What are the common causes of basophilia?

Causes of Basophilia

Basophilia is most commonly caused by chronic myeloid leukemia (CML) and other myeloproliferative neoplasms (MPNs), with allergic/inflammatory conditions and parasitic infections representing the primary reactive causes. 1, 2

Neoplastic Causes (Most Important)

Chronic Myeloid Leukemia and Myeloproliferative Neoplasms

• CML is the most frequent neoplastic cause of basophilia, with basophilia present in the majority of cases and considered a hallmark feature. 1, 3

• Basophilia ≥20% in blood or bone marrow is a defining criterion for accelerated phase CML according to both WHO and European LeukemiaNet guidelines. 1

• Primary myelofibrosis (PMF), especially CALR-positive cases, shows strong association with persistent basophilia, which may predict progression to acute myeloid leukemia. 4

• Essential thrombocythemia and polycythemia vera can present with basophilia as part of the MPN spectrum. 5

• Hyperbasophilia (absolute basophil count ≥1000/μL) is highly indicative of an underlying myeloid neoplasm and requires immediate hematologic investigation including bone marrow biopsy, cytogenetics, and molecular testing for BCR-ABL1 and other tyrosine kinase fusions. 6

Acute Leukemias

• Acute basophilic leukemia (ABL) is rare but represents a distinct entity requiring ≥20% basophils among bone marrow blasts. 6

• Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes (PDGFRA, PDGFRB, FGFR1, ABL1, JAK2) frequently present with concurrent basophilia. 1

Reactive (Secondary) Causes

Allergic and Inflammatory Conditions

• Allergic disorders including asthma, allergic rhinitis, atopic dermatitis, and food allergies account for approximately 80% of reactive basophilia cases in non-endemic regions. 7, 8, 9

• Chronic inflammatory conditions and autoimmune diseases can produce mild basophilia. 8

Infectious Causes

• Parasitic infections, particularly tissue-invasive helminths (Strongyloides, Ascaris, hookworm, Schistosoma), are the second most common cause of reactive basophilia, especially in travelers and migrants from endemic areas. 7, 8, 9

• Strongyloides stercoralis infection can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients, making exclusion mandatory even in asymptomatic basophilia. 7, 9

Medication-Induced

• Drug reactions, particularly to beta-lactam antibiotics, nitrofurantoin, and non-steroidal anti-inflammatory drugs, can cause basophilia. 8, 9

Other Reactive Causes

• Chronic infections, including tuberculosis in resource-limited settings, may present with basophilia. 8

• Solid tumors in advanced stages can rarely cause paraneoplastic basophilia. 8

Critical Diagnostic Approach

When to Suspect Neoplastic Basophilia

• Absolute basophil count ≥1000/μL mandates bone marrow evaluation with cytogenetics (including FISH for BCR-ABL1) and molecular testing for tyrosine kinase fusions. 6

• Persistent basophilia >3 months despite treatment of reactive causes requires hematology referral for evaluation of myeloid neoplasm. 4, 2

• Basophilia accompanied by splenomegaly, thrombocytosis, leukocytosis with myeloid immaturity, or constitutional symptoms strongly suggests MPN. 1

Diagnostic Pitfalls to Avoid

• Automated hematology analyzers significantly underestimate basophil counts in myeloid neoplasms (mean 2.7% by analyzer vs 7.1% by manual differential); manual differential and flow cytometry are required for accurate quantitation in suspected MPN. 5

• Do not attribute basophilia solely to known allergic conditions without excluding helminth infections in travelers/migrants or myeloid neoplasms in persistent cases. 9, 2

• Spurious basophilia from platelet clumping, nucleated red blood cells, or other interfering substances must be excluded by manual review before pursuing extensive workup. 2

Systematic Evaluation Algorithm

• Step 1: Confirm true basophilia by manual differential to exclude spurious elevation from automated analyzer artifact. 5, 2

• Step 2: If basophilia confirmed, assess for reactive causes—obtain detailed travel/exposure history, medication review, and evaluate for allergic/atopic conditions. 2

• Step 3: In travelers/migrants, perform three concentrated stool specimens for ova/parasites, Strongyloides serology, and Schistosomiasis serology based on exposure history. 7, 9

• Step 4: If absolute basophil count ≥1000/μL or basophilia persists >3 months without identified reactive cause, proceed to bone marrow biopsy with cytogenetics and molecular testing for BCR-ABL1 and other tyrosine kinase fusions. 2, 6

• Step 5: In confirmed myeloid neoplasm with basophilia, monitor for disease progression—basophilia ≥20% defines accelerated phase in CML, and persistent marked basophilia in PMF predicts AML transformation. 1, 4