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Published in: European Journal of Pediatrics 6/2013

01-06-2013 | Original Article

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

Authors: Ourania Alexandropoulou, Lydia Kossiva, Fotis Haliotis, Maria Giannaki, Maria Tsolia, I. P. Panagiotou, Kyriaki Karavanaki

Published in: European Journal of Pediatrics | Issue 6/2013

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Abstract

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.
Literature
1.
go back to reference 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):533–537PubMedCrossRef 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):533–537PubMedCrossRef
2.
go back to reference 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):431–433PubMedCrossRef 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):431–433PubMedCrossRef
3.
go back to reference Beausejour C (2007) Bone marrow-derived cells: the influence of aging and cellular senescence. Handb Exp Pharmacol 180:67–88PubMedCrossRef Beausejour C (2007) Bone marrow-derived cells: the influence of aging and cellular senescence. Handb Exp Pharmacol 180:67–88PubMedCrossRef
4.
go back to reference 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):181–186PubMed 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):181–186PubMed
5.
go back to reference Capsoni F, Sarzi-Puttini P, Zanella A (2005) Primary and secondary autoimmune neutropenia. Arthritis Res Ther 7(5):208–214PubMedCrossRef Capsoni F, Sarzi-Puttini P, Zanella A (2005) Primary and secondary autoimmune neutropenia. Arthritis Res Ther 7(5):208–214PubMedCrossRef
6.
go back to reference Citak EC, Arman D (2011) Brucella melitensis: a rare cause of febrile neutropenia. Pediatr Hematol Oncol 28(1):83–85PubMedCrossRef Citak EC, Arman D (2011) Brucella melitensis: a rare cause of febrile neutropenia. Pediatr Hematol Oncol 28(1):83–85PubMedCrossRef
7.
go back to reference 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):82–93CrossRef 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):82–93CrossRef
8.
go back to reference Galanakis E, Bourantas KL, Leveidiotou S, Lapatsanis PD (1996) Childhood brucellosis in north-western Greece: a retrospective analysis. Eur J Pediatr 155(1):1–6PubMedCrossRef Galanakis E, Bourantas KL, Leveidiotou S, Lapatsanis PD (1996) Childhood brucellosis in north-western Greece: a retrospective analysis. Eur J Pediatr 155(1):1–6PubMedCrossRef
9.
go back to reference 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 17:277–282PubMedCrossRef 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 17:277–282PubMedCrossRef
10.
go back to reference 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 11:1 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 11:1
11.
go back to reference 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):575–577PubMedCrossRef 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):575–577PubMedCrossRef
12.
go back to reference 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):531–533PubMedCrossRef 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):531–533PubMedCrossRef
13.
go back to reference James RM, Kinsey SE (2006) The investigation and management of chronic neutropenia in children. Arch Dis Child 91:852–858PubMedCrossRef James RM, Kinsey SE (2006) The investigation and management of chronic neutropenia in children. Arch Dis Child 91:852–858PubMedCrossRef
14.
go back to reference 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):803–806PubMed 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):803–806PubMed
15.
go back to reference 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 95:565–572CrossRef 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 95:565–572CrossRef
16.
go back to reference 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):3468–3471PubMedCrossRef 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):3468–3471PubMedCrossRef
17.
go back to reference Lehmann HW, von Landenberg P, Modrow S (2003) Parvovirus B19 infection and autoimmune disease. Autoim Rev 2:218–223CrossRef Lehmann HW, von Landenberg P, Modrow S (2003) Parvovirus B19 infection and autoimmune disease. Autoim Rev 2:218–223CrossRef
18.
go back to reference Nickerson C, Lurtha H, David C (1991) Antigenic mimicry and autoimmune diseases. Int Rev Immunol 7:205–224PubMedCrossRef Nickerson C, Lurtha H, David C (1991) Antigenic mimicry and autoimmune diseases. Int Rev Immunol 7:205–224PubMedCrossRef
19.
go back to reference Panepinto JA, Brousseau DC (2005) Acute idiopathic thrombocytopenic purpura of childhood-diagnosis and therapy. Pediatr Emerg Care Oct 21(10):691–5CrossRef Panepinto JA, Brousseau DC (2005) Acute idiopathic thrombocytopenic purpura of childhood-diagnosis and therapy. Pediatr Emerg Care Oct 21(10):691–5CrossRef
20.
go back to reference Rajantie J, Kurki S, Juvonen E, Hovi L (1993) Prolonged pure granulocytopenia in children. Acta Paediatrica 82(10):839–842PubMedCrossRef Rajantie J, Kurki S, Juvonen E, Hovi L (1993) Prolonged pure granulocytopenia in children. Acta Paediatrica 82(10):839–842PubMedCrossRef
21.
go back to reference 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):593–600CrossRef 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):593–600CrossRef
22.
go back to reference 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 26:831–833PubMedCrossRef 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 26:831–833PubMedCrossRef
23.
go back to reference Sheen JM, Kuo HC, Yu HR, Huang EY, Wu CC, Yang KD (2009) Prolonged acquired neutropenia in children. Pediatr Blood Cancer 53(7):1284–1288PubMedCrossRef Sheen JM, Kuo HC, Yu HR, Huang EY, Wu CC, Yang KD (2009) Prolonged acquired neutropenia in children. Pediatr Blood Cancer 53(7):1284–1288PubMedCrossRef
24.
go back to reference 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):790–794 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):790–794
25.
go back to reference Sloand E (2005) Hematological complications of HIV infection. AIDS Rev 7(4):187–196PubMed Sloand E (2005) Hematological complications of HIV infection. AIDS Rev 7(4):187–196PubMed
26.
go back to reference 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):401–406CrossRef 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):401–406CrossRef
27.
go back to reference 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):362–366CrossRef 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):362–366CrossRef
28.
go back to reference Valliaveedan R, Rao S, Miller S, Brown A (1987) Transient neutropenia of childhood. Clinical Pediatr (Phila) 26(12):639–642CrossRef Valliaveedan R, Rao S, Miller S, Brown A (1987) Transient neutropenia of childhood. Clinical Pediatr (Phila) 26(12):639–642CrossRef
29.
go back to reference Vlacha V, Feketea G (2007) The clinical significance of non-malignant neutropenia in hospitalized children. Ann Hematol 86(12):865–870PubMedCrossRef Vlacha V, Feketea G (2007) The clinical significance of non-malignant neutropenia in hospitalized children. Ann Hematol 86(12):865–870PubMedCrossRef
30.
go back to reference 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 1902 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 1902
Metadata
Title
Transient neutropenia in children with febrile illness and associated infectious agents: 2 years’ follow-up
Authors
Ourania Alexandropoulou
Lydia Kossiva
Fotis Haliotis
Maria Giannaki
Maria Tsolia
I. P. Panagiotou
Kyriaki Karavanaki
Publication date
01-06-2013
Publisher
Springer-Verlag
Published in
European Journal of Pediatrics / Issue 6/2013
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-013-1965-z

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