What are the causes of monocytosis?

Causes of Monocytosis

Monocytosis is primarily caused by infections, inflammatory conditions, hematologic malignancies, and certain autoimmune disorders, with persistent unexplained monocytosis warranting follow-up to rule out underlying hematologic malignancy. 1

Infectious Causes

• Bacterial infections:

  • Tuberculosis
  • Subacute bacterial endocarditis
  • Brucellosis
  • General bacterial infections 1

• Viral infections:

  • HIV
  • Cytomegalovirus (CMV)
  • Epstein-Barr virus (EBV) 1

• Parasitic infections:

  • Malaria
  • Leishmaniasis 1

Inflammatory and Autoimmune Conditions

• Inflammatory bowel disease
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Sarcoidosis
• Adult-onset Still's disease 2, 1

Hematologic Malignancies

• Chronic myelomonocytic leukemia (CMML)
  • Diagnostic criteria: persistent peripheral blood monocytosis >1×10⁹/L, no Philadelphia chromosome or BCR-ABL1 fusion gene, <20% blasts in peripheral blood and bone marrow, plus either dysplasia, acquired clonal cytogenetic/molecular genetic abnormality, or persistence of monocytosis for ≥3 months 1
• Acute myeloid leukemia with monocytic differentiation
• Myelodysplastic syndromes (MDS) 1

Other Causes

• Cardiovascular disease (associated with worse outcomes) 3
• Recovery phase of neutropenia
• Post-splenectomy
• Chronic myeloproliferative disorders
• Certain medications
• Tissue injury or trauma 1

Diagnostic Approach

Initial Evaluation

1. Complete blood count with differential:

   • Confirm monocytosis (>0.8×10⁹/L or >10% of leukocytes)
   • Check for other abnormalities (anemia, thrombocytopenia, other white cell abnormalities) 1

2. Peripheral blood smear examination:

   • Assess monocyte morphology
   • Look for dysplastic features
   • Check for presence of immature cells 1

3. Basic laboratory testing:

   • Inflammatory markers (ESR, CRP)
   • Liver function tests
   • Renal function tests
   • Appropriate cultures and serologic testing for infections 1

Advanced Testing (if initial evaluation suggests hematologic malignancy)

1. Bone marrow aspiration and biopsy

2. Flow cytometry for immunophenotyping:

   • Detect aberrancies in monocytic lineage
   • Look for abnormal CD11b/HLA-DR, CD36/CD14
   • Check for overexpression of CD56 1

3. Cytogenetic analysis:

   • Conventional karyotyping
   • Detect clonal chromosomal abnormalities
   • Exclude specific translocations (t(9;22), t(5;12)) 1

4. Molecular testing for mutations commonly associated with myeloid neoplasms 1

Management Approach

Transient Monocytosis

• Identify and treat the underlying cause (infection, inflammation)
• Follow-up CBC to confirm normalization 1

Persistent Unexplained Monocytosis

• Regular CBC monitoring every 2-4 weeks initially
• Hematology referral if persistent beyond 3 months
• Repeat evaluation if other cytopenias develop or clinical status changes 1

Prognostic Implications

• In emergency department patients, monocytosis is associated with higher 30-day mortality and longer hospital stays, particularly with cardiological diagnoses 3
• In pediatric patients with fever and neutropenia, monocyte recovery may be a positive prognostic sign 1
• Persistent monocytosis with clonal hematopoiesis in older individuals may represent early development of myeloid malignancy 4

Important Clinical Considerations

• Monocytosis itself is not a disease but a sign of an underlying condition
• The presence of monocytosis with clonal hematopoiesis in older individuals requires careful monitoring as it may represent early clonal dominance in developing malignant myelomonocytic disease 4
• In patients with monocytosis and suspected myeloid neoplasm, flow cytometry and molecular testing are essential for accurate diagnosis 1