What are the causes of neutropenia and lymphocytosis in pediatric patients?

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Last updated: February 26, 2025View editorial policy

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From the Guidelines

Neutropenia with lymphocytosis in pediatric patients is most commonly caused by congenital neutropenia syndromes, such as severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome (SDS), as well as viral infections and bone marrow disorders. According to the most recent study 1, SCN is a rare disorder that usually presents in infancy with absolute neutrophil counts <0.5 × 10^9/L, accompanied by recurrent life-threatening infections. The study also highlights that Shwachman-Diamond syndrome is a rare autosomal recessive syndrome caused by defective ribosome biogenesis, which can lead to neutropenia and an increased risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Other important causes of neutropenia with lymphocytosis in pediatric patients include:

  • Viral infections, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), influenza, and parvovirus B19
  • Bacterial infections, particularly overwhelming sepsis
  • Certain medications, such as antibiotics and chemotherapy agents
  • Autoimmune disorders, such as lupus and rheumatoid arthritis
  • Bone marrow disorders, such as leukemia and aplastic anemia

The mechanism behind viral-induced neutropenia involves direct viral suppression of neutrophil production in the bone marrow, increased neutrophil destruction in peripheral tissues, and a compensatory increase in lymphocyte production as part of the immune response. Most viral-induced cases are self-limiting and resolve within 1-2 weeks without specific treatment. However, persistent neutropenia (ANC <1000/μL for more than 2 weeks) warrants further investigation with complete blood count monitoring, possibly bone marrow examination, and referral to pediatric hematology if severe or prolonged.

It is essential to note that the use of granulocyte colony-stimulating factor (G-CSF) can be beneficial in the management of congenital and acquired neutropenias, as recommended by the Neutropenia Committee of the Marrow Failure Syndrome Group of the Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) 1. Additionally, the American Society of Clinical Oncology (ASCO) recommends the use of CSFs in pediatric patients with a high likelihood of febrile neutropenia, as well as in patients with certain types of cancer, such as Ewing sarcoma 1.

In terms of lymphocytosis, it is often seen as a compensatory response to neutropenia, and its causes are closely related to those of neutropenia. However, lymphocytosis can also be caused by viral infections, such as EBV and CMV, which can lead to an increase in lymphocyte production.

Overall, the management of neutropenia with lymphocytosis in pediatric patients requires a comprehensive approach, including diagnosis, treatment, and follow-up, to prevent complications and improve outcomes.

From the Research

Causes of Neutropenia in Pediatric Patients

  • Neutropenia in children can be caused by various factors, including infections, autoimmune disorders, and congenital conditions 2, 3, 4, 5
  • The most common cause of neutropenia in children is post-infectious neutropenia, which accounts for approximately 58.5% of cases 4
  • Other causes of neutropenia in children include:
    • Autoimmune neutropenia 2, 3, 5
    • Congenital neutropenia 2, 3, 5
    • Drug-induced neutropenia 3, 4
    • Vitamin B12 deficiency 4
    • Chronic benign neutropenia 4
    • Immune deficiency 4
    • Autoimmune lymphoproliferative syndrome 4
    • Hemophagocytic lymphohistiocytosis secondary to a previous infection 4

Causes of Lymphocytosis in Pediatric Patients

  • There is limited information available on the causes of lymphocytosis in pediatric patients in the provided studies
  • However, it is known that lymphocytosis can be caused by various factors, including infections, autoimmune disorders, and allergic reactions 6

Clinical Significance of Neutropenia and Lymphocytosis

  • Neutropenia can increase the risk of severe infections in children, particularly in those with congenital or autoimmune neutropenia 2, 3, 5
  • However, most children with neutropenia have a benign clinical course and do not require extensive medical attention 3, 4
  • The prognosis for children with neutropenia is generally good, with approximately 96.8% of patients recovering from the condition 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Etiology, clinical outcome, and laboratory features in children with neutropenia: analysis of 104 cases.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 2014

Research

Etiological causes and prognosis in children with neutropenia.

Northern clinics of Istanbul, 2021

Research

[Evaluation of neutropenia in children].

Archives de pediatrie : organe officiel de la Societe francaise de pediatrie, 2003

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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