Neutropenia in the acute phase of Kawasaki disease and prevention of coronary artery aneurysm
Corresponding Author
Zenshiro Onouchi
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Zenshiro Onouchi, MD, PhD, Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 2-1-119 Hatoyama, Uji City, Kyoto 611-0012, Japan. Email: [email protected]Search for more papers by this authorKenji Hamaoka
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Search for more papers by this authorSeiichiro Ozawa
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Search for more papers by this authorKoichi Sakata
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Search for more papers by this authorNobuyuki Kiyosawa
Department of Pediatrics, Second Kyoto Red Cross Hospital, Kyoto, Japan
Search for more papers by this authorHisato Ito
Department of Pediatrics, Second Kyoto Red Cross Hospital, Kyoto, Japan
Search for more papers by this authorCorresponding Author
Zenshiro Onouchi
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Zenshiro Onouchi, MD, PhD, Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 2-1-119 Hatoyama, Uji City, Kyoto 611-0012, Japan. Email: [email protected]Search for more papers by this authorKenji Hamaoka
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Search for more papers by this authorSeiichiro Ozawa
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Search for more papers by this authorKoichi Sakata
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine and
Search for more papers by this authorNobuyuki Kiyosawa
Department of Pediatrics, Second Kyoto Red Cross Hospital, Kyoto, Japan
Search for more papers by this authorHisato Ito
Department of Pediatrics, Second Kyoto Red Cross Hospital, Kyoto, Japan
Search for more papers by this authorAbstract
Background: The significance of neutropenia in Kawasaki disease (KD) has not been fully elucidated as yet.
Methods: Subjects were retrospectively sampled from two clinical trials. These patients treated with aspirin alone (ASA) and PolyglobinN-Bayel (PolyN) given as i.v. immunoglobulin were categorized as ASA-early (n = 0), ASA-late (n = 8), PolyN-early (n = 18), or PolyN-late (n = 27) based on the therapy administered and the incidence of neutropenia before the 10th day of illness (DI) and after 11 DI. Data regarding the time of onset of neutropenia, and incidence of coronary artery lesion (CAL) formation were obtained. P < 0.05 was considered statistically significant.
Results: No patients in the ASA group exhibited neutropenia within 10 DI. The time of onset of neutropenia in the PolyN-early group was 8 ± 1.3 DI. That in the PolyN-late group (19.8 ± 8 DI) was earlier than in the ASA-late group (26.6 ± 14 DI; P < 0.025). PolyN-early patients had a lower incidence of CAL formation than ASA-non patients (patients without neutropenia in the ASA group; P = 0.00019) and ASA-late patients (P = 0.04). That in the PolyN-early group tended to be lower than in the PolyN-late group (P < 0.1).
Conclusion: Early neutropenia indicated that circulating neutrophils within 10 DI may play an indispensable role in the following sequence to CAL formation in KD.
References
- 1 Onouchi Z, Tomizawa M, Goto M, Nakata K, Goto M. Cardiac involvement and prognosis in acute mucocutaneous lymph node syndrome. Chest 1975; 68: 297–301.
- 2 Research committee on Kawasaki disease. Report of Subcommittee on Standardization of Diagnostic Criteria and Reporting of Coronary Artery Lesions in Kawasaki Disease. Ministry of Health and Welfare, Tokyo, 1994.
- 3 Hicks RY, Melish ME. Kawasaki disease. Pediatr. Clin. North Am. 1986; 33: 1151–75.
- 4 Kawano Y, Hosoya R, Yamamoto K, Nishimura K. Kawasaki disease and agranulocytosis. Acta Paediatr. Jpn. 1984; 26: 576–80.
- 5 Tsuneta H, Kojima K, Takahashi T, Ishii T. Four cases of Kawasaki disease with transient neutropenia: A possible role of high-dose gammaglobulin on neutropenia. J. Jpn. Pediatr. Soc. 1988; 92: 936–41 (in Japanese).
- 6 Newburger JW, Takahashi M, Burns JC et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N. Engl. J. Med. 1986; 315: 341–7.
- 7 Onouchi Z, Isogai Y, Yanagisawa M et al. Multicenter randomized controlled study of intravenous immunoglobulin in Kawasaki disease. J. Jpn. Pediatr. Soc. 1988; 92: 2367–76 (in Japanese).
- 8 Morikawa Y, Ohashi Y, Harada K et al. A multicenter, randomized controlled trial of intravenous gammaglobulin therapy in children with Kawasaki disease. Acta Paediatr. Jpn. 1994; 36: 347–54.
- 9 Hara T, Mizuno Y, Ueda K et al. Neutropenia in Kawasaki disease. Eur. J. Pediatr. 1989; 148: 580.
- 10 Onouchi Z. Inhibition of CAL formation in the different daily doses of Polyglobin N in the acute phase of Kawasaki disease. Prog. Med. 2003; 23: 1512–17 (in Japanese).
- 11 Oki I, Yashiro M, Uehara R et al. Comparison of principal symptoms of Kawasaki disease between early stage (1971) and recent (2003) nationwide surveys. J. Jpn. Pediatr. Soc. 2005; 109: 484–91 (in Japanese).
- 12 Tsujimoto H, Takeshita S, Nakatani K, Kawamura Y, Tokutomi T, Sekine I. Delayed apoptosis of circulating neutrophils in Kawasaki disease. Clin. Exp. Immunol. 2001; 126: 355–64.
- 13 Homburg CHE, Roos D. Apoptosis of neutrophils. Curr. Opin. Hematol. 1996; 3: 94–9.
- 14 Squer MK, Schnert AJ, Cohen JJ. Apoptosis in leukocytes. J. Leukoc. Biol. 1995; 57: 2–10.
- 15 Leung DYM, Cotran RS, Kurt-Jones E, Burns JC, Newburger JW, Pober JS. Endothelial cell activation and high interleukin-1 secretion in the pathogenesis of acute Kawasaki disease. Lancet 1989; 2: 1298–302.
- 16 Furukawa S, Matsubara T, Yone K, Hirano Y, Okumura K, Yabuta K. Kawasaki disease differs from anaphylactic purpura and measles with regard to tumour necrosis factor-alpha and interleukin-6 in serum. Eur. J. Pediatr. 1992; 151: 44–7.
- 17 Lin CY, Lin CC, Hwang B, Chiang B. Serial changes of serum interleukin-6, interleukin-8,and tumor necrosis factor alpha among patients with Kawasaki disease. J. Pediatr. 1992; 121: 924–6.
- 18 Igarashi H, Hatake K, Tomizuka H, Yamada M, Gunji Y, Momoi MY. High serum level of M-CSF and G-CSF in Kawasaki disease. Br. J. Hematol. 1999; 105: 613–15.
- 19 Terai M, Jibiki T, Harada A et al. Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after γ globulin treatment. J. Leukoc. Biol. 1999; 65: 566–72.
- 20 Yoshioka T, Matsutani T, Iwagami S et al. Polyclonal expansion of TCRBV2- and TCRBV6-bearing T cells in patients with Kawasaki disease. Immunology 1999; 96: 465–72.
- 21 Schiller B, Elinder G. Inflammatory parameters and soluble cell adhesion molecules in Swedish children with Kawasaki disease: Relationship to cardiac lesions and intravenous immunoglobulin treatment. Acta. Paediatr. 1999; 88: 844–8.
- 22 Onouchi Z, Hamaoka K, Sakata K, Ozawa S, Kiyosawa N, Ito H. Effects of IVIG on neutrophilia in Kawasaki disease. J. Jpn. Pediatr. Soc. 2003; 107: 289 [in Japanese].
- 23 Dwyer JM. Manipulating the immune system with immune globulin. N. Engl. J. Med. 1992; 326: 107–16.
- 24 Prasad NK, Papoff G, Zeuner A et al. Therapeutic preparations of normal polyspecific IgG (IVIg) induce apoptosis in human lymphocytes and monocytes, a novel mechanism of action of IVIg involving the Fas apoptotic pathway. J. Immunol. 1998; 161: 3781–90.
- 25 Igarashi H, Hatake K, Shiraishi H, Samada K, Tomizuka H, Momoi MY. Elevated serum levels of macrophage colony-stimulating factor in patients with Kawasaki disease complicated by cardiac lesions. Clin. Exp. Rheumatol. 2001; 19: 751–6.
- 26 Durongpisitkul K, Soongswang J, Laohaprasitiporn D, Nana A, Prachuabmoh C, Kangkagate C. Immunoglobulin failure and retreatment in Kawasaki disease. Pediatr. Cardiol. 2003; 24: 145–8.
- 27 Asai T, Tatara K, Sonobe T et al. Follow-up results of prospective study of the three groups of therapies for Kawasaki disease and analysis of clinical data. Shonika 1985; 26: 995–1004 (in Japanese).
- 28 Stossel TP. The phagocyte system: Structure and function. In: DG Nathan, FA Oski (eds). Hematology of Infancy and Childhood. Saunders, Philadelphia, 1987; 779–96.
- 29 Naoe S, Takahashi K, Masuda H, Tanaka N. Kawasaki disease with particular emphasis on arterial lesions. Acta Pathol. Jpn. 1991; 41: 785–97.
- 30 Hirono K, Foell D, Xing Y et al. Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease. J. Am. Coll. Cardiol. 2006; 48: 1257–64.
- 31 Leung DY. Immunologic aspects of Kawasaki syndrome. J. Rheumatol. Suppl. 1990; 24: 15–18.
- 32 Suzuki H, Noda E, Miyawaki M, Takeuchi T, Uemura S, Koike M. Serum levels of neutrophil activation cytokines in Kawasaki disease. Pediatr. Int. 2001; 43: 115–19.
- 33 Nakatani K, Takeshita S, Tsujimoto H, Kawamura Y, Sekine I. Inhibitory effect of serine protease inhibitors on neutrophil-mediated endothelial cell injury. J. Leukoc. Biol. 2001; 69: 241–7.