Síndrome inflamatorio multisistémico asociado a COVID-19 en pediatría: serie de casos en servicios públicos de salud de Neuquén / Multisystem inflammatory syndrome associated with COVID-19 in children: case series in Neuquén public health services

INTRODUCCIÓN: Durante la pandemia por SARS-CoV-2 se reportaron casos de un síndrome de inflamación multisistémica similar a la enfermedad de Kawasaki con antecedente de infección reciente o contacto con casos de COVID-19, generando una relación temporal con dicha enfermedad (SIM-C). El objetivo de este trabajo fue caracterizar los aspectos clínicos y epidemiológicos de los casos de SIM-C en menores de 18 años. MÉTODOS: Se realizó un estudio transversal, observacional y descriptivo de casos de SIM-C en menores de 18 años asistidos entre marzo de 2020 y junio de 2022 en el sistema público de la provincia de Neuquén. RESULTADOS: Serie de casos: Se incluyó a 9 pacientes con SIM-C: 55,5% de sexo femenino, con una media de edad de 6,1 años. El 77,7% de los casos de COVID-19 fueron confirmados por nexo epidemiológico. Todos los pacientes presentaron fiebre previa a la internación, el 88,8% tuvo manifestaciones mucocutáneas y compromiso abdominal. Otras manifestaciones frecuentes fueron compromiso ocular y edema de manos. El 33,3% de los pacientes requirieron internación en unidades de cuidados intensivos pediátricos. Solo 1 necesitó asistencia respiratoria mecánica por 48 horas por shock. Todos los pacientes fueron tratados con inmunoglobulina intravenosa (IGIV) 2 g/kg, y 3 pacientes recibieron corticoterapia. No hubo fallecimientos ni complicaciones en el seguimiento. DISCUSIÓN: Aunque el pronóstico es favorable, se sugiere realizar estudios que monitoreen los efectos a largo plazo de SIM-C.

Características clínicas y evolución de los pacientes con enfermedad de Kawasaki en un hospital general / Clinical characteristics and course of patients with Kawasaki disease at a general hospital

La enfermedad de Kawasaki (EK) es la principal causa de cardiopatía adquirida en menores de cinco años. Nuestro objetivo fue conocer las características clínicas, el compromiso coronario y la evolución de pacientes atendidos en nuestra institución. Se revisó una serie de casos desde 2001 hasta 2018. Se incluyeron 63 pacientes, 58 % varones; la mediana de edad fue 2,6 años. La mediana de días de fiebre al diagnóstico fue 5,5 días. El 33 % presentó la forma incompleta y se detectó compromiso coronario en el 20 %. El 60 % de los pacientes con afectación coronaria presentaron EK incompleta versus el 28 % de presentación incompleta en los pacientes sin compromiso coronario (p 0,06). No se observaron diferencias en datos de laboratorio entre los grupos según el compromiso coronario. En conclusión, 33 % presentó EK incompleta y el 20 %, afectación coronaria. Hubo una tendencia de mayor riesgo para daño coronario en la forma incompleta.

Kawasaki disease (KD) is considered the leading cause of acquired heart disease in children younger than 5 years. Our objective was to know the clinical characteristics, coronary involvement, and course of patients seen at our facility. A case series from 2001 to 2018 was reviewed. Sixty-three patients were included; their median age was 2.6 years; 58% were males. The median duration of fever at the time of diagnosis was 5.5 days. The incomplete form was observed in 33% and coronary involvement, in 20%. Among patients with coronary involvement, 60% had incomplete KD versus 28% among those without coronary involvement (p: 0.06). No differences were observed between groups in laboratory data based on coronary involvement. To conclude, 33% had incomplete KD and 20%, coronary involvement. There was a trend to a higher risk for coronary artery damage in the incomplete form of KD.

Canalización del crecimiento entre los 2 y los 5 años en niños aparentemente sanos con talla baja a los 2 años / Canalization of growth between 2 and 5 years of age in apparently healthy children with short stature at age 2 years

Introducción. El tamaño del recién nacido se asocia a condiciones intrauterinas. El potencial genético se expresa más tarde; la canalización del crecimiento se describe clásicamente hasta los 24 meses. Objetivo. Describir la canalización del crecimiento entre los 2 y los 5 años en niños aparentemente sanos con talla baja a los 2 años. Población y métodos. Estudio de cohorte retrospectiva. Se incluyeron niños seguidos en un hospital universitario de comunidad entre 2003 y 2019, con puntaje Z de talla menor a -2 DE para edad y sexo a los 2 años. Se excluyeron los nacidos prematuros, con bajo peso y con enfermedades crónicas. Se evaluó la trayectoria de crecimiento. Se definió canalización como la adquisición de talla normal para la población general. Resultados. Se incluyeron 64 niños, de los cuales 37 (58 %) presentaron canalización del crecimiento a los 5 años (20 a los 3 años, 8 a los 4 años, y 9 a los 5 años). La velocidad de crecimiento a los 3 y a los 5 años fue significativamente mayor en los que canalizaron en comparación con los que no lo hicieron; hubo una tendencia similar a los 4 años. De los 27 niños con talla baja a los 5 años, 25 tuvieron al menos un registro de velocidad de crecimiento anual menor al percentil 25. Conclusiones. La mayoría de los niños aparentemente sanos con baja talla a los 2 años alcanzan una talla normal a los 5 años. La velocidad de crecimiento anual permite detectar a los niños con riesgo de no canalizar.

Introduction. Newborn size is associated with intrauterine conditions. Genetic potential is expressed later; the canalization of growth is typically described up to 24 months of age. Objective. To describe the canalization of growth between 2 and 5 years of age in apparently healthy children with short stature at age 2 years. Population and methods. Retrospective, cohort study. Children seen at a community teaching hospital between 2003 and 2019, who had a Z-score for height below -2 SDs for age and sex at age 2 years were included. Infants born preterm, with a low birth weight, and chronic conditions were excluded. Growth patterns were assessed. Canalization was defined as reaching a normal stature for the general population. Results. Sixty-four children were included; 37 (58%) showed canalization of growth at 5 years old (20 at 3 years, 8 at 4 years, and 9 at 5 years). The growth rate at 3 and 5 years of age was significantly higher among those who showed canalization compared to those who did not; a similar trend was observed at 4 years of age. Among 27 children with short stature at 5 years of age, 25 had at least 1 annual growth velocity below the 25th centile. Conclusions. Most apparently healthy children with short stature at 2 years old reached a normal stature at 5 years old. The annual growth velocity allows to detect children at risk of not showing canalization.

Multisystemic inflammatory syndrome in children after severe acute respiratory syndrome coronavirus 2 infection: a clinical analysis of four cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features and treatment strategies of multisystemic inflammatory syndrome in children (MIS-C) after severe acute respiratory syndrome coronavirus 2 infection.@*METHODS@#A retrospective analysis was performed on the medical data of four children with MIS-C who were admitted to the Department of Cardiology, Xuzhou Children's Hospital, Xuzhou Medical Universityfrom January to February 2023.@*RESULTS@#All four children had multiple organ involvements and elevated inflammatory markers, with a poor response to standard therapy for Kawasaki disease after admission. Two children were treated with intravenous immunoglobulin therapy pulse therapy twice, and all four children were treated with glucocorticoids. The children had a good prognosis after the treatment.@*CONCLUSIONS@#MIS-C often appears within 4-6 weeks or a longer time after severe acute respiratory syndrome coronavirus 2 infection, and anti-inflammatory therapy in addition to the standard treatment regimen for Kawasaki disease can help to achieve a favorable treatment outcome.

Recent research on platelet-leukocyte aggregates and their role in the pathogenesis of Kawasaki disease / 中国当代儿科杂志

Activated platelets may interact with various types of leukocytes such as monocytes, neutrophils, dendritic cells, and lymphocytes, trigger intercellular signal transduction, and thus lead to thrombosis and synthesis of massive inflammatory mediators. Elevated levels of circulating platelet-leukocyte aggregates have been found in patients with thrombotic or inflammatory diseases. This article reviews the latest research on the formation, function, and detection methods of platelet-leukocyte aggregates and their role in the onset of Kawasaki disease, so as to provide new ideas for studying the pathogenesis of Kawasaki disease.

Role and mechanism of platelet-derived growth factor BB in thrombocytosis in Kawasaki disease / 中国当代儿科杂志

OBJECTIVES@#To study the role and mechanism of platelet-derived growth factor BB (PDGF-BB) on platelet production in Kawasaki disease (KD) mice and human megakaryocytic Dami cells through in vitro and invivo experiments.@*METHODS@#ELISA was used to measure the expression of PDGF in the serum of 40 children with KD and 40 healthy children. C57BL/6 mice were used to establish a model of KD and were then randomly divided into a normal group, a KD group, and an imatinib group (30 mice in each group). Routine blood test was performed for each group, and the expression of PDGF-BB, megakaryocyte colony forming unit (CFU-MK), and the megakaryocyte marker CD41 were measured. CCK-8, flow cytometry, quantitative real-time PCR, and Western blot were used to analyze the role and mechanism of PDGF-BB in platelet production in Dami cells.@*RESULTS@#PDGF-BB was highly expressed in the serum of KD children (P<0.001). The KD group had a higher expression level of PDGF-BB in serum (P<0.05) and significant increases in the expression of CFU-MK and CD41 (P<0.001), and the imatinib group had significant reductions in the expression of CFU-MK and CD41 (P<0.001). In vitro experiments showed that PDGF-BB promoted Dami cell proliferation, platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05). Compared with the PDGF-BB group, the combination group (PDGF-BB 25 ng/mL + imatinib 20 μmol/L) had significantly lower levels of platelet production, mRNA expression of PDGFR-β, and protein expression of p-Akt (P<0.05).@*CONCLUSIONS@#PDGF-BB may promote megakaryocyte proliferation, differentiation, and platelet production by binding to PDGFR-β and activating the PI3K/Akt pathway, and the PDGFR-β inhibitor imatinib can reduce platelet production, which provides a new strategy for the treatment of thrombocytosis in KD.

Clinical features of Kawasaki disease complicated by macrophage activation syndrome: an analysis of 27 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical manifestations and laboratory examination results of children with Kawasaki disease complicated by macrophage activation syndrome (KD-MAS), and to provide a basis for identifying early warning indicators for the early diagnosis and treatment of KD-MAS.@*METHODS@#A retrospective study was performed on 27 children with KD-MAS (KD-MAS group) and 110 children with KD (KD group) who were admitted to Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2014 to January 2022. Clinical and laboratory data were compared between the two groups. The receiver operating characteristic (ROC) curve was used to investigate the value of laboratory markers with statistical significance in the diagnosis of KD-MAS.@*RESULTS@#Compared with the KD group, the KD-MAS group had significantly higher incidence rates of hepatomegaly, splenomegaly, incomplete KD, no response to intravenous immunoglobulin, coronary artery damage, multiple organ damage, and KD recurrence, as well as a significantly longer length of hospital stay (P<0.05). Compared with the KD group, the KD-MAS group had significantly lower levels of white blood cell count, absolute neutrophil count, hemoglobin, platelet count (PLT), erythrocyte sedimentation rate, serum albumin, serum sodium, prealbumin, and fibrinogen (FIB), a significantly lower incidence rate of non-exudative conjunctiva, and significantly higher levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and serum ferritin (SF) (P<0.05). The ROC curve analysis showed that SF, PLT, FIB, and LDH had high value in the diagnosis of KD-MAS, with areas under the curve (AUC) of 0.989, 0.966, 0.932, and 0.897, respectively (P<0.001), and optimal cut-off values of 349.95 μg/L, 159×109/L, 3.85 g/L, and 403.50 U/L, respectively. The combination of SF, PLT, FIB, and LDH had a larger AUC than PLT, FIB, and LDH alone in the diagnosis of KD-MAS (P<0.05), but there was no significant difference in the AUC between the combination of SF, PLT, FIB, and LDH and SF alone (P>0.05).@*CONCLUSIONS@#KD-MAS should be considered when children with KD have hepatosplenomegaly, no response to intravenous immunoglobulin, coronary artery damage, and KD recurrence during treatment. SF, PLT, FIB, and LDH are of high value in the diagnosis of KD-MAS, especially SF is of great significance in the diagnosis of KD-MAS.

Clinical application of plasma exchange combined with continuous veno-venous hemofiltration dialysis in children with refractory Kawasaki disease shock syndrome / 中国当代儿科杂志

OBJECTIVES@#To study the role of plasma exchange combined with continuous blood purification in the treatment of refractory Kawasaki disease shock syndrome (KDSS).@*METHODS@#A total of 35 children with KDSS who were hospitalized in the Department of Pediatric Intensive Care Unit, Hunan Children's Hospital, from January 2019 to August 2022 were included as subjects. According to whether plasma exchange combined with continuous veno-venous hemofiltration dialysis was performed, they were divided into a purification group with 12 patients and a conventional group with 23 patients. The two groups were compared in terms of clinical data, laboratory markers, and prognosis.@*RESULTS@#Compared with the conventional group, the purification group had significantly shorter time to recovery from shock and length of hospital stay in the pediatric intensive care unit, as well as a significantly lower number of organs involved during the course of the disease (P<0.05). After treatment, the purification group had significant reductions in the levels of interleukin-6, tumor necrosis factor-α, heparin-binding protein, and brain natriuretic peptide (P<0.05), while the conventional group had significant increases in these indices after treatment (P<0.05). After treatment, the children in the purification group tended to have reductions in stroke volume variation, thoracic fluid content, and systemic vascular resistance and an increase in cardiac output over the time of treatment.@*CONCLUSIONS@#Plasma exchange combined with continuous veno-venous hemofiltration dialysis for the treatment of KDSS can alleviate inflammation, maintain fluid balance inside and outside blood vessels, and shorten the course of disease, the duration of shock and the length of hospital stay in the pediatric intensive care unit.

Recent research on the nuclear factor-kappa B signaling pathway in cardiac injury in children with Kawasaki disease / 中国当代儿科杂志

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is a systemic acute vasculitis belonging to autoimmune disease. Up to now, the specific pathogenesis of this disease remains unclear, and it may involve various factors such as immune response, inflammatory response, and vascular endothelial injury caused by the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. In particular, children with KD and cardiac injury tend to have a poor prognosis, and researchers hope to explore the specific pathogenesis of cardiac injury in KD to provide new options for clinical diagnosis and treatment and reduce the incidence rate of this disorder. This article reviews the recent research on the role of the NF-κB signaling pathway in cardiac injury in children with KD, so as to provide a basis for future studies.

Expression of interleukin-17A in serum of children with intravenous immunoglobulin-resistant Kawasaki disease and its clinical significance / 中国当代儿科杂志

OBJECTIVES@#To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance.@*METHODS@#A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD.@*RESULTS@#Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001).@*CONCLUSIONS@#Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.

Diagnosis and treatment of incomplete Kawasaki disease in children / 中国当代儿科杂志

Kawasaki disease (KD) is a febrile disease mainly observed in children aged <5 years, with medium- and small-vessel vasculitis as the main lesion. Although KD has been reported for more than 50 years and great progress has been made in the etiology and pathology of KD in recent years, there is still a lack of specific indicators for the early diagnosis of KD, especially with more difficulties in the diagnosis of incomplete Kawasaki disease (IKD). At present, there are no clear diagnostic criteria for IKD, which leads to the failure of the timely identification and standardized treatment of IKD in clinical practice and even induce the development of coronary artery lesion. This article reviews the concept, epidemiological features, diagnosis, treatment, and follow-up management of IKD, in order to deepen the understanding of IKD among clinical workers and help to improve the clinical diagnosis and treatment of KD in China.

Características clínicas, tratamiento y evolución de una serie de niños con síndrome inflamatorio multisistémico asociado a SARS-CoV-2 hospitalizados en dos centros de salud / Clinical characteristics, treatment and evolution of a series of children with multisystemic inflammatory syndrome associated with SARS-CoV-2 hospitalized in two health centers / Características clínicas, tratamento e evolução de uma série de crianças com síndrome inflamatória multissistêmica associada ao SARS-CoV-2 internadas em dois centros de saúde

Introducción: en marzo del 2021 se registró el pico de incidencia de COVID-19 en Uruguay y un aumento de la infección en pediatría. Objetivo: describir las características clínicas, el tratamiento y la evolución de una serie de menores de 15 años con SIM-Ped S hospitalizados en dos centros de salud. Metodología: estudio descriptivo, retrospectivo, de los niños hospitalizados entre el 1/3 y el 31/6 de 2021 que cumplieron los criterios diagnósticos de SIM-Ped de la OMS. Se analizan variables clínicas, paraclínicas, tratamiento y evolución. Resultados: se incluyeron 12 niños, mediana de edad 7 años (22 meses-10 años). Se presentaron complicación posinfecciosas en 8 y en el curso de la infección en 4. Las manifestaciones fueron: fiebre (media 6 días, rango 3-10), digestivas 10 y mucocutáneas 7. Se presentaron como enfermedad Kawasaki símil 5 y como shock 2. La infección por SARS CoV-2 se confirmó por PCR en 6, serología 4 y test antigénico 2. Recibieron tratamiento en cuidados moderados 8 e intensivos 4: inmunoglobulina 9, corticoides 11, heparina 7 y ácido acetilsalicílico 7. Presentaron dilatación de arterias coronarias 2, alteraciones valvulares 2, disminución de la FEVI 2 y derrame pericárdico 2. Todos evolucionaron favorablemente. Conclusiones: en estos centros, los primeros casos de SIMS-Ped S coincidieron con el pico de incidencia de COVID-19 en el país. Predominaron las formas postinfecciosas en escolares con manifestaciones digestivas. Este estudio puede contribuir al reconocimiento de esta entidad y adecuar los algoritmos nacionales de manejo.

Introduction: in March 2021, there was a peak incidence of COVID-19 and an increase in pediatric infections in Uruguay. Objective: describe the clinical characteristics, treatment and evolution of a group of children under 15 years of age with SIM-Ped S hospitalized in two health centers. Methodology: descriptive, retrospective study of children hospitalized between 3/1 and 6/31 of 2021 who met the WHO diagnostic criteria for SIM-Ped. Clinical and paraclinical variables, as well as treatment and evolution were analyzed. Results: 12 children were included, median age 7 years (22 months-10 years). Eight of them showed post-infectious complications and 4 of them had complications during the course of the infection. The manifestations were: fever (mean 6 days, range 3-10), digestive symptoms 10 and mucocutaneous 7. Five of them presented a Kawasaki-like disease and 2 of them shock. SARS CoV-2 infection was confirmed by PCR in 6 cases, serology in 4 and antigenic test in 2. Eight of them received treatment in moderate care and 4 of them in intensive care: immunoglobulin 9, corticosteroids 11, heparin 7 and acetylsalicylic acid 7. Two of them presented dilated arteries coronary , valvular alterations 2, decreased LVEF 2 and pericardial effusion 2. All progressed favorably. Conclusions: in these centers, the first cases of SIMS-Ped S coincided with the peak incidence of COVID-19 in the country. Post-infectious forms predominated in schoolchildren who showed digestive manifestations. This study may contribute to the recognition of this entity and to the adaptation of national management algorithms.

Introdução: em março de 2021, foi registrado no Uruguai um pico de incidência da COVID-19 e um aumento dos casos da infecção pediátrica. Objetivo: descrever as características clínicas, tratamento e evolução de uma série de crianças menores de 15 anos com SIM-Ped S internadas em dois centros de saúde. Metodologia: estudo descritivo, retrospectivo, de crianças internadas entre 1/3 e 31/6 de 2021 que preencheram os critérios diagnósticos da OMS para o SIM-Ped. Foram analisadas variáveis clínicas e para-clinicas, tratamento e evolução. Resultados: foram incluídas 12 crianças, com idade média de 7 anos (22 meses-10 anos). Oito delas apresentaram complicações pós-infecciosas e 4 delas durante o curso da infecção. As manifestações foram: febre (média de 6 dias, intervalo 3-10), digestivas 10 e mucocutânea 7. Cinco delas apresentaram doença de Kawasaki-like e 2 delas sofreram Shock. A infecção por SARS CoV-2 foi confirmada por PCR em 6, sorologia em 4 e teste antigênico em 2. Oito delas receberam tratamento em cuidados moderados e 4 delas em cuidados intensivos: imunoglobulina 9, corticosteroides 11, heparina 7 e ácido acetilsalicílico 7. Duas delas apresentaram artérias coronárias dilatadas 2, alterações valvares 2, diminuição da FEVE 2 e derrame pericárdico 2. Todas evoluíram favoravelmente. Conclusões: nesses centros, os primeiros casos de SIMS-Ped S coincidiram com um pico de incidência de COVID-19 no país. As formas pós-infecciosas predominaram em escolares com manifestações digestivas. Este estudo pode contribuir para o reconhecimento desta entidade e adaptar algoritmos nacionais de gestão.

Kawasaki disease in Colombia: A systematic review and contrast with multisystem inflammatory syndrome in children associated with COVID-19

Introduction: Kawasaki disease (KD) is an acute vasculitis with multisystem involvement. Recently, the increasing incidence of a condition that closely resembles KD in many cases, named multisystem inflammatory syndrome in children (MIS-C), has set off alarms amid the current worldwide coronavirus disease-19 (COVID-19) pandemic. Hence, the aim is to conduct a systematic review of the literature about KD in Colombia and contrast it with COVID-19-related MIS-C. Materials and methods: A search was carried out in both international and Latin American electronic databases for publications concerning patients with KD in the Colombian population. Records were then screened by titles and/or abstracts, assessed for eligibility, and reviewed. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. The search included studies reporting MIS-C associated with COVID-19, and compared these patients with our findings of KD in Colombia. Results: Out of 36 publications retrieved, 17 were included, representing 120 individuals. Male to female ratio was 1.6, and most patients (90.4%) were aged 5 years or less. Among the main features of KD, fever was the most frequent (96.2% of the patients), while cervical lymphadenopathy was present in only 40.6%. Intravenous immunoglobulin was administered in 91.4% cases and 6.2% were resistant. Cardiac involvement was found in around 30%, and 20% had coronary artery lesions. Comparison between MIS-C associated with COVID-19 and KD in Colombia indicates that patients affected by MIS-C were older (72.2% of MIS-C patients > 5 years), had higher rates of cardiac involvement, and required critical care more often. Conclusions: Our findings of KD in Colombia are consistent with the available descriptions of KD in the scientific literature. Given the increasing rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in Colombia and Latin America, our study raises awareness about MIS-C in pediatric patients with COVID-19 and its relationship with KD.

Introducción: La enfermedad de Kawasaki (EK) es una vasculitis aguda con compromiso multisistémico. Recientemente, la incidencia creciente de una condición que se asemeja en forma considerable a la EK en muchos casos, denominada síndrome inflamatorio multisistémico (SIMS) en niños, ha encendido las alarmas en medio de la actual pandemia mundial de la enfermedad COVID-19. Por consiguiente, nos propusimos realizar una revisión sistemática de la literatura acerca de la EK en Colombia y contrastarla con el SIMS relacionado con COVID-19 en niños. Materiales y métodos: Buscamos publicaciones respecto a pacientes con EK en población colombiana, en bases de datos electrónicas tanto internacionales como latinoamericanas. Los registros hallados fueron tamizados por títulos o resúmenes, evaluados para elegibilidad y revisados. Se siguieron las guías Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Posteriormente, buscamos estudios que reportaran SIMS temporalmente asociado con COVID-19 en niños y comparamos estos pacientes con nuestros hallazgos de EK en Colombia. Resultados: De 36 publicaciones encontradas se incluyeron 17, las cuales representaron 120 individuos. La razón hombre a mujer fue de 1,6 y la mayoría de los pacientes (90,4%) tenía 5 anos o menos. Entre las principales características de EK, la fiebre fue la más frecuente (96,2%), mientras que la linfadenopatía cervical estuvo presente solo en el 40,6%. La inmunoglobulina intravenosa se administró en el 91,4% de los casos y 6,2% presentaron resistencia. Se encontró compromiso cardiaco en alrededor del 30% de los pacientes, en tanto que el 20% tuvo lesiones de arterias coronarias. La comparación entre las características clínicas de la EK y el SIMS asociado a COVID-19 mostró que los individuos afectados por el SIMS eran mayores (72,2% con SIMS tenían más de cinco anos), tuvieron mayores índices de compromiso cardiaco y requirieron cuidado crítico con mayor frecuencia. Conclusiones: Nuestros hallazgos de EK en Colombia son consistentes con las descripciones disponibles de esta enfermedad en la literatura científica. Debido al aumento de infección por SARS-CoV-2 en Colombia y Latinoamérica, nuestro estudio busca crear conciencia sobre el SIMS en pacientes pediátricos con COVID-19 y su relación con la EK.

Síndrome inflamatória multissistêmica em crianças infectadas por coronavírus: uma revisão integrativa / Multisystemic inflamatory syndrome in children infected by coronavirus: an integrative review / Síndrome inflamatorio multisistémico en niños infectados por coronavirus: una revisión integradora

Durante a pandemia de COVID-19, foram observadas manifestações atípicas em pacientes pediátricos em diversas regiões do mundo, e o conjunto desses sintomas caracterizou uma nova patologia denominada Síndrome Inflamatória Multissistêmica em Crianças (MIS-C), ou Síndrome Inflamatória Multissistêmica Pediátrica Temporariamente associada ao COVID-19 (PIMS- TS). O objetivo desta revisão foi analisar as manifestações clínicas e as possíveis complicações relacionadas a tal quadro inflamatório. Foi realizada uma busca por artigos científicos nas bases de dados Embase, PubMed e Web of Science, por meio da combinação dos descritores "MIS-C", "PIMS- TS" e "COVID-19". Após a análise dos artigos encontrados, e considerando critérios de inclusão e exclusão, foram selecionados 15 estudos para compor esta revisão. A maioria dos estudos mencionaram complicações gastrointestinais, cardiovasculares, respiratórias e mucocutâneas. Ademais, foram encontrados marcadores que indicavam estado inflamatório generalizado e coagulopatia. Assim, concluiu-se que MIS-C provavelmente é uma síndrome manifestada após a infecção por SARS-CoV-2, podendo ocasionar quadros mais graves, mas com baixas taxas de mortalidade.

During the COVID-19 pandemic, atypical manifestations were observed in pediatric patients in different regions of the world, and the set of these symptoms characterized a new pathology called Multisystemic Inflammatory Syndrome in Children (MIS-C), or Pediatric Multisystemic Inflammatory Syndrome Temporarily associated with COVID-19 (PIMS-TS). The purpose of this review was to analyze the clinical manifestations and possible complications related to such an inflammatory condition. A search for scientific articles was carried out in the databases Embase, PubMed and Web of Science, by combining the descriptors "MIS-C", "PIMS-TS" and "COVID-19". After analyzing the articles found, and considering inclusion and exclusion criteria, 15 studies were selected to compose this review. Most studies mentioned gastrointestinal, cardiovascular, respiratory and mucocutaneous complications. In addition, markers were found that indicated generalized inflammatory status and coagulopathy. Thus, it was concluded that MIS-C is probably a syndrome manifested after infection by SARS-CoV-2, which can cause more severe conditions, but with low mortality rates.

Durante la pandemia de COVID-19 se observaron manifestaciones atípicas en pacientes pediátricos de diferentes regiones del mundo, y el conjunto de estos síntomas caracterizó una nueva patología denominada Síndrome Inflamatorio Multisistémico en Niños (SMI-C), o Síndrome Inflamatorio Multisistémico Pediátrico Asociado Temporalmente a COVID-19 (SIPM-TS). El propósito de esta revisión fue analizar las manifestaciones clínicas y las posibles complicaciones relacionadas con dicha condición inflamatoria. Se realizó una búsqueda de artículos científicos en las bases de datos Embase, PubMed y Web of Science, combinando los descriptores "MIS-C", "PIMS- TS" y "COVID-19". Tras analizar los artículos encontrados, y teniendo en cuenta los criterios de inclusión y exclusión, se seleccionaron 15 estudios para componer esta revisión. La mayoría de los estudios mencionaron complicaciones gastrointestinales, cardiovasculares, respiratorias y mucocutáneas. Además, se encontraron marcadores que indicaban un estado inflamatorio generalizado y coagulopatía. Así pues, se concluyó que el SMI-C es probablemente un síndrome que se manifiesta tras la infección por el SARS-CoV-2, que puede causar cuadros más graves, pero con bajas tasas de mortalidad.

Síndrome Inflamatória Multissistêmica Pediátrica (SIM-P) em crianças e adolescente com até 19 anos de idade, temporalmente associada à Covid-19 / Pediatric Multisystem Inflammatory Syndrome (P-SIM) in children and adolescents up to 19 years of age, temporally associated with Covid-19

A Síndrome Inflamatória Multissistêmica Pediátrica (SIM-P) é uma condição que afeta e prejudica diversas partes do corpo, incluindo coração, pulmões, rins, cérebro, pele, olhos ou órgãos gastrointestinais. É uma síndrome rara que ainda necessita de estudo. No entanto, é sabido que muitas crianças que apresentaram SIM-P tiveram o vírus que causa a COVID-19 ou entraram em contato com alguém com COVID-19. A SIM-P pode ser grave e fatal, e grande parte dos casos pode necessitar de internação em unidade de terapia intensiva

A comparative study of pediatric patients with Complete vs. Incomplete Kawasaki Disease in a tertiary Hospital: An eleven year review

Introduction@#Kawasaki disease (KD) is the leading cause of acquired heart disease in childhood, but its diagnosis remains challenging since a significant number of cases do not meet the diagnostic criteria (Incomplete KD). This may delay the diagnosis and initiation of treatment, and increase the risk of morbidity from coronary artery complications.@*Objectives@#This study compared the clinical profile and treatment outcomes of children with complete and incomplete KD. @*Methods@#This is a cross-sectional, retrospective study of pediatric patients diagnosed with KD and admitted in a tertiary hospital from January 1, 2010 to December 31, 2020. Demographics, clinical manifestations, laboratories, 2D echocardiography (2DE) findings and treatment outcomes were obtained by review of medical records and analyzed using descriptive statistics. @*Results@#Among 135 patients studied, 71% were classified as Incomplete Kawasaki Disease. Majority (89%) were children more than 1 year old and predominantly male (55%). Five classic features, other than fever, were more frequent in complete KD – bilateral bulbar conjunctivitis, mucosal changes in the lip and oral cavity, polymorphous exanthem, changes in extremities, and cervical lymphadenopathy. Fever (100%), conjunctivitis (100%), rashes (97%) and oral changes (90%) were the most common findings in complete KD, while fever (100%), rashes (56%), conjunctivitis (46%) and oral changes (35%) were noted in incomplete KD. Higher CRP (167 mg/L vs. 100 mg/L) and lower albumin levels (30 g/L vs. 38 g/L) were seen in complete KD. Coronary artery dilatation (56% vs. 48%) was frequently detected in both complete and incomplete KD. Majority (96%) of cases received only one dose of IVIG and 4% needed additional treatment with methylprednisone. @*Conclusion@#The five principal features of KD other than fever, elevated CRP and lower albumin levels were significantly more common in complete cases. No significant differences in the demographics and 2DE findings of children with complete and incomplete KD were observed.

A systematic review and meta-analysis on the safety and efficacy of Second Dose Immunoglobulin versus High Dose Pulse Methylprednisolone in Refractory Kawasaki Disease

Background@#There is limited information available regarding the management of IVIG-refractory Kawasaki Disease (KD). @*Objective@#This study aimed to evaluate the safety and efficacy of a second intravenous immunoglobulin (IVIG) infusion versus intravenous methylprednisolone (IVMP) in patients with IVIG-refractory KD.@*Methodology@#Cochrane Library, PubMed, Medline, Elsevier (Science Direct), Springer Link and BMJ databases were searched from May 1, 2020 to December 31, 2020. We included randomized controlled trials (RCTs) and high-quality prospective and retrospective studies, with population restricted to children 0 months to 18 years, with KD refractory to initial IVIG at 2g/kg, who remained febrile for 24-48 hours after completion of initial IVIG, and who received second-line monotherapy with either a second dose IVIG or IVMP. We conducted a meta-analysis using Review Manager [RevMan] 5.4.1 software.@*Results@#A total of six studies (n=188 patients) were analyzed. The incidence of coronary artery lesions was comparable between a second dose of IVIG and IVMP (RR 0.82, 0.34-1.96, P=0.66) in patients with IVIG-refractory KD. The rate of fever resolution to a second IVIG, compared to IVMP, was not significantly different between groups (RR 0.97, 0.84-1.13, P=0.72). There was a significantly higher incidence of adverse events in the IVMP group (RR 0.42, 0.26-0.57, P=0.0002), but these were all transient and resolved without further treatment. @*Conclusion@#There is no significant difference in the incidence of coronary artery lesions and rate of fever resolution post-retreatment with a second dose of IVIG versus IVMP in IVIG-refractory KD. More adverse events were reported in the IVMP group.

Síndrome multisistémico post COVID-19 y dificultad en su diagnóstico etiológico: a propósito de un caso clínico / Multisystem post COVID-19 syndrome and its difficult etiological diagnosis: a clinical case / Síndrome multissistêmica pós COVID-19 e a dificuldade no seu diagnóstico etiologico: relato de caso clínico

El SARS-CoV-2 afecta a un reducido número de pacientes pediátricos, que en su mayoría son asintomáticos o presentan compromiso respiratorio leve y evolución favorable. Sin embargo, en niños previamente sanos puede aparecer el síndrome inflamatorio multisistémico (SIM-C) o similar a Kawasaki (Kawasaki-like) asociado a la enfermedad por COVID-19, que evolucionan al shock y requiere internación en la unidad de cuidados intensivo. Presentamos el caso de un adolescente con antecedentes ambientales de SARS-CoV-2 37 días antes de su ingreso, que no se testeó en ese momento. Recibe la primera dosis de vacuna Pfizer 15 días antes de la presentación de un cuadro de sintomatología digestiva con dolor abdominal y fiebre, con test de antígenos COVID-19 y PCR viral negativos. Luego de una laparoscopia exploratoria, al sexto día de fiebre y dolor instaló conjuntivitis bilateral no supurada y exantema en tórax, odinofagia, astenia y lengua saburral con fenotipo Kawasaki. La serológica IgG anti spike fue positiva y la IgM negativa, con parámetros inflamatorios elevados, por lo que se planteó un síndrome multisistémico post COVID-19. Recibió tratamiento con inmunoglobulina intravenosa, ácido acetilsalicílico y metilprednisolona. Dada la necesidad de descartar la posibilidad de un evento atribuible a vacunación o inmunización (ESAVI), se realizó la búsqueda serológica para SARS-CoV-2, en un estudio cualitativo, buscando anticuerpos que no se generan con la vacuna Pfizer, que fueron positivos. De esta forma confirmamos la etiología post COVID-19 y descartamos la etiología por ESAVI, realizándose además el estudio cuantitativo de los anticuerpos anti spike con disminución de estos al mes del debut.

Summary: SARS-CoV-2 affects a low number of pediatric patients, most asymptomatic or with mild respiratory compromise and favorable evolution. However, in previously healthy children, Multisystem Inflammatory Syndrome (SIM-C) or Kawasaki-like Syndrome(Kawasaki-like) may appear linked to the COVID-19 disease, progressing to shock and requiring admission to the intensive care unit. We present the case of an adolescent with an environmental history of SARS-CoV-2 37 days prior to her admission, who was not tested at that time. She had received the first dose of Pfizer vaccine 15 days before the presentation of digestive symptoms with abdominal pain and fever. She had a negative Covid-19 antigen test and viral PCR. After an exploratory laparoscopy, on the sixth day of fever and pain, she developed bilateral non-suppurative conjunctivitis and a rash on the chest, odynophagia, asthenia, and coated tongue with the Kawasaki phenotype. The anti-spike IgG serology was positive and the IgM negative, with elevated inflammatory parameters, so a post-COVID-19 multisystem syndrome was suggested. She received treatment with intravenous immunoglobulin, ASA and methylprednisolone. In order to rule out the possibility of an event allegedly caused by vaccination or immunization (ESAVI), the serological search for SARS-CoV-2 was carried out through a qualitative study, looking for antibodies that are not generated with the Pfizer vaccine. The result was positive. Therefore, we confirmed the post-Covid etiology and ruled out the ESAVI etiology, and also performed the quantitative study of the anti-spike antibodies, which showed a decrease one month after the debut.

O SARS-CoV-2 afeta um número reduzido de pacientes pediátricos, em sua maioria, assintomáticos ou apresentando comprometimento do nível respiratório e evolução favorável. Porém, em crianças previamente sãs, pode aparecer a Síndrome Inflamatória Multissistêmica (SIM-C) ou similar a Kawasaki (Kawasaki-like) associada à doença por COVID-19, que pode evoluir a choque e requer a internação na UTI. Apresentamos o caso de um adolescente com antecedentes ambientais de SARS-CoV-2 37 dias antes do seu ingresso, que não se testou nesse momento. Recebendo a dose da primeira vacina Pfizer 15 dias antes da apresentação de sintomatologia digestiva com dor abdominal e febre. Teve um teste de antígenos COVID-19 viral negativo. Depois de una laparoscopia exploratória, ao sexto dia de febre e dor, teve conjuntivite bilateral não supurada e exantema en tórax, odinofagia, astenia e língua saburral com fenótipo Kawasaki. A sorologia IgG anti-spike foi positiva e a gM negativa, com parâmetros inflamatórios superiores, indicando uma síndrome multissistêmica pós Covid 19. O tratamento recebido foi imunoglobulina intravenosa, AAS e Metilprednisolona. Com o fim de descartar a possibilidade de um evento supostamente atribuível à vacinação ou vacinação positiva (ESAVI), realizou-se uma busca sorológica para SARS COV2, através de um estúdio qualitativo, procurando anticorpos não gerados pela vacina Pfizer, os quais foram confirmados. Nesta forma, confirmamos a etiologia pós-Covid e descartamos a etiologia por ESAVI. Aliás, realizamos um estudo quantitativo dos anticorpos anti-spike e comprovamos a sua diminuição a um mês de ter acontecido o debut.

Análise de variantes genéticas patogênicas na Síndrome Inflamatória Multissistêmica Pediátrica / Analysis of pathogenic genetic variants in Pediatric Multisystem Inflammatory Syndrome

Introdução. Alguns meses após o início da pandemia de COVID-19, houve o surgimento de uma nova síndrome que acomete crianças e adolescentes. Suas manifestações clínicas são potencialmente graves e se assemelham à doença de Kawasaki, sendo caracterizadas por resposta inflamatória exacerbada e acometimento de múltiplos órgãos. Esse fenótipo recebeu o nome de síndrome inflamatória multissistêmica pediátrica (SIM-P). Apesar do grande número de publicações sobre a resposta imune de pacientes com SIM-P nos meses que se seguiram, permanecem obscuros os fatores determinantes na evolução destes pacientes. Estas respostas podem residir, pelo menos em parte, na genética. Especula-se que pelo menos uma parte dos pacientes com SIM-P possa ter um algum Erro Inato da Imunidade (EII) subjacente, seja de origem monogênica, digênica ou mesmo oligogênica. Objetivo. Identificar pacientes que apresentem o fenótipo da SIM-P, descrever suas manifestações clínicas, exames laboratoriais e evolução, além de buscar variantes genéticas patogênicas e provavelmente patogênicas que possam estar relacionadas ao fenótipo através do sequenciamento de exoma completo. Metodologia. Estudo observacional, descritivo, do tipo série de casos, longitudinal (retrospectivo e prospectivo) e multicêntrico. Foi realizada revisão de prontuário médico, além de exames laboratoriais e de imagem. Foram coletadas amostras de sangue dos pacientes participantes para realização de sequenciamento de exoma. Durante a análise das variantes genéticas encontradas, foram consideradas a frequência alélica, preditores para avaliação da patogenicidade das variantes e a relevância clínica das mesmas. Resultados. Um total de 29 pacientes foram incluídos, a mediana de idade foi de 6 anos, a maioria dos pacientes eram do sexo feminino (62%) e apenas 10% apresentavam comorbidades, sendo a asma a mais comum (7%). Os pacientes apresentaram uma mediana de 6 dias de febre e o fenótipo clínico mais frequente foi disfunção cardíaca aguda (48,1%) seguido de pacientes com manifestações Kawasaki-like (33,3%). Foram identificados 16 pacientes com variantes patogênicas ou provavelmente patogênicas. Nesses casos, um total de 22 variantes foram identificadas em 11 genes diferentes: BLK, CFB, ERAP1, FCN3, INFA21, IFIH1, MASP2, MPO, PRF1, TNFRSF13B e ZFHX3. Conclusão. Dentre os genes identificados, há uma predominância de genes relacionados ao sistema complemento, a resposta à infecção viral e a função das células B, todas vias importantes na infecção pelo SARS-CoV-2. Para melhor compreender quais são os fatores determinantes desta doença, são necessárias outras estratégias de busca de variantes, coortes maiores, estudos com controles saudáveis e outras formas de investigação como análise de HLA, proteômica e RNAseq.

Introduction. A few months after the beginning of the COVID-19 pandemic, there was the emergence of a new syndrome that affects children and adolescents. Its clinical manifestations are potentially severe and resemble Kawasaki's disease, being characterized by an exacerbated inflammatory response and involvement of multiple organs. This phenotype was named multisystem inflammatory syndrome in children (MIS-C). Despite the large number of publications on MIS C patients' immune response in the months that followed, the determining factors in the evolution of these patients remain elusive. Answers may lie, at least in part, in genetics. It is speculated that at least a part of MIS-C patients may have some underlying innate error of immunity (IEI), whether of monogenic, digenic or even oligogenic origin. Goal. Identify patients who present the clinical phenotype of SIM-P, describe their clinical manifestations, laboratory tests and evolution, in addition to search for pathogenic and likely pathogenic genetic variants that may be related to the phenotype through whole exome sequencing. Methodology. Observational, descriptive, case series, longitudinal (retrospective and prospective) and multicenter study. A review of medical records was performed, in addition to laboratory and imaging tests. Blood samples were collected from participating patients for exome sequencing. During the analysis of the genetic variants found, the allele frequency, predictors for evaluating the pathogenicity of the variants and their clinical relevance were considered. Results. A total of 29 patients were included, the median age was 6 years, most patients were female (62%) and only 10% had comorbidities, with asthma being the most common (7%). Patients had a median of 6 days of fever and the most frequent clinical phenotype was acute cardiac dysfunction (48%) followed by patients with Kawasaki-like manifestations (33%). Sixteen patients with pathogenic or likely pathogenic variants were identified. In these cases, a total of 22 variants were identified in 11 different genes: BLK, CFB, ERAP1, FCN3, INFA21, IFIH1, MASP2, MPO, PRF1, TNFRSF13B e ZFHX3. Conclusion. Among the genes identified, there is a predominance of genes related to the complement system, response to viral infection and the B cell function, all important pathways in SARS-CoV-2 infection. To better understand what are the determining factors of this disease, other strategies are needed to search for variants, larger cohorts, studies with healthy controls and other forms of investigation such as analysis of HLA, proteomics and RNAseq.