Causes of Neutrophilia Besides Bacterial Infection
Neutrophilia (elevated neutrophil count) can be caused by numerous conditions beyond bacterial infections, including physiological stress responses, inflammatory disorders, malignancies, medications, and certain hematologic disorders. 1
Definition and Classification
- Neutrophilia is defined as an absolute neutrophil count (ANC) above the normal range (typically >7500 cells/mm³)
- Normal neutrophil count ranges from 1500-7500 cells/mm³ in adults
- Neutropenia, in contrast, is defined as ANC <1500 cells/mm³ 1, 2
Non-Infectious Causes of Neutrophilia
Physiological Causes
- Stress response (physical or emotional)
- Exercise
- Pregnancy (especially third trimester)
- Postpartum period
- Exposure to extreme temperatures
- Surgery/trauma
- Seizures
Inflammatory and Autoimmune Disorders
- Rheumatoid arthritis
- Inflammatory bowel disease
- Vasculitis
- Systemic lupus erythematosus
- Gout and pseudogout
- Tissue necrosis or infarction
- Burns
Malignancies
- Hematologic malignancies:
- Chronic myeloid leukemia
- Polycythemia vera
- Myelofibrosis
- Acute myeloid leukemia
- Solid tumors (particularly with bone marrow metastases)
Medications and Substances
- Corticosteroids
- Lithium
- Epinephrine
- Granulocyte colony-stimulating factor (G-CSF)
- Beta-agonists
- Certain chemotherapy regimens
- Smoking
Hematologic Disorders
- Myeloproliferative neoplasms
- Leukemoid reactions (extreme neutrophilia mimicking leukemia)
- Chronic neutrophilic leukemia
- Hereditary neutrophilia (rare genetic disorders)
Other Causes
- Splenectomy (due to loss of splenic sequestration)
- Recovery phase of neutropenia
- Chronic inflammation in COPD and severe asthma 3
- Metabolic disorders (diabetic ketoacidosis, uremia)
- Hemolysis
Viral Infections and Neutrophilia
While bacterial infections are classically associated with neutrophilia, certain viral infections can also cause neutrophilia:
- Early stages of some viral infections
- Adenovirus
- Influenza
- Certain herpesvirus infections 4
Evaluation of Neutrophilia
When evaluating neutrophilia without evidence of bacterial infection:
Complete blood count with differential to assess other cell lines
Review of peripheral blood smear to look for morphological abnormalities
Comprehensive medical history focusing on:
- Recent medications
- Underlying chronic conditions
- Recent stressors or trauma
- Smoking status
- Family history of hematologic disorders
Physical examination with attention to:
- Signs of inflammation
- Lymphadenopathy
- Hepatosplenomegaly
- Evidence of autoimmune disease
Additional testing based on clinical suspicion:
- Inflammatory markers (ESR, CRP)
- Bone marrow examination (if hematologic malignancy suspected)
- Specific autoimmune markers
- Imaging studies
Clinical Significance
- Transient neutrophilia due to physiologic causes typically resolves without intervention
- Persistent neutrophilia warrants investigation for underlying causes
- Extreme neutrophilia (>50,000 cells/mm³) should prompt evaluation for myeloproliferative disorders or leukemoid reactions
- Chronic neutrophilia may contribute to tissue damage in inflammatory conditions 5
Common Pitfalls in Evaluation
- Attributing neutrophilia solely to bacterial infection without considering other causes
- Failing to recognize medication-induced neutrophilia
- Not considering physiologic causes before extensive workup
- Overlooking chronic inflammatory conditions as a source of persistent neutrophilia
- Missing early hematologic malignancies that present with neutrophilia