Oral manifestations of multisystemic inflammatory syndrome in children (MIS-C) and Kawasaki disease associated to COVID-19: A systematic review.
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ABSTRACT: Aims
Multisystemic inflammatory syndrome in children (MIS-C) is a condition noted in some children asymptomatic but positive to Sars-cov-2 antibody and it presents clinical and laboratory changes similar to Kawasaki disease (KD). Oral changes have also been observed. This systematic review evaluated oral manifestations detected in children with MIS-C and KD associated to COVID-19.Methods and results
This work was registered at PROSPERO (#CRD42020225909), following PRISMA guidelines. A comprehensive research was conducted in MEDLINE, Web of Science, EMBASE, LILACS, Scopus, and Grey Literature through August 2021, based on original research evaluating children diagnosed with MIS-C or KD related to COVID-19. Two authors independently screened all retrieved references. Twenty five selected studies evaluated 624 children, mean age 8.78 years. The assessment of the risk of bias (ROB) showed that most of them presented low ROB. Oral manifestations were erythematous mucous membrane, oral ulcers lesions, dry, swollen and cracked lips, and strawberry tongue.Conclusion
MIS-C and KD share the same oral manifestations and their identification may lead to an early diagnosis.
SUBMITTER: Nascimento RB
PROVIDER: S-EPMC8662078 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease.
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Project description:In early 2020, at the beginning of the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare cases were reported in children and adolescents of multisystem inflammatory syndrome in children (MIS-C). MIS-C is characterized by fever, systemic inflammation, and multiorgan dysfunction and usually presents late in SARS-CoV-2 infection. Since May 2020, the Centers for Disease Control and Prevention (CDC) has recorded all reported cases of COVID-19 and MIS-C in children and adolescents in the USA. In April 2021, the American College of Rheumatology (ACR) revised its clinical guidelines for diagnosing and managing hyperinflammation and MIS-C. There are several challenges ahead for preventing, diagnosing, and managing MIS-C, particularly following the rapid emergence of new strains of SARS-CoV-2. This Editorial aims to present an update on the current status of the clinical presentation, diagnosis, and management of MIS-C and includes some updates from population studies and clinical guidelines.
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Project description:Purpose of reviewIn this article, I have reviewed current reports that explore differences and similarities between multisystem inflammatory syndrome in children (MIS-C) and other known multisystem inflammatory diseases seen in children, particularly Kawasaki disease.Recent findingsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronavirus causing the COVID-19 disease which emerged in China in December 2019 and spread rapidly to the entire country and quickly to other countries. Currently, there is a pandemic of SARS-CoV-2 infection that results in 20% of patients admitted to hospital with illness, with 3% developing intractable acute respiratory distress syndrome (ARDS) with high mortality. However, pediatric COVID-19 is still reported to be a mild disease, affecting only 8% of children. Pathogenesis in children is comparable to adults. There are suggested impaired activation of IFN-alpha and IFN regulator 3, decreased cell response causing impaired viral defense, yet the clinical course is mild, and almost all children recover from the infection without major complications. Interestingly, there is a subset of patients that develop a late but marked immunogenic response to COVID-19 and develop MIS-C. Clinical features of MIS-C resemble certain pediatric rheumatologic diseases, such as Kawasaki disease (mucocutaneous lymph node syndrome) which affects small-medium vessels. Other features of MIS-C resemble those of macrophage activation syndrome (MAS). However, recent research suggests distinct clinical and laboratory differences between MIS-C, Kawasaki disease, and MAS. Since the start of the SARS-CoV-2 pandemic, MIS-C has become the candidate for the most common cause of acquired heart disease in children.
| S-EPMC8254432 | biostudies-literature
Project description:ImportanceTo date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms.ObjectiveTo describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020.Design, setting, and participantsA retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C.Main outcomes and measuresLaboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists.ResultsTwenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity.Conclusions and relevanceIn this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.
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Project description:BackgroundAlthough the radiographic features of coronavirus disease 2019 (COVID-19) in children have been described, the distinguishing features of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 are not well characterized.ObjectiveWe compared the chest radiographic findings of MIS-C with those of COVID-19 and described other distinguishing imaging features of MIS-C.Materials and methodsWe performed a retrospective case series review of children ages 0 to 18 years who were hospitalized at Children's Healthcare of Atlanta from March to May 2020 and who either met the Centers for Disease Control and Prevention (CDC) case definition for MIS-C (n=11) or who had symptomatic, laboratory-confirmed COVID-19 (n=16). Two radiologists reviewed the most severe chest radiographs for each patient. The type and distribution of pulmonary opacities and presence or absence of pleural effusions were recorded. The chest radiographs were categorized based on potential COVID-19 imaging findings as typical, indeterminate, atypical or negative. An imaging severity score was also assigned using a simplified version of the Radiographic Assessment of Lung Edema Score. Findings were statistically compared between patients with MIS-C and those with COVID-19. Additional imaging findings of MIS-C were also described.ResultsRadiographic features of MIS-C included pleural effusions (82% [9/11]), pulmonary consolidations (73% [8/11]) and ground glass opacities (91% [10/11]). All of the lung opacities (100% [10/10]) were bilateral, and the majority of the pleural effusions (67% [6/9]) were bilateral. Compared to children with COVID-19, children with MIS-C were significantly more likely to develop pleural effusions on chest radiograph (82% [9/11] vs. 0% [0/0], P-value <0.01) and a lower zone predominance of pulmonary opacifications (100% [10/10] vs. 38% [5/13], P-value <0.01). Children with MIS-C who also had abdominal imaging had intra-abdominal inflammatory changes.ConclusionKey chest radiographic features of MIS-C versus those of COVID-19 were pleural effusions and lower zone pulmonary opacifications as well as intra-abdominal inflammation. Elucidating the distinguishing radiographic features of MIS-C may help refine the case definition and expedite diagnosis and treatment.
| S-EPMC7785920 | biostudies-literature
Project description:BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening hyperinflammatory syndrome that occurs after primary SARS-CoV-2 infection. The pathogenesis of MIS-C remains undefined, and whether specific inflammatory biomarker patterns can distinguish MIS-C from other hyperinflammatory syndromes, including Kawasaki disease and macrophage activation syndrome (MAS), is unknown. Therefore, we aimed to investigate whether inflammatory biomarkers could be used to distinguish between these conditions.MethodsWe studied a prospective cohort of patients with MIS-C and Kawasaki disease and an established cohort of patients with new-onset systemic juvenile idiopathic arthritis (JIA) and MAS associated with systemic JIA (JIA-MAS), diagnosed according to established guidelines. The study was done at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA). Clinical and laboratory features as well as S100A8/A9, S100A12, interleukin (IL)-18, chemokine (C-X-C motif) ligand 9 (CXCL9), and IL-6 concentrations were assessed by ELISA and compared using parametric and non-parametric tests and receiver operating characteristic curve analysis.FindingsBetween April 30, 2019, and Dec 14, 2020, we enrolled 19 patients with MIS-C (median age 9·0 years [IQR 4·5-15·0]; eight [42%] girls and 11 [58%] boys) and nine patients with Kawasaki disease (median age 2·0 years [2·0-4·0]); seven [78%] girls and two [22%] boys). Patients with MIS-C and Kawasaki disease had similar S100 proteins and IL-18 concentrations but patients with MIS-C were distinguished by significantly higher median concentrations of the IFNγ-induced CXCL9 (1730 pg/mL [IQR 604-6300] vs 278 pg/mL [54-477]; p=0·038). Stratifying patients with MIS-C by CXCL9 concentrations (high vs low) revealed differential severity of clinical and laboratory presentation. Compared with patients with MIS-C and low CXCL9 concentrations, more patients with high CXCL9 concentrations had acute kidney injury (six [60%] of ten vs none [0%] of five), altered mental status (four [40%] of ten vs none [0%] of five), shock (nine [90%] of ten vs two [40%] of five), and myocardial dysfunction (five [50%] of ten vs one [20%] of five); these patients also had higher concentrations of systemic inflammatory markers and increased severity of cytopenia and coagulopathy. By contrast, patients with MIS-C and low CXCL9 concentrations resembled patients with Kawasaki disease, including the frequency of coronary involvement. Elevated concentrations of S100A8/A9, S100A12, and IL-18 were also useful in distinguishing systemic JIA from Kawasaki disease with high sensitivity and specificity.InterpretationOur findings show MIS-C is distinguishable from Kawasaki disease primarily by elevated CXCL9 concentrations. The stratification of patients with MIS-C by high or low CXCL9 concentrations provides support for MAS-like pathophysiology in patients with severe MIS-C, suggesting new approaches for diagnosis and management.FundingCincinnati Children's Research Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, the Deutsche Forschungsgemeinschaft, and The Jellin Family Foundation.
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Project description:Multisystem Inflammatory Syndrome in Children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by SARS-CoV-2 antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism, distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that the hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature.
2022-11-05 | GSE217370 | GEO
Project description:To conduct a systematic review and meta-analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS-C) versus severe/non-severe COVID-19, severe MIS-C versus non-severe MIS-C, and among age groups of MIS-C. Nine databases were searched for studies on inflammatory markers of MIS-C. After quality checks, data were pooled using a fixed or random effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), ferritin, D-dimer, lactate dehydrogenase (LDH), fibrinogen, and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty-one studies with 1735 participants yielded 787 MIS-C patients. Compared to non-severe COVID-19 patients, MIS-C patients had lower ALC and higher ANC, CRP, and D-dimer levels. Compared to severe COVID-19 patients, MIS-C patients had lower LDH and PLT counts and higher ESR levels. Severe MIS-C patients had higher levels of WBC, ANC, CRP, D-dimer, and ferritin than non-severe MIS-C patients. For MIS-C, younger children (0-5 years) had lower CRP and ferritin levels than middle-aged/older children/adolescents. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS-C and the associated disorders.
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Project description:In recent months, there are increasing reports of a Kawasaki disease-like syndrome in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed 'Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS)' in the UK. Debate is ongoing regarding the nature of these pro-inflammatory syndromes. We herein propose that the platelet count may, at least in part, be able to help us differentiate between the two aforementioned syndromes. In a recent report, compared to a historical 'classical' Kawasaki disease (KD) cohort, patients with PIMS-TS had significantly lower platelet counts (188 vs 383 g/L, p < 0.0001). A possible explanation for this is their difference in underlying immunopathogenesis. In KD, the fundamental pathogenesis is thought to be immune complex-mediated, hence, the use of intravenous immunoglobulin (IVIg) which competes with the immunoglobulin Fc receptors (FcRs) on inflammatory cells, preventing the activation of these cells and thereby ameliorating the inflammatory response. If left untreated, these immune complexes activates the inflammatory cells (including monocytes and neutrophils), which also results in recruitment of platelets, resulting in the thrombocytosis we commonly see in KD. These immune complexes may also bind to platelets directly via FcRs on platelet membranes. In contrast, in viral-associated hyperinflammatory syndromes (e.g. PIMS-TS or MIS-C), there are mediators being secreted in the process of eradication of the virus (mainly to stimulate CD8+ cells to kill viral infected cells), which would inadvertently suppress bone marrow function and activate platelets, culminating in thrombocytopenia.
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Project description:To evaluate the macular and optic nerve head (ONH) vascular density, foveal avascular zone area, and outer retina and choriocapillaris flow in Multisystemic Inflammatory Syndrome in Children (MIS-C) using optical coherence tomography angiography (OCTA). Thirty-four eyes of 34 patients with MIS-C and 36 age and sex-matched healthy controls were investigated in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus (DCP), ONH, FAZ parameters, the flow area of the outer retina, and choriocapillaris were evaluated using OCTA. All VD parameters in SCP were significantly lower in MIS-C patients. There was no significant difference between the groups in VD parameters of both DCP and ONH, as well as FAZ area and FAZ perimeter. However, foveal density (FD-300) was significantly decreased in the MIS-C group. (p = 0.024). The outer retina flow area at 1 mm, 2 mm, and 3 mm radius and CC flow area at 1 mm and 2 mm radius were significantly lower in the MIS-C group than in the control group. Although CC flow area at 3 mm radius was decreased in the MIS-C group compared to healthy controls, the difference was not statistically significant. We demonstrated a decreased vessel density in SCP, choriocapillaris flow area, and outer retinal flow area in MIS-C patients. Hence, we proposed that OCTA could reveal retinal and choroidal microvascular changes in MIS-C patients who were completely healthy before the diagnosis of MIS-C.
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