What can cause elevated monocytes?

Causes of Elevated Monocytes

Elevated monocytes (monocytosis) can be caused by various inflammatory, infectious, malignant, and hematologic disorders, with chronic myelomonocytic leukemia being the most concerning cause due to its significant mortality risk.

Common Causes of Monocytosis

Inflammatory Conditions

• Rheumatoid arthritis and other autoimmune disorders 1
• Systemic lupus erythematosus 2
• Inflammatory bowel disease
• Sarcoidosis 3
• Vasculitis

Infectious Causes

• Bacterial infections 3
• Tuberculosis 3
• Subacute bacterial endocarditis
• Fungal infections
• Parasitic infections

Hematologic Malignancies

• Chronic myelomonocytic leukemia (CMML) 4, 5
• Acute myeloid leukemia
• Myelodysplastic syndromes
• Myeloproliferative neoplasms
• Lymphomas 3

Other Malignancies

• Solid tumors (though less commonly than lymphomas) 3

Medication-Related

• Certain antibiotics (including ceftriaxone) 6
• Glucocorticoids
• Colony-stimulating factors 7

Other Causes

• Recovery from bone marrow suppression
• Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes 4
• Still's disease 4

Diagnostic Approach

When evaluating monocytosis, a systematic approach is essential:

1. Complete blood count with differential to assess for other cytopenias or abnormalities 5
2. Peripheral blood smear examination to look for dysplasia, blasts, or other abnormal cells 4
3. Basic metabolic panel and liver function tests 5
4. Inflammatory markers (ESR, CRP) 4
5. Specific testing based on clinical suspicion:
   • Autoimmune serologies (ANA, ANCA) for suspected autoimmune disease
   • Microbiology studies for suspected infection
   • Serum protein electrophoresis for suspected paraproteinemia

For persistent unexplained monocytosis (>3 months), consider:

• Bone marrow aspiration and biopsy with immunohistochemistry 4, 5
• Cytogenetic analysis to detect clonal abnormalities 4
• Molecular testing for mutations commonly seen in CMML (TET2, SRSF2, ASXL1) 5

Clinical Pearls and Pitfalls

Important Considerations

• Persistent monocytosis (>1,000/μL for >3 months) without an obvious cause requires hematologic evaluation 5
• Monocytosis may be the first sign of a serious underlying condition like CMML, which carries significant morbidity and mortality risks 4, 5
• In inflammatory diseases, monocytes may show increased metabolic activity and produce more inflammatory cytokines 3, 1

Pitfalls to Avoid

• Don't ignore persistent monocytosis even if mild - it could be the only early sign of a myeloid neoplasm
• Don't attribute monocytosis to infection without appropriate workup, especially if it persists after treatment
• Don't forget medication review as certain drugs can cause monocytosis 6

Special Considerations

Monocyte Subsets

Different monocyte subsets may predominate in different conditions:

• Intermediate monocytes (CD14++CD16+) are often increased in rheumatoid arthritis and produce pro-inflammatory cytokines 1
• Classical monocytes may differentiate into osteoclasts in rheumatoid arthritis, contributing to bone erosion 1

Monocytosis in Children

In pediatric patients with fever and neutropenia, monocyte recovery may be a positive prognostic sign, but persistent monocytosis requires evaluation 4

Monocytosis as a Biomarker

Monocyte abnormalities may serve as biomarkers in certain conditions:

• Predictive of response to certain treatments in psoriasis 8
• Associated with cardiovascular risk in inflammatory conditions 8

By systematically evaluating the potential causes of monocytosis and following a structured diagnostic approach, clinicians can identify and address the underlying condition, potentially improving patient outcomes.