Can headaches cause leukocytosis (an increase in white blood cell count)?

Can Headache Cause Leukocytosis?

No, headaches themselves do not cause leukocytosis—instead, both may be concurrent manifestations of an underlying infectious, inflammatory, or malignant process that requires immediate evaluation. 1, 2

Understanding the Relationship

Headache and leukocytosis are not causally related but rather co-occurring symptoms that demand investigation for serious underlying pathology:

• Leukocytosis is a reactive process driven by infection, inflammation, physical/emotional stress, medications (corticosteroids, lithium, beta agonists), or primary bone marrow disorders—not by headache itself 1, 2
• The peripheral white blood cell count can double within hours in response to stressors including surgery, exercise, trauma, and emotional stress, but headache alone does not trigger this response 2

Critical Conditions to Exclude When Both Are Present

When a patient presents with both headache and leukocytosis, immediately evaluate for:

Infectious Causes (Most Common)

• Bacterial meningitis: Requires CSF analysis showing neutrophilic pleocytosis (though 10% of cases have <100 cells/mm³ early in illness), elevated protein, and low glucose 3
• Aseptic or septic meningitis: Must be excluded in any patient with headache, particularly if fever, meningismus, or altered mental status are present 4
• Sinus thrombosis: Especially in patients with antiphospholipid antibodies, can present with headache and reactive leukocytosis 4

Inflammatory/Autoimmune Causes

• Systemic lupus erythematosus (SLE): Headache is frequently reported but shows no increased prevalence compared to general population; however, must exclude concurrent meningitis, sinus thrombosis, or cerebral hemorrhage 4
• Autoimmune encephalitis: Can present with headache, psychiatric symptoms, seizures, and CSF lymphocytic pleocytosis (50-70% of neuropsychiatric SLE cases) 3

Malignant Causes (Red Flags)

• Primary bone marrow disorders should be suspected with extremely elevated WBC counts (>100,000/mm³ represents a medical emergency due to risk of brain infarction and hemorrhage) 1
• Acute leukemia: Patients more likely to be acutely ill with fever, weight loss, bruising, fatigue, and concurrent abnormalities in red blood cells or platelets 1, 2
• Chronic myeloid leukemia: Leukostatic symptoms (including headache, drowsiness, confusion) can occur despite WBC often exceeding 100 × 10⁹/L 4

Diagnostic Algorithm

Step 1: Assess for high-risk features requiring immediate intervention 4

• Fever or concomitant infection
• Immunosuppression
• Focal neurological signs
• Altered mental status
• Meningismus
• Use of anticoagulants

Step 2: Obtain complete blood count with differential 2, 5

• Left shift (≥16% band neutrophils or ≥1,500 absolute band count) has likelihood ratios of 4.7 and 14.5 respectively for bacterial infection 6
• Elevated total WBC ≥14,000 cells/mm³ has likelihood ratio of only 3.7 for bacterial infection 6
• Review peripheral smear for blast cells, toxic granulations, or abnormal cell morphology 2, 5

Step 3: If high-risk features present, obtain lumbar puncture 3

• CSF lactate <2 mmol/L effectively rules out bacterial disease 3
• Low CSF:plasma glucose ratio (<0.5) with lymphocytic pleocytosis suggests tuberculosis, fungal infection, or partially treated bacterial meningitis 3
• Normal glucose with lymphocytic pleocytosis suggests viral infection 3

Step 4: Neuroimaging 4, 3

• Brain MRI with contrast to evaluate for parenchymal involvement, abscess, hemorrhage, or sinus thrombosis 3
• Particularly important if age <60 years, focal neurological signs, or immunosuppression 4

Common Pitfalls to Avoid

• Do not assume isolated headache causes leukocytosis—always search for the underlying etiology driving both symptoms 1, 2
• Do not delay empiric antibiotics if bacterial meningitis cannot be excluded—treatment must begin within one hour of presentation when suspected, including ceftriaxone + vancomycin + ampicillin if >50 years or immunocompromised 3
• Do not overlook stress-induced leukocytosis—physical stress from seizures or emotional stress can elevate WBC counts without infection 1, 2
• Do not miss leukostatic emergency—WBC counts >100,000/mm³ require urgent intervention due to risk of brain infarction and hemorrhage 1
• In SLE patients with headache alone and no high-risk features, no further investigation is needed beyond what would be performed for non-SLE patients 4