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Kawasaki disease and immunodeficiencies in children: case reports and literature review

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Abstract

Kawasaki disease (KD) has features that appear supporting an infectious cause with a secondary deranged inflammatory/autoimmune response. The association of KD in adults with human immunodeficiency virus infection and the presence of KD in patients with immunodeficiency disorders support the infectious theory. We present four KD patients associated with immunodeficiencies: one with X-linked agammaglobulinemia, one with HIV infection, and two with leukemia; one of these patients also had Down syndrome. We did a literature search to find out all reported cases of immunodeficiency with KD in children. In immunodeficiency disorders, the inability of the immune system to eradicate the pathogens coupled to an exaggerated inflammatory response, especially in chronic granulomatous disease, may lead to the development of KD. The study of patients with immunodeficiencies complicated with KD may shed light into the etiopathogenesis of the disease.

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References

  1. Rowley AH (2018) Is Kawasaki disease an infectious disorder? Int J Rheum Dis 21:20–25

    Article  PubMed  Google Scholar 

  2. Marrani E, Burns JC, Cimaz R (2018) How should we classify kawasaki disease? Front Immunol 14:2974

    Article  CAS  Google Scholar 

  3. Yamazaki-Nakashimada MA, Ramírez-Vargas N, De Rubens-Figueroa J (2008) Chronic granulomatous disease associated with atypical Kawasaki disease. Pediatr Cardiol 29:169–171

    Article  CAS  PubMed  Google Scholar 

  4. Muneuchi J, Ishimura M, Takada H, Hoshina T, Utsunomiya R, Ikeda K, Yamaguchi K, Ohga S, Kusuhara K, Hara T (2010) Incomplete Kawasaki disease in a patient with chronic granulomatous disease. Pediatr Int 52:e134–e136

    Article  PubMed  Google Scholar 

  5. Tsuge M, Shigemitsu Y, Yano Y, Fujiwara M, Miyai T, Ueda K, Takata K, Moriwake T (2012) Immunoglobulin resistance in Kawasaki disease with chronic granulomatous disease. Pediatr Int 54:e32–e34

    Article  PubMed  Google Scholar 

  6. Hule GP, Kanvinde PR, Kulkarni MA, van Leeuwen K, de Boer M, Bargir UA, Taur PD, Desai MM, Madkaikar MR (2018) p47phox−/− chronic granulomatous disease patient with incomplete Kawasaki disease. J Clin Immunol 38:638–641

    Article  CAS  PubMed  Google Scholar 

  7. Kimata H (1995) High-dose intravenous gamma-globulin treatment for hyperimmunoglobulinemia E syndrome. J Allergy Clin Immunol 95:771–774

    Article  CAS  PubMed  Google Scholar 

  8. Sharma D, Guleria S, Suri D, Rawat A, Garg R, Singh S (2017) A child with X-linked agammaglobulinemia and Kawasaki disease: an unusual association. Rheumatol Int 37:1401–1403

    Article  CAS  PubMed  Google Scholar 

  9. Behniafard N, Aghamohammadi A, Abolhassani H, Pourjabbar S, Sabouni F, Rezaei N (2012) Autoimmunity in X-linked agammaglobulinemia: Kawasaki disease and review of the literature. Expert Rev Clin Immunol 8(2):155–159

    Article  CAS  PubMed  Google Scholar 

  10. Malekzadeh I, Moradinejad MH, Ziaee V, Malek A, Khalili A (2013) Autoimmunity in X-linked agammaglobulinemia; a patient with several episodes autoimmunity Iranian. J Pediatr 23(1 Suppl):75–75

    Google Scholar 

  11. Nishikawa T, Nomura Y, Kono Y, Kawano Y (2008) Selective IgA deficiency complicated by Kawasaki syndrome. Pediatr Int 50(6):816–818

    Article  CAS  PubMed  Google Scholar 

  12. Anzai T, Minami T, Sato T, Furui S, Yamagata T (2016) Treatment of a patient with Kawasaki disease associated with selective IgA deficiency by continuous infusion of cyclosporine A without intravenous immunoglobulin. Turk J Pediatr 58(6):666–668

    Article  PubMed  Google Scholar 

  13. Kawakami C, Miyake M, Tamai H (2003) Kawasaki disease in a patient with Wiskott–Aldrich syndrome: an increase in the platelet count. Int J Hematol 77(2):199–200

    Article  PubMed  Google Scholar 

  14. Şanlidag B, Balkan C, Bahçeciler N (2018) A case report: incomplete Kawasaki disease in a hypogammaglobulinémie child. Arch Argent Pediatr 116(2):e322–e324

    PubMed  Google Scholar 

  15. Nigro G, Pisano P, Krzysztofiak A (1993) Recurrent Kawasaki disease associated with co-infection with parvovirus B19 and HIV-1. AIDS 7(2):288–290

    Article  CAS  PubMed  Google Scholar 

  16. Aladhami SM, Arrowsmith WA, Inglis J, Madlom MM (1996) A young child with Kawasaki syndrome and AIDS. Lancet 347(9005):912–913

    Article  CAS  PubMed  Google Scholar 

  17. Belostotsky O, Chowdhury D, Schuval SJ (2004) Atypical Kawasaki disease in an HIV-infected adolescent. J Allergy Clin Immunol 113(2 Suppl):S126

    Article  Google Scholar 

  18. Akita H, Matsuoka S, Takahashi Y, Watanabe T, Takaue Y, Kuroda Y (1992) Kawasaki-like disease in early course of acute monocytic leukaemia. Eur J Pediatr 151(3):177–178

    Article  CAS  PubMed  Google Scholar 

  19. Lee B, Kofman CD, Tremoulet AH, Kuo DJ (2017) Fever without a source: evolution of a diagnosis from Kawasaki disease to acute myelogenous leukaemia. BMJ Case Rep. https://doi.org/10.1136/bcr-2016-217937 (pii: bcr-2016-217937)

    Article  PubMed  PubMed Central  Google Scholar 

  20. Takatsuki S, Ogata S, Ishii M, Yokozawa M, Ono M, Fujiwara M, Ida H, Motomura H, Moriuchi H, Taketazu M, Kawamura Y, Kawano T, Izumi T, Shiono J, Tsuchiya S, Tsuchiya K, Goushi T, Ichida F, Saji T (2017) Low risk of treatment resistance in Down syndrome with Kawasaki disease. Pediatr Int 59(12):1236–1239

    Article  CAS  PubMed  Google Scholar 

  21. Fukushige J, Takahashi N, Ueda Y, Ueda K (1994) Incidence and clinical features of incomplete Kawasaki disease. Acta Paediatr 83(10):1057–1060

    Article  CAS  PubMed  Google Scholar 

  22. Rieber N, Hector A, Kuijpers T, Roos D, Hartl D (2012) Current concepts of hyperinflammation in chronic granulomatous disease. Clin Dev Immunol. https://doi.org/10.1155/2012/252460 (Epub 2011 Jul 25)

    Article  PubMed  Google Scholar 

  23. García-Pavón S, Yamazaki-Nakashimada MA, Báez M, Borjas-Aguilar KL, Murata C (2017) Kawasaki disease complicated with macrophage activation syndrome: a systematic review. J Pediatr Hematol Oncol 39(6):445–451

    Article  PubMed  Google Scholar 

  24. Álvarez-Cardona A, Rodríguez-Lozano AL, Blancas-Galicia L, Rivas-Larrauri FE, Yamazaki-Nakashimada MA (2012) Intravenous immunoglobulin treatment for macrophage activation syndrome complicating chronic granulomatous disease. J Clin Immunol 32(2):207–211

    Article  PubMed  Google Scholar 

  25. Andreozzi L, Bracci B, D’Errico F, Rigante D (2017) A master role for neutrophils in Kawasaki syndrome. Immunol Lett 184:112–114

    Article  CAS  PubMed  Google Scholar 

  26. Bagaitkar J, Pech NK, Ivanov S, Austin A, Zeng MY, Pallat S, Huang G, Randolph GJ, Dinauer MC (2015) NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1α/G-CSF axis. Blood 126(25):2724–2733. https://doi.org/10.1182/blood-2015-05-644773 (Epub 2015 Oct 6)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, Yel L, Sullivan KE (2014) Autoimmunity and inflammation in X-linked agammaglobulinemia. J Clin Immunol 34(6):627–632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. López-Herrera G, Vargas-Hernández A, González-Serrano ME, Berrón-Ruiz L, Rodríguez-Alba JC, Espinosa-Rosales F, Santos-Argumedo L (2014) Bruton’s tyrosine kinase—an integral protein of B cell development that also has an essential role in the innate immune system. J Leukoc Biol 95(2):243–250

    Article  CAS  PubMed  Google Scholar 

  29. González-Serrano ME, Estrada-García I, Mogica-Martínez D, González-Garay A, López-Herrera G, Berrón-Ruiz L, Espinosa-Padilla SE, Yamazaki-Nakashimada MA, Vargas-Hernández A, Santos-Argumedo L, Estrada-Parra SA, Espinosa-Rosales FJ (2012) Increased pro-inflammatory cytokine production after lipopolysaccharide stimulation in patients with X-linked agammaglobulinemia. J Clin Immunol 32(5):967–974

    Article  CAS  PubMed  Google Scholar 

  30. Liu X, Pichulik T, Wolz OO, Dang TM, Stutz A, Dillen C et al (2017) Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase. J Allergy Clin Immunol 140(4):1054–1067.e10. https://doi.org/10.1016/j.jaci.2017.01.017 (Epub 2017 Feb)

    Article  CAS  PubMed  Google Scholar 

  31. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E, American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention (2017) Diagnosis, treatment, and long-term management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation 135(17):e927–e999

    Article  PubMed  Google Scholar 

  32. Zenone T, Souillet G (1996) X-linked agammaglobulinemia presenting as pseudomonas aeruginosa septicemia. Scand J Infect Dis 28(4):417–418

    Article  CAS  PubMed  Google Scholar 

  33. Keren G, Barzilay Z, Alpert G, Spirer Z, Danon Y (1983) Mucocutaneous lymph node syndrome (Kawasaki dIsease) in Israel. A review of 13 cases: is pseudomonas infection responsible? Acta Paediatr Scand 72(3):455–458

    Article  CAS  PubMed  Google Scholar 

  34. Candotti F (2018) Clinical manifestations and pathophysiological mechanisms of the Wiskott–Aldrich Syndrome. J Clin Immunol 38(1):13–27

    Article  CAS  PubMed  Google Scholar 

  35. Freeman AF, Avila EM, Shaw PA, Davis J, Hsu AP, Welch P, Matta JR, Hadigan C, Pettigrew RI, Holland SM, Gharib AM (2011) Coronary artery abnormalities in Hyper-IgE syndrome. J Clin Immunol 31:338–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hambleton S, Goodbourn S, Young DF, Dickinson P, Mohamad SM, Valappil M et al (2013) STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci USA 19(110):3053–3058

    Article  Google Scholar 

  37. Johnson RM, Bergmann KR, Manaloor JJ, Yu X, Slaven JE, Kharbanda AB (2016) Pediatric Kawasaki disease and adult human immunodeficiency virus kawasaki-like syndrome are likely the same malady. Open Forum Infect Dis 3(3):160 (eCollection 2016 Sep)

    Article  Google Scholar 

  38. Stankovic K, Miailhes P, Bessis D, Ferry T, Broussolle C, Sève P (2007) Kawasaki-like syndromes in HIV-infected adults. J Infect 55(6):488–494

    Article  CAS  PubMed  Google Scholar 

  39. Velez AP, Menezes L, Crespo A (2006) Kawasaki-like disease in an HIV-infected patient. AIDS Read 16(9):464–466

    PubMed  Google Scholar 

  40. Barbaro G, Di Lorenzo G, Barbarini G (2003) Kawasaki-like syndrome in an HIV-infected adult. Rheumatol (Oxf) 42(11):1427–1429

    Article  CAS  Google Scholar 

  41. Johnson RM, Barbarini G, Barbaro G (2003) Kawasaki-like syndromes and other vasculitic syndromes in HIV-infected patients. AIDS 17(Suppl 1):S77–S82

    Article  PubMed  Google Scholar 

  42. Blanchard JN, Powell HC, Freeman WR, Letendre S, Blanchard D, Shimizu C, Burns JC (2003) Recurrent Kawasaki disease-like syndrome in a patient with acquired immunodeficiency syndrome. Clin Infect Dis 36(1):105–111

    Article  PubMed  Google Scholar 

  43. Muniain-Ezcurra M, Bueno-Mariscal C, Rodríguez-Baño J, Domínguez-Castellano A, Balonga-Tomás B, Ríos-Villegas MJ, Borobio-Enciso MV, Pérez-Cano R (1998) Kawasaki disease and parvovirus B19 infection in an adult HIV-1-infected patient. Clin Microbiol Infect 4(10):609–610

    Article  PubMed  Google Scholar 

  44. Anderson MS (2002) Kawasaki-like illness in Human Immuno-deficiency Virus-infected patients: is the etiologic agent the same as in pediatric Kawasaki disease? Clin Infect Dis 34(6):875–878

    Article  PubMed  Google Scholar 

  45. Johnson RM, Little JR, Storch GA (2001) Kawasaki-like syndromes associated with human immunodeficiency virus infection. Clin Infect Dis 32(11):1628–1634

    Article  CAS  PubMed  Google Scholar 

  46. Martínez-Escribano JA, Redondo C, Galera C, Sánchez-Pedreño P, Abel JL, Frías JF (1998) Recurrent Kawasaki syndrome in an adult with HIV-1 infection. Dermatology 197(1):96–97

    PubMed  Google Scholar 

  47. Porneuf M, Sotto A, Barbuat C, Ribou G, Jourdan J (1996) Kawasaki syndrome in an adult AIDS patient. Int J Dermatol 35(4):292–294

    Article  CAS  PubMed  Google Scholar 

  48. Yoganathan K, Goodman F, Pozniak A (1995) Kawasaki-like syndrome in an HIV positive adult. J Infect 30(2):165–166

    Article  CAS  PubMed  Google Scholar 

  49. Viraben R, Dupre A (1987) Kawasaki disease associated with HIV infection. Lancet 1(8547):1430–1431

    Article  CAS  PubMed  Google Scholar 

  50. Komatsu H, Tateno A (2007) Failure to distinguish systemic-onset juvenile idiopathic arthritis from incomplete Kawasaki disease in an infant. J Paediatr Child Health 43(10):707–709

    Article  PubMed  Google Scholar 

  51. Binstadt BA, Levine JC, Nigrovic PA, Gauvreau K, Dedeoglu F, Fuhlbrigge RC, Weindling SN, Newburger JW, Sundel RP (2005) Coronary artery dilation among patients presenting with systemic-onset juvenile idiopathic arthritis. Pediatrics 116(1):e89–e93

    Article  PubMed  Google Scholar 

  52. Murray JC, Bomgaars LR, Carcamo B, Mahoney DH Jr (1995) Lymphoid malignancies following Kawasaki disease. Am J Hematol 50(4):299–300

    Article  CAS  PubMed  Google Scholar 

  53. Lim YJ, Jung JW, Jung HJ, Park JE (2013) Two cases of Kawasaki disease with hidden neuroblastoma. Indian J Pediatr 80(10):881–883

    Article  PubMed  Google Scholar 

  54. Swinson S, Hall G, Pollard AJ (2004) Reactivation of the bacille Calmette-Guérin scar following immune reconstitution during treatment of infant acute lymphoblastic leukemia. J Pediatr Hematol Oncol 26(2):112–115

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr. Alberto Unzueta for editing and helpful discussions.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Clinical Immunology Department, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, Col. Insurgentes Cuicuilco, 04530, Mexico City, Mexico

    Francisco Rivas-Larrauri, Lorena Aguilar-Zanela, Paola Castro-Oteo, Luis Adrian Rosales-Hernandez & Marco Antonio Yamazaki-Nakashimada

  2. Pediatric Infectology Department, Instituto Nacional de Pediatría, Mexico City, Mexico

    Francisco Otero-Mendoza & Javier Ordoñez-Ortega

  3. Immunodeficiencies Research Unit, Instituto Nacional de Pediatría, Mexico City, Mexico

    Gabriela López-Herrera

  4. Pediatric Cardiology Department, Instituto Nacional de Pediatría, Mexico City, Mexico

    Martín Garrido-García

Authors
  1. Francisco Rivas-Larrauri
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  2. Lorena Aguilar-Zanela
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  3. Paola Castro-Oteo
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  4. Luis Adrian Rosales-Hernandez
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  5. Francisco Otero-Mendoza
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  6. Gabriela López-Herrera
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  7. Javier Ordoñez-Ortega
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  8. Martín Garrido-García
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  9. Marco Antonio Yamazaki-Nakashimada
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Contributions

Case 1 was diagnosed and followed up by LAZ, PCO, LARH, JOO and MAYN. FRL, MGG, and MAYN were involved in the caring of Case 2 and Case 3, and Case 4 was diagnosed and followed up by FOM, GLH, and MAYN. LAZ, PCO, LARH, and MAYN wrote the manuscript. Literature data were searched and analyzed by all the authors. The final version was read corrected and approved by all the authors.

Corresponding author

Correspondence to Marco Antonio Yamazaki-Nakashimada.

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Conflict of interest

Dr. Marco Antonio Yamazaki-Nakashimada has received lecture fees from Shire, CSL Behring and Octapharma, and the other authors declare that they do not have any conflict of interests.

Ethical approval

All the procedures performed in this study were in accordance with the ethical standards of the institutional and or national research committee and with the 1964 Helsinki Declaration and its later amendments.

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Written informed consent was obtained from the patients for publication of the case reports.

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Rivas-Larrauri, F., Aguilar-Zanela, L., Castro-Oteo, P. et al. Kawasaki disease and immunodeficiencies in children: case reports and literature review. Rheumatol Int 39, 1829–1838 (2019). https://doi.org/10.1007/s00296-019-04382-w

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