Harvey's Garden

Cyclic neutropenia

2 min read

  • Patho/Etiology

    • Autosomal Dominant inheritance (most common).
    • Mutation in ELANE gene (encodes neutrophil elastase).
    • Defective enzyme leads to accumulation of misfolded proteins → accelerated apoptosis of myeloid precursors.
    • Characterized by regular, periodic oscillations in Absolute Neutrophil Count (ANC). The cycle is driven by waves of precursor apoptosis followed by compensatory G-CSF surges.
    • Classic cycle duration: 21 days (± 3 days).

  • Clinical Presentation

    • Usually presents in infancy or early childhood.
    • Patients are asymptomatic between episodes. During neutropenic periods, they experience:

  • Diagnosis

    • Key diagnostic step: Serial CBC with differential count 2-3 times per week for 6-8 weeks.
    • This documents the cyclical pattern of neutropenia, with absolute neutrophil count (ANC) dropping to < 500/µL (often < 200/µL) during nadirs, followed by recovery to normal or near-normal levels.
    • Genetic testing for ELANE gene mutation confirms the diagnosis.
    • Bone marrow biopsy during a neutropenic episode shows myeloid hypoplasia or maturational arrest at the myelocyte stage.

  • DDx (Differential Diagnosis)

    • Severe Congenital Neutropenia (SCN): Also caused by ELANE mutations, but neutropenia is persistent and severe, not cyclical. SCN carries a higher risk of transformation to AML/MDS.
    • Autoimmune Neutropenia: Can be associated with other autoimmune conditions (e.g., SLE, Felty syndrome); diagnosed by anti-neutrophil antibodies.
    • Drug-induced Neutropenia: Onset is related to a new medication; resolves after discontinuation.
    • Viral Infections: (e.g., EBV, Parvovirus B19) can cause transient neutropenia.

  • Management/Treatment

    • First-line: Granulocyte colony-stimulating factor (G-CSF, e.g., filgrastim).
      • G-CSF shortens the duration and lessens the severity of neutropenic episodes, reducing the frequency of infections.
    • Infections: Prompt treatment with broad-spectrum antibiotics for febrile neutropenia.
    • Supportive care: Good oral hygiene is crucial to manage gingivitis and mouth sores.
    • Hematopoietic stem cell transplant (HSCT) is rarely needed but can be considered for severe cases unresponsive to G-CSF.

  • Key Associations/Complications

    • Complications: Severe bacterial infections (e.g., sepsis, pneumonia, necrotizing enterocolitis) are the main risk, especially during neutropenic nadirs.
    • Unlike SCN, cyclic neutropenia does not typically carry an increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
    • Symptoms may become milder after puberty.

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