Journal of Yeungnam Medical Science

Yeungnam University College of Medicine, Yeungnam University Institute Medical Science (영남대 의대 학술지 편집위원회)
권호 표지
DOI QR코드

DOI QR Code

Severe congenital neutropenia mimicking chronic idiopathic neutropenia: a case report

  • Juhyung Kim (Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University) ;
  • Soyoon Hwang (Department of Infectious Diseases, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University) ;
  • Narae Hwang (Department of Clinical Pathology, School of Medicine, Kyungpook National University) ;
  • Yeonji Lee (Department of Internal Medicine, Kyungpook National University Hospital) ;
  • Hee Jeong Cho (Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University) ;
  • Joon Ho Moon (Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University) ;
  • Sang Kyun Sohn (Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University) ;
  • Dong Won Baek (Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University)
  • Received : 2022.05.16
  • Accepted : 2022.06.27
  • Published : 2023.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Severe chronic neutropenia is classified as severe congenital, cyclic, autoimmune, or idiopathic. However, there is a lot of uncertainty regarding the diagnosis of severe congenital neutropenia (SCN) and chronic idiopathic neutropenia, and this uncertainty affects further evaluations and treatments. A 20-year-old man presented with fever and knee abrasions after a bicycle accident. On admission, his initial absolute neutrophil count (ANC) was 30/µL. He had no medical history of persistent severe neutropenia with periodic oscillation of ANC. Although his fever resolved after appropriate antibiotic therapy, ANC remained at 80/µL. Bone marrow (BM) aspiration and biopsy were performed, and a BM smear showed myeloid maturation arrest. Moreover, genetic mutation test results showed a heterozygous missense variant in exon 4 of the neutrophil elastase ELANE: c597+1G>C (pV190-F199del). The patient was diagnosed with SCN. After discharge, we routinely checked his ANC level and monitored any signs of infection with minimum use of granulocyte colony-stimulating factor (G-CSF), considering its potential risk of leukemic transformation. Considering that SCN can be fatal, timely diagnosis and appropriate management with G-CSF are essential. We report the case of a patient with SCN caused by ELANE mutation who had atypical clinical manifestations. For a more accurate diagnosis and treatment of severe chronic neutropenia, further studies are needed to elucidate the various clinical features of ELANE.

Keywords

References

  1. Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, Boxer LA, et al. Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hematol 2003;72:82-93. https://doi.org/10.1002/ajh.10255
  2. Wan C, Yu HH, Lu MY, Lee JH, Wang LC, Lin YT, et al. Clinical manifestations and outcomes of pediatric chronic neutropenia. J Formos Med Assoc 2012;111:220-7. https://doi.org/10.1016/j.jfma.2010.12.003
  3. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis 2011;6:26.
  4. Boxer LA. How to approach neutropenia. Hematology Am Soc Hematol Educ Program 2012;2012:174-82. https://doi.org/10.1182/asheducation.V2012.1.174.3798251
  5. Walkovich K, Boxer LA. How to approach neutropenia in childhood. Pediatr Rev 2013;34:173-84. https://doi.org/10.1542/pir.34.4.173
  6. Dale DC, Bolyard AA. An update on the diagnosis and treatment of chronic idiopathic neutropenia. Curr Opin Hematol 2017;24:46-53. https://doi.org/10.1097/MOH.0000000000000305
  7. Newburger PE, Pindyck TN, Zhu Z, Bolyard AA, Aprikyan AA, Dale DC, et al. Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes. Pediatr Blood Cancer 2010;55:314-7. https://doi.org/10.1002/pbc.22537
  8. Sicre de Fontbrune F, Moignet A, Beaupain B, Suarez F, Galicier L, Socie G, et al. Severe chronic primary neutropenia in adults: report on a series of 108 patients. Blood 2015;126:1643-50. https://doi.org/10.1182/blood-2015-03-634493
  9. Munshi HG, Montgomery RB. Severe neutropenia: a diagnostic approach. West J Med 2000;172:248-52. https://doi.org/10.1136/ewjm.172.4.248
  10. Kurnikova M, Maschan M, Dinova E, Shagina I, Finogenova N, Mamedova E, et al. Four novel ELANE mutations in patients with congenital neutropenia. Pediatr Blood Cancer 2011;57:332-5. https://doi.org/10.1002/pbc.23104
  11. Cho HK, Jeon IS. Different clinical phenotypes in familial severe congenital neutropenia cases with same mutation of the ELANE gene. J Korean Med Sci 2014;29:452-5. https://doi.org/10.3346/jkms.2014.29.3.452
  12. Germeshausen M, Schulze H, Ballmaier M, Zeidler C, Welte K. Mutations in the gene encoding neutrophil elastase (ELA2) are not sufficient to cause the phenotype of congenital neutropenia. Br J Haematol 2001;115:222-4. https://doi.org/10.1046/j.1365-2141.2001.03069.x
  13. Makaryan V, Zeidler C, Bolyard AA, Skokowa J, Rodger E, Kelley ML, et al. The diversity of mutations and clinical outcomes for ELANE-associated neutropenia. Curr Opin Hematol 2015;22:3-11. https://doi.org/10.1097/MOH.0000000000000105
  14. Gupta A, Dhingra A. Incidental chronic neutropenia in an asymptomatic adult. Cureus 2017;9:e1779.
  15. Solomou EE, Salamaliki C, Lagadinou M. How to make the right diagnosis in neutropenia. Clin Hematol Int 2021;3:41-6. https://doi.org/10.2991/chi.k.210216.001
  16. Rotulo GA, Beaupain B, Rialland F, Paillard C, Nachit O, Galambrun C, et al. HSCT may lower leukemia risk in ELANE neutropenia: a before-after study from the French Severe Congenital Neutropenia Registry. Bone Marrow Transplant 2020;55:1614-22. https://doi.org/10.1038/s41409-020-0800-1
  17. Rotulo GA, Plat G, Beaupain B, Blanche S, Moushous D, Sicre de Fontbrune F, et al. Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE-related neutropenia: a French Severe Chronic Neutropenia Registry study. Br J Haematol 2021;194:908-20. https://doi.org/10.1111/bjh.17695
  18. Dale DC, Bonilla MA, Davis MW, Nakanishi AM, Hammond WP, Kurtzberg J, et al. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 1993;81:2496-502. https://doi.org/10.1182/blood.V81.10.2496.2496
  19. Dale DC. The discovery, development and clinical applications of granulocyte colony-stimulating factor. Trans Am Clin Climatol Assoc 1998;109:27-36.
  20. Skokowa J, Dale DC, Touw IP, Zeidler C, Welte K. Severe congenital neutropenias. Nat Rev Dis Primers 2017;3:17032.