Differential Diagnosis for Leukocytosis without Infection
When infection has been ruled out as the cause of leukocytosis, the differential diagnosis broadens to include various non-infectious conditions. The following categories help organize the potential causes:
Single Most Likely Diagnosis
- Stress or Corticosteroid-Induced Leukocytosis: This is often seen in patients under physical stress, such as after surgery, trauma, or severe burns, and in those taking corticosteroids. The body's stress response leads to the release of endogenous corticosteroids, which can cause demargination of white blood cells from the endothelium, leading to an increase in circulating white blood cells.
Other Likely Diagnoses
- Chronic Myeloid Leukemia (CML): A myeloproliferative disorder characterized by the overproduction of mature and immature granulocytes. It often presents with a high white blood cell count and can be diagnosed with specific genetic tests (e.g., BCR-ABL1 fusion gene).
- Polycythemia Vera: Another myeloproliferative neoplasm that can present with an elevated white blood cell count, along with increased red blood cells and platelets. Diagnosis involves demonstrating an increase in red cell mass and the presence of the JAK2 mutation.
- Acute Myeloid Leukemia (AML): Although AML can present with a low white blood cell count (aleukemic leukemia), it can also cause leukocytosis. The diagnosis is based on bone marrow biopsy findings and specific immunophenotyping.
- Chronic Lymphocytic Leukemia (CLL): A disorder of mature lymphocytes that can cause an elevated white blood cell count. Diagnosis is based on the immunophenotypic characteristics of the lymphocytes.
Do Not Miss Diagnoses
- Hemorrhage: Significant blood loss can lead to a stress response, causing leukocytosis. It's crucial to consider internal or external bleeding as a cause, especially in patients with risk factors or symptoms suggestive of hemorrhage.
- Tumor Lysis Syndrome: Although more commonly associated with acute kidney injury and electrolyte disturbances, tumor lysis syndrome can also cause leukocytosis, particularly in the context of rapidly proliferating malignancies undergoing treatment.
- Adrenal Insufficiency: In some cases, adrenal insufficiency can present with leukocytosis, among other symptoms like hypotension and electrolyte imbalances. It's a critical diagnosis to consider due to its potential for severe consequences if left untreated.
Rare Diagnoses
- Leukocyte Adhesion Deficiency (LAD): A rare genetic disorder affecting the ability of leukocytes to migrate to sites of infection, leading to recurrent infections and sometimes leukocytosis due to the accumulation of non-functional white blood cells in the circulation.
- Myeloproliferative Neoplasms (Other than CML and Polycythemia Vera): Conditions like essential thrombocythemia and primary myelofibrosis can also cause an elevated white blood cell count, though they are less common and often present with other prominent features such as thrombocytosis or splenomegaly.
- Lymphoma: Certain types of lymphoma can cause leukocytosis, especially if there is significant bone marrow involvement. The diagnosis typically involves lymph node biopsy or bone marrow examination.