From the Guidelines
Chronic leukocytosis is most commonly caused by a combination of reactive and primary hematologic disorders, with the most significant primary cause being chronic myeloid leukemia (CML), as evidenced by the presence of the BCR-ABL1 fusion gene 1. The etiology of chronic leukocytosis can be broadly categorized into:
- Reactive causes, including:
- Chronic infections (e.g., tuberculosis, osteomyelitis)
- Inflammatory conditions (such as rheumatoid arthritis, inflammatory bowel disease)
- Certain medications (corticosteroids, lithium)
- Smoking, which is a common cause of mild chronic leukocytosis
- Primary hematologic disorders, including:
- Myeloproliferative neoplasms (particularly CML and polycythemia vera)
- Lymphoproliferative disorders (like chronic lymphocytic leukemia)
- Bone marrow failure syndromes
- Hereditary disorders, such as hereditary neutrophilia It is essential to perform a thorough history, physical examination, and appropriate laboratory tests to differentiate between these causes, as the pattern of cell line involvement and the presence of immature cells in the peripheral blood can provide important clues to the underlying etiology 1. In the case of CML, the diagnosis is generally straightforward, with a characteristic blood count and differential, and confirmation of diagnosis is obtained by the identification of the Philadelphia chromosome, 22q- or BCR-ABL1 transcripts, or both, in peripheral blood or bone marrow cells 1.
From the Research
Etiology of Chronic Leukocytosis
The etiology of chronic leukocytosis, or elevated white blood cell count, can be broadly categorized into primary malignant diseases and secondary causes that are expected physiologic responses of the bone marrow 2.
Primary Malignant Diseases
Primary bone marrow disorders, such as acute leukemias, chronic leukemias, and myeloproliferative disorders, can cause chronic leukocytosis 3, 4. These disorders can lead to an overproduction of white blood cells, resulting in elevated counts. Chronic granulocytic leukemia (CGL) is a specific type of leukemia that is characterized by a pathognomonic differential leukocyte count and the presence of the Ph chromosome 5.
Secondary Causes
Secondary causes of chronic leukocytosis include:
- Infections, such as bacterial infections, which can stimulate the bone marrow to produce more white blood cells 3, 6
- Chronic inflammatory conditions, such as autoimmune disorders or allergic reactions, which can also lead to an increase in white blood cell production 3, 6
- Physical stress, such as seizures, anesthesia, or overexertion, which can cause a temporary increase in white blood cell count 3
- Emotional stress, which can also lead to an increase in white blood cell count 3
- Certain medications, such as corticosteroids, lithium, and beta agonists, which can cause leukocytosis 3, 6
- Other nonmalignant etiologies, such as asplenia, smoking, obesity, and chronic inflammatory conditions, which can also contribute to elevated white blood cell counts 6
Clinical Presentation
Patients with chronic leukocytosis may present with a range of symptoms, including: