Key Concept
Rare hematological disorder characterized by regular (cyclic) fluctuations in the neutrophil count, leaving the patient vulnerable to serious infections during the nadir.
Pathophysiology
Genetics
Mutation in the gene ELANE (neutrophil elastase). Mostly autosomal dominant.
The Cycle
Typical oscillation each 21 days (range 14 to 35 days).
Cycle Viewer
Simulation of a typical 21-day cycle
Clinical Findings
Symptoms appear almost exclusively during the 3 to 6 days of severe neutropenia (Nadir). Between attacks, the child is usually completely asymptomatic.
Classic Presentation
- Fever: Often recurrent, high grade (every ~3 weeks).
- Mouth: Severe oral thrush, gingivitis, stomatitis.
- Pharynx: Pharyngotonsillitis, cervical lymphadenopathy.
Red Flags in Emergencies
Monitor closely during nadir for risk of invasive and opportunistic bacterial infections.
- Acute cellulitis or skin abscesses.
- Rapidly progressive pneumonia.
- Omphalitis (typical in neonatal presentation).
- Neutropenic enterocolitis (acute abdominal pain).
- Bacteremia/Severe sepsis.
Laboratory Findings
Key Diagnostic Criteria
(Absolute Neutrophil Count < 0.2 × 10⁹/L)
for 3 to 6 consecutive days per cycle.
For definitive diagnosis, it is imperative to perform complete blood counts (HMG) 2 to 3 times a week for a period of 6 weeks to document the cyclical nature (peaks and valleys).
During the phase of deep neutropenia, it is classic to observe compensatory increases in other cell lines:
- Monocytosis (very common)
- Eosinophilia
- Mild reticulocytosis
- Occasionally thrombocytosis
- Genetic Study: Sequencing of the ELANE gene (confirms the diagnosis).
- Bone marrow aspirate (non-routine): Shows “maturation arrest” at the promyelocyte stage during nadir.
Management Protocol
Emergency Box: Febrile Neutropenia
Any child with cyclic neutropenia who presents with fever (≥ 38.3°C or > 38.0°C for 1 hr) in the nadir phase is a medical emergency.
1. Immediate Evaluation (Golden Hour)
- ABCDE stabilization.
- Blood cultures (peripheral and central catheter if present).
- Rapid analysis (HMG, PCR, PCT, metabolic profile).
- Urine culture / Chest X-ray / Smear of lesions (according to clinical signs).
2. Immediate Empirical Antibiotherapy
Do not wait for culture results. Start anti-pseudomonal coverage:
- > Cefepime 50mg/kg/dose IV every 8h
- > or Piperacillin-Tazobactam 80mg/kg IV every 6h
- > + Vancomycin (if instability, infected catheter or severe mucositis)
Prophylactic Management and Maintenance
G-CSF (Filgrastim)
Pillar of treatment. Shortens the days of neutropenia and reduces the severity of infections. Typical dose: 1-3 mcg/kg/day (titratable).
Strict Hygiene
Special emphasis on thorough oral hygiene to prevent ulcerative gingivitis and premature tooth loss.
Vaccination
Complete vaccination schedule. The annual flu vaccine and complete anti-pneumococcal guidelines are essential.