From the Guidelines
Neutropenia in pediatric patients is primarily caused by severe congenital neutropenia (SCN), Shwachman-Diamond syndrome (SDS), and other genetic disorders, as well as viral and bacterial infections, medication side effects, and bone marrow infiltration from leukemia or other malignancies. The causes of neutropenia can be categorized into congenital and acquired conditions. Congenital disorders include SCN, SDS, and other rare genetic syndromes such as those associated with mutations in the ELANE, USP9X, TYK2, GAB2, SH2B3, MBD4, ERCC6L2, GATA1, and MECOM genes 1. These conditions often present with recurrent infections, failure to thrive, and other systemic symptoms. Acquired causes of neutropenia in children include viral infections, bacterial infections, medication side effects, and bone marrow infiltration from leukemia or other malignancies.
Some key points to consider in the management of neutropenia in pediatric patients include:
- The severity of neutropenia is classified based on the absolute neutrophil count (ANC), with severe neutropenia (ANC <500 cells/μL) carrying the highest risk of infection.
- Management depends on the underlying cause, ranging from observation for viral-induced cases to antibiotics for febrile neutropenia, G-CSF administration for severe cases, and specific treatments for underlying conditions.
- Children with neutropenia require prompt medical attention if they develop fever or signs of infection, as their immune system's ability to fight bacterial infections is compromised.
- Recent studies have highlighted the importance of surveillance for children with predisposition to hematopoietic malignancy, including those with SCN and SDS, due to the increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) 1.
In terms of specific genetic disorders, 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, and is often associated with mutations in the ELANE gene. SDS is a rare autosomal recessive syndrome caused by defective ribosome biogenesis, which manifests as pancreatic exocrine insufficiency, skeletal abnormalities, growth impairment, immune dysfunction, and/or cytopenia, particularly neutropenia, with an increased risk of MDS/AML 1. Other genetic disorders, such as those associated with mutations in the USP9X, TYK2, GAB2, SH2B3, MBD4, ERCC6L2, GATA1, and MECOM genes, have also been linked to an increased risk of hematopoietic malignancies 1.
From the Research
Causes of Neutropenia in Pediatric Patients
The causes of neutropenia in pediatric patients can be categorized into several groups, including:
- Congenital neutropenia syndromes, which are usually recognized when there are recurrent infections, severe neutropenia, and congenital anomalies suggesting a genetic disorder 2
- Autoimmune disorders, which are often associated with relatively minor symptoms 2
- Viral infections, which can trigger autoimmune neutropenia 3
- Isoimmune or alloimmune mechanisms, which can cause neutropenia in newborns 2
- Acute neutropenia, which is mainly due to infections 4
- Chronic idiopathic neutropenia (CIN), which is the most frequent form of chronic neutropenia in children 4
- Autoimmune neutropenia (AIN), which is a relatively uncommon hematological disorder characterized by the autoantibody-induced destruction of neutrophils 4, 3
Clinical Features and Diagnosis
The clinical features and diagnosis of neutropenia in pediatric patients vary depending on the underlying cause. Some common features include:
- Recurrent infections 2, 4, 5
- Severe neutropenia 2, 4, 5
- Congenital anomalies 2
- Autoantibody-induced destruction of neutrophils 3
- Positive results for serum antineutrophil antibodies 3
- Mutations in neutropenia targeted panel 3
Treatment and Management
The treatment and management of neutropenia in pediatric patients depend on the underlying cause and severity of the condition. Some common treatments include: