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

2021 ◽  
Vol 9 ◽  
Author(s):  
Satoshi Takasago ◽  
Aiko Sakai ◽  
Masaya Sugiyama ◽  
Masashi Mizokami ◽  
Hiromichi Hamada ◽  
...  

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.

2021 ◽  
Vol 8 ◽  
pp. 2333794X2199661
Author(s):  
Anuja R. Shikhare ◽  
Rimsha M. Iqbal ◽  
Rabail Tariq ◽  
Daniel R. Turner ◽  
Bassam M. Gebara ◽  
...  

COVID-19 is generally a benign or asymptomatic infection in children, but can occasionally be severe or fatal. Delayed presentation of COVID-19 with hyperinflammation and multi-organ involvement was recently recognized, designated the Multisystem Inflammatory Syndrome in Children (MIS-C). Six children with MIS-C with molecular and serologic evidence of SARS-CoV-2 infection were admitted to our hospital between May 5, 2020 and June 25, 2020. All had fever and weakness; 4/6 presented with gastrointestinal symptoms. Two children had features of complete Kawasaki disease, 3 had incomplete Kawasaki disease, while 1 had terminal ileitis with delayed onset of circulatory shock. Treatment consisted of intravenous immunoglobulin and aspirin for Kawasaki-like disease. Remdesivir, corticosteroids, and infliximab were used when indicated. Median hospitalization was 7 days. Immediate treatment resulted in rapid clinical improvement. In children presenting with hyperinflammatory syndromes without cardiac manifestations, testing for SARS-CoV-2 RNA and antibodies, with close cardiac monitoring should be pursued due to the manifold presentations of SARS-CoV-2 infection in children.


2020 ◽  
Vol 99 (6) ◽  
pp. 209-219
Author(s):  
L.V. Bregel ◽  
◽  
M.M. Kostik ◽  
L.Z. Fell ◽  
O.S. Efremova ◽  
...  

During the COVD-19 pandemic, some pediatric patients in many countries around the world experienced a syndrome resembling a severe Kawasaki disease (KD), often accompanied by shock. Due to the incomplete signs of the classic KD in the era before the present pandemic, in many publications from European countries and the United States, this condition was called «multisystem inflammatory syndrome in children – MIS-C» or «hyperinflammatory shock» or «Kawasaki-like syndrome». This syndrome with a new coronavirus infection is characterized by refractory fever, frequent gastrointestinal symptoms, heart damage (including coronary dilation in some patients, and acute left ventricular failure in the majority), increased ESR and CRP levels, neutrophilia, extremely high troponin levels, increased ferritin, AST, ALT, lactate dehydrogenase, creatine phosphate kinase, interleukin-6 and interleukin-10, coagulopathy with an increase in D-dimer and fibrinogen, thrombocytopenia, sometimes procalcitonin increase. The manifestations of a cytokine storm may meet the criteria for secondary hemophagocytic syndrome. The mechanism of myocardial damage remains unclear. Treatment with high-dose intravenous immunoglobulin is effective, and in the presence of signs of hemophagocytic syndrome, dexamethasone or methylprednisolone. Further research is needed to understand the pathogenesis, resemblance and differences of this syndrome with classic KD, understanding of heart injuiry and early recognition for the need of urgent care.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Carles Bautista ◽  
Joan Sanchez-de-Toledo ◽  
Clark C Bradley ◽  
Jetrho Herberg ◽  
Fanny Bajolle ◽  
...  

Introduction: Following the SARS-CoV-2 pandemic peak, children suffering from a multiorgan inflammatory disease that often leads to shock have been reported. This condition shares features with Kawasaki disease, but its etiopathogenesis is unknown. Hypothesis: We aimed to describe presentation and hospital course for this pediatric inflammatory multisystemic syndrome associated with COVID-19 (PIMS-TS). Methods: Data were collected from a retrospective review of children from 33 participating European, Asian and American sites. Results: We included 183 patients (109 males, 59·6%) with PIMS-TS, at a mean age of 7·0 (±4·7) years. Fifty-six (30·6%) had black ethnicity and obesity was present in 48 (26·2%) cases. Overall, 114/183 (62·3%) had biological evidence of current or recent SARS-CoV-2 infection. At admission, all presented with fever, 117/183 (63·9%) with gastrointestinal symptoms and 79/183 (43·2%) with shock, that was associated with more frequent black ethnicity, higher inflammatory markers and more cardiac involvement. Twenty-seven patients (14·7%) fulfilled criteria for Kawasaki disease. They were younger with no shock, fewer gastrointestinal, cardio-respiratory and neurological symptoms. Among the remaining PIMS-TS patients, 77 (49·3%) had mainly fever and inflammation with less cardiac involvement. For the entire cohort of 183 patients, the mean duration of admission was 8·6 (±5·6) days. Inotropic support, mechanical ventilation and ECMO were indicated in 72 (39·3%), 43 (23·5%) and 4 (2·2%) patients, respectively. Three patients (1·6%) died. A shorter duration of symptoms before admission was a risk factor for worse outcome and for ECMO/death, with 63% increased risk per day reduction (95%CI 0·39-0·93, p=0·03) and with 51·4% increased risk per day reduction (95%CI 0·36-0·9, p=0·03), respectively. Conclusions: We describe the first largest international series of children with PIMS-TS. Life-threatening shock is a common presentation. A shorter duration of symptoms prior to admission characterizes the fulminant form of the disease with potentially worse outcome.


Author(s):  
Stasa Krasic ◽  
Sergej Prijic ◽  
Predrag Minic ◽  
Gordana Petrovic ◽  
Dejan Nesic ◽  
...  

The novel coronavirus disease (COVID-19) may induce multisystem inflammatory syndrome in children, which may be associated with Kawasaki-like disease, and cardiac injury. In this study, we presented three male adolescents with multisystem inflammatory syndrome and myocardial injury admitted to the hospital during the peak of COVID-19 pandemic. All of the three patients had a history of fever, gastrointestinal symptoms, polymorph rash, non-exudative conjunctivitis, and signs of acute myocarditis. One of them had renal failure. Previously, they did not have an acute infection. Upon admission, they were hypotensive and tachycardic. A nasopharyngeal swab for SARS-CoV-2 on reverse transcription-polymerase chain reaction (PCR) assay was negative, but neutralizing viral antibodies were positive. In combination with blood tests, ECG, echocardiography and computerized tomography (CT), a multisystem inflammatory syndrome associated with acute myocarditis with mild to moderate systolic dysfunction and dilated coronary arteries were diagnosed. Two of three patients had shock syndrome and required inotropic support. All patients were treated with intravenous immunoglobulins. The second patient had a fever up to 102.2°F (39°C) three days after intravenous immunoglobulins. Further, he was treated according to protocols for refractory Kawasaki disease, with an intravenous methylprednisolone pulse therapy and aspirin. After a few hours, he became afebrile and the clinical signs disappeared. The favorable short-term outcome may reflect the early recognition and adequate therapy; however, the long-term outcomes are currently unknown.


2021 ◽  
Vol 26 (4) ◽  
pp. 318-338
Author(s):  
Van L. Tran ◽  
Sarah Parsons ◽  
Andrew Nuibe

Multisystem Inflammatory Syndrome in Children (MIS-C) was first recognized as a novel illness in 2020 with manifestations similar to other hyperinflammatory syndromes, such as Kawasaki disease or macrophage activation syndrome. Severity varies from a self-limited febrile illness to shock requiring inotropes and mechanical ventilation. Gastrointestinal symptoms and persistent fevers are the most common clinical symptoms, with the addition of cardiac manifestations inclusive of ventricular dysfunction and coronary artery aneurysms. With no controlled trials or comparative effectiveness studies evaluating treatment of MIS-C to date, current treatment with immunomodulatory agents has mainly been derived from previous experience treating Kawasaki disease. This article provides a comprehensive review summarizing published data for the evaluation and management of MIS-C, with a focus on pharmacotherapy treatment considerations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Men-Ren Chen ◽  
Ho-Chang Kuo ◽  
Yann-Jinn Lee ◽  
Hsin Chi ◽  
Sung Chou Li ◽  
...  

Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-β). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called “Know thyself, enemy (pathogen), and ever-victorious” strategy for the prevention and immunotherapy of KD and/or MIS-C.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1114.2-1114
Author(s):  
P. Ostojic ◽  
M. Atanaskovic ◽  
M. Vujovic ◽  
M. Perovic

Objectives:This study aims to assess prevalence, severity and clinical correlates of symptoms of autonomic dysfunction in patients with SScMethods:Fifty five consecutively recruited SSc patients were included in this study. Thirty seven (67.3%) patients had limited (lcSSc), whilst 18 (32.7%) patients had diffuse cutaneous SSc (dcSSc). Anticentromere antibodies (ACA) were positive in 31 (56.4%) of patients, whilst 20 (26.4%) patients had anti-topoisomerase I antibodies (ATA). All patients completed the Composite Autonomic Symptom Score (COMPASS-31) questionnaire, which consists of 31 items, quantifying six autonomic domains: orthostatic intolerance (OI), vasomotor (VD), secretomotor (SD), gastrointestinal (GD), bladder (BD) and pupillomotor dysfunction (PD). The total score ranges from 0 to 100, whilst scores for particular domains range as follows: 0-40 for OI, 0-5 for VD, 0-15 for SD, 0-25 for GD, 0-10 BD, and 0-5 for PD. Higher values representing more severe symptoms. Differences in total COMPASS-31 score and domain-specific scores were assessed with respect to disease form, antibody status, capillaroscopic findings, lung diffusing capacity and joint involvement. Moreover, we assessed the correlation between COMPASS-31 scores, disease status (assesed using the Scleroderma Assessment Questionnaire – SAQ) and severity of gastrointestinal symptoms (assessed using the UCLA SCTC GIT 2.0 questionnaire)Results:Percentage of SSc with a score >0 in particular domains of the COMPASS-31 were as follows: OI – 32/55 (58.2%), VD – 49/55 (89.1%), SD – 36/55 (65.5%), GD – 40/55 (72.7%), BD - 26/55 (47.3%), PD – 30/55 (54.5%). The COMAPSS-31 score did not correlate with age or disease duration. There was no relationship between the COMPASS-31 total or subdomain scores and SSc subtype or autoantibody status. Similar mean values for total and subdomain scores were found among patients with different capillaroscopic patterns. Patients with DLCO < 80% had significantly higher mean values of GD, BD and PD scores, compared to patients with DLCO≥80% (4.42 vs 2.75, 1.51 vs 0.38, 1.93 vs 1.09, respectively). Moreover, the total COMAPSS-31 score was significantly higher in patients with decreased DLCO (16.24 vs 11.34, p=0.008). Patients with joint involvement had higher COMPASS-31 score than patients without (17.74 vs 9.85, p=0.012). We have found a statistically significant (p<0.001) correlation between the COMPASS-31 score and the Index of disease status (IDS), as well as the the total UCLA SCTC GIT score (rho=+0.45, rho=+0.51, respectively).Conclusion:Symptoms of dysautonomia are common in SSc patients. Patients with a more severe disease, especially decreased lung diffusing capacity, joint pain, and severe gastrointestinal involvement, report more symptoms of autonomic dysfunction.Disclosure of Interests:None declared


2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Rahul D. Bhiwgade ◽  
M. C. Nischitha ◽  
Bhushan Shahare ◽  
Shobhna Bitey

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ji-Gan Wang ◽  
Zhi-Juan Zhong ◽  
Meng Li ◽  
Jun Fu ◽  
Yu-Heng Su ◽  
...  

Background. This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice. Methods. We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity. Results. A total of 57 articles (2,290 pediatric patients) were included in the study. Clinical Manifestations. :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67–100%), 82.72% (95% CI: 78.19–86.81%), 53.02% (45.28–60.68%), and 14.16% (95% CI: 8.4–21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73–63.87%), 55.23% (95% CI: 50.22–60.19%), 27.07% (95% CI: 19.87–34.93%), 46.37% (95% CI: 39.97–52.83%), 28.87% (95% CI: 22.76–35.40%), 28.75% (95% CI: 21.46–36.64%), 17.32% (95% CI: 15.44–19.29%), and 36.19% (95% CI: 21.90–51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and N-terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. PICU Hospitalization Rate and Mortality. The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. Conclusion and Relevance. PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.


Author(s):  
Jun Yasuhara ◽  
Kae Watanabe ◽  
Hisato Takagi ◽  
Naokata Sumitomo ◽  
Toshiki Kuno

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has been increasingly recognized. However, the clinical features of MIS-C and the differences from Kawasaki disease remain unknown. The study aims to investigate the epidemiology and clinical course of MIS-C. Methods: PubMed and EMBASE were searched through August 30, 2020. Observational studies describing MIS-C were included. Data regarding demographic features, clinical symptoms, laboratory, echocardiography and radiology findings, treatments, and outcomes were extracted. Study-specific estimates were combined using one-group meta-analysis in a random-effects model. Results: A total of 27 studies were identified including 917 MIS-C patients. The mean age was 9.3 (95% confidence interval [CI], 8.4-10.1). The pooled proportions of Hispanic and Black cases were 34.6% (95% CI, 28.3-40.9) and 31.5% (95% CI, 24.8-38.1), respectively. The common manifestations were gastrointestinal symptoms (87.3%; 95% CI, 82.9-91.6) and cardiovascular involvement such as myocardial dysfunction (55.3%; 95% CI, 42.4-68.2), coronary artery aneurysms (21.7%; 95% CI, 12.8-30.1) and shock (65.8%; 95% CI, 51.1-80.4), with marked elevated inflammatory and cardiac markers. The majority of patients received intravenous immunoglobulin (81.0%; 95% CI, 75.0-86.9), aspirin (67.3%; 95% CI, 48.8-85.7), and corticosteroids (63.6%; 95% CI, 53.4-73.8) with a variety of anti-inflammatory agents. Although myocardial dysfunction improved in 55.1% (95% CI, 33.4-76.8) at discharge, the rate of extracorporeal membrane oxygenation use was 6.3% (95% CI, 2.8-9.8) and the mortality was 1.9% (95% CI, 1.0-2.8). Conclusion: Our findings suggest that MIS-C leads to multiple organ failure, including gastrointestinal manifestations, myocardial dysfunction and coronary abnormalities, and has distinct features from Kawasaki disease.


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