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Pediatric intestinal Behçet disease complicated by myeloid malignancies

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Abstract

Behçet disease (BD) is rarely seen in children. Its clinical manifestations are believed to differ between pediatric and adult patients. The characteristics of BD complicated by myelodysplastic syndrome (MDS) are well established for adult patients; however, because only a few cases of pediatric-onset BD complicated by MDS have been reported, its clinical characteristics remain unknown. We here retrospectively review pediatric-onset BD complicated by myeloid malignancies in Japan, having identified five such patients. All patients were female and had gastrointestinal involvements, but lacked both major features of BD, i.e., uveitis and association with HLA-B51. All patients had advanced MDS or acute myeloid leukemia and received chemotherapy followed by hematopoietic stem cell transplantation. These five cases suggest that intestinal BD and myeloid malignancies have one or more pathophysiological mechanisms in common.

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Abbreviations

5-ASA:

5-Aminosalicylic acid

AML:

Acute myeloblastic leukemia

BD:

Behçet disease

BMT:

Bone marrow transplantation

GVHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem cell transplantation

MDS:

Myelodysplastic syndrome

RAEB-t:

Refractory anemia with excess of blasts in transformation

TBI:

Total body irradiation

References

  1. Davatchi F, Shahram F, Chams-Davatchi C, Shams H, Nadji A, Akhlaghi M, et al. Behcet’s disease: from East to West. Clin Rheumatol. 2010;29:823–33.

    Article  PubMed  Google Scholar 

  2. Koné-Paut I, Yurdakul S, Bahabri SA, Shafae N, Ozen S, Ozdogan H, et al. Clinical features of Behçet’s disease in children: an international collaborative study of 86 cases. J Pediatr. 1998;132:721–5.

    Article  PubMed  Google Scholar 

  3. Fujikawa S, Suemitsu T. Behçet disease in children: a nationwide retrospective survey in Japan. Acta Paediatr Jpn. 1997;39:285–9.

    Article  CAS  PubMed  Google Scholar 

  4. Glaubach T, Robinson LJ, Corey SJ. Pediatric myelodysplastic syndromes: they do exist! J Pediatr Hematol Oncol. 2014;36:1–7.

    Article  PubMed  Google Scholar 

  5. Eder L, Rozenbaum M, Boulman N, Aayubkhanov E, Wolfovitz E, Zisman D, et al. Behçet’s disease, myelodysplastic syndrome, trisomy 8, gastroenterological involvement–an association. Clin Exp Rheumatol. 2005;23:S91–5.

    CAS  PubMed  Google Scholar 

  6. Fujimura T, Yukawa N, Nakashima R, Imura Y, Kawabata D, Nojima T, et al. Periodic fever and erythema nodosum associated with MDS with trisomy 8: report of two cases and review of the literature. Mod Rheumatol. 2010;20:413–9.

    Article  PubMed  Google Scholar 

  7. Kawabata H, Sawaki T, Kawanami T, Shimoyama K, Karasawa H, Fukushima T, et al. Myelodysplastic syndrome complicated with inflammatory intestinal ulcers: significance of trisomy 8. Intern Med. 2006;45:1309–14.

    Article  PubMed  Google Scholar 

  8. Yamato K. Successful cord blood stem cell transplantation for myelodysplastic syndrome with Behçet disease. Int J Hematol. 2003;77:82–5.

    Article  PubMed  Google Scholar 

  9. Shigemura T, Agematsu K, Yamazaki T, Sakashita K, Nakayama Y, Higuchi Y, et al. A case of Behcet’s disease associated with myelodysplastic syndrome involving trisomy 8 and a gain-of-function mutation in SHP-2. Rheumatology (Oxford). 2011;50:1342–4.

    Article  CAS  Google Scholar 

  10. Ohta A, Nagai M, Nishina M, Shibazaki S, Ishijima H, Izumida M. Age at the onset of intractable disease: based on a clinical database for patients receiving financial aid for treatment (in Japanese). Nihon Koshu Eisei Zasshi. 2007;54:3–14.

    PubMed  Google Scholar 

  11. Evereklioglu C, Er H, Türköz Y, Cekmen M. Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease. Mediators Inflamm. 2002;11:87–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Misumi M, Hagiwara E, Takeno M, Takeda Y, Inoue Y, Tsuji T, et al. Cytokine production profile in patients with Behcet’s disease treated with infliximab. Cytokine. 2003;24:210–8.

    Article  CAS  PubMed  Google Scholar 

  13. Musto P, Matera R, Minervini MM, Checchia-de Ambrosio C, Bodenizza C, Falcone A, et al. Low serum levels of tumor necrosis factor and interleukin-1 beta in myelodysplastic syndromes responsive to recombinant erythropoietin. Haematologica. 1994;79:265–8.

    CAS  PubMed  Google Scholar 

  14. Stasi R, Brunetti M, Bussa S, Conforti M, Martin LS, La Presa M, et al. Serum levels of tumour necrosis factor-alpha predict response to recombinant human erythropoietin in patients with myelodysplastic syndrome. Clin Lab Haematol. 1997;19:197–201.

    Article  CAS  PubMed  Google Scholar 

  15. Touma Z, Farra C, Hamdan A, Shamseddeen W, Uthman I, Hourani H, et al. TNF polymorphisms in patients with Behçet disease: a meta-analysis. Arch Med Res. 2010;41:142–6.

    Article  CAS  PubMed  Google Scholar 

  16. Claessens Y-E, Bouscary D, Dupont J-M, Picard F, Melle J, Gisselbrecht S, et al. In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis. Blood. 2002;99:1594–601.

    Article  CAS  PubMed  Google Scholar 

  17. Maciejewski J, Selleri C, Anderson S, Young NS. Fas antigen expression on CD34 + human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro. Blood. 1995;85:3183–90.

    CAS  PubMed  Google Scholar 

  18. Arimura K, Arima N, Matsushita K, Akimoto M, Park CY, Uozumi K, et al. High incidence of morphological myelodysplasia and apoptotic bone marrow cells in Behçet’s disease. J Clin Immunol. 2007;27:145–51.

    Article  PubMed  Google Scholar 

  19. Chen G, Zeng W, Miyazato A, Billings E, Maciejewski JP, Kajigaya S, et al. Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities. Blood. 2004;104:4210–8.

    Article  CAS  PubMed  Google Scholar 

  20. Sloand EM, Kim S, Fuhrer M, Risitano AM, Nakamura R, Maciejewski JP, et al. Fas-mediated apoptosis is important in regulating cell replication and death in trisomy 8 hematopoietic cells but not in cells with other cytogenetic abnormalities. Blood. 2002;100:4427–32.

    Article  CAS  PubMed  Google Scholar 

  21. Sloand EM, Mainwaring L, Fuhrer M, Ramkissoon S, Risitano AM, Keyvanafar K, et al. Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome. Blood. 2005;106:841–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sloand EM, Pfannes L, Chen G, Shah S, Solomou EE, Barrett J, et al. CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins. Blood. 2007;109:2399–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Drs. Akiko Ohta and Masaki Nagai (Department of Public Health, Saitama Medical University Faculty of Medicine) for helping to collect epidemiological data on Behçet disease in Japan.

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology, Okayama University Hospital, Okayama, 2-5-1, Shikatacho, Kitaku, Okayama, 700-8558, Japan

    Kiichiro Kanamitsu, Akira Shimada & Hirokazu Tsukahara

  2. Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan

    Ritsuo Nishiuchi

  3. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan

    Tomonari Shigemura, Yozo Nakazawa & Kenichi Koike

  4. Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Yuichi Kodama, Yuichi Shinkoda & Yoshifumi Kawano

  5. Department of Pediatrics, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan

    Kozo Yasui

  6. Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Koji Sasaki & Ryosuke Kajiwara

  7. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    Atsushi Manabe

Authors
  1. Kiichiro Kanamitsu
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  2. Akira Shimada
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  3. Ritsuo Nishiuchi
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  4. Tomonari Shigemura
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  5. Yozo Nakazawa
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  6. Kenichi Koike
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  7. Yuichi Kodama
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  8. Yuichi Shinkoda
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  9. Yoshifumi Kawano
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  10. Kozo Yasui
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  11. Koji Sasaki
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  12. Ryosuke Kajiwara
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  13. Hirokazu Tsukahara
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  14. Atsushi Manabe
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Corresponding author

Correspondence to Akira Shimada.

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Conflict of interest

This study was supported in part by a Grant-in-Aid for Cancer Research and a grant for Clinical Cancer Research and Research on Children and Families from the Ministry of Health, Labour and Welfare of Japan. The authors declare no conflict of interest associated with this manuscript.

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Kanamitsu, K., Shimada, A., Nishiuchi, R. et al. Pediatric intestinal Behçet disease complicated by myeloid malignancies. Int J Hematol 105, 377–382 (2017). https://doi.org/10.1007/s12185-016-2127-7

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  • DOI: https://doi.org/10.1007/s12185-016-2127-7

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