What causes monocytosis?

Causes of Monocytosis

Monocytosis results from either reactive conditions (infections, inflammation, autoimmune disorders) or clonal hematologic disorders (chronic myelomonocytic leukemia, myelodysplastic syndromes, acute myeloid leukemia), with the distinction between these categories being critical for determining prognosis and management. 1

Reactive (Non-Clonal) Causes

Infectious Etiologies

• Chronic infections including tuberculosis, endocarditis, and parasitic infections (particularly Strongyloides with travel history) commonly cause monocytosis 2, 1
• Viral infections such as HIV and hepatitis C can produce monocytosis that may be clinically indistinguishable from primary hematologic disorders 1
• Ehrlichiosis (E. chaffeensis, E. ewingii) presents with monocytosis alongside leukopenia, thrombocytopenia, and elevated hepatic transaminases, with morulae visible in monocytes on peripheral smear 1

Inflammatory and Autoimmune Conditions

• Systemic lupus erythematosus and other autoimmune disorders frequently cause monocytosis 1
• Adult-onset Still's disease demonstrates monocytosis as part of its inflammatory profile 1
• Inflammatory bowel disease and rheumatoid arthritis are associated with elevated monocyte counts 1

Other Reactive Causes

• Physical stress (seizures, anesthesia, overexertion) and emotional stress can elevate monocyte counts 3
• Medications including corticosteroids, lithium, and beta agonists are commonly associated with leukocytosis and monocytosis 3
• Recovery from bone marrow suppression represents a physiologic cause of transient monocytosis 1
• Solid tumors can produce reactive monocytosis 1

Clonal (Neoplastic) Causes

Primary Myeloid Neoplasms

• Chronic myelomonocytic leukemia (CMML) is the prototypical disorder, requiring persistent peripheral blood monocytosis (≥1 × 10⁹/L), absence of Philadelphia chromosome or BCR-ABL1 fusion gene, and less than 20% blasts in peripheral blood and bone marrow 1
• Myelodysplastic syndromes (MDS) can present with monocytosis, though absolute monocyte count typically remains <1 × 10⁹/L; the presence of monocytosis, macrocytosis, pseudo Pelger-Huet anomaly, or dysgranulopoietic changes suggests MDS rather than essential thrombocythemia 4, 1
• Acute myeloid leukemia with monocytic differentiation presents with monocytosis and typically more acute clinical presentation 1, 3
• Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes may present with monocytosis on peripheral blood smear 1

Secondary Hematologic Malignancies

• Chronic lymphocytic leukemia (CLL) with elevated absolute monocyte count correlates with inferior outcomes and accelerated disease progression 1

Diagnostic Approach to Distinguish Causes

Initial Assessment

• Confirm absolute monocytosis (not just relative) by calculating absolute monocyte count from complete blood count with differential 1
• Obtain detailed history focusing on travel exposure, new medications, recurrent infections, family history of hematologic malignancies, constitutional symptoms (weight loss, night sweats, fever), and bleeding or bruising 1, 3
• Physical examination must assess spleen size, cutaneous lesions, lymphadenopathy, and signs of organ damage 1

Laboratory Evaluation

• Peripheral blood smear examination is critical to assess monocyte morphology, presence of dysgranulopoiesis, promonocytes, blasts, neutrophil precursors, rouleaux formation (suggesting plasma cell dyscrasia), and morulae in monocytes (suggesting ehrlichiosis) 1
• Comprehensive metabolic panel including calcium, albumin, creatinine, and liver function tests 1
• Serum protein electrophoresis with immunofixation and serum-free light chains if plasma cell dyscrasia is suspected 1

Indications for Bone Marrow Evaluation

Bone marrow aspiration and biopsy are indicated for: 1

• Persistent unexplained monocytosis without clear reactive cause
• Absolute monocyte count ≥1 × 10⁹/L sustained over time (typically >3 months)
• Concurrent cytopenias or other blood count abnormalities
• Constitutional symptoms or organomegaly
• Dysplastic features on peripheral smear

Advanced Testing When Malignancy Suspected

• Conventional cytogenetic analysis to identify clonal abnormalities and exclude Philadelphia chromosome, BCR-ABL1 fusion gene, t(5;12) translocation, del(5q), t(3;3)(q21;q26), or inv(3)(q21q26) 4, 1
• Molecular testing for mutations commonly found in CMML (TET2, SRSF2, ASXL1, RAS) 1
• Bone marrow biopsy staining with Gomori's silver impregnation for fibrosis 1
• Flow cytometry to assess CD34+ cells and monocyte repartitioning, which can distinguish CMML from reactive causes 5

Critical Clinical Pitfalls

• Failing to distinguish between relative and absolute monocytosis can lead to unnecessary workup or missed diagnoses 1
• Not performing comprehensive bone marrow evaluation in cases of persistent unexplained monocytosis delays diagnosis of treatable malignancies 1
• Missing underlying infections or malignancies by attributing monocytosis solely to inflammatory conditions without adequate investigation 1
• White blood cell counts above 100,000 per mm³ represent a medical emergency due to risk of brain infarction and hemorrhage, regardless of etiology 3

Prognostic Implications

• Monocytosis at emergency department admission predicts higher 30-day mortality and longer length of stay when adjusted for age, gender, comorbidities, and diagnosis, with cardiological diagnoses showing the highest mortality risk (odds ratio 3.91) 2
• Patients with monocytosis more frequently present with respiratory symptoms and infections, and have more comorbidities including congestive heart failure, chronic obstructive pulmonary disease, tumor, diabetes, and renal failure 2