Clinical profile and management of patients with pediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 - single-center experience

Introduction and aim. Pediatric Inflammatory Multisystem Syndrome (PIMS-TS) is a new condition that has emerged in children during the COVID-19 pandemic. Many clinical signs and symptoms resemble those found in Kawasaki disease (KD). Material and methods. The following data were considered: clinical presentation, comorbidities, laboratory findings, abnormalities in additional tests, exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the child and his family members, applied treatment and return to full health. Results. In the presented study nineteen children were analyzed. Fever was a universal finding in our group and it's mean duration was 7 days (range 5-9). Other common symptoms included abdominal pain and severe weakness (in 89.5%), rash and conjunctivitis (in 84.2%), vomiting (in 73.7%) and mucous membrane involvement (in 63.2%). In nearly half of cases, echocardiography revealed fluid in the pericardial sac and left ventricular systolic dysfunction (in 52.6% and 47.4% respectively). 21.1% of patients had coronary artery abnormalities. 26, 3% of the children required treatment with dopamine and/or milrinone. In 15.7% ICU admissions and assisted ventilation was necessary. No deaths were recorded. Conclusion. One should bear in mind that PIMS-TS can mimic KD, appendicitis and meningitis, which may pose a diagnostic challenge. © 2022 Publishing Office of the University of Rzeszow. All Rights Reserved.

Covid-19: Cases of inflammatory syndrome in children surge after urgent alert

Thirty fold increase In the province of Bergamo, Italy, researchers have reported a 30 fold increased incidence of Kawasaki like disease since the start of the covid-19 outbreak. Among the covid-19 group more children had cardiac symptoms (6 out of 10), Kawasaki disease shock syndrome (5 out of 10), macrophage activation syndrome (5 out of 10), and the need for adjunctive steroid treatment (8out of 10). In the pre-covid-19 group only two of 19 children had cardiac involvement and just three required adjunctive steroid treatment. A distinct syndrome Julia Kenny, a consultant in paediatric infectious diseases and immunology at Evelina London Children's Hospital, said that the Italian findings appear consistent with cases seen in the south east of England.

Tomisaku Kawasaki: identified and named Kawasaki disease

"Kawasaki was an icon in the paediatric world,” Jane Burns, professor and director of the Kawasaki Disease Research Centre at the University of California San Diego School of Medicine, told The BMJ. In 1949 he became a staff paediatrician at the Red Cross Hospital outside Tokyo and began to undertake research. ” "Ten years after starting at the Japanese Red Cross Central Hospital (now the Japanese Red Cross Medical Centre) in Tokyo, I examined on 5 January 1961 a boy aged four years and three months with a curious clinical symptom complex I had never seen,” he explained.3 "The patient had a high fever of about two weeks' duration, marked bilateral conjunctival hyperaemia without discharge, reddening dry fissured lips, diffuse redness of the mucous membrane of oral cavity, strawberry like tongue, left non-purulent cervical adenopathy, polymorphous erythema on the body, and marked redness of palms and soles, with indurative oedema of hands and feet following desquamation from the fingertips.”

Cyclosporin for treatment of refractory multisystemic inflammatory syndrome in a child.

Multisystemic inflammatory syndrome in children is an inflammatory condition with multiorgan dysfunction that manifest late in the course of Severe acute respiratory syndrome coronavirus 2 infection. We present a 12-year-old boy with a history of fever, vomiting, diarrhoea, and abdominal pain. He developed shock with ventricular dysfunction and pericardial effusion. He was diagnosed with multisystemic inflammatory syndrome in children and treatment with intravenous immunoglobulins, corticosteroids, and tocilizumab proved to be ineffective. Eventually, the patient responded to cyclosporin-A treatment. Multisystemic inflammatory syndrome in children has been treated with immunoglobulins and glucocorticoids and in refractory cases biologics and cyclosporin-A have been used. Intravenous and oral cyclosporin-A seems to be a safe and effective alternative treatment for refractory multisystemic inflammatory syndrome in children patients.

Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland.

Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular system is commonly involved. Acute heart failure (AHF) is the most severe complication of MIS-C, leading to cardiogenic shock. The aim of the study was to characterise the course of MIS-C with a focus on cardiovascular involvement, based on echocardiographic (echo) evaluation, in 498 children (median age 8.3 years, 63% boys) hospitalised in 50 cities in Poland. Among them, 456 (91.5%) had cardiovascular system involvement: 190 (48.2%) of patients had (most commonly atrioventricular) valvular insufficiency, 155 (41.0%) had contractility abnormalities and 132 (35.6%) had decreased left ventricular ejection fraction (LVEF < 55%). Most of these abnormalities improved within a few days. Analysis of the results obtained from two echo descriptions (a median of 5 days apart) revealed a >10% increase in LVEF even in children with primarily normal LVEF. Lower levels of lymphocytes, platelets and sodium and higher levels of inflammatory markers on admission were significantly more common among older children with contractility dysfunction, while younger children developed coronary artery abnormality (CAA) more often. The incidence of ventricular dysfunction might be underestimated. The majority of children with AHF improved significantly within a few days. CAAs were relatively rare. Children with impaired contractility as well as other cardiac abnormalities differed significantly from children without such conditions. Due to the exploratory nature of this study, these findings should be confirmed in further studies.

Kawasaki Disease in the Time of COVID-19 and MIS-C - The International Kawasaki Disease Registry.

BACKGROUND: Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics/clinical presentation, management, and outcomes of patients by evidence of prior SARS-CoV-2 infection. METHODS: The International KD Registry (IKDR) enrolled KD and MIS-C patients from sites from North, Central and South America, Europe, Asia and Middle East. Evidence of prior infection was defined as: Positive (+ve household contact or positive PCR/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible 89 (4%), Negative 404 (17%) and Unknown for 311 (13%) patients. Clinical outcomes varied significantly between the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to Intensive Care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, while patients in the Negative and Unknown groups had more severe coronary artery abnormalities. results CONCLUSION: : There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for prior acute SARS CoV2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS) and Serous Effusions in a Child With Severe Hypoalbuminemia: A Case Report.

In April 2020, Pediatric Inflammatory Multisystem Syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 or SARS­CoV­2 (PIMS-TS) was described for the first time in children. Since then, many countries have registered hundreds of cases with clinical similarities to Kawasaki disease. We report the case of a five-year-old boy diagnosed with PIMS-TS who presented myocarditis with serous effusions (pleurisy, ascites, pericarditis) due to severe hypoalbuminemia. This case sheds light on the importance of hypoalbuminemia in evaluating the severity of PIMS-TS and preventing its complications. The patient was successfully treated with intravenous immunoglobulins and oral prednisone.

Immunological basis that supports the treatment of Multi-System Inflammatory Syndrome in Children (MIS-C/PIMS)

Pediatric inflammatory multisystemic syndrome temporarily associated with COVID-19 (MIS-C/PIMS) is a new post-infectious condition, secondary to SARS-CoV2 infection. It has been characterized by an inflammatory response with multisystem involvement, involving several mechanisms of immune damage such as an exaggerated increase in cytokines and epithelial damage. Immunomodulatory treatment is aimed at controlling the manifestations of hyperinflammation, to stabilize and prevent long-term sequelae. © 2023 Instituto Nacional de Pediatria. All rights reserved.

Specific cytokine patterns in Epstein-Barr virusassociated hemophagocytic lymphohistiocytosis compared to Kawasaki disease in children.

The aim of the study was to test whether the cytokine profile could be used as a marker to differentiate between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and Kawasaki disease (KD). A total of 70 hospitalized children with HLH and KD admitted to hospital for the first time from March 2017 to December 2021 were enrolled in this study. Fifty-five healthy children were enrolled as normal controls. All patients and normal controls were tested for the six cytokines including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) by flow cytometry. IL-10 and IFN-γ levels were significantly higher in children with EBV-HLH than in the KD, IL-6 was lower in EBV-HLH patients than in the KD. IL-10/IL-6 ratio, IFN-γ/IL-6 ratio and IL10/IFN-γ ratio in children with EBV-HLH were significantly much higher than children in the KD group. When the diagnostic cutoff values of IL-10, IFN-γ, IL-10/IL-6 ratio and IFN-γ/IL-6 ratio were >13.2 pg/ml, >71.0 pg/ml, >0.37 and >1.34, respectively, the sensitivity and specificity of the diagnosis of EBV-HLH disease were 91.7% and 97.1%, 72.2% and 97.1%, 86.1% and 100.0%, and 75.0% and 97.1%, respectively. Notably high IL-10 and IFN-γ and moderately elevated IL-6 suggest the diagnosis of EBV-HLH, while high IL-6 levels with low IL-10 or IFN-γ concentration would suggest KD. Additionally, IL-10/IL-6 ratio or IFN-γ/IL-6 ratio could be used as an index to differentiate between EBV-HLH and KD.

Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment.

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.

Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease.

Background: Multisystem inflammatory syndrome in children (MIS-C), is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammatory response, and organ failure. MIS-C with a history of COVID-19 may share clinical features with other well-defined syndromes such as macrophage activation syndrome, Kawasaki disease, hemophagocytic syndrome and toxic shock syndrome. Case 1: An 11-year-old male with a history of hypothyroidism and precocious puberty with positive antibody test for COVID-19 was admitted for fever, poor general condition, severe respiratory distress, refractory shock, and multiple organ failure. His laboratory examination showed elevated inflammatory parameters, and bone marrow aspirate showed hemophagocytosis. Case 2: A 13-year-old male with a history of attention deficit hyperactivity disorder and cognitive delay presented clinical manifestations of Kawasaki disease, fever, conjunctival congestion, exanthema, and hyperemia in oral mucosa, tongue, and genitals, with refractory shock and multiple organ failure. Reverse transcriptase polymerase chain reaction (RT-PCR) and antibodies for COVID-19 were negative, inflammation parameters were elevated, and bone marrow aspirate showed hemophagocytosis. Patients required intensive care with invasive mechanical ventilation, vasopressor support, intravenous gamma globulin, systemic corticosteroids, low molecular weight heparin, antibiotics, and monoclonal antibodies and, patient 2 required renal replacement therapy. Conclusions: Multisystemic inflammatory syndrome in children can have atypical manifestations, and identifying them early is very important for the timely treatment and prognosis of patients.

A Ukrainian infant with giant coronary aneurysms: A case report and literature review.

Key Clinical Message: COVID may manifest multisystem inflammatory syndrome in children (MIS-C) which mimics Kawasaki disease (KD). Differentiating KD and MIS-C is difficult. Immunomodulatory treatment should be initiated promptly without accurate diagnosis. Abstract: A febrile Ukrainian infant developed giant aneurysms in coronary arteries. Differentiating between Kawasaki disease and multisystem inflammatory syndrome in children was difficult. In both illnesses, coronary aneurysm may develop unless treated promptly. Therefore, guidelines should synthesize these clinical entities so that treatment can be initiated before rigorous diagnosis.

Clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19

The multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is infre-quent but potentially lethal. There are few reports of this disease and its phenotypes in Latin America. Objective: To describe the characteristics of the clinical phenotypes of MIS-C in hospitalized patients in Lima, Peru. Patients and Method: A descriptive and retrospective study in patients under 14 years old with a diagnosis of MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (Lima, Peru), from April 2020 to August 2021. Clinical-demographic and microbiological variables were recorded. According to these, patients with MIS-C were classified into the shock phenotype, Kawasaki disease (KD) without shock, and the fever and inflammation phenotype, analyzing their clinical outcomes. Results: 58 patients were analyzed. 32 (55.2%) presented the shock phenotype, 15 (25.8%) Kawasaki disease (KD) phenotype without shock, and 11 (19%) fever and inflammation phenotype. In the shock phenotype, 17 had KD. The mean age was 7 +/- 3.5 years and 67.2% were males. Gastrointes-tinal and mucocutaneous manifestations predominated in all phenotypes. The mortality was 3.5%. The frequency of coronary aneurysms was 10.2%. Most patients received immunomodulatory and antiplatelet treatment. Patients with shock phenotype showed greater involvement in inflammatory markers, hematological dysfunction, and myocardial injury, with a higher frequency of respiratory failure and invasive mechanical ventilation. Conclusions: In our case series, patients with shock phenotype were the most frequent and had worse clinical outcomes. Active surveillance of clinical phenotypes is needed to make an early diagnosis and management to improve the prognosis in these patients.

Kawasaki-like disease related to COVID-19. Perioperative management of a pediatric case

The recently identified COVID-19-related Kawasaki-like disease has been considered one of the phenotypes of the cardiovascular manifestations of the Pediatric Multisystem Inflammatory Syndrome associated with SARS-CoV-2 (PIMS-TS), which stands out for few respiratory symptoms and multiple manifestations cardiovascular, the most important being dilation and eventual coronary aneurysms associated or not with cardiogenic shock. The literature is scarce, so perioperative management is challenging for the anesthesiology team. We present the case of an infant with severe cardiovascular manifestations as a result of this disease that required anesthetic interventions to perform a plethysmography and amputation of his lower extremity. The article describes the most relevant considerations in the perioperative management of patients with this pathology. © 2023 Sociedad de Anestesiologia de Chile. All rights reserved.

Diagnostic features of multiple organic system disorders associated with COVID-19 in a child of primary school age.

The advent of the COVID-19, specialists are increasingly encountering previously unknown pathological conditions in their practice. For some time, we have believed, that COVID-19 in children is most often mild and asymptomatic. However, with the passage of time and. the accumulation, of the experience, it became obvious that the new infectious disease it will be quite severe in children. Differential diagnosis of multiple organ disorders in children during the COVID-19 pandemic should, be primary carried out with the Multisystem. Inflammatory Syndrome in Children, associated, with COVID-19 (MIS-C), as well as Long-COVID-19. According to published, data, the manifestations of these conditions are due to frequent lesions of the gastrointestinal tract (60-100%), cardiovascular (80%), nervous (29-58%) and respiratory (21-65%) systems. At present, there is no exact idea of these pathological conditions, the criteria for their diagnosis and. the tactics of managing children, not only at the stage of diagnosis, but also at the stage of observation. The authors present a diagnostically complex clinical case describing the development of multiple organ damage in a 7-year-old. child, after contact with a mother who was sick with COVID-19. The data on the course features, the results of the examination and. the difficulties of differential diagnosis of this case with other diseases with a similar clinic are summarized.Copyright © 2022 Authors. All rights reserved.

Incomplete Kawasaki Disease with Peripheral Facial Nerve Palsy and Lung Nodules: A Case Report and Literature Review.

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.