European Journal of Pediatrics

, Volume 172, Issue 6, pp 811–819 | Cite as

Transient neutropenia in children with febrile illness and associated infectious agents: 2 years’ follow-up

  • Ourania AlexandropoulouEmail author
  • Lydia Kossiva
  • Fotis Haliotis
  • Maria Giannaki
  • Maria Tsolia
  • I. P. Panagiotou
  • Kyriaki Karavanaki
Original Article


The aim of the study was to identify the relationship of acquired neutropenia with childhood infections and to assess its clinical course, complications, and outcome. Children admitted to two pediatric wards over a 4-year period with febrile neutropenia were prospectively investigated for underlying infections with inflammatory markers, cultures of body fluids, and serological tests. The study included 161 previously healthy children with febrile neutropenia/leukopenia aged (mean ± SD) 3.02 ± 3.86 years (range, 0.1–14). One hundred and thirty-six out of 161 patients (84.5 %) had transient neutropenia (TN), while in 25 patients, neutropenia was chronic (CN) and persisted for ≥180 days. An infectious agent was isolated in 98/161 (60.9 %) cases, in 68.4 % patients with TN, and in 20 % of those with CN (p = 0.001). Among the patients with CN, seven had positive antineutrophil antibodies (autoimmune neutropenia) and four were eventually diagnosed with hematological malignancy. In all age groups, TN was of short duration (<1 month), of mild to moderate severity, and was predominantly associated with viral infections. Two years after diagnosis, 143/161 children (88.8 %) were available for follow-up. One hundred and thirty-seven of 143 (95.8 %) had recovered completely, while the rest remained neutropenic. The latter patients had a benign course despite severe neutropenia. In conclusion, febrile neutropenia during childhood is usually transient, often following viral and common bacterial infections, without serious complications and in the majority of cases it resolves spontaneously. However, in a considerable percentage of patients, neutropenia is discovered incidentally during the course of an infection on the ground of an underlying hematological disease.


Infection Children Transient neutropenia Fever 



Transient neutropenia


Chronic neutropenia


Autoimmune neutropenia


Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Alexandropoulou O, Tsolia M, Kossiva L, Giannaki M, Karavanaki K (2012) Visceral leishmaniasis: a common cause of postinfectious febrile pancytopenia in children in an endemic area: experience of a children’s tertiary hospital. Pediatr Emerg Care 28(6):533–537PubMedCrossRefGoogle Scholar
  2. 2.
    Auner H, Klintschar M, Crevenna R, Beham-Schmid C, Hoefler G, Mitterbauer G, Linkesch W, Sill H (1999) Two case studies of chronic idiopathic neutropenia preceding acute myeloid leukaemia. Br J Haematol 105(2):431–433PubMedCrossRefGoogle Scholar
  3. 3.
    Beausejour C (2007) Bone marrow-derived cells: the influence of aging and cellular senescence. Handb Exp Pharmacol 180:67–88PubMedCrossRefGoogle Scholar
  4. 4.
    Bux J, Behrens G, Jaeger G, Welte K (1998) Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases. Blood 91(1):181–186PubMedGoogle Scholar
  5. 5.
    Capsoni F, Sarzi-Puttini P, Zanella A (2005) Primary and secondary autoimmune neutropenia. Arthritis Res Ther 7(5):208–214PubMedCrossRefGoogle Scholar
  6. 6.
    Citak EC, Arman D (2011) Brucella melitensis: a rare cause of febrile neutropenia. Pediatr Hematol Oncol 28(1):83–85PubMedCrossRefGoogle Scholar
  7. 7.
    Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, Boxer LA, Cham B, Freedman MH, Kannourakis G, Kinsey SE, Davis R, Scarlata D, Schwinzer B, Zeidler C, Welte K (2003) Severe chronic neutropenia: treatment and follow-up of patients with severe chronic neutropenia international registry. Am J Haematol 72(2):82–93CrossRefGoogle Scholar
  8. 8.
    Galanakis E, Bourantas KL, Leveidiotou S, Lapatsanis PD (1996) Childhood brucellosis in north-western Greece: a retrospective analysis. Eur J Pediatr 155(1):1–6PubMedCrossRefGoogle Scholar
  9. 9.
    Hasle H, Niemeyer CM, Chessels JM, Baumann I, Bennett NK, Kerndrup G, Head DR (2003) A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 17:277–282PubMedCrossRefGoogle Scholar
  10. 10.
    Hollowell JG, van Assendelft OW, Gunter EW, Lewis BG, Najjar M, Pfeiffer C (2005) Hematological and iron-related analytes-reference data for persons aged 1 year and over: Unites States, 1988–94. Vital Health Stat 11:1Google Scholar
  11. 11.
    Husain EH, Mullah-Ali A, Al-Sharidah S, Azab AF, Adekile A (2012) Infectious etiologies of transient neutropenia in previously healthy children. Pediatr Infect Dis J 31(6):575–577PubMedCrossRefGoogle Scholar
  12. 12.
    Istomin V, Slade E, Grossman Z, Rudich H, Zudich H, Sofer O, Hassin D (2004) Agranulocytosis associated with parvovirus B19 infection in otherwise healthy patients. Eur J Intern Med 15(8):531–533PubMedCrossRefGoogle Scholar
  13. 13.
    James RM, Kinsey SE (2006) The investigation and management of chronic neutropenia in children. Arch Dis Child 91:852–858PubMedCrossRefGoogle Scholar
  14. 14.
    Karakukcu M, Patiroglu T, Ozdemir MA, Gunes T, Gumus H, Karakukcu C (2004) Pancytopenia, a rare hematologic manifestation of brucellosis in children. J Pediatr Hematol Oncol 26(12):803–806PubMedGoogle Scholar
  15. 15.
    Karavanaki K, Polychronopoulou S, Giannaki M, Haliotis F, Sider B, Brisimitzi M, Dimitriou C, Scordias G, Marangou F, Stamatiadou A, Avlonitis S (2006) Transient and chronic neutropenias detected in children with different viral and bacterial infections. Acta Pediatr 95:565–572CrossRefGoogle Scholar
  16. 16.
    Kobayashi M, Nakamura K, Kawaguchi H, Sato T, Kihara H, Hiraoka A, Tanihiro M, Taniguchi K, Takata N, Ueda K (2002) Significance of the detection of antineutrophil antibodies in children with chronic neutropenia. Blood 99(9):3468–3471PubMedCrossRefGoogle Scholar
  17. 17.
    Lehmann HW, von Landenberg P, Modrow S (2003) Parvovirus B19 infection and autoimmune disease. Autoim Rev 2:218–223CrossRefGoogle Scholar
  18. 18.
    Nickerson C, Lurtha H, David C (1991) Antigenic mimicry and autoimmune diseases. Int Rev Immunol 7:205–224PubMedCrossRefGoogle Scholar
  19. 19.
    Panepinto JA, Brousseau DC (2005) Acute idiopathic thrombocytopenic purpura of childhood-diagnosis and therapy. Pediatr Emerg Care Oct 21(10):691–5CrossRefGoogle Scholar
  20. 20.
    Rajantie J, Kurki S, Juvonen E, Hovi L (1993) Prolonged pure granulocytopenia in children. Acta Paediatrica 82(10):839–842PubMedCrossRefGoogle Scholar
  21. 21.
    Serwint JR, Dias MM, Chang H, Sharkey M, Walker AR (2005) Outcomes of febrile children presumed to be immunocompetent who present with leucopenia or neutropenia to an ambulatory setting. Clin Pediatr (Phila) 44(7):593–600CrossRefGoogle Scholar
  22. 22.
    Sevilla J, del Carmen Escudero M, Jimenez R, Gonzalez Vincent M, Sevilla J, Díaz MA, Madero L (2004) Severe systemic autoimmune disease associated with Epstein–Barr virus infection. J Pediatr Hematol Oncol 26:831–833PubMedCrossRefGoogle Scholar
  23. 23.
    Sheen JM, Kuo HC, Yu HR, Huang EY, Wu CC, Yang KD (2009) Prolonged acquired neutropenia in children. Pediatr Blood Cancer 53(7):1284–1288PubMedCrossRefGoogle Scholar
  24. 24.
    Singh KJ, Ahluwalia G, Sharma SK, Saxena R, Chaudhary VP, Anant M (2001) Significance of haematological manifestations in patients with tuberculosis. J Assoc Phys India 49(788):790–794Google Scholar
  25. 25.
    Sloand E (2005) Hematological complications of HIV infection. AIDS Rev 7(4):187–196PubMedGoogle Scholar
  26. 26.
    SuI J, Wang CH, Cheng AL, Chen RL (1995) Hemophagocytic syndrome in Epstein-Barr virus-associated T-lymphoproliferative disorders: disease spectrum, pathogenesis and management. Leuk Lymhoma 19(5–6):401–406CrossRefGoogle Scholar
  27. 27.
    Suqita K, Haqisawa S, Satoh Y, Equchi M, Furukawa T (1998) Recurrent hepatosplenomegaly and peripheral blood cytopenia, persistent Epstein–Barr virus infection and central nervous system manifestation in a patient with lymphadenopathy and low serum uric acid. Acta Paediatr Jpn 40(4):362–366CrossRefGoogle Scholar
  28. 28.
    Valliaveedan R, Rao S, Miller S, Brown A (1987) Transient neutropenia of childhood. Clinical Pediatr (Phila) 26(12):639–642CrossRefGoogle Scholar
  29. 29.
    Vlacha V, Feketea G (2007) The clinical significance of non-malignant neutropenia in hospitalized children. Ann Hematol 86(12):865–870PubMedCrossRefGoogle Scholar
  30. 30.
    Weatherall DJ, Kwiatkowski D. Hematologic manifestations of systemic diseases in children of the developing world. In: Nathan D, Orkin (eds) Hematology of infancy and childhood, 5th edn. Saunders, Philadelphia, p 1902Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ourania Alexandropoulou
    • 1
    Email author
  • Lydia Kossiva
    • 2
  • Fotis Haliotis
    • 3
  • Maria Giannaki
    • 4
  • Maria Tsolia
    • 2
  • I. P. Panagiotou
    • 2
  • Kyriaki Karavanaki
    • 2
  1. 1.Agrinio General HospitalAgrinioGreece
  2. 2.2nd Department of Pediatrics, University of Athens, “P&A Kyriakou” Children’s HospitalAthensGreece
  3. 3.2nd Pediatric Department, “Aghia Sophia” Children’s HospitalAthensGreece
  4. 4.Microbiology Department, “Aghia Sophia” Children’s HospitalAthensGreece

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