Non-Infectious Causes of Leukocytosis
The most common non-infectious causes of leukocytosis include physiologic stress responses, inflammatory conditions, hematologic malignancies, medications, and specific disease states such as Adult-Onset Still's Disease (AOSD). 1, 2
Inflammatory and Autoimmune Conditions
- Adult-Onset Still's Disease (AOSD) commonly presents with marked leukocytosis due to neutrophilia, which often accompanies increased disease activity 3
- Chronic inflammatory conditions can cause persistent leukocytosis through ongoing stimulation of bone marrow granulocyte hyperplasia 3
- Patients with AOSD may have white blood cell counts exceeding 15,000 cells/μL in 50% of cases, with 37% having counts >20,000 cells/μL 3
Physiologic and Stress-Related Causes
- Physical stressors including surgery, trauma, seizures, anesthesia, and overexertion can trigger significant leukocytosis 1, 2
- Emotional stress can elevate white blood cell counts through catecholamine-mediated demargination 1
- The peripheral white blood cell count can double within hours after certain stimuli due to the large bone marrow storage and marginated pools of neutrophils 2
Hematologic Malignancies
- Chronic lymphocytic leukemia (CLL) often presents with progressive lymphocytosis with increases of >50% over a 2-month period or lymphocyte doubling time of <6 months 3
- Acute myeloid leukemia (AML) can present with hyperleukocytosis (WBC >100,000/μL), which constitutes a medical emergency due to risk of hemorrhagic events, tumor lysis syndrome, and leukostasis 3
- Myeloproliferative disorders cause sustained leukocytosis with abnormalities in other cell lines (red blood cells, platelets) 1, 4
Medication-Induced Leukocytosis
- Corticosteroids commonly cause leukocytosis through demargination of neutrophils from the vascular endothelium 1, 2
- Lithium therapy can induce leukocytosis through stimulation of granulocyte colony-stimulating factor 1
- Beta-agonists can cause transient elevations in white blood cell counts 1
Other Non-Infectious Causes
- Smoking is associated with chronic leukocytosis, with a dose-dependent relationship 2
- Obesity can lead to chronic low-grade inflammation resulting in mild leukocytosis 2
- Splenectomy or functional asplenia leads to persistent leukocytosis due to lack of splenic sequestration 2
- Tissue damage without infection can drive persistent leukocytosis through damage-associated molecular patterns (DAMPs) 5
Specific Leukocyte Abnormalities
- Eosinophilia (increased eosinophil count) can result from allergic reactions, parasitic infections, and certain medications 1, 5
- Basophilia can occur in allergic conditions and myeloproliferative disorders 1
- Lymphocytosis is common in viral illnesses, particularly in children 2
Management Considerations for Severe Leukocytosis
- Hyperleukocytosis (WBC >100,000/μL) represents a medical emergency due to risk of brain infarction and hemorrhage 1
- Aggressive hydration (2.5-3 liters/m²/day) should be implemented immediately in cases of severe leukocytosis 6
- Hydroxyurea (50-60 mg/kg/day) can be used to rapidly reduce white blood cell counts in hyperleukocytosis 3, 6
- Monitor for and prevent tumor lysis syndrome with allopurinol or rasburicase in high-risk patients 6
Diagnostic Approach
- Peripheral blood smear examination is essential to identify types and maturity of white blood cells, uniformity, and toxic granulations 2
- Constitutional symptoms (fever, weight loss, bruising, fatigue) along with abnormal peripheral blood smear suggest malignancy 4
- Patients with chronic leukemias usually present with less severe symptoms than those with acute leukemias 4
- Extremely elevated white blood cell counts or concurrent abnormalities in red blood cell or platelet counts increase suspicion for primary bone marrow disorders 1
When evaluating leukocytosis without obvious infectious cause, it is crucial to consider these non-infectious etiologies to guide appropriate management and avoid unnecessary antibiotic use 5.