Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition

Introduction: Hemophagocytic lymphohistiocytosis(HLH) is a systemic inflammatory disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis and up-regulation of inflammatory cytokines. Thus, both HLH and Kawasaki disease(KD) are characterized by prolonged fever, and are diagnosed by a clinical and laboratory scoring system, concurrent manifestation of HLH and KD has been described in the literature. We describe two cases of children who diagnosed as KD initially, but after intravenous gamma globulin(IVIG) failed to produce clinical response, were found to have HLH. Case report: A 3-year-old boy who had previous KD history 5 months ago was admitted for 9day fever and skin rash. His symptoms were fulfilled KD criteria, and echocardiography showed dilated right coronary artery of 4.2mm. He was treated with 2 cycles of IVIG until fever subsided. However, 2 days later, he got fever again and cytopenia(Hb<9.0), hypertriglyceridemia, high level of ferritin was shown and had splenomegaly on physical examination. In the suspicion of HLH, bone marrow biopsy was done and revealed hemophagocytosis, consistent with HLH. A second case of 11-month-old boy admitted for 8-day fever with Kawasaki feature. Although, he showed incomplete feature(fever, skin rash, conjunctival injection, cervical lymphadenopathy), echocardiography showed dilated left main coronary artery(3.5mm) and treated with IVIG. However, 2days after IVIG administration, he was still pyrexial. The laboratory findings fulfilled 5 diagnostic criteria of HLH; bicytopenia(anemia, thrombocytopenia), hypofibrinogenemia, hyperferritinemia, hemophagocytosis in bone marrow, raised level of soluble IL-2 receptor. In both cases, the patients treated according to the HLH protocol 2004, and after that clinical symptoms and laboratory findings were improved. Several causes of febrile illness, EBV, CMV, rubella, parvo-viral infection, for example, were excluded. Comment: There is considerable overlap between the clinical syndromes of KD and HLH and early recognition and treatment of these two disease entity is imperative to avoid fatal outcomes in severe cases. Thus, these should both be considered and excluded in any child with unremitting fever and rash.

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Clinical characteristics of 10 children with a pediatric inflammatory multisystem syndrome associated with COVID-19 in Iran

BMC Pediatrics ◽

10.1186/s12887-020-02415-z ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Leila Shahbaznejad ◽

Mohammad Reza Navaeifar ◽

Ali Abbaskhanian ◽

Fatemeh Hosseinzadeh ◽

Golnar Rahimzadeh ◽

...

Keyword(s):

Kawasaki Disease ◽

Clinical Characteristics ◽

Multiorgan Failure ◽

Gastrointestinal Symptoms ◽

Coronary Aneurysm ◽

Tertiary Hospital ◽

Mazandaran Province ◽

Northern Iran ◽

Therapeutic Modalities ◽

Protein Levels

Abstract Background Although symptoms and signs of COVID-19 (Coronavirus disease 2019) in children are milder than adults, there are reports of more severe cases which were defined as pediatric inflammatory multisystem syndrome (PIMS). The purpose of this report was to describe the possible association between COVID-19 and PIMS in children. Methods From 28 March to 24 June 2020, 10 febrile children were admitted with COVID-19 infection showing characteristics of PIMS in Buali tertiary hospital of Sari, in Mazandaran province, northern Iran. Demographic and clinical characteristics, laboratory and imaging findings, and therapeutic modalities were recorded and analyzed. Results The mean age of the patients was 5.37 ± 3.9 years (13 months to 12 years). Six of them were boys. Kawasaki disease, myocarditis, toxic shock syndrome, appendicitis, sepsis, urosepsis, prolonged febrile seizure, acute hemorrhagic edema of infancy, and COVID-19-related pneumonia were their first presentation. All of them had increased C-reactive protein levels, and most of them had elevated erythrocyte sedimentation rate, lymphopenia, anemia, and hypoalbuminemia. Three of them had thrombocytopenia(PLT < 106). Six of them were serologically or polymerase chain reaction positive for COVID-19, and 4 of them were diagnosed as COVID-19 just by chest computed tomography scan. Most of the patients improved without a residual sequel, except one who died with multiorgan failure and another case was discharged with a giant coronary aneurysm. Conclusions Children with COVID-19 may present symptoms similar to Kawasaki disease and inflammatory syndromes. PIMS should be considered in children with fever, rash, seizure, cough, tachypnea, and gastrointestinal symptoms such as vomiting, diarrhea, and abdominal pain.

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The Augmented Productions of Neopterin and Cytokines from Macrophages/monocytes in vitro

Pteridines ◽

10.1515/pteridines.1996.7.3.72 ◽

1996 ◽

Vol 7 (3) ◽

pp. 72-76

Author(s):

Tadashi Lizuka ◽

Mitsuyo Sasaki ◽

Hitomi Kamisako ◽

Ko Oishi ◽

Shigeru Uemura ◽

...

Keyword(s):

Kawasaki Disease ◽

Interleukin 1 ◽

Poly I:C ◽

Recombinant Interferon ◽

Preliminary Examination ◽

Tnf Α ◽

Ifn Γ ◽

Factor Α ◽

Necrosis Factor

Summary In Kawasaki disease patients, increases in excretion of urinary neopterin coincided with fever and monocytosis in peripheral blood. We examined the products of neopterin, tumor necrosis factor-α (TNFα) and Interleukin-1 β (1L-1β) from healthy adult macrophages/monocytes (Mφ>/M), after stimulation with several activators to obtain some understanding of Kawasaki disease. Upon stimulation with either lipopolysaccharide (LPS) or polyinosinate-polycytidylate (Poly I:C), the Mφ/M released neopterin and pyogenic products (TNF-α or 1L-1β). The release of neopterin was eliminated by the addition of the anti-interferon-y antibody. The production of both TNF-α, 1L-1β and neopterin from Mφ/M upon stimulation of LPS was augmented in a co-culture with low dose recombinant interferon-y (rIFN-γ). Upon stimulation with rIFN-γ alone, however, the Mφ/M released neopterin but not the pyogenic products. A preliminary examination failed to detect. any difference in the response of the Mφ/M in adults annd children after stimulation with LPS. We concluded that some endotoxins could trigger the onset of Kawasaki disease and that endogenous IFN-γ can play an important role in the abnormality of Kawasaki disease patients

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Clinical Characteristics of Hemophagocytic Lymphohistiocytosis Related to Kawasaki Disease

Pediatric Hematology and Oncology ◽

10.3109/08880018.2010.526685 ◽

2011 ◽

Vol 28 (3) ◽

pp. 230-236 ◽

Cited By ~ 17

Author(s):

Hyun Kwon Kim ◽

Han Gyu Kim ◽

Su Jin Cho ◽

Young Mi Hong ◽

Sejung Sohn ◽

...

Keyword(s):

Kawasaki Disease ◽

Hemophagocytic Lymphohistiocytosis ◽

Clinical Characteristics

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Clinical Characteristics and Outcomes of Iranian Patients With Kawasaki Disease

Journal of Comprehensive Pediatrics ◽

10.17795/compreped-13971 ◽

2014 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Iraj Sedighi ◽

Mansoureh Biglari ◽

Mehrnaz Olfat ◽

Habibollah Yadolahi ◽

Asadolah Tanasan ◽

...

Keyword(s):

Kawasaki Disease ◽

Clinical Characteristics ◽

Iranian Patients

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Clinical characteristics of myocardial infarction following Kawasaki disease: Report of 11 cases

The Journal of Pediatrics ◽

10.1016/s0022-3476(86)80982-9 ◽

1986 ◽

Vol 108 (2) ◽

pp. 198-203 ◽

Cited By ~ 36

Author(s):

Hiroyuki Nakana ◽

Akihiro Saito ◽

Ken Ueda ◽

Keiko Nojima

Keyword(s):

Myocardial Infarction ◽

Kawasaki Disease ◽

Clinical Characteristics

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Study of Bone Marrow Mesenchymal Stem Cells Regulating NK Cells Function through Tigit/ CD226 in Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2021-152389 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2685-2685

Author(s):

Rong Fu ◽

Ling Deng ◽

Zhaoyun Liu ◽

Hui Liu ◽

Zonghong Shao

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Nk Cells ◽

Clinical Characteristics ◽

P Values ◽

Marrow Mesenchymal Stem Cells ◽

Ifn Γ ◽

Immune Phenotypes ◽

Killing Function

Abstract Introduction：Bone marrow microenvironment plays a significant supporting role in the proliferation, differentiation, migration, survival and drug resistance of myeloma cells. To detect the expression of the co-inhibitory receptor TIGIT and the co-stimulatory receptor CD226 on the surface of natural killer cells (NK cells) in multiple myeloma (MM) patients, and changes in the immune phenotypes and killing function of NK cells. Furthermore, to explore the underlying mechanism of bone marrow mesenchymal stem cells (BMSCs) regulating NK cells function through TIGIT/CD226 in patients with MM. The expressions of TIGIT, CD226, activated molecules NKG2D and CD107a and functional molecules IFN-γ and Perforin on the NK cells in bone marrow or peripheral blood were detedted by FCM. BMSCs and NK cells were co-cultured at a ratio of 1:4 in vitro, which was grouped according to different monoclonal antibodies (mAbs) added. After co-cultured, the changes in the expression of NKG2D, NKp30, NKp44 and CD69 of NK cells and IFN-γ concentration were examined by FCM. NK cells and U266 were co-cultured with different E:T ratio and the apoptosis of U266 was detected to evaluate the killing function of NK cells by FCM. The expressions of CD155 on BMSCs in the bone marrow were detected by FCM. The correlations between CD155 expression on BMSCs and the production of IFN-γ and Perforin in bone marrow NK cells, as well as clinical characteristics were analyzed. Results: 1. In bone marrow, expression of TIGIT was significantly higher in patients with NDMM than those in patients with CR and HC (both P values <0.01). CD226 was significantly lower in NDMM patients than those in patients with CR and HC (both P values <0.01). NK cell surface activated molecules NKG2D and CD107a, and functional molecules IFN-γ and Perforin were significantly decreased in NDMM (Fig. A). In peripheral blood, TIGIT, CD226 and above immune phenotype expression levels were basically consistent with the trend in bone marrow. 2. In co-culture experiments of BMSCs and NK cells, only added anti-TIGIT mAbs, compared to both added anti-TIGIT and CD226 mAbs, the immune phenotypes of NK cells significantly increased (Fig. B). And the concentration of IFN-γ in the co-culture supernatants also increased (Fig. C). 3. After co-cultured with BMSCs, NK cells were co-cultured again with U266 in vitro, the apoptosis level of U266 in TIGIT mAbs group increased than those in TIGIT+ CD226 mAbs group at different E: T ratio (Fig. D). 4. The expression of CD155, the ligand of TIGIT and CD226, increased notably on the surface of BMSCs in MM patients(P<0.01) (Fig. E). 5. The expression of CD155 on BMSCs was negatively correlated with the production of IFN-γ and perforin in bone marrow NK cells with NDMM patients. And it has correlation with clinical characteristics including β2-MG, LDH, ALB, Hb, ISS stage and R-ISS stage in patients with MM. Summary: BMSCs may regulate NK cells through TIGIT/CD226. High expression of TIGIT on NK cells may mediate the inhibitory effect of BMSCs in MM patients. Blocking TIGIT could restore NK cells activation and killing function. CD155, a common ligand of TIGIT and CD226, was overexpressed on BMSCs in NDMM patients, but was low expressed on bone marrow MM cells. And it has correlation with NK cells function and clinical characteristics, indicating that CD155 may be involved in the regulation of NK cells function by BMSCs. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Coronary lesions suggestive of kawasaki disease in young patients presenting with acute myocardial infarction

European Heart Journal ◽

10.1093/eurheartj/ehab724.2769 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

F Solis-Jimenez ◽

H Gonzalez Pacheco ◽

J Calderon Colmenero ◽

J Cervantes Salazar ◽

D Manzur Sandoval ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Young Adults ◽

Coronary Artery ◽

Kawasaki Disease ◽

Coronary Angiography ◽

Clinical Characteristics ◽

Young Patients ◽

Coronary Aneurysms ◽

Coronary Lesions

Abstract Background Approximately 25% of patients with untreated Kawasaki disease (KD) in childhood develop coronary aneurysms, which represent a higher likelihood for the occurrence of acute myocardial infarction (AMI) in young adults. Although the clinical characteristics of young adults with KD and suspected ischemia have been studied, the available data about suggestive lesions of KD in AMI is scarce. Purpose To describe the prevalence, clinical characteristics and in-hospital mortality of young adults with AMI and coronary artery lesions suggestive of KD. Methods We conducted a retrospective study of consecutive ≤40-year old patients hospitalized with AMI and coronary angiography in a coronary care unit of a Mexican teaching hospital between 2006–2020. Patients were classified according to the presence or absence of suggestive lesions of KD sequelae such as proximal aneurysms, larger size and normal distal segments Results There were included 488 patients of 40 years of age and younger, diagnosed with AMI, in whom a coronary angiography was performed. Among them, 44 patients (9%) showed coronary aneurysm or ectasia, within this group, 16 patients (36.3%) had angiographic lesions compatible with KD. The patients were classified according to the type of coronary lesions: Angiographic lesions compatible with KD, 3.3% (n=16); Diffuse coronary artery ectasia (CAE), 5.7% (n=28); and Obstructive coronary disease (OCD), 91% (n=444). The prevalence of smoking, dyslipidemia, and hypertension were similar between the groups, whereas a history of diabetes was absent in KD patients (0%, 10.7%, and 22.1% for KD, CAE and OCD, respectively; P=0.04). At admission, ST-elevation myocardial infarction was more frequent in patients with KD (81.3%, 75%, and 67.1% for KD, CAE and OCD, respectively; P=0.35). More than half of patients with KD had coronary aneurysms in two or more vessels. The right coronary artery was the most commonly affected artery followed by the left anterior descending artery and left circumflex coronary artery (87.5%, 56.3% and 56.3%, respectively). The presence of intracoronary thrombus identified at the time of angiography was more frequent in patients with KD (62.5%, 60.7% and 44.1% for KD, CAE and OCD, respectively; P=0.09). Overall, unadjusted in-hospital mortality was 3.9% and there were no deaths in the KD group (0%, 0% and 4.3% for KD, CAE, and OCD, respectively; P=0.37). Conclusion In young patients with AMI, the sequelae of KD should be considered as a possible etiology, based on their angiographic characteristics. To bear in mind the nature of the pathogenesis is crucial to assess medical and interventional management strategies, which are not well defined yet, in order to evaluate cardiovascular risk and optimize a patient-tailored treatment, which could differ from the treatment of atherosclerotic coronary artery disease FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

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Kawasaki disease: the importance of early recognition

Residência Pediátrica ◽

10.25060/residpediatr-2019.v9n3-05 ◽

2019 ◽

Vol 9 (3) ◽

pp. 222-227

Author(s):

Rafaela Gonçalves ◽

Sidnei Silva

Keyword(s):

Kawasaki Disease ◽

Early Recognition

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