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Diagnosis of Kawasaki Disease and Development of New Biomarkers

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Abstract

Since first described by Dr. Tomisaku Kawasaki in 1961, the clinical diagnosis of Kawasaki disease (KD) has remained relatively unchanged. However, studies have suggested that diagnosis using that original clinical criteria alone may have led to an underdiagnosis of Kawasaki disease. In this chapter, we review widely accepted diagnostic criteria for Kawasaki disease, diagnostic criteria for “atypical” Kawasaki disease, diagnostic pitfalls, and other differential diagnoses. We also review the current literature regarding new biomarkers, scoring systems, and microRNA panels that may aid in the diagnosis of KD.

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References

  1. Kawasaki T. [Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children]. Arerugi. 1967;16(3):178–222.

    Google Scholar 

  2. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927–99.

    Article  PubMed  Google Scholar 

  3. Ayusawa M, Sonobe T, Uemura S, Ogawa S, Nakamura Y, Kiyosawa N, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int. 2005;47(2):232–4.

    Article  PubMed  Google Scholar 

  4. Gong GW, McCrindle BW, Ching JC, Yeung RS. Arthritis presenting during the acute phase of Kawasaki disease. J Pediatr. 2006;148(6):800–5.

    Article  PubMed  Google Scholar 

  5. Baker AL, Lu M, Minich LL, Atz AM, Klein GL, Korsin R, et al. Associated symptoms in the ten days before diagnosis of Kawasaki disease. J Pediatr. 2009;154(4):592–5.e2.

    Article  PubMed  Google Scholar 

  6. Colomba C, La Placa S, Saporito L, Corsello G, Ciccia F, Medaglia A, et al. Intestinal involvement in Kawasaki disease. J Pediatr. 2018;202:186–93.

    Article  PubMed  Google Scholar 

  7. Liu X, Zhou K, Hua Y, Wu M, Liu L, Shao S, et al. Neurological involvement in Kawasaki disease: a retrospective study. Pediatr Rheumatol Online J. 2020;18(1):61.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kanegaye JT, Wilder MS, Molkara D, Frazer JR, Pancheri J, Tremoulet AH, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123(5):e783–9.

    Article  PubMed  Google Scholar 

  9. Gamez-Gonzalez LB, Moribe-Quintero I, Cisneros-Castolo M, Varela-Ortiz J, Munoz-Ramirez M, Garrido-Garcia M, et al. Kawasaki disease shock syndrome: unique and severe subtype of Kawasaki disease. Pediatr Int. 2018;60(9):781–90.

    Article  CAS  PubMed  Google Scholar 

  10. Rossi Fde S, Silva MF, Kozu KT, Camargo LF, Rossi FF, Silva CA, et al. Extensive cervical lymphadenitis mimicking bacterial adenitis as the first presentation of Kawasaki disease. Einstein (Sao Paulo). 2015;13(3):426–9.

    Article  Google Scholar 

  11. Kao HT, Huang YC, Lin TY. Kawasaki disease presenting as cervical lymphadenitis or deep neck infection. Otolaryngol Head Neck Surg. 2001;124(4):468–70.

    Article  CAS  PubMed  Google Scholar 

  12. Wang CL, Wu YT, Liu CA, Kuo HC, Yang KD. Kawasaki disease: infection, immunity and genetics. Pediatr Infect Dis J. 2005;24(11):998–1004.

    Article  PubMed  Google Scholar 

  13. Uehara R, Igarashi H, Yashiro M, Nakamura Y, Yanagawa H. Kawasaki disease patients with redness or crust formation at the Bacille Calmette–Guerin inoculation site. Pediatr Infect Dis J. 2010;29(5):430–3.

    Article  PubMed  Google Scholar 

  14. Tseng HC, Ho JC, Guo MM, Lo MH, Hsieh KS, Tsai WC, et al. Bull’s eye dermatoscopy pattern at bacillus Calmette–Guerin inoculation site correlates with systemic involvements in patients with Kawasaki disease. J Dermatol. 2016;43(9):1044–50.

    Article  CAS  PubMed  Google Scholar 

  15. Muthuvelu S, Lim KS, Huang LY, Chin ST, Mohan A. Measles infection causing Bacillus Calmette–Guerin reactivation: a case report. BMC Pediatr. 2019;19(1):251.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kuo HC, Lo CC, Lin PX, Kao CC, Huang YH, Lin BS. Wireless optical monitoring system identifies limb induration characteristics in patients with Kawasaki disease. J Allergy Clin Immunol. 2018;142(2):710–1.

    Article  PubMed  Google Scholar 

  17. Fukushige J, Takahashi N, Ueda Y, Ueda K. Incidence and clinical features of incomplete Kawasaki disease. Acta Paediatr. 1994;83(10):1057–60.

    Article  CAS  PubMed  Google Scholar 

  18. Yeom JS, Woo HO, Park JS, Park ES, Seo JH, Youn HS. Kawasaki disease in infants. Korean J Pediatr. 2013;56(9):377–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rosenfeld EA, Corydon KE, Shulman ST. Kawasaki disease in infants less than one year of age. J Pediatr. 1995;126(4):524–9.

    Article  CAS  PubMed  Google Scholar 

  20. Newburger JW, Takahashi M, Gerber MA, Gewitz MH, Tani LY, Burns JC, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2004;110(17):2747–71.

    Article  PubMed  Google Scholar 

  21. Chang FY, Hwang B, Chen SJ, Lee PC, Meng CC, Lu JH. Characteristics of Kawasaki disease in infants younger than six months of age. Pediatr Infect Dis J. 2006;25(3):241–4.

    Article  PubMed  Google Scholar 

  22. Salgado AP, Ashouri N, Berry EK, Sun X, Jain S, Burns JC, et al. High risk of coronary artery aneurysms in infants younger than 6 months of age with Kawasaki disease. J Pediatr. 2017;185:112–6.e1.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cai Z, Zuo R, Liu Y. Characteristics of Kawasaki disease in older children. Clin Pediatr (Phila). 2011;50(10):952–6.

    Article  Google Scholar 

  24. Chang LY, Lu CY, Shao PL, Lee PI, Lin MT, Fan TY, et al. Viral infections associated with Kawasaki disease. J Formos Med Assoc. 2014;113(3):148–54.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Huang SM, Huang SH, Weng KP, Chien KJ, Lin CC, Huang YF. Update on association between Kawasaki disease and infection. J Chin Med Assoc. 2019;82(3):172–4.

    Article  PubMed  Google Scholar 

  26. Group JCSJW. Guidelines for diagnosis and management of cardiovascular sequelae in Kawasaki disease (JCS 2013). Digest version. Circ J. 2014;78(10):2521–62.

    Article  Google Scholar 

  27. de Zorzi A, Colan SD, Gauvreau K, Baker AL, Sundel RP, Newburger JW. Coronary artery dimensions may be misclassified as normal in Kawasaki disease. J Pediatr. 1998;133(2):254–8.

    Article  PubMed  Google Scholar 

  28. Kobayashi T, Fuse S, Sakamoto N, Mikami M, Ogawa S, Hamaoka K, et al. A new Z score curve of the coronary arterial internal diameter using the Lambda-Mu-Sigma method in a pediatric population. J Am Soc Echocardiogr. 2016;29(8):794–801.e29.

    Article  PubMed  Google Scholar 

  29. Lin MT, Chang CH, Hsieh WC, Chang CE, Chang YM, Chen YC, et al. Coronary diameters in Taiwanese children younger than 6 years old: Z-score regression equations derived from body surface area. Acta Cardiol Sin. 2014;30(4):266–73.

    PubMed  PubMed Central  Google Scholar 

  30. Tsuda E, Singhal M. Role of imaging studies in Kawasaki disease. Int J Rheum Dis. 2018;21(1):56–63.

    Article  PubMed  Google Scholar 

  31. Chaiyarak K, Durongpisitkul K, Atta T, Soongswang J, Laohaprasitiporn D, Nana A. Clinical manifestations of Kawasaki disease: what are the significant parameters? Asian Pac J Allergy Immunol. 2009;27(2–3):131–6.

    CAS  PubMed  Google Scholar 

  32. Ling XB, Kanegaye JT, Ji J, Peng S, Sato Y, Tremoulet A, et al. Point-of-care differentiation of Kawasaki disease from other febrile illnesses. J Pediatr. 2013;162(1):183–8.e3.

    Article  PubMed  Google Scholar 

  33. Hao S, Jin B, Tan Z, Li Z, Ji J, Hu G, et al. A classification tool for differentiation of Kawasaki disease from other febrile illnesses. J Pediatr. 2016;176:114–20.e8.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tsai CM, Chu CH, Liu X, Weng KP, Liu SF, Huang YH, et al. A novel score system of blood tests for differentiating Kawasaki disease from febrile children. PLoS One. 2021;16(1):e0244721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang Y, Wang W, Gong F, Fu S, Zhang Q, Hu J, et al. Evaluation of intravenous immunoglobulin resistance and coronary artery lesions in relation to Th1/Th2 cytokine profiles in patients with Kawasaki disease. Arthritis Rheum. 2013;65(3):805–14.

    Article  CAS  PubMed  Google Scholar 

  36. Kuo HC, Wang CL, Liang CD, Yu HR, Huang CF, Wang L, et al. Association of lower eosinophil-related T helper 2 (Th2) cytokines with coronary artery lesions in Kawasaki disease. Pediatr Allergy Immunol. 2009;20(3):266–72.

    Article  PubMed  Google Scholar 

  37. de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease. Lancet. 2003;362(9380):316–22.

    Article  PubMed  CAS  Google Scholar 

  38. Lin KH, Chang SS, Yu CW, Lin SC, Liu SC, Chao HY, et al. Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis. BMJ Open. 2015;5(4):e006703.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Nir A, Lindinger A, Rauh M, Bar-Oz B, Laer S, Schwachtgen L, et al. NT-pro-B-type natriuretic peptide in infants and children: reference values based on combined data from four studies. Pediatr Cardiol. 2009;30(1):3–8.

    Article  PubMed  Google Scholar 

  40. Chen CS, Korobkova E, Chen H, Zhu J, Jian X, Tao SC, et al. A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli. Nat Methods. 2008;5(1):69–74.

    Article  CAS  PubMed  Google Scholar 

  41. Esposito S, Polinori I, Rigante D. The gut microbiota-host partnership as a potential driver of Kawasaki syndrome. Front Pediatr. 2019;7:124.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Watanabe T. Pyuria in patients with Kawasaki disease. World J Clin Pediatr. 2015;4(2):25–9.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Husain EH, Al-Rashid M. Kawasaki disease in association with urinary tract infection. Indian Pediatr. 2011;48(10):808–9.

    PubMed  Google Scholar 

  44. Nagata S, Yamashiro Y, Ohtsuka Y, Shimizu T, Sakurai Y, Misawa S, et al. Heat shock proteins and superantigenic properties of bacteria from the gastrointestinal tract of patients with Kawasaki disease. Immunology. 2009;128(4):511–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. Gut Microbes. 2012;3(1):4–14.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kuo HC, Huang YH, Chung FH, Chen PC, Sung TC, Chen YW, et al. Antibody profiling of Kawasaki disease using Escherichia coli proteome microarrays. Mol Cell Proteomics. 2018;17(3):472–81.

    Article  CAS  PubMed  Google Scholar 

  47. Chen CS, Sullivan S, Anderson T, Tan AC, Alex PJ, Brant SR, et al. Identification of novel serological biomarkers for inflammatory bowel disease using Escherichia coli proteome chip. Mol Cell Proteomics. 2009;8(8):1765–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chen PC, Syu GD, Chung KH, Ho YH, Chung FH, Chen PH, et al. Antibody profiling of bipolar disorder using Escherichia coli proteome microarrays. Mol Cell Proteomics. 2015;14(3):510–8.

    Article  CAS  PubMed  Google Scholar 

  49. Faruq O, Vecchione A. microRNA: diagnostic perspective. Front Med (Lausanne). 2015;2:51.

    Google Scholar 

  50. Chen Y, Ding YY, Ren Y, Cao L, Xu QQ, Sun L, et al. Identification of differentially expressed microRNAs in acute Kawasaki disease. Mol Med Rep. 2018;17(1):932–8.

    CAS  PubMed  Google Scholar 

  51. Chu M, Wu R, Qin S, Hua W, Shan Z, Rong X, et al. Bone marrow-derived microRNA-223 works as an endocrine genetic signal in vascular endothelial cells and participates in vascular injury from Kawasaki disease. J Am Heart Assoc. 2017;6(2):e004878.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Wang X, Ding YY, Chen Y, Xu QQ, Qian GH, Qian WG, et al. MiR-223-3p alleviates vascular endothelial injury by targeting IL6ST in Kawasaki disease. Front Pediatr. 2019;7:288.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Rong X, Ge D, Shen D, Chen X, Wang X, Zhang L, et al. miR-27b suppresses endothelial cell proliferation and migration by targeting Smad7 in Kawasaki disease. Cell Physiol Biochem. 2018;48(4):1804–14.

    Article  CAS  PubMed  Google Scholar 

  54. Wu R, Shen D, Sohun H, Ge D, Chen X, Wang X, et al. miR186, a serum microRNA, induces endothelial cell apoptosis by targeting SMAD6 in Kawasaki disease. Int J Mol Med. 2018;41(4):1899–908.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Wu MH, Lin MT, Chen HC, Kao FY, Huang SK. Postnatal risk of acquiring Kawasaki disease: a nationwide birth cohort database study. J Pediatr. 2017;180:80–6.e2.

    Article  PubMed  Google Scholar 

  56. He M, Chen Z, Martin M, Zhang J, Sangwung P, Woo B, et al. miR-483 targeting of CTGF suppresses endothelial-to-mesenchymal transition: therapeutic implications in Kawasaki disease. Circ Res. 2017;120(2):354–65.

    Article  CAS  PubMed  Google Scholar 

  57. Zhang W, Wang Y, Zeng Y, Hu L, Zou G. Serum miR-200c and miR-371-5p as the useful diagnostic biomarkers and therapeutic targets in Kawasaki disease. Biomed Res Int. 2017;2017:8257862.

    PubMed  PubMed Central  Google Scholar 

  58. Rong X, Jia L, Hong L, Pan L, Xue X, Zhang C, et al. Serum miR-92a-3p as a new potential biomarker for diagnosis of Kawasaki disease with coronary artery lesions. J Cardiovasc Transl Res. 2017;10(1):1–8.

    Article  PubMed  Google Scholar 

  59. Wang YF, Lian XL, Zhong JY, Su SX, Xu YF, Xie XF, et al. Serum exosomal microRNA let-7i-3p as candidate diagnostic biomarker for Kawasaki disease patients with coronary artery aneurysm. IUBMB Life. 2019;71(7):891–900.

    CAS  PubMed  Google Scholar 

  60. Nakaoka H, Hirono K, Yamamoto S, Takasaki I, Takahashi K, Kinoshita K, et al. MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki disease. Sci Rep. 2018;8(1):1016.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19(1):92–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kuo HC, Hsieh KS, Ming-Huey Guo M, Weng KP, Ger LP, Chan WC, et al. Next-generation sequencing identifies micro-RNA-based biomarker panel for Kawasaki disease. J Allergy Clin Immunol. 2016;138(4):1227–30.

    Article  CAS  PubMed  Google Scholar 

  63. Ogata S, Tremoulet AH, Sato Y, Ueda K, Shimizu C, Sun X, et al. Coronary artery outcomes among children with Kawasaki disease in the United States and Japan. Int J Cardiol. 2013;168(4):3825–8.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Mindy Ming-Huey Guo .

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Guo, M.MH. (2022). Diagnosis of Kawasaki Disease and Development of New Biomarkers. In: Kuo, HC. (eds) Kawasaki Disease. Springer, Singapore. https://doi.org/10.1007/978-981-19-2944-1_3

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  • DOI: https://doi.org/10.1007/978-981-19-2944-1_3

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