◽

...

Keyword(s):

Kawasaki Disease ◽

Clinical Laboratory ◽

Troponin T ◽

Inflammatory Diseases ◽

Age At Onset ◽

Laboratory Data ◽

Clinical Manifestations ◽

Chi Square ◽

Multicenter Survey ◽

Inflammatory Syndrome

Abstract Background: There is mounting evidence on the existence of a Pediatric Multi-inflammatory Syndrome related to SARS-CoV-2 (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities.Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groupsResults: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis and 37,8% with hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated Ferritin and Troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p=0.04 and 71,9% vs 43,4%; p=0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p<0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p<0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data.Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Download Full-text

Abstract O.43: Partial and Complete Non-response to Intravenous Immunoglobulin in the Acute Treatment of Kawasaki Disease: A Matched Case-control Study

Circulation ◽

10.1161/circ.131.suppl_2.o43 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

Mallory L Downie ◽

Cedric Manlhiot ◽

Giuseppe A Latino ◽

Tanveer H Collins ◽

Nita Chahal ◽

...

Keyword(s):

Kawasaki Disease ◽

Temperature Profile ◽

Intravenous Immunoglobulin ◽

Ivig Treatment ◽

Second Line ◽

Second Line Therapy ◽

Ivig Infusion ◽

Total N ◽

Line Therapy ◽

Hourly Temperature

Introduction: Patients non-responsive to intravenous immunoglobulin (IVIG) in the acute phase of Kawasaki disease (KD) are usually considered a single patient group; however, response to second-line therapy varies significantly. We sought to characterize the pattern of temperature response to IVIG infusion, and to define whether the profile was associated with response to second-line therapy in non-responders. Methods: Patients non-responsive to IVIG (temperature >37.5°C >24 hours after the end of IVIG) were identified. Each IVIG non-responder was matched to a IVIG-responsive control patient of the same age and gender, and with the same duration of fever prior to IVIG. Hourly temperature profiles were obtained from immediately before the start of the IVIG infusion until complete defervescence. Results: n=202 patients non-responsive to IVIG were matched (total n=404). For all, temperature reduced by 0.17 (0.06)°C per g/hr IVIG (p=0.006). Important variation in the temperature profile was noted for patients who did not defervesce with IVIG. Thus, non-responders were further classified as partial non-responders (31%) (temperature decreased to <37.5°C within 24 hours of the end of IVG infusion, but fever recurred) and complete non-responders (69%) (temperature consistently >37.5°C throughout IVIG treatment). The temperature profile during IVIG infusion was similar between complete and partial responders [(EST: -0.26 (0.11)°C per g/hr IVIG (p=0.02) for complete responders vs. EST: -0.20 (0.09)°C (p=0.02) for IVIG responders (responders vs. partial non-responders, p=0.65)]. In complete non-responders, IVIG was not associated with significant decreases in temperature (EST: -0.11 (0.14)°C, p=0.43). Factors associated with complete (vs. partial) non-response included presence of infectious symptoms, differences in multiple laboratory values and IVIG brand. Defervescence in partial non-responders was achieved with a second IVIG dose for 88% of patients compared to only 47% of complete non-responder (p<0.001). Conclusions: Non-response to initial IVIG can be further characterized by the temperature profile, and complete non-responders may require more aggressive second-line therapy.

Download Full-text

Peculiarities of the course of multisystem inflammatory syndrome associated with COVID-19 in children: from literature review to own clinical observations

ACTUAL INFECTOLOGY ◽

10.22141/2312-413x.9.3.2021.236228 ◽

2021 ◽

Vol 9 (3) ◽

pp. 31-38

Author(s):

L.V. Pypa ◽

N.V. Piljujko ◽

I.V. Odarchuk ◽

A.V. Filyk ◽

N.O. Zymak-Zakutnja ◽

...

Keyword(s):

Kawasaki Disease ◽

Gastrointestinal Symptoms ◽

Current Data ◽

Current Evidence ◽

Toxic Shock ◽

Clinical Observations ◽

Global Pandemic ◽

The Usa ◽

Therapy Strategies ◽

Inflammatory Syndrome

Current data suggest that during the global pandemic of COVID-19 children are less affected than adults and most of them are asymptomatic or with mild symptoms. However, recently, cases of pediatric patients who have developed severe inflammatory syndrome temporally related to SARS-CoV-2 have been reported both in the USA and Europe. These reports, although sharing features with other pediatric syndromes such as Kawasaki disease (KD), Kawasaki disease shock syndrome, macrophage activated syndrome, and toxic shock syndrome, seem to outline a novel entity syndrome, characterized by cytokine storm with elevated inflammatory markers and typical clinical finding. Clinical characteristics are greater median age than KD, higher frequency of cardiac involvement and gastrointestinal symptoms, lower frequency of coronary anomalies. We report a summary of the current evidence about clinical features, pathogenesis, therapy strategies, and outcome of this novel syndrome.

Download Full-text

Abstract 95: Increased Circulating Endothelial Microparticles In The Acute Phase Of Kawasaki Disease

Circulation ◽

10.1161/circ.131.suppl_2.95 ◽

2015 ◽

Vol 131 (suppl_2) ◽

Author(s):

Hideyuki Nakaoka

Keyword(s):

Endothelial Dysfunction ◽

Kawasaki Disease ◽

Initial Treatment ◽

Systemic Vasculitis ◽

Disease Onset ◽

Ivig Treatment ◽

Healthy Children ◽

Ivig Infusion ◽

Endothelial Microparticles ◽

Coronary Syndrome

Backgroud: Kawasaki disease (KD) is a typically acute inflammatory syndrome that takes the form of systemic vasculitis. The acute inflammation and subsequent reparative process may lead to lasting changes in arterial structure even in the convalescence of KD including increased endothelial dysfunction. Endothelial microparticles (EMPs) are vesicles formed by the cell membrane after endothelial activation, and their composition can be used to characterize the status of the parent endothelial cell. EMPs were reported in cardiovascular diseases with endothelial dysfunction, such as acute coronary syndrome, pulmonary hypertension, diabetes, and vasculitis. Our aim of this study is to elucidate whether EMPs are involved in vasculitis during acute stage of Kawasaki disease. Method: We enrolled 9 patients (aged 3 months to 14 years, 6 male, 3 female), 7 common febrile children and 5 healthy children. KD patients in the convalescent phase were divided into two subgroups; coronary artery lesion (CAL, n=2) and no coronary lesion (NCAL, n=7). Blood samples were collected at the time of diagnosis before the initiation of IVIG treatment, then immediately after the first IVIG infusion and at 2-4 weeks after disease onset. Samples were measured using flow cytometry. Result: The percentage counts of EMPs were 2.90±1.26% in KD children before initial treatment, which were significantly higher (P<0.005) than those of disease controls (0.12±0.13%) and healthy controls (0.09±0.08%) before initial treatment, and reached normal levels within 4 weeks (0.05±0.05%). The highest percentage count of EMPs (5.47%) was observed in the patient with CAL before initial treatment. Further, prolonged high percentage count of EMPs (3.34%) was recognized in the patient with multiple gaint aneurysms at 2 weeks after onset. Conclusion: The relation between the increased levels of EMPs and the involvement of CAL may suggest that EMPs could serve as a sensitive marker of the severity of endothelial dysfunction and vasculitis in patients with KD. Although the function of EMPs has not been fully elucidated, there is evidence that it plays an important role for distinct inflammatory reactions in endothelium.

Download Full-text