The cerebrospinal fluid changes and clinical characteristics of aseptic meningitis in Kawasaki disease

The cerebrospinal fluid changes and clinical characteristics of aseptic meningitis in Kawasaki disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research article The cerebrospinal fluid changes and clinical characteristics of aseptic meningitis in Kawasaki disease Fan Hu, Xiaoqing Shi, Yang Fan, Hanmin Liu, Kaiyu Zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-16533/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Aseptic meningitis is not a common feature in Kawasaki disease (KD). However, it could cause difficulty in making correct and in-time diagnosis Methods: We retrospectively investigated patients of KD and bacterial meningitis (BM). Totally 38 KD patients and 126 BM patients were brought into this study. Clinical symptoms, signs and laboratory examinations were compared between the two groups, which included: duration of fever before lumbar puncture, conjunctiva injection, oral cavity change, rash, cervical lymphadenopathy and extremities change, vomiting, front fontanel bulging, neck stiffness, leukocytes, hemoglobin, platelets, C-reactive protein, cerebrospinal fluid examinations, liver function and urinalysis. Results: In clinical signs, vomit and neck stiffness were more prevalent in BM. KD patients showed higher blood leukocyte (p<0.001) and C-reactive protein (p<0.001) in the early febrile stage. Glucose in cerebrospinal fluid of BM patients was significantly lower than KD patients (p=0.003). In ROC curve, the optimal cutoff value of CSF glucose was 2.945mmol/L with the sensitivity of 84.2% and specificity of 71.4%. Pyuria was more prevalent in KD patients (p<0.001). There was no significant difference in front fontanel bulging, hemoglobin, platelet, alanine transaminase, aspartate transaminase, albumin, cerebrospinal fluid leukocytes, cerebrospinal fluid protein and cerebrospinal fluid lactate dehydrogenase. Conclusions ： Full investigation of clinical manifestation and laboratory tests is necessary to distinguish KD with aseptic meningitis and BM. In CSF study, glucose level is more efficient than other items to distinguish these two diseases. Decreased CSF glucose is possibly an indicator of BM rather than KD. Rheumatology Pediatrics Kawasaki disease aseptic meningitis bacterial meningitis cerebrospinal fluid. Figures Figure 1 Background Kawasaki disease (KD) is an acute febrile disease that happens major in children < 5 years [ 1 ] . As a kind of systemic vasculitis, except for the principal clinical features including fever, extremity changes, conjunctivitis, rash, oral changes and cervical lymphadenopathy, it has various clinical manifestations [ 2 ] . Aseptic meningitis is not a common feature in KD. However, it could cause difficulty in making correct and in-time diagnosis [ 3 ] . Although lumbar puncture is suggested to distinguish infectious disease from KD, sometimes the abnormal cerebrospinal fluid (CSF) results in confused diagnosis especially at the beginning of the disease [ 4 ] . There are plenty of children with atypical clinical characteristics which make it difficult to draw to a definite diagnosis. The clinicians had to use both immunogloubulin and antibiotics simultaneously. Patient of KD with elevated leukocytes, neutrophil cells and C-reactive protein (CRP) in blood and pleocytosis in CSF may easily be misdiagnosed as bacterial meningitis (BM) in the early febrile stage. Besides, limited studies [ 5 , 6 ] focused on the characteristic of cerebral fluid in KD, and the data was adopted from American and Japanese patients. In this study, we retrospectively investigated the KD patients with aseptic meningitis in our hospital and compared it with BM in order to establish the characteristic of KD patients with aseptic meningitis and to find out how to distinguish this disease from bacterial meningitis. Methods Population KD patients with aseptic meningitis and BM patients admitted in our department were enrolled for retrospective investigation from January 2011 to December 2019. Totally 38 patients of KD with the diagnosis of aseptic meningitis met the inclusive criteria. Besides, the patients of bacterial meningitis were also investigated as control group. Since most of the KD patients were admitted with duration of fever within10 days, we chose the BM patients with fever ≤ 10 days in order to study the early change of CSF. Totally 126 patients of bacterial meningitis were brought into the control group. All the patients in this study should have the following data: CSF results, count of blood cells,C-reactive protein (CRP), liver function, urinalysis. Patients with CSF erythrocyte ༞1 × 10 6 /L, which suggested trauma lumbar puncture, was excluded. Patients with lumbar puncture after intravenous immunogloubulin (IVIG) treatment were excluded to avoid confusion with aseptic meningitis induced by IVIG [ 7 , 8 ] . Moreover, in case records, there should be complete description of the symptoms and physical examination including oral cavity, skin change, conjunctiva, lymph nodes, extremities, and nerves system change. Clinical Data The following clinical data were collected from the groups: Age; gender; duration of fever before lumbar puncture; the five clinical features of KD (conjunctiva injection, oral cavity change, Rash, cervical lymphadenopathy and extremities change); nerves system change including vomiting, front fontanel bulging and neck stiffness. In laboratory tests, we investigated blood leukocytes, hemoglobin, platelets (PLT), CRP; CSF parameters including leukocytes, glucose, protein and lactate dehydrogenase (LDH); liver function and urinalysis. Statistics Data were studied by SPSS 23.0 software. The data in two groups were compared with independent samples t test. Pearson chi-squre test or Fisher’s exact test was used for the compare of constituent ratio in the two groups. In order to study the glucose level in CSF distinguishing KD patients from BM patients, receiver operating characteristic (ROC) curve was constructed. Statistical significance was considered p value < 0.05 Results Clinical characteristics The clinical characteristics of the patients in the two groups are summarized in Table 1 . The age and gender in the two groups showed no significant difference. Since the BM patients were chosen with duration of fever no more than 10 days, which was similar with the acute stage of KD, the two groups showed no significant difference on this point (p = 0.867). Only a very little portion of the BM patients manifested the five typical features of KD including 1 patients with oral cavity change, 3 patients with rash, 7 patients with cervical lymphadenopathy (p < 0.05). We also investigated the nerves system changes. Vomiting, which could be a symptom of intracranial hypertension, appeared in 49 out of 126 patients in BM group. However, only 2 out of 38 KD patients with aseptic meningitis had vomiting (p < 0.001). Neck stiffness appeared in 17 KD patients and 99 BM patients (p = < 0.001). Besides, either in KD patients or in BM patients, front fontanel bulging seemed to be a frequent sign (p = 0.594) if the front fontanel was unclosed. Table 1 Clinical characteristics of Kawasaki disease and bacterial meningitis patients KD (n = 38) BM (n = 126) P Age (months) 22.0 ± 23.4 26.3 ± 25.4 0.345 Gender Male 17 67 0.362 Female 21 59 Duration of fever (days) 5.7 ± 1.4 5.5 ± 1.8 0.446 Conjunctiva injection 35 0 < 0.001* Oral cavity change 34 1 < 0.001* Rash 32 3 < 0.001* Cervical lymphadenopathy a 15 7 < 0.001* Extremities change 19 0 < 0.001* Vomiting 2 49 < 0.001* Neck stiffness 17 99 < 0.001* Front fontanel bulging b 15 (n = 19) 38 (n = 45) 0.594 a: the cervical lymphadenopathy means the typically enlarged cervical lymph nodes ≥ 1.5 cm which meet the criteria of KD. b: Front fontanel bulging could only be observed in young children with unclosed front fontanel. In KD group there were 19 patients with unclosed front fontanel and in BM group 48 patients. * p < 0.05 Abbreviations: KD = Kawasaki disease BM = bacterial meningitiss Laboratory Examinations The laboratory examinations of the two groups are listed in Table 2 . The leukocyte count, protein and LDH in CSF showed no significant difference between the two groups. Notably, BM group showed a lower level of glucose compared with KD group (p = 0.003). The leukocytes and CRP in the blood of KD group were significantly higher than BM group (p < 0.001). Although anemia and thrombocytosis were prevalent in KD, in this study the hemoglobin and platelet level in the two groups seemed to have no significant difference. In both groups, there was elevation of alanine transaminase (ATL) and aspartate transaminase (AST) level. However, neither ALT and AST nor albumin in the two groups showed significant difference. There was 7 patient in KD group and no patient in BM group with pyuria, and the difference showed significance (p < 0.001). We constructed ROC curve (Fig. 1 ) to learn the glucose level in CSF, the area under the curve was 0.868. The optimal cutoff value of glucose level in CSF to distinguish KD and BM was 2.945 mmol/L with the sensitivity of 84.2% and specificity of 71.4%. Table 2 Laboratory examinations of Kawasaki disease and bacterial meningitis patients Laboratory examination (median, range) KD (n = 38) BM (n = 126) P CSF Leukocytes (× 10 6 /L) 107.5(10–340) 115 (10-2270) 0.097 Glucose (mmol/L) 3.37(2.50–5.30) 2.71(1.18-4.00) 0.003* Protein (mg/L) 632.4(270.8-1054.6) 610(196.2-2722.1) 0.276 LDH (U/L) 37.5(16–56) 34.5(14–98) 0.253 Blood Leukocytes (× 10 9 /L) 17.2(9.7–27.5) 13.65(7.7–23.8) < 0.001* Hemoglobin (g/L) 110.5(78–126) 114(79–142) 0.241 Platelets (× 10 9 /L) 368(123–604) 397.5(109–744) 0.137 C-reactive protein 64.5(28–180) 26(8–81) < 0.001* Liver function ALT 35.5(7-173) 37(9-460) 0.541 AST 31(16–213) 39.5(15–432) 0.356 Albumin 37.35(27.3–46.0) 38.25(30.8–47.4) 0.059 Pyuria 7 0 < 0.001* * p < 0.05 Abbreviations: KD = Kawasaki disease BM = bacterial meningitis CSF = cerebrospinal fluid LDH = lactate dehydrogenase ALT = alanine transaminase AST = aspartate transaminase Discussion Except for the typical five clinical features, KD could have multiple other manifestations including arthritis, aseptic meningitis, colitis, etc [ 9 – 11 ] . Indeed, KD in early stage with atypical manifestations often leads to misdiagnosis. The persistent fever, nerves system symptom and signs, elevated leukocyte count and CRP could sometimes result in confusion with bacterial meningitis [ 12 ] . In this study, we investigated the symptoms, physical examinations and laboratory tests of KD and BM patients. The typical five features of KD seemed to be rare in BM patients. Neck stiffness and vomit were more prevalent in BM patients. Front fontanel bulging in younger patients was common in both KD patients and BM patients. In CSF examination, the glucose in BM patients showed a lower level compared with KD patients. The leukocytes and protein in CSF of both groups were in a wide range, however, the difference showed no significance. KD patients showed higher blood leukocytes and CRP than BM patients. The examination of liver function and urine test in the two groups remained no significant difference. None of the BM patients in this study had pyuria which was not rare in KD patients. KD is a kind of systemic vasculitis with multiple manifestations. On the other hand, BM is sort of a focalized disease mainly affects central nerves system. The typical five features, which suggest a systemic inflammation, rarely appear in BM patients. Rash especially haemorrhagic rash may be found in BM patients of children. However, it is more frequent in meningococcal meningitis (61%) rather than in pneumococcal meningitis (9%) [ 13 ] . In this study, none of the patients in BM group was documented meningococcal meningitis and only 3 patient had skin rash. Vomiting is reported in 55–67% children with BM [ 13 – 15 ] . However, previous studies did not focus on this symptom in KD [ 5 , 6 ] . Besides, in 3 case reports, vomiting appeared in none of the patients of KD with aseptic meningitis [ 4 , 16 , 17 ] . In this study, only two of the KD patients presented with vomiting. Based on the findings above, we consider maybe vomiting is less frequent in KD compared with BM patients. The possible reason is that the intracranial hypertension of aseptic meningitis in KD is less prominent than that in BM. Lumbar puncture is often considered to exclude infectious disease from KD [ 18 ] . However, in this study, the CSF results suggested that leukocytes, protein, LDH in the two groups showed no significant difference. However, glucose in BM patients was at a lower level than KD group. ROC curve indicates 2.945 mmol/L as the optimal cutoff value. Other studies also suggested that decrease in CSF glucose was not prevalent in KD patients [ 5 , 6 ] . Although we can’t easily exclude BM only with normal glucose in CSF because CSF glucose in either KD patients or BM patients could be normal, it seems that obvious decreased CSF glucose level strongly suggests the diagnosis of BM. Both KD and bacterial infection could result in elevation of blood leukocytes and CRP. Previous study suggested that CRP was not specific in diagnosis of KD compared with bacterial infections [ 18 ] . However, we observed in our study a higher leukocyte and CRP level in KD patients compared with BM patients. The possible reasons may be as follows. First, the sample size is quite limited. Second, in order to be comparable with KD, we chose BM patients with fever no more than 10 days. At this period, the inflammatory reaction of KD possibly reached the highest level, but in BM, it was still in an early stage. Anyhow, relative higher CRP level might be helpful in excluding BM in a relative early stage of fever. The change in liver function including ALT and albumin is considered as auxiliary laboratory findings in the diagnosis of KD [ 1 ] . Meanwhile, bacterial infections including BM could also result in elevated ALT and AST level and decreased albumin level [ 20 – 21 ] . In this study, the change of ALT, AST and albumin manifested no significant difference in the two groups and the result suggested that ALT, AST and albumin were not indicators in distinguishing between KD and BM patients. Pyuria is another clinical manifestation of KD with an incidence of 38% [22] . In this study, 7 out of the 38 KD patients had pyuria while none of the BM patients had. As a kind of systemic vasculitis, KD is more likely than BM to manifest both pyuria and CSF pleocytosis. In summary, full investigation of clinical manifestation and laboratory tests is necessary to distinguish KD with aseptic meningitis and BM. In CSF study, glucose level is more efficient than other items to distinguish these two diseases. Decreased CSF glucose is possibly an indicator of BM rather than KD. Abbreviations ALT= alanine transaminase AST= aspartate transaminase BM= bacterial meningitis CRP=C-reactive protein CSF=cerebrospinal fluid IVIG=intravenous immunoglobulin KD= Kawasaki disease LDH=lactate dehydrogenase PLT=platelet ROC=receiver operating characteristic Declarations Ethics approval and consent to participate All the patients in this study have given informed consent including permission of using clinical data. The study was approved by the ethic committee of West China Second University Hospital of Sichuan University. Consent for publication Not applicable Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was supported by grants from the National Natural Science Foundation of China (No. 81570369, 81741025) and Sichuan Province Science and Technology Support Program, China (No.2018SZ0180). Authors' contributions FH contributed to the design of the work, interpretation of data and has drafted the work. XQS was a major contributor to acquisition of data. YF contributed to acquisition and analysis of data. HML contributed the conception of the work and substantively revised it. KYZ was a major contributor to design of the work and substantively revised it. Acknowledgements Not applicable References [1] McCrindle BW, Rowley AH, Newburger JW. et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-e999. [2] Singh S, Jindal AK, Pilania RK. Diagnosis of Kawasaki disease. Int J Rheum Dis. 2018 Jan; 21(1): 36-44. [3] Rossi M, Siani P, Grossi A, et al. Aseptic meningitis as onset of Kawasaki disease. Minerva Pediatr. 2019 Jan 17. [Epub ahead of print] [4] Türel O, Güzeltaş A, Aydoğmuş C. Kawasaki disease presenting as meningitis in a two months old infant. Anadolu Kardiyol Derg. 2011 Jun; 11(4): 369-70. [5] Dengler LD, Capparelli EV, Bastian, et al. Cerebrospinal fluid profile in patients with acute Kawasaki disease. Pediatr Infect Dis J. 1998 Jun;17(6):478-81. [6] Yeom JS, Park JS, Seo JH, et al. Initial characteristics of Kawasaki disease with cerebrospinal fluid pleocytosis in febrile infants. Pediatr Neurol. 2012 Oct;47(4):259-62. [7] Yasushi K, Tomotaka N, Hiroyuki M, et al. Clinical characteristics of aseptic meningitis induced by intravenous immunoglobulin in patients with Kawasaki disease[J]. Pediatr Rheumatolon Online, 2011, 9(1):28-28. [8] Cho A R, Park J Y, Kim K H, et al. Aseptic Meningitis Secondary to High-Dose Intravenous Immunoglobulin Therapy in Kawasaki Disease[J]. Korean Journal of Pediatrics, 2004, 47(5). [9] Peng Y , Liu X , Duan Z , et al. Prevalence and characteristics of arthritis in Kawasaki disease: a Chinese cohort study[J]. Clinical and Experimental Medicine, 2019. [10] Zhang Y, Wan H, Du M, et al. Capillary leak syndrome and aseptic meningitis in a patient with Kawasaki disease: A case report[J]. Medicine, 2018, 97(23):e10716. [11] Ohnishi Y, Mori, Kazuhiro, Inoue, Miki, et al. A case of Kawasaki disease presenting as sigmoid colitis[J]. Journal of Medical Ultrasonics, 2017, 45(2):1-4. [12] Eleftheriou D, Levin M, Shingadia D et al. Management of Kawasaki disease. Arch Dis Child 2014;99:74_83. [13] Vasilopoulou VA, Karanika M, Theodoridou K, Katsioulis AT, Theodoridou MN, Hadjichristodoulou CS. Prognostic factors related to sequelae in childhood bacterial meningitis: data from a Greek meningitis registry. BMC Infect Dis 2011;11:214. [14] Snaebjarnardottir K, Erlendsdottir H, Reynisson IK, Kristinsson K, Halldórsdóttir S, Hardardóttir H, et al. Bacterial meningitis in children in Iceland, 1975–2010: a nationwide epidemiological study. Scand J Infect Dis 2013;45:819–24. [15] Franco-Paredes C, Lammoglia L, Hernandez I, Santos-Preciado JI. Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993–2003). Int J Infect Dis 2008;12: 380–6. [16] Cabral M , Correia P , Maria João Brito, et al. Kawasaki disease in a young infant: Diagnostic challenges[J]. Acta reumatologica portuguesa, 2011, 36(3):304-308. [17] Husain E , Hoque E . Meningoencephalitis as a Presentation of Kawasaki Disease[J]. Journal of Child Neurology, 2006, 21(12):1080-1081. [18] De Graeff N , Groot N , Ozen S , et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease – the SHARE initiative[J]. Rheumatology, 2018. [19] Huang MY, Gupta-Malhotra M, Huang JJ, Syu FK, Huang TY. Acutephase reactants and a supplemental diagnostic aid for Kawasaki disease. Pediatr Cardiol 2010;31:1209e13. [20] Van Ettekoven C , Diederik V D B , Brouwer M C . Update on Community-acquired bacterial meningitis: Guidance and challenges[J]. Clinical Microbiology and Infection, 2017:S1198743X17302306. [21] Lars L , Anna-Karin P , Gunnar J , et al. Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis[J]. PLOS ONE, 2017, 12(7):e0181704. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-16533","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":393203,"identity":"9600a2ee-c03e-436d-abbf-a5687765f188","order_by":1,"name":"Fan Hu","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fan","middleName":"","lastName":"Hu","suffix":""},{"id":393204,"identity":"08df4348-c3c3-4541-94d9-687d3aea0dd9","order_by":2,"name":"Xiaoqing Shi","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaoqing","middleName":"","lastName":"Shi","suffix":""},{"id":393205,"identity":"4aae5681-1f6d-46b0-86bb-32560b4fb62d","order_by":3,"name":"Yang Fan","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Fan","suffix":""},{"id":393206,"identity":"61335e78-75fa-4fec-9b48-1ab5eff2b72b","order_by":4,"name":"Hanmin Liu","email":"","orcid":"","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hanmin","middleName":"","lastName":"Liu","suffix":""},{"id":393207,"identity":"794831c9-5bc1-4c3d-a575-1b123c29fa09","order_by":5,"name":"Kaiyu Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIie3PMQrCMBSA4ScVXYJdUwI9w5OCKBTPYhHq4uARIkJdPICDh/AI1Yeurh0cLIKTQ0eHDibi4pLWTTD/EgLvyyMANtsPxqEh1ZECuPPFpcBw+AXhlHTXs3hcg7xSBCZSsGL/esGYt6REsPLsY7qTQYipA206bE1EsEgRdguQ5vI6xXMHWBxnJuKDJpyird4yxZsDnPXMxM0VQU0iKfpIDVlFBNdbRm8CdYi3zheDTUqBl+2S7grjcavqL/w0ybN7SX7ntLxeHmU4dNt0NBJVk39cWxXjOqeoMWSz2Wz/3BNHEVFj/QJenQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4783-4243","institution":"West China Second University Hospital of Sichuan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kaiyu","middleName":"","lastName":"Zhou","suffix":""}],"badges":[],"createdAt":"2020-03-04 16:21:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-16533/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-16533/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":620728,"identity":"04dd88f6-834b-4a82-bb14-ad746a73e339","added_by":"auto","created_at":"2020-03-10 15:01:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":26289,"visible":true,"origin":"","legend":"ROC curve of CSF glucose level in KD group and BM group. The area under the curve was 0.868. The optimal cutoff value of CSF glucose level was 2.945mmol/L with the sensitivity of 84.2% and specificity of 71.4%.","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-16533/v1/figure1.png"},{"id":13493519,"identity":"63976b4e-f8ee-49a0-9b00-61cf24cbb5fb","added_by":"auto","created_at":"2021-09-16 22:35:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":275637,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-16533/v1/b1303e07-4563-4d45-8e93-16a2c6dbbf58.pdf"}],"financialInterests":"","formattedTitle":"The cerebrospinal fluid changes and clinical characteristics of aseptic meningitis in Kawasaki disease","fulltext":[{"header":"Background","content":" \u003cp\u003eKawasaki disease (KD) is an acute febrile disease that happens major in children\u0026thinsp;\u0026lt;\u0026thinsp;5\u0026nbsp;years \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. As a kind of systemic vasculitis, except for the principal clinical features including fever, extremity changes, conjunctivitis, rash, oral changes and cervical lymphadenopathy, it has various clinical manifestations \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Aseptic meningitis is not a common feature in KD. However, it could cause difficulty in making correct and in-time diagnosis \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Although lumbar puncture is suggested to distinguish infectious disease from KD, sometimes the abnormal cerebrospinal fluid (CSF) results in confused diagnosis especially at the beginning of the disease \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. There are plenty of children with atypical clinical characteristics which make it difficult to draw to a definite diagnosis. The clinicians had to use both immunogloubulin and antibiotics simultaneously. Patient of KD with elevated leukocytes, neutrophil cells and C-reactive protein (CRP) in blood and pleocytosis in CSF may easily be misdiagnosed as bacterial meningitis (BM) in the early febrile stage. Besides, limited studies \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e focused on the characteristic of cerebral fluid in KD, and the data was adopted from American and Japanese patients.\u003c/p\u003e \u003cp\u003eIn this study, we retrospectively investigated the KD patients with aseptic meningitis in our hospital and compared it with BM in order to establish the characteristic of KD patients with aseptic meningitis and to find out how to distinguish this disease from bacterial meningitis.\u003c/p\u003e "},{"header":"Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePopulation\u003c/h2\u003e \u003cp\u003eKD patients with aseptic meningitis and BM patients admitted in our department were enrolled for retrospective investigation from January 2011 to December 2019. Totally 38 patients of KD with the diagnosis of aseptic meningitis met the inclusive criteria. Besides, the patients of bacterial meningitis were also investigated as control group. Since most of the KD patients were admitted with duration of fever within10 days, we chose the BM patients with fever\u0026thinsp;\u0026le;\u0026thinsp;10 days in order to study the early change of CSF. Totally 126 patients of bacterial meningitis were brought into the control group. All the patients in this study should have the following data: CSF results, count of blood cells,C-reactive protein (CRP), liver function, urinalysis. Patients with CSF erythrocyte ༞1\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e6\u003c/sup\u003e/L, which suggested trauma lumbar puncture, was excluded. Patients with lumbar puncture after intravenous immunogloubulin (IVIG) treatment were excluded to avoid confusion with aseptic meningitis induced by IVIG \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Moreover, in case records, there should be complete description of the symptoms and physical examination including oral cavity, skin change, conjunctiva, lymph nodes, extremities, and nerves system change.\u003c/p\u003e \u003c/div\u003e \n\u003ch2\u003eClinical Data\u003c/h2\u003e\n \u003cp\u003eThe following clinical data were collected from the groups: Age; gender; duration of fever before lumbar puncture; the five clinical features of KD (conjunctiva injection, oral cavity change, Rash, cervical lymphadenopathy and extremities change); nerves system change including vomiting, front fontanel bulging and neck stiffness. In laboratory tests, we investigated blood leukocytes, hemoglobin, platelets (PLT), CRP; CSF parameters including leukocytes, glucose, protein and lactate dehydrogenase (LDH); liver function and urinalysis.\u003c/p\u003e \n\u003ch2\u003eStatistics\u003c/h2\u003e\n \u003cp\u003eData were studied by SPSS 23.0 software. The data in two groups were compared with independent samples t test. Pearson chi-squre test or Fisher\u0026rsquo;s exact test was used for the compare of constituent ratio in the two groups. In order to study the glucose level in CSF distinguishing KD patients from BM patients, receiver operating characteristic (ROC) curve was constructed. Statistical significance was considered p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e "},{"header":"Results","content":" \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics\u003c/h2\u003e \u003cp\u003eThe clinical characteristics of the patients in the two groups are summarized in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The age and gender in the two groups showed no significant difference. Since the BM patients were chosen with duration of fever no more than 10 days, which was similar with the acute stage of KD, the two groups showed no significant difference on this point (p\u0026thinsp;=\u0026thinsp;0.867). Only a very little portion of the BM patients manifested the five typical features of KD including 1 patients with oral cavity change, 3 patients with rash, 7 patients with cervical lymphadenopathy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). We also investigated the nerves system changes. Vomiting, which could be a symptom of intracranial hypertension, appeared in 49 out of 126 patients in BM group. However, only 2 out of 38 KD patients with aseptic meningitis had vomiting (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Neck stiffness appeared in 17 KD patients and 99 BM patients (p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Besides, either in KD patients or in BM patients, front fontanel bulging seemed to be a frequent sign (p\u0026thinsp;=\u0026thinsp;0.594) if the front fontanel was unclosed.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eClinical characteristics of Kawasaki disease and bacterial meningitis patients\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eKD (n\u0026thinsp;=\u0026thinsp;38)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eBM (n\u0026thinsp;=\u0026thinsp;126)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eP\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAge (months)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e22.0\u0026thinsp;\u0026plusmn;\u0026thinsp;23.4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e26.3\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.345\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003eGender\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e17\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e67\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.362\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e59\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eDuration of fever (days)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e5.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.446\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eConjunctiva injection\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e35\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eOral cavity change\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eRash\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e32\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCervical lymphadenopathy \u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e15\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eExtremities change\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e19\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eVomiting\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e49\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeck stiffness\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e17\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e99\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eFront fontanel bulging \u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e15 (n\u0026thinsp;=\u0026thinsp;19)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e38 (n\u0026thinsp;=\u0026thinsp;45)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.594\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ea: the cervical lymphadenopathy means the typically enlarged cervical lymph nodes\u0026thinsp;\u0026ge;\u0026thinsp;1.5\u0026nbsp;cm which meet the criteria of KD.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eb: Front fontanel bulging could only be observed in young children with unclosed front fontanel. In KD group there were 19 patients with unclosed front fontanel and in BM group 48 patients.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eKD\u0026thinsp;=\u0026thinsp;Kawasaki disease\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eBM\u0026thinsp;=\u0026thinsp;bacterial meningitiss\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \n\u003ch2\u003eLaboratory Examinations\u003c/h2\u003e\n \u003cp\u003eThe laboratory examinations of the two groups are listed in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The leukocyte count, protein and LDH in CSF showed no significant difference between the two groups. Notably, BM group showed a lower level of glucose compared with KD group (p\u0026thinsp;=\u0026thinsp;0.003). The leukocytes and CRP in the blood of KD group were significantly higher than BM group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Although anemia and thrombocytosis were prevalent in KD, in this study the hemoglobin and platelet level in the two groups seemed to have no significant difference. In both groups, there was elevation of alanine transaminase (ATL) and aspartate transaminase (AST) level. However, neither ALT and AST nor albumin in the two groups showed significant difference. There was 7 patient in KD group and no patient in BM group with pyuria, and the difference showed significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). We constructed ROC curve (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) to learn the glucose level in CSF, the area under the curve was 0.868. The optimal cutoff value of glucose level in CSF to distinguish KD and BM was 2.945\u0026nbsp;mmol/L with the sensitivity of 84.2% and specificity of 71.4%.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eLaboratory examinations of Kawasaki disease and bacterial meningitis patients\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLaboratory examination\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003e(median, range)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eKD (n\u0026thinsp;=\u0026thinsp;38)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eBM (n\u0026thinsp;=\u0026thinsp;126)\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003eP\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCSF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eLeukocytes (\u0026times;\u0026thinsp;10\u003csup\u003e6\u003c/sup\u003e/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e107.5(10\u0026ndash;340)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e115 (10-2270)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.097\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eGlucose (mmol/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e3.37(2.50\u0026ndash;5.30)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e2.71(1.18-4.00)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.003*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eProtein (mg/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e632.4(270.8-1054.6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e610(196.2-2722.1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.276\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eLDH (U/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e37.5(16\u0026ndash;56)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e34.5(14\u0026ndash;98)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.253\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003eBlood\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eLeukocytes (\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e17.2(9.7\u0026ndash;27.5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e13.65(7.7\u0026ndash;23.8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eHemoglobin (g/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e110.5(78\u0026ndash;126)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e114(79\u0026ndash;142)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.241\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003ePlatelets (\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e368(123\u0026ndash;604)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e397.5(109\u0026ndash;744)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.137\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eC-reactive protein\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e64.5(28\u0026ndash;180)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e26(8\u0026ndash;81)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e \u003cdiv class=\"SimplePara\"\u003eLiver function\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eALT\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e35.5(7-173)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e37(9-460)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.541\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eAST\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e31(16\u0026ndash;213)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e39.5(15\u0026ndash;432)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.356\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eAlbumin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e37.35(27.3\u0026ndash;46.0)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e38.25(30.8\u0026ndash;47.4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0.059\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003ePyuria\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e0\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001*\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations:\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eKD\u0026thinsp;=\u0026thinsp;Kawasaki disease\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eBM\u0026thinsp;=\u0026thinsp;bacterial meningitis\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eCSF\u0026thinsp;=\u0026thinsp;cerebrospinal fluid\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eLDH\u0026thinsp;=\u0026thinsp;lactate dehydrogenase\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eALT\u0026thinsp;=\u0026thinsp;alanine transaminase\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAST\u0026thinsp;=\u0026thinsp;aspartate transaminase\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eExcept for the typical five clinical features, KD could have multiple other manifestations including arthritis, aseptic meningitis, colitis, etc \u003csup\u003e[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Indeed, KD in early stage with atypical manifestations often leads to misdiagnosis. The persistent fever, nerves system symptom and signs, elevated leukocyte count and CRP could sometimes result in confusion with bacterial meningitis \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, we investigated the symptoms, physical examinations and laboratory tests of KD and BM patients. The typical five features of KD seemed to be rare in BM patients. Neck stiffness and vomit were more prevalent in BM patients. Front fontanel bulging in younger patients was common in both KD patients and BM patients. In CSF examination, the glucose in BM patients showed a lower level compared with KD patients. The leukocytes and protein in CSF of both groups were in a wide range, however, the difference showed no significance. KD patients showed higher blood leukocytes and CRP than BM patients. The examination of liver function and urine test in the two groups remained no significant difference. None of the BM patients in this study had pyuria which was not rare in KD patients.\u003c/p\u003e \u003cp\u003eKD is a kind of systemic vasculitis with multiple manifestations. On the other hand, BM is sort of a focalized disease mainly affects central nerves system. The typical five features, which suggest a systemic inflammation, rarely appear in BM patients. Rash especially haemorrhagic rash may be found in BM patients of children. However, it is more frequent in meningococcal meningitis (61%) rather than in pneumococcal meningitis (9%) \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. In this study, none of the patients in BM group was documented meningococcal meningitis and only 3 patient had skin rash.\u003c/p\u003e \u003cp\u003eVomiting is reported in 55\u0026ndash;67% children with BM \u003csup\u003e[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. However, previous studies did not focus on this symptom in KD \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Besides, in 3 case reports, vomiting appeared in none of the patients of KD with aseptic meningitis \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. In this study, only two of the KD patients presented with vomiting. Based on the findings above, we consider maybe vomiting is less frequent in KD compared with BM patients. The possible reason is that the intracranial hypertension of aseptic meningitis in KD is less prominent than that in BM.\u003c/p\u003e \u003cp\u003eLumbar puncture is often considered to exclude infectious disease from KD \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. However, in this study, the CSF results suggested that leukocytes, protein, LDH in the two groups showed no significant difference. However, glucose in BM patients was at a lower level than KD group. ROC curve indicates 2.945\u0026nbsp;mmol/L as the optimal cutoff value. Other studies also suggested that decrease in CSF glucose was not prevalent in KD patients \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Although we can\u0026rsquo;t easily exclude BM only with normal glucose in CSF because CSF glucose in either KD patients or BM patients could be normal, it seems that obvious decreased CSF glucose level strongly suggests the diagnosis of BM.\u003c/p\u003e \u003cp\u003eBoth KD and bacterial infection could result in elevation of blood leukocytes and CRP. Previous study suggested that CRP was not specific in diagnosis of KD compared with bacterial infections \u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. However, we observed in our study a higher leukocyte and CRP level in KD patients compared with BM patients. The possible reasons may be as follows. First, the sample size is quite limited. Second, in order to be comparable with KD, we chose BM patients with fever no more than 10 days. At this period, the inflammatory reaction of KD possibly reached the highest level, but in BM, it was still in an early stage. Anyhow, relative higher CRP level might be helpful in excluding BM in a relative early stage of fever.\u003c/p\u003e \u003cp\u003eThe change in liver function including ALT and albumin is considered as auxiliary laboratory findings in the diagnosis of KD \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Meanwhile, bacterial infections including BM could also result in elevated ALT and AST level and decreased albumin level \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. In this study, the change of ALT, AST and albumin manifested no significant difference in the two groups and the result suggested that ALT, AST and albumin were not indicators in distinguishing between KD and BM patients.\u003c/p\u003e \u003cp\u003ePyuria is another clinical manifestation of KD with an incidence of 38% \u003csup\u003e[22]\u003c/sup\u003e. In this study, 7 out of the 38 KD patients had pyuria while none of the BM patients had. As a kind of systemic vasculitis, KD is more likely than BM to manifest both pyuria and CSF pleocytosis.\u003c/p\u003e \u003cp\u003eIn summary, full investigation of clinical manifestation and laboratory tests is necessary to distinguish KD with aseptic meningitis and BM. In CSF study, glucose level is more efficient than other items to distinguish these two diseases. Decreased CSF glucose is possibly an indicator of BM rather than KD.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eALT= alanine transaminase\u003c/p\u003e\n\u003cp\u003eAST= aspartate transaminase\u003c/p\u003e\n\u003cp\u003eBM= bacterial meningitis\u003c/p\u003e\n\u003cp\u003eCRP=C-reactive protein\u003c/p\u003e\n\u003cp\u003eCSF=cerebrospinal fluid\u003c/p\u003e\n\u003cp\u003eIVIG=intravenous immunoglobulin\u003c/p\u003e\n\u003cp\u003eKD= Kawasaki disease\u003c/p\u003e\n\u003cp\u003eLDH=lactate dehydrogenase\u003c/p\u003e\n\u003cp\u003ePLT=platelet\u003c/p\u003e\n\u003cp\u003eROC=receiver operating characteristic\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the patients in this study have given informed consent including permission of using clinical data. The study was approved by the ethic committee of West China Second University Hospital of Sichuan University.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from the National Natural Science Foundation of China (No. 81570369, 81741025) and Sichuan Province Science and Technology Support\u0026nbsp;Program, China (No.2018SZ0180).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFH contributed to the design of the work, interpretation of data and has drafted the work. XQS was a major contributor to acquisition of data. YF contributed to acquisition and analysis of data. HML contributed the conception of the work and substantively revised it. KYZ was a major contributor to design of the work and substantively revised it.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e[1] McCrindle BW, Rowley AH, Newburger JW. et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-e999.\u003c/p\u003e\n\u003cp\u003e[2] Singh S, Jindal AK, Pilania RK. Diagnosis of Kawasaki disease. Int J Rheum Dis. 2018 Jan; 21(1): 36-44.\u003c/p\u003e\n\u003cp\u003e[3] Rossi M, Siani P, Grossi A, et al. Aseptic meningitis as onset of Kawasaki disease. Minerva Pediatr. 2019 Jan 17. [Epub ahead of print]\u003c/p\u003e\n\u003cp\u003e[4] T\u0026uuml;rel O, G\u0026uuml;zeltaş A, Aydoğmuş C. Kawasaki disease presenting as meningitis in a two months old infant. Anadolu Kardiyol Derg. 2011 Jun; 11(4): 369-70.\u003c/p\u003e\n\u003cp\u003e[5] Dengler LD, Capparelli EV, Bastian, et al. Cerebrospinal fluid profile in patients with acute Kawasaki disease. Pediatr Infect Dis J. 1998 Jun;17(6):478-81.\u003c/p\u003e\n\u003cp\u003e[6] Yeom JS, Park JS, Seo JH, et al. Initial characteristics of Kawasaki disease with cerebrospinal fluid pleocytosis in febrile infants. Pediatr Neurol. 2012 Oct;47(4):259-62.\u003c/p\u003e\n\u003cp\u003e[7] Yasushi K, Tomotaka N, Hiroyuki M, et al. Clinical characteristics of aseptic meningitis induced by intravenous immunoglobulin in patients with Kawasaki disease[J]. Pediatr Rheumatolon Online, 2011, 9(1):28-28.\u003c/p\u003e\n\u003cp\u003e[8] Cho A R, Park J Y, Kim K H, et al. Aseptic Meningitis Secondary to High-Dose Intravenous Immunoglobulin Therapy in Kawasaki Disease[J]. Korean Journal of Pediatrics, 2004, 47(5).\u003c/p\u003e\n\u003cp\u003e[9] Peng Y , Liu X , Duan Z , et al. Prevalence and characteristics of arthritis in Kawasaki disease: a Chinese cohort study[J]. Clinical and Experimental Medicine, 2019.\u003c/p\u003e\n\u003cp\u003e[10] Zhang Y, Wan H, Du M, et al. Capillary leak syndrome and aseptic meningitis in a patient with Kawasaki disease: A case report[J]. Medicine, 2018, 97(23):e10716.\u003c/p\u003e\n\u003cp\u003e[11] Ohnishi Y, Mori, Kazuhiro, Inoue, Miki, et al. A case of Kawasaki disease presenting as sigmoid colitis[J]. Journal of Medical Ultrasonics, 2017, 45(2):1-4.\u003c/p\u003e\n\u003cp\u003e[12] Eleftheriou D, Levin M, Shingadia D et al. Management of Kawasaki disease. Arch Dis Child 2014;99:74_83.\u003c/p\u003e\n\u003cp\u003e[13] Vasilopoulou VA, Karanika M, Theodoridou K, Katsioulis AT, Theodoridou MN, Hadjichristodoulou CS. Prognostic factors related to sequelae in childhood bacterial meningitis: data from a Greek meningitis registry. BMC Infect Dis 2011;11:214.\u003c/p\u003e\n\u003cp\u003e[14] Snaebjarnardottir K, Erlendsdottir H, Reynisson IK, Kristinsson K, Halld\u0026oacute;rsd\u0026oacute;ttir S, Hardard\u0026oacute;ttir H, et al. Bacterial meningitis in children in Iceland, 1975\u0026ndash;2010: a nationwide epidemiological study. Scand J Infect Dis 2013;45:819\u0026ndash;24.\u003c/p\u003e\n\u003cp\u003e[15] Franco-Paredes C, Lammoglia L, Hernandez I, Santos-Preciado JI. Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993\u0026ndash;2003). Int J Infect Dis 2008;12: 380\u0026ndash;6.\u003c/p\u003e\n\u003cp\u003e[16] Cabral M , Correia P , Maria Jo\u0026atilde;o Brito, et al. Kawasaki disease in a young infant: Diagnostic challenges[J]. Acta reumatologica portuguesa, 2011, 36(3):304-308.\u003c/p\u003e\n\u003cp\u003e[17] Husain E , Hoque E . Meningoencephalitis as a Presentation of Kawasaki Disease[J]. Journal of Child Neurology, 2006, 21(12):1080-1081.\u003c/p\u003e\n\u003cp\u003e[18] De Graeff N , Groot N , Ozen S , et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease \u0026ndash; the SHARE initiative[J]. Rheumatology, 2018.\u003c/p\u003e\n\u003cp\u003e[19] Huang MY, Gupta-Malhotra M, Huang JJ, Syu FK, Huang TY. Acutephase reactants and a supplemental diagnostic aid for Kawasaki disease. Pediatr Cardiol 2010;31:1209e13.\u003c/p\u003e\n\u003cp\u003e[20] Van Ettekoven C , Diederik V D B , Brouwer M C . Update on Community-acquired bacterial meningitis: Guidance and challenges[J]. Clinical Microbiology and Infection, 2017:S1198743X17302306.\u003c/p\u003e\n\u003cp\u003e[21] Lars L , Anna-Karin P , Gunnar J , et al. Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis[J]. PLOS ONE, 2017, 12(7):e0181704.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Kawasaki disease; aseptic meningitis; bacterial meningitis; cerebrospinal fluid.","lastPublishedDoi":"10.21203/rs.3.rs-16533/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-16533/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Aseptic meningitis is not a common feature in Kawasaki disease (KD). However, it could cause difficulty in making correct and in-time diagnosis Methods: We retrospectively investigated patients of KD and bacterial meningitis (BM). Totally 38 KD patients and 126 BM patients were brought into this study. Clinical symptoms, signs and laboratory examinations were compared between the two groups, which included: duration of fever before lumbar puncture, conjunctiva injection, oral cavity change, rash, cervical lymphadenopathy and extremities change, vomiting, front fontanel bulging, neck stiffness, leukocytes, hemoglobin, platelets, C-reactive protein, cerebrospinal fluid examinations, liver function and urinalysis. Results: In clinical signs, vomit and neck stiffness were more prevalent in BM. KD patients showed higher blood leukocyte (p\u0026lt;0.001) and C-reactive protein (p\u0026lt;0.001) in the early febrile stage. Glucose in cerebrospinal fluid of BM patients was significantly lower than KD patients (p=0.003). In ROC curve, the optimal cutoff value of CSF glucose was 2.945mmol/L with the sensitivity of 84.2% and specificity of 71.4%. Pyuria was more prevalent in KD patients (p\u0026lt;0.001). There was no significant difference in front fontanel bulging, hemoglobin, platelet, alanine transaminase, aspartate transaminase, albumin, cerebrospinal fluid leukocytes, cerebrospinal fluid protein and cerebrospinal fluid lactate dehydrogenase. Conclusions ： Full investigation of clinical manifestation and laboratory tests is necessary to distinguish KD with aseptic meningitis and BM. In CSF study, glucose level is more efficient than other items to distinguish these two diseases. Decreased CSF glucose is possibly an indicator of BM rather than KD.\u003c/p\u003e","manuscriptTitle":"The cerebrospinal fluid changes and clinical characteristics of aseptic meningitis in Kawasaki disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-03-10 15:01:15","doi":"10.21203/rs.3.rs-16533/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3f193e6b-1660-4b70-8659-0b978682a695","owner":[],"postedDate":"March 10th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":67826,"name":"Rheumatology"},{"id":67827,"name":"Pediatrics"}],"tags":[],"updatedAt":"2020-05-14T07:15:59+00:00","versionOfRecord":[],"versionCreatedAt":"2020-03-10 15:01:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-16533","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-16533","identity":"rs-16533","version":["v1"]},"buildId":"cTy_lsJlmDsVRNrSptgXS","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}