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

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.

Neutropénies de découverte fortuite chez l’enfant : diagnostic et suivi

“…La neutropénie était plus fréquente chez l'enfant que chez l'adulte, la prévalence étant toutefois très probablement surestimée, variable en fonction de l'âge. Dans notre étude, 52 % des enfants présentant une neutropénie étaient âgés de moins de 2 ans, ce qui confirme la fréquence relativement importante des neutropénies chez le nourrisson, constatée dans la majorité des études disponibles [5,7,9,10,17,18]. Pettiti et al se sont intéressés à l'incidence des neutropénies [ ( F i g u r e _ 2 ) T D $ F I G ] [ ( F i g u r e _ 3 ) T D $ F I G ] inférieures à 0,5 Â 10 9 /L dans une population ambulatoire de patients, en incluant les sujets sur des critères biologiques, comme dans notre étude [12].…”

“…Outre la profondeur de la neutropénie, une thrombocytose et un âge supérieur à 12 mois étaient associés dans leur étude à la persistance de la neutropénie. L'origine infectieuse a été majoritaire, comme dans des travaux antérieurs [7][8][9][10], la survenue d'une neutropénie n'étant pas rare au cours d'une infection virale [7][8][9][10][11][12]22]. L'étiologie des neutropénies de découverte fortuite est tout à fait diffé-rente de celle de l'adulte chez qui les causes infectieuses sont plutôt minoritaires [23].…”

“…On distingue également les neutropénies transitoires (moins de 3 mois) des chroniques (plus de 3 mois) plus pourvoyeuses de complications infectieuses [3,5]. Plusieurs études suggèrent que la majorité des neutropénies découvertes chez les enfants hospitalisés résultent d'infections virales et sont le plus souvent bénignes, car transitoires, légères à modérées et ne se compliquent pas d'infections sévères [5][6][7][8][9][10][11] à l'inverse des neutropénies constitutionnelles très précocement symptomatiques, pouvant nécessiter des traitements lourds comme les facteurs de croissance granulopoïétiques [3,4]. Peu d'études ont évalué la prévalence et la signification clinique des neutropénies de découverte fortuite dans la population pédiatrique générale [12].…”

Neutropenia in the Febrile Child

“…In an otherwise healthy pediatric patient, neutropenia can be the result of viral infection and subsequent suppression of neutrophil production, which is usually benign, resulting in mild or moderate neutropenia, and transient, resolving within 1 month. 38 Transient neutropenia can also be the result of medications, such as analgesics and antiinflammatory agents, antibiotics, anticonvulsants, antidepressants and antipsychotics, antithyroid, and cardiac medications, and resolves after discontinuation of inciting medication. 39 Chronic neutropenia is defined as lasting longer than 2 months and can have multiple causes including autoimmune and alloimmune neutropenia, chronic idiopathic neutropenia, cyclic neutropenia, severe congenital neutropenia, Shwachman-Diamond syndrome, and bone marrow failure syndromes, such as aplastic anemia and Fanconi anemia.…”

Diagnosis and management of primary autoimmune neutropenia in children: insights for clinicians

“…In addition to the different clinical pictures and the contribution of cultural, serological and genetic methods for identification of infectious agents, an efficient tool for DD is, in the newborn, a ratio of immature to total neutrophils higher than 0.2-0.3 (immatures, or bands, are intended neutrophils with a single-lobed nucleus and forms less mature than bands) that it is reported to have a strong predictive negative value [Engle and Rosenfeld,1984;Hornik et al 2012]. The duration is usually less than 1-3 months [Sheen et al 2009;Alexandropoulou et al 2013] and therefore, a diagnosis of infection-related neutropenia can be considered appropriate if after 8-12 weeks ANC returns to normal and no other cause has become evident. Nevertheless it must be emphasized that some infections, i.e.…”